ALLERGY
Diagnosis,
Diagnostics, Immunodiagnosis & Immunodiagnostics:
ABSTRACTS
January 2003
5880.
Adamek-Guzik T, Guzik TJ, Czerniawska-Mysik G, Korpanty G, Mastalerz L,
Radwan J, Szczeklik A. Urinary leukotriene levels are increased during
exacerbation of atopic eczema/dermatitis syndrome. Relation to clinical status.
Allergy. 2002 Aug;57(8):732-6.
BACKGROUND:
Leukotrienes are potent mediators of allergic inflammation and their role in the
pathogenesis of allergic disorders, particularly asthma, is well established.
Their importance in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS)
is still unclear. We aimed to compare urinary cysteinyl leukotriene (Cys-LT)
levels during exacerbation and remission of AEDS in relation to clinical status,
IgE levels, and eosinophil counts. METHODS: Urinary Cys-LTs were measured by
direct enzyme immunoassay in 17 adult patients with AEDS and in 17 healthy
controls in whom atopy had been excluded. Cys-LTs were compared during
exacerbation and remission of AEDS in relation to the clinical status measured
by SCORAD. Total IgE levels were measured by enzyme-linked immunoassay (ELISA).
RESULTS: Mean clinical score during the exacerbation was 64.3 +/- 3.1 and during
remission 22.4 +/- 4 (P < 0.01). Cys-LTs levels were significantly higher
during the exacerbation of AEDS than in the control group (230.9 +/- 20.8 vs
123.2 +/- 9.9 pg/mg creatinine; P < 0.005). During the remission, the
difference between AEDS patients and the control group was not significant (96.3
+/- 8.7 vs 123.2 +/- 9.9 pg/mg creatinine; P = 0.8). During AEDS exacerbation
Cys-LTs levels were significantly correlated with the clinical status (rS =
0.73, P < 0.01) and with eosinophil counts (r = 0.86; P < 0.01) but not
with the duration of the disease, age of patients, or IgE levels. CONCLUSIONS:
Our results point to enhanced biosynthesis of Cys-LTs during the AEDS
exacerbations. Inflammatory cells, e.g. eosinophils are the most probable source
of Cys-LTs. A strong correlation between Cys-LT levels and clinical status may
in part explain preliminary clinical observations of efficacy of leukotriene
antagonists in alleviating symptoms of AEDS.
5881.
Alonso-Llamazares A, Martinez-Cocera C, Dominguez-Ortega J,
Robledo-Echarren T, Cimarra-Alvarez M, Mesa del Castillo M. Nasal provocation
test (NPT) with aspirin: a sensitive and safe method to diagnose aspirin-induced
asthma (AIA). Allergy. 2002 Jul;57(7):632-5.
BACKGROUND:
We have aimed to determine the sensitivity and specificity of a
simpler
technique with less risk than oral provocation to diagnose aspirin-induced
asthma (AIA). METHODS: We studied a group of 20 AIA patients compared to a
control group with 40 aspirin-tolerant patients (confirmed by oral provocation
test): 10 asthmatic patients and 30 healthy subjects. A nasal provocation test (NPT)
with lysine acetylsalicylic acid (L-ASA) was carried out. Nasal and pulmonary
functions were monitored with anterior active rhinomanometry (AAR) and
spirometry. An L-ASA solution (900 mg/ml L-ASA, equivalent to 500 mg/ml
acetylsalicylic acid) was diluted with saline solution. We administered four
increasing doses: 5, 25, 50 and 100 mg/ml acetylsalicylic acid (ASA) with saline
solution control. Nasal and pulmonary functions were monitored with
rhinomanometry and spirometry. The patients were controlled for nasal
inspiratory peak flow and expiratory peak flow. RESULTS: The results showed high
sensitivity and specificity: 80% and 92.5%, respectively, with an 84.2% positive
predictive value and an 89.2% negative predictive value. The patients had no
bronchial or systemic symptoms, and no decreases over 20% were recorded in the
FEV1. CONCLUSION: NPT has a high sensitivity and specificity in the diagnosis of
AIA. An oral provocation should be performed to confirm the result whenever the
clinical situation of the patient permits it.
5882.
Baldo BA, Pham NH. Immunoglobulin
E binding determinants on beta-lactam drugs. Curr Opin Allergy Clin Immunol.
2002 Aug;2(4):297-300. Review.
PURPOSE
OF REVIEW: Allergies to penicillins and cephalosporins remain an important
clinical problem, but structural and immunochemical knowledge of the allergenic
structures involved has tended to lag behind the heavy usage, consequent adverse
reactions and introduction of new therapeutic members of these two families of
antibiotics. Evidence of the increasing incidence of reactions to cephalosporins
and to "minor" determinants of the beta-lactams is accumulating. Also,
although numerous reports detail unique allergic recognitions of individual
members of the two families, particularly the cephalosporins, information
remains predominantly clinical. The present review summarizes the most recent
advances in studies of structural aspects of beta-lactams as allergens. RECENT
FINDINGS: For the cephalosporins, a pyrazinone allergenic degradation product of
cefaclor and cephalexin has been identified and characterized. The widely used
cephalosporin cephalothin was shown to cross-react allergenically with
benzylpenicillin and the common cross-reacting structure was identified. The
fine structural features on the amoxicillin molecule recognized by antibodies
that distinguish "major" and "minor" determinants were
identified, and steric factors were used to explain antibody recognition of the
amoxicillin determinants. A recent study elucidated the molecular basis of some
cases of the multiple drug allergy syndrome and its relationship to beta-lactam
allergy. SUMMARY: Findings of the type described in the present review provide
fundamental insights into the nature and size of antigenic determinants on
"small" molecules such as drugs and other chemicals. At the clinical
level, such structure/activity findings have implications for our understanding
of drug allergenic cross-reactions, for selection for therapy
of
an appropriate member from a family of structurally related drugs and,
ultimately, for desensitization of drug-allergic patients.
5883.
Ballmer-Weber BK, Scheurer S, Fritsche P, Enrique E, Cistero-Bahima A,
Haase T, Wuthrich B. Component-resolved diagnosis with recombinant allergens in
patients with cherry allergy. J Allergy Clin Immunol. 2002 Jul;110(1):167-73.
BACKGROUND:
In pollen-related food allergy, extracts for skin prick tests (SPTs) are often
not standardized, and the test reliability is affected by false-negative
reactions. OBJECTIVE: We sought to evaluate a panel of recombinant allergens
(RAs) derived from one allergenic food for use in component-resolved in vivo
diagnosis, taking cherry as a model food. METHODS: Seventy-nine subjects were
included in the study: 24 Swiss patients (group 1) with a positive double-blind
placebo-controlled food challenge result to cherries, 23 patients with birch
pollen allergy but without cherry allergy (group 2), 23 nonatopic subjects
(group 3), and 9 Spanish patients with a history of a cherry allergy (group 4).
SPTs were performed in duplicate by using recombinant cherry allergens (Bet v
1-related allergen: recombinant (r) Pru av 1; profilin: rPru av 4; and lipid
transfer protein: rPru av 3) in concentrations of 10, 50, and 100 microg/mL.
Furthermore, IgE reactivity to rPru av 1, rPru av 4, and rPru av 3 was assessed
by means of immunoblot analysis. RESULTS: SPT responses with rPru av 1, rPru av
4, and rPru av 3 were positive in 92%, 17%, and 4% of the patients in group 1;
in 74%, 30%, and 0% of the patients in group 2; in 0%, 22%, and 89% of the
patients in group 4; and negative for all nonatopic subjects (group 3). Thus the
sensitivity of a positive SPT response to at least one of the 3 RAs was 96%. The
specificities, negative predictive values, and positive predictive values with
the 3 RAs were 100%, 96%, and 100% if calculated in relation to the nonatopic
control group but 17%, 79%, and 60% when calculated in relation to the control
group with birch pollen allergy. The correlation between SPT and immunoblotting
results was excellent. Sensitization to rPru av 3 was associated with more
severe symptoms than sensitization to rPru av 1. CONCLUSIONS: SPTs with RAs
proved to be highly sensitive for diagnosis of cherry allergy.
Component-resolved in vivo diagnosis with standardized amounts of stable RAs
allows us to determine sensitization patterns directly, to correlate them with
severity of clinical symptoms, and to analyze geographic differences.
5884.
Bernstein DI, Cartier A, Cote J, Malo JL, Boulet LP, Wanner M, Milot J,
L'Archeveque J, Trudeau C, Lummus Z. Diisocyanate
antigen-stimulated monocyte chemoattractant protein-1 synthesis has greater test
efficiency than specific antibodies for identification of diisocyanate asthma.
Am J Respir Crit Care Med. 2002 Aug 15;166(4):445-50.
We
previously reported that diisocyanate-human serum albumin (DIISO-HSA) stimulated
production of monocyte chemoattractant protein-1 (MCP-1) by peripheral blood
mononuclear cells is significantly associated with a clinical diagnosis of
diisocyanate asthma (DA). Others have reported that antibodies for DIISO-HSA are
specific but insensitive markers of DA. This study was performed to evaluate
test characteristics of the in vitro MCP-1 assay compared with
DIISO-HSA-specific immunoglobulin (Ig) G and IgE in identifying workers with DA.
MCP-1 was quantitated in peripheral blood mononuclear cell supernatants 48 hours
after incubation with DIISO-HSA antigens. Assay results were compared with
outcomes of specific inhalation challenge (SIC) testing. Nineteen of 54 (35%)
workers assayed for antibodies and MCP-1 stimulation had SIC-confirmed DA. Mean
MCP-1 produced by SIC-positive workers was greater than SIC-negative workers (p
< or = 0.001). Diagnostic sensitivity, specificity, and test efficiency for
specific IgG were 47%, 74%, and 65%, respectively, and for specific IgE were
21%, 89%, and 65%, respectively. Sensitivity, specificity, and test efficiency
of the MCP-1 test were 79%, 91%, and 87%, respectively. This study indicates
that the MCP-1 stimulation assay has greater sensitivity and specificity than
the specific antibody assays in correctly identifying DA.
5885.
Bernstein JA. Material safety data sheets: are they reliable in
identifying human hazards? J Allergy Clin Immunol. 2002 Jul;110(1):35-8. Review.
The
material safety data sheet (MSDS) is an integral part of a worker's evaluation
for suspected occupational asthma and dermatitis. However, established US
federal guidelines for creating an MSDS do not require that certain key
information relevant to the diagnosis of these disorders be included. This
rostrum is intended to highlight the limitations of MSDSs as they pertain to the
diagnosis of occupational asthma and occupational dermatitis so that future
consideration can be given to modification of the existing MSDS guidelines. This
article summarizes the origins of MSDS documents, provides an overview of their
format, and discusses some of their inherent limitations, which at times impede
proper medical evaluation by physicians and other health care professionals.
MSDSs are an essential part of making the workplace a safer environment. More
complete disclosure about both irritation and sensitization risks in these
documents would facilitate the evaluation of workers for OA and OD. Their
current ambiguity often delays the diagnosis of these occupational diseases and
places the worker at further risk for development of occupational-related
long-term disorders. Health care professionals have an obligation to better
educate themselves regarding the interpretation of MSDSs and to recognize that
they sometimes provide incomplete data.
5886.
Beyer K, Grishina G, Bardina L, Grishin A, Sampson HA. Identification of
an 11S globulin as a major hazelnut food allergen in hazelnut-induced systemic
reactions. J Allergy Clin Immunol. 2002 Sep;110(3):517-23.
BACKGROUND:
Hazelnuts are a common cause of food allergy. Allergic reactions to hazelnuts
range from oral allergy syndrome caused by cross-reactivity between tree pollen
and hazelnut proteins to severe anaphylactic reactions. Little information is
available regarding the identification of pollen-independent hazelnut allergens.
OBJECTIVE: The aim of the study was to identify these pollen-independent
allergens in patients with hazelnut allergy with systemic reactions. METHODS:
Extracted hazelnut proteins were separated by means of 2-dimensional PAGE, and
immunolabeling was performed with individual sera from 14 patients with
hazelnut-induced systemic reactions. Edman sequencing was performed on a 40-kd
protein identified as an allergen. In parallel, RNA isolated from hazelnuts was
used to construct a cDNA library. By using the peptide sequence data,
oligonucleotide primers were synthesized and used to screen the library.
Full-length cDNA clones were isolated, sequenced, expressed, and screened with
patient sera. RESULTS: By using 2-dimensional proteomics, a protein fraction at
40 kd was recognized by serum IgE from 86% (12/14) of the patients with hazelnut
allergy with systemic reactions. Two internal amino acid sequences were
determined by means of Edman sequencing. Screening of the prepared hazelnut cDNA
library with oligonucleotides based on these internal peptide sequences resulted
in isolation of a novel protein cDNA. The new protein, named Cor a 9, belongs to
the 11S globulin seed storage protein family. This family comprises known food
allergens in peanut (Ara h 3) and soybean
(glycine
max). The pairwise homology among these 3 proteins ranges from 45% to 50%.
Interestingly, one known IgE-binding epitope of Ara h 3 shares 67% of homologous
amino acid residues with the corresponding area of Cor a 9. The amino acids that
differ were previously shown not to be critical for IgE binding in Ara h 3.
CONCLUSION: Cor a 9 is the first tree pollen unrelated hazelnut allergen
isolated, sequenced, and cloned. The identification of food allergens is the
first step toward generating recombinant allergens for use in future
immunotherapeutic approaches. In addition, the detection of conserved IgE
epitopes in common food allergens, such as seed storage proteins, might be a
useful tool for predicting cross-reactivity to certain foods.
5887.
Bickel A, Axelrod FB, Schmelz M, Marthol H, Hilz MJ. Dermal microdialysis
provides evidence for hypersensitivity to noradrenaline in patients with
familial dysautonomia. J Neurol Neurosurg Psychiatry. 2002 Sep;73(3):299-302.
OBJECTIVES:
To use the technique of dermal microdialysis to examine sensitivity of skin
vessels to noradrenaline (NA) in patients with familial dysautonomia (FD) and in
healthy controls. METHODS: In 14 patients with FD and 12 healthy controls,
plasma extravasation, local laser Doppler blood flow, and skin blanching were
observed before, during, and after application of 10(-6) M NA through a
microdialysis membrane, located intradermally in the skin of the lower leg.
RESULTS: Maximum local vasoconstriction measured by laser Doppler blood flow did
not differ between patients with FD and controls. In contrast, patients with FD
had an earlier onset of vasoconstriction (p = 0.02). Moreover, reaction to NA
was more prominent and prolonged in FD, shown by a larger zone of skin blanching
around the microdialysis membrane (p < 0.001) and delayed reduction of the
protein content in the dialysate after termination of NA application (p = 0.03).
CONCLUSION: These data support the hypothesis that peripheral blood vessels of
patients with FD show a denervation hypersensitivity to catecholamines. This may
be one mechanism contributing to the major hypertension that frequently occurs
during "dysautonomic crises" in FD.
5888.
Bochenek G, Niz Ankowska E, Szczeklik A. Testing for aspirin
hypersensitivity. Allergy. 2002 Jul;57(7):562-5. Review.
No abstract.
5889.Bokulic
RE. Screening for exercise-induced asthma. J Pediatr. 2002 Sep;141(3):306-8. No
abstract.
5890.Caballero
ML, Moneo I. Specific IgE determination to Ani s 1, a major allergen from
Anisakis simplex, is a useful tool for diagnosis. Ann Allergy Asthma Immunol.
2002 Jul;89(1):74-7.
BACKGROUND:
The most serious limitation of the serodiagnosis of parasitoses is the
occurrence of cross-reactions. OBJECTIVE: The possible use of Anisakis simplex
major allergen Ani s 1 for diagnosis. PATIENTS AND METHODS: Forty-nine
non-fish-allergic patients with Anisakis simplex hypersensitivity, 21 patients
without allergic episodes suffering intestinal anisakiasis with obstruction of
the intestinal lumen, and 10 unrelated sera as a control were included in this
study to determine specific immunoglobulin (Ig)E and IgG to Anisakis simplex
major allergen Ani s 1 by immunoblotting. RESULTS: Eighty-six percent of
patients with Anisakis simplex hypersensitivity showed specific IgE directed to
Ani s 1. Identical result was obtained for IgG detection in this group. Among
patients with intestinal anisakiasis, 86% showed specific IgE, but only 29% had
specific IgG (P < 0.001, two-tailed Fisher exact test). One of the 10 control
subjects was positive both for IgE and IgG (P < 0.001). CONCLUSIONS:
Determination of specific IgE directed to Anisakis simplex major allergen Ani s
1 is a useful tool for the diagnosis of hypersensitivity and intestinal
anisakiasis. Further, measurement of specific IgG directed to Anisakis simplex
major allergen Ani s 1 is only valid for Anisakis simplex allergy.
5891.
Carroll NG, Mutavdzic S, James AL. Increased mast cells and neutrophils
in submucosal mucous glands and mucus plugging in patients with asthma. Thorax.
2002 Aug;57(8):677-82.
BACKGROUND:
Mucus plugging of the airways is invariably seen in cases of fatal asthma, mucus
production is associated with asthma attacks, and the area of submucosal glands
is increased in asthma. Mediators secreted from mast cells and neutrophils can
stimulate mucous gland secretion. A study was undertaken to count the mast cells
and neutrophils in submucosal glands and to relate cell numbers to the presence
of mucus in the airway lumen. METHODS: Cartilaginous airways obtained at
necropsy from cases of fatal asthma (n=8), non-fatal asthma (n=8), and control
cases (n=8) were examined. Contiguous transverse sections were stained for mast
cell tryptase and neutrophil elastase, and with Periodic Acid Schiff solution to
identify mucus. Mucous gland area, lumen area, and the percentage of the relaxed
lumen area occupied by mucus (mucus occupying ratio, MOR) were measured. Mast
cells (intact and degranulated) and neutrophils per area of submucosal gland
were calculated. RESULTS: Compared with controls, the cases of fatal asthma had
increased mucous gland area, MOR, percentage of degranulated mast cells, and
numbers of neutrophils in the submucosal glands (p<0.05). In cases of
non-fatal asthma the MOR and the numbers of mast cells and neutrophils in the
submucosal glands were increased (p<0.05). When all cases were pooled
together, the MOR correlated with the total number of mast cells (r=0.55,
p=0.005) and with the number of degranulated mast cells in the submucosal glands
(r=0.51, p=0.013), but not with the number of neutrophils (r=0.21, p=0.121).
CONCLUSION: These results show that mucous gland area, MOR, and mucous gland
inflammation are increased in asthma and that degranulation of mast cells may
contribute to secretion of mucus into the lumen in cases of fatal asthma.
5892.
Cavallo GP, Elia M, Giordano D, Baldi C, Cammarota R. Decrease of
specific and total IgE levels in allergic patients after BCG vaccination:
preliminary report. Arch Otolaryngol Head Neck Surg. 2002 Sep;128(9):1058-60.
BACKGROUND:
A systemic reaction to mycobacteria biases the balance of T helper cell types 1
and 2 toward T helper cell type 1. BCG vaccination mimics some characteristics
of mycobacterial infection. Children who have undergone tuberculin conversion
after BCG vaccination seem to be more likely to lose their atopic symptoms.
Inhibition of both allergic response and airway hyperreactivity after
vaccination for mycobacteria has been observed in animal experiments. OBJECTIVE:
To evaluate the effects that BCG vaccination has on the serological status of
allergic people. PARTICIPANTS AND METHODS: This study included 20 volunteers
with a history of allergic rhinitis who were required to undergo BCG vaccination
by Italian law. Epicutaneous allergy testing with a panel of common seasonal and
perennial inhalational allergens and 2 blood withdrawals were performed. The
serum total IgE levels and the serum allergen-specific IgE levels of each
individual were measured just before BCG vaccination and again 4 months later.
Total IgE levels were determined using the paper radioimmunosorbent test, and
allergen-specific IgE levels were determined using the radioallergosorbent test.
RESULTS: Total IgE and allergen-specific IgE levels were significantly decreased
after BCG vaccination (P =.004 and P<.001, respectively). CONCLUSION: BCG, an
effective stimulus for cell-mediated immunity, deserves further study to
evaluate its ability to modulate the immune response associated with allergic
rhinitis.
5893.
Chardin H, Raulf-Heimsoth M, Chen Z, Rihs HP, Mayer C, Desvaux FX,
Senechal H, Peltre G. Interest of two-dimensional electrophoretic analysis for
the characterization of the individual sensitization to latex allergens. Int
Arch Allergy Immunol. 2002 Jul;128(3):195-203.
BACKGROUND/OBJECTIVE:
Latex allergy is a type 1 hypersensitivity reaction that mainly affects
high-risk populations such as health care workers, spina bifida-affected or
multiply-operated children. Ten molecules have so far been identified and
registered as latex allergens (Hev b 1 to Hev b 10). The aim of the present
investigation was to identify the major latex allergens by an individual
analysis of the IgE response of latex-allergic patients to latex proteins
separated by two-dimensional (2-D) gel electrophoresis. MATERIALS AND METHODS:
Latex proteins from a sap or a glove extract were separated by 2-D
electrophoresis and transferred to a nitrocellulose membrane. Each membrane was
incubated with the serum of one latex-allergic patient. The most frequently
recognized latex allergens were characterized in sap and glove extracts using
monoclonal antibodies or amino acid microsequencing. RESULTS: The
one-dimensional screening of 54 patient sera revealed 4 major bands recognized
by IgE. The 2-D analysis of the sensitization to latex allergens allows the
identification of allergen isoforms and the characterization of an individual
response diversity. Hev b 6.01 was recognized by 88.9% of the patients. Protein
spots around 14 kD were recognized by 48.1% of the patients and corresponded to
Hev b 6.03 as well as other proteins. A not yet characterized doublet of acidic
proteins with molecular masses of 43 and 94 kD was recognized by 20.4% of the
sera. Only 5.5% of the sera did not recognize any of these 4 major allergens.
Hev b 1 is the main protein from the glove extract but was not constantly found
in sap extracts. CONCLUSIONS: One-dimensional electrophoretic analysis of the
allergen is usually not sufficient to characterize the individual specificity of
the IgE response to latex allergens. Latex-glove proteins which are allergens
can be absent from the sap extracts and the sensitization to these allergens
could be underestimated. Individual 2-D analysis of the sensitization to latex
allergens is useful to define the best allergen mixture required for diagnosis
and needed for individual therapy monitoring. Copyright 2002 S. Karger AG, Basel
5894.
Cloutier MM. Neutrophils or eosinophils in young children with wheezing:
which comes first? Chest. 2002 Sep;122(3):761-3.
No abstract.
5895.
Duarte I, Lazzarini R, Buense R. Interference of the position of
substances in an epicutaneous patch test battery with the occurrence of
false-positive results. Am J Contact Dermat. 2002 Sep;13(3):125-32.
BACKGROUND:
Epicutaneous patch tests represent a practical and objective method that help in
the etiologic diagnosis of allergic contact dermatitis. The technique of patch
test application is an important factor in obtaining good results. OBJECTIVES:
The aims of this study were (1) to determine whether the substances that form
the test battery interfere with the patch test result and (2) to establish a
rule for positioning the substances during patch test application. METHODS: Two
hundred patients were studied. The standard patch test battery was applied in 3
versions. The original, with the substances applied in alphabetical order was
called version 1 (V1) and tested on the left back in all patients In 100
patients, on the right side, the same substances were tested but applied at
different positions, avoiding the proximity of elements with a tendency to cross
reaction and/or cosensitizing. This version of the battery was named version 2
(V2). Another 100 patients had V1 applied to the left back, and, on the right
side, the version 3 of the battery (V3) was applied, consisting of the same
allergens but placed close to those with a tendency for cross reaction and/or
cosensitization. RESULTS: In the group V1-V2, 163 results were positive in V1
and 124 in V2, with the difference being statistically significant (P <.05).
In the group V1-V3, 134 results were positive in V1 and 207 in V3, with the
difference also being significant (P <.005). The substances with the largest
number of positive results, when tested close to other elements with a tendency
for chemical affinity, were parabens, fragrance-mix, thimerosal, balsam of Peru,
potassium dichromate, cobalt chloride, mercapto mix, and propylene glycol.
CONCLUSIONS: (1) The substances of a patch test battery eliciting positive
responses may interfere with test positivity to neighboring substances. (2) In
addition to the already established techniques, the position of the substances
forming the test battery needs to be determined; substances with a tendency to
cross reaction or cosensitizing substances should be tested distant from one
another, thus preventing the occurrence of false-positive results. Copyright
2002, Elsevier Science (USA). All rights reserved.
5896.
Ebo DG, Lechkar B, Schuerwegh AJ, Bridts CH, De Clerck LS, Stevens WJ.
Validation of a two-color flow cytometric assay detecting in vitro basophil
activation for the diagnosis of IgE-mediated natural rubber latex allergy.
Allergy. 2002 Aug;57(8):706-12.
BACKGROUND:
IgE-dependent triggering of basophils not only elicits the release of different
mediators but also the up-regulation of certain markers, e.g. CD63, which can be
detected by flow cytometry. We intended to investigate if flow cytometric
analysis of basophil activation could be a valuable tool in the diagnosis of
latex allergy, and to evaluate if the basophil activation test (BAT) could be
helpful in determining the clinical significance of a positive latex IgE in
individuals with negative history and negative latex skin test. Additionally we
aimed to determine the role of cross-reactive carbohydrate determinants (CCDs)
in causing positive latex IgE without apparent clinical significance. METHODS:
Twelve healthy controls without a history of latex hypersensitivity with a
negative latex IgE and skin test (group 1), 24 individuals without a history of
latex hypersensitivity with a negative latex IgE and skin test but with other
inhalant allergies (group 2), and 29 latex allergic patients with a compelling
history of latex allergy with a positive latex IgE and prick test (group 3) were
enrolled. The diagnostic performances of the BAT were further evaluated in 13
individuals with a history of latex allergy but with negative specific IgE
and/or skin test (group 4). Twenty-four individuals with positive latex IgE
without apparent clinical relevance, i.e. without history of latex
hypersensitivity and negative latex skin tests, were also analyzed (group 5).
The putative role of CCDs causing positive latex IgE results without apparent
clinical significance was evaluated by quantification of IgE for bromelain.
RESULTS: According, to the receiver operating characteristics(ROC)-generated
threshold value of 17% between latex allergic patients and the pooled group of
nonlatex allergic individuals, the sensitivity and specificity of the basophil
activation test was 93.1% and 91.7%, respectively. In healthy controls, allergic
patients without latex hypersensitivity and latex allergic patients the number
of positive BATs was 0/12, 3/24 and 27/29, respectively. In the individuals with
an evocative history of latex allergy but with negative latex IgE and/or skin
test the BAT was positive in all 13 cases. Twenty of 24 individuals without
apparent latex allergy but with positive latex IgE had a negative BAT. IgE for
bromelain was positive in 1/19 sera from group 2, 1/24 sera from group 3, none
of the 8 sera from group 4, but in 16/18 sera from group 5, respectively.
CONCLUSION: Flow cytometric analysis of activated basophils seems a highly
sensitive and specific tool for diagnosing latex allergy. In addition, the
technique might help to determine the clinical relevance of positive IgE
quantification in the absence of overt latex allergy. CCDs of natural rubber
latex allergens were confirmed to mimic latex sensitization.
5897.
Fremeaux-Bacchi V, Guinnepain MT, Cacoub P, Dragon-Durey MA, Mouthon L,
Blouin J, Cherin P, Laurent J, Piette JC, Fridman WH, Weiss L, Kazatchkine MO.
Prevalence of monoclonal gammopathy in patients presenting with acquired
angioedema type 2. Am J Med. 2002 Aug 15;113(3):194-9.
PURPOSE:
Acquired angioedema type 1 is characterized by a C1 inhibitor deficiency in
patients with lymphoproliferative disorders, whereas acquired angioedema type 2
is characterized by anti-C1 inhibitor antibodies, and has not been thought to be
associated with lymphoproliferative disease. We studied the clinical features,
complement profiles, and associated diseases in 19 new patients with diagnosed
acquired angioedema type 2. SUBJECTS AND METHODS: Plasma concentrations and
functional activity of complement components were measured by conventional
techniques. Functional C1 inhibitor activity was assessed by a chromogenic
assay. Autoantibodies to C1 inhibitor were detected using an enzyme-linked
immunosorbent assay. RESULTS: The 11 men and 8 women (median age, 60 years)
presented with recurrent attacks of angioedema. All patients had detectable
anti-C1 inhibitor antibodies in serum. A monoclonal gammopathy was detected in
12 patients (63%) at the time of diagnosis, 11 of whom had an immunoglobulin
peak of the same heavy- and light-chain isotypes as the acquired anti-C1
inhibitor antibody. Three of these 12 patients developed a malignant
lymphoproliferative disease. CONCLUSION: As with type 1 disease, a large
proportion of patients with acquired angioedema type 2 have a
lymphoproliferative disorder.
5898.
Ghobrial G, Naser SA, Sweeney M, White R. Identification and
characterization of the allergenic proteins of Bahia grass (Paspalum notatum)
pollen. Int Arch Allergy Immunol. 2002 Aug;128(4):304-9.
BACKGROUND:
Pollen of Bahia grass (Paspalum notatum) represents a major cause of type I
allergy in diverse geographical areas, particularly in the southeastern coastal
plain area of the United States. The aqueous protein extract of Bahia grass
pollen contains the allergenically active components that produce
skin-test-positive reactions in sensitive patients. OBJECTIVE: The emphasis of
this study included the identification and characterization of the allergenic
proteins present in the crude protein aqueous extract of Bahia grass pollen.
METHODS: The crude extract of Bahia grass pollen, partially purified by
isoelectric focusing and fractionated by sodium dodecyl sulfate-polyacrylamide
gel electrophoresis (SDS-PAGE), was electroblotted onto nitrocellulose
membranes, probed with sera from patients skin test positive to Bahia grass and
detected using anti-human IgE conjugated peroxidase. RESULTS: Four allergenic
proteins of Bahia grass pollen with estimated molecular weights of 45, 33, 31
and 28 kD were identified and characterized. Following treatments with
deglycosylation enzymes, the 4 allergens retained their antigenic reactivity
with Bahia-grass-allergic patient sera containing polyclonal IgE antibodies.
CONCLUSION: The crude extract of Bahia grass pollen contains many proteins but
only 4 have allergenic reactivity. Following deglycosylation treatment, Bahia
grass allergenic proteins have retained their antigenic reactivity with Bahia-grass-allergic
patient sera containing polyclonal IgE antibodies. Four proteins reactive with
IgE were detected, but the 33-kD protein (pI of 6.59) was the most reactive.
Copyright 2002 S. Karger AG, Basel
5899.
Graif Y, Yigla M, Tov N, Kramer MR.
Value of a negative aeroallergen skin-prick test result in the diagnosis
of asthma in young adults: correlative study with methacholine challenge
testing. Chest. 2002 Sep;122(3):821-5.
BACKGROUND:
None of the existing tests for the diagnosis of asthma are considered to be
definitive. Certain circumstances require prompt diagnosis, and a test able to
predict the absence of asthma would be very useful. OBJECTIVE: To evaluate the
contribution of a skin-prick test (SPT) to the diagnostic workup of subjects
with suspected asthma. PATIENTS AND METHODS: The study included three groups of
subjects aged 18 to 24 years: group A, asthmatic patients (n = 175); group B,
control subjects (n = 100); and group C, subjects with suspected asthma (n =
150) with normal spirometry findings and a negative exercise challenge test
result. All underwent an SPT to a battery of common aeroallergens, and group C
underwent a methacholine challenge test (MCT) in addition. The sensitivity,
specificity,
positive predictive value, and negative predictive values (NPV) of the SPT were
calculated using provocative concentrations of methacholine causing a 20% fall
in FEV(1) (PC(20)) of < 4 mg/mL and < 8 mg/mL as diagnostic cutoff values
for asthma in the MCT. Bayes' formula was used to determine posttest
probabilities of having asthma, both for positive and negative SPT results.
RESULTS: A positive SPT result to at least one allergen was found in 95.5%, 54%,
and 69% of patients in the three groups, respectively. The sensitivity,
specificity, and NPV of the SPT were 90.7%, 52.0%, and 84.8%, respectively, with
a cutoff value of PC(20) < 8 mg/mL. The lower cutoff, PC(20) < 4 mg/mL,
increased the sensitivity and NPV to 98.2% and 97.8%, respectively. A negative
SPT result decreased the probability of having asthma by 10-fold to 20-fold in
subjects whose pretest probability was low to moderate. CONCLUSIONS:
Incorporating an SPT into the workup of subjects with suspected asthma can
reduce the cost of this process significantly. The SPT may be used as a simple,
fast, safe, inexpensive, and reliable method to predict the absence of asthma in
young adults.
5900.
Hallstrand TS, Curtis JR, Koepsell TD, Martin DP, Schoene RB, Sullivan
SD, Yorioka GN, Aitken ML. Effectiveness
of screening examinations to detect unrecognized exercise-induced
bronchoconstriction. J Pediatr. 2002 Sep;141(3):343-8.
OBJECTIVE:
To determine if a physician-administered physical examination and screening
questionnaire accurately detects exercise-induced bronchoconstriction (EIB) in
adolescent athletes.Study design: Cross-sectional study of 256 adolescents
participating in organized sports from 3 suburban high schools. The number of
persons screened positive for EIB by physical examination and questionnaire was
compared with the number of persons with EIB diagnosed by a "gold
standard" test that consisted of a 7-minute exercise challenge followed by
serial spirometry. RESULTS: We diagnosed EIB in 9.4% of adolescent athletes. The
screening history identified persons with symptoms or a previous diagnosis
suggestive of EIB in 39.5% of the participants, but only 12.9% of these persons
actually had EIB. Among adolescents with a negative review of symptoms of asthma
or EIB, 7.8% had EIB. Among adolescents with no previous diagnosis of asthma,
allergic rhinitis, or EIB, 7.2% had EIB diagnosed by exercise challenge. Persons
who screened negative on all questions about symptoms or history of asthma, EIB,
and allergic rhinitis accounted for 45.8% of the adolescents with EIB.
CONCLUSIONS: EIB occurs frequently in adolescent athletes, and screening by
physical examination and medical history does not accurately detect it.
5901.
Hamilton RG, Peterson EL, Ownby DR.
Clinical and laboratory-based methods in the diagnosis of natural rubber
latex allergy. J Allergy Clin Immunol. 2002 Aug;110(2 Suppl):S47-56. Review.
The
accurate diagnosis of hypersensitivity to natural rubber latex is the initial
step in the effective management of individuals with latex allergy and in
ensuring the quality of epidemiologic studies. The diagnostic algorithm used in
the evaluation of an individual with suspected latex allergy begins with a
comprehensive clinical history during which risk factors (atopy, food allergies,
hand dermatitis) and temporal relationships between symptoms and natural rubber
product exposure are identified. If type IV hypersensitivity is suspected
because of the delayed nature (hours to days) and confinement of symptoms to the
skin-latex product contact areas, patch testing can be conducted to confirm the
presence of activated T cells with specificity for rubber chemicals. If type I
hypersensitivity is suspected because of ocular, upper and lower airway, and/or
systemic symptoms that have rapid onset (minutes) after a definable latex
exposure, a confirmatory skin or blood test for IgE antibody may be conducted to
verify a state of sensitization within the individual. The definitive diagnosis
would then be made only after consideration of the individual's clinical history
and confirmatory in vivo and/or in vitro laboratory test results. If discordance
remains between highly convincing latex-associated symptoms as identified in the
history and repetitively negative confirmatory IgE antibody test results, then
one of several types of in vivo provocation tests may be performed for
adjudication. This overview examines the current state of the art in both in
vivo and in vitro diagnostic methods for latex-specific IgE antibody detection
in skin and blood. The performance, advantages, and limitations of each
diagnostic method are compared.
5902.Hendrick
DJ. Diagnostic tests for
occupational asthma. Am J Respir Crit Care Med. 2002 Aug 15;166(4):436-7.
No abstract.
5903.
Homa DM, Mannino DM, Redd SC. Regional differences in hospitalizations
for asthma in the United States, 1988-1996. J Asthma. 2002 Aug;39(5):449-55.
Hospitalization
rates for asthma are higher in the Northeast United States than in other
regions, despite similar regional prevalence rates. Whether these higher rates
reflect differences in asthma presentation or severity or else general
differences in hospitalizations is unclear. We examined regional differences in
asthma hospitalizations for the United States from 1988 through 1996 using data
from the National Hospital Discharge Survey. We classified asthma
hospitalizations into those in which asthma was either the primary diagnosis or
any listed diagnosis. From 1988 through 1996, the rate of hospitalizations for
asthma as the primary diagnosis, per 10,000 population, increased in the
Northeast, but declined in other regions. By 1996, these rates were 24.5 in the
Northeast, 18.4 in the Midwest, 15.8 in the South, and 14.2 in the West. The
Northeast also had the highest absolute rate and the highest rate of increase
for asthma as any listed diagnosis during the study period. These higher rates
of asthma hospitalizations in the Northeast occurred despite a 9.3% decline in
the age-adjusted rate for all hospitalizations in the region. These results
indicate a greater rate of hospitalization for asthma in the Northeast than in
other regions, suggesting that asthma there may be more severe.
5904.
Jogi R, Bjorksten B, Boman G, Janson C. Serum eosinophil cationic protein
(S-ECP) in a population with low prevalence of atopy. Respir Med. 2002
Jul;96(7):525-9.
The
study is a part of the European Community Respiratory Health Survey. A random
sample (n = 351) of 20-44-year olds and persons of the same age with asthma-like
symptoms or current asthma medication according to a postal questionnaire (n =
95) were studied. Interview was taken, methacholine challenge was done and ECP,
total and specific IgE were measured from serum. The median S-ECP value was 8.0
micrograms/l in the random sample. The geometric mean of S-ECP was higher in
subjects with, than without atopy (10.2 vs 8.9 micrograms/l, P < 0.01) and in
subjects with bronchial hyperresponsiveness (BHR) than in subjects without BHR
(9.9 vs 8.0 micrograms/l, P < 0.01). The levels correlated weakly to forced
expiratory volume in one second (FEV1) (r = 0.13, P < 0.01) and were not
independently correlated with respiratory symptoms, asthma or FEV1 after
adjusting for BHR, IgE, sensitisation and smoking. Our results indicate that the
level of eosinophil activation is low in a population with a low prevalence of
atopy, even when BHR is common.
5905.
Leon AD, Tellez Araiza M, Arellano Garcia J, Martinez-Cordero E.
Interference by rheumatoid factor activity in the detection of antiavian
antibodies in pigeon breeders disease. Clin Exp Med. 2002 Jul;2(2):59-67.
The
assessment of antiavian antibodies is relevant for the study of pigeon
breeder's
disease; nevertheless, different factors may hamper their accurate detection.
The objective of this study was to determine whether an endogenous interfering
effect in pigeon breeder's disease might explain the simultaneous presence of
IgM, IgG, and IgA antiavian antibodies in high titers as assessed by ELISA.
Fifty-nine patients with pigeon breeder's disease, 80 healthy controls, and 47
asymptomatic breeders were studied. To assess possible interfering effects by
endogenous immunoglobulins, serum IgG was separated through protein A-Sepharose
CL-4B chromatography. Antiavian antibodies were measured in whole and separated
samples by ELISA. Since a decline of IgM antiavian antibodies following IgG
removal was consistent with a false-positive effect, the causes were studied.
High values of IgM, IgG, and IgA antiavian antibodies were found in 47.4%
[corrected] of patients with pigeon breeder's disease. An IgM rheumatoid factor
activity against IgG was found through ELISA in sera with false-positive IgM
antiavian antibodies. Rheumatoid factor binding was confirmed by Western blot.
Experimental addition of purified rheumatoid factor to sera with IgG antiavian
antibodies replicated the interfering effect. A control group of rheumatoid
arthritis with high rheumatoid factor values did not show positive antiavian
antibodies tests. No IgG with anti-IgM or anti-IgA activity was found, and the
detection of IgA against IgM and IgG was negative. In conclusion, the study of
antiavian antibodies might be affected by different immunoassay conditions. An
endogenous rheumatoid factor activity produced false-positive IgM results. Other
similar interferences warrant a careful evaluation during the serological
assessment of pigeon breeder's disease.
5906.
Li JT. Allergy testing. Am
Fam Physician. 2002 Aug 15;66(4):621-4. Review.
Percutaneous
and intradermal skin tests and laboratory assays of specific IgE antibodies may
be useful in selected cases of allergy management. Percutaneous testing kits are
available from various manufacturers. A number of common allergens are available
in standardized preparations. Positive and negative skin controls are important
in establishing reliable results. Antihistamine medications can interfere with
skin testing and should be stopped beforehand. Serious reactions to skin testing
are rare. Establishing the sensitivity and specificity of percutaneous testing
is difficult because there is no widely accepted gold standard for defining a
true allergic reaction. Intradermal testing is more sensitive than percutaneous
methods but much less specific. Its use is restricted to testing for allergy to
insect stings or penicillin. In cases where skin testing is not available or
desirable, laboratory assays for IgE antibodies to specific allergens may be
used. These assays are generally less sensitive than skin testing methods.
Selected patients with allergic rhinitis or asthma that is not controlled with
standard therapy may benefit from allergy testing, especially when it can target
allergen avoidance measures or guide immunotherapy.
5907.
Niggemann B, Ziegert M, Reibel S. Importance of chamber size for the
outcome of atopy patch testing in children with atopic dermatitis and food
allergy. J Allergy Clin Immunol. 2002 Sep;110(3):515-6.
Because
the small backs of young children offer little space for atopy patch testing, it
would be helpful to use smaller chambers. We therefore compared 6-mm chambers
with the 12-mm chambers used in previous studies. We performed 55 double-blind,
placebo-controlled food challenges in 30 children (17 boys, 13 girls) aged 3 to
58 months (median, 13 months). Sensitivity, specificity, positive predictive
value, negative predictive value, and efficiency results show that the 12-mm
chamber size yields much better results than the 6-mm chamber size. Therefore,
12-mm cups should be used for atopy patch tests with food, even in infants and
small children.
5908.
Perkins DN, Keith PK. Food- and exercise-induced anaphylaxis: importance
of history in diagnosis. Ann Allergy Asthma Immunol. 2002 Jul;89(1):15-23.
No abstract.
5909.
Seidenari S, Giusti F, Massone F, Mantovani L. Sensitization to disperse
dyes in a patch test population over a five-year period. Am J Contact Dermat.
2002 Sep;13(3):101-7.
BACKGROUND:
In spite of sporadic data pointing at the role of textile dyes as important
contact allergens, only few studies have addressed the issue of the frequency of
sensitization to textile dyes in populations of consecutive patients. OBJECTIVE:
The purpose of this study was to evaluate the prevalence of sensitization to
disperse dyes, to investigate cross reactivity between azo dyes and para-amino
compounds, to describe azo-dye-positive patients, and to study the correlation
between clinical aspects and sensitization to different disperse dyes. METHODS:
From January 1996 to December 2000, 6,478 consecutive patients were tested with
7 textile dyes: Disperse Blue 124, Disperse Blue 106, Disperse Red 1, Disperse
Yellow 3, Disperse Orange 3 (DO3), para-aminoazobenzene (PAAB), and
para-dimethylaminoazobenzene (PDAAB). RESULTS: Of the above, 437 patients were
allergic. The most common sensitizers were Disperse Blue (DB) dyes and Disperse
Orange 3. Both the clinical aspect and the localization of the lesions were
unusual in a fair percentage of cases, especially in DB-positive subjects.
Involvement of skin folds was observed in 27% of disperse dye-positive patients,
mainly comprising DB-sensitive women. Cross-reactivity between azo-dyes and
paraphenylenediamine (PPD) was frequent in DO3-, PAAB-, and PDAAB-positive
subjects, but not in DB-allergic ones. Moreover, cross reactions between DB106
and DB124 were observed in 59% of DB106- and/or DB124-positive patients.
CONCLUSIONS: The frequency of disperse dye allergy is higher than generally
estimated. Further studies, using routine diagnostic testing with disperse dyes,
are needed to investigate whether this increasing trend is present outside of
Europe. Copyright 2002, Elsevier Science (USA). All rights reserved.
5910.
Sterk PJ. Airway hyperresponsiveness: using bronchial challenge tests in
research and management of asthma. J Aerosol Med. 2002 Summer;15(2):123-9.
Review.
Bronchial
challenge tests have been standardized in detail during the past two decades.
They are providing relevant pathophysiological and clinical information about
patients with asthma or chronic obstructive pulmonary disease (COPD), by
allowing the measurement of the degree of airway hyperresponsiveness, which
includes an increased sensitivity as well as increased maximal response to
bronchoconstrictor stimuli. There are various types of challenges, to which the
responses are not interchangeable. Responses to so-called "indirect"
challenges are largely dependent on the state of activation of inflammatory or
resident cells within the airways, and the state of activation can vary rapidly,
either spontaneously or through intervention. Responses to "direct"
challenges are dependent on less variable, rather chronic features of airways
inflammation or remodeling. Bronchoprovocation tests provide integrated
information about
multiple
pathophysiological pathways within the airway. This is in contrast to the
measurements of cells, mediators, or cytokines in biological fluids, which
provide only very specific information on selected inflammatory pathways. It has
recently been shown that the outcome of asthma can substantially be improved
when long-term treatment is not only guided by symptoms and lung function, but
also by the degree of airway hyperresponsiveness to direct stimuli. Taken
together, current data warrant a broader usage of bronchoprovocation tests in
the research as well as clinical management of asthma and COPD. In asthma, it
allows selective, individually targeted therapy of the patient as opposed to the
currently recommended regimens that are (increasingly) unselective in their
approach. The potential benefits of monitoring other phenotypic disease markers
is currently under investigation.
5911.
Tan RA, Spector SL. Exercise-induced asthma: diagnosis and management.
Ann Allergy Asthma Immunol. 2002 Sep;89(3):226-35; quiz 235-7, 297. Review.
OBJECTIVE:
To review the diagnosis and management of exercise-induced asthma (EIA). DATA
SOURCES: Computer-assisted literature searches on MEDLINE for articles,
abstracts, and other relevant data on exercise-induced asthma STUDY SELECTION:
Published articles, abstracts, and conference proceedings were selected.
RESULTS: EIA is seen in 40 to 90% of asthmatic patients. Exercise can be the
sole trigger or be one of multiple triggers of asthma exacerbations. A good
history and physical examination can diagnose most cases of EIA. Spirometry can
confirm the diagnosis. Exercise testing may be necessary in certain cases.
Prevention through both pharmacologic and nonpharmacologic measures is the key
to EIA management. Inhaled beta-agonists remain the medications of choice for
EIA prophylaxis. Inhaled cromolyn and antileukotrienes are alternatives. Good
long-term control of asthma with anti-inflammatory medications such as inhaled
steroids will also decrease the incidence of EIA. CONCLUSIONS: Early diagnosis
and proper preventive and maintenance therapy can reduce episodes of EIA and
enable patients to continue to engage in sports and lead an active life.
5912.
Xu X, Weiss ST. Asthma, rhinitis, and skin test reactivity to
aeroallergens in families of asthmatic subjects in Anqing, China. Am J Respir
Crit Care Med. 2002 Sep 1;166(5):774-5. No
abstract.
Pathogenesis:
5913.
Crane J, Wickens K, Beasley R, Fitzharris P. Asthma and allergy: a
worldwide problem of meanings and management? Allergy. 2002 Aug;57(8):663-72.
Review. No
abstract.
5914.
Fujisawa T, Fujisawa R, Kato Y, Nakayama T, Morita A, Katsumata H,
Nishimori H, Iguchi K, Kamiya H, Gray PW, Chantry D, Suzuki R, Yoshie O.
Presence of high contents of thymus and activation-regulated chemokine in
platelets and elevated plasma levels of thymus and activation-regulated
chemokine and macrophage-derived chemokine in patients with atopic dermatitis. J
Allergy Clin Immunol. 2002 Jul;110(1):139-46.
BACKGROUND:
T(H)2 cells and eosinophils selectively express CC chemokine receptor 4 and
CCR3, respectively, and their chemokine ligands are likely to play important
roles in the pathogenesis of atopic dermatitis (AD). OBJECTIVE: The purpose of
this study was to demonstrate the presence of thymus and activation-regulated
chemokine (TARC) in platelets and its release during clotting and to evaluate
the circulating levels of TARC, macrophage-derived chemokine (MDC), and eotaxin
in control subjects and patients with AD. METHODS: We compared plasma and serum
contents of TARC, MDC, and eotaxin. We measured TARC contents in platelet
lysates. We analyzed the correlation of plasma levels of TARC, MDC, and eotaxin
with various clinicolaboratory parameters in patients with AD. RESULTS: Serum
contents of TARC rapidly increased during clotting, whereas those of MDC and
eotaxin increased only slightly. We demonstrated that platelets contained TARC,
and its levels were dramatically elevated in patients with AD. Platelets also
released TARC on stimulation with thrombin. We therefore evaluated circulating
levels of these chemokines in control subjects and patients with AD by using
plasma samples. Plasma TARC levels were significantly increased in patients with
AD (P <.0001) and showed significant correlations with severity scoring of
atopic dermatitis (SCORAD) index (r = 0.665, P <.00001), serum lactate
dehydrogenese levels (r = 0.696, P =.00001), eosinophil counts (r = 0.381, P
=.007), and platelet counts (r = 0.562, P <.0001). Similarly, plasma MDC
levels were significantly increased in patients with AD (P <.0001) and showed
significant correlations with SCORAD index (r = 0.727, P <.0001), serum
lactate dehydrogenese levels (r = 0.861, P <.0001), eosinophil counts (r =
0.505, P =.005), and platelet counts (r = 0.370, P =.01). On treatment, plasma
TARC and MDC levels were dramatically decreased in accordance with improved
SCORAD scores (P =.0012 and P =.0007, respectively). On the other hand, plasma
eotaxin levels did not show any significant increase or correlation with any of
the clinical parameters in patients with AD. CONCLUSION: Platelets from patients
with AD contain high levels of TARC. Thus platelets might play an important role
in AD pathogenesis by releasing T(H)2-attracting TARC on activation.
Furthermore, circulating levels of TARC and MDC, but not those of eotaxin,
correlate well with the disease activity of AD.
5915.
Hunt LW, Kelkar P, Reed CE, Yunginger JW. Management of occupational
allergy to natural rubber latex in a medical center:
the importance of quantitative latex allergen measurement and objective
follow-up. J Allergy Clin Immunol. 2002 Aug;110(2 Suppl):S96-106. Review.
When
our employees began coming to the Occupational Health Service, Dermatology, and
Allergy Clinics with symptoms of allergy to rubber gloves 12 years ago, the Mayo
Clinic initiated 3 responses. (1) The Allergic Disease Research Laboratory
adapted well-established technology to measure both the IgE antibody specific to
natural rubber allergens, and by use of this IgE antibody, the allergens in
rubber products and in the air of the workplace. (2) The Division of Allergic
Diseases and Internal Medicine reviewed the prevalence and severity of the
problem. (3) The Clinical Practice Committee appointed a multidisciplinary task
force to implement measures to reduce exposure. The 3 sections of this article
describe the Mayo Clinic's experience of successful control of this occupational
health problem. Use of only gloves with low or undetectable allergen content
greatly reduced the concentration of allergen in the work site, reduced the
number of new cases of occupational allergy to rubber, and allowed individuals
with latex allergy to work at their usual jobs.
5916.
Kumagai N, Yamamoto K, Fukuda K, Nakamura Y, Fujitsu Y, Nuno Y, Nishida
T. Active matrix metalloproteinases in the tear fluid of individuals with vernal
keratoconjunctivitis. J Allergy Clin Immunol. 2002 Sep;110(3):489-91.
Corneal
epithelial lesions distinguish vernal keratoconjunctivitis (VKC) from other
ocular allergic diseases. Such lesions result from degradation of the corneal
epithelial basement membrane, which comprises mostly type IV collagen and
laminin. Matrix metalloproteinase 2 (MMP-2) and MMP-9 catalyze the degradation
of these 2 extracellular matrix proteins. The possible role of MMP-2 and MMP-9
in the pathogenesis of corneal lesions associated with VKC was investigated by
assaying tear fluid for the presence of these enzymes. Tear fluid was collected
from 6 eyes of 6 patients with active VKC, 14 eyes of 14 patients with active
allergic conjunctivitis, and 6 eyes of 6 nonallergic healthy volunteers. Gelatin
zymography revealed that the tear fluid of healthy volunteers contained inactive
proforms of both MMP-2 and MMP-9 but not the active forms of these enzymes.
Active forms of MMP-2 or MMP-9 were detected in a minority of patients with
allergic conjunctivitis. However, with the exception of one individual for whom
active MMP-9 was not detected, tear fluid from all patients with VKC contained
both proforms and active forms of MMP-2 and MMP-9. These results implicate MMP-2
and MMP-9 in the pathogenesis of corneal epithelial disorders associated with
VKC.
5917.
Martin S, Weiss JM, Simon JC. Advances in allergy research -- basic and
clinical science make progress. Trends Immunol. 2002 Jul;23(7):329-30.
No abstract.
5918.
Raivio T, Palvimo JJ, Kannisto S, Voutilainen R, Janne OA.
Transactivation assay for determination of glucocorticoid bioactivity in human
serum. J Clin Endocrinol Metab. 2002 Aug;87(8):3740-4.
We
have developed a mammalian cell (COS-1) bioassay, which measures glucocorticoid
bioactivity (GBA) directly from a small amount of human serum. The assay is
based on the expression of human glucocorticoid receptor (GR) together with a
coactivator protein and reporter plasmid containing GR response elements
upstream of the luciferase gene. Ten microliters of human serum, in duplicate,
are added directly to the cell culture medium, and GBA is derived from reporter
gene activity. The assay differentiates between biopotencies of synthetic
steroids, and importantly, mifepristone (RU486) is able to block glucocorticoid-induced
response. The assay is sensitive (<15.6 nM cortisol in fetal calf serum) and
precise, with the within- and between-assay coefficients of variation less than
8% and 10%, respectively. We measured serum GBA (bioassay) and cortisol (RIA)
levels in 34 asthmatic children (age range, 5.7-14.2 yr) at baseline and after
treatment with either inhaled budesonide (800 microg/d, n = 14), fluticasone
propionate (500 microg/d, n = 14), or cromones (control group, n = 6).
Pretreatment serum GBA and cortisol levels correlated strongly (r = 0.90, P <
0.0001, n = 34). Two months of treatment with inhaled budesonide resulted in
excess GBA in circulation, which was not attributable to endogenous cortisol (P
< 0.001). In the fluticasone propionate group, the presence of serum excess
GBA was at the borderline of statistical significance (P < 0.08) after 2
months of inhalation therapy, and no excess GBA was detected in the cromone
group. In conclusion, our bioassay enables measurement of mammalian cell
response to bioactive glucocorticoids in circulation and provides a novel means
to investigate patients receiving drugs acting through the GR.
5919.
Stratakos G, Kalomenidis J, Routsi C, Papiris S, Roussos C. Transient
lactic acidosis as a side effect of inhaled salbutamol. Chest. 2002
Jul;122(1):385-6. No
abstract.
5920.
Toyoda M, Nakamura M, Makino T, Hino T, Kagoura M, Morohashi M. Nerve
growth factor and substance P are useful plasma markers of disease activity in
atopic dermatitis. Br J Dermatol. 2002 Jul;147(1):71-9.
BACKGROUND:
Neurogenic components, such as neurotrophic factors and neuropeptides, are
probably involved in the pathogenesis of atopic dermatitis (AD) via the
neuroimmunocutaneous system. Numerous in vitro and in vivo studies have shown
that nerve growth factor (NGF), the best-characterized member of the
neurotrophin family, modulates the synthesis of the neuropeptide substance P
(SP), both of which may be associated with the pathogenesis of human allergic
diseases. OBJECTIVES: To evaluate the levels of NGF and SP in the plasma of
patients with AD and to examine their possible correlation with disease
activity. METHODS: We measured plasma levels of NGF by an immunoenzymatic assay
and of SP by aradioimmunoassay in 52 patients with AD, and compared them with 35
normal non-atopic controls. The severity of the disease in AD patients was
evaluated using validated clinical scoring systems. RESULTS: Patients with AD
had significant increases in plasma levels of NGF and SP compared with controls
(P < 0.0005 and P < 0.0001, respectively). A positive correlation between
the plasma levels of NGF and SP was found in AD patients (correlation
coefficient, Cc = 0.920, P < 0.0001). There was a significant correlation of
plasma NGF and SP levels with disease activity evaluated using three different
scoring systems: the grading system of Rajka and Langeland (P < 0.001 and P
< 0.01, respectively), the objective Severity Scoring of AD (Cc = 0.656, P
< 0.005 and Cc = 0.752, P < 0.0005, respectively) and the Eczema Area and
Severity Index (Cc = 0.740, P < 0.001 and Cc = 0.765, P < 0.005,
respectively). CONCLUSIONS: These data represent the first reported evidence of
increased plasma levels of NGF and SP in an allergic human skin disease. They
suggest that these neurogenic factors systemically modulate the allergic
response in AD, probably through interactions with cells of the
immune-inflammatory component. In addition, NGF and SP may be useful markers of
disease activity in patients with AD.
5921.
Weisel CP. Assessing exposure to air toxics relative to asthma. Environ
Health Perspect. 2002 Aug;110 Suppl 4:527-37. Review.
Asthma
is a respiratory disease whose prevalence has been increasing since the mid
1970s and that affects more than 14.6 million residents of the United States.
Environmental triggers of asthma include air pollutants that are respiratory
irritants. Air toxics emitted into the ambient air are listed in the 1990 Clean
Air Act Amendments as hazardous air pollutants (HAPs) if they can adversely
affect human health, including the respiratory tract. HAPs include particulate
and gaseous-phase pollutants, individual organic compounds and metals, and
mixtures. Associations between asthma exacerbation and both particles and indoor
volatile organic compounds (VOCs), often referred to as indoor air quality, have
been reported. Studies conducted in the United States, Canada, and Europe over
the past two decades have shown that most people living in the developed
countries spend the majority of their time indoors and that the air
concentrations of many air toxics or HAPs are higher indoors than in the ambient
air in urban, suburban, and rural settings. Elevated indoor air concentrations
result from emissions of air toxics from consumer products, household
furnishings, and personal activities. The Relationship of Indoor, Outdoor and
Personal Air (RIOPA) study was designed to oversample homes in close proximity
to ambient sources, excluding residences where smokers lived, to determine the
contribution of ambient emissions to air toxics exposure. The ratios of indoor
to outdoor air concentrations of some VOCs in homes measured during RIOPA were
much greater than one, and for most other VOCs that had indoor-to-outdoor ratios
close to unity in the majority of homes, elevated ratios were found in the
paired samples with the highest concentration. Thus, although ambient emissions
contribute to exposure of some air toxics indoors as well as outdoors, this was
not true for all of the air toxics and especially for the higher end of
exposures to most volatile organic air toxics examined. It is therefore
critical, when evaluating potential effects of air toxics on asthma or other
adverse health end points, to determine where the exposure occurs and the source
contributions for each air toxic and target population separately and not to
rely solely on ambient air concentration measurements.
5922.
Yang Y, Li L, Wong GW, Krilis SA, Madhusudhan MS, Sali A, Stevens RL.
RasGRP4, a new mast cell-restricted Ras guanine nucleotide-releasing protein
with calcium- and diacylglycerol-binding motifs. Identification of defective
variants of this signaling protein in asthma, mastocytosis, and mast cell
leukemia patients and demonstration of the importance of RasGRP4 in mast cell
development and function. J Biol Chem. 2002 Jul 12;277(28):25756-74.
A
cDNA was isolated from interleukin 3-developed, mouse bone marrow-derived mast
cells (MCs) that contained an insert (designated mRasGRP4) that had not been
identified in any species at the gene, mRNA, or protein level. By using a
homology-based cloning approach, the approximately 2.6-kb hRasGRP4 transcript
was also isolated from the mononuclear progenitors residing in the peripheral
blood of normal individuals. This transcript information was then used to locate
the RasGRP4 gene in the mouse and human genomes, to deduce its exon/intron
organization, and then to identify 10 single nucleotide polymorphisms in the
human gene that result in 5 amino acid differences. The >15-kb hRasGRP4 gene
consists of 18 exons and resides on a region of chromosome 19q13.1 that had not
been sequenced by the Human Genome Project. Human and mouse MCs and their
progenitors selectively express RasGRP4, and this new intracellular protein
contains all of the domains present in the RasGRP family of guanine nucleotide
exchange factors even though it is <50% identical to its closest homolog.
Recombinant RasGRP4 can activate H-Ras in a cation-dependent manner.
Transfection experiments also suggest that RasGRP4 is a diacylglycerol/phorbol
ester receptor. Transcript analysis of an asthma patient, a mastocytosis
patient, and the HMC-1 cell line derived from a MC leukemia patient revealed the
presence of substantial amounts of non-functional forms of hRasGRP4 due to an
inability to remove intron 5 in the precursor transcript. Because only abnormal
forms of hRasGRP4 were identified in the HMC-1 cell line, this immature MC
progenitor was used to address the function of RasGRP4 in MCs. HMC-1 leukemia
cells differentiated and underwent granule maturation when induced to express a
normal form of RasGRP4. Thus, RasGRP4 plays an important role in the final
stages of MC development.
Therapy:
5923.
Heffler LC, Kastman AL, Jacobsson Ekman G, Scheynius A, Fransson J.
Langerhans cells that express matrix metalloproteinase 9 increase in human
dermis during sensitization to diphenylcyclopropenone in patients with alopecia
areata. Br J Dermatol. 2002 Aug;147(2):222-9. No
abstract.
5924.
Murphy LA, Atherton D. A retrospective evaluation of azathioprine in
severe childhood atopic eczema, using thiopurine methyltransferase levels to
exclude patients at high risk of myelosuppression. Br J Dermatol. 2002
Aug;147(2):308-15. No abstract.
April 2003
6448.
Abraham D, Saltoun CA. Facial swelling
and eosinophilia in a 44-year-old woman. Ann Allergy Asthma Immunol. 2002
Dec;89(6):561-5. No abstract.
6449.
Ahlstedt S, Holmquist I, Kober A, Perborn H. Accuracy of specific IgE
antibody assays for diagnosis of cow's milk allergy. Ann Allergy Asthma Immunol.
2002 Dec;89(6 Suppl 1):21-5.
OBJECTIVE:
The primary objective of this report was to discuss the accuracy of specific
immunoglobulin (Ig)E antibody determinations in the diagnosis and prognosis of
reactions to allergens, especially cow's milk, in the context of other relevant
clinical information. DATA SOURCES: A review was undertaken of the relevant
literature on IgE antibody assays in conjunction with some unpublished
information from the authors' investigations. STUDY SELECTION: The pertinent
data for this article were selected on the basis of the expert opinion of the
authors. RESULTS: IgE antibody formation and allergy commence early in life,
which can be reflected by specific IgE antibody determinations in serum samples
with use of particular systems developed for commercial use. After the first
such system was introduced in 1974, development of the technology has ensued.
Some systems using excess of allergen extracts of good quality have proven to
yield highly accurate results over time. Assays that detect all antibodies
present in the serum sample and that demonstrate parallelism between dilutions
of specific IgE antibodies and total IgE concentration allow quantitative
determinations of specific IgE antibodies. Such specific IgE antibody data can
be used not only for a dichotomized evaluation of the presence or absence of
sensitization in an individual patient, but also for an evaluation of the
relative risk for a clinical reaction to an allergen such as cow's milk.Thus,
the specific IgE antibody information can be used in the diagnosis, prediction
of the course, and followup management of allergic disease, particularly when
sensitization to multiple allergens is present. CONCLUSIONS: Specific IgE
antibodies can be accurately determined with certain technologic systems. Such
determinations provide information, not available by other means, for the
diagnosis, prognosis, and followup of patients with allergy-like symptoms.
6450.
Anderson SD, Brannan JD, Chan HK. Use of aerosols for bronchial
provocation testing in the laboratory: where we have been and where we are
going. J Aerosol Med. 2002 Fall;15(3):313-24. Review.
Bronchial
provocation testing with pharmacological agents that act directly on airway
smooth muscle has important limitations. These include the inability to identify
exercise-induced asthma (EIA), to differentiate the airway hyperresponsiveness (AHR)
of airway remodelling from the AHR of active inflammation and to differentiate
between doses of steroids. Recent studies show that tests that act indirectly to
narrow airways are more sensitive than pharmacological agents for identifying
airway inflammation and response to treatment. Adenosine monophosphate (AMP) is
an indirect challenge that acts on mast cells to cause release of mediators.
Hypertonic saline is another and, since its development in the 1980s, has become
widely used in Australia. Hypertonic (4.5%) saline is used to identify those
with active asthma, those with EIA and those who wish to enter certain
occupations or sports (e.g., diving). The recent development, again in
Australia, of a test that uses dry powder mannitol has promise for use in the
laboratory, the office, or for testing in the field. AHR to mannitol identifies
people with EIA and is an estimate of its severity. The mannitol response is
modified by drugs used to prevent EIA, implying that similar mediators are
involved. A mannitol test can be used to monitor response to steroids and is
more sensitive than histamine for identifying persistent airway
hyperresponsiveness in asthmatics well controlled on steroids. These findings
suggest that indirect challenges give more useful clinical information about
currently active asthma and the response to treatment than direct challenge and they
will become more widely used.
6451.
Bag R, Bandi V, Fromm RE Jr, Guntupalli KK. The effect of heliox-driven
bronchodilator aerosol therapy on pulmonary function tests in patients with
asthma. J Asthma. 2002 Oct;39(7):659-65.
To
compare the effects of heliox-driven (He 80:O2 20) to air-driven (N 79:O2 21)
beta2-agonist aerosol therapy on pulmonary function tests (PFTs) in patients
with asthma, a prospective randomized crossover study was undertaken in the
asthma clinic of the university-affiliated county hospital in Houston, TX.
Thirty-one patients (22 female, age range 18-44) with clinically stable asthma
consented. All patients were studied on two different days with both heliox and
air as driving gas, therefore serving as their own controls. The PFTs including
forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), maximal
mid-expiratory flow rate (FEF(25-75)), and maximal expiratory flow rate (FEFmax)
were obtained while breathing ambient air at baseline and 30 min after the
bronchodilator treatment. Albuterol sulfate 2.5 mg was nebulized with either
heliox or compressed air at 8 L/min for 8 min. When heliox was used as driving
agent, additional heliox was delivered via a closed system and no entrainment of
external air was allowed. Primary outcome measure was absolute change in FEV1
(deltaFEV1). There were no statistically significant differences in baseline
PFTs on the two days of the study. All patients had good bronchodilator response
(> or = 12% improvement in FEV1) with either driving gas. The deltaFEV1 after
heliox-driven bronchodilator (HDBD) and air-driven bronchodilator (ADBD) were
0.68+/-0.38 L/sec (CI: 0.54-0.82) vs. 0.51+/-0.26 L/sec (CI: 0.42-0.60),
respectively (p=0.004). The deltaFEV1 with HDBD was 49+/-90% (range -36% to
433%) more than ADBD. A subgroup analysis showed this was largely due to better
response rates in patients with moderate to severe obstruction. There was more
improvement in both FVC and FEFmax with HDBD than ADBD (p<0.05). The changes
in FEF (25-75) were similar. We conclude that HDBD therapy improves FEV1, FVC,
and FEFmax significantly more than ADBD in patients with asthma. Further large
randomized studies are needed to better characterize responders and the impact
on clinical outcomes.
6452.
Bahna SL. Cow's milk allergy versus cow milk intolerance. Ann Allergy
Asthma Immunol. 2002 Dec;89(6 Suppl 1):56-60. Review.
BACKGROUND:
Although cow's milk allergy (CMA) and cow's milk intolerance (CMI) are two
different terms, they are often used interchangeably, resulting in confusion
both in clinical practice and in research reports. OBJECTIVE: To promote the
appropriate differential use of the terms CMA and CMI. METHODS: Highlighting the
differences in clinical and laboratory findings between CMA and CMI. Information
was derived from reviewing the literature on these two topics, supplemented by
the clinical experience of the author. RESULTS: CMA is an immunologically
mediated reaction to cow's milk proteins that may involve the gastro-intestinal
tract, skin, respiratory tract, or multiple systems, ie, systemic anaphylaxis.
Its prevalence in the general population is probably 1 to 3%, being highest in
infants and lowest in adults. Even though it can cause severe morbidity and even
fatality, dietary elimination is associated with good prognosis. However, CMI
should refer to nonimmunologic reactions to cow's milk (CM), such as disorders
of digestion, absorption, or metabolism of certain CM components. The most
common cause of CMI is lactase deficiency, which is mostly acquired during late
childhood or adulthood. It has high racial predilection, being highest in
dark-skinned populations and lowest in northern Europeans. Lactose intolerance
is generally a benign condition, with symptoms limited to the gastro-intestinal
tract, yet the primary acquired type lasts for a lifetime.Symptoms can be well
ameliorated by reducing the intake of CM or using lactose-hydrolyzing agents.
CONCLUSIONS: Adverse reactions to CM should be differentiated into immunologic
(CMA) and nonimmunologic (CMI). The latter is still a general term that
comprises several conditions and requires further differentiation.
6453.
Bernsen RM, van der Wouden JC. Does the sibling effect have its origin in
utero? Investigating birth order, cord blood immunoglobulin E concentration, and
allergic sensitization at age 4 years. Am J Epidemiol. 2002 Nov 1;156(9):882. No
abstract.
6454.
Blaisdell CJ, Weiss SR, Kimes DS, Levine ER, Myers M, Timmins S,
Bollinger ME. Using seasonal
variations in asthma hospitalizations in children to predict hospitalization
frequency. J Asthma. 2002 Oct;39(7):567-75.
Asthma
hospitalization rates have increased in the United States since 1980. The
exposure risk of many environmental factors, which contribute to respiratory
disease, vary throughout the year. The objective of this study was to
investigate the seasonal variation of pediatric asthma hospitalizations and
predict hospitalization frequency. This was a longitudinal analysis of all
pediatric asthma hospitalizations in the state of Maryland by age, gender, race,
and residence using non-confidential discharge data sets from 1986 to 1999. Of
the 631,422 pediatric hospitalizations in the state of Maryland during the years
1986-1999, 45,924 (7%) had a primary admission diagnosis of asthma. Frequency of
hospitalization for asthma was lowest in the summer in all age groups, and
highest in the fall. Seasonal variation in severe asthma episodes was least
striking in children aged 15-18. This was in contrast to non-asthma admissions,
which were highest in winter in preschool children, but relatively flat in
school- and teenaged children. Using neural network modeling, weekly asthma
hospitalizations could be predicted with an R2 between 0.71 and 0.8. Temporal
trends in asthma hospitalizations were seen in each age group, gender, race, and
location. The seasonal variability in asthma hospitalizations suggests that
acute asthma is influenced by variables beyond socioeconomic factors and
adherence to medical regimens. Strategies to combat exacerbations of asthma
should take into consideration seasonal effects on a population. In addition,
temporal trends examined over many years can be used to predict frequency of
severe asthma episodes in a population.
6455.
Budde IK, Lopuhaa CE, de Heer PG, Langdon JM, MacDonald SM, van der Zee
JS, Aalberse RC. Lack of
correlation between bronchial late allergic reaction to Dermatophagoides
pteronyssinus and in vitro immunoglobulin E reactivity to histamine-releasing
factor derived from mononuclear cells. Ann Allergy Asthma Immunol. 2002
Dec;89(6):606-12.
BACKGROUND:
Activity of immunoglobulin (Ig)E-dependent histamine-releasing factor (HRF) is
dependent on the IgE molecules bound to the surface of basophils. Sera capable
of passively sensitizing basophils to release histamine to HRF were designated
IgE+ sera. IgE+ and HRF have been suggested to play a role in late allergic
reaction (LAR). OBJECTIVE: The working hypothesis was tested that IgE+ induces a
LAR. Further, activity of HRF produced by mononuclear cells (HRF(mn)) was
compared with that of recombinant HRF p23. METHODS: Atopic patients (n = 82)
were bronchially provoked with Dermatophagoides pteronyssinus extract and the
change in forced expiratory volume in 1 second was monitored. A LAR was defined
as forced expiratory volume in 1 second as percentage of baseline < 80% 4 to
10 hours after allergen challenge. The presence of HRF-responsive IgE in serum
was determined using basophils sensitized in vitro by serum. RESULTS: The
presence of HRF(mn)-responsive IgE (IgE(mn+)) in serum was shown not be
essential for a LAR: 63% of the patients with a LAR had no IgE(mn+) in their
serum. Further, 71% of patients with IgE(mn+) did not have a LAR. HRF(mn) and
recombinant HRF p23 were not equivalent in the bioassay: serum of 38 of 82
atopic patients sensitized basophils to release histamine to HRF(mn), whereas
this was found with serum of 1 of 82 patients to HRF p23. CONCLUSIONS: The
results do not support the hypothesis that IgE(mn+) induces a LAR, but do not
exclude the alternative hypothesis that HRFs are released during a LAR and
contribute to asthma severity. PMID: 12487227 [PubMed - indexed for MEDLINE]
6456.
Burgdorff T, Venemalm L, Vogt T, Landthaler M, Stolz W. IgE-mediated
anaphylactic reaction induced by succinate ester of methylprednisolone. Ann
Allergy Asthma Immunol. 2002 Oct;89(4):425-8.
BACKGROUND:
In systemic administration the prevalence of anaphylactic reactions attributable
to corticosteroids is approximately 0.3%. Positive prick tests with different
corticosteroids have been reported suggesting an immunoglobulin (Ig)E-mediated
mechanism. OBJECTIVE: A 42-year-old man with multiple sclerosis developed flush,
erythema, and itching a few minutes after the begin of an intravenous infusion
of methylprednisolone-21-sodium succinate. DIAGNOSTIC AND RESULTS: Prick tests
were found to be positive with methylprednisolone-21-sodium succinate and
prednisolone-21-sodium succinate, whereas prick tests with prednisolone without
ester and betamethasone-21-dihydrogen phosphate showed negative results. Oral
challenge with prednisolone without ester and intravenous challenge with
betamethasone-21-dihydrogen phosphate were well tolerated. Specific IgE-antibodies
against methylprednisolone-21-sodium succinate were found in the serum of the
patient. Because of the positive prick test and specific IgE antibodies against
methylprednisolone-21-sodium succinate, the diagnosis of IgE-mediated
anaphylactic reaction could be proven. Succinate ester was suspected to be
immunogenic, as other corticosteroids without this particular ester or with
other substitutions at the C21 remained negative both in the prick and the
challenge tests. CONCLUSIONS: This patient showed an adverse reaction caused by
methylprednisolone-21-sodium succinate. The uniqueness in this case was the
presence of specific IgE antibodies against this esterified corticosteroid in
the patient's serum proving that this reaction was based upon a true IgE-mediated
mechanism. PMID: 12392389 [PubMed - indexed for MEDLINE]
6457.
Busse PJ, Nowak-Wegrzyn AH, Noone SA, Sampson HA, Sicherer SH. Recurrent
peanut allergy. N Engl J Med. 2002 Nov 7;347(19):1535-6. No abstract.
6458.
Butani L. Corticosteroid-induced hypersensitivity reactions. Ann Allergy
Asthma Immunol. 2002 Nov;89(5):439-45; quiz 445-6, 502. Review.
OBJECTIVE:
To review and present data on the prevalence, clinical manifestations,
diagnostic techniques, and management options in patients with hypersensitivity
reactions to corticosteroid preparations. DATA SOURCES: All English language
articles pertaining to human subjects were reviewed using the Pubmed database
from 1964 to June 2002. Indexing terms used were anaphylaxis OR allergic OR
anaphylactoid OR hypersensitivity AND steroid OR corticosteroid. Further
cross-references were obtained after reviewing articles from the aforementioned
search. STUDY SELECTION: A total of 11,493 articles were identified with the
above search terms. Only those articles, including letters and editorials,
describing systemic reactions to steroids were included in the review. Excluded
from our review were articles dealing with contact dermatitis to topical steroid
preparations. This resulted in a total of 80 articles which were reviewed.
RESULTS: Although rare, steroid-induced hypersensitivity reactions do occur.
They range from minor rashes to the more serious cardiovascular collapse. The
mechanisms of steroid-induced adverse events vary from patient to patient, some
being classic immunoglobulin E-mediated whereas others are pseudoallergic in
nature. Skin testing and provocative challenges offer two ways to diagnose such
reactions. Treatment consists of substituting the steroid with an alternative
preparation, which can be tolerated by the patient. CONCLUSIONS: Although little
is known about the epidemiology of steroid-induced hypersensitivity, because
most data are derived from case reports, it is clear that steroid-induced
hypersensitivity is a heterogeneous entity, with no single uniform mechanism. A
great deal of work still needs to be done so that the pathogenesis of such
adverse events can be clearly determined and effective therapeutic interventions
devised.
6459.
Csoma Z, Kharitonov SA, Balint B, Bush A, Wilson NM, Barnes PJ. Increased
leukotrienes in exhaled breath condensate in childhood asthma. Am J Respir Crit
Care Med. 2002 Nov 15;166(10):1345-9
Cysteinyl
leukotrienes (cys-LTs; LTC4, LTD4, and LTE4) are generated predominantly by mast
cells and eosinophils and induce airway smooth muscle contraction, microvascular
leakage, and mucous hypersecretion whereas leukotriene B4 (LTB4) is a potent
chemoattractant of neutrophils. We measured cys-LTs and LTB4 in exhaled breath
condensate from children aged 7-14 years including healthy nonatopic children (n
= 11) and children with mild intermittent asthma (steroid naive, n = 11), mild
persistent asthma (low-dose inhaled steroid treatment, n = 13), or moderate to
severe persistent asthma (high-dose inhaled steroid treatment, n = 13). Exhaled
LTB4 levels were increased in patients with mild and moderate to severe
persistent asthma compared with patients with mild intermittent asthma (126.0
+/- 8.8 and 131.9 +/- 7.1 versus 52.7 +/- 3.8 pg/ml, p < 0.001 and p <
0.0001) and normal subjects (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 47.9 +/- 4.1
pg/ml, p < 0.0001). Elevated exhaled cys-LT levels were found in patients
with mild and moderate to severe persistent asthma compared with normal subjects
(27.9 +/- 2.8 and 31.5 +/- 4.5 versus 18.5 +/- 0.5 pg/ml, p < 0.01 and p <
0.05). There was an inverse correlation between exhaled cys-LTs and LTB4 in
patients with mild persistent asthma. We conclude that exhaled cys-LTs and LTB4
may be noninvasive markers of airway inflammation in pediatric asthma.
6460.
Deramo M. Food challenges vs. skin antigen testing. Am Fam Physician.
2002 Dec 1;66(11):2048. No abstract.
6461.
Desai PR, Babu M. Scimitar syndrome as a differential diagnosis in a
child with recurrent wheeze. Arch Dis Child. 2002 Oct;87(4):357. No abstract.
6462.
Diaz-Perales A, Tabar AI, Sanchez-Monge R, Garcia BE, Gomez B, Barber D,
Salcedo G. Characterization of
asparagus allergens: a relevant role of lipid transfer proteins. J Allergy Clin
Immunol. 2002 Nov;110(5):790-6.
BACKGROUND:
No asparagus allergen has been characterized to date. Lipid transfer proteins (LTPs)
have an ubiquitous distribution in plant foods and have been identified as
relevant allergens in some fruits, seeds, and pollens. OBJECTIVE: We sought to
identify asparagus allergens and to evaluate the potential involvement of the
panallergen LTP family in asparagus allergy. METHODS: Eighteen patients with
asthma, anaphylaxis, and/or contact urticaria after asparagus ingestion or
exposure and positive skin prick test (SPT) responses and serum-specific IgE
levels to asparagus were selected. Two LTPs were isolated from crude asparagus
extract by using chromatographic methods and characterized by means of
N-terminal amino acid sequencing. Both isolated proteins were tested by means of
immunodetection, CAP inhibition assays, and SPTs. Additional aspara gus
allergens were located by using immunodetection with a pool of sera from
patients allergic to asparagus and with rabbit polyclonal antibodies to
sunflower pollen profilin and anti-complex asparagine-linked glycans antibodies.
RESULTS: The purified LTPs showed an N-terminal amino acid sequence similar to
that of Pru p 3 and a strong reaction to anti-Pru p 3 antibodies. Each isolated
protein reached inhibition values of up to 60% in CAP inhibition assays against
asparagus extracts and elicited positive SPT responses in 9 of 18 patients with
asparagus allergy. Immunodetection assays allowed us to identify profilin and
cross-reacting carbohydrate determinants as asparagus IgE-binding components.
CONCLUSION: Asparagus LTPs are relevant allergens. In addition, profilin and
glycoproteins harboring complex asparagine-linked glycans can also be involved
in asparagus allergy.
6463.
Eishi K, Lee JB, Bae SJ, Takenaka M, Katayama I. Impaired sweating
function in adult atopic dermatitis: results of the quantitative sudomotor axon
reflex test. Br J Dermatol. 2002 Oct;147(4):683-8.
BACKGROUND:
Impaired sweating is thought to be a cause of barrier dysfunction in atopic
dermatitis (AD). OBJECTIVES: To examine the sweating function in AD in a
quantitative manner. METHODS: We investigated the sweating response of lesional
and non-lesional skin of adult patients with AD by a quantitative sudomotor axon
reflex test in which the axon reflex is stimulated by acetylcholine
iontophoresis. Sweat volume on the volar aspect of the forearm was measured in
18 adult patients with AD and in 40 non-atopic controls; five patients with
Sjogren's syndrome were also studied as disease comparators. We also evaluated
the sweating function in four AD patients after topical corticosteroid therapy.
Latency time, direct (DIR) sweat volume and axon reflex-mediated indirect (AXR)
sweat volumes were the variables studied. RESULTS: The latency time in AD
patients was significantly prolonged and AXR sweat volume significantly reduced
compared with those in non-atopic control subjects. The latency time and AXR
sweat volume of lesional AD skin were significantly more prolonged and reduced,
respectively, than those of non-lesional skin. In contrast, the DIR sweat volume
of lesional or non-lesional AD skin induced by direct stimulation with
acetylcholine was only slightly reduced when compared with that in non-atopic
controls. Latency time and sweat volumes of lesional and non-lesional AD skin
improved after topical corticosteroid therapy. CONCLUSIONS: These results
suggest that the impaired sweat response in AD is attributable to an abnormal
sudomotor axon reflex, which is reversed by topical corticosteroid
administration.
6464.
El-Asrar AM, Al-Kharashi SA. Full panretinal photocoagulation and early
vitrectomy improve prognosis of retinal vasculitis associated with
tuberculoprotein hypersensitivity (Eales' disease). Br J Ophthalmol. 2002
Nov;86(11):1248-51.
BACKGROUND/AIMS:
Eales' disease is an uncommon vasoproliferative retinal disease affecting
otherwise healthy young men that is characterised by obliterative retinal
periphlebitis, with sequelae such as recurrent vitreous haemorrhage and traction
retinal detachment. This study was undertaken to determine whether visual
prognosis of Eales' disease could be improved by appropriate medical and
surgical treatment. METHODS: The authors retrospectively studied 30 patients (46
eyes) who were treated from 1992 to 2001. Recorded data included patient age,
sex, race, medical history, medications, results of the ophthalmological
examination, results of diagnostic laboratory evaluation, and details of
systemic and surgical treatments. The mean follow up was 10.6 months. RESULTS:
19 patients (23 eyes) who presented with active periphlebitis received systemic
steroids and antituberculous therapy. Extensive full panretinal photocoagulation
was performed in 21 eyes that presented with new vessel formation and peripheral
capillary closure with or without vitreous haemorrhage. Vitrectomy and endolaser
panretinal photocoagulation was necessary in 15 eyes, for severe non-clearing
vitreous haemorrhage in 11 eyes and vitreous haemorrhage with traction retinal
detachment in four eyes. Complete regression of the disease was achieved in all
eyes. Vitrectomy resulted in a significant visual improvement with 14 of the 15
eyes (93.3%) achieving > or =20/200 visual acuity. Overall, the distribution
of visual acuities among eyes improved from presentation to final follow up,
with 36.4% of eyes having 20/40 or better acuity at presentation compared with
63.6% of eyes by final follow up. CONCLUSIONS: These results suggest that
aggressive treatment of Eales' disease with systemic steroids and
antituberculous therapy, full panretinal photocoagulation and early vitrectomy,
when necessary, may result in improving the anatomic and visual outcome.
6465.
El-Azhary RA, Yiannias JA. Allergic contact dermatitis to epoxy resin in
immersion oil for light microscopy. J Am Acad Dermatol. 2002 Dec;47(6):954-5.
Allergic
contact dermatitis caused by immersion oil used for microscopy is a recently
recognized phenomenon. We report a case with characteristic findings of
periorbital erythema and edema in a cytogenetics technician. Positive patch test
responses to epoxy resin, epoxy acrylate, and the immersion oil were noted. This
case represents yet another contact allergic reaction, possibly airborne, to
epoxy resin present in immersion oil used for microscopy.
6466.
Fiocchi A, Bouygue GR, Restani P, Bonvini G, Startari R, Terracciano L.
Accuracy of skin prick tests in IgE-mediated adverse reactions to bovine
proteins. Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):26-32. Review.
OBJECTIVES:
To review the recent literature on the diagnostic accuracy of skin prick tests (SPTs)
in pediatric food allergy, focusing on adverse reactions to milk and beef. To
present data about the test performance characteristics of beef extracts used in
SPTs among children with atopic dermatitis (AD) reporting immediate
hypersensitivity to beef. DATA SOURCES: MEDLINE search using the following
algorithm ["skin prick test" AND "food allergy" OR allergen;
1997-2002; English; all children]. Prospective sensitivity study of SPTs in 34
patients. STUDY SELECTION: Thirty-four children with AD (median age 2.29 years)
were consecutively recruited between 1992 and 2000 because of immediate
reactions to beef. On double-blind, placebo-controlled food challenges (entry
criterion), 20 of the patients reacted to beef and 14 did not. Cut-off points
for skin prick test wheal positivity was selected by receiving-operator
characteristic analysis for fresh and commercial beef allergens. Sensitivity and
specificity of skin tests and indices of reproducibility were calculated.
RESULTS: In the literature, the positive predictive accuracies of skin prick
tests vary between 69 and 100% and the negative predictive accuracies between 20
to 86% for cow's milk. In our series, SPTs with commercial beef extracts were
highly diagnostic (100% sensitivity; 10% false positive rate) and SPTs with
fresh beef were highly specific (100%), albeit with a false-positive rate of
21.42%. CONCLUSIONS: From the literature, we conclude that the diagnostic
accuracy of SPTs with milk should be reappraised in the workup of cow's milk
allergy. Carrying out commercial and fresh food SPTs at the same time
substantially reduces costs and diagnostic work. Oral provocation is necessary
in 20.68% of children with AD who have immediate symptoms to beef. Greater
allergen standardization and streamlining of the workup of cow's milk allergy
are desirable future goals.
6467.
Friedmann PS. The pathogenesis of atopic eczema. Hosp Med. 2002
Nov;63(11):653-6.
Atopic
eczema is associated with a genetic predisposition to dysregulation of the
immune system. T lymphocytes differentiate towards the Th2 type with promotion
of immunoglobulin E antibodies. Allergic responses to environmental allergens
develop and microbes, including staphylococci and pityrosporum yeasts, may
contribute to the inflammatory process.
6468.
Fung MA. The clinical and histopathologic spectrum of "dermal
hypersensitivity reactions," a nonspecific histologic diagnosis that is not
very useful in clinical practice, and the concept of a "dermal
hypersensitivity reaction pattern". J Am Acad Dermatol. 2002
Dec;47(6):898-907.
BACKGROUND:
"Dermal hypersensitivity reaction" (DHR) is diagnosed by
dermatopathologists but is not an accepted clinical disease entity. There are no
clear guidelines for its diagnosis, differential diagnosis, or management.
OBJECTIVES:
The objectives were to define the histologic criteria for cases histologically
diagnosed as DHR and identify corresponding clinical disorders. METHODS: Skin
biopsy specimens from 130 patients diagnosed as "consistent with DHR"
were reviewed. Additional information was obtained from patients, their
dermatologists, and medical records. RESULTS: Follow-up in 74 of 110 patients
(median, 26.6 mo) revealed, most commonly, diagnoses of urticaria, drug
reactions, and spongiotic (eczematous) dermatitis. Among the remaining cases, 37
of 59 reported persistence of disease, some exhibiting a uniform phenotype
characterized by excoriated, edematous papules on the trunk. Histopathologic
features present in more than 90% of 143 biopsy specimens included superficial
and mid-perivascular lymphocytic infiltrates with eosinophils. CONCLUSION: DHR
is a perivascular lymphocytic dermatitis with eosinophils involving the
papillary and upper reticular dermis and minimal, if any, primary epidermal
alteration. The term DHR does not represent any known clinical disorder; rather,
it corresponds to many clinical disorders. The use of the phrase "dermal
hypersensitivity reaction pattern" may be helpful in conveying the idea
that a particular histologic pattern may be seen in a number of clinical
disorders.
6469.
Gavrovic-Jankulovic M, cIrkovic T, Vuckovic O, Atanaskovic-Markovic M,
Petersen A, Gojgic G, Burazer L, Jankov RM. Isolation and biochemical
characterization of a thaumatin-like kiwi allergen. J Allergy Clin Immunol. 2002
Nov;110(5):805-10.
BACKGROUND:
Kiwi fruit allergy, as well as its association with hypersensitivity to other
foods and to pollen, has been extensively reported in the last few years.
Several IgE-binding components have been detected in kiwi extract, but only one
30- kd allergen has been isolated; it was identified as actinidin (Act
c 1). Recently, we have reported a 24-kd kiwi protein to be a potential
major allergen in a group of patients with oral allergy syndrome (OAS).
OBJECTIVE:
The aim of this study was to purify and characterize the 24-kd kiwi allergen
biochemically. METHODS: Seven polysensitized patients with OAS to kiwi were used
in this study. The kiwi allergen was isolated by using a combination of gel
permeation, ion exchange, and immobilized metal ion affinity chromatography. Its
biochemical characterization included determination of its isoelectric point,
molecular weight, N-terminal sequencing, concanavalin A -binding ability,
digestibility in simulated gastric fluid, and antifungal activity. Western
blotting, 2-dimensional PAGE immunoblotting, and skin prick tests were performed
to characterize the isolated protein immunochemically. RESULTS: All 7 patients
recognized the isolated 24-kd kiwi protein as an allergen. The isolated protein
consisted of 2 isoforms with isoelectric points of 9.4 and 9.5 migrated as one
protein band of 20 kd after SDS-PAGE under nonreducing conditions or at 24 kd
under reducing conditions. The partial N-terminal sequence revealed that it is a
thaumatin-like protein (TLP) with concanavalin A -binding ability. The protein
showed antifungal activity toward Saccharomyces carlsbergensis, and Candida
albicans. The protein was degraded by the simulated gastric fluid within 1
minute. Both isoforms bound IgE from a pool of sera in a 2-dimensional PAGE
immunoblot. The TLP elicited positive skin prick test responses in 4 (80 %) of 5
patients with OAS. CONCLUSION: This study reported isolation and full
characterization of a new kiwi allergen, TLP (isoelectric points of 9.4 and 9.5
and molecular weight of 24 kd), which belongs to the family of
pathogenesis-related proteins. The isolated protein expressed antifungal
activity toward S carlsbergensis and C albicans.
6470.
Gehring U, Bischof W, Fahlbusch B, Wichmann HE, Heinrich J. House dust
endotoxin and allergic sensitization in children. Am J Respir Crit Care Med.
2002 Oct 1;166(7):939-44.
A
higher exposure to endotoxin was hypothesized to contribute to lower prevalence
of allergic sensitization and hay fever in children growing up on a farm. We
studied the association between house dust endotoxin and allergic sensitization.
We randomly selected 740 children, aged between 5 and 10 years, from a group of
children who participated in two cross-sectional surveys performed in Saxony-Anhalt,
Germany, from 1992 to 1993 and from 1995 to 1996, such that 50% of the children
were atopic or had a diagnosis of asthma. From 1996 to 1998, we collected
living-room floor dust in the homes of 454 of these children (61%). The content
of endotoxin in house dust was quantified using a chromogenic kinetic limulus
amoebocyte lysate test and was related with health outcomes measured in the
preceding cross-sectional surveys. Multiple logistic regression analyses
adjusted for place of residence, sex, age, parental education, parental atopy,
and pet ownership showed a negative association between exposure to endotoxin
and sensitization to one or more allergens (aOR [95% CI] 0.95 [0.83; 1.10]) and
two or more allergens (aOR [95% CI] 0.80 [0.67; 0.97]) using 0.35 kU/L as the
cutoff value for sensitization. The protective effect was strengthened with
increasing degree of sensitization. In conclusion, exposure to higher levels of
house dust endotoxin is associated with lower prevalence of allergic
sensitization in children.
6471.
Gorelick MH, Stevens MW, Schultz TR. Comparability of acute asthma
severity assessments by parents and respiratory therapists. Arch Pediatr Adolesc
Med. 2002 Dec;156(12):1199-202.
OBJECTIVE:
To compare the assessments of parents and respiratory therapists (RTs) of acute
asthma severity in children discharged after emergency department (ED)
treatment. DESIGN: Prospective cohort study. SETTING: Home care visit within 24
hours of discharge from an urban children's hospital ED. PARTICIPANTS: Children
aged 2 to 17 years discharged to home after treatment in the ED (at least 1
inhaled bronchodilator treatment administered) were randomly selected to have a
home care visit. MAIN OUTCOME MEASURES: Registered RTs went to the child's home
and asked the parent questions about his or her perception of the child's
symptoms. The RT performed a clinical assessment including pulse oximetry.
RESULTS: Ninety children were selected for home care, and 51 patients (57%)
successfully completed the home care visit; 48 (53%) underwent a complete
assessment by both raters. There were no differences in demographic features or
ED clinical variables between those successfully contacted and those not
reached. Of those evaluated, 43 parents (84%) reported their child's asthma was
improved, and the rest reported no change. Parents underestimated the degree of
wheezing or work of breathing relative to the RT in 3 of 48 patients (6%), but
only 1 of these was considered substantial (>1 point discrepancy). Findings
were overestimated in 14 (29%) of 48 cases, but only 5 (10%) were substantial.
CONCLUSIONS: Parents and RTs provide comparable assessments of acute asthma
severity in children within 24 hours of discharge from the ED. Clinically
important discrepancies are uncommon, and underestimation of severity by parents
is rare.
6472.
Green RH, Brightling CE, McKenna S, Hargadon B, Parker D, Bradding P,
Wardlaw AJ, Pavord ID. Asthma exacerbations and sputum eosinophil counts: a
randomised controlled trial. Lancet. 2002 Nov 30;360(9347):1715-21.
BACKGROUND:
Treatment decisions in asthma are based on assessments of symptoms
and
simple measures of lung function, which do not relate closely to underlying
eosinophilic airway inflammation. We aimed to assess whether a management
strategy that minimises eosinophilic inflammation reduces asthma exacerbations
compared with a standard management strategy. METHODS: We recruited 74 patients
with moderate to severe asthma from hospital clinics and randomly allocated them
to management either by standard British Thoracic Society asthma guidelines (BTS
management group) or by normalisation of the induced sputum eosinophil count and
reduction of symptoms (sputum management group). We assessed patients nine times
over 12 months. The results were used to manage those in the sputum management
group, but were not disclosed in the BTS group. The primary outcomes were the
number of severe exacerbations and control of eosinophilic inflammation,
measured by induced sputum eosinophil count. Analyses were by intention to
treat. FINDINGS: The sputum eosinophil count was 63% (95% CI 24-100) lower over
12 months in the sputum management group than in the BTS management group
(p=0.002). Patients in the sputum management group had significantly fewer
severe asthma exacerbations than did patients in the BTS management group (35 vs
109; p=0.01) and significantly fewer patients were admitted to hospital with
asthma (one vs six, p=0.047). The average daily dose of inhaled or oral
corticosteroids did not differ between the two groups. INTERPRETATION: A
treatment strategy directed at normalisation of the induced sputum eosinophil
count reduces asthma exacerbations and admissions without the need for
additional anti-inflammatory treatment.
6473.
Greenberger PA. Allergic bronchopulmonary aspergillosis. J Allergy Clin
Immunol. 2002 Nov;110(5):685-92. Review.
Allergic
bronchopulmonary aspergillosis (ABPA) complicates asthma and cystic fibrosis.
The survival factors in Aspergillus fumigatus that support saprophytic growth in
bronchial mucus are not understood. Prednisone remains the most definitive
treatment but need not be administered indefinitely. MHC II -restricted CD4(+)
T( H)2 clones have been derived from patients with ABPA. The total serum IgE
concentration is elevated sharply but is "nonspecific. " IgE serum
isotypic antibodies to A fumigatus are useful in diagnosis; this is in contrast
to the situation for patients with asthma without ABPA. High-resolution computed
tomography of the chest demonstrates multiple areas of bronchiectasis in most
patients with ABPA and is a useful radiologic tool. Some asthma control patients
might have a few bronchiectatic airways, but not to the extent seen in or of the
same character as those in ABPA. This review discusses clinical, radiologic,
investigational, pathogenetic, and treatment issues of ABPA.
6474.
Greenberger PA. Corresponding patterns of rhinitis and asthma during
pregnancy. Ann Allergy Asthma Immunol. 2002 Nov;89(5):437-8. No abstract.
6475.
Grob M, Reindl J, Vieths S, Wuthrich B, Ballmer-Weber BK. Heterogeneity
of banana allergy: characterization of allergens in banana-allergic patients.
Ann Allergy Asthma Immunol. 2002 Nov;89(5):513-6.
BACKGROUND:
Banana is a frequent cause of food allergy, particularly in latex-sensitized
patients.
OBJECTIVE:
The aim of the study was to get insights in immunoglobulin (Ig)E antibody
responses of patients with a history of allergic reaction to banana but not to
latex. METHODS: In four patients who complained about symptoms after banana
consumption, skin prick tests (SPTs) with aeroallergens, latex, banana, avocado,
and kiwi were performed. Total and specific serum IgE to birch pollen, rBet v 1
and rBet v 2, latex, banana, avocado, and kiwi were determined by the CAP method
(Pharmacia Diagnostics, Uppsala, Sweden). Allergens were identified by
immunoblotting with banana extract and recombinant banana profilin. Two patients
underwent double-blind, placebo-controlled food challenges (DBPCFC) with banana.
RESULTS: All patients showed a positive SPT to banana, and three were IgE-CAP
positive (> or = class 2). Two patients were also sensitized (SPT and CAP) to
latex, avocado, kiwi, and birch pollen. In the immunoblot these two patients'
sera reacted to 32- to 34-kDa proteins, which had already been described as
major banana allergens. In both patients banana allergy was confirmed by DBPCFC.
The third patient also had a sensitization to avocado, but not to latex or
pollen. Immunoblot analysis detected a single band at 70 kDa. The fourth patient
was sensitized to birch pollen, rBet v 1 and rBet v 2, but not to latex.
Immunoblot analysis in this patient's serum was positive with recombinant banana
profilin. CONCLUSIONS: The relevance of banana as a source of food allergy was
confirmed in two patients by DBPCFC. In 1 of 2 patients, in whom banana allergy
was not a consequence of latex sensitization, a 70-kDa protein was identified as
a banana allergen, and in the other patient profilin was detected as a putative
cross-reactive allergen.
6476.
Hall SW. Idiopathic environmental intolerances. Minn Med. 2002
Oct;85(10):33-6.
Health
concerns related to the quality of the environment in offices, schools, homes,
and residences have increased dramatically over the past 2 decades. One health
problem frequently confronting medical practitioners and often attributed to
environmental quality problems is idiopathic environmental intolerances (IEI).
Formerly known as multiple chemical sensitivities, IEI is an acquired disorder
characterized by adverse reactions attributed to exposure to a variety of
substances under ordinary conditions. Alleged precipitants include solvents,
pesticides, detergents, dusts, and fragrances. Symptoms include fatigue,
malaise, headache, concentration and memory difficulties, lightheadedness,
cough, hoarseness, and rhinitis without objective physical signs or consistent
laboratory abnormalities. The role of the environment in precipitating these
complaints continues to be controversial, and no intervention or treatment has
thus far been proven to be effective. While not progressive or life threatening,
IEI is often functionally disabling and very distressing to affected
individuals. The investigation of IEI should involve, at a minimum, a clinical
evaluation of the affected person and in most cases an environmental evaluation
as well. IEI should be managed without overutilization of diagnostic tests or
prescription of unnecessary environmental, occupational, or dietary
restrictions.
6477.
Howard TD, Postma DS, Koppelman GA, Koppelman GH, Zheng SL, Wysong AK, Xu
J, Meyers DA, Bleecker ER. Fine
mapping of an IgE-controlling gene on chromosome 2q: Analysis of CTLA4 and CD28.
J Allergy Clin Immunol. 2002 Nov;110(5):743-51.
BACKGROUND: Several genomic regions have been
identified that might contain genes contributing to the development of asthma
and atopy. These include chromosome 2q33, where we have observed evidence for
linkage for variation in total serum IgE levels in a Dutch asthma population.
Two candidate genes, CTLA4 and CD28, important homeostatic regulators of T-cell
activation and subsequent IgE production, map within this candidate region.
OBJECTIVE: We sought to fine-map the chromosome
2q33 region and evaluate CTLA4 and CD28 as candidate genes for the regulation of
total serum IgE levels and related phenotypes. METHODS: The coding regions of
CTLA4 and CD28 were resequenced in 96 individuals; 4 novel SNPs in CTLA4 and 10
in CD28 were identified. Polymorphisms in both genes were analyzed in 200
asthmatic probands and their spouses (n = 201). RESULTS: Subsequent fine-
mapping in this region has resulted in an increased log of the odds (lod) score
(1.96 to 3.16) for total serum IgE levels. For CTLA4, the +49 A/G single
nucleotide polymorphism (SNP) in exon 1 and the 3 ' untranslated region
microsatellite were significantly associated with total serum IgE levels (P
=.0005 and.006, respectively). For the combined +49 A/G and 3 'untranslated
region genotypes, individuals homozygous for the risk allele for both
polymorphisms (AA and 86/86) had the highest total serum IgE values (87.1 IU/mL),
whereas those individuals with the GG and XX/XX genotypes (anything but the
86-bp allele) had the lowest IgE values (29.3 IU/mL). Significant association
was also observed for the CTLA4 -1147 C/T SNP with bronchial hyperresponsiveness
(BHR) and asthma (P =.008 and.012, respectively), but not for allergy-related
phenotypes. Promoter luciferase assays examining the –1147 polymorphism
suggested that the T allele, which was associated with increased BHR
susceptibility, was expressed at half the level of the C allele. Individuals
with the risk genotypes for both BHR (-1147 CT or TT) and elevated IgE levels
(+49 AA) were 4.5 times more likely to have asthma than individuals with both
nonrisk genotypes (P =.0009). No significant associations were observed for SNPs
in CD28. CONCLUSION: These data suggest that the costimulatory pathway,
specifically CTLA4, is important in the development of atopy and asthma.
6478.
Kanazawa H, Hirata K, Yoshikawa J. Involvement of vascular endothelial
growth factor in exercise induced bronchoconstriction in asthmatic patients.
Thorax. 2002 Oct;57(10):885-8.
BACKGROUND:
There is evidence that the bronchial microcirculation has the potential to
contribute to the pathophysiological mechanisms of exercise induced
bronchoconstriction (EIB) in asthmatic subjects. Vascular endothelial growth
factor (VEGF), which is highly expressed in asthmatic airways, increases
vascular permeability. The relationship between VEGF levels in induced sputum
and the severity of EIB in asthmatic subjects was studied. METHODS: The
concentration of VEGF in induced sputum was examined in 23 asthmatic subjects
and 11 normal controls. The asthmatic subjects performed an exercise test and
the % maximal fall in forced expiratory volume in 1 second (FEV(1)) was
measured. Beclomethasone dipropionate (BDP) 400 micro g twice daily was
administered to the asthmatic subjects for 8 weeks and the exercise test and
sputum induction were repeated. RESULTS: The concentration of VEGF in induced
sputum was significantly higher in asthmatic subjects than in normal controls.
There was a significant correlation between the concentration of VEGF and the %
maximal fall in FEV(1) (r=0.826, p=0.0001) and between the concentration of VEGF
and airway vascular permeability index (r=0.621, p=0.0037). After treatment with
inhaled BDP there was a significant decrease in the concentration of VEGF in the
asthmatic subjects (before treatment: 7051 (2361) pg/ml, after treatment: 4498
(2135) pg/ml, p<0.0001). The change in the concentration of VEGF was
significantly correlated with the change in the % maximal fall in FEV(1)
(r=0.463, p=0.031). CONCLUSIONS: Excessive production of VEGF in asthmatic
airways may contribute to the pathogenesis of EIB via increased airway vascular
permeability.
6479.
Kim HK, Shin BK, Cho SJ, Moon JS, Kim MK, Kim CY, Park SH, Kim KT, In KH,
Oh YH, Kang EY, Park SH, Kim I. Transthoracic
fine needle aspiration and core biopsy of pulmonary lesions. A study of 296
patients. Acta Cytol. 2002 Nov-Dec;46(6):1061-8.
OBJECTIVE:
To retrospectively investigate and compare the usefulness of transthoracic fine
needle aspiration (FNA), core biopsy and a combination of the two in the
diagnosis of pulmonary lesions. STUDY DESIGN: Two hundred ninety-six patients
who had undergone FNA, core biopsy or both for lung lesions were divided into
malignant and benign groups according to the final diagnoses, which were based
on the cytologic and histopathologic findings combined with clinical features.
In each group, the diagnostic usefulness of FNA, core biopsy and a combination
of the two were evaluated by comparing the results of each with the final
diagnoses. RESULTS: In the malignant group, FNA was diagnostically helpful in
188 of 205 patients (91.7%) and core biopsy in 158 of 180 patients (87.8%). The
combination of the two methods improved the result to 172 of 178 patients
(96.6%). The sensitivities were 94.6%, 88.3% and 97.2%, respectively, for each
result. In the benign group, 71.1% (64/90), 70.1% (47/67) and 74.2% (49/66) of
cases received specific or nonspecific diagnoses by FNA, core biopsy and their
combination, respectively. The rates of specific diagnoses were 20.1%, 21.0% and
31.8%, respectively. CONCLUSION: The combination of FNA and core biopsy markedly
improved the diagnostic yields in the malignant group and, to a lesser degree,
also in the benign group.
6480.
Kleine-Tebbe J, Vogel L, Crowell DN, Haustein UF, Vieths S. Severe oral
allergy syndrome and anaphylactic reactions caused by a Bet v 1-related PR-10
protein in soybean, SAM22. J Allergy Clin Immunol. 2002 Nov;110(5):797-804.
BACKGROUND: Anaphylactic reactions to soy products
have been attributed to stable class 1 food allergens. OBJECTIVE: IgE- mediated
reactions to a soy-containing dietary food product in patients allergic to birch
pollen were investigated. METHODS: Detailed case histories were taken from 20
patients. Their sera were analyzed for IgE (UniCAP) specific for birch, grass,
mugwort, the recombinant birch allergens rBet v 1 and rBet v2, and soy protein.
Extracts from birch pollen, soy isolate, rBet v 1, and the recombinant PR-10 soy
protein rSAM22 were coupled to paper disks or nitrocellulose for IgE
measurements (enzyme allergosorbent test) or Western blot analysis. Enzyme
allergosorbent testing, Western blot inhibition, and histamine release studies
were performed with the same allergens. RESULTS: Most patients (17/20)
experienced facial, oropharyngeal, and/or systemic allergic symptoms within 20
minutes after ingesting the soy product for the first time. Birch pollen allergy
(16/20) was common, along with oral allergy syndrome to apple (12/20) or
hazelnut (11/20). IgE levels to birch and Bet v 1 but not to other inhalants
were high in 18 of 20 patients. Significant IgE binding to rSAM22 occurred in 17
of 20 patients. Blot experiments with the soy isolate revealed IgE-binding bands
at 17 kd (15/20), 22 kd (1/20), and 35 to 38 kd (2/20); the former was inhibited
by preincubation of the sera with rBet v 1 or rSAM22. Birch extract and soy
isolate, rBet v 1, and rSAM22 induced dose-dependent histamine release in the
nanomolar range. CONCLUSION: Immediate-type allergic symptoms in patients with
birch pollen allergy after ingestion of soy protein-containing food items can
result from cross-reactivity of Bet v 1 -specific IgE to homologous
pathogenesis-related proteins, particularly the PR-10 protein SAM22.
6481.
Kopp MV, Brauburger J, Riedinger F, Beischer D, Ihorst G, Kamin W, Zielen
S, Bez, Friedrichs F, Von Berg A, Gerhold K, Hamelmann E, Hultsch, Kuehr J. The
effect of anti-IgE treatment on in vitro leukotriene release in children with
seasonal allergic rhinitis. J Allergy Clin Immunol. 2002 Nov;110(5):728-35.
BACKGROUND:
Binding of allergens with IgE to the IgE receptors on mast cells and basophils
results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs),
triggering allergic cascades that result in allergic symptoms, such as asthma
and rhinitis. OBJECTIVE: We sought to investigate whether anti-IgE (Oma-lizumab),
a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy
(SIT) affects the leukotriene pathway. METHODS: Ninety-two children (age range,
6-17 years) with sensitization to birch and grass pollens and with seasonal
allergic rhinitis were included in a phase III, placebo- controlled, multicenter
clinical study. All subjects were randomized to one of 4 treatment groups. Two
groups subcutaneously received birch SIT and 2 groups received grass SIT for at
least 14 weeks before the start of the birch pollen season. After 12 weeks of
SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical
efficacy variable was symptom load (ie, the sum of daily symptom severity score
and rescue medication score during pollen season). Blood samples taken at
baseline and at the end of study treatment after the grass pollen season were
used for separation of leukocytes in this substudy. After in vitro stimulation
of the blood cells with grass and birch pollen allergens, SLT release (LTC4,
LTD4, and LTE4) was quantified by using the ELISA technique. RESULTS: Before the
study treatment, SLT release to birch and grass pollen exposure did not differ
significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n =
23), a lower symptom load occurred during the pollen season compared to placebo
+ SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch
SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the
combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT,
resulted in significantly lower SLT release after stimulation with the
corresponding allergen (416 ng/L [5th-95th percentile, 1-1168] and 207 ng/L
[1-860 ng/L], respectively) compared with placebo plus SIT (2490 ng/L [384-6587
ng/L], P =.001; 2489 ng/L [1-5670 ng/L], P =.001). In addition, treatment with
anti-IgE was also followed by significantly lower SLT releases to the allergens
unrelated to SIT (grass SIT 300 ng/L [1-2432 ng/L] in response to birch
allergen; birch SIT: 1478 ng/L [1-4593 ng/L] in response to grass pollen) in
comparison with placebo (grass SIT: 1850 ng/L [1-5499 ng/L], P =.001; birch SIT:
2792 ng/L [154-5839 ng/L], P =.04]. CONCLUSION: Anti-IgE therapy reduces
leukotriene release of peripheral leukocytes stimulated with allergen in
children with allergic rhinitis undergoing allergen immunotherapy independent of
the type of SIT allergen used.
6482.
Krumbiegel P, Denk E, Russow R, Rolle-Kampczyk U, Metzner G, Herbarth O.
(15)N(2)]arginine as a first potential inhaled diagnostic agent to characterize
respiratory diseases. Exp Lung Res. 2002 Oct-Nov;28(7):535-42.
Conventional
diagnosis of the pulmonary tract uses physical methods such as spirometry and
oscillometry. However, the inhalation of a chemical diagnostic agent ought to
provide novel ways of more specific diagnosis, for instance of inflammatory
states of the bronchial and lung mucosa. The stable isotope technique using a
(15)N-labeled substrate appears to be a suitable tool for this application. In a
pilot study, defined amounts of the amino acid L-[guanidino-(15)N(2)]arginine
monohydrochloride (aqueous solution, 20 atom % (15)N) were inhaled as a
diagnostic agent by healthy volunteers and pulmonary patients suffering from
asthma bronchiale. The amino acid is resorbed and partly metabolized to (15)NO.
The exhaled air was collected under defined conditions in 10-L breath bags and
analyzed for NO using chemiluminescence. Under standardized test conditions,
healthy persons (n = 6) exhaled 0.97 +/- 0.08 micromol NO/m(3) and asthmatic
patients (n = 7) 1.17 +/- 0.14 micromol NO/m(3). A better distinction was
expected comparing the (15)NO exhalation. The (15)N abundance of NO was
determined using a Cryotrap gas chromatography - mass spectrometry set-up.
Between 30 and 80 minutes after inhaling 700 mg [(15)N]arginine, a maximum with
a plateau of the (15)NO abundance was found in the exhaled air. At this time,
healthy and asthmatic subjects exhibited clear differences in their exhaled
(15)NO amounts. Under standardized test conditions, the healthy persons (n = 6)
exhaled 102.3 +/- 6.7 nmol (15)NO/m(3), whereas asthmatic patients (n =7)
exhaled only 76.1 +/- 10.9 nmol (15)NO/m(3). It is concluded that (15)NO yielded
after the inhalation of (15)N-labeled arginine could be a potential marker for
demonstrating pathophysiological changes in the lung epithelium. This method
could pave a new diagnostic principle of "inhalative breath test."
6483.
Kukurin GW. Chronic pediatric asthma and chiropractic spinal
manipulation: a prospective clinical series and randomized clinical pilot study.
J Manipulative Physiol Ther. 2002 Oct;25(8):540-1. No abstract.
6484.
Lai DS, Lue KH, Hsieh JC, Lin KL, Lee HS. The comparison of the efficacy
and safety of cetirizine, oxatomide, ketotifen, and a placebo for the treatment
of childhood perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2002
Dec;89(6):589-98.
BACKGROUND:
There has been no study comparing the long-term effects of ketotifen, oxatomide,
and cetirizine for the treatment of perennial allergic rhinitis among children.
OBJECTIVE: We conducted a study to compare the efficacy of the three agents for
the treatment of perennial allergic rhinitis among children. METHODS: The study
consisted of a double-blind, placebo-controlled, randomized design, comprising
69 perennial allergic rhinitis patients with mite allergy, aged 6 to 12 years,
randomly assigned to 1 of 4 test treatment groups for 3 months: 19 in the
cetirizine group (10 mg daily), 18 in the ketotifen group (1 mg, twice daily),
16 in the oxatomide group (1 mg/kg, twice daily), and 16 in the placebo group.
We used the nasal symptom score of diary card and the Pediatric
Rhinoconjunctivitis Quality of Life Questionnaire and eosinophil cation protein
peripheral blood total eosinophil count and immunoglobulin E level, eosinophil
proportion from a nasal smear, and nasal peak expiratory flow rate to evaluate
the effect of the four agents. RESULTS: Cetirizine was significantly more
effective at reducing the mean rhinorrhea score compared with oxatomide for both
weeks 8 and 12 (P < 0.01). Before the end of week 12, cetirizine was
significantly more effective than ketotifen (P < 0.01). Cetirizine and
oxatomide significantly decreased the mean Pediatric Rhinoconjunctivitis Quality
of Life Questionnaire score compared with the placebo for week 12 (P < 0.05).
CONCLUSIONS: Cetirizine was more effective than oxatomide and ketotifen for the
relief of nasal congestion and rhinorrhea, and was responsible for significantly
decreasing the eosinophil representation of a posttreatment nasal smear.
6485.
Lapid-Gortzak R, Rosen S, Weitzman S, Lifshitz T. Videokeratography
findings in children with vernal keratoconjunctivitis versus those of healthy
children. Ophthalmology. 2002 Nov;109(11):2018-23.
PURPOSE:
To determine videokeratographic topography of eyes with vernal
keratoconjunctivitis (VKC) and to assess whether the severity of the VKC is
related to the presence of changes compatible with keratoconus. PARTICIPANTS:
Seventy-six persons aged 6 to 21 years: 40 patients with VKC and 36 healthy
controls. DESIGN: A comparative, observational case series. METHODS: We examined
76 persons, of whom 40 were patients with VKC and 36 were control subjects, and
compared the outcomes of videokeratography (VKG) patterns (EyeSys Laboratories,
Houston, TX), numerical corneal indices, and spherical equivalent refraction.
MAIN OUTCOME MEASURES: Corneal topographic patterns, corneal numeric indices,
and corneal mirror imagery. RESULTS: We found many more abnormal patterns on VKG
among the VKC patients than expected when compared with 'normal' eyes (P = 0.02
for the right eye and P = 0.001 for the left eye). Videokeratography allowed us
to define a subgroup of patients with infraclinical keratoconus. A trend of
superior corneal steepening ('superior keratoconus') was also found.
CONCLUSIONS:
Vernal keratoconjunctivitis patients have more abnormal corneal topographic
patterns than non VKC controls. Videokeratography may help decide how to
follow-up and treat a presumed self-limiting disease.
6486.
Laube BL, Curbow BA, Costello RW, Fitzgerald ST. A pilot study examining
the relationship between stress and serum cortisol concentrations in women with
asthma. Respir Med. 2002 Oct;96(10):823-8.
The
mechanism (s) by which stress exacerbates asthma is unknown. One explanation
could be a reduction in endogenous serum cortisol concentrations as a result of
stress. Our objective was to determine if a reduction in morning serum cortisol
concentrations is associated with higher levels of stress in women with asthma.
In this pilot study, seven women with a history of allergic-asthma were
prospectively assigned to either low, moderate, or high stress groups based on a
combination of their level of current stress and their resources to cope with
the stress. After stress group assignment, women donated a morning blood sample,
which was analyzed for serum cortisol concentration by an independent laboratory
whose personnel were blinded to the subjects' stress status. Three women were
assigned to the low stress group, two to the moderate stress group and two to
the high stress group. Serum cortisol concentrations ranged from 8 to 23 microg/dl,
averaging 14 +/- 6 microg/dl. A Spearman rank correlation indicated that serum
cortisol concentrations were significantly inversely related to the stress
groupings (r(s) = -0.915; P = 0.025). These results suggest that a reduction in
morning serum cortisol concentration may be associated with higher levels of
stress and lower resources to cope with the stress in women with
allergic-asthma.
6487.
Lewith GT, Hyland ME, Shaw S. Do attitudes toward and beliefs about
complementary medicine affect treatment outcomes? Am J Public Health. 2002
Oct;92(10):1604-6. No abstract.
6488.
Litonjua AA, Milton DK, Celedon JC, Ryan L, Weiss ST, Gold DR. A
longitudinal analysis of wheezing in young children: the independent effects of
early life exposure to house dust endotoxin, allergens, and pets. J Allergy Clin
Immunol. 2002 Nov;110(5):736-42.
BACKGROUND:
It has been postulated that exposure to bacterial endotoxins and animals early
in life might confer protection against the development of asthma and allergies.
OBJECTIVE: We investigated the longitudinal effects of exposure to house dust
endotoxin (HDE), allergen levels, and the presence of a dog in the home on
wheezing in young children over a 4-year period. METHODS: Two hundred twenty-six
children younger than 5 years were followed for 4 years. Endotoxin and allergen
levels were measured from house dust collected at baseline. Longitudinal
associations were investigated by using a proportional hazards technique that
allowed for multiple outcomes per subject. RESULTS: Exposure to high
concentrations of HDE of greater than the median level was associated with an
increased risk for wheezing over the period of observation (multivariate
relative risk, 1.52; 95 % CI, 1.07-2.14), but this risk rapidly decreased over
time (P for trend =.005). Exposure to cockroach allergen was associated with
increased risk for wheezing, whereas exposure to cat allergen and the presence
of a dog in the home were both associated with decreased risk for wheezing. The
risks associated with cockroach allergen, cat allergen, and dog did not change
over the period of observation. CONCLUSION: The negative associations between
exposures to dogs and cat allergen and wheeze appear to be independent of the
effects of endotoxin and suggest that separate mechanisms might mediate the
effects of HDE exposure and pet exposure on the developing immune system.
6489.
Mattos W, Lim S, Russell R, Jatakanon A, Chung KF, Barnes PJ. Matrix
metalloproteinase-9 expression in asthma: effect of asthma severity, allergen
challenge, and inhaled corticosteroids. Chest. 2002 Nov;122(5):1543-52.
BACKGROUND:
Asthma is associated with remodeling of the extracellular matrix (ECM) and
increased airway obstruction, and the mechanisms of this process are unknown.
Matrix metalloproteinases (MMPs) are a group of enzymes capable of degrading the
ECM. They are released along with their inhibitors, tissue inhibitor of MMP (TIMP).
STUDY OBJECTIVE:s: To determine whether severe, persistent asthma is associated
with increased levels of MMP-9 in the airway compared with mild asthma, and to
assess the effect of both allergen exposure and steroid treatment on MMP-9 and
TIMP-1 levels. DESIGN: Prospective analysis of levels and activity of MMP-9 and
TIMP-1 in BAL fluid (BALF) and induced sputum obtained from asthmatics of
differing disease severity. In patients with mild asthma, MMP-9 and TIMP-1
levels were studied in induced sputum following allergen challenge and in BALF
after inhaled steroid therapy. PATIENTS: Eighteen patients with mild asthma, 10
patients with severe asthma, and 10 nonsmoking, atopic subjects had their sputum
studied. Fourteen of the patients with mild
asthma
underwent allergen challenge. BAL was collected from 16 patients with mild
asthma before and after 4 weeks treatment with inhaled budesonide, 800 micro g
bid, or placebo. RESULTS: Patients with severe asthma had increased levels and
activity of sputum MMP-9 in their sputum compared with patients with mild asthma
and normal subjects. Allergen challenge increased the MMP-9/TIMP-1 ratio and
MMP-9 activity. Inhaled budesonide had no effect on MMP-9 or TIMP-1 in patients
with mild asthma. CONCLUSIONS: MMP-9 may play a role in chronic airway
inflammation and remodeling in asthma, as concentrations are increased in
severe, persistent asthma and following allergen challenge. Inhaled steroids may
not affect MMP-9 and TIMP in patients with mild asthma, and additional studies
in patients with more severe asthma are needed.
6490.
Maziak W. Does the sibling effect have its origin in utero? Investigating
birth order, cord blood immunoglobulin E concentration, and allergic
sensitization at age 4 years. Am J Epidemiol. 2002 Nov 1;156(9):882;
No abstract.
6491.
McCann WA, Ownby DR. The reproducibility of the allergy skin test scoring
and interpretation by board-certified/board-eligible allergists. Ann Allergy
Asthma Immunol. 2002 Oct;89(4):368-71.
BACKGROUND:
Allergy skin testing is a cornerstone in the evaluation of the allergic patient.
This seemingly simple test is subject to multiple variables that can affect the
result. OBJECTIVE: To evaluate the degree of variability among
board-certified/board-eligible allergists in the scoring and interpretation of
allergen skin tests. MATERIALS AND METHODS: A series of allergen prick skin
tests were digitally photographed and a questionnaire generated. Approximately
70 board-certified/board-eligible allergists were asked to grade each test item
and to interpret them as positive, negative, or indeterminate or if they desired
a followup intradermal test. RESULTS: Thirty-three interpretable responses were
obtained. The majority of respondents (24) used a grading scale of 0 to 4.
Agreement among physicians using a 0 to 4+ scale ranged from a standard
deviation of 0.26 to 1.35, with greatest agreement on items with median/mode
scores of 4+. The largest standard deviations were found on test items with
median/mode scores of 1+ to 2+. Interpretation of the test items also showed
greatest variation for those items with median/mode scores of 1+ to 2+. The
number of intradermal tests requested ranged from 0 to 11 (of 22 test items).
CONCLUSIONS: The results demonstrate interphysician variation in the scoring and
interpretation of epicutaneous skin tests. A questionnaire such as the one used
here may serve a useful quality control instrument to ensure reproducible
scoring of skin tests. In addition, the results highlight the need for greater
study on the clinical utility of intradermal skin testing when epicutaneous
tests are negative or equivocal.
6492.
Morell F, Roger A, Cruz MJ. Usefulness of specific skin tests in the
diagnosis of hypersensitivity pneumonitis. J Allergy Clin Immunol. 2002
Dec;110(6):939. No abstract.
6493.
Naimer SA, Cohen AD, Mumcuoglu KY, Vardy DA. Household papular urticaria.
Isr Med Assoc J. 2002 Nov;4(11 Suppl):911-3.
BACKGROUND:
Papular urticaria often occurs after bites of insects such as mosquitoes,
sandflies, bed bugs and fleas. Multiple bites and local pruritus are
characteristic symptoms. Treatment is usually symptomatic and includes
antihistamines and corticosteroids. The reappearance of the symptoms can be
prevented by successful control of the parasite. OBJECTIVES: To find the
causative agent of papular urticaria in afflicted households with involvement of
numerous family members, all in a narrow geographic area. PATIENTS: We describe
the cases of 20 patients belonging to seven families, who presented to the local
primary clinic, suffering from papular urticaria. RESULTS: The cat flea,
Ctenocephalides felis, was the hematophagous insect responsible for all
infestations. The pruritus and the papular urticaria were treated
symptomatically with calamine lotion, topical corticosteroids or oral
antihistamines. All clinical symptoms disappeared within a few weeks after
effective control of the parasites by spraying and fumigating the infested
locations. CONCLUSIONS: Thorough investigation--including, at times,
environmental inspection--is necessary to reach the rewarding discovery of the
etiology of household papular urticaria. This condition may arise in other
environments of similar character.
6494.
Nakayama K, Shinkawa M, Ohrui T, Hirai H, Sasaki H. Interferon-gamma
responses to mycobacterial antigens in Heaf-positive children. Lancet. 2002 Oct
26;360(9342):1335. No abstract.
6495.
Paredi P, Kharitonov SA, Barnes PJ. Analysis of expired air for oxidation
products. Am J Respir Crit Care Med. 2002 Dec 15;166(12 Pt 2):S31-7. Review.
Chronic
inflammation is a critical feature of chronic obstructive pulmonary disease,
cystic fibrosis, and asthma. This inflammation is associated with the increased
production of reactive oxygen species or oxidative stress in the lungs.
Oxidative stress may have several adverse effects and may amplify the
inflammatory process; however, monitoring oxidative stress is difficult and may
not be reflected by changes in blood markers. We have therefore developed
several noninvasive markers in the exhaled breath that may indicate oxidative
stress in the lungs, and we studied these in relationship to the severity of
chronic inflammatory lung diseases. We analyzed the exhaled breath for the
content of nitric oxide as a marker of inflammation, carbon monoxide as a
marker of oxidative stress, and ethane, which is one of the end products
of lipid peroxidation. In addition, we measured the concentration of markers of
oxidative stress such as isoprostanes in exhaled breath condensate. Our results
confirm that there are increased inflammation, oxidative stress, and lipid
peroxidation in lung disease, as shown by elevated levels of nitric oxide,
carbon monoxide, and ethane, respectively. The finding of lower levels of these
gases in patients on steroid treatment and of higher levels in those with more
severe lung disease, as assessed by lung function tests and clinical symptoms,
reinforces the hypothesis that the noninvasive measurement of exhaled gases
maybe useful in monitoring the underlying pathologic pathways of lung disease.
Longitudinal studies are required to assess the clinical usefulness of these
measurements in the monitoring of chronic inflammatory lung disease.
6496.
Peng Z, Rasic N, Liu Y, Simons FE. Mosquito saliva-specific IgE and IgG
antibodies in 1059 blood donors. J Allergy Clin Immunol. 2002 Nov;110(5):816-7.
No abstract.
6497.
Platts-Mills TA. The future of allergy and clinical immunology lies in
evaluation, treatment, and research on allergic disease. J Allergy Clin Immunol.
2002 Oct;110(4):565-6. Review. No abstract.
6498.
Roller C, Namjou K, Jeffers JD, Camp M, Mock A, McCann PJ, Grego J.
Nitric oxide breath testing by tunable-diode laser absorption spectroscopy:
application in monitoring respiratory inflammation. Appl Opt. 2002 Oct
1;41(28):6018-29.
We
used a high-resolution mid-IR tunable-laser absorption spectroscopy (TLAS)
system with a single IV-VI laser operating near 5.2 microm to measure the level
of exhaled nitric oxide (eNO) in human breath. A method of internal calibration
using simultaneous eNO and exhaled CO2 measurements eliminated the need for
system calibration with gas standards. The results observed from internally
calibrating the instrument for eNO measurements were compared with measurements
of eNO calibrated to gas standards and were found to be similar. Various
parameters of the TLAS system for eNO breath testing were examined and include
gas cell pressure, exhalation time, and ambient NO concentrations. A reduction
in eNO from elevated concentrations (approximately 44 parts in 10(9)) to
near-normal levels (<20 parts in 10(9)) from an asthmatic patient was
observed after the patient had received treatment with an inhaled glucocorticoid
anti-inflammatory medication. Such measurements can help in evaluating airway
inflammation and in monitoring the effectiveness of anti-inflammatory therapies.
6499.
Romano A, Viola M, Mondino C, Pettinato R, Di Fonso M, Papa G, Venuti A,
Montuschi P. Diagnosing
nonimmediate reactions to penicillins by in vivo tests. Int Arch Allergy Immunol.
2002 Oct;129(2):169-74.
BACKGROUND:
Maculopapular and urticarial rashes are nonimmediate manifestations common
during penicillin treatment; the former often represent cell-mediated
hypersensitivity. Our objectives were to assess the incidence of allergy in
adults reporting nonimmediate manifestations during penicillin therapy and to
evaluate the diagnostic potential of patch tests, delayed-reading skin tests and
challenges in such cases. METHODS: We used prick and intradermal tests as well
as patch tests with penicillin determinants, ampicillin, amoxicillin and any
other suspect penicillins. We also performed challenges with the suspect
antibiotics. RESULTS: Such antibiotics were aminopenicillins in 93.1% of 259
patients, most of whom had suffered from maculopapular rashes followed by
piperacillin (4.2%). Three subjects displayed immediate skin test positivity.
Ninety-four subjects showed patch test and delayed intradermal test positivity
to the culprit penicillin (90 to aminopenicillins and 4 to piperacillin) and
were considered as having had delayed hypersensitivity reactions. Five of the 8
subjects who displayed delayed intradermal test positivity and patch test
negativity to the suspect penicillin underwent challenges, 2 reacted positively
to the responsible aminopenicillin. Among the remaining 154 with negative
results in allergologic tests, 125 agreed to undergo challenges; only 3 reacted.
In all, 98 patients -- 93 of whom had experienced maculopapular rashes --
displayed delayed hypersensitivity (94 to aminopenicillins and 4 to piperacillin).
CONCLUSIONS:
Both patch and intradermal tests are useful in evaluating nonimmediate reactions
to penicillins, particularly maculopapular rashes. Patch test and delayed
intradermal positivity together indicate delayed hypersensitivity. Intradermal
testing appears to be slightly more sensitive than patch testing. Copyright 2002
S. Karger AG, Basel.
6500.
Schmidt MH, Raulf-Heimsoth M, Posch A. Evaluation of patatin as a major
cross-reactive allergen in latex-induced potato allergy. Ann Allergy Asthma
Immunol. 2002 Dec;89(6):613-8.
BACKGROUND:
Potential cross-reactions between natural rubber latex and fruit/vegetable
specific immunoglobulin (Ig)E antibodies have been reported for many years. This
study was designed to investigate the molecular basis of acquired food
sensitization focusing on the storage protein patatin and the patatin-like latex
protein Hev b 7. OBJECTIVE: The amount of potato-specific IgE in the serum of
latex-allergic health care workers and children with atopic dermatitis was
determined to evaluate cross-reactivity between Hev b 7 and patatin.
Additionally, the stability of potato patatin to digestion was investigated.
METHODS: Human serum was tested on its reactivity to latex and potato proteins
by IgE immunoblotting after one-dimensional (1-D) and 2-D electrophoresis.
Latex- and potato-specific IgE concentrations were measured in fluorescence
enzyme immunoassays (CAP, Pharmacia, Uppsala, Sweden). Further, potato patatin
was chromatographically isolated to perform auto-inhibition tests. Stability of
patatin to degradation was determined by digestion in vitro.
RESULTS:
Patatin was identified as major cross-reactive potato allergen by N-terminal
sequencing. Seventy-five percent of the potato-sensitized people reacted with
patatin in 1-D immunoblots, and 25% of the positive reactions to Hev b 7 could
be blocked by preincubation of the patients' sera with purified potato patatin.
Examination of children with atopic dermatitis showed that most sera contained
patatin-specific IgE, whereas no Hev b 7-specific IgE was detected. Finally,
patatin has been found partially stable to digestion in vitro.
CONCLUSIONS:
Patatin was identified as a major cross-reactive protein in latex-associated
potato allergy and appears to be relevant for atopic dermatitis. Therefore,
patatin could be a suitable marker for the determination of potato
sensitization, and it may also constitute an important food allergen.
Cross-reactivity between Hev b 7 and patatin was restricted to primarily
latex-sensitized adults, suggesting a different mechanism of sensitization in
children with atopic dermatitis.
6501.
Sousa AR, Parikh A, Scadding G, Corrigan CJ, Lee TH. Leukotriene-receptor
expression on nasal mucosal inflammatory cells in aspirin-sensitive
rhinosinusitis. N Engl J Med. 2002 Nov 7;347(19):1493-9.
BACKGROUND:
Patients with asthma who have aspirin sensitivity have greater cysteinyl
leukotriene production and greater airway hyperresponsiveness to the effects of
inhaled cysteinyl leukotrienes than their aspirin-tolerant counterparts. We
hypothesized that the latter effect reflects elevated expression of the
cysteinyl leukotriene receptor CysLT1 on inflammatory cells in the target organ
and that its expression is down-regulated by aspirin desensitization. METHODS:
We obtained nasal-biopsy specimens from 22 aspirin-sensitive and 12
non-aspirin-sensitive patients with chronic rhinosinusitis and nasal polyps.
Additional specimens were then obtained from subgroups of the aspirin-sensitive
patients after intranasal application of lysine aspirin or placebo for two weeks
(five and four patients, respectively) or for six months (five and four
patients, respectively). The numbers of leukocytes expressing the CysLT1 and
leukotriene B4 (LTB4) receptors per unit area of sections of the nasal submucosa
were determined by immunohistochemistry.
RESULTS:
The absolute number of cells expressing the CysLT1 receptor was significantly
higher in the aspirin-sensitive patients than in the non-aspirin-sensitive
patients (median, 542 cells per square millimeter [range,148 to 1390] vs. 116
cells per square millimeter [range, 40 to 259]; P<0.001). The percentage of
CD45+ leukocytes expressing the CysLT1 receptor was also higher in the
aspirin-sensitive subjects (25 percent of CD45+ leukocytes [range, 4 to 50] vs.
5 percent of CD45+ leukocytes [range, 2 to 11]; P<0.001); the percentage of
CD45+ leukocytes expressing the LTB4 receptor did not differ significantly
between these two groups. Desensitization was associated with a decrease in the
numbers of inflammatory cells expressing CysLT1.
CONCLUSIONS:
The elevated numbers of nasal inflammatory leukocytes expressing the CysLT1
receptor in aspirin-sensitive patients with chronic rhinosinusitis as compared
with their non-aspirin-sensitive counterparts and the down-regulation of
receptor expression after desensitization to aspirin are probably fundamental in
the pathogenesis of aspirin sensitivity and in the mechanism of
aspirindesensitization. Copyright 2002 Massachusetts Medical Society
6502.
Stablein JJ, Bucholtz GA, Lockey RF. Melaleuca tree and respiratory
disease. Ann Allergy Asthma Immunol. 2002 Nov;89(5):523-30.
BACKGROUND:
The role of Melaleuca quinquenervia tree as a source of allergen(s) and
respiratory irritant(s) is controversial. OBJECTIVE: Determine whether Melaleuca
tree pollen or odor is medically important. METHODS: A 2-year aeroallergen
survey and skin test (ST) results of 1,017 subjects were reviewed. Sixteen
subjects were selected based on positive Melaleuca pollen extract (MPE) STs.
Double-blind nasal challenges with MPE were performed on six subjects.
Single-blind bronchial challenges with MPE were performed on four. To evaluate
the irritant effect, 11 subjects received 34 different Melaleuca odor challenges
(blossoms, bark, and leaves) through a closed system for up to 30 minutes. Four
inhaled an odor from cajeput oil (derived from Melaleuca leaves) for 1 hour.
Spirometry was performed before and after odor challenges. Radioallergosorbent
test using MPE was compared with MPE STs in 15 subjects. RESULTS: The
aeroallergens survey revealed insignificant numbers of Melaleuca pollen.
Ninety-seven of 1,017 subjects were a 2+ or greater intradermal MPE ST. One of 6
double-blind nasal challenges and 1 of 4 single-blind bronchial challenges using
MPE were positive in subjects with positive MPE STs. All 38 odor challenges with
blossoms, bark, leaves, and cajeput oil were nonreactive. The MPE
radioallergosorbent test correlated with MPE ST results. CONCLUSIONS: The
Melaleuca tree is not a significant source
of aeroallergen. The Melaleuca odor is not a respiratory irritant. MPE
antigen(s) has been shown to cross-react with pollen extracts from a proven
aeroallergen (Bahia grass pollen) possibly explaining the few cases of positive
MPE STs with positive nasal/bronchial challenges.
6503.
Stewart AE, Hunsaker DH. Fungus-specific IgG and IgE in allergic fungal
rhinosinusitis. Otolaryngol Head Neck Surg. 2002 Oct;127(4):324-32.
OBJECTIVE:
Our study goal was to study fungus-specific immunoglobulins G (sIgG) and E (sIgE)
in polypoid rhinosinusitis with and without evidence of allergic fungal
rhinosinusitis (AFS). STUDY DESIGN AND SETTING: A prospective analysis was
conducted of fungal sIgG and sIgE using a 9-mold RAST panel in 13 AFS, 11 AFS-like,
and 27 non-AFS polypoid rhinosinusitis patients. Nonpolyp controls included 17
volunteers with allergic rhinitis and 11 with no atopic history. RESULTS: All
groups had elevated fungal sIgG levels. Polyps, increasing polyp severity, and
AFS were associated with elevated fungal sIgG to a greater number of molds. The
AFS group had sIgE elevations (>or=class II) to an average of 5 molds versus
only 0.1 in the non-AFS polyp group. Total IgE was 971 U/mL versus 64 U/mL,
respectively. CONCLUSIONS: Multiple elevations of fungal sIgE are adequate
diagnostic evidence of these fungi when fungal cultures and histologic
examinations are negative in diagnosing AFS. The significance of increased
fungal sIgG remains unclear. SIGNIFICANCE: Early recognition of AFS may be
facilitated by screening polypoid rhinosinusitis patients with total serum IgE
and RAST testing.
6504.
Strunk RC, Korenblat PE. Choice of a medication to treat asthma: is an
improvement in symptoms sufficient for deciding? J Allergy Clin Immunol. 2002
Dec;110(6):832-3. No abstract.
6505.
Suissa S, Ernst P, Kezouh A. Regular use of inhaled corticosteroids and
the long term prevention of hospitalisation for asthma. Thorax. 2002
Oct;57(10):880-4.
BACKGROUND: Inhaled corticosteroids are effective
at preventing asthma morbidity and mortality. Most studies, however, have
focused on short term effects, raising uncertainty about their effectiveness in
the long term. METHODS: The Saskatchewan Health databases were used to form two
population based cohorts of asthma patients aged 5-44 between 1975 and 1991. The
first cohort included all subjects from the start of asthma treatment, while the
second included subjects hospitalised for asthma from the date of discharge.
Subjects were followed up,starting 1 year after cohort entry and continuing
until 1997, 54 years of age, or death. The outcome was the first asthma hospital
admission and readmission, respectively, to occur during follow up. A nested
case-control design was used by which all cases were matched on calendar time
and several markers of asthma severity to all available controls within the
cohort. RESULTS: The full cohort included 30 569 asthmatic subjects of which
3894 were admitted to hospital for asthma and 1886 were readmitted. The overall
rate of asthma hospitalisation was 42.4 per 1000 asthma patients per year.
Regular use of inhaled corticosteroids was associated with reductions of 31% in
the rate of hospital admissions for asthma (95% confidence interval (CI) 17 to
43) and 39% in the rate of readmission (95% CI 25 to 50). The rate reduction
found during the first 4 years of follow up was sustained over the longer term.
Regular use of inhaled corticosteroids can potentially prevent between five
hospital admissions and 27 readmissions per 1000 asthma patients per year.
CONCLUSION: Regular use of low dose inhaled corticosteroids prevents a large
proportion of hospital admissions with asthma, both early and later on in the
course of the disease.
6506.
Tomimori Y, Tsuruoka N, Fukami H, Saito K, Horikawa C, Saito M, Muto T,
Sugiura N, Yamashiro K, Sumida M, Kakutani S, Fukuda Y. Role of mast cell
chymase in allergen-induced biphasic skin reaction. Biochem Pharmacol. 2002 Oct
1;64(7):1187.
Intradermal
injection of human chymase (EC 3.4.21.39) into the mouse ear elicited an
edematous skin reaction in a biphasic manner, with a transient reaction peaking
at 1 hr, followed by a delayed response persisting for at least 24hr. The
kinetics of this reaction was analogous to the biphasic skin reaction induced by
ascaris extract in actively sensitized mice. A similarity between the two
dermatitis models was also shown by histological analysis, i.e. accumulation of
inflammatory cells was observed exclusively in the later phases of the skin
reaction. A chymase inhibitor, SUN-C8077
[3-(3-aminophenylsulfonyl)-7-chloroquinazorine 2,4(1H, 3H)-dione], significantly
inhibited both the early- and late-phase responses of the skin reaction induced
by ascaris extract. These findings suggest that chymase may play an important
role in the allergen-induced biphasic skin reaction. A histamine receptor
antagonist, homochlorcyclizine, inhibited the early-phase but not the late-phase
of the chymase-induced skin reaction. In addition, human chymase showed
chemotactic activity to human polymorphonuclear leukocytes in vitro. Mast cell
chymase may participate in the two phases of allergic skin inflammation by two
distinct mechanisms, i.e. histamine- and leukocyte-dependent mechanisms,
respectively.
6507.
Tripathi DM. Role of allergy testing and immunotherapy in the management
of respiratory allergic disease. Bombay
Hospital Journal. 2002 Jul; 44(3): 419-
ABSTRACT: The central point of allergy diagnosis remains the skin testing even- to-day, when the test results can be better guaranteed and differentiated through modern process like provocation test or RAST. In the diagnosis of allergic conditions such as bronchial asthma, allergic rhinitis in which allergy may be a pathogenic factor has been substantially facilitated by allergy skin testing. Skin testing demonstrates the presence of IgE directed against the specific allergen tested. Although, there are a variety of in-vivo and in-vitro methods for assessing the presence of specific IgE antibodies, the skin testing is preferred because it is simple, inexpensive, specific and results are immediately available. Allergy skin tests correlate well with clinical history, provocative challenge and in-vitro allergy assays such as RAST, modified RAST, QUIDEL, allergen screens, histamine release and immunocap system.
6508.
Turner SW, Young S, Landau LI, Le Souef PN. Reduced lung function both
before bronchiolitis and at 11 years. Arch Dis Child. 2002 Nov;87(5):417-20.
BACKGROUND
AND AIMS: We have previously shown an association between reduced premorbid lung
function (V'maxFRC) and bronchiolitis. We hypothesised that individuals with
bronchiolitis will go on to have reduced lung function and increased respiratory
symptoms in childhood. METHODS: V'maxFRC was measured at 1 month of age;
individuals with bronchiolitis were prospectively identified. Annual symptom
questionnaires were completed from 3 to 6 years. At 11 years of age, children
underwent an assessment including questionnaire, lung function, airway response
to histamine (AR), and skin prick testing. RESULTS: Eighteen individuals with
bronchiolitis were ascertained from 253 cohort members. Children with
bronchiolitis had increased viral induced wheeze at 3 (OR 5.8, 95% CI 1.4 to
25.2; n = 103) and 5 years (OR 5.3, 95% CI 1.1 to 25.5; n = 101). At 11 years of
age, 194 children were assessed including 16 with past bronchiolitis. These 16
individuals had reduced mean z scores for % V'maxFRC compared with other
children (-0.56 and 0.06 respectively) and mean z scores for % FEF(25-75) at 11
years (-0.53 and 0.06 respectively). At 11 years, FEV(1), FVC PEF, AR, atopy,
wheeze, and diagnosed asthma were not different between groups. CONCLUSIONS:
Reduced lung function is present before and after bronchiolitis; the level of
reduction is comparable. The mechanism for wheeze and reduced lung function
after bronchiolitis appears to be related to premorbid lung function and not
bronchiolitis per se.
6509.
Wenzel SE, Trudeau JB, Barnes S, Zhou X, Cundall M, Westcott JY, McCord
K, Chu HW. TGF-beta and IL-13
synergistically increase eotaxin-1 production in human airway fibroblasts. J
Immunol. 2002 Oct 15;169(8):4613-9.
Chronic
diseases may involve an "innate" response followed by an adaptive
immune response, of a Th1 or Th2 variety. Little is known regarding the
interactions of these responses. We hypothesized that TGF-beta1 (innate response
factor associated with wound repair) in combination with IL-13 (Th2 factor)
might augment inflammatory processes associated with asthma. Airway fibroblasts
were cultured from asthmatic subjects and normal controls. These fibroblasts
were exposed to TGF-beta1 and IL-13 alone or in combination, and eotaxin-1
expression and production were evaluated. At 48 h, eotaxin-1 production was
markedly increased with the combination of TGF-beta1 and I L-13 (p < 0.0001)
compared with either stimulus alone. mRNA increased slightly at 1 h with IL-13
or TGF-beta1 plus IL13, peaked, and became significantly increased over IL-13
alone at 24 h. Protein was measurable from 6 h with IL-13 and TGF-beta1 plus
IL-13, but greater levels were measured over time with the combination.
Actinomycin ablated the increase in mRNA and protein seen with IL-13 alone and
with TGF-beta1 plus IL-13. Cycloheximide blocked the increase in mRNA at 6 h in
both conditions, but also blocked the increase at 24 h with TGF-beta1 plus
IL-13. STAT-6 was rapidly activated with both IL-13 and the combination, without
difference. Finally, eotaxin-1-positive fibroblasts were identified in severe
asthma biopsies in greater numbers than in normals. These results support the
concept that interactions of innate and adaptive immune systems may be important
in promoting the tissue eosinophilia of asthma, particularly in those with more
severe disease.
6510.
Yang YH, Wang SJ, Chuang YH, Lin YT, Chiang BL. The level of IgA
antibodies to human umbilical vein endothelial cells can be enhanced by TNF-alpha
treatment in children with Henoch-Schonlein purpura. Clin Exp Immunol. 2002
Nov;130(2):352-7.
Anti-endothelial
cell antibodies (AECA) have been found to play an important role in many
vascular disorders. In order to determine the presence of AECA in children with
Henoch-Schonlein purpura (HSP), and to elucidate the pathogenic and clinical
value of their measurement in this disease, AECA were detected by
immunofluorescence staining and a human umbilical vein endothelial cell (HUVEC)-based
enzyme-linked immunosorbent assay (ELISA) in 20 children with HSP, 10 children
with juvenile rheumatoid arthritis (JRA) without vasculitis and 10 normal
healthy children. Antibodies against another endothelial cells, human dermal
microvascular endothelial cells (HMVEC-d) were also detected by cell-based
ELISA. In some experiments, we compared the binding activity of antibodies to
HUVEC with and without tumour necrosis factor-alpha (TNF-alpha) or interleukin-1
(IL-1) pretreatment. Patients with acute onset of HSP had higher serum levels of
IgA antibodies, both against HUVEC and against HMVEC-d, than healthy controls (P
= 0.001, P = 0.008, respectively). Forty-five per cent of patients had positive
IgA AECA to HUVEC, and 35% had positive IgA AECA to HMVEC-d. The titres of IgA
antibodies to HUVEC paralleled the disease activity. After TNF-alpha treatment,
the values of IgA AECA to HUVEC in HSP patients were significantly increased (P
= 0.02). For IgG and IgM AECA, there was no difference between HSP patients and
controls (P = 0.51, P = 0.91). Ten JRA children without vasculitis had no
detectable IgG, IgM or IgA AECA activity. The results of this study showed that
children with HSP had IgA AECA, which were enhanced by TNF-alpha treatment.
Although the role of these antibodies is not clear, IgA AECA provide another
immunological clue for the understanding of HSP.
Pathogenesis:
6511.
Arm JP, Austen KF. Leukotriene receptors and aspirin sensitivity. N Engl
J Med. 2002 Nov 7;347(19):1524-6. No abstract.
6512.
Banerjee B, Kurup VP, Greenberger PA, Kelly KJ, Fink JN. C-terminal
cysteine residues determine the IgE binding of Aspergillus fumigatus allergen
Asp f 2. J Immunol. 2002 Nov 1;169(9):5137-44.
The
knowledge of the structure function relationship of the allergen is essential to
design allergenic variants with reduced IgE binding capacity but intact T cell
reactivity. Asp f 2 is a major allergen from the fungus Aspergillus fumigatus
and >90% of A. fumigatus-sensitized individuals displayed IgE binding to Asp
f 2. In the present study, we evaluated the involvement of C-terminal cysteine
residues in IgE binding conformation of Asp f 2. The deletion mutants were
constructed by adding three C-terminal cysteines of the native Asp f 2 one at a
time to the non-IgE binding Asp f 2 (68-203). The point mutants of Asp f 2
(68-268) with C204A and C257A substitutions were constructed to study the role
of C-terminal cysteines in IgE binding. Immunological evaluation of reduced and
alkylated Asp f 2 and its mutants were conducted to determine the contribution
of free sulfhydryl groups as well as the disulfide bonds in allergen Ab
interaction. Four-fold increase in IgE Ab binding of Asp f2 (68-267) compared
with Asp f 2 (68-266) and complete loss in IgE binding of C204A mutant of Asp f
2 (68-268) indicate the involvement of C(204) and C(267) in IgE binding
conformation of Asp f 2. A significant reduction in IgE binding of wild and
mutated Asp f 2 after reduction and alkylation emphasizes the importance of
cysteine disulfide bonds in epitope Ab interaction. The hypoallergenic variants
may be explored further to develop safe immunotherapeutic strategy for allergic
disorders.
6513.
Borger P, Black JL, Roth M. Asthma and the CCAAT-enhancer binding
proteins: a holistic view on airway inflammation and remodeling. J Allergy Clin
Immunol. 2002 Dec;110(6):841-6. Review.
Asthma
is an airway disease with increasing prevalence characterized by intermittent
reversible airway obstruction, airway inflammation, and airway wall remodeling.
The disease is generally triggered by inhalation of allergens, but nonallergic
asthma triggers are quite common. The pathogenesis of asthma is well documented,
and a great deal of research has been carried out to elucidate the underlying
mechanisms. A multitude of articles have focused on cells alleged to be involved
in the pathogenesis, including circulating cells from the immunologic
compartment (ie, eosinophils and T lymphocytes) and resident cells, such as
fibroblasts, airway smooth muscle cells, and, more recently, the airway
epithelium. Despite the enormous amount of research, it is still unclear what
exactly causes asthma. A general feature of most studies is an enhanced
activation status of asthmatic cells, suggesting a general defect with respect
to regulation of cellular responses. Here we discuss the ubiquitous
transcription factor family of CCAAT-enhancer binding proteins (C/EBPs) and its
involvement in inflammation and proliferation. We propose that an imbalance of
C/EBP isoform expression might lead to an enhanced activity of asthmatic cells
and provide an overall hypothesis that both airway inflammation and remodeling
can be conceived as the result of an imbalance of C/EBP isoform expression.
6514.
Budde IK, de Heer PG, Natter S, Mahler V, van der Zee JS, Valenta R,
Aalberse RC. Studies on the association between immunoglobulin E autoreactivity
and immunoglobulin E-dependent histamine-releasing factors. Immunology. 2002
Oct;107(2):243-51.
It has been reported that serum immunoglobulin E (IgE)
from certain atopic patients can sensitize basophils to release histamine in
response to IgE-dependent histamine-releasing factors (HRFs). It has also been
shown that patients suffering from severe forms of atopy may contain IgE
autoantibodies. It was investigated whether HRF-responsive sera contained IgE
autoantibodies and if there was an association between IgE autoreactivity and
IgE-dependent responsiveness to HRF. The presence of HRF-responsive IgE (IgE+)
in serum of patients with respiratory atopy was determined by stimulating
stripped human basophils sensitized by serum with peripheral blood mononuclear
cell (PBMC)-derived HRF, and measuring the release of histamine. In parallel,
these sera were screened for the presence of IgE autoantibodies to
nitrocellulose-blotted human cellular extracts. The capacity of IgE autoantigen-containing
preparations to induce histamine release was tested in the stripped basophil
assay. Eleven out of 52 sera contained IgE autoantibodies to blotted cellular
extracts of human PBMCs or of the human epithelial cell line A431. No
significant association was found between IgE autoreactivity and IgE-dependent
responsiveness to HRF: 7/26 IgE+ sera contained IgE to human cellular extracts,
and 4/26 of the sera without IgE+ did also. IgE autoantigen-containing extracts
did not induce histamine release of appropriately sensitized basophils. By
size-exclusion chromatography it was shown that a 32 000 MW autoantigen eluted
in the >55 000 MW fraction, which indicates that this protein forms polymers
or complexes with other macromolecules.
This might explain the discrepancy between binding and histamine-releasing
activity. A 20 000 MW IgE-defined autoantigen cross-reacted with a shrimp
allergen. Our results indicate that IgE-reactivity to immunoblotted human
protein and IgE-dependent HRF activity are distinct entities that may co-occur
in atopic patients.
6515.
Choi IS. Disappearance of aspirin intolerance with antiasthma treatment.
J Allergy Clin Immunol. 2002 Oct;110(4):665-6. No abstract.
6516.
Cloutier MM, Wakefield DB, Hall CB, Bailit HL. Childhood asthma in an
urban community: prevalence, care system, and treatment. Chest. 2002
Nov;122(5):1571-9.
OBJECTIVES:
We describe the system of asthma care in Hartford, CT, an urban,minority
community. METHODS: The health field concept was used to organize factors
influencing asthma prevalence and severity. Data were obtained from national,
state, and municipal reports, and from surveys of children in Hartford seeking
medical care in an asthma program called Easy Breathing. RESULTS: Between June
1, 1998, and May 1, 2000, 21% of children receiving Medicaid in Hartford did not
file a medical claim. Between 1998 and 2000, the number of providers in Hartford
decreased by 37% while the number of outpatient visits increased by 8%. Using
claims data, we found the following: 19.0% of Hartford children had asthma (data
from the International Classification of Disease, ninth revision, and the
National Drug Code); and 12% of children with asthma filled a prescription for
inhaled corticosteroid therapy, 83% for a bronchodilator, and 36% for an oral
corticosteroid. Children with asthma were more likely to be hospitalized (10% vs
5%, respectively) and to visit an emergency department (45% vs 29%,
respectively), and, on average, they had more hospital days (0.603 vs 0.415 days
per child, respectively) and more outpatient visits per year (4.7 vs 2.5 visits,
respectively) compared to children without asthma. Asthma prevalence in the
6,643 children surveyed in the Easy Breathing program was 41%. Persistent asthma
was diagnosed in 50% of the children with asthma. Asthma prevalence varied by
ethnic origin, age, and gender, and was highest in Hispanic/Puerto Rican
children, in children 5 to 10 years of age, in boys up to 10 years of age, and
in girls after 15 years of age. CONCLUSION: Improved personal behaviors and
medical care will have a limited sustained impact on childhood asthma until
basic environmental issues are modified. The health field concept provides a
mechanism with which to address the issues surrounding asthma in urban
communities.
6517.
Dreskin SC, Dale SN, Foster SM, Martin D, Buchmeier A, Nelson HS.
Measurement of changes in mRNA for IL-5 in noninvasive scrapings of nasal
epithelium taken from patients undergoing nasal allergen challenge. J Immunol
Methods. 2002 Oct 15;268(2):189-95.
Nasal
allergen challenge of patients with allergic rhinitis results in increased
numbers of inflammatory cells and increased production of pro-inflammatory
cytokines including interleukin 5 (IL-5). We report a sensitive, noninvasive
method to measure changes in the amount of mRNA for IL-5 in nasal epithelium and
have used this method to detect alterations of IL-5 mRNA from patients
undergoing a nasal allergen challenge. Ten grass or ragweed allergic adults were
challenged out of season with appropriate pollen extracts at sufficient dose to
give a rhinitis total symptom score of 5 on a scale of 12. After allergen
exposure, symptoms were recorded hourly. At 0, 3, and 6 h after allergen
exposure, secreted proteins were collected on filter paper strips and two
superficial scrapings of nasal epithelium were obtained. The scrapings of
epithelium were immediately immersed in 100 microl of RNAlater (Ambion, Austin,
TX) and stored at 4 degrees C for up to 1 month without loss of RNA quality.
Total RNA was isolated and RT-PCR was performed. cDNA for IL-5 was then measured
by real-time fluorescence quantitative PCR with Pre-Developed TaqMan Assay
Reagents (PE Biosystems, Foster City, CA). Sufficient RNA was isolated from
eight subjects to measure IL-5 mRNA. Data were normalized for content of
ribosomal RNA. The relative amount of cDNA for IL-5 was calculated by comparison
with internal standards prepared from phytohemagluttinin-stimulated peripheral
blood mononuclear cells. Messenger RNA for IL-5 was increased 8.7+/-2.7-fold at
3 h (p<0.01) and 39.5+/-20.9-fold at 6 h (p<0.01). Increased IL-5 mRNA
levels at 6 h closely correlate with total symptom scores at 6 h (r=0.88;
p=0.007). IL-5 protein was measured by ELISA in eluates from the filter papers.
At 6 h, there was increased IL-5 protein (7.7+/-2.8 ng/ml) compared with time
zero (1.8+/-0.5 ng/ml) (p=0.02). The levels of IL-5 protein did not correlate
significantly with the symptoms score or with changes in the levels of IL-5
protein with IL-5 mRNA. These data show that changes in IL-5 mRNA in patients
with allergic rhinitis undergoing an allergen challenge correlate with total
symptom scores better than changes in IL-5 protein eluted from filter paper.
Furthermore, these changes can be measured quantitatively in very small amounts
of tissue.
6518.
Guilbert T, Morgan W. Increased asthma symptoms and healthcare
utilization during the fall and winter seasons in children with asthma living in
the inner city: opportunity for school-based intervention. J Pediatr. 2002
Nov;141(5):604-5. No abstract.
6519.
Jousilahti P, Salomaa V, Hakala K, Rasi V, Vahtera E, Palosuo T. The
association of sensitive systemic inflammation markers with bronchial asthma.
Ann Allergy Asthma Immunol. 2002 Oct;89(4):381-5.
BACKGROUND:
Airway inflammation is a characteristic feature of bronchial asthma. Previous
studies have shown an increased local inflammatory activity in the airway mucosa
of asthma patients. OBJECTIVES: To analyze the association of asthma with three
sensitive markers of systemic inflammation, C-reactive protein, serum amyloid-A
(SAA), and plasma fibrinogen. METHODS: A cross-sectional, population-based study
including 1,513 Finnish men aged 45 to 74 years, who participated in a chronic
disease risk factor survey in 1997. Of the participating men, 97 were classified
as asthma patients. The odds ratios of asthma were analyzed by quartile of each
inflammation marker. RESULTS: In logistic regression models the age-adjusted
odds ratios (second, third, and fourth quartile as compared with the first
quartile) of asthma increased gradually with increasing quartile of C-reactive
protein (1.28, 1.19, 1.96, P for trend = 0.039), SAA (1.20, 3.00, 3.49, P for
trend < 0.001), and fibrinogen (1.22, 1.79, 3.16, P for trend < 0.001).
The associations were independent of smoking. Further adjustment for
waist-to-hip ratio, a marker of central obesity, and symptoms of chronic
bronchitis weakened the observed association, but the increasing trend in the
association of SAA and fibrinogen with asthma remained highly significant.
CONCLUSIONS: Sensitive markers of systemic inflammation, particularly SAA and
fibrinogen, were positively and significantly associated with asthma prevalence.
These findings support the hypothesis that not only local, but also systemic,
inflammation exist in bronchial asthma.
6520.
Karlsson H, Hessle C, Rudin A. Innate immune responses of human neonatal
cells to bacteria from the normal gastrointestinal flora. Infect Immun. 2002
Dec;70(12):6688-96.
The
hygiene hypothesis postulates that the prevalence of allergy has increased due
to decreased microbial stimulation early in life, leading to delayed maturation
of the immune system. The aim of this study was to examine the cytokine pattern
produced from cord blood mononuclear cells relative to adult cells after
stimulation with bacterial strains from the normal flora. Mononuclear cells from
cord and adult blood samples were stimulated with the following bacteria:
Bifidobacterium adolescentis, Enterococcus faecalis, Lactobacillus plantarum,
Streptococcus mitis, Corynebacterium minutissimum, Clostridium perfringens,
Bacteroides vulgatus, Escherichia coli, Pseudomonas aeruginosa, Veillonella
parvula, and Neisseria sicca. The levels of interleukin 12 (IL-12), tumor
necrosis factor alpha (TNF-alpha), IL-10, and IL-6 were measured by
enzyme-linked immunosorbent assay. The TNF-alpha production was also analyzed
after blocking CD14, Toll-like receptor 2 (TLR-2), and TLR-4 prior to
stimulation with bacteria. The levels of IL-12 and TNF-alpha were similar in
cord and adult cells. Gram-positive bacteria induced considerably higher levels
of IL-12 and TNF-alpha than gram-negative bacteria in both cord and adult cells.
The levels of IL-6 were significantly higher in newborns than in adults, whereas
the levels of IL-10 were similar in newborns and adults. Gram-negative and
gram-positive bacteria induced similar levels of IL-6 and IL-10 in cord cells.
L. plantarum bound or signaled through CD14, TLR-2, and TLR-4, whereas E. coli
acted mainly through CD14 and TLR-4. These results indicate that the innate
immune response in newborns to commensal bacteria is strong and also suggest
that different bacterial strains may have differential effects on the maturation
of the immune system of infants.
6521.
Levinson AI. Novel immunomodulatory therapies for immunoglobulin
E-mediated diseases. Isr Med Assoc J. 2002 Nov;4(11 Suppl):881-3. Review. No abstract.
6522.
Lipworth BJ. Adrenal insufficiency after treatment with fluticasone.
Second line controller treatment might have been tried. BMJ. 2002 Oct
12;325(7368):836. No abstract.
6523.
Liu LY, Sedgwick JB, Bates ME, Vrtis RF, Gern JE, Kita H, Jarjour NN,
Busse WW, Kelly EA. Decreased expression of membrane IL-5 receptor alpha on
human eosinophils: II. IL-5 down-modulates its receptor via a proteinase-mediated
process. J Immunol. 2002 Dec 1;169(11):6459-66.
In
the accompanying study, we demonstrated that following Ag challenge, membrane
(m)IL-5Ralpha expression is attenuated on bronchoalveolar lavage eosinophils,
soluble (s)IL-5Ralpha is detectable in BAL fluid in the absence of increased
steady state levels of sIL-5Ralpha mRNA, and BAL eosinophils become refractory
to IL-5 for ex vivo degranulation. We hypothesized that IL-5 regulates its
receptor through proteolytic release of mIL-5Ralpha, which in turn contributes
to the presence of sIL-5Ralpha. Purified human peripheral blood eosinophils were
incubated with IL-5 under various conditions and in the presence of different
pharmacological agents. A dose-dependent decrease in mIL-5Ralpha was accompanied
by an increase in sIL-5Ralpha in the supernatant. IL-5 had no ligand-specific
effect on mIL-5Ralpha or sIL-5Ralpha mRNA levels. The matrix metalloproteinase-specific
inhibitors BB-94 and GM6001 and tissue inhibitor of metalloproteinase-3
partially inhibited IL-5-mediated loss of mIL-5Ralpha, suggesting that
sIL-5Ralpha may be produced by proteolytic cleavage of mIL-5Ralpha. IL-5
transiently reduced surface expression of beta-chain, but had no effect on the
expression of GM-CSFRalpha. Pretreatment of eosinophils with a dose of IL-5 that
down-modulated mIL-5Ralpha rendered these cells unable to degranulate in
response to further IL-5 stimulation, but they were fully responsive to GM-CSF.
These findings suggest that IL-5-activated eosinophils may lose mIL-5Ralpha and
release sIL-5Ralpha in vivo, which may limit IL-5-dependent inflammatory events
in diseases such as asthma.
6524.
Narasimhan R, Lakshman R, Amos RS, Williams LH, Egner W, Finn A. Juvenile
dermatomyositis associated with hereditary angioneurotic oedema. Arch Dis Child.
2002 Dec;87(6):563. No abstract.
6525.
Ostergaard MS, Stauning JA, Andersen JS, Jorgensen M. The PAT study's
methods, asthma classification, and results are questionable. J Allergy Clin
Immunol. 2002 Oct;110(4):671; author reply, 671-2. No abstract.
6526.
Peroni DG, Chatzimichail A, Boner AL. Food allergy: what can be done to
prevent progression to asthma? Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl
1):44-51. Review.
OBJECTIVES:
The primary objective of this review is to discuss risk factors for asthma
development in food allergen-sensitized children. In the paper we discuss the
possible measures to prevent progression to asthma by allergen and other
adjuvant factor avoidance. DATA SOURCES: A review from literature of articles on
these topics was performed. STUDY SELECTION: Relevant publications on asthma
risk factors and implementation of protective factors were critically evaluated.
RESULTS: Children with familiar history of atopy and sensitization to food
proteins in early infancy are at high risk of subsequent respiratory allergic
diseases and require specific prevention. Because early allergic sensitization
is a significant risk factor for later development of asthma, prevention of
asthma by early allergen avoidance is mandatory in high-risk children. Adjuvant
factors such as tobacco smoke and mold exposure may act as nonspecific triggers
for the development of atopy. The role of protective factors such as infections
in early life, breast-feeding, a "healthy" diet needs to be evaluated
in prospective studies. Pharmacologic intervention with antihistamines led to
significant reduction in incidence of asthma in high-risk children, but
confirmatory longitudinal studies in large populations are necessary.
CONCLUSIONS: There is now accumulating evidence that preventing exposure to
house-dust mite may significantly reduce the prevalence of childhood asthma.
However,
allergen avoidance can not be recommended as the only strategy. Avoidance of
adjuvant factors and implementation of potential protective factors aimed to
reduce the risk to progression to asthma need to be evaluated in prospective
studies.
6527.
Phanish MK, Owen A, Parry DH. Spontaneous regression of acquired C1
esterase inhibitor deficiency associated with splenic marginal zone lymphoma
presenting with recurrent angio-oedema. J Clin Pathol. 2002 Oct;55(10):789-90.
A
52 year old woman with marginal zone lymphoma developed recurrent episodes of
angio-oedema and was found to have C1 esterase inhibitor deficiency. She
declined chemotherapy for the lymphoma. Fourteen months after her initial
presentation she was found to be in partial remission, and this was confirmed by
peripheral blood film and bone marrow examinations. This was associated with
normalisation of C1 esterase inhibitor, C1q, and C4 values. Regression of
acquired C1 esterase inhibitor deficiency associated with spontaneous partial
remission of lymphoma has not been reported previously.
6528.
Riegert-Johnson DL, Volcheck GW. The incidence of anaphylaxis following
intravenous phytonadione (vitamin K1): a 5-year retrospective review. Ann
Allergy Asthma Immunol. 2002 Oct;89(4):400-6. Review.
BACKGROUND:
Phytonadione (vitamin K1) administered intravenously (i.v.) has been associated
with anaphylaxis, although the incidence is not known. The anaphylaxis is
thought to be attributable to the solubilizing vehicle, polyethoxylated castor
oil (Cremophor EL, BASF AG, Ludwingshafen, Germany). OBJECTIVE: To estimate the
incidence of anaphylaxis after i.v. administration of phytonadione. METHODS: A
retrospective review of anaphylaxis after i.v. phytonadione over a 58-month
period at a large academic center was performed. During the period of the study
a protocol for the administration of i.v. phytonadione was in place. A review of
computerized records and survey of staff identified cases of anaphylaxis meeting
predefined inclusion criteria. Inaddition, a literature review was performed for
articles concerning anaphylaxis after i.v. phytonadione. RESULTS: Over the 58
months of the study, a total of 6,572 doses of i.v. phytonadione were
administered. Two cases of anaphylaxis after i.v. phytonadione were identified.
The incidence of anaphylaxis was 3 per 10,000 doses with 95% confidence
intervals of 0.04 to 11 per 10,000 doses. The literature review identified 14
cases meeting inclusion criteria with no reviews of the literature or estimates
of incidence. CONCLUSIONS: The incidence of anaphylaxis after i.v. phytonadione
is overall comparable or slightly less than other drugs known to cause
anaphylaxis. We do not recommend routine pretreatment with antihistamines or
corticosteroids before administration of phytonadione.
6529.
Sanklecha MU. Cefaclor induced serum sickness like reaction. Indian J
Pediatr. 2002 Oct;69(10):921. No abstract.
6530.
Schott M, Feldkamp J, Klucken M, Kobbe G, Scherbaum WA, Seissler J.
Calcitonin-specific antitumor immunity in medullary thyroid carcinoma following
dendritic cell vaccination. Cancer Immunol Immunother. 2002 Dec;51(11-12):663-8.
In this study, we investigated the immune response
following immunotherapy with calcitonin-pulsed dendritic cells (DC) in 7
patients with metastasized medullary thyroid carcinoma. After immunization with
1-5 x 10(6) autologous DC, significant calcitonin-specific T cell proliferation
was detectable in 3 patients. Measurement of cytokine release from T lymphocytes
demonstrated high post-treatment interferon-gamma (IFN-gamma) secretion after
stimulation with calcitonin in 5 patients, one of whom experienced significant
tumor regression. In contrast, antigen-specific interleukin-4 (IL-4) production
was only slightly increased in 4 patients. All 7 patients developed a strong
delayed-type hypersensitivity (DTH) skin reaction, which was confirmed to be
mediated by infiltrating CD4+ T-helper cells and CD8+ cytotoxic T cells in all 3
patients who underwent skin biopsy. This is the first study to show that a
polypeptide hormone can be used to develop a DC vaccination strategy for the
immunotherapy of highly malignant endocrine cancers.
6531.
Siltanen M, Kajosaari M, Savilahti EM, Pohjavuori M, Savilahti E. IgG and
IgA antibody levels to cow's milk are low at age 10 years in children born
preterm. J Allergy Clin Immunol. 2002 Oct;110(4):658-63.
BACKGROUND:
Both innate and specific defenses of the preterm infant are even less developed
than those of term infants, and the immune systems of preterm infants might be
skewed differently at birth. Their immune responses to food antigens started
early in life might therefore differ from those of term infants. OBJECTIVE: We
sought to compare antibody levels to cow's milk, ovalbumin, and gliadin at age
10 years in children who had been born either preterm or at term. METHODS: IgG
and IgA isotype antibodies to whole cow's milk, beta-lactoglobulin,
alpha-casein, and ovalbumin, as well as IgG antibody levels to gliadin and to
tetanus and diphtheria toxoids, were measured for a group of 62 children born
preterm and 61 control subjects born at term. These children were studied at the
same time for atopy. RESULTS: Children born preterm had markedly lower levels of
antibodies to cow's milk and to its protein fractions (P <.0001 for IgA and
IgG antibodies to cow's milk and alpha-casein and IgG beta-lactoglobulin
antibodies). IgG gliadin antibodies were also significantly lower in the preterm
group (P =.03), although the difference was not significant for IgG ovalbumin
antibodies. In the preterm group both those born before gestational week 30 and
those given cow's milk-based formula early (before day 50) had the lowest levels
of cow's milk antibodies. In the preterm group atopy was associated with low
levels of IgG cow's milk antibodies but with high levelsof IgG ovalbumin
antibodies. CONCLUSIONS: Early introduction of food antigens into the immature
gastrointestinal tract of preterm infants might result in tolerance. The
presence of less atopy in these children might also be a result of tolerance
development.
6532.
Terashima T, Amakawa K, Matsumaru A, Yamaguchi K. Correlation between
cysteinyl leukotriene release from leukocytes and clinical response to a
leukotriene inhibitor. Chest. 2002 Nov;122(5):1566-70.
STUDY
OBJECTIVES: Antileukotriene drugs are widely used in patients with bronchial
asthma, but not all patients show significant clinical improvements, and no
factors have been identified that are correlated with the clinical response to
these drugs. This study was designed to examine the factors correlated with a
response to a leukotriene receptor antagonist, pranlukast, in patients with
asthma. DESIGN: WBC counts, IgE, and ex vivo leukotriene release from leukocytes
were measured, and 31 patients with asthma were treated with pranlukast, a
leukotriene receptor antagonist, for 4 weeks. MEASUREMENTS: Outcome measurements
included twice-daily peak expiratory flow rate (PEFR), daytime and nocturnal
symptoms, and frequency of beta(2)-agonist use. Subjects with a reduction of
> 20% in symptom scores or beta(2)-agonist use, or an improvement of PEFR of
> 10% were designated as responders; others were designated as nonresponders.
Logistic regression analysis assessed the efficacy of models using various
allergic markers correlated with the response to pranlukast. RESULTS: There were
16 responders and 15 nonresponders. The release of cysteinyl leukotrienes from
the leukocytes of the responders was higher than that of the nonresponders (p
< 0.05). There was a significant correlation between the clinical response
and the release of cysteinyl leukotrienes, but not demographic features, WBC
counts, percentage of eosinophils, or serum IgE levels (p < 0.05). Subjects
with a release of cysteinyl leukotrienes of > 3,500 pg/mL were 11.0 times
more likely to respond to pranlukast than those with < 3,500 pg/mL (95%
confidence interval, 2.0 to 60.5). CONCLUSION: Cysteinyl leukotriene release
from leukocytes is correlated with leukotriene receptor antagonist response.
6533.
Tousi P, Rahmati M, Korshid SM. Urticaria and hepatitis C infection: is
there a relationship? Int J Dermatol. 2002 Oct;41(10):712-3. No abstract.
6534.
Wagner CW. The ongoing evaluation of the impact of depression on asthma.
Ann Allergy Asthma Immunol. 2002 Dec;89(6):540-1. No abstract.
6535.
Ward KM, Celebi JT, Gmyrek R, Grossman ME. Acute infectious purpura
fulminans associated with asplenism or hyposplenism. J Am Acad Dermatol. 2002
Oct;47(4):493-6.
Acute
infectious purpura fulminans is a rapidly progressive syndrome of hemorrhagic
skin necrosis associated with acute infection and disseminated intravascular
coagulation. We report 5 cases of purpura fulminans and briefly review the
literature. All cases were associated with encapsulated organisms (Streptococcus
pneumoniae or Group A streptococcus), and 4 of the 5 patients had asplenism or
functional hyposplenism.
6536.
Wentworth P Jr, McDunn JE, Wentworth AD, Takeuchi C, Nieva J, Jones T,
Bautista C, Ruedi JM, Gutierrez A, Janda KD, Babior BM, Eschenmoser A, Lerner
RA. Evidence for antibody-catalyzed
ozone formation in bacterial killing and inflammation. Science. 2002 Dec
13;298(5601):2195-9.
Recently,
we showed that antibodies catalyze the generation of hydrogen peroxide (H2O2)
from singlet molecular oxygen (1O2*) and water. Here, we show that this process
can lead to efficient killing of bacteria, regardless of the antigen specificity
of the antibody. H2O2 production by antibodies alone was found to be not
sufficient for bacterial killing. Our studies suggested that the
antibody-catalyzed water-oxidation pathway produced an additional molecular
species with a chemical signature similar to that of ozone. This species is also
generated during the oxidative burst of activated human neutrophils and during
inflammation. These observations suggest that alternative pathways may exist for
biological killing of bacteria that are mediated by potent oxidants previously
unknown to biology.
6537.
Yousef E, McGeady SJ. Lactic acidosis and status asthmaticus: how common
in pediatrics? Ann Allergy Asthma Immunol. 2002 Dec;89(6):585-8. Review.
BACKGROUND:
Lactic acidosis is a well described phenomenon in adult patients with severe
asthma. However, this entity is rarely reported in children with status
asthmaticus. OBJECTIVE: To report our experience in a 13-year-old girl who
developed lactic acidosis as a complication of status asthmaticus and to
investigate the prevalence of this complication of severe asthma. We sought to
determine the frequency of lactic acidosis in such patients and to review
etiologies of lactic acidosis. METHODS: 1) Observations on the clinical and
laboratory findings in an adolescent girl with status asthmaticus who developed
lactic acidosis were recorded. 2) The medical records of 100 children and
adolescents with status asthmaticus admitted to an intensive care unit were
reviewed for laboratory evidence of lactic acidosis. 3) We also reviewed our own
previous experience of status asthmaticus with respiratory failure. RESULTS:
Among 100 patients admitted to a pediatric intensive care unit for status
asthmaticus, a single case of isolated metabolic acidosis was identified. This
proved to be attributable to lactic acidosis. When records of patients with
severe respiratory failure were examined, no cases of metabolic acidosis were
found. CONCLUSIONS: Although rare, lactic acidosis does occur in pediatric-aged
patients
during status asthmaticus. It is important that this complication be recognized
and treated because acidosis may inhibit the effectiveness of bronchodilator
therapy, produce electrolyte disturbances, and cause serious adverse effects on
the patient's cardiovascular system.
6538.
Zerbib F, Guisset O, Lamouliatte H, Quinton A, Galmiche JP, Tunon-De-Lara
JM. Effects of bronchial
obstruction on lower esophageal sphincter motility and gastroesophageal reflux
in patients with asthma. Am J Respir Crit Care Med. 2002 Nov 1;166(9):1206-11.
The
relationship between gastroesophageal reflux and asthma remains unclear. The aim
of this study was to analyze the effect of bronchial obstruction on lower
esophageal sphincter (LES) motility and reflux in patients with asthma. LES
motility and esophageal pH were assessed in eight subjects with intermittent
asthma and eight healthy volunteers during three consecutive 30-minute periods:
baseline, methacholine-induced bronchospasm, and after inhalation of the
beta2-agonist salbutamol. Healthy subjects inhaled 2 mg of methacholine, whereas
subjects with asthma inhaled the dose of methacholine causing a 15% fall in
FEV(1), as determined by a previous methacholine challenge. LES motility,
esophageal pH, and FEV(1) were not significantly different between the three
periods in healthy subjects. In patients with asthma, methacholine induced a
21.9 +/- 2.6% decrease in FEV(1) and a concomitant increase in the rate of
transient LES relaxation (TLESR) and reflux episodes. Inhalation of salbutamol
decreased the rate of TLESRs but not the number of reflux episodes. We conclude
that in patients with asthma, methacholine-induced bronchospasm increases the
rate of TLESR and the number of reflux episodes. These results support the
belief that, in asthma, bronchial obstruction may be responsible for reflux or
may aggravate reflux through a mechanism that remains to be further clarified.
Therapy:
6539.
Busse WW, Lenfant C, Lemanske RF Jr. Asthma guidelines: a changing
paradigm to improve asthma care. J Allergy Clin Immunol. 2002 Nov;110(5):703-5.
No abstract.
6540.
Kawashima M, Harada S, Tango T. Review of fexofenadine in the treatment
of chronic idiopathic urticaria. Int J Dermatol. 2002 Oct;41(10):701-6.
Chronic
idiopathic urticaria (CIU), characterized by the appearance of itchy wheals of
unknown etiology, can be extremely debilitating and can significantly reduce a
patient's quality of life (QOL). Fexofenadine, a non-sedating, H1-receptor
selective, long-acting antihistamine, is licensed worldwide for the treatment of
CIU. A number of dose-ranging studies have evaluated the efficacy and safety of
fexofenadine for the the treatment of CIU. In two similar North American
studies, patients received either fexofenadine HCI (20, 60, 120, or 240 mg bid)
or placebo. All four doses of fexofendine were statistically superior to placebo
at reducing pruritus and reducing the number of wheals (P < or = 0.0238). A
dose-finding study undertaken in Japanese patients confirmed that fexofenadine
HCI (60 mg and 120 mg bid) is an effective treatment for CIU. A similar dose
response was shown in all three studies when the results were compared.
Furthermore, health outcome analyses of the North American studies indicated
that fexofenadine HCI 60 mg bid significantly improved patient's QOL. In these
studies, fexofenadine had a consistently comparable safety profile to placebo,
with no dose-related trends in the incidence of adverse events. In conclusion,
fexofenadine is an effective and well-tolerated treatment for CIU, with a wide
therapeutic window. Importantly, the lack of ethnic differences between the
studies from North America and Asia indicate that the efficacy and safety of
fexofenadine demonstrated in these studies are cross-culturally applicable.
6541.
Kull I, Wickman M, Lilja G, Nordvall SL, Pershagen G. Breast feeding and
allergic diseases in infants-a prospective birth cohort study. Arch Dis Child.
2002 Dec;87(6):478-81.
AIMS:
To investigate the effect of breast feeding on allergic disease in infants up to
2 years of age. METHODS: A birth cohort of 4089 infants was followed
prospectively in Stockholm, Sweden. Information about various exposures was
obtained by parental questionnaires when the infants were 2 months old, and
about allergic symptoms and feeding at 1 and 2 years of age. Duration of
exclusive and partial breast feeding was assessed separately. Symptom related
definitions of various allergic diseases were used. Odds ratios (OR) and 95%
confidence intervals (CI) were estimated in a multiple logistic regression
model. Adjustments were made for potential confounders. RESULTS: Children
exclusively breast fed during four months or more exhibited less asthma (7.7% v
12%,
OR(adj) = 0.7, 95% CI 0.5 to 0.8), less atopic dermatitis (24% v 27%, OR(adj) =
0.8, 95% CI 0.7 to 1.0), and less suspected allergic rhinitis (6.5% v 9%, OR(adj)
= 0.7, 95% CI 0.5 to 1.0) by 2 years of age. There was a significant risk
reduction for asthma related to partial breast feeding during six months or more
(OR(adj) = 0.7, 95% CI 0.5 to 0.9). Three or more of five possible allergic
disorders-asthma, suspected allergic rhinitis, atopic dermatitis, food allergy
related symptoms, and suspected allergic respiratory symptoms after exposure to
pets or pollen-were found in 6.5% of the children. Exclusive breast feeding
prevented children from having multiple allergic disease (OR(adj) = 0.7, 95% CI
0.5 to 0.9) during the first two years of life. CONCLUSION: Exclusive breast
feeding seems to have a preventive effect on the early development of allergic
disease-that is, asthma, atopic dermatitis, and suspected allergic rhinitis, up
to 2 years of age. This protective effect was also evident for multiple allergic
disease.
6542.
McDonald E, Cook D, Newman T, Griffith L, Cox G, Guyatt G. Effect of air
filtration systems on asthma: a systematic review of randomized trials. Chest.
2002 Nov;122(5):1535-42.
STUDY
OBJECTIVES: To systematically review the evidence of randomized trials
evaluating the effects of residential air filtration systems on patients with
asthma. DATA SOURCES: We searched for published and unpublished studies using
MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, and the
Cochrane Collaboration. We reviewed all reference lists for additional articles
of relevance, and contacted experts in the field and air filter manufacturers.
STUDY SELECTION: We identified 10 relevant randomized controlled trials that
examined the influence of a residential air filtration system on patients with
asthma. DATA EXTRACTION: In duplicate and independently, we abstracted data on
the methodologic quality, population, intervention, and outcomes. DATA
SYNTHESIS: Five of 10 studies enrolled adults only. One study included children
only. The sample size ranged from 9 to 45 participants in each study, for a
total of 216 patients across all studies. Two studies reported a statistically
significant decrease in airway responsiveness associated with air filter
utilization. Air filters were associated with significantly lower total symptom
scores (weighted mean difference of 0.47; 95% confidence interval [CI], 0.69 to
0.25) on a 10-point scale, and lower sleep disturbance score (weighted mean
difference of 0.93; 95% CI, 1.44 to 0.42); however, heterogeneity of results
weakens the inferences from these trials. Air filtration systems were not
associated with any differences in medication use or morning peak expiratory
flow values. None of these trials employed validated scales to measure clinical
symptoms or quality of life. CONCLUSIONS: Among patients with allergies and
asthma, use of air filters is associated with fewer symptoms. Rigorous
sufficiently powered randomized clinical trials are
6543.
Rapoport D. Overdrugged patients: enough is enough needed to more
precisely define the influence of air filtration on health-related quality of
life and symptom control for asthmatic patients.. Can Fam Physician. 2002
Nov;48:1764. No abstract.
6544.
Sampson HA. Food allergy: from biology toward therapy. IJCP. 2002 Aug;
13(3): 17-27
ABSTRACT: Studies confirm that food allergies affect as much as 2.5 percent of the adult population. Emerging knowledge of the mechanisms is opening avenues for specific immunologic interventions, some of which have now entered clinical trials. At present, physicians can help patients to avoid allergens and can address the risk of anaphylaxis.
7057.
Aguilar Leon DE, Novelo Retana V, Martinez-Cordero E. Anti-avian
antibodies and rheumatoid factor in pigeon hypersensitivity pneumonitis. Clin
Exp Allergy. 2003 Feb;33(2):226-32.
BACKGROUND: Although several immunological abnormalities may be present in pigeon hypersensitivity pneumonitis (HP), few specific hallmarks have been described. OBJECTIVE: To determine whether the presence of rheumatoid factor (RF) could be useful to discriminate pigeon HP from asymptomatic breeders (AB) and other interstitial lung diseases. METHODS: Fifty-three patients with pigeon HP, 47 AB, 31 idiopathic pulmonary fibrosis (IPF) patients and a rheumatoid arthritis (RA) group were studied. IgM RF was determined through enzyme-linked immunosorbent assay (ELISA) and western blot using human IgG and IgG Fc fragment as antigens. IgG and IgA anti-avian antibodies (AA) against pigeon serum antigen were also measured. The use of F(ab')2 fraction of peroxidase-labelled anti-human immunoglobulins prevented endogenous interferences. Possible cross-binding of RF with avian antigens and the reactivity against human IgG by AA were studied. RESULTS: RF tests were frequently positive in HP (52.8%) in comparison to AB (4.2%) and IPF (12.9%; P = 2.6 x 10-10 and 4.1 x 10-5). Therefore, the presence of RF in pigeon HP showed a sensitivity of 52% and was highly specific considering the results of AB and IPF (95 and 87%, respectively). The RA group revealed positive RF but negative AA tests. RF activity was confirmed through western blot using purified IgG Fc fragment. Overlapping levels of IgG and IgA AA were found in HP and AB. The frequency of AA was low in IPF. The cross-reaction of RF with avian antigens was excluded, and no reactivity against human IgG by AA was detected. Other endogenous interferences were ruled out. CONCLUSION: No single immunological test may definitively distinguish pigeon HP from AB and other interstitial lung disorders; however, positive RF, together with high AA levels, seems to be useful in differentiating the diagnosis.
7058.
Alvarez-Puebla MJ, Garcia-Figueroa BE, Tabar-Purroy AI, Olaguibel-Rivera
JM. Discriminant analysis in
allergic rhinitis and asthma: methacholine dose-response slope allows a good
differentiation between mild asthma and rhinitis. Respir Med. 2003
Jan;97(1):30-6.
Asthma and rhinitis frequently coexist in allergic patients, but nasal symptoms may predominate, leading to asthma underdiagnosis and undertreatment. Discriminant analysis obtains the best differentiation between groups using one or one set of variables. Our aim was to identify the laboratory test [allergen exposure, total and specific serum IgE, lung function, blood eosinophils and, bronchial response and sensitivity to methacholine (Mth) and allergen] or combination of them that allowed the best differentiation between mild asthma and allergic rhinitis. A cross-sectional analysis was performed in 86 Dermatophogoides pteronyssinus allergic rhinitis patients, who were classified according to clinical data as rhinitis plus mild asthma (n = 62) or "pure" rhinitis (n = 24). Bronchial symptoms had been exhaustively evaluated during a 2-years pre-inclusion period. Patients underwent skin tests and bronchial challenge with Mth and allergen. The exposure to D. pteronyssinus allergen (Der pl) was quantified in dust samples. Dose-response curves with Mth [until the FEV1 fell by 40% or the maximal dose (200 mg/ml) was inhaled] were attained. We developed multiple models of discriminant analysis in order to evaluate the capacity of the above variables to differentiate groups. Asthma patients had higher total and specific IgE levels and a greater sensitivity (PD20 values) and response [dose-response slope (DRS)] to both Mth and allergen. The model entering these variables was the one that correctly classified more patients (79.2%). The discriminative power of the model that only included Mth-DRS values was similar to the above (78.8%). Bronchial response to Mth is quantitatively different in allergic rhinitis patients who display mild asthma symptoms when compared to those that only report rhinitis, suggesting a distinct bronchial intrinsic behavior. The utilization of complete dose-response curves with Mth allows a good separation between mild asthma and "pure" rhinitis patients and might be useful in the diagnosis of mild asthma. Whether the early detection and treatment of these patients prevents the development of symptomatic asthma needs further evaluation.
7059.
Andre F, Cavagna S, Andre C. Gelatin prepared from tuna skin: a risk
factor for fish allergy or sensitization? Int Arch Allergy Immunol. 2003
Jan;130(1):17-24.
BACKGROUND:
Although fish gelatin may represent a useful alternative to bovine or porcine
gelatin, the clearly recognized high prevalence of fish allergy could increase
the risk of anaphylaxis to gelatin. The rationale for investigating tuna gelatin
rather than gelatin from more allergenic fishes is the availability of an
industrial gelatin under development. The infrequent occurrence of tuna allergy
should influence the safety of a derived product. The present study investigated
IgE antibodies to tuna-skin-derived gelatin in adults and children with
documented fish allergy or sensitization. METHODS: Serum samples were taken from
100 consecutive patients with fish allergy or sensitization and tested for IgE
antibodies against hydrolyzed or nonhydrolyzed gelatin extracted from tuna skin
as compared to extracts from tuna flesh, tuna skin as well as bovine or porcine
gelatin. Patients with tuna allergies or sensitization were sensitive to the
same tuna species (yellowfin) as that from which the gelatin was obtained. IgE
antibodies to these various extracts were analyzed using SDS-PAGE and
immunoblotting. RESULTS: Only 3 of the 100 serum samples tested gave evidence of
reactivity to gelatin extracted from tuna skin. Cross-reactivity between
bovine/porcine and fish gelatin was not observed. CONCLUSION: The risk of
adverse reactions to tuna skin gelatin seems to be significantly lower than the
risk of fish allergy. Fish gelatin may represent a valuable alternative to
bovine or porcine gelatin. Copyright 2003 S. Karger AG, Basel
7060.
Aoyagi M, Shimojo N, Sekine K, Nishimuta T, Kohno Y. Respiratory
syncytial virus infection suppresses IFN-gamma production of gammadelta T cells.
Clin Exp Immunol. 2003 Feb;131(2):312-7.
The immunological mechanisms by which respiratory syncytial virus (RSV) contributes to the development of asthma are poorly understood. gammadelta T cells are important in mucosal defence, and may contribute to the establishment of primary immune responses by producing cytokines early during respiratory infections. Thus, we used flow cytometry and intracellular cytokine staining to investigate the expression of interferon (IFN)-gamma and interleukin (IL)-4 by mitogen-stimulated gammadelta T cells from the peripheral blood of 15 hospitalized infants with RSV bronchiolitis, seven rotavirus-infected infants and eight normal controls. gammadelta T cells from RSV-infected infants had a lower proportion of IFN-gamma-producing cells (median, 4.00%; range, 0.58-6.60%) and a slightly but significantly higher proportion of IL-4-producing cells (median, 0.40%; range, 0.13-2.76%) than rotavirus-infected infants (median, 32.10%; range, 14.43-61.21%; P < 0.01, median, 0.00%; range, 0.00-0.00%; P < 0.05) in the acute phase. By contrast, differences in cytokine production by total CD3+ T cells did not differ significantly between patient groups. Thus, reduced IFN-gamma-production by gammadelta T cells in the peripheral blood of RSV-infected infants is accompanied by increased Th2 cytokine production during the acute phase of disease. At follow-up, eight children had recurrent episodes of wheezing. The frequencies of IFN-gamma-producing gammadelta T cells were significantly lower in patients who developed recurrent wheezing (median, 0.65%; range, 0.02-1.75%) than in patients without recurrent wheezing (median, 6.90%; range, 5.25-10.98%; P < 0.005). Cytokine production by gammadelta T cells may therefore be important in the pathogenesis of acute RSV disease, and play a part in the development of recurrent childhood wheezing after bronchilolitis.
7061.
Bender BG, Leung SB, Leung DY. Actigraphy assessment of sleep disturbance
in patients with atopic dermatitis: an objective life quality measure. J Allergy
Clin Immunol. 2003 Mar;111(3):598-602.
BACKGROUND:
Patients with atopic dermatitis (AD) frequently report compromised quality of
life because of disturbed sleep and daytime fatigue secondary to their skin
disease, but few studies provide objective measurement of sleep change in this
population. OBJECTIVE: The purpose of this investigation was to contrast
subjective and objective measures of sleep quality in patients with AD. METHODS:
Fourteen adult patients with AD and 14 adult control subjects with no skin
disease wore actigraphs for 1 week and completed questionnaires about sleep,
itch, and quality of life. RESULTS: As measured by self-report and actigraphy,
the AD group slept more poorly and reported more daytime fatigue than the
control group. Actigraphy alone was correlated with itch and quality of life and
was able to discriminate movement during sleep, number of awakenings, minutes
asleep, and minutes awake. CONCLUSIONS: Results from this study demonstrate that
sleep is significantly compromised in patients with AD. Patients' perception of
their sleep provides less detail and accuracy than actigraphy. The actigraph is
an objective, unobtrusive measure of sleep at home in patients with skin disease
and can provide an important outcome measure in clinical trials.
7062.
Boumiza R, Monneret G, Forissier MF, Savoye J, Gutowski MC, Powell WS,
Bienvenu J. Marked improvement of the basophil activation test by detecting
CD203c instead of CD63. Clin Exp Allergy. 2003 Feb;33(2):259-65.
BACKGROUND:
The flow cytometric basophil activation test by detection of CD63 expression has
been developed as an alternative method for in vitro diagnosis of IgE-mediated
reactions to various allergens. Despite promising initial studies, the test
remains disappointing in terms of sensitivity. CD203c has recently been
demonstrated as a specific activation marker of basophils that is rapidly
up-regulated after allergen challenge in sensitized patients. OBJECTIVE: The
goal of the present study was to compare basophil activation tests by using
either CD203c or CD63 in the diagnosis of immediate-type allergy to latex.
METHODS: Twenty-seven patients (health care workers of our institution) who
developed clinical features evocative of allergy after contact with latex were
included and classified into two groups. Group 1 (n = 16) comprised true
allergic patients who presented with typical signs of immediate allergic
reaction associated with a positive skin test (prick test). Group 2 (n = 11)
consisted of patients whose clinical history was not typical and had negative
skin test. Twelve healthy subjects were also studied as controls. We compared
the sensitivity of two triple-staining flow cytometric protocols measuring
basophil activation after latex stimulation: CD45-IgE-CD63 and CD45-IgE-CD203c.
RESULTS: The CD203c protocol showed a higher sensitivity than the CD63 protocol
(75% vs. 50%). In comparison, latex-specific IgE sensitivity was found to be
69%. Furthermore, the magnitude of the basophil response was significantly
higher with CD203c in comparison with CD63. Specificity was 100% for both
protocols. CONCLUSION: Due to superior gating of basophils and a higher range of
activation in response to allergen, the basophil activation test is markedly
improved by use of CD203c instead of CD63.
7063.
Chou H, Chang CY, Tsai JJ, Tang RB, Lee SS, Wang SR, Peng HJ, Shen HD.
The prevalence of IgE antibody reactivity against the alkaline serine
protease major allergen of Penicillium chrysogenum increases with the age of
asthmatic patients. Ann Allergy Asthma Immunol. 2003 Feb;90(2):248-53.
BACKGROUND:
Penicillium species are prevalent airborne fungi. However, the prevalence of
allergic sensitization to Penicillium antigens and the true impact of these
ubiquitous fungi on atopic respiratory disorders remain to be determined.
OBJECTIVE: The purpose of this study was to analyze the prevalence of
immunoglobulin (Ig)E and IgG antibodies against Penicillium chrysogenum (Pen ch
13), the alkaline serine protease major allergen of P. chrysogenum, in asthmatic
patients of different age groups. METHODS: Pen ch 13 was purified from a culture
medium of P. chrysogenum. The reactivity of IgE and IgG antibodies to Pen ch 13
in the serum samples of 212 asthmatic patients was analyzed by immunoblotting
methods. RESULTS: Sixty-nine (33%) of the 212 sera analyzed showed IgE and/or
IgG immunoblot reactivity to Pen ch 13. Significant differences in the
prevalence of IgE and/or IgG antibody reactivity to Pen ch 13 were found among
eight different age groups of 212 asthmatic patients. The frequency of IgE-binding
reactivity to Pen ch 13 increased significantly with the age of the patients. It
was 7% for the group less than 10 years old and 42% for the group older than 70
years old. In addition, a significant difference between the prevalence of IgE
(7%) and IgG (33%) antibodies against Pen ch 13 in the group aged 10 or less was
also found. CONCLUSIONS: Our study demonstrates that IgE and IgG antibodies
specific for Pen ch 13 were detected in approximately one-third of the 212
asthmatic patients analyzed. Our results suggest that allergic sensitization to
Pen ch 13, and possibly to other airborne Penicillium species, is more common in
older asthmatic patients. PMID: 12602675 [PubMed - indexed for MEDLINE]
7064.
Corradi M, Folesani G, Andreoli R, Manini P, Bodini A, Piacentini G,
Carraro S, Zanconato S, Baraldi E. Aldehydes and glutathione in exhaled breath
condensate of children with asthma exacerbation. Am J Respir Crit Care Med. 2003
Feb 1;167(3):395-9.
Oxidative
stress is implicated in the pathogenesis of asthma, and clinical studies show an
imbalance in the level of oxidants to the level of antioxidants in subjects with
asthma. Aldehydes and glutathione are examples of biomarkers of oxidant-induced
damage and antioxidant status in asthma, respectively. In the study, we applied
analytical techniques based on liquid chromatography for the assessment of
aldehydes and glutathione in the exhaled breath condensate of children with
asthma and in control subjects without asthma. Twelve subjects with asthma were
evaluated at exacerbation and after 5 days of therapy with prednisone. At
exacerbation, malondialdehyde levels were higher in patients with asthma (30.2
+/- 2.4 nM) than in control subjects (19.4 +/- 1.9 nM, p = 0.002) and were
reduced after steroid therapy (18.5 +/- 1.6 nM, p = 0.001). At exacerbation,
glutathione levels were lower in subjects with asthma (5.96 +/- 0.6 nM) than in
control subjects (14.1 +/- 0.8 nM, p < 0.0001) and were increased after the
therapy (8.44 +/- 1.2 nM, p = 0.04). Malondialdehyde and glutathione both in
subjects with asthma and control subjects were negatively correlated (r = -0.5,
p = 0.001). The study shows that aldehydes and glutathione are detectable in the
exhaled breath condensate of children with asthma and healthy children and that
their levels are modified during asthma exacerbation and after a 5-day course of
therapy with oral prednisone. PMID: 12411284 [PubMed - indexed for MEDLINE]
7065.
De Boissieu D, Waguet JC, Dupont C. The atopy patch tests for detection
of cow's milk allergy with digestive symptoms. J Pediatr. 2003 Feb;142(2):203-5.
Infants
(n = 35) with digestive symptom were investigated for diagnosis of cow's milk
allergy (CMA). Milk atopy patch tests (APTs) were positive in 19 of 24 CMA
versus 1 of 11 in non-CMA patients (P <.001). This sensitivity (79%) and
specificity (91%) suggest that the APT could improve the detection of conditions
related to CMA. Publication Types: Validation Studies PMID: 12584547 [PubMed -
indexed for MEDLINE]
7066.
Eaton DA, Roland PS, Mabry RL, Shoup AG. Electrocochleography and
intranasal allergen challenge as investigational tools in patients with inhalant
allergy and Meniere's disease. Laryngoscope. 2003 Jan;113(1):33-6.
OBJECTIVES:
To expand on a prior study investigating the relation between inhalant allergy
and Meniere's disease using electrocochleography and to present data from five
patients heretofore unmentioned in previous reports. STUDY DESIGN: Prospective
study of five patients identified with Meniere's disease and inhalant allergy in
the practices of two faculty otolaryngologists. METHODS: Patients were tested
twice using electrocochleography: once as a baseline and again 20 minutes
following intranasal challenge with the allergen to which they were most
sensitive. RESULTS: Three patients had no prior history of immunotherapy, and
all were found to have a >15% increase in summating potential (SP)/action
potential (AP) ratio after antigen challenge. However, only one of these
patients developed audiovestibular symptoms. Two patients had a history of
immunotherapy. One of these patients was tested using three different antigens
to which she was highly sensitive on skin testing, one of which provoked
audiovestibular symptoms on environmental exposure. Postchallenge
electrocochleography, however, demonstrated normal SP/AP ratios with only one
antigen causing a >15% increase. The other patient had elevated SP/AP ratios
both before and after challenge and developed no audiovestibular symptoms
despite a >15% increase. CONCLUSIONS: Previous work using this
investigational tool has identified that all patients with a normal
electrocochleography were asymptomatic from an audiovestibular standpoint at the
time of postchallenge testing. An elevated SP/AP was not reliably correlated
with audiovestibular symptoms in this group of patients. Further investigation
in this area will examine the utility of using the variability of the SP and AP
to predict audiovestibular symptoms.PMID: 12514378 [PubMed - indexed for
MEDLINE]
7067.
Gonzalez-Quintela A, Gude F, Boquete O, Rey J, Meijide LM, Suarez F,
Fernandez-Merino MC, Perez LF, Vidal C. Association of alcohol consumption with
total serum immunoglobulin E levels and allergic sensitization in an adult
population-based survey. Clin Exp Allergy. 2003 Feb;33(2):199-205.
BACKGROUND:
Chronic alcoholism is associated with increased total serum IgE levels.
OBJECTIVE: The study aimed to investigate the relationship between alcohol
intake and both total serum IgE levels and allergic sensitization in a general
adult population. MATERIALS AND METHODS: A total of 720 subjects was randomly
selected (stratified by age) from the population older than 18 years of
A-Estrada (Spain) and invited to participate in the study. From 697 eligible
subjects, 469 (67%, median age 54 years, range 18 to 92 years, 44% males, 75% of
cases from a rural environment) agreed to participate. A battery of 13 skin
prick tests to common aeroallergens was performed in all subjects. Cases with at
least one positive test (n = 121, 26%) were considered to have allergic
sensitization. The most frequent sensitisers were mites and pollens (24% and 10%
of subjects, respectively). Total serum IgE was measured in 465 subjects (99%).
Alcohol consumption was registered as the number of standard (approximately 10
g) drinking units habitually consumed per week. A total of 244 subjects (52%)
were alcohol consumers (median intake, 14 units/week, range 1 to 147
units/week). Abstainers (n = 225, 48%) constituted the reference category.
RESULTS: Alcohol consumption of more than 14 units/week was associated with an
increase in serum IgE levels after adjusting for age, gender, allergic
sensitization and smoking (P = 0.02). Alcohol consumption was not significantly
associated with either overall allergic sensitization or mite sensitization
after adjusting for age, gender and smoking. However, alcohol consumption of
more than 14 units/week was associated with an increased prevalence of pollen
sensitization (adjusted OR 3.15, 95% CI 1.19 to 8.34, P = 0.02). CONCLUSION:
Alcohol consumption above a certain threshold is associated with an increase in
total serum IgE levels. Alcohol consumption may also be associated with an
increased prevalence of pollen sensitization. PMID: 12580912 [PubMed - indexed
for MEDLINE]
7068.
Hamilton RG, Adkinson NF Jr. Clinical laboratory assessment of IgE-dependent
hypersensitivity. J Allergy Clin Immunol. 2003 Feb;111(2 Suppl):S687-701.
Review.
This
chapter reviews clinical and laboratory analyses that aid in the diagnosis and
management of human allergic (IgE-dependent) diseases. The diagnostic algorithm
for immediate-type hypersensitivity begins with a thorough clinical history and
physical examination. Once signs and symptoms compatible with an allergic
disorder have been identified, a skin test and/or blood test for
allergen-specific IgE antibodies may serve as primary confirmation to strengthen
the diagnosis. Puncture and intradermal skin testing provide a biologically
relevant immediate-type hypersensitivity response in the skin, with resultant
wheal and flare reactions within 15 minutes of allergen application. Bleeding,
dermatographism, and antihistamines may confound the quality of the skin test.
Allergen-specific IgE antibody may also be detected in the blood using a
radioallergosorbent test (RAST). Nonisotopic "second-generation" RAST-type
assays have evolved to provide more quantitative, sensitive, precise IgE
antibody results. In vivo provocation tests may serve as secondary confirmatory
tests when the clinical history is discordant with a primary IgE antibody test
result. The multiallergen screen is a qualitative RAST-type assay that detects
specific IgE antibody to approximately 15 allergens that evoke a large majority
of aeroallergen or food-related allergic disorders. Other useful serological
assays performed in the diagnostic allergy laboratory include total serum IgE,
Hymenoptera venom-specific IgG antibody, IgG precipitins for organic dusts, mast
cell tryptases, and the venom RAST inhibition test. Above all, in vivo or
laboratory confirmatory test results that are inconsistent with the clinical
history should be repeated as for any laboratory assessment. Publication Types:
Review Review,
Tutorial PMID: 12592314 [PubMed - indexed for MEDLINE]
7069.
Holgate ST, Peters-Golden M. Introduction: the anti-inflammatory role of
cysteinyl leukotriene receptor antagonists in asthma. J Allergy Clin Immunol.
2003 Jan;111(1 Suppl):S1-4. No abstract availabe.
7070.
Jin GB, Nakayama H, Shmyhlo M, Inoue S, Kondo M, Ikezawa Z, Ouchi Y,
Cyong JC. High positive frequency
of antibodies to metallothionein and heat shock protein 70 in sera of patients
with metal allergy. Clin Exp Immunol. 2003 Feb;131(2):275-9.
Two
principal types of stress protein, heat shock proteins (hsps) and
metallothionein (MT), are induced in cells responding to a variety of stresses.
They play an important role in protecting cells from these stresses. However,
many reports indicate that antibodies to hsps are present in human serum and are
associated with several autoimmunity diseases. Metals, which are commonly
allergenic to humans, induce both MT and hsp70 (one of the hsps family). Until
now, there has been no report of any antibody to MT in human serum. In the
present study, serum samples from healthy controls (Group I), and patients
suffering from atopic dermatitis without (Group II) or with (Group III) metal
allergy, were measured for antibodies to MT and hsp70, using an enzyme-linked
immunosorbent assay (ELISA). Metal allergy was confirmed by patch testing. We
first found that antibody to MT exists in human serum. We also found a high
positive frequency of antibody to MT (51.3%) and to hsp70 (43.6%) in the sera of
Group III, compared to those of Group I (3.8% and 5.1%) or Group II (6.4% and
5.1%). Furthermore, there was a strong positive correlation between antibody to
MT and antibody to hsp70 in Group III (P = 0.0013), but not in Group I and Group
II. Our results indicate that antibody to MT exists in human serum, as do
antibodies to hsps, and suggest that elevated levels of MT and hsp70 antibodies
are associated with metal allergy in atopic patients. PMID: 12562388 [PubMed -
indexed for MEDLINE]
7071.
Kaito K, Otsubo H, Ogasawara Y, Kimura H, Kurihara E, Koike M, Aiso M,
Kobayashi M. Serum soluble interleukin-2 receptor in eosinophilia. Acta Haematol.
2003;109(1):23-8.
The
relationship between soluble interleukin-2 receptor (sIL-2R) levels and clinical
characteristics was evaluated in patients with eosinophilia. Thirty-eight out of
60 patients showed sIL-2R levels of more than 800 U/ml. In these patients,
sIL-2R was closely related to the eosinophil count, but not the IgE level. Their
underlying diseases were heterogeneous, including neoplasms and collagen
diseases. In patients with lower sIL-2R levels, there was no relationship to the
eosinophil count, but sIL-2R was correlated with the IgE level. These findings
indicate that patients with eosinophilia and higher sIL-2R levels tend to have
underlying diseases other than allergy, and might be more severely ill than
patients with lower sIL-2R levels. sIL-2R may be a good marker for evaluating
patients with eosinophilia, as an indicator of the probable etiology and
severity of their diseases. Copyright 2003 S. Karger AG, Basel PMID: 12486319 [PubMed
- indexed for MEDLINE]
7072.
Linneberg A, Petersen J, Nielsen NH, Madsen F, Frolund L, Dirksen A,
Jorgensen T. The relationship of alcohol consumption to total immunoglobulin E
and the development of immunoglobulin E sensitization: the Copenhagen Allergy
Study. Clin Exp Allergy. 2003 Feb;33(2):192-8.
BACKGROUND:
Several studies in patient populations have reported a positive association
between alcohol consumption and serum total IgE. Furthermore, we have previously
reported a positive association between alcohol consumption and the prevalence
of skin prick test (SPT positivity) to inhalant allergens in a population-based
cross-sectional study. OBJECTIVE: To investigate the relationship of alcohol
consumption to levels of serum total IgE and the development of IgE
sensitization to inhalant allergens. METHODS: In 1990, self-reported consumption
of alcohol, serum total IgE, SPT positivity and specific IgE positivity to
inhalant allergens were assessed in 1112 subjects, aged 15-69 years,
participating in a population-based cross-sectional study in Copenhagen,
Denmark. In 1998, they were invited to a follow-up and 734 were re-examined
(participation rate 69.0%). Adjustment for potential confounders was performed
by using multivariable regression analyses. RESULTS: In non-atopic (specific IgE
negative) subjects there was a positive association between alcohol consumption
and the concentration of total IgE (P = 0.001). During the follow-up period, 45
and 33 subjects developed SPT positivity and specific IgE positivity,
respectively. There was no significant association between alcohol consumption
and the development of SPT positivity or specific IgE positivity. However, the
risk of developing SPT positivity tended to increase with increasing consumption
of alcohol (P = 0.055). CONCLUSIONS: This epidemiological study confirms that
alcohol consumption has an influence on levels of serum total IgE. A significant
association between alcohol consumption and the development of IgE sensitization
was not established. However, there seems to be a lack epidemiological data on
this issue. PMID: 12580911 [PubMed - indexed for MEDLINE]
7073.
Mayorga C, Torres MJ, Corzo JL, Alvarez J, Garcia JA, Rodriguez CA,
Blanca M, Jurado A. Immediate allergy to tetanus toxoid vaccine: determination
of immunoglobulin E and immunoglobulin G antibodies to allergenic proteins. Ann
Allergy Asthma Immunol. 2003 Feb;90(2):238-43.
BACKGROUND:
Adverse reactions to tetanus toxoid (TT) vaccine are mostly mild and limited to
the injection site. However, immunoglobulin (Ig)E-mediated reactions may occur,
and the incidence of anaphylactic responses to TT immunization is 0.001%. When
TT induces an allergic reaction, the potential causative agents can be TT
antigens, thimerosal or aluminum phosphate. OBJECTIVE: We studied four children
who developed immediate urticaria after TT vaccine, soon after the reaction and
5 years later. METHODS: Skin tests were performed separately with TT vaccine and
two vaccine components, thimerosal and aluminum phosphate, and the diagnosis was
confirmed by provocation test. IgE and IgG antibodies to TT and their
specificities were determined. Sodium dodecyl sulfate-polyacrylamide gel
electrophoresis and immunoblotting were performed to characterize the antigenic
proteins. RESULTS: All four children were immediate skin test-positive to TT,
but negative to thimerosal and aluminum phosphate; 3 developed a reaction after
intramuscular provocation using increasing doses of TT vaccine; and 1 refused to
be tested. All these tests were negative in five controls, all of whom received
TT vaccine and developed only local swelling at the site of application 24 hours
after vaccine administration. After 5 years the IgG antibodies were still high
in all cases and the IgE antibody values fell by 50%. Patients allergic to TT
vaccine produced IgE and IgG antibodies, which decreased at different rates but
remained for at least 5 years. The pattern of antibody decrease was confirmed by
radioallergosorbent test, enzyme-linked immunoadsorbent assay, or immunoblotting
assay. IgE and IgG antibodies recognized two proteins derived from TT, of 150
and 50 kDa, corresponding to the intracellular form and to a chain of the
extracellular form of the tetanus neurotoxin. CONCLUSIONS: In children with
immediate allergic reactions to TT vaccine, antibodies may persist for at least
5 years, requiring evaluation by skin and/or in vitro tests before subsequent
treatment.PMID: 12602673 [PubMed - indexed for MEDLINE]
7074.
Oura H, Bertoncini J, Velasco P, Brown LF, Carmeliet P, Detmar M. A
critical role of placental growth factor in the induction of inflammation and
edema formation. Blood. 2003 Jan 15;101(2):560-7.
Angiogenesis
is a prominent feature of a number of inflammatory human diseases, including
rheumatoid arthritis, psoriasis, and cutaneous delayed-type hypersensitivity (DTH)
reactions. Up-regulation of placental growth factor (PlGF), a member of the
vascular endothelial growth factor (VEGF) family, has been found in several
conditions associated with pathologic angiogenesis; however, its distinct role
in the control of angiogenesis has remained unclear. To directly investigate the
biologic function of PlGF in cutaneous inflammation and angiogenesis, DTH
reactions were investigated in the ear skin of wild-type mice, of PlGF-deficient
mice, and of transgenic mice with targeted overexpression of human PlGF-2 in
epidermal keratinocytes, driven by a keratin 14 promoter expression construct.
Chronic transgenic delivery of PlGF-2 to murine epidermis resulted in a
significantly increased inflammatory response, associated with more pronounced
vascular enlargement, edema, and inflammatory cell infiltration than seen in
wild-type mice. Conversely, PlGF deficiency resulted in a diminished and
abbreviated inflammatory response, together with a reduction of inflammatory
angiogenesis and edema formation. VEGF expression was up-regulated at a
comparable level in the inflamed skin of all genotypes. These findings reveal
that placental growth factor plays a critical role in the control of cutaneous
inflammation, and they suggest inhibition of PlGF bioactivity as a potential new
approach for anti-inflammatory therapy. PMID: 12393422 [PubMed - indexed for
MEDLINE]
7075.
Pham DN, Chu HW, Martin RJ, Kraft M. Increased matrix metalloproteinase-9
with elastolysis in nocturnal asthma. Ann Allergy Asthma Immunol. 2003
Jan;90(1):72-8.
BACKGROUND:
Matrix metalloproteinase-9 (MMP-9) is capable of degrading elastin, whereas
tissue inhibitor of metalloproteinase-1 (TIMP-1) can inhibit MMP-9 activity. We
observed reduced airway tissue elastin volume density in six subjects with
nocturnal asthma (NA) as compared with seven subjects with nonnocturnal asthma (NNA)
and seven normal controls (NL) when endobronchial biopsies were evaluated
morphometrically at 4:00 PM and 4:00 AM. OBJECTIVE: We hypothesized that
increased metalloproteinases and decreased tissue inhibitors of
metalloproteinases in the airways of subjects with NA may be responsible for
reduced elastin volume density. METHODS: Ten additional subjects with NA, 10
subjects with NNA, and 7 normal control subjects underwent bronchoscopy with
bronchoalveolar lavage at 4:00 PM and 4:00 AM. Levels of MMP-2, MMP-9, TIMP-1,
and TIMP-2 were determined in bronchoalveolar lavage by enzyme-linked
immunosorbent assay. RESULTS: There was a fourfold circadian increase in
bronchoalveolar lavage levels of MMP-9, and there was a twofold increase in
MMP-9:TIMP-1 ratio in NA subjects from 4:00 PM to 4:00 AM. There were no
circadian changes in the NNA and NL subjects. At 4:00 AM, MMP-9 levels and the
MMP-9:TIMP-1 ratio were highest in NA subjects. At 4:00 PM, no significant group
differences were observed. The MMP-9 levels positively correlated with the
overnight fall in forced expiratory volume in 1 second and the MMP-9/TIMP-1
ratio negatively correlated with the 4:00 AM % predicted forced expiratory
volume in 1 second. CONCLUSIONS: Our results from these two pilot studies
suggest that increased MMP-9 and decreased TIMP-1 at night in NA may lead to
reduced elastin density. PMID: 12546341 [PubMed - indexed for MEDLINE]
7076.
Silkoff P. Exhaled nitric
oxide as a diagnostic tool. Am J Respir Crit Care Med. 2003 Feb 15;167(4):665-6.
No abstract available.
7077.
Skowron M, Perret E, Marano F, Caput D, Tournier F. Interleukin-13 alters
mucociliary differentiation of human nasal epithelial cells. Chest. 2003
Mar;123(3 Suppl):373S-4S. Review. No abstract available.
7078.
Tamura Y, Kawaguchi J, Serizawa N, Hirahara K, Shiraishi A, Nigi H,
Taniguchi Y, Toda M, Inouye S, Takemori T, Sakaguchi M. Analysis of sequential
immunoglobulin E-binding epitope of Japanese cedar pollen allergen (Cry j 2) in
humans, monkeys and mice. Clin Exp Allergy. 2003 Feb;33(2):211-7.
BACKGROUND:
Japanese cedar (Cryptomeria japonica; CJ) pollinosis has been reported to occur
naturally in Japanese monkeys (Macaca fuscata) as well as in humans. Most human
patients and monkeys with pollinosis have specific IgE for Cry j 2, a major
allergen of CJ pollen. OBJECTIVE: The main purpose of this study was to identify
IgE B cell epitopes of Cry j 2 using a synthetic peptide in humans, monkeys and
mice. METHODS: We synthesized 38 overlapping peptides that span the entire
length of Cry j 2. We examined the B cell epitopes of Cry j 2 that are
recognized by IgE in the sera of human patients and monkeys with pollinosis and
immunized mice using synthetic peptides of Cry j 2. We also examined the
reaction of Cry j 2-specific mouse monoclonal IgG antibodies to the peptides.
Furthermore, we conducted a histamine release assay with leucocytes from a
pollinosis patient using human serum albumin (HSA) conjugated with the peptides
as a B cell epitope. RESULTS: We found that 16 of the 20 pollinosis patients who
had specific IgE to Cry j 2 also exhibited IgE reaction with some Cry j 2
peptides. Of these 16 patients, 10 exhibited IgE reaction with Cry j 2 peptide
no. 13 (121GQCKWVNGREICNDRDRPTA140). Five of the seven monkeys with CJ
pollinosis exhibited a reaction with peptide no. 13. Furthermore, IgE in mice
immunized with Cry j 2 and two mouse monoclonal IgG antibodies reacted with
peptide no. 13. Peptide no. 13-conjugated HSA showed the release of histamine
from basophils. Furthermore, to determine the minimum epitope in peptide no. 13,
we conducted an enzyme-linked immunosorbent assay inhibition test. The core of
the epitope in humans, monkeys and mice was 124KWVNGREI131. CONCLUSION: We found
that 124KWVNGREI131 is an important B cell epitope recognized by IgE in humans,
monkeys and mice. PMID: 12580914 [PubMed - indexed for MEDLINE]
7079.
Wang CL, Wu YT, Liu CA, Lin MW, Lee CJ, Huang LT, Yang KD. Expression of
CD40 ligand on CD4+ T-cells and platelets correlated to the coronary artery
lesion and disease progress in Kawasaki disease. Pediatrics. 2003
Feb;111(2):E140-7.
OBJECTIVE:
Kawasaki disease (KD) is an acute febrile vasculitic syndrome in children. CD40
ligand (CD40L) has been implicated in certain types of vasculitis. We proposed
that CD40L expression might be correlated with coronary artery lesions in KD.
METHODS: Blood samples were collected from 43 patients with KD before
intravenous immunoglobulin (IVIG) treatment and 3 days afterward. Forty-three
age-matched febrile children with various diseases were studied in parallel as
controls. CD40L expression on T-cells and platelets were detected by flow
cytometry, and soluble CD40L (sCD40L) levels were measured by enzyme-linked
immunosorbent assay. RESULTS: We found that CD40L expression on CD4(+) T-cells
was significantly higher in patients with KD than in the febrile control (FC)
group (28.69 +/- 1.17% vs 4.37 +/- 0.36%). CD40L expression decreased
significantly 3 days after IVIG administration (28.69 +/- 1.17% vs 13.53 +/-
0.55%). CD40L expression on platelets from patients with KD was also
significantly higher than in the FC group (8.20 +/- 0.41% vs 1.26 +/- 0.12%) and
decreased after IVIG therapy. sCD40L levels were also significantly higher in KD
patients with those of FC (9.69 +/- 0.45 ng/mL vs 2.25 +/- 0.19 ng/mL) but were
not affected by IVIG treatment 3 days afterward (9.69 +/- 0.45 ng/mL vs 9.03 +/-
0.32 ng/mL). More interesting, we found that in KD patients, CD40L expression on
CD4(+) T-cells and platelets but not on CD8(+) T-cells or sCD40L was correlated
with the occurrence of coronary artery lesions. CONCLUSIONS: CD40L might play a
role in the immunopathogenesis of KD. IVIG therapy might downregulate CD40L
expression, resulting in decrease of CD40L-mediated vascular damage in KD. This
implicates that modulation of CD40L expression may benefit to treat KD
vasculitis. PMID: 12563087 [PubMed - indexed for MEDLINE]
7080.
Wang L, McParland BE, Pare PD. The functional consequences of structural
changes in the airways: implications for airway hyperresponsiveness in asthma.
Chest. 2003 Mar;123(3 Suppl):356S-62S. Review. No abstract available.
7081.
Wessler I, Reinheimer T, Kilbinger H, Bittinger F, Kirkpatrick CJ, Saloga
J, Knop J. Increased acetylcholine levels in skin biopsies of patients with
atopic dermatitis. Life Sci. 2003 Mar 28;72(18-19):2169-72.
Recent
experimental evidence indicates that non-neuronal acetylcholine is involved in
the regulation of basic cell functions. Here we investigated the cholinergic
system in the skin of healthy volunteers and patients with atopic dermatitis
(AD). The synthesizing enzyme, choline-acetyltransferase (ChAT), was studied by
anti-ChAT immunohistochemistry and enzyme assay. Skin biopsies taken from
healthy volunteers and from AD patients were separated into the 2 mm superfical
(epidermis and upper dermis) and 3 mm underlying portion (deeper dermis and
subcutis). ChAT enzyme activity was detected in homogenized skin and
subcutaneous fat (about 13 nmol/mg protein/h). ChAT immunoreactivity was
expressed in keratinocytes, hair papilla, sebaceous and eccrine sweat glands,
endothelial cells and mast cells. In healthy volunteers the superficial and
underlying portion of skin biopsies contained 130 +/- 30 and 550 +/- 170 pmol/g
acetylcholine (n = 12), respectively. In AD patients (n = 7) acetylcholine was
increased 14-fold in the superficial and 3-fold in the underlying biopsy
portion. The present study demonstrates the widespread expression of ChAT
protein in the vast majority of human skin cells. Tissue levels of acetylcholine
are greatly (14-fold) enhanced in the superficial 2 mm skin of AD patients.
Copyright 2003 Elsevier Science Inc. Publication Types:
Clinical Trial PMID: 12628475 [PubMed - indexed for MEDLINE]
7082.
Yu CJ, Lin YF, Chiang BL, Chow LP. Proteomics and immunological analysis
of a novel shrimp allergen, Pen m 2. J Immunol. 2003 Jan 1;170(1):445-53.
Shellfish
are a common cause of adverse food reactions in hypersensitive individuals and
shrimp is one of the most frequently reported causes of allergic reactions. A
novel allergen from Penaeus monodon, designated Pen m 2, was identified by
two-dimensional immunoblotting using sera from subjects with shrimp allergy,
followed by matrix-assisted laser desorption ionization time-of-flight mass
spectrometry analysis of the peptide digest. This novel allergen was then cloned
and the amino acid sequence deduced from the cDNA sequence. The cloned cDNA
encoded a 356-aa protein with an acetylated N terminus at Ala2, identified by
postsource decay analysis. Comparison of the Pen m 2 sequence with known protein
sequences revealed extensive similarity with arginine kinase (EC 2.7.3.3) from
crustaceans. Pen m 2 was purified by anion exchange chromatography and shown to
have arginine kinase activity and to react with serum IgE from shrimp allergic
patients and induce immediate type skin reactions in sensitized patients. Using
Pen m 2-specific antisera and polyclonal sera from shrimp-sensitive subjects in
a competitive ELISA inhibition assay, Pen m 2 was identified as a novel
cross-reactive Crustacea allergen. This novel allergen could be useful in
allergy diagnosis and in the treatment of Crustacea-derived allergic disorders.
PMID: 12496430 [PubMed - indexed for MEDLINE]
7083.
Zheng X, Nakamura K, Furukawa H, Nishibu A, Takahashi M, Tojo M, Kaneko
F, Kakinuma T, Tamaki K. Demonstration of TARC and CCR4 mRNA expression and
distribution using in situ RT-PCR in the lesional skin of atopic dermatitis. J
Dermatol. 2003 Jan;30(1):26-32.
Thymus-
and activation-regulated chemokine (TARC/CCL17) and its receptor, CC chemokine
receptor 4 (CCR4), have been proven to be involved in a number of allergic
diseases, especially atopic dermatitis (AD). The purpose of this study was to
examine the expression and distribution of TARC and CCR4 mRNAs in samples of AD
(n=15, acute lesions 8, chronic lesions 7) and normal skin (n=6). The expression
and distribution of TARC and CCR4 mRNAs were detected with the in situ reverse
transcription (RT) -polymerase chain reaction (PCR) technique. TARC mRNA was
expressed in epidermal keratinocytes, dermal endothelial cells and infiltrating
cells. CCR4 mRNA was expressed in dermal endothelial cells and infiltrating
cells. In acute AD lesional skin, there were more positive cells, and the
staining intensity was stronger than in chronic lesions (p<0.05). The
distribution of positive cells was as follows: In the epidermis, keratinocytes
in the basal layer showed the strongest staining, and keratinocytes in the
spinous layer showed moderate staining; the superficial area showed faint
staining. In the dermis, infiltrating cells located in the superficial area of
the dermis showed the strongest staining, positive staining intensity became
weaker and the percentage of positive cells became less as the location became
deeper. There were no positive cells in normal skin. These data further
substantiate the role of TARC/CCR4 in the pathogenesis of AD. PMID: 12598706 [PubMed
- indexed for MEDLINE]
Pathogenesis:
7084.
Bergeron C, Page N, Barbeau B, Chakir J. Interleukin-4 promotes airway
remodeling in asthma: regulation of procollagen I (alpha1) gene by
interleukin-4. Chest. 2003 Mar;123(3 Suppl):424S. Review. No abstract available.
7085.
Dibbern DA Jr, Palmer GW, Williams PB, Bock SA, Dreskin SC. RBL cells
expressing human Fc epsilon RI are a sensitive tool for exploring functional IgE-allergen
interactions: studies with sera from peanut-sensitive patients. J Immunol
Methods. 2003 Mar 1;274(1-2):37-45.
Rat basophilic leukemia cells (RBL SX-38) express the alpha, beta, and gamma chains of human Fc varepsilon RI. Following sensitization with IgE from a subset of allergic human donors, these cells can be triggered by exposure to anti-IgE or to very low concentrations of specific allergens. We examined 18 sera from patients who were highly sensitive to peanuts by history and had anti-peanut IgE by in vitro testing. The ability of these sera to sensitize the RBL SX-38 cells for degranulation with peanut allergens correlates very well with the absolute amount of anti-peanut IgE (r=0.95; p<0.001). The most effective sera contained at least 50 kU/l of total IgE and at least 15 kU/l of peanut-specific IgE. RBL SX-38 cells sensitized with these sera degranulated optimally upon exposure to anti-IgE (net degranulation of 40+/-8%, means+/-S.D.; n=8) and to a 10(5)-10(6) dilution of crude peanut extract (CPE) (37+/-7% net degranulation; 93+/-13% of that seen with anti-IgE). This assay is quite sensitive. Cells sensitized with selected sera are activated by exposure to a 1:10(7) dilution of the CPE containing picogram amounts of peanut allergens. This assay is also quite specific. Cells sensitized with sera from patients with anti-peanut IgE and no detectable IgE against soybean, walnut or grass pollen did not degranulate following exposure to these latter antigens. The converse was also true; cells sensitized with sera from patients without anti-peanut IgE did not react to peanut. These data demonstrate that RBL cells expressing human Fc varepsilon RI form the basis of a useful model system for the detection of allergens and for the study of IgE-allergen interactions.
7086.
El Bahlawan L, Christensen M, Binaei S, Murphy C, Zhang Q, Quasney M.
Lack of association between the tumor necrosis factor-alpha regulatory
region genetic polymorphisms associated with elevated tumor necrosis
factor-alpha levels and children with asthma. Chest. 2003 Mar;123(3 Suppl):374S-5S.
No abstract available
7087.
Lobos E, Nutman TB, Hothersall JS, Moncada S. Elevated immunoglobulin E
against recombinant Brugia malayi gamma-glutamyl transpeptidase in patients with
bancroftian filariasis: association with tropical pulmonary eosinophilia or
putative immunity. Infect Immun. 2003 Feb;71(2):747-53.
A
major allergen of the lymphatic filarial nematode Brugia malayi, a homologue of
gamma-glutamyl transpeptidase (gamma-GT), is involved in the pathology of
tropical pulmonary eosinophilia (TPE) through its potent allergenicity and the
induction of antibodies against the host pulmonary epithelium. To investigate
the immunoglobulin G (IgG) subclass and IgE responses to recombinant B. malayi
gamma-GT, we analyzed the results obtained from 51 patients with differing
clinical manifestations of bancroftian filariasis. gamma-GT-specific IgG1,
rather than IgG4, was the predominant IgG subclass, particularly in patients
with TPE (geomean, 6,321 ng/ml; range, 78 to 354,867 ng/ml) and was 75 times
higher than in patients with elephantiasis (CP) (P < 0.003) and 185 times
higher than in endemic normal individuals (ENL) (P < 0.010). IgG2 responses
were low and IgG3 was almost absent, with no significant differences among the
groups. gamma-GT-specific IgG4 responses were significantly elevated in those
with subclinical microfilaremia (MF) compared to the CP and ENL groups and
correlated with the presence of circulating filarial antigen (CAg). More
significantly, gamma-GT-specific IgE antibody levels were strikingly elevated in
patients with TPE (geomean, 681 ng/ml; range, 61 to 23,841 ng/ml) and in the ENL
group (geomean, 106 ng/ml; range, 13 to 1,405 ng/ml) whereas the gamma-GT-specific
IgE level was 44 and 61 times lower in those with MF and CP, respectively (P
< 0.001). Elevated gamma-GT-specific IgE/IgG4 ratios were demonstrated in
patients with TPE (ratio, 45) and ENL (ratio, 107). Because expression of gamma-GT
in Brugia infective third-stage larvae (L3) was demonstrated by immunoblot
analysis, the elevated gamma-GT-specific IgE antibodies appear to be associated
not only with pulmonary pathology but also with possible resistance to infection
in lymphatic filariasis.
7088.
Roche N, Stirling RG, Lim S, Oliver BG, Oates T, Jazrawi E, Caramori G,
Chung KF. Effect of acute and chronic inflammatory stimuli on expression of
protease-activated receptors 1 and 2 in alveolar macrophages. J Allergy Clin
Immunol. 2003 Feb;111(2):367-73.
BACKGROUND:
Protease-activated receptors 1 and 2 (PAR-1 and PAR-2) are 7-transmembrane G
protein-coupled receptors activated by serine proteases in many cell types,
including monocytes-macrophages, leading to the production of pro-inflammatory
mediators, cytokines, and growth factors. OBJECTIVE: We determined the influence
of chronic smoking and asthma on the expression of PAR-1 and PAR-2 receptors on
alveolar macrophages (AMs). METHODS: We used RT-PCR and immunocytochemistry with
confocal microscopy to determine mRNA and protein expression of PAR-1 and PAR-2
in AMs obtained from healthy smokers, asthmatic patients, and healthy subjects.
In addition, we examined the effect of IL-1beta and LPS. RESULTS: PAR1 mRNA was
decreased, whereas PAR2 mRNA was increased in 24-hour cultured AMs from smokers
when compared with values in AMs from healthy subjects. Paradoxically, there was
a higher degree of PAR-1 protein staining in AMs from smokers, whereas PAR-2
staining was similar in smokers and healthy subjects. PAR-1 and PAR-2 mRNA and
protein expression were similar in asthmatic patients and control subjects.
IL-1beta and LPS had no effect on PAR1 and PAR2 gene expression by AMs.
CONCLUSIONS: There is a dissociation between gene and protein expression of
PAR-1 and PAR-2. PAR-1 protein overexpression in AMs from smokers might be
important in the pathophysiology of chronic airways disease.
7089.
Sekiya T, Tsunemi Y, Miyamasu M, Ohta K, Morita A, Saeki H, Matsushima K,
Yoshie O, Tsuchiya N, Yamaguchi M, Yamamoto K, Tamaki K, Hirai K.
Variations in the human Th2-specific chemokine TARC gene. Immunogenetics.
2003 Jan;54(10):742-5.
Th2-specific
chemokine thymus and activation-regulated chemokine (TARC)/CC chemokine ligand
(CCL)17 is highly implicated in the pathogenesis of Th-2-dominated allergic
diseases such as bronchial asthma (BA) and atopic dermatitis (AD). We performed
polymorphism screening of the coding and promoter regions of the TARC gene. We
found two rare variations in the coding region of exon 3 (2134C>T and
2037G>A) and a single nucleotide polymorphism (SNP) in the 5'-flanking region
(-431C>T). Individuals carrying the 431T allele showed significantly
increased serum levels of TARC compared with those not carrying the 431T allele,
suggesting that this SNP has functional significance. However, when the
genotypes at the SNP site were determined for 158 healthy individuals, 105
patients with BA and 148 patients with AD, we observed no significant
association of the SNP with susceptibility to BA or AD.
7090.
Vercelli D. Learning from discrepancies: CD14 polymorphisms, atopy and
the endotoxin switch. Clin Exp Allergy. 2003 Feb;33(2):153-5. No abstract
available.
Vaccines:
7091.
Himly M, Jahn-Schmid B, Dedic A, Kelemen P, Wopfner N, Altmann F, van Ree
R, Briza P, Richter K, Ebner C, Ferreira F. Art v 1, the major allergen of
mugwort pollen, is a modular glycoprotein with a defensin-like and a
hydroxyproline-rich domain. FASEB J. 2003 Jan;17(1):106-8.
In
late summer, pollen grains originating from Compositae weeds (e.g., mugwort,
ragweed) are a major source of allergens worldwide. Here, we report the
isolation of a cDNA clone coding for Art v 1, the major allergen of mugwort
pollen. Sequence analysis showed that Art v 1 is a secreted allergen with an
N-terminal cysteine-rich domain homologous to plant defensins and a C-terminal
proline-rich region containing several (Ser/Ala)(Pro)2-4 repeats. Structural
analysis showed that some of the proline residues in the C-terminal domain of
Art v 1 are posttranslationally modified by hydroxylation and O-glycosylation.
The O-glycans are composed of 3 galactoses and 9-16 arabinoses linked to a
hydroxyproline and represent a new type of plant O-glycan. A 3-D structural
model of Art v 1 was generated showing a characteristic "head and
tail" structure. Evaluation of the antibody binding properties of natural
and recombinant Art v 1 produced in Escherichia coli revealed the involvement of
the defensin fold and posttranslational modifications in the formation of
epitopes recognized by IgE antibodies from allergic patients. However,
posttranslational modifications did not influence T-cell recognition. Thus,
recombinant nonglycosylated Art v 1 is a good starting template for engineering
hypoallergenic vaccines for weed-pollen therapy.
7092.
Smithers M, O'Connell K, MacFadyen S, Chambers M, Greenwood K, Boyce A,
Abdul-Jabbar I, Barker K, Grimmett K, Walpole E, Thomas R. Clinical response
after intradermal immature dendritic cell vaccination in metastatic melanoma is
associated with immune response to particulate antigen. Cancer Immunol
Immunother. 2003 Jan;52(1):41-52.
Metastatic
melanoma is poorly responsive to treatment, and immunotherapeutic approaches are
potentially beneficial. Predictors of clinical response are needed to identify
suitable patients. We sought factors associated with melanoma-specific clinical
response following intradermal vaccination with autologous melanoma peptide and
particulate hepatitis B antigen (HBsAg)-exposed immature monocyte-derived
dendritic cells (MDDC). Nineteen patients with metastatic melanoma received a
maximum of 8, 2-weekly vaccinations of DC, exposed to HBsAg in addition to
autologous melanoma peptides. A further 3 patients received an otherwise
identical vaccine that did not include HBsAg. Patients were assessed 1-2 monthly
for safety, disease volume, and cellular responses to HBsAg and melanoma
peptide. There was no significant toxicity. Of 19 patients receiving HBsAg-exposed
DC, 9 primed or boosted a cellular response to HBsAg, and 10 showed no HBsAg
response. HBsAg-specific responses were associated with in vitro T cell
responses to melanoma peptides and to phytohemagglutinin (PHA). Zero out of 10
non-HBsAg-responding and 4/9 HBsAg-responding patients achieved objective
melanoma-specific clinical responses or disease stabilization - 1 complete and 2
partial responses and 1 case of stable disease ( P=0.018). Development of
melanoma-specific cellular immunity and T cell responsiveness to mitogen were
greater in the group of patients responding to HBsAg. Therefore stimulation of
an immune response to nominal particulate antigen was necessary when presented
by melanoma peptide-exposed immature DC, to achieve clinical responses in
metastatic melanoma. Since general immune competence may be a determinant of
treatment response, it should be assessed in future trials on DC immunotherapy.
October 2003
7691.
Adams BK, Cydulka RK. Asthma
evaluation and management. Emerg Med Clin North Am. 2003 May;21(2):315-30.
Asthma
is a chronic inflammatory illness with acute exacerbations, which often is
encountered in the ED setting. Knowledge of the presentation and treatment of
asthma is crucial for any physician treating patients with this disease.
Beta-agonist, anticholinergic, and corticosteroid therapy continue to be the
mainstay of emergency therapy despite advances in newer medications. Proper
attention to long-term treatment of asthma and aggressive treatment of acute
exacerbations should help reduce morbidity and mortality.
7692.
Akdis M, Trautmann A, Klunker S, Daigle I, Kucuksezer UC, Deglmann W,
Disch R, Blaser K, Akdis CA. T helper (Th) 2 predominance in atopic diseases is
due to preferential apoptosis of circulating memory/effector Th1 cells. FASEB J.
2003 Jun;17(9):1026-35.
T
cells constitute a large population of cellular infiltrate in atopic/allergic
inflammation and a dysregulated, Th2-biased peripheral immune response appears
to be an important pathogenetic factor. In atopic dermatitis, circulating
cutaneous lymphocyte-associated antigen-bearing (CLA+) CD45RO+ T cells with
skin-specific homing property represent an activated memory/effector T cell
subset. They express high levels of Fas and Fas ligand and undergo
activation-induced apoptosis. The freshly purified CLA+ CD45RO+ T cells of
atopic individuals display distinct features of in vivo-triggered apoptosis such
as pro-caspase degradation and active caspase-8 formation. In particular, the
Th1 compartment of activated memory/effector T cells selectively undergoes
activation-induced cell death, skewing the immune response toward surviving Th2
cells in atopic dermatitis patients. The apoptosis of circulating memory/effector
T cells was confined to atopic individuals whereas non-atopic patients such as
psoriasis, intrinsic-type asthma, contact dermatitis, intrinsic type of atopic
dermatitis, bee venom allergic patients, and healthy controls showed no evidence
for enhanced T cell apoptosis in vivo. These results define a novel mechanism
for peripheral Th2 response in atopic diseases.
7693.
Anees W. Use of pulmonary
function tests in the diagnosis of occupational asthma. Ann Allergy Asthma
Immunol. 2003 May;90(5 Suppl 2):47-51.
OBJECTIVE:
To discuss the different methods of assessing lung function measurements for the
diagnosis of occupational asthma, focusing in particular on serial peak
expiratory flow rate (PEFR) monitoring, including details on how PEFR records
should be kept, plotted, and analyzed and limitations of the method. DATA
SOURCES: Published studies on the use of diagnostic methods in occupational
asthma, expert opinion, and recently obtained data from studies performed at a
large occupational lung disease clinic. STUDY SOURCES: The expert opinion of the
author was used to select the relevant data for review. RESULTS: Objective
methods are necessary for the diagnosis of occupational asthma, since clinical
history alone is not a satisfactory means of diagnosis. Serial PEFR monitoring
has a high diagnostic sensitivity and specificity for occupational asthma and is
more useful than evaluation of cross-shift change in forced expiratory volume in
1 second or change in nonspecific bronchial hyperresponsiveness. Interpretation
is best performed by expert visual evaluation of plots of maximum, mean, and
minimum daily PEFR readings. CONCLUSIONS: Despite some limitations of the
method, serial PEFR monitoring is usually the most appropriate first-line
investigation in workers suspected of having occupational asthma.
7694.
Baraldi E, Carraro S, Alinovi R, Pesci A, Ghiro L, Bodini A, Piacentini
G, Zacchello F, Zanconato S. Cysteinyl
leukotrienes and 8-isoprostane in exhaled breath condensate of children with
asthma exacerbations. Thorax. 2003 Jun;58(6):505-9.
BACKGROUND:
Cysteinyl leukotrienes (Cys-LTs) and isoprostanes are inflammatory
metabolites derived from arachidonic acid whose levels are increased in
the airways of asthmatic patients. Isoprostanes are relatively stable and
specific for
lipid peroxidation, which makes them potentially reliable biomarkers for
oxidative stress. A study was undertaken to evaluate the effect of a
course of oral
steroids on Cys-LT and 8-isoprostane levels in exhaled breath condensate of
children with an asthma exacerbation. METHODS: Exhaled breath condensate was
collected and fractional exhaled nitric oxide (FE(NO)) and spirometric
parameters were measured before and after a 5 day course of oral prednisone (1
mg/kg/day) in 15 asthmatic children with an asthma exacerbation. Cys-LT and
8-isoprostane concentrations were measured using an enzyme immunoassay. FE(NO)
was measured using a chemiluminescence analyser. Exhaled breath condensate was
also collected from 10 healthy children. RESULTS: Before prednisone treatment
both Cys-LT and 8-isoprostane concentrations were higher in asthmatic subjects (Cys-LTs,
12.7 pg/ml (IQR 5.4-15.6); 8-isoprostane, 12.0 pg/ml (9.4-29.5)) than in healthy
children (Cys-LTs, 4.3 pg/ml (2.0-5.7), p=0.002; 8-isoprostane, 2.6 pg/ml
(2.1-3.0), p<0.001). After prednisone treatment there was a significant
decrease in both Cys-LT (5.2 pg/ml (3.9-8.8), p=0.005) and 8-isoprostane (8.4
pg/ml (5.4-11.6), p=0.04) concentrations, but 8-isoprostane levels remained
higher than in controls (p<0.001). FE(NO) levels, which fell significantly
after prednisone treatment (p<0.001), did not correlate significantly with
either Cys-LT or 8-isoprostane concentrations. CONCLUSION: After a 5 day course
of oral prednisone there is a reduction in Cys-LT and 8-isoprostane levels in
EBC of children with an asthma exacerbation, although 8-isoprostane levels
remain higher than in controls. This finding suggests that corticosteroids may
not be fully effective in reducing oxidative stress in children with an
exacerbation of asthma.
7695.
Barczyk A, Pierzchala W, Sozanska E.
Interleukin-17 in sputum correlates with airway hyperresponsiveness to
methacholine. Respir Med. 2003 Jun;97(6):726-33.
BACKGROUND:
Interleukin-17 (IL-17) is a novel cytokine secreted by activated human memory
CD4+ T cells. In vivo IL-17 recruits neutrophils into the airways via the
release of CXC chemokines (interleukin-8) from bronchial epithelial cells. Since
neutrophils are implicated in pathogenesis of chronic obstructive pulmonary
disease (COPD) chronic bronchitis (CB) and asthma, we hypothesized that there
would be increased concentration of IL-17 in the airways of these patients. To
test this hypothesis, we measured levels of IL-17 in induced sputum of COPD
patients, chronic bronchitis and asthmatics and compared them with healthy
controls. METHODS: Levels of IL-17 in induced sputum were measured via ELISA
method in 19 COPD, 16 CB, 10 asthma and 11 control subjects. Airway
responsiveness to methacholine was performed in people with FEV1 higher than 70%
of predicted. RESULTS: There were no significant differences in IL-17 levels
between control group and the other groups. However, levels of IL-17 in sputum
of COPD patients were significantly lower than in asthma (P=0.004) and in CB
(P=0.01) groups. Medians and (ranges) were as follows: asthma--37.6 pg/ml
(18.8-55.7 pg/ml), CB 293 pg/ml (18.8-49.7 pg/ml) and COPD 24.6 pg/ml (0-34.1
pg/ml). Comparison of healthy control subjects (PC20 > 8 mg/ml) to a group
with bronchial hyperreactivity, which consisted of asthmatics and CB patients,
whose PC20 was less than 8 mg/ml, revealed that levels of IL-17 were
significantly increased in the second group (P=0.02). Also, levels of IL-17 were
significantly increased (P=0.02) in the asthmatic patients with bronchial
hyperreactivity compared to healthy subjects. Moreover levels of IL-17 in sputum
of all studied subjects correlated negatively with PC20 (r=-0.51, P=0.002).
CONCLUSIONS: According to our results IL-17 is probably not involved in
pathogenesis of stable COPD, but it may play a role in people with airway
hyperresponsiveness.
7696.
Baroody FM. Allergic
rhinitis: broader disease effects and implications for management.Otolaryngol
Head Neck Surg. 2003 May;128(5):616-31.
Allergic
rhinitis is a burdensome disease for a significant part of the population in
both adults and children. Poorly controlled allergic rhinitis can trigger
exacerbations of asthma, sinusitis, and otitis media, diseases with which it
shares common pathophysiologic elements. Consequently, early diagnosis and
treatment should be a priority for patients and physicians, not only to control
the symptoms of allergic rhinitis but also to improve the management of
associated diseases. Several pharmacologic therapies can be considered in an
armamentarium that includes antihistamines (intranasal and systemic), intranasal
cromolyn, intranasal anticholinergic agents, intranasal steroids, systemic
steroids, immunotherapy, and, most recently, leukotriene receptor antagonists.
Often, combinations of these treatments are used to maximize control of
refractory symptoms.
7697.
Bellia V, Battaglia S, Catalano F, Scichilone N, Incalzi RA, Imperiale C,
Rengo F. Aging and disability
affect misdiagnosis of COPD in elderly asthmatics: the SARA study. Chest. 2003
Apr;123(4):1066-72.
STUDY
OBJECTIVES: This study investigated to what extent a diagnosis of COPD is
erroneously made or the disease remains unrecognized in elderly asthmatic
patients, and identified factors leading to misdiagnosis and underdiagnosis of
asthma in such patients. DESIGN: A multicenter study involving 24 Italian
pulmonary or geriatric institutions. PATIENTS: One hundred twenty-eight
asthmatic patients (98 women, 76.6%) aged 73 +/- 6.4 years (mean +/- SD) were
selected from the cohort of the Salute Respiratoria nell'Anziano (respiratory
health in the elderly) study. METHODS: All patients underwent a clinical
evaluation that included clinical history and spirometry with a bronchodilator
test. A diagnosis of asthma was based on criteria proposed by international
guidelines adapted to the elderly population. A multidimensional geriatric
assessment was performed to estimate physical and cognitive impairments and
1mood state. Finally, the diagnosis of respiratory disease previously made by a
doctor, if any, was recorded. RESULTS: Of asthmatic patients, COPD had been
improperly diagnosed in 19.5%, whereas 27.3% of asthmatic patients did not
report any previous diagnosis of asthma. The main correlates of misdiagnosis
were older age and disability. Conversely, underdiagnosis was associated with
better functional conditions, expressed by spirometry, even when wheezing or a
significant response to the bronchodilator test occurred. CONCLUSIONS: Asthma in
the elderly is frequently confused with COPD. Misdiagnosis can be related to
older age and to greater degree of disability. Asthma in patients with mild
functional impairment may be underdiagnosed in spite of overt respiratory
symptoms suggestive of asthma.
7698.
Bhattarai MD. Asthma
mistaken for chronic obstructive pulmonary disease. Lancet. 2003 May
31;361(9372):1914-5. No abstract
7699.
Burks W. Peanut allergy: a
growing phenomenon. J Clin Invest. 2003 Apr;111(7):950-2. No abstract
7700.
Cameron HL, Yang PC, Perdue MH. Glucagon-like
peptide-2-enhanced barrier function reduces pathophysiology in a model of food
allergy. Am J Physiol Gastrointest Liver Physiol. 2003 Jun;284(6):G905-12. Epub
2003 Jan 29.
Penetration
of the gut epithelial barrier by intact luminal antigen is necessary for
immunologically mediated pathophysiology in the context of food allergy. We
investigated if glucagon-like peptide-2 (GLP-2) could affect immediate
hypersensitivity and late-phase allergic inflammation in a murine model. Mice
were sensitized to horseradish peroxidase (HRP); studies were conducted 14 days
later. Mice were treated with 5 microg GLP-2 subcutaneously 4 h before antigen
challenge. For immediate hypersensitivity, jejunal segments in Ussing chambers
were challenged by luminal HRP antigen. GLP-2 treatment reduced the uptake of
HRP and the antigen-induced secretory response after luminal challenge. GLP-2
appears to reduce macromolecular uptake independent of the CD23-mediated
enhanced
antigen uptake pathway. For the late phase, mice were gavaged with antigen, and
48 h later the function and histology of the jejunum were examined. GLP-2
prevented the usual prolonged permeability defect and reduced the number of
inflammatory cells in the mucosa. Our studies demonstrate that a single
treatment of sensitized mice with GLP diminishes both immediate and late-phase
hypersensitivity reactions characteristic of food allergy by inhibiting
transepithelial uptake of antigen.
7701.
Chakir J, Shannon J, Molet S, Fukakusa M, Elias J, Laviolette M, Boulet
LP, Hamid Q. Airway
remodeling-associated mediators in moderate to severe asthma: effect of steroids
on TGF-beta, IL-11, IL-17, and type I and type III collagen expression. J
Allergy Clin Immunol. 2003 Jun;111(6):1293-8.
BACKGROUND:
Important features of airway remodeling in asthma include the formation of
subepithelial fibrosis and increased deposition of types I and III collagen. TGF-beta,
IL-11, and IL-17 are profibrotic cytokines involved in the formation of
subepithelial fibrosis and are increased in patients with asthma, particularly
in those with severe disease. OBJECTIVE: The purpose of this study was to
investigate the effect of corticosteroids on the expression of these profibrotic
cytokines and on extracellular matrix deposition. METHODS: We used
immunocytochemistry to measure the expression of TGF-beta, IL-11, IL-17, and
collagen types I and III in the airways of patients with mild asthma (n = 9),
patients with moderate-to-severe asthma (n = 10), and control subjects without
asthma (n = 6). Baseline bronchial biopsy specimens were obtained in all groups.
In addition, repeat biopsies were obtained in the patients with
moderate-to-severe asthma after a 2-week course of oral corticosteroids.
RESULTS: TGF-beta expression was significantly higher in all groups with asthma,
and it did not decrease after treatment with oral corticosteroids. Levels of
IL-11 and IL-17 were increased in patients with moderate-to-severe asthma
compared with patients with mild asthma and normal controls (P <.05). The
expression of these cytokines decreased with oral corticosteroids in the
moderate-to-severe group to levels that were comparable to those seen in the
patients with mild asthma and in the normal controls (P <.005). Expression of
types I and III collagens was higher in the patients with moderate-to-severe
asthma than in the patients with mild asthma and the controls (P <.05; P
<.001). Treatment with corticosteroids did not decrease the expression of
types I and III collagens. CONCLUSIONS: These results confirm the association of
increased levels of TGF-beta, IL-11, IL-17, and types I and III collagens with
severe disease and suggest that the failure of cortico-steroids to decrease
collagen deposition might be due to persistently elevated TGF-beta expression.
7702.
Chetta A, Castagnaro A, Foresi A, Del Donno M, Pisi G, Malorgio R,
Olivieri D. Assessment of
breathlessness perception by Borg scale in asthmatic patients: reproducibility
and applicability to different stimuli. J Asthma. 2003 May;40(3):323-9.
In
asthmatics, the score of bronchoconstriction-associated breathlessness at 20%
fall in forced expiratory volume at first second FEV1) evaluated on a Borg scale
(PS20) is a tool successfully used to measure the perception of symptoms. This
prospective laboratory study evaluated the applicability of PS20 to assess the
breathlessness induced by ultrasonically nebulized distilled water (UNDW) and
methacholine (M) and its reproducibility. Twenty-two mild and clinically stable
asthmatic patients performed UNDW and M challenge tests. The PS20 was calculated
by linear interpolation of the last two points of the perception/fall in FEV1
curve of the UNDW and M tests. The reproducibility of PS20 M was assessed by
repeating measurements on 2 separate days by 3 weeks. PS20 UNDW and PS20 M did
not differ and were respectively 1.82 +/- 1.85 and 2.03 +/- 1.86. They were
significantly related (rs=0.63; p<0.01) and the bias between PS20 UNDW and
PS20 M was -0.21 with the limits of agreement ranging from -3.2 to 3.6. The
intraclass correlation coefficient for repeated measurement of PS20 M was 0.82;
the bias between the two measurements was 0.2 with the limits of agreement
ranging from -2.8 to 3.2. All patients had a measurable breathlessness
perception degree on a Borg scale during both distilled water challenges and
methacholine. Asthmatic patients with normal, exaggerated or poor breathlessness
perception were also similar for both stimuli. In addition, PS20 showed a good
reproducibility and this allows the serial evaluation of patient's
breathlessness perception by this technique in clinical settings and in the
physiology laboratory.
7703.
Cisternas MG, Blanc PD, Yen IH, Katz PP, Earnest G, Eisner MD, Shiboski
S, Yelin EH. A comprehensive study
of the direct and indirect costs of adult asthma. J Allergy Clin Immunol. 2003
Jun;111(6):1212-8.
BACKGROUND:
Asthma is a common and costly health condition, but most estimates of its
economic effect have relied on secondary sources with limited condition-specific
detail. OBJECTIVE: We sought to estimate the magnitude of direct and indirect
costs of adult asthma from the perspective of society. METHODS: We used
cross-sectional survey data from an ongoing community-based panel study of 401
adults with asthma originally derived from random samples of northern California
pulmonologists, allergist-immunologists, and family practitioners to assess
health care use for asthma, to assess purchase of items to assist with asthma
care, and to measure work and other productivity losses. Unit costs derived from
public-use and proprietary data sources were then assigned to the survey items.
RESULTS: Total per-person annual costs of asthma averaged $4912 US dollars, with
direct and indirect costs accounting for $3180 US dollars (65%) and $1732 US
dollars (35%), respectively. The largest components within direct costs were
pharmaceuticals ($1605 US dollars [50%]), hospital admissions ($463 US
dollars[15%]), and non-emergency department ambulatory visits ($342 US dollars
[11%]). Within indirect costs, total cessation of work accounted for $1062 US
dollars (61%), and the loss of entire work days among those remaining employed
accounted for another $486 US dollars (28%). Total per-person costs were $2646,
$4530, and $12,813 US dollars for persons self-reporting mild, moderate, and
severe asthma, respectively (P <.0001, 1-way ANOVA). CONCLUSION:
Asthma-related costs are substantial and are driven largely by pharmaceuticals
and work loss.
7704.
Cooper PJ, Chico ME, Rodrigues LC, Ordonez M, Strachan D, Griffin GE,
Nutman TB. Reduced risk of atopy
among school-age children infected with geohelminth parasites in a rural area of
the tropics. J Allergy Clin Immunol. 2003 May;111(5):995-1000.
BACKGROUND:
Childhood infections might protect against the expression of atopy. Geohelminths
are among the most prevalent infections of childhood and might contribute to the
low prevalence of allergic disease reported from rural areas of the tropics.
OBJECTIVE: We sought to establish whether geohelminth infections protect against
atopy and to explore whether this protection is dependent on infection
chronicity. METHODS: The risk of atopy (measured by means of allergen skin test
reactivity) associated with active geohelminth infections (measured by means of
the presence of eggs in stool samples) or with chronic geohelminth infections
(measured by means of high levels [>/=3564 IU/mL] of total serum IgE or the
presence of detectable anti-Ascaris lumbricoides IgG4 antibodies) was
investigated in an analytic cross-sectional study conducted among school-age
children attending rural schools in Pichincha Province in Ecuador. RESULTS: A
total of 2865 children aged 5 to 19 years from 55 schools was examined. Active
infection with any geohelminth and infections with A lumbricoides or Ancylostoma
duodenale were associated with significant protective effects against allergen
skin test reactivity. Children with the highest levels of total IgE or with
anti-A lumbricoides IgG4 antibodies were protected against skin test reactivity
also, and the protective effects of high IgE or anti-A lumbricoides IgG4 and or
active geohelminth infections were statistically independent. CONCLUSION: Active
infections with geohelminth parasites and the presence of serologic markers of
chronic infections (high levels of total serum IgE or anti-A lumbricoides
IgG4)are independent protective factors against allergen skin test reactivity
among school-age children living in an endemic region of the rural tropics.
7705.
Covar RA, Szefler SJ, Martin RJ, Sundstrom DA, Silkoff PE, Murphy J,
Young DA, Spahn JD. Relations between exhaled nitric oxide and measures of
disease activity among children with mild-to-moderate asthma. J Pediatr. 2003
May;142(5):469-75.
OBJECTIVE:
Exhaled nitric oxide (FE(NO)) was evaluated in children with asthma after 4 to 6
years of treatment with budesonide, nedocromil, or albuterol as needed. STUDY
DESIGN: FE(NO), spirometry, total eosinophil count, and serum eosinophil
cationic protein levels were obtained from 118 children at the Denver site of
the Childhood Asthma Management Program upon completion of treatment and after a
2- to 4-month washout. RESULTS: Budesonide-treated patients had significantly
lower median (1st, 3rd quartile) FE(NO) (21.5 [13.2, 84.4] vs 62.5 [26.2, 115.0]
ppb, P <.01) and eosinophil cationic protein levels (17.4 [10.1, 24.3] vs
24.0 [15.4, 33.9] mg/dL, P =.05) compared with placebo, whereas no differences
were noted between nedocromil and placebo groups. After washout, FE(NO) levels
were similar between the three treatments. FE(NO) levels significantly
correlated with degree of bronchial hyperresponsiveness, bronchodilator
reversibility, allergen skin prick tests, serum IgE, and total eosinophil count.
FE(NO) levels were also higher in patients with nocturnal symptoms and in
patients requiring beta-agonist use at least once weekly. CONCLUSIONS:
Budesonide therapy was more effective than nedocromil in reducing FE(NO).
Unfortunately, the effects of long-term budesonide were not sustained after its
discontinuation. FE(NO) may be a complementary tool to current practice
guidelines in assessing asthma control and medication response.
7706.
Dagoye D, Bekele Z, Woldemichael K, Nida H, Yimam M, Hall A, Venn AJ,
Britton JR, Hubbard R, Lewis SA. Wheezing, allergy, and parasite infection in
children in urban and rural Ethiopia. Am J Respir Crit Care Med. 2003 May
15;167(10):1369-73. Epub 2003 Jan 24.
Epidemiological
studies in developing countries suggest that intestinal parasite infection may
reduce the risk of asthma. Because this evidence is all derived from adults and
older children, we have investigated the relation between parasite infection,
wheezing, and allergen skin sensitization in nested case-control studies drawn
from a survey of 7,155 children aged 1 to 4 years living in urban and rural
areas of Jimma, Ethiopia. Infection with parasites was common, predominantly
with Trichuris (54%), Ascaris (38%), and hookworm (10%). Wheezing in the past
year was significantly more prevalent in urban (4.4%) than rural children
(2.0%), and was less prevalent in those infected with Ascaris (age, sex, and
urban/rural adjusted odds ratio, 0.5; 95% confidence interval, 0.3 to 0.9),
particularly in relation to high-intensity infection. Similar,although
nonsignificant, associations were found for hookworm (adjusted odds ratio, 0.6;
95% confidence interval, 0.2 to 1.8), but there was no suggestion of any
relation to Trichuris infection. Dermatophagoides pteronyssinus and cockroach (Blattella
germanica) skin sensitization was more prevalent in rural than urban children,
and was unrelated to wheeze. We conclude that Ascaris and possibly hookworm
infection protects against wheeze in young Ethiopian children, and that this
effect is not mediated by inhibition of allergen sensitization.
7707.
Di Franco A, Bartoli ML, Carnevali S, Cianchetti S, Bacci E, Dente FL,
Giannini D, Taccola M, Vagaggini B, Paggiaro PL.
Analysis of sputum cell counts during spontaneous moderate exacerbations
of asthma in comparison to the stable phase. J Asthma. 2003 Apr;40(2):155-62.
BACKGROUND:
Acute airway inflammation is considered to characterize asthma exacerbations,
but its specific cellular pattern has not yet been completely evaluated. AIM: To
evaluate the prevalence of sputum eosinophilia during acute asthma exacerbations
of moderate severity, compared with a stable phase of the disease, and to assess
the concordance between changes in pulmonary function and sputum eosinophilia in
the period between exacerbation and post exacerbation. METHODS: We compared
sputum and blood inflammatory cell counts in 29 asthmatic subjects during a
spontaneous moderate exacerbation of asthma (visit 1) with sputum and blood cell
counts measured 4 weeks after the resolution of asthma exacerbation (visit 2).
At visit 1, all subjects required an appropriate 1 week treatment with oral
corticosteroids. RESULTS: At visit 1, all subjects were able to collect
spontaneous sputum, whereas at visit 2 sputum was induced by inhalation of
hypertonic saline (NaCl 3, 4, and 5%, 10 minutes each) with beta2-agonist
pretreatment. Asthma exacerbation was accompanied by a significant increase in
sputum eosinophil percentages compared with levels after exacerbation [25%
(1-78) versus 4% (0-23), p<0.05). Only four subjects showed low sputum
eosinophil percentages during exacerbation, and these showed no differences in
main clinical findings with respect to subjects with sputum eosinophilia. At
visit 2, the stability of asthma was assessed on the basis of PEF, FEV1,
symptoms, and use of rescue beta2-agonist. Asthma was defined as stable in 21
out of 29 subjects. Sputum eosinophil percentages fell significantly between
visit 1 and visit 2 in both stable and unstable patients, but at visit 2 sputum
eosinophil percentages were still high in subjects with unstable asthma. In
patients who proved to be stable at visit 2, there was a significant correlation
between the changes recorded in sputum eosinophil percentages and in FEV1
between the two visits (rho: 0.723, p<0.001).
CONCLUSION:
Sputum cosinophil but not neutrophil percentages increase in most asthmatic
subjects during moderate exacerbation of asthma. Changes in the degree of airway
eosinophilic inflammation are related to changes in the severity of airway
obstruction during asthma exacerbation.
7708.
Ebo DG, Stevens WJ, Bridts C, De
Clerck LS. Clinical laboratory
assessment of IgE. J Allergy Clin Immunol. 2003 Jun;111(6):1414; No abstract
7709.
Ferguson J. Diagnosis and
treatment of the common idiopathic photodermatoses. Australas J Dermatol. 2003
May;44(2):90-6.
The
idiopathic photodermatoses are the most common cause of photosensitivity and the
commonest of these are polymorphic light eruption, actinic prurigo, chronic
actinic dermatitis and solar urticaria. The clinical presentation, investigation
and treatment of these four disorders are presented. Spontaneous improvement
does occur.
7710.
Foetisch K, Westphal S, Lauer I, Retzek M, Altmann F, Kolarich D,
Scheurer S, Vieths S. Biological
activity of IgE specific for cross-reactive carbohydrate determinants. J Allergy
Clin Immunol. 2003 Apr;111(4):889-96.
BACKGROUND:
The clinical relevance of IgE specific for cross-reactive carbohydrate
determinants (CCDs) has been a matter of controversy. Until now, no convincing
experiments have been performed to test the biologic significance of individual
multivalent allergens that carry multiple carbohydrate epitopes. OBJECTIVE: We
sought to contribute to the understanding of the role of CCD-specific IgE
antibodies and to study whether CCD-specific IgE antibodies are able to activate
basophils using different multivalent glycoproteins as antigens. METHODS:
Purified natural tomato beta-fructofuranosidase (nLyc e 2)and rLyc e 2.02
expressed in Escherichia coli were compared by means of histamine release tests.
In addition, native and deglycosylated horseradish peroxidase and a
neoglycoprotein consisting of a defined glycopeptide
(Manalpha1-6[Xylbeta1-2]Manbeta1-4GlcNAcbeta1-4[Fucalpha1-3]GlcNAc) coupled to
BSA were used in histamine release assays using stripped basophils from normal
donors resensitized with IgE from CCD-reactive patients with food allergy to
tomato. RESULTS: Ten CCD-positive and 2 CCD-negative sera from patients with
tomato allergy underwent histamine release testing by using the glycoproteins
and nonglycosylated controls as antigens, respectively. All sera induced
histamine release with tomato extract (up to 100%), confirming the allergic
status of the donors. Four of the CCD-positive sera induced releases ranging
from 12% to 82% with all of the glycoproteins but not with the nonglycosylated
or monovalent controls. All other sera showed no response or only very weak
response to the glycoproteins. CONCLUSION: Approximately one third of the CCD-positive
sera from patients with tomato allergy have biologically relevant CCD-specific
IgE antibodies. Therefore the general claim that CCD-specific IgE is clinically
irrelevant has to be reconsidered critically. Hence IgE specific for CCDs should
be taken into consideration in the diagnosis and therapy of certain allergies.
In the subgroup of patients sensitized to CCDs, the use of natural allergens
should be preferred over the use of recombinant allergens expressed in
prokaryotic organisms.
7711.
Fritsche R. Animal models in
food allergy: assessment of allergenicity and preventive activity of infant
formulas. Toxicol Lett. 2003 Apr 11;140-141:303-9.
Food
allergies occur in about 5-10% of the overall infant and small-child population.
Cow's milk protein allergy (CMPA) is the most common in young infants, with a
2-4% incidence. When breastfeeding is not possible, hypoallergenic (HA) cow's
milk based formulas are usually given during the first months of life for
prevention of CMPA. Depending on primary (sensitization) or secondary
(triggering) prevention, the requested quality of HA formulas may be different.
Besides in vitro methods, in vivo and ex vivo animal models are helpful in
assessing residual allergenicity and the preventive effect of HA formulas. The
sensitizing capacity of a formula can be examined by either the parenteral rat (IgE),
the guinea pig (IgG1a mediated) or the oral mouse (IgE)models. The triggering
IgE mediated allergenicity is tested by a parenteral rat model with oral gavage
for intestinal mast cell protease (RMCPII) release. These animal models are also
used for testing the oral tolerance inducing capacities of formulas. Together
with cellular in vitro assays, animal models are very helpful in predicting
allergenicity and the tolerogenic potential of HA infant formulas.
7712.
Goldrick BA. Allergic
aspergillosis. Am J Nurs. 2003 Apr;103(4):89. No
abstract
7713.
Gruchalla RS, Gan V, Roy L, Bokovoy J, McDermott S, Lawrence G, Hynan L,
Luckett P. Results of an inner-city
school-based asthma and allergy screening pilot study: a combined approach using
written questionnaires and step testing. Ann Allergy Asthma Immunol. 2003
May;90(5):491-9.
BACKGROUND:
A questionnaire alone may not be an adequate screening tool for asthma.
OBJECTIVE: To determine whether an asthma questionnaire used in
combination
with an exercise step test is better than a questionnaire alone in screening for
asthma in children and to evaluate the validity of a rhinitis questionnaire in
determining atopy. METHODS: The International Study of Asthma and Allergies in
Childhood (ISAAC) asthma core questionnaire was used to screen for asthma in 307
inner-city first through third graders. All children who had scores consistent
with a diagnosis of asthma underwent step testing, as did a subset of children
who had negative overall scores. All children who had inconsistent asthma scores
and step test results underwent methacholine challenge testing. The same 307
children underwent rhinitis screening and children who had one or more positive
responses on the ISAAC rhinitis questionnaire underwent skin testing as did a
subset of children who had all negative responses. RESULTS: Three hundred of 307
asthma and rhinitis questionnaires were returned. Twenty-eight children (9%) had
global asthma scores that were considered to be positive (5 or above).
Twenty-four of these children underwent step testing as did 34 randomly selected
children who had negative global asthma scores. Thirty-one (91%) of the 34
children who had negative global asthma scores had negative step tests.
Similarly, 20 of 24 children (83%) of the children who had positive global
asthma scores had negative step tests. Only 4 children who had positive global
asthma scores were step test-positive or had reversible airway obstruction at
baseline. Using a positive methacholine challenge as the gold standard for
establishing bronchial hyperresponsiveness, the global asthma score derived from
the eight-item ISAAC asthma questionnaire yielded a sensitivity of 64%, a
specificity of 11%, a positive predictive value of 47%, and a negative
predictive value of 20%. Comparing the six-item ISAAC rhinitis questionnaire
results to the gold standard, skin test reactivity, the questionnaire yielded a
sensitivity of 76%, a specificity of 21%, a positive predictive value of 56%,
and a negative predictive value of 40%. CONCLUSIONS: Step testing was not useful
as a screening tool for asthma. In addition, the ISAAC asthma questionnaire may
not be a good asthma screening tool for inner-city pediatric populations,
especially if the form is self-administered. Investigators should first validate
both the ISAAC asthma and rhinitis screening questionnaires in the particular
population to be studied before widespread asthma and allergy screening efforts
are initiated using these tools.
7714.
Halpern MT, Khan ZM, Stanford RH, Spayde KM, Golubiewski M. Asthma: resource use and costs for inhaled
corticosteroid vs leukotriene modifier treatment--a meta-analysis. J Fam Pract.
2003 May;52(5):382-9.
OBJECTIVE:
To compare the effects of inhaled corticosteroid treatment with leukotriene
modifier treatment on medical resource use and costs for asthma patients. STUDY
DESIGN: Meta-analysis combining results from published and unpublished studies.
DATA SOURCES: Studies were identified from the MEDLINE and EMBASE databases and
the GlaxoSmithKline internal database study registers. Two independent reviewers
evaluated the identified studies; studies meeting specified inclusion criteria
were abstracted and summarized by meta-analysis with a random effects model.
OUTCOMES MEASURED: Hospitalization rate, emergency department visit rate,
emergency department costs, drug costs, total asthma-related costs, and total
medical care costs. RESULTS: Patients taking inhaled corticosteroids had: a
significantly lower annual rate of hospitalization than those taking leukotriene
modifiers (2.2% vs 4.3%, respectively; P<.05); a greater decline in
hospitalization rate (before vs after therapy initiation) than those taking
leukotriene modifiers (decline of 2.4% vs 0.55%; P<.01); a lower annual rate
of emergency department visits than those taking leukotriene modifiers (6.2% vs
7.7%; P<.005); lower total asthma-related medical costs than those taking
leukotriene modifiers (P<.05) and a 17% reduction in overall total medical
care costs (P not significant). CONCLUSIONS: Patients with asthma treated with
inhaled corticosteroids have significantly fewer asthma-related hospitalizations
and emergency department visits and lower total asthma-related health care costs
than patients treated with leukotriene modifiers. These meta-analysis findings
are consistent with results from randomized controlled trials showing
improvements in lung function for patients taking inhaled corticosteroids as
opposed to leukotriene modifiers.
7715.
Hammarsten R, Hammarsten J, Jemsby P.
Preoperative skin testing of materials used in surgical procedures. AORN
J. 2003 Apr;77(4):762-6, 769-71.
Postoperative
skin complications increase health care costs and cause patient suffering. In
the OR, patients are exposed to materials with adhesive substances that have the
potential to cause allergic or toxic effects on the skin. Intraoperatively and
postoperatively, these reactions can result in skin complications. The objective
of this study was to investigate the incidence of skin reactions in connection
with the application of different materials. Skin reactions after preoperative
skin testing occurred in 3% to 50% of patients with atopic or contact eczema,
allergy, or asthma in their medical history.
7716.
Han Z, Junxu, Zhong N. Expression
of matrix metalloproteinases MMP-9 within the airways in asthma. Respir Med.
2003 May;97(5):563-7.
The
matrix metalloproteinase (MMP) enzymes MMP-9, have relevance to chronic
structural airway changes in asthma, which can be generated by structural and
inflammatory cells, and have the ability to degrade proteoglycans and thus
potentially enhance airway fibrosis and smooth muscle proliferation through
their ability to release and activate latent, matrix-bound growth factors.
Immunostaining for MMP-9 was undertaken in acetone-fixed and glycolmethacrylate-embedded
endobronchial biopsy specimens obtained by fibreoptic bronchoscopy under local
anaesthesia. The findings from 30 asthmatic subjects were compared with those
from 18 chronic obstructive pulmonary disease (COPD) subjects and 10 healthy
controls. Meanwhile, pulmonary function test and airway responsiveness were
performed. Immunoreactivity for MMP-9 was assessed by an image analysis system.
The biopsy specimens from asthmatic subjects contained significantly more
eosinophils (P < 0.001) than those from COPD subjects, and healthy control
did not contain eosinophils. MMP-9 immunoreactivity could be identified in
endobronchial biopsy specimens from all the asthmatic subjects and 40% ofthe
COPD subjects, but could not be identified in healthy controls. Gelatinase B
(MMP-9) immunoreactivity was located in bronchial epithelium and extracellular
matrix in submucosa, prominent in denuded epithelium. The immunohistochemical
score for MMP-9 was significantly correlated with eosinophilic number in
bronchial mucosa. FEV1% predicted FEV1/FVC (%) (r = 0.52,0.41, 0.37,
respectively P < 0.01 did not correlate with PD20 FEV1 from asthmatic
subjects. MMP-9 is expressed by bronchial epithelium and may be a important
factor for eosinophil infiltraed into airway from asthma subjects.
7717.
Hepner DL, Castells MC. Latex
allergy: an update. Anesth Analg. 2003 Apr;96(4):1219-29. No abstract
7718.
Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up
of a randomised placebo-controlled trial. Lancet. 2003 May 31;361(9372):1869-71.
Perinatal
administration of the probiotic Lactobacillus rhamnosus strain GG(ATCC 53103),
reduces incidence of atopic eczema in at-risk children during the first 2 years
of life (infancy). We have therefore assessed persistence of the potential to
prevent atopic eczema at 4 years. Atopic disease was diagnosed on the basis of a
questionnaire and a clinical examination. 14 of 53 children receiving
lactobacillus had developed atopic eczema, compared with 25 of 54 receiving
placebo (relative risk 0.57, 95% CI 0.33-0.97). Skin prick test reactivity was
the same in both groups: ten of 50 children previously given lactobacillus
compared with nine of 50 given placebo tested positive. Our results suggest that
the preventive effect of lactobacillus GG on atopic eczema extends beyond
infancy.
7719.
Kanazawa H, Asai K, Hirata K, Yoshikawa J.
Possible effects of vascular endothelial growth factor in the
pathogenesis of chronic obstructive pulmonary disease. Am J Med. 2003 Apr
1;114(5):354-8.
PURPOSE:
Expression of vascular endothelial growth factor (VEGF) is reduced in the lungs
of patients with emphysema. We examined whether VEGF levels in sputum differed
in patients with emphysema, bronchitis, or asthma, as compared with controls.
METHODS: Fifty-nine patients with chronic obstructive pulmonary disease (COPD)
(25 with emphysema, 19 with chronic bronchitis, and 15 with a mixed type), 20
patients with bronchial asthma, and 11 normal controls were included in the
study. The concentration of VEGF in induced sputum and the correlations between
VEGF levels and pulmonary function were examined. RESULTS: The mean (+/- SD)
concentration of VEGF in induced sputum was significantly higher in patients
with asthma (6440 +/- 1820 pg/mL, P <0.0001) or bronchitis (4120 +/- 1100 pg/mL,
P <0.0001) than in normal controls (1860 +/- 1220 pg/mL), but significantly
lower in patients with emphysema (500 +/- 300 pg/mL, P =0.03). The concentration
of VEGF in sputum from patients with bronchitis correlated inversely with forced
expiratory volume in 1 second (r = -0.87; P =0.0002); in contrast, there was a
positive correlation between these two measurements in patients with emphysema
(r = 0.82; P <0.0001). In addition, sputum VEGF concentrations correlated
with the diffusing capacity of carbon monoxide in patients with emphysema (r =
0.87; P <0.0001), but not in those with bronchitis (r = -0.22; P =0.36).
CONCLUSION: In patients with bronchitis, increased levels of VEGF in induced
sputum were associated with airflow limitation. In contrast, decreased levels of
VEGF were associated with airflow limitation and alveolar destruction in
patients with emphysema. Thus, our findings suggest that VEGF may affect the
pathogenesis of these two common types of COPD. Copyright 2003 by Excerpta
Medica Inc.
7720.
Kerschenlohr K, Decard S, Przybilla B, Wollenberg A.
Atopy patch test reactions show a rapid influx of inflammatory dendritic
epidermal cells in patients with extrinsic atopic dermatitis and patients with
intrinsic atopic dermatitis. J Allergy Clin Immunol. 2003 Apr;111(4):869-74.
BACKGROUND:
Normal human skin harbors a single epidermal dendritic cell (DC) population, the
CD1a(+++)CD11b(-) Langerhans cells. In many chronic inflammatory skin diseases,
the epidermal DC pool bears a second population, the CD1a(+)CD11b(+++)
inflammatory dendritic epidermal cells (IDECs). Immunophenotypic,
ultrastructural, and functional aspects of IDECs have been investigated in
chronic untreated skin lesions of intrinsic and extrinsic atopic dermatitis
(AD), contact dermatitis (CD), and psoriasis, but little is known about freshly
induced early skin lesions. OBJECTIVE: We sought to characterize enumerative and
immunophenotypic changes in the epidermal DC pool during the development of
eczematous skin lesions. METHODS: The atopy patch test with aeroallergens and
food-protein allergens and a conventional patch test with standard-series
haptens were performed as models for early skin lesions of extrinsic and
intrinsic AD and CD, respectively. After 72 hours, epidermal cell suspensions
were prepared, analyzed in a standardized flow cytometric technique, and
compared with the results obtained from chronic lesions. RESULTS: The migration
of IDECs into the epidermis occurs within 72 hours and is thus an early event.
It continues in chronic AD, but not in chronic CD, lesions. The specific
upregulation of FcepsilonRI, especially on IDECs, occurs later during formation
of extrinsic but not intrinsic AD lesions. LCs were negative for Cd36 in patch
test lesions, whereas in chronic skin lesions, LCs expressed Cd36. CONCLUSION:
The DC alteration during skin lesion formation can be subdivided into early and
late events, with the influx of IDECs as an early event and the alteration of
the DC phenotype as a late event.
7721.
Lierl MB. Exhaled nitric
oxide: a useful aide in pediatric asthma management? J Pediatr. 2003
May;142(5):461-2. No abstract
7722.
Lieutier-Colas F, Purohit A, Meyer P, Fabries JF, Kopferschmitt MC,
Dessanges JF, Pauli G, de Blay F. Bronchial challenge tests in patients with
asthma sensitized to cats: the importance of large particles in the immediate
response. Am J Respir Crit Care Med. 2003 Apr 15;167(8):1077-82.
Our
aim was to compare bronchial responses to major cat allergen (Fel d 1) in
individuals with intermittent asthma sensitized to cats (19 subjects) according
to the droplet particle size. We used three nebulizers, which delivered
particles with mass median aerodynamic diameters of 1.4, 4.8, and 10.3 microm. A
dosimeter nebulizer was used. The cat allergen was diluted to obtain the same
amount of Fel d 1 per puff with each nebulizer. Each patient underwent three
methacholine bronchial challenge tests (BCT), each followed 24 hours later by a
cat allergen BCT, each performed with a different nebulizer (randomly selected
each time, with patient and tester always blinded). Subjects did not differ for
methacholine responsiveness, FEV1, mean forced expiratory flow during the middle
half of the FVC (FEF25-75), PEF, or dyspnea (Borg scale) before any of the three
cat BCTs. Cat allergen PD20 was 271 ng of Fel d 1 with the 1.4 microm nebulizer,
46 ng with the 4.8 microm nebulizer, and 13.5 ng with the 10.3 microm nebulizer
(p = 0.00001). Inhalation of small particles (1.4 microm) resulted in
significantly lower FEF25-75 24 hours after provocation than large particles
did. In conclusion, immediate bronchial response appears to be localized in
large airways, and the use of large particles is more appropriate for cat
allergen BCTs.
7723.
Lim AY, Chambers DC, Ayres JG, Stableforth DE, Honeybourne D.
Exhaled nitric oxide in cystic fibrosis patients with allergic
bronchopulmonary aspergillosis. Respir Med. 2003 Apr;97(4):331-6.
Exhaled
nitric oxide (NO) is thought to be a marker of asthmatic inflammation. Levels in
cystic fibrosis (CF) are generally low. This study aimed to measure exhaled NO
in CF patients at high risk of developing ABPA and patients at low risk. We
studied nine patients at high risk of developing ABPA and 36 at low risk. The
two groups were similar in age and spirometry. All patients in the high-risk
group were taking oral or inhaled glucocorticoids, compared to 56% in the
low-risk group (P=0.02). The exhaled NO levels were lower in the high-risk group
than in the low-risk group (2.0 vs. 3.6 ppb), mean difference (95% CI) 1.6 (-3.6
to 0.4) ppb, P=0.001. On subgroup analysis of patients on oral glucocorticoids,
the exhaled NO levels were significantly lower in patients with a high risk of
developing ABPA (n=7) than patients with a low risk (n=8) (P=0.011). The number
of patients who were on inhaled, but not oral glucocorticoids was too small to
analyse usefully. Exhaled NO levels were lower in CF patients with a high risk
of developing ABPA and on glucocorticoids. This may be because oral
glucocorticoids exert a greater effect on exhaled NO than inhaled
glucocorticoids. Alternatively, inducible nitric oxide synthase may be
down-regulated by Aspergillus toxin.
7724.
Litonjua AA, Sparrow D, Guevarra L, O'Connor GT, Weiss ST, Tollerud DJ.
Serum interferon-gamma is associated with longitudinal decline in lung
function among asthmatic patients: the Normative Aging Study. Ann Allergy Asthma
Immunol. 2003 Apr;90(4):422-8.
BACKGROUND:
Cytokines are important mediators of the asthmatic response. A retrospective
pilot study showed that serum levels of interleukin (IL)-5 and interferon (IFN)-gamma
were related to lung function decline among asthmatic patients over the
preceding 3 years. To confirm these findings, we tested the hypothesis that
serum cytokines are associated with longitudinal lung function decline. METHODS:
We conducted a prospective, longitudinal study of 25 asthmatic and 50
nonasthmatic men (median age, 63 years; range, 45 to 80 years)participating in
the Normative Aging Study. All study subjects completed two consecutive
triennial examinations, including spirometry, methacholine challenge testing,
allergy skin testing, and phlebotomy. Serum levels were measured for IL-4, IL-5,
IL-6, IL-8, IL-10, and IFN-gamma. RESULTS: Among asthmatic patients, a higher
initial serum level of IFN-gamma was associated with a greater rate of decline
of forced expiratory volume in 1 second (FEV1; beta = -67 mL/year per log
increase in serum IFN-gamma, P = 0.04) and, to a lesser extent, of FEV1/forced
vital capacity ratio (beta = -0.91%/year per log increase in serum IFN-gamma, P
= 0.07) after adjusting for age, smoking status, and baseline level of lung
function. Serum IL-5 level was associated with a rate of decline in FEV1 of
borderline significance (beta = -61 mL/year per log increase in serum IL-5, P =
0.08) among asthmatic patients. These relationshipswere not observed among
nonasthmatic patients. CONCLUSIONS: Serum levels of IFN-gamma are associated
with subsequent rate of change in lung function among asthmatic patients in this
cohort of middle-aged and older men, and may be useful as biologic markers of
risk for accelerated lung function decline in population studies.
7725.
Macy E, Mangat R, Burchette RJ. Penicillin
skin testing in advance of need: multiyear follow-up in 568 test result-negative
subjects exposed to oral penicillins. J Allergy Clin Immunol. 2003
May;111(5):1111-5.
BACKGROUND:
There are few published data on adverse drug reactions and/or resensitization
associated with oral penicillin use in penicillin allergy
history-positive/penicillin skin test-negative individuals during routine
clinical care with multiyear follow-up. OBJECTIVES: We sought to provide
long-term follow-up data on the type, severity, and frequency of adverse
reactions associated with oral penicillin use in individuals who have histories
of penicillin "allergy" yet also have negative results on penicillin
skin tests done in advance of need. We also aimed to repeat testing on
individuals with penicillin-associated adverse reactions. METHODS: Medical
records were reviewed for penicillin use and associated adverse reactions in all
568 penicillin skin test-negative individuals who had received at least 1 course
of oral penicillin after testing but before December 31, 2001, during routine
care. These individuals were drawn from a group of 1246 penicillin skin
test-negative individuals seen initially between November 16, 1994, and August
13, 2001. RESULTS: The mean length of follow-up was 4.26 +/- 1.64 years (range,
0.39-7.12 years). The mean penicillin exposure was 3.94 +/- 3.91 courses (range,
1-22 courses). Only 65 (11.4%) of 568 subjects had any penicillin-associated
reactions, and 6 subjects had 2 reactions each. A reaction occurred in 27
subjects (4.8%) with their first penicillin reexposure. There were 71
(3.2%)reactions with 2236 total penicillin courses. There were no serious
reactions. Repeated testing was done in 33 subjects older than age 18 years.
Only 1 subject was positive on repeated penicillin skin testing. CONCLUSION:
Penicillin use after negative penicillin skin testing done in advance of need is
safe, and
resensitization
is rare.
7726.
Malmberg LP, Pelkonen AS, Haahtela T, Turpeinen M.
Exhaled nitric oxide rather than lung function distinguishes preschool
children with probable asthma. Thorax. 2003 Jun;58(6):494-9.
BACKGROUND:
Respiratory function and airway inflammation can be evaluated in preschool
children with special techniques, but their relative power in identifying young
children with asthma has not been studied. This study was undertaken to compare
the value of exhaled nitric oxide (FE(NO)), baseline lung function, and
bronchodilator responsiveness in identifying children with newly detected
probable asthma. METHODS: Ninety six preschool children (age 3.8-7.5 years) with
asthmatic symptoms or history and 62 age matched healthy non-atopic controls
were studied. FE(NO) was measured with the standard online single exhalation
technique, and baseline lung function and bronchodilator responsiveness were
measured using impulse oscillometry (IOS). RESULTS: Children with probable
asthma (n=21), characterised by recent recurrent wheeze, had a significantly
higher mean (SE) concentration of FE(NO) than controls (22.1 (3.4) ppb v 5.3
(0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher
baseline respiratory resistance, lower reactance, and larger bronchodilator
responses expressed as the change in resistance after inhalation of salbutamol.
Children with chronic cough only (n=46) also had significantly raised mean FE(NO)
(9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0)but their lung
function was not significantly reduced. Children on inhaled steroids due to
previously diagnosed asthma (n=29) differed from the controls only in their
baseline lung function. The analysis of receiver operating characteristics (ROC)
showed that FE(NO) provided the best power for discriminating between children
with probable asthma and healthy controls, with a sensitivity of 86% and
specificity of 92% at the cut off level of 1.5 SD above predicted. CONCLUSIONS:
FE(NO) is superior to baseline respiratory function and bronchodilator
responsiveness in identifying preschool children with probable asthma. The
results emphasise the presence of airway inflammation in the early stages of
asthma, even in young children.
7727.
Medeiros M Jr, Figueiredo JP, Almeida MC, Matos MA, Araujo MI, Cruz AA,
Atta AM, Rego MA, de Jesus AR, Taketomi EA, Carvalho EM.
Schistosoma mansoni infection is associated with a reduced course of
asthma. J Allergy Clin Immunol. 2003 May;111(5):947-51.
BACKGROUND:
Helminthic infections decrease skin reactivity to indoor allergens, but data on
whether they influence asthma severity are lacking. OBJECTIVE: This study
evaluated the course of asthma in patients with and without Schistosoma mansoni
infection. METHODS: Asthmatic subjects were enrolled from 3 low-socioeconomic
areas: a rural area endemic for schistosomiasis (group 1) in addition to a rural
area (group 2) and a slum area (group 3), both of which were not endemic for
schistosomiasis. A questionnaire on the basis of the International Study of
Asthma and Allergies in Childhood study was applied in these 3 areas, and from
each area, 21 age- and sex-matched asthmatic subjects were selected for a
prospective 1-year study. Pulmonary function tests, skin prick tests with indoor
allergens, stool examinations, and serum evaluations were performed in these
subjects. Every 3 months, the subjects were evaluated for asthma exacerbation
through physical examination, and a questionnaire regarding asthma symptoms and
use of antiasthma medicine was administered. RESULTS: The prevalence of S
mansoni infection was greater in group 1 compared with in groups 2 and 3 (P
<.0001), whereas the frequency of other helminth and protozoa infections was
similar among the 3 groups. The frequency of positive skin test responses to
indoor allergens was less (19.0%) in group 1 subjects relative to those in group
2 (76.2%) and group 3 (57.1%; P <.001). The frequencies of symptoms, use of
antiasthma drugs, and pulmonary abnormal findings at physical examination were
less in group 1 subjects than in group 2 and 3 subjects (P =.0001). CONCLUSION:
Our results suggest that S mansoni infection is associated with a milder course
of asthma.
7728.
Moneret-Vautrin DA, Kanny G, Fremont S.
Laboratory tests for diagnosis of food allergy: advantages, disadvantages
and future perspectives. Allerg Immunol (Paris). 2003 Apr;35(4):113-9.
Numerous
biological tests point to the diagnosis of food sensitization: detection of
specific IgEs by Rast techniques, multi-detection assays, immunoblotting,
screening of basophil activation (BAT or FAST), assays for leukotriene LTC4
release (CAST), measurement of plasma histamine, serum tryptase, serum ECP,
urinary EDN, completed by mannitol-lactulose test evaluating intestinal
permeability, assay of fecal IgEs, Rast for specific IgG4. Primary screening for
anti-food IgEs by multi-detection assays seeks justification from insufficient
clinical data and false positive tests are common in patients sensitized to
pollens or latex, on account of in vitro cross reactivities (CR). Multiple CR
explain positive Rast to vegetal food allergens in such patients. Biological
tests should not be performed as the first line of diagnosis. In vivo
sensitisation is assessed by positive prick-tests, demonstrating the bivalence
of allergens, as well as the affinity of specific IgEs, two conditions necessary
to bridge membrane bound specific IgEs, leading to the release of mediators.
Prick-tests are closer to clinical symptoms than biological tests. However, the
diagnosis of food allergy is based on standardised oral challenges. Exceptions
are high levels of specific IgEs to egg (> 6 kUl/l), peanut (> 15 kUl/l),
fish (> 20 kUl/l) and milk (> 32 kUl/l), reaching a 95% predictive
positive value. Rast inhibition tests are useful to identify masked allergens in
foods. Research developments will have impact on the development of new
diagnostic tools: allergen mixes reinforcing a food extract by associated
recombinant major allergens, multiple combination of recombinant allergens
(chips) or tests with synthetic epitopes aimed a the prediction of recovery.
Laboratory tests take place in the decision free for the diagnosis for the food
allergy and the follow-up of the levels specific IgEs is a tool to assess
outcome and contributes to predict recovery or persistent allergy. Up to now the
significance of positive laboratory tests showing the implication of IgEs is at
the crossroads of the allergist's and biologist's expertise.
7729.
Munoz-Furlong A. Daily
coping strategies for patients and their families. Pediatrics. 2003 Jun;111(6 Pt
3):1654-61.
The
diagnosis of food allergy in a child has an impact on every minute of every day
for the child and the child's family. The patient and family must learn how to
read labels, adapt recipes, and educate other family members, child care
providers, camp counselors, and teachers. They must know how to recognize
symptoms of a reaction and what to do during a reaction. Decisions such as which
restaurant to go to and where to go on vacation take on new meaning, as family
decisions must be centered on avoidance of the child's food allergen. It is
possible to manage food allergies successfully while allowing the child to
participate in common childhood activities. Education of the family is key. This
discussion provides the pediatrician or primary care physician with practical
information for educating patients and their families about managing food
allergy.
7730.
Noga O, Hanf G, Kunkel G. Immunological
and clinical changes in allergic asthmatics following treatment with omalizumab.
Int Arch Allergy Immunol. 2003 May;131(1):46-52.
IgE
plays a key role in allergic asthma. We investigated whether omalizumab
treatment of patients with moderate to severe allergic asthma leads to changes
in inflammatory mediators and clinical symptoms. This sub-study was conducted on
35 patients with a positive skin prick test (SPT) requiring daily administration
of beclomethasone dipropionate (500-1,000 microg), who participated in a
multicentre, randomised, double-blind, placebo-controlled study. Omalizumab or
placebo was administered at 0.016 mg/kg/IgE every 4 weeks. Patients recorded
peak expiratory flow, asthma symptom score and beta(2)-agonist use in daily
diaries and spirometry was performed at each visit. beta(2)-Agonist use and SPT
wheal reaction decreased significantly (p < 0.05). Circulating levels of
IL-5, IL-6, IL-8, IL-10, IL-13 and s-ICAM were measured before and after 16
weeks of treatment. IL-13 and s-ICAM were measured before and after 16 weeks of
treatment. IL-13 decreased significantly (p < 0.01). IL-5 and IL-8 decreased
in the omalizumab group compared to baseline. The other circulating mediators
did not demonstrate any changes. Histamine release was significantly reduced (p
< 0.01). Airway resistance (p < 0.05) and the provocative concentration
inducing a 20% decrease in FEV(1) (p < 0.05) were measured before, after 16
weeks, and 3 months after completion of treatment. Both parameters decreased
significantly (p < 0.05). Peripheral eosinophil count decreased significantly
compared to placebo (p < 0.01). These findings suggest that omalizumab has
potential as a novel treatment for allergic asthma.
7731.
Novak N, Tepel C, Koch S, Brix K, Bieber T, Kraft S.
Evidence for a differential expression of the FcepsilonRIgamma chain in
dendritic cells of atopic and nonatopic donors.
J Clin Invest. 2003 Apr;111(7):1047-56.
While
mast cells and basophils constitutively express the high-affinity IgE receptor (Fc
epsilon RI), it is absent or weakly expressed on APCs from normal donors. Fc
epsilon RI is strongly upregulated on APCs from atopic donors and involved in
the pathophysiology of atopic diseases. Despite its clinical relevance, data
about Fc epsilon RI regulation on APCs are scarce. We show that in all donors
intracellular alpha chain of the Fc epsilon RI (Fc epsilon RI alpha) accumulates
during DC differentiation from monocytes. However, expression of gamma chains of
the Fc epsilon RI (Fc epsilon RI gamma), mandatory for surface expression, is
downregulated. It is low or negative in DCs from normal donors lacking surface
Fc epsilon RI (Fc epsilon RI(neg) DCs). In contrast, DCs from atopics express
surface Fc epsilon RI (Fc epsilon RI(pos) DCs) and show significant Fc epsilon
RI gamma expression, which can be coprecipitated with Fc epsilon RI alpha. In Fc
epsilon RI(neg) DCs lacking Fc epsilon RI gamma, immature and core glycosylated
Fc epsilon RI alpha accumulates in the endoplasmic reticulum. In Fc epsilon
RI(pos) DCs expressing Fc epsilon RI gamma, an additional mature form of Fc
epsilon RI alpha exhibiting complex glycosylation colocalizes with Fc epsilon RI
gamma in the Golgi compartment. IgE binding sustains surface-expressed Fc
epsilon RI on DCs from atopic donors dependent on baseline protein synthesis and
transport and enhances their IgE-dependent APC function. We propose that
enhanced Fc epsilon RI on DCs from atopic donors is driven by enhanced
expression of otherwise limiting amounts of Fc epsilon RI gamma and is preserved
by increased IgE levels.
7732.
Nowak-Wegrzyn A. Future
approaches to food allergy. Pediatrics. 2003 Jun;111(6 Pt 3):1672-80.
BACKGROUND:
Infantile food protein-induced enterocolitis syndrome (FPIES) is a severe,
cell-mediated gastrointestinal food hypersensitivity typically provoked by cow's
milk or soy. Solid foods are rarely considered a cause. OBJECTIVE: To describe
the clinical characteristics and natural history of FPIES provoked by solid
foods. METHODS: Patients with FPIES induced by solid foods were identified and
their clinical course compared with a control group with FPIES caused by cow's
milk and/or soy evaluated over the same time period. RESULTS: Fourteen infants
with FPIES caused by grains (rice, oat, and barley), vegetables (sweet potato,
squash, string beans, peas), or poultry (chicken and turkey) were identified.
Symptoms were typical of classical FPIES with delayed (median: 2 hours) onset of
vomiting, diarrhea, and lethargy/dehydration. Eleven infants (78%) reacted to
>1 food protein, including 7 (50%) that reacted to >1 grain. Nine (64%) of
all patients with solid food-FPIES also had cow's milk and/or soy-FPIES. Initial
presentation was severe in 79% of the patients, prompting sepsis evaluations
(57%) and hospitalization (64%) for dehydration or shock. The diagnosis of FPIES
was delayed, after a median of 2 reactions (range: 2-5).
Thirty
patients with typical cow's milk- and/or soy-FPIES were identified for
comparison. Overall, 48% of the 44 infants with FPIES were reactive to >1
food protein, and the risk for multiple food hypersensitivity approached 80% in
the infants with solid food or soy-induced FPIES. None of the patients developed
FPIES to maternally ingested foods while breastfeeding unless the causal food
was fed directly to the infant. CONCLUSIONS: Cereals, vegetables, and poultry
meats, typically regarded as of low allergenic potential, must be considered in
the evaluation of FPIES, particularly in infants previously diagnosed with FPIES
to cow's milk or soy, and as an initial cause in patients who have been
exclusively breastfed. Infants with FPIES are at risk for multiple dietary
protein hypersensitivities during an apparent period of immunologic
susceptibility. Pediatricians should consider FPIES in the differential
diagnosis of shock and sepsis.
7733.
Nugent JS, Quinn JM, McGrath CM, Hrncir DE, Boleman WT, Freeman TM.
Determination of the incidence of sensitization after penicillin skin
testing. Ann Allergy Asthma Immunol. 2003 Apr;90(4):398-403.
BACKGROUND:
Concerns for sensitization after penicillin skin testing are afactor in limiting
the timing and population for whom this testing is offered. The sensitizing
potential of the penicillin skin test has never been studied directly. METHODS:
A total of 329 volunteers underwent prick and intradermal skin testing with
penicillin G, benzylpenicilloyl-polylysine, and a minor determinant mixture.
Those with negative skin testing had repeat testing 4 weeks later. Medical
history and antibiotic use were determined by interview, questionnaire, and
electronic pharmacy records. RESULTS: Seventy-two of the 329 subjects (22%)
reported a history of previous beta-lactam reaction, of which 10 (14%) had a
positive initial skin test. Overall, the initial skin test was positive in 23 of
329 (7%). Of the subjects with a negative initial skin test, 239 completed the
second test 4 weeks later. Of these, 6 subjects (2.5%, 95% confidence interval
0.5% to 4.5%) converted to a positive skin test. None had taken a beta-lactam
antibiotic between the two tests, and none had any previous history of beta-lactam
reaction. One subject reported having never taken a beta-lactam antibiotic
before. In comparison to the 233 subjects who did not convert their skin test,
the statistically significant factors favoring sensitization were: female sex
(odds ratio [OR] 6.53, P = 0.05), atopy (OR 5.31, P = 0.04), and history of food
allergy (OR 6.35, P = 0.02). There was a trend toward more recent penicillin use
in the newly sensitized subjects, but this was not statistically significant..
CONCLUSION: Penicillin skin testing may sensitize a small number of individuals
to penicillin.
7734.
Ohga S, Nomura A, Ihara K, Takahata Y, Suga N, Akeda H, Shibata R,
Okamura J, Kinukawa N, Hara T. Cytokine
imbalance in hyper-IgE syndrome: reduced expression of transforming growth
factor beta and interferon gamma genes in circulating activated T cells. Br J
Haematol. 2003 Apr;121(2):324-31.
Hyper-IgE
syndrome (HIES) is a primary immunodeficiency disease characterized by recurrent
infections and marked immunoglobulin (Ig)E elevation. To assess the proper
T-cell defects of HIES, the cytokine profile of naturally activated T cells was
compared between HIES, atopic dermatitis and chronic granulomatous disease (CGD).
Intracellular flow cytometric analysis after in vitro stimulation showed no
difference in the proportion of interferon (IFN)gamma- or interleukin 4
(IL-4)-producing T cells among these diseases. Quantitative polymerase chain
reaction (PCR) for the cytokine genes was performed using circulating highly
fractionated HLA-DR+ and HLA-DR- T cells. The IFNgamma/IL-4 or IFNgamma/IL-10
ratios were lower in HLA-DR+ T cells of HIES than in CGD (P = 0.0106, 0.0445),
but did not differ between HIES and atopy. The transforming growth factor-beta (TGFbeta)/IL-4
ratio in HLA-DR+ T cells of HIES was lower than that of atopy (0.0106) or CGD
(0.0062). The TGFbeta/IL-4 ratio in HLA-DR- T cells of HIES was also lower than
that of atopy (0.0285). Stepwise logistic regression analysis identified TGFbeta/IL-4
ratios in HLA-DR+ (0.0001) or HLA-DR- (0.0086) T cells as the most powerful
parameters to distinguish HIES from atopy and/or CGD. Serum IgE levels
negatively correlated with IFNgamma/IL-4 (0.0108), IFNgamma/IL-10 (0.0254), or
TGFbeta/IL-4 (0.0163) ratios in HLA-DR+, but not HLA-DR-, T cells. These results
suggested that the in vivo activated T cells of HIES did not sufficiently
express the IFNgamma and TGFbeta genes, which could affect IL-4-dependent IgE
production. The reduced TGFbeta expression may involve the indigenous T-cell
defects of HIES.
7735.
Ownby DR. Strategies for
distinguishing asymptomatic latex sensitization from true occupational allergy
or asthma. Ann Allergy Asthma Immunol. 2003 May;90(5 Suppl 2):42-6.
OBJECTIVE:
To evaluate strategies for distinguishing those individuals with true
occupational asthma caused by exposure to natural rubber latex from those
individuals with allergic disease related to other allergens. DATA SOURCES:
Article published between January 1, 1981, and December 31, 2001, were
identified via a MEDLINE search with the following keywords: latex, allergy,
asthma, occupation asthma, and adverse reactions. STUDY SELECTION:
English-language reports concerning diagnostic methods in latex and other forms
of occupational asthma. RESULTS: Many methods have been evaluated for the
diagnosis of latex allergy, including medical history, skin prick tests, in
vitro tests, and various challenge tests. Skin prick tests with well
characterized latex extracts are highly sensitive and specific predictors of
latex-specific IgE antibodies; however, direct pulmonary challenge with latex
allergen appears to be the only highly reliable method for diagnosis of
latex-related occupational asthma. CONCLUSIONS: It is difficult to optimally
distinguish between occupational latex asthma and asymptomatic latex
sensitization in a person with preexisting asthma using currently available
techniques.
7736.
Palosuo K, Varjonen E, Nurkkala J, Kalkkinen N, Harvima R, Reunala T,
Alenius H. Transglutaminase-mediated
cross-linking of a peptic fraction of omega-5 gliadin enhances IgE reactivity in
wheat-dependent, exercise-induced anaphylaxis.
Allergy Clin Immunol. 2003 Jun;111(6):1386-92.
BACKGROUND:
Patients with wheat-dependent, exercise-induced anaphylaxis (WDEIA) experience
recurrent anaphylactic reactions when exercising after ingestion of wheat
products. We have identified omega-5 gliadin (Tri a 19) as a major allergen in
WDEIA, but the role of exercise in eliciting the symptoms remains obscure.
OBJECTIVE: The aim was to examine whether tissue transglutaminase (tTG)-mediated
cross-linking could be involved in modulating the IgE-binding ability and in
vivo reactivity of digested omega-5 gliadin peptides in WDEIA. METHODS: Purified
omega-5 gliadin was digested with pepsin or with pepsin and trypsin and treated
with tTG. The binding of IgE antibodies in pooled sera from 10 patients with
WDEIA was studied by means of immunoblotting before and after tTG treatment of
the digested peptides. The peptides derived from pepsin digestion were separated
by means of gel-filtration chromatography, and IgE reactivity of 4 different
peptide fractions was studied by immunoblotting before and after tTG treatment.
The fraction showing the greatest degree of cross-linking by tTG was further
studied by means of IgE ELISA, ELISA inhibition, and skin prick testing.
RESULTS: The IgE-binding ability of omega-5 gliadin was retained after pepsin
and pepsin-trypsin digestion. tTG treatment of the whole peptic digest formed
large peptide complexes, with molecular weights ranging from 40 to greater than
200 kd. These cross-linked aggregates bound IgE antibodies in immunoblotting
more intensely than untreated, pepsin-digested, or pepsin-trypsin-digested
omega-5 gliadin. A gel-filtration fraction of the whole peptic digest
corresponding to the highest peak of the chromatogram and showing the greatest
degree of tTG-mediated cross-linking showed an increase in serum IgE reactivity
in ELISA after tTG treatment, as well as a shift of reactivity to cross-linked
complexes. In the 20 patients with WDEIA, the mean skin prick test wheal
elicited by this tTG-treated peptic fraction was 77% larger (P <.001) than
that elicited by the untreated peptic fraction and 56% larger (P <.01) than
that elicited by intact omega-5 gliadin. CONCLUSIONS: Omega-5 gliadin-derived
peptides are cross-linked by tTG, which causes a marked increase in IgE binding
both in vitro and in vivo. Activation of tTG during exercise in the intestinal
mucosa of patients with WDEIA could lead to the formation of large allergen
complexes capable of eliciting anaphylactic reactions.
7737.
Ramos JD, Cheong N, Lee BW, Chua KY.
Peptide mapping of immunoglobulin E and immunoglobulin G immunodominant
epitopes of an allergenic Blomia tropicalis paramyosin, Blo t 11. Clin Exp
Allergy. 2003 Apr;33(4):511-7.
BACKGROUND:
The identification of immunodominant peptides containing the IgE and IgG
epitopes on allergen molecules is an important step in understanding the
interaction of the allergen with the immune system and, thus, essential for the
development of effective immunotherapeutic and diagnostic reagents. The present
study aimed to map the IgE and IgG immunodominant peptides of Blomia tropicalis
(Bt) allergen Blo t 11, a high molecular weight allergen homologous to
paramyosin, exhibiting important allergenic activity. METHODS: Eleven
overlapping fragments of Blo t 11 cDNA gene were expressed as glutathione s-transferase
(GST) fusion peptides, which were affinity-purified using the
glutathione-Sepharose column. Human IgE and IgG immunodominant peptides were
determined by dot blot immunoassay using crude Bt extract-positive sera from
asthmatic patients. Evaluation of allergenicity, specific hIgG subclass
analysis, and cross- and self-inhibition studies were determined by
enzyme-linked immunosorbent assay. RESULTS: Blo t 11 contains multiple IgE and
IgG immunodominant peptides scattered throughout the molecule. The dominant IgE
and IgG peptides were mapped at amino acid positions 336-557 and 698-875,
respectively. An immunodominant peptide (fD) registered a higher percentage of
IgE and IgG reactivity compared to the rFL-Blo t 11. Significant serum levels of
Blo t 11- and fD-specific IgG1, IgG2 and IgG4, but not IgG3 were detected in the
Bt extract-positive sera tested. Cross-inhibition study revealed the rFL-Blot 11
was significantly inhibited by fD. CONCLUSION: The IgE and IgG immunodominant
peptides of Blo t 11 have been mapped. Our data suggest that utilization of Blo
t 11 fragment(s) or chimeric fusion fragments containing IgE and IgG epitopes
could be a better alternative in the development of diagnostic and therapeutic
reagents for mite allergy.
7738.
Redline S, Larkin EK, Kercsmar C, Berger M, Siminoff LA. Development and validation of school-based asthma and allergy
screening instruments for parents and students. Ann Allergy Asthma Immunol. 2003
May;90(5):516-28.
BACKGROUND:
The increasing morbidity attributable to asthma among school-aged children
suggests the potential utility of school-based asthma screening programs.
OBJECTIVE: We report our efforts to develop and validate culturally sensitive
and clinically useful screening questionnaires (parent and child versions) for
asthma and allergies among urban US school children. METHODS: Instrument
development was accomplished through literature review, expert medical and child
developmental input, focus group feedback, and a rigorous trial of the
instruments in a public school setting. Questionnaires were distributed to 2,800
children and their families in an urban public school system (grades
kindergarten through 6). Validity was evaluated by blinded comparison of results
against a standardized clinical evaluation in 107 children, with final
designations determined by an expert panel. RESULTS: Questionnaires pertaining
to 2,083 children were returned (participation rate of 74%). A moderate level of
agreement was observed between parent and student questionnaire responses (r
values = 0.36 to 0.50; P values < 0.001). The highest frequency of
asthma-like symptoms was reported for African-American boys and the lowest for
Caucasian girls. The items from the parent questionnaire that best predicted
asthma were "breathing problems" (occurring rarely or more; odds ratio
12.8; 95% confidence interval, 4.5 to 36.1) and "problems coughing"
(sometimes or more; odds ratio 9.7; 95% confidence interval, 3.6 to 26.5).
Considering the presence of cough (sometimes or more) and/or breathing problem
(rarely or more)yielded a sensitivity of 80%; a specificity of 75%, a positive
predictive value of 50%, and a negative predictive value of 92%. Similar levels
of prediction were observed for the items "trouble breathing" and
"noisy breathing" as directly reported by the students. Allergic
rhinitis was best predicted by report of a runny/stuffy no se (sometimes or
more; sensitivity of 83%, specificity of 61%).Allergic conjunctivitis was best
predicted by "itchy eyes." CONCLUSIONS: Administration of a
school-based questionnaire is feasible, with a high response rate and excellent
internal consistency. A high sensitivity and acceptable specificity was achieved
by using one to two questions for asthma, allergic rhinitis, and allergic
conjunctivitis. Among the children in grades 2 or above, comparable levels of
prediction could be achieved with the student or parent version.
7739.
Remes ST, Iivanainen K, Koskela H, Pekkanen J.
Which factors explain the lower prevalence of atopy amongst farmers'
children? Clin Exp Allergy. 2003 Apr;33(4):427-34.
BACKGROUND:
The inverse association between farming and atopy in children has been
attributed to microbial exposure, especially through livestock. Very little is
known about other potential explanatory factors. OBJECTIVE: To explore potential
differences in lifestyle and environmental factors between farmer and non-farmer
families, and whether these factors could explain the association between
farming and childhood atopy. METHODS: A cross-sectional study, including 366
farmers' and 344 non-farmers' children in eastern Finland. Information regarding
exposure and background characteristics was gathered by a written questionnaire.
Atopy was defined as having one or more positive skin prick test reactions (>
3 mm) against the six common aeroallergens. RESULTS: Regardless of the current
farming type, atopy was less frequent among the farmers' children than the
non-farmers' children (aOR 0.56, 95% CI 0.40-0.78). Remarkable differences were
seen in many lifestyle factors (including diet) between the farmer and
non-farmer families, but only a few of the explored factors were associated with
atopy. The frequency of current livestock contacts seemed to have an inverse,
dose-dependent association with atopy (aOR 0.46, 95% CI 0.22-0.97 for daily vs.
no contact). Having lived on a dairy farm in infancy (aOR 0.51, 95% CI
0.28-0.93), or having had cats or dogs in infancy (aOR 0.60, 95% CI 0.42-0.85),
decreased the risk of atopy at school age. The inverse association between
farming and atopy was not explained by the sociodemographic factors, or by
differences in conventional risk factors of atopy. Animal contacts explained
partially, but not completely, the association. CONCLUSION: Higher frequency of
animal contacts is one factor, but probably not the only one, explaining the
inverse association of farming and atopy in children. The importance of early
life exposures may have recently been over-emphasized, and current exposures
discounted, when studying the risk factors of childhood atopy.
7740.
Roberts EM. Does your child
have asthma? Parent reports and medication use for pediatric asthma. Arch
Pediatr Adolesc Med. 2003 May;157(5):449-55.
OBJECTIVE:
To assess parental reporting of diagnosis used in surveys as an indicator of
pediatric asthma prevalence. METHODS: Analysis of the Medical Expenditure Panel
Survey, 1996 and 1997 (10 404 children aged from 0 to 17 years). All values are
expressed as mean (SE). RESULTS: Asthma medications were purchased for 2.5%
(0.2%) of children. Parents of 45.4% (4.0%) of these children failed to report
asthma, including 41.3 (10.5%) of those for whom maintenance medications were
purchased. These findings remained unchanged when very young children were
excluded from the sample. Controlling for insurance coverage, no racial, ethnic,
or socioeconomic disparities in reported asthma were found; however, poor
children were more likely to have maintenance medications purchased (odds ratio,
4.9; 95% confidence interval, 2.3-10.4). CONCLUSIONS: Surveys of parental
reports of asthma overlook many children with active disease. Dependence on
parental reports may underestimate the prevalence of serious asthma among poor
children. The parents in this study who fail to report asthma may represent a
group that perceives their children's disease as less serious a problem despite
active purchasing of medications.
7741.
Sastre J, Fernandez-Nieto M, Rico P, Martin S, Barber D, Cuesta J, de las
Heras M, Quirce S. Specific
immunotherapy with a standardized latex extract in allergic workers: a
double-blind, placebo-controlled study. J Allergy Clin Immunol. 2003
May;111(5):985-94.
BACKGROUND:
Preventive measures have been proposed to reduce the risk of sensitization to
natural rubber latex (NRL), but this is not always feasible. OBJECTIVE: The aim
of this study was to determine the efficacy and safety of specific immunotherapy
with a standardized latex extract in sensitized workers. METHODS: Twenty-four
patients allergic to NRL with contact urticaria (n = 8) and rhinitis or asthma
(n = 16) were included (16 in the active group and 8 in the placebo group).
Treatment started in a cluster immunotherapy protocol, with injections every
week for 3 months and then every other week for another 3 months. RESULTS:
Patients in the active group had significantly lower values than patients in the
placebo group in skin terms of reactivity to NRL (P <.01), rubbing test
results (P =.047), and latex glove use test results (P =.046) after 6 months of
treatment. There were no significant differences between the active and placebo
groups in symptom scores, use of medication, self-assessment, or methacholine
test results either before or after treatment. Differences in nasal and
bronchial symptoms during specific inhalation challenges (P = not significant
and P =.05, respectively) were observed in favor of the active
group. In the
active group 32 systemic reactions were observed (8% of doses), mostly during
the build-up period, being more frequent in patients with respiratory symptoms
(P =.004). All reactions responded promptly to treatment. CONCLUSION: Clinical
efficacy was shown mainly on cutaneous symptoms, although an improvement in
rhinitis and asthma symptoms was also observed during specific inhalation
challenges. Latex-specific immunotherapy might be a useful approach for the
treatment of latex allergy in sensitized workers.
7742.
Saxena S, Madan T, Shah A, Muralidhar K, Sarma PU. Association of
polymorphisms in the collagen region of SP-A2 with increased levels of total IgE
antibodies and eosinophilia in patients with allergic bronchopulmonary
aspergillosis. J Allergy Clin Immunol. 2003 May;111(5):1001-7
BACKGROUND:
Studies from our group have shown a protective role of pulmonary surfactant
protein A (SP-A) against lung allergy and infections caused by Aspergillus
fumigatus. OBJECTIVE: Present study investigated the association of
polymorphisms in the collagen region of SP-A1 and SP-A2 (genes encoding SP-A)
with allergic bronchopulmonary aspergillosis (ABPA) and its clinical markers.
METHODS: Genomic DNA was extracted from blood samples of patients with ABPA and
age-matched, unrelated control subjects. The polymorphisms were detected by
means of PCR amplification and sequencing of the collagen region of SP-A1 and
SP-A2. RESULTS: Two exonic (SP-A2 G1649C and SP-A2 A1660G, 10 patients and 11
control subjects) and 2 intronic (SP-A2 T1492C, 8 patients and 8 control
subjects; SP-A1 C1416T, 5 patients and 7 control subjects) polymorphisms in the
collagen region of SP-A2 and SP-A1 showed significant association with patients
with ABPA. A significantly higher frequency of the AGA allele (A1660G) of SP-A2
was observed in patients with ABPA in comparison with control subjects (P
=.0156, odds ratio [OR] = 4.78, 95% CI = 1.23 < OR < 18.52). This
polymorphism, when existing along with a nonredundant polymorphism, SP-A2 G1649C
(Ala91Pro) resulted in a stronger association with ABPA (A1660G and G1649C: P
=.0079, OR = 10.4, 95% CI = 1.62 < OR < 66.90). Patients with ABPA with
GCT and AGG alleles showed significantly high levels of total IgE and percentage
eosinophilia versus patients with ABPA with CCT and AGA alleles. CONCLUSION: The
results indicated that SP-A2 G1649C and SP-A2 A1660G, polymorphisms in the
collagen region of SP-A2, might be one of the contributing factors to genetic
predisposition and severity of clinical markers of ABPA.
7743.
Simpson JL, Moric I, Wark PA, Johnston SL, Gibson PG.
Use of induced sputum for the diagnosis of influenza and infections in
asthma: a comparison of diagnostic techniques. J Clin Virol. 2003
Apr;26(3):339-46.
BACKGROUND:
Influenza (Flu) and respiratory syncytial virus (RSV) are important viral
pathogens that cause lower respiratory tract infections and severe exacerbations
of asthma. Molecular biological techniques are permitting a rapid and accurate
diagnosis of infections caused by respiratory pathogens, and have typically been
applied to upper respiratory samples. Sputum induction provides an opportunity
to directly sample secretions from the lower respiratory tract. OBJECTIVES/STUDY
DESIGN: To determine the role of induced sputum reverse-transcription polymerase
chain reaction (RT-PCR) in the detection of respiratory pathogens and compare
this with detection using serology and immunofluorescent antigen (IFA) testing,
we recruited 49 adults from emergency room with exacerbations of asthma. After a
medical assessment and spirometry, sputum was induced using ultrasonically
nebulised normal saline. Sputum was assayed using IFA and RT-PCR for flu and
RSV. Flu serology was performed acutely and at convalescence, 4-5 weeks later.
RESULTS: Influenza A or B was detected in 24% of the samples by PCR,
significantly more than the nine cases detected using serology and the one case
using IFA (P<0.05). RSV was detected in 37% of samples using PCR and 20% by
IFA (P<0.05). CONCLUSION: The combination of induced sputum and RT-PCR
provides a useful means of detecting respiratory infection. The technique is
safe in both adults and children, and RT-PCR is more sensitive than conventional
serology and IFA. The improved sensitivity of induced sputum RT-PCR also permits
a more rapid diagnosis and the opportunity of early administration of effective
treatments.
7744.
Stempel DA. Assessing the
economic burden of asthma. J Allergy Clin Immunol. 2003 Jun;111(6):1203-4. No abstract
7745.
Szczeklik A, Stevenson DD. Aspirin-induced
asthma: advances in pathogenesis, diagnosis, and management. J Allergy Clin
Immunol. 2003 May;111(5):913-21
In
some asthmatic individuals, aspirin and other nonsteroidal anti-inflammatory
drugs (NSAIDs) that inhibit cyclooxygen-ase 1 (COX-1) exacerbate the condition.
This distinct clinical syndrome, called aspirin-induced asthma (AIA), is
characterized by an eosinophilic rhinosinusitis, nasal polyposis, aspirin
sensitivity, and asthma. There is no in vitro test for the disorder, and
diagnosis can be established only by provocation challenges with aspirin or
NSAIDs. Recent major advances in the molecular biology of eicosanoids,
exemplified by the cloning of 2 cysteinyl leukotriene receptors and the
discovery of a whole family of cyclooxygenase enzymes, offer new insights into
mechanisms operating in AIA. The disease runs a protracted course even if COX-1
inhibitors are avoided, and the course is often severe, many patients requiring
systemic corticosteroids to control their sinusitis and asthma. Aspirin and
NSAIDs should be avoided, but highly specific COX-2 inhibitors, known as coxibs,
are well tolerated and can be safely used. Aspirin desensitization, followed by
daily aspirin treatment, is a valuable therapeutic option in most patients with
AIA, particularly those with recurrent nasal polyposis or overdependence on
systemic corticosteroids.
7746.
Tarlo SM. Laboratory
challenge testing for occupational asthma. J Allergy Clin Immunol. 2003
Apr;111(4):692-4.
OBJECTIVE:
To describe the features of irritant-induced asthma and discuss the diagnosis in
relation to differing workplace irritant exposures and symptomatic responses.
DATA SOURCES: A review of MEDLINE articles on this topic from January 1, 1985,
through December 31, 2023 was performed. STUDY SELECTION: The author selected
relevant articles for inclusion in the review. RESULTS: Many reports indicate
that unintentional high-level respiratory irritant exposures can induce the new
onset of asthma. Cases that meet strict criteria for a syndrome of
irritant-induced asthma, termed reactive airways dysfunction syndrome, can be
diagnosed with relative certainty. Several reports of irritant-induced asthma,
especially prevalence studies, have relied on historical data or have otherwise
modified the reactive airways dysfunction syndrome criteria for diagnosis (eg,
expanding the definition to include the symptom onset several days after
exposure). Such modifications, or inclusion of cases with incomplete
documentation, likely increase diagnostic sensitivity but may reduce the
certainty of diagnosis for individual cases. Expanding exposure criteria to
moderate or
long-term low-level irritant exposures causes difficulty in excluding transient
irritant exacerbation of underlying asthma or coincidental onset of asthma
during working life. Although recent population studies suggest a greater
relative risk of asthma in occupations with expected low-to-moderate respiratory
irritant exposures, currently no objective laboratory tests exist to exclude
coincidental asthma in such patients. CONCLUSIONS: Irritant-induced asthma can
be produced by high-level unintentional respiratory irritant exposures at work
or outside the workplace. Lower levels of exposure to respiratory irritants at
work are more common, and additional studies are needed to determine the airway
effects of such exposures.
7747.
Taube C, Kanniess F, Gronke L, Richter K, Mucke M, Paasch K, Eichler G,
Jorres RA, Magnussen H. Reproducibility
of forced inspiratory and expiratory volumes after bronchodilation in patients
with COPD or asthma. Respir Med. 2003 May;97(5):568-77.
The
aim of the present study was to assess the reproducibility of changes in forced
inspiratory volumes after bronchodilator inhalation. Thirteen patients with
chronic obstructive pulmonary disease (COPD) (FEV1, 32-75%pred) and 10 patients
with asthma (FEV1, 43-75%pred) inhaled either 200 microg fenoterol or 200 microg
oxitropium bromide or placebo, each of them on three occasions, on nine
different days in a randomised, cross-over, double-blind fashion. Forced
expiratory (FEV1) and inspiratory (FIV1) volumes were measured before and 30 min
after inhalation. In patients with COPD, the increase in FEV1 (coefficient of
variation) was 221 ml (43%) after fenoterol and 235 ml (33%) after oxitropium;
changes in FIV1 were 301 ml (45%) and 360 ml (29%). In patients with asthma,
FEV1 improved by 618 ml (26%) and 482 ml (25%), FIV1 by 553 ml (41%) and 475 ml
(23%). In less severe COPD or asthma, the reduction in dyspnoea was associated
with the improvements in both FIV1 and FEV1, but in severe COPD with the
improvement in FIV1 only. The data demonstrate that, at least in terms of
relative changes, the reproducibility of bronchodilator responses in terms of
FIV1 is similar to that of FEV1 and they underline the assertion of FIV1 being a
sensible
parameter particularly in severe COPD.
7748.
Tsen YC, Kao GY, Chang CL, Lai
FY, Huang CH, Ouyang S, Yu MH, Wang CP, Chiou YN.
Evaluation and validation of a duck IgY antibody-based immunoassay for
high-sensitivity C-reactive protein: avian antibody application in clinical
diagnostics. Clin Chem. 2003 May;49(5):810-3. No abstract.
7749.
Von Bubnoff D, Bezold G, Matz H, Hanau D, De La Salle H, Bieber T.
Quantification of indoleamine 2,3-dioxygenase gene induction in atopic
and non-atopic monocytes after ligation of the high-affinity receptor for IgE,
Fc(epsilon)RI and interferon-gamma stimulation. Clin Exp Immunol. 2003
May;132(2):247-53.
Antigen-presenting
cells (APCs) are crucial in regulating the outcome of T cell responses. Certain
APCs are able to down-regulate T cell proliferation in vitro by inducing the
enzyme indoleamine 2,3-dioxygenase (IDO) upon interferon-gamma (IFN-gamma)
stimulation. IDO is the rate-limiting enzyme in the catabolism of the essential
amino acid tryptophan. A lack of extracellular tryptophan creates environments
in which cells become starved for this amino acid. The high-affinity receptor
for IgE, Fc(epsilon)RI, is the principal receptor for the binding of specific
IgE in type I-mediated allergies. We demonstrated recently that IDO is
overexpressed in Fc(epsilon)RI-stimulated monocytes. In the present study, we
performed quantification of IDO gene induction after treatment of atopic (Fc(epsilon)RI(high))
and non-atopic (Fc(epsilon)RI(low/-)) monocytes with IgE/anti-IgE and IFN-gamma.
By quantitative PCR ELISA, we found IDO molecule induction in atopic monocytes
was enhanced about 50-fold over non-atopic monocytes after ligation of
Fc(epsilon)RI. Stimulation with IFN-gamma at a concentration of 100 U/ml in
culture medium caused an increase in IDO gene copy numbers in atopics of about
fourfold over that of non-atopics. This comparative quantification study
demonstrates clearly the regulation of IDO gene expression by Fc(epsilon)RI and
discloses differences thereof in atopic and non-atopic cells upon inflammatory
stimuli.
7750.
Wagers S. Polarized helium:
changing our view of asthma. J Allergy Clin Immunol. 2003 Jun;111(6):1201-2. No abstract
7751.
Warner JO. The blood lung function test: does it exist for asthma? Am J
Respir Crit Care Med. 2003 Jun 1;167(11):1465-6. No abstract
7752.
Wenzel SE, Balzar S, Cundall M, Chu HW. Subepithelial basement membrane
immunoreactivity for matrix metalloproteinase 9: association with asthma
severity, neutrophilic inflammation, and wound repair. J Allergy Clin Immunol.
2003 Jun;111(6):1345-52.
BACKGROUND:
Asthma likely involves an active injury and repair process, including components
such as neutrophils and matrix metalloproteinase 9 (MMP-9). Although MMP-9 is
increased in lavage fluid and sputum in patients with asthma, controversy exists
as to the role of tissue MMP-9. OBJECTIVE: The purpose of this study was to
determine whether increases in submucosal cellular MMP-9, matrix MMP-9 (subepithelial
basement membrane [SBM]), or both would be associated with severe asthma,
neutrophilic inflammation, and wound repair. METHODS: Immunohistochemical
staining and analyses of MMP-9, inflammatory cells, transforming growth factor
beta, and collagen I were performed in endobronchial biopsy specimens,
bronchoalveolar lavage fluid, or both from 38 patients with severe asthma and
compared with results in 10 patients with mild asthma, 8 patients with moderate
asthma, and 10 healthy control subjects. RESULTS: A significantly greater
proportion of patients with severe asthma demonstrated MMP-9 staining of the SBM
than control subjects (P =.02). Bronchoalveolar lavage MMP-9 levels were also
increased in patients with severe asthma (P =.0004). The numbers of submucosal
neutrophils and macrophages, but not eosinophils, were significantly higher in
asthmatic individuals with MMP-9 staining of the SBM (P =.004 and P =.01,
respectively). However, the presence of SBM MMP-9 was associated with a high
correlation between lavage and tissue eosinophils (r = 0.58, P =.009). Although
the SBM thickness did not differ between groups, higher numbers of transforming
growth factor beta-positive cells were seen in subjects with SBM MMP-9 staining.
Pulmonary function was significantly lower in those asthmatic subjects with SBM
staining. CONCLUSIONS: These results suggest that localized tissue MMP-9 might
play an important role in wound repair and cell trafficking.
7753.
White A, Slade P, Hunt C, Hart A, Ernst E.
Individualised homeopathy as an adjunct in the treatment of childhood
asthma: a randomised placebo controlled trial. Thorax. 2003 Apr;58(4):317-21.
BACKGROUND:
Homeopathy is frequently used to treat asthma in children. In the common
classical form of homeopathy, prescriptions are individualised for each patient.
There has been no rigorous investigation into this form of treatment for asthma.
METHODS: In a randomised, double blind, placebo controlled trial the effects of
individualised homeopathic remedies were compared with placebo medication in 96
children with mild to moderate asthma as an adjunct to conventional treatment.
The main outcome measure was the active quality of living subscale of the
Childhood Asthma Questionnaire administered at baseline and follow up at 12
months. Other outcome measures included other subscales of the same
questionnaire, peak flow rates, use of medication, symptom scores, days off
school, asthma events, global assessment of change, and adverse reactions.
RESULTS: There were no clinically relevant or statistically significant changes
in the active quality of life score. Other subscales, notably those measuring
severity, indicated relative improvements but the sizes of the effects were
small. There
were no differences between the groups for other measures. CONCLUSIONS: This
study provides no evidence that adjunctive homeopathic remedies, as prescribed
by experienced homeopathic practitioners, are superior to placebo in improving
the quality of life of children with mild to moderate asthma in addition to
conventional treatment in primary care.
7754.
Yao TC, Kuo ML, See LC, Chen LC, Yan DC, Ou LS, Shaw CK, Huang JL.
The RANTES promoter polymorphism: a genetic risk factor for near-fatal
asthma in Chinese children. J Allergy Clin Immunol. 2003 Jun;111(6):1285-92.
BACKGROUND:
RANTES promoter polymorphisms were found associated with asthma/atopy in some
studies but not others, possibly reflecting the genetic heterogeneity among
different ethnicities and different asthma severity. OBJECTIVE: The purpose of
this investigation was to test the genetic association between the RANTES -28C/G
and -403G/A polymorphisms and asthma/atopy in a cohort of Chinese children, with
particular emphasis on those patients who had experienced life-threatening
asthma attacks. METHODS: Forty-eight children with near-fatal asthma, 134
children with mild-to-moderate asthma, 69 children with allergic disorders but
no asthma, and 107 nonasthmatic nonatopic control children were genotyped
through use of a PCR-based assay. RESULTS: No significant difference was
demonstrated for frequency of the RANTES -28C/G polymorphism when the
mild-to-moderate asthma, atopic/nonasthmatic, and normal control groups were
compared. The RANTES -28G allele was present in a significantly higher
proportion of the children with near-fatal asthma compared with the nonasthmatic
nonatopic controls (odds ratio, 2.93 [1.41-6.06]; P =.006) and the children with
mild-to-moderate asthma (odds ratio, 3.52 [1.73-7.16]; P =.001). The frequency
of -28G allele carriage correlated with asthma severity. The RANTES -28G allele
was also associated with an increased blood eosinophil count and a higher degree
of bronchial hyperresponsiveness. The RANTES -403G/A polymorphism did not
influence asthma/atopy susceptibility, blood eosinophil count, or bronchial
hyperresponsiveness. Interestingly, a higher frequency of -403A allele carriage
was observed in the moderate asthma subgroup compared with the mild asthma
analog. CONCLUSIONS: We conclude that the RANTES -28C/G polymorphism exacerbates
asthma severity, representing a genetic risk factor for life-threatening asthma
attacks in Chinese children. In addition, the linkage disequilibrium between
these 2 polymorphisms is a potential confounder that must be considered in the
design and interpretation of RANTES gene association studies.
BACKGROUND:
RANTES promoter polymorphisms were found associated with asthma/atopy in some
studies but not others, possibly reflecting the genetic heterogeneity among
different ethnicities and different asthma severity. OBJECTIVE: The purpose of
this investigation was to test the genetic association between the RANTES -28C/G
and -403G/A polymorphisms and asthma/atopy in a cohort of Chinese children, with
particular emphasis on those patients who had experienced life-threatening
asthma attacks. METHODS: Forty-eight children with near-fatal asthma, 134
children with mild-to-moderate asthma, 69 children with allergic disorders but
no asthma, and 107 nonasthmatic nonatopic control children were genotyped
through use of a PCR-based assay. RESULTS: No significant difference was
demonstrated for frequency of the RANTES -28C/G polymorphism when the
mild-to-moderate asthma, atopic/nonasthmatic, and normal control groups were
compared. The RANTES -28G allele was present in a significantly higher
proportion of the children with near-fatal asthma compared with the nonasthmatic
nonatopic controls (odds ratio, 2.93 [1.41-6.06]; P =.006) and the children with
mild-to-moderate asthma (odds ratio, 3.52 [1.73-7.16]; P =.001). The frequency
of -28G allele carriage correlated with asthma severity. The RANTES -28G allele
was also associated with an increased blood eosinophil count and a higher degree
of bronchial hyperresponsiveness. The RANTES -403G/A polymorphism did not
influence asthma/atopy susceptibility, blood eosinophil count, or bronchial
hyperresponsiveness. Interestingly, a higher frequency of -403A allele carriage
was observed in the moderate asthma subgroup compared with the mild asthma
analog. CONCLUSIONS: We conclude that the RANTES -28C/G polymorphism exacerbates
asthma severity, representing a genetic risk factor for life-threatening asthma
attacks in Chinese children. In addition, the linkage disequilibrium between
these 2 polymorphisms is a potential confounder that must be considered in the
design and interpretation of RANTES gene association studies.
7755.
Zaitsu M, Hamasaki Y, Matsuo M,
Ichimaru T, Fujita I, Ishii E. Leukotriene
synthesis is increased by transcriptional up-regulation of 5-lipoxygenase,
leukotriene A4 hydrolase, and leukotriene C4 synthase in asthmatic children. J
Asthma. 2003 Apr;40(2):147-54.
Leukotrienes
(LTs) are recognized to be important mediators in asthma. Recent studies
revealed that LT synthesis is controlled by the regulation of LT-synthesizing
enzymes. We determined the synthesis of LTB4 and LTC4 by
specific
radioimmunoassay, and the messenger RNA (mRNA) expression of LT-synthesizing
enzymes by reverse transcriptase polymerase chain reaction in peripheral
polymorphonuclear leukocytes, which were obtained from controls and asthmatic
children. The synthesis of LTB4 and LTC4, and the mRNA expression of
5-lipoxygenase, LTA4 hydrolase, and LTC4 synthase were enhanced in the patients.
The mRNA expression of LT-synthesizing enzymes was up-regulated, resulting in
increased LT synthesis, which may play an important role in the pathogenesis of
childhood asthma.
Pathogenesis:
7756.
Ananworanich J, Nuesch R, Teeratakulpisarn S, Srasuebkul P, Chuenyam T,
Siangphoe U, Ungsedhaphand C, Phanuphak P, Ruxrungtham K.
In vivo cell-mediated immunity in subjects with undetectable viral load
on protease inhibitor-based versus non-protease inhibitor-based highly active
antiretroviral therapy. J Acquir Immune Defic Syndr. 2003 Apr 15;32(5):570-2. No
abstract.
7757.
Asero R, Lorini M, Tedeschi A.
Association of chronic urticaria with thyroid autoimmunity and Raynaud
phenomenon with anticentromere antibodies. J Allergy Clin Immunol. 2003
May;111(5):1129-30. No abstract.
7758.
Bachert C, Gevaert P, Howarth P,
Holtappels G, van Cauwenberge P, Johansson SG.
IgE to Staphylococcus aureus enterotoxins in serum is related to severity
of asthma. J Allergy Clin Immunol. 2003 May;111(5):1131-2. No
abstract.
7759.
Beeh KM, Beier J, Kornmann O, Meier C, Taeumer T, Buhl R. A single nasal allergen challenge increases induced sputum
inflammatory markers in non-asthmatic subjects with seasonal allergic rhinitis:
correlation with plasma interleukin-5. Clin Exp Allergy. 2003 Apr;33(4):475-82.
BACKGROUND:
Seasonal allergic rhinitis (SAR) is a risk factor for asthma in affected
individuals. Nasal allergic inflammation enhances bone-marrow eosinophil
production, mainly via IL-5, and rhinitis patients have increased airway
inflammation during the pollen season. OBJECTIVE: To assess the impact of nasal
allergy on sputum inflammatory markers. METHODS: In an open-labelled,
randomized, placebo-controlled cross-over study with 16 non-asthmatic SAR
patients (median age 25 years, 56% males), the effect of a single nasal allergen
challenge performed out of season on induced sputum inflammatory parameters was
evaluated. SAR patients were identified by history, skin-prick test and specific
IgE. All patients had normal lung function/bronchial hyper-responsiveness out of
season and a negative asthma/wheezing history. Sputum cells and supernatant
levels of ECP, sICAM, IL-5 and IL-10, and plasma levels of IL-5 and ECP, were
measured before and 24 h after nasal allergen challenge. After a washout period
of at least 4 weeks, the procedure was repeated with placebo challenge (diluent).
RESULTS: Nasal allergen challenge led to an increase in sputum ECP (pre = 60 +/-
12, post = 212 +/- 63 micro g/L, P = 0.02 vs. placebo), and sICAM (4.8 +/- 2.7
to 6.5 +/- 2.9 ng/mL, P = 0.02 vs. placebo), whereas IL-10 decreased after
provocation (44 +/- 11 to 29 +/- 6 pg/mL, P = 0.06 vs. placebo). Sputum IL-5 was
undetectable in all patients. The absolute number of blood and sputum
eosinophils did not change significantly after allergen or placebo challenge (P
> 0.07, both comparisons). Plasma levels of IL-5 increased after allergen
challenge (8.7 +/- 2.9 to 14.5 +/- 3.9 pg/mL, P = 0.001), and the increase in
plasma IL-5 was positively correlated with the rise in sputum ECP in a subgroup
of 'responders' (n = 12, r = 0.71, P = 0.01). CONCLUSIONS: A single nasal
allergen challenge in SAR patients increased markers of allergic inflammation in
the lower respiratory tract, possibly via pronounced activation of inflammatory
cells through circulating immediate-type reaction cytokines like IL-5. These
findings may provide additional explanatory data for the high susceptibility of
SAR patients to incident asthma.
7760.
Bochenek G, Nagraba K, Nizankowska E, Szczeklik A.
A controlled study of 9alpha,11beta-PGF2 (a prostaglandin D2 metabolite)
in plasma and urine of patients with bronchial asthma and healthy controls after
aspirin challenge. J Allergy Clin Immunol. 2003 Apr;111(4):743-9.
BACKGROUND:
Prostaglandin D(2) (PGD(2)) is the predominant cyclooxygenase product of mast
cells, the number of which is increased in bronchial asthma. Release of PGD(2)
might reflect mast cell activation and disordered function of the asthmatic
lung. OBJECTIVE: We sought to determine blood and urinary levels of
9alpha,11beta-PGF(2), a major stable PGD(2) metabolite in 2 well-defined
phenotypes of asthma, aspirin-induced asthma (AIA) and aspirin-tolerant asthma
(ATA), and in healthy control subjects and to study the effects of aspirin on
PGD(2) release. METHODS: Using gas chromatography/mass spectrometry, we
determined plasma and urinary concentrations of 9alpha,11beta-PGF(2) at baseline
in 131 stable asthmatic patients, 65 of whom had AIA and 66 of whom had ATA.
Fifty healthy nonatopic subjects served as the control group. The measurements
were also performed after an aspirin challenge in 26 of 65 patients with AIA and
in 24 of 50 control subjects. RESULTS: At baseline, patients with AIA had
significantly higher plasma levels of 9alpha,11beta-PGF(2) than either patients
with ATA or healthy subjects. A similar significant elevation of serum tryptase
was observed in patients with AIA compared with patients with ATA and control
subjects. Mean urinary 9alpha,11beta-PGF(2) values did not differ among the 3
groups. In patients with AIA, as opposed to healthy subjects, aspirin challenge
invariably precipitated a clinical reaction, accompanied in most patients by a
further rise in plasma levels of PGD(2) metabolite and tryptase. CONCLUSIONS: In
stable AIA, though not in ATA, there is a steady release of PGD(2) into the
blood, accompanied by the release of tryptase. Aspirin enhances this reaction in
most patients. Release of bronchoconstrictive PGD(2) might contribute to the
severe clinical course of AIA.
7761.
Brown V, Warke TJ, Shields MD, Ennis M.
T cell cytokine profiles in childhood asthma. Thorax. 2003
Apr;58(4):311-6.
BACKGROUND:
An imbalance of T cell subsets in asthma with a predominance of Th2 type cells
has been proposed. The aim of this study was simultaneously to detect surface
markers and intracellular production of cytokines in T cells from the airways of
children with and without asthma. METHODS: Bronchoalveolar lavage (BAL) fluid
was obtained by wedging a suction catheter into the distal airway immediately
before elective surgery. Cells were stimulated with phorbol 12-myristrate
13-acetate (PMA) and ionomycin and intracytoplasmic cytokine retention was
achieved using monensin. The cells were stained with the relevant antibodies and
analysed by flow cytometry. RESULTS: No statistical difference was observed
between children with atopic asthma, atopic non-asthmatic subjects, and normal
controls in the percentage of CD3+ cells producing interleukin (IL)-2 or IL-4.
Interferon (IFN)gamma+ T cells were, however, present in a much higher
percentage than either IL-2 or IL-4 positive cells. The percentage of IFNgamma+
T cells was significantly increased in subjects with atopic asthma (median
71.3%, interquartile range (IQR) 65.1-82.2, n=13) compared with both atopic
non-asthmatic subjects (51.9%, IQR 37.2-70.3, n=12), p<0.05 and normal
controls (58.1%, IQR 36.1-66.1, n=23), p<0.01. CONCLUSIONS: These findings
indicate that IFNgamma producing T cells are more abundant in the airways of
children with atopic asthma than in atopic non-asthmatic subjects and controls.
The proinflammatory activities of IFNgamma may play an important role in the
pathogenesis of childhood asthma and may suggest that asthma is not simply a Th2
driven response.
7762.
Calder PC. Polyunsaturated fatty acids and cytokine profiles: a clue to
the changing prevalence of atopy? Clin Exp Allergy. 2003 Apr;33(4):412-5. No
abstract.
7763.
Colilla S, Nicolae D, Pluzhnikov A, Blumenthal MN, Beaty TH, Bleecker ER,
Lange EM, Rich SS, Meyers DA, Ober C, Cox NJ; Collaborative Study for the
Genetics of Asthma. Evidence for
gene-environment interactions in a linkage study of asthma and smoking exposure.
J Allergy Clin Immunol. 2003 Apr;111(4):840-6.
BACKGROUND:
Asthma, a common and chronic disease of the airways, has a multifactorial cause
involving both genetic and environmental factors. As a
result,
mapping genes that influence asthma susceptibility has been challenging.
OBJECTIVE:
This study tests the hypothesis that inclusion of exposure to environmental
tobacco smoke (ETS), a potential risk factor for asthma, would improve the
ability to map genes for asthma. METHODS: By using 144 white families from the
Collaborative Study for the Genetics of Asthma, environmental information about
exposure to ETS during infancy was incorporated into a genome-wide multipoint
linkage analysis. Statistical significance of observed gene-environment
interactions was assessed by means of simulation. RESULTS: Three regions with
nominal evidence for linkage when stratified on the basis of ETS exposure were
identified (P <.01) and showed a significant increase from the baseline lod
score (1p at 97 cM, D1S1669-D1S1665; 5q at 135 cM, D5S1505-D5S816; and 9q at 106
cM, D9S910; all P <.05). In addition, 2 other regions, although not meeting
nominal significance after stratification on the basis of ETS exposure, showed a
significant increase from baseline lod score when ETS was taken into account (1q
at 240 cM, D1S549; 17p at 3 cM, D17S1308; all P <.01). CONCLUSION: These
results illustrate how evidence for linkage of asthma can
depend on
exposure to an environmental factor, such as ETS. Future linkage analyses should
include information on suspected environmental factors for asthma to help target
new candidate susceptibility genes for asthma.
7764.
Flais MJ. Literature reports
of angiotensin receptor antagonist-induced angioedema in patients with a history
of angiotensin-converting enzyme inhibitor-induced angioedema. Arch Intern Med.
2003 Jun 23;163(12):1488. No abstract.
7765.
Groneberg DA, Welker P, Fischer TC, Dinh QT, Grutzkau A, Peiser C, Wahn
U, Henz BM, Fischer A. Down-regulation
of vasoactive intestinal polypeptide receptor expression in atopic dermatitis. J
Allergy Clin Immunol. 2003 May;111(5):1099-105.
BACKGROUND:
Receptors for vasoactive intestinal polypeptide (VIP) have recently been
suggested to play a key role in immunomodulation with genetically modified mice.
However, it is not known whether changes in receptor gene regulation are
involved in the pathogenesis of human immune disorders. OBJECTIVE: We studied
the expression of VPAC(2) in acute lesions of the human immune disease atopic
dermatitis. METHODS: By using nonradioactive in situ hybridization, quantitative
immunohistochemistry, RT-PCR, and gene array studies, the expression status of
VPAC(2) was assessed in atopic dermatitis and control tissues and in the human
mast cell line HMC-1. RESULTS: In situ hybridization and immunohistochemistry
demonstrated VPAC(2) mRNA and protein expression in human mast cells surrounded
by VIP positive nerve fibers. Gene array experiments and RT-PCR studies showed
high levels of VPAC(2) mRNA expression in mast cells that were increased
compared to other receptors such as VPAC(1) or VIP in the human mast cell line
HMC-1. Stimulation of HMC-1 cells led to a downregulation of VPAC(2). Similarly,
quantitative immunohistochemistry for VPAC(2) in acute atopic dermatitis lesions
showed a significantly decreased VPAC(2) immunoreactivity in mast cells.
CONCLUSION:
The downregulation of VPAC(2) in human mast cells in acute lesions of atopic
dermatitis suggests a role of this G-protein;coupled receptor in the
pathophysiology of the disease.
7766.
Hashida R, Ogawa K, Miyagawa M, Sugita Y, Takahashi E, Nagasu T,
Katsunuma T, Akasawa A, Tsujimoto G, Matsumoto K, Saito H.
Analysis of gene expression in peripheral blood eosinophils from patients
with atopic dermatitis by differential display. Int Arch Allergy Immunol. 2003
Jun;131 Suppl 1:26-33.
To identify
the genes related to atopic dermatitis (AD), we compared gene expression in
eosinophils from AD patients and healthy volunteers. RNA was prepared from
peripheral blood eosinophils. Gene expression was monitored by fluorescent
differential display (DD) and real-time RT-PCR. Eighteen new sequences,
including expressed sequence tags (ESTs), were expressed at higher levels in
eosinophils from AD patients than in those from healthy volunteers. The
functions of most of these genes are unknown. We found no correlation between
the expression of a particular gene and clinical markers such as the number of
eosinophils and the amount of IgE. Multivariate analysis of the gene expression
data in each sample showed a very high coefficient of correlation among the copy
numbers of each gene. The genes under investigation were also expressed in
cultured blood eosinophils after IL-4, IL-5 and IFN-gamma stimulation. We were
able to predict the function of some of the sequences by scanning for homologies
within either the human or mouse genome databases. The mouse counterpart of one
of these genes, intersectin 2, was expressed dramatically, as measured by ear
edema, in 1-fluoro-2,4-dinitrobenzene-induced mouse contact dermatitis and in
NC/Nga mouse dermatitis.
7767.
Huang JL, Chen LC, Yeh KW, Lin SJ, Hsieh KH, Kuo ML.
TH1 and TH2 cytokine production among asthmatic children after
immunotherapy. J Asthma. 2003 May;40(3):273-9.
Allergen
immunotherapy results in a number of changes in clinical and immunological
parameters. To study the kinetic influence of immunotherapy on cytokine
production, we evaluated the ratios of Th1/Th2 for patients receiving
mite-extract immunotherapy with 3-month intervals. Changes in Th1/Th2 ratio were
calculated based on the intracellular cytokine and surface CD4 staining of
peripheral blood mononuclear cells (PBMC). No significantly different Th1/Th2
ratios were detected after immunotherapy, although ratios were lower for
asthmatic children when compared with normal controls. Cytokine production was
also determined on supernatants from mite- or mitogen-activated PBMC cells. A
significantly increased production of all cytokines was detected from activated
PBMC from patients after immunotherapy. Thus hyposensitization with mite extract
for 1 year might improve the cytokine production capacity of asthma patients'
PBMC.
7768.
Kabesch M, Peters W, Carr D, Leupold W, Weiland SK, von Mutius E.
Association between polymorphisms in caspase recruitment domain
containing protein 15 and allergy in two German populations. J Allergy Clin
Immunol. 2003 Apr;111(4):813-7.
BACKGROUND:
Early exposure to microbial matter such as LPS may influence the development of
asthma and allergies by activation of innate immunity pathways as indicated by
studies in farming environments. Recently, polymorphisms in caspase recruitment
domain containing protein 15 (CARD15), an intracellular LPS receptor protein,
have been associated with Crohn's disease. Because these polymorphisms lead to
changes in LPS recognition, they may affect the development of asthma and
allergies. OBJECTIVE: We genotyped a large population of German schoolchildren
(N = 1872) from East and West Germany for 3 functional relevant CARD15
polymorphisms for their role in the development of asthma and allergy.
METHODS: By
use of parental questionnaires, skin prick testing, pulmonary function tests,
bronchial challenge tests, and measurements of serum IgE levels, children were
phenotyped for the presence of atopic diseases. Genotyping was performed with
PCR-based restriction enzyme assays. To assess associations between atopic
phenotypes and genotypes standard statistical procedures were applied.
RESULTS:
Children with the polymorphic allele C2722 had a more than 3-fold risk to
develop allergic rhinitis (P <.001) and an almost 2-fold risk for atopic
dermatitis (P <.05). Furthermore, the T2104 allele was associated with an
almost 2-fold risk for allergic rhinitis (P <.05). When a C insertion at
position 3020 was present, the risk of atopy increased by 50% (P <.05) and
serum IgE levels were elevated (P <.01). CONCLUSION: The shared genetic
background between Crohn's disease and atopy may indicate that an impaired
recognition of microbial exposures results in an insufficient downregulation of
excessive immune responses, giving rise to either T(H)2 dominated allergies or
T(H)1 related Crohn's disease.
7769.
Kelly-Welch AE, Hanson EM, Boothby MR, Keegan AD.
Interleukin-4 and interleukin-13 signaling connections maps. Science.
2003 Jun 6;300(5625):1527-8.
Cytokines
are inflammatory mediators important in responding to pathogens and other
foreign challenges. Interleukin-4 (IL-4) and IL-13 are two cytokines produced by
T helper type 2 cells, mast cells, and basophils. In addition to their
physiological roles, these cytokines are also implicated in pathological
conditions such as asthma and allergy. IL-4 can stimulate two receptors, type I
and type II, whereas IL-13 signaling is mediated only by the type II receptor
(see the STKE Connections Maps). These cytokines activate the Janus kinase/signal
transducer and activator of transcription (JAK/STAT) signaling cascades, which
may contribute to allergic responses. In addition, stimulation of the
phosphatidylinositol 3-kinase (PI3K) pathway through recruitment of members of
the insulin receptor substrate family may contribute to survival and
proliferation.
7770.
MacLean JA, Hannaway PJ.
Angioedema and AT1 receptor blockers: proceed with caution. Arch Intern
Med. 2003 Jun 23;163(12):1488-9; No
abstract.
7771.
Malling HJ. Immunotherapy
for rhinitis. Curr Allergy Asthma Rep. 2003 May;3(3):204-9.
Allergen-specific
immunotherapy in the treatment of allergic rhinitis has a well-documented
clinical efficacy that indicates a statistically significant and clinically
relevant reduction in symptom scores and the need for pharmacotherapy. The
clinical efficacy of recently published studies is equivalent to or superior to
the effect of standard anti-allergic drugs. Additional advantages are related to
a downregulation of the allergic phenotype with the additional induction of a
Th1 cytokine profile. The immunoregulatory capacity and the global
downregulation of the allergic inflammation in mucous membranes might be
important factors in the capacity to ensure long-term clinical efficacy (after
termination of treatment) and the preventive capacity of immunotherapy in
reducing the progression of rhinitis to asthma as well as deflowering the
development of new sensitizations. Subcutaneous immunotherapy is optimal in
severe allergic rhinitis with signs of bronchial hyperreactivity; however,
sublingual immunotherapy might be an option for patients with milder disease.
7772.
Maziak W. The Th1-Th2
paradigm and asthma: how far should we go? J Asthma. 2003 Apr;40(2):201-5. No abstract
7773.
Mucha SM, Baroody FM. Relationships
between atopy and bacterial infections. Curr Allergy Asthma Rep. 2003
May;3(3):232-7.
Atopy in its
most common forms (asthma, allergic rhinitis, and atopic dermatitis) has a
significant impact on society in terms of health care costs and quality of life.
Aside from having significant morbidity from these diseases, patients with atopy
have also been noted to have a high incidence of comorbidities, including
bacterial infections such as otitis media and sinusitis. In this paper, current
evidence is reviewed that supports the close associations among allergic
rhinitis and the two commonly diagnosed bacterial diseases, otitis media and
sinusitis.
7774.
Obase Y, Shimoda T, Kawano T, Saeki S, Tomari SY, Mitsuta-Izaki K,
Matsuse H, Kinoshita M, Kohno S. Polymorphisms
in the CYP1A2 gene and theophylline metabolism in patients with asthma. Clin
Pharmacol Ther. 2003 May;73(5):468-74.
BACKGROUND:
Cytochrome p450 (CYP) 1A2 gene polymorphisms are thought to be involved in
theophylline metabolism. OBJECTIVE: We analyzed the effect of genetic
polymorphisms in the 5'-flanking region to the first intron of the CYP1A2 gene
on theophylline metabolism in 75 Japanese patients with asthma and 159 healthy
Japanese volunteers. METHODS: Genetic polymorphisms were detected at 4 sites of
the CYP1A2 gene, -2964(G/A) and -1569(T/del) in the 5'-flanking region and
155(T/G) and 731(A/C) in the first intron. RESULTS: There were no significant
differences in the distribution of gene polymorphisms between the asthmatic and
control groups. Among asthmatic patients, theophylline clearance was
significantly lower in patients with the polymorphism at site -2964(G/A) whose
genotype was G/A (0.029 +/- 0.001 L x h(-1) x kg(-1)) or A/A (0.029 +/- 0.002 L
x h(-1) x kg(-1)) than in those whose genotype was G/G (0.034 +/- 0.001 L x
h(-1) x kg(-1)) (P <.01 and P <.05, respectively). High theophylline
clearance levels significantly correlated with age in the G/G subgroup of site
-2964(G/A) (P <.05, r = -0.35) but not in the G/A or A/A subgroup.
CONCLUSION:
Given its potential side effects, theophylline may need to be used with care in
patients with the A allele at site -2964(G/A) in the CYP1A2 gene, because
theophylline metabolism levels are lower in such patients, particularly in young
asthmatic individuals.
7775.
Ogawa K, Kaminuma O, Kikkawa H, Akiyama K, Mori A.
Interaction with monocytes enhances IL-5 gene transcription in peripheral
T cells of asthmatic patients. Int Arch Allergy Immunol. 2003 Jun;131 Suppl
1:20-5.
BACKGROUND:
The regulatory mechanisms of IL-5 gene transcription in human peripheral T cells
are unclear because the transfection efficiency of plasmid constructs into
nontransformed T cells is very low. METHODS: Concanavalin A (ConA)-stimulated
blastocytes derived from peripheral blood lymphocytes of asthmatic subjects were
transiently transfected with the human IL-5 gene promoter/enhancer-luciferase
gene construct, pIL-5 (-511)Luc, and cultured with THP-1 cells (human monocytoid
cells) and anti-CD3 monoclonal antibody (mAb). IL-5 level in the culture medium
was determined by an enzyme-linked immunosorbent assay. Transcriptional activity
of the IL-5 gene was measured by luciferase reporter analysis. RESULTS: ConA-blast
lymphocytes of asthmatic patients produced a significant amount of IL-5 upon
combined stimulation with anti-CD3 mAb and THP-1 cells, but not with anti-CD3
mAb alone. Costimulation with anti-CD28 mAb also enhanced the anti-CD3 mAb-
induced IL-5 production. Accordingly, luciferase activity induced by anti-CD3
mAb stimulation in pIL-5(-511)Luc-transfected ConA-blast lymphocytes was
increased 1.9- and 3.4-fold by the addition of anti-CD28 mAb and THP-1 cells,
respectively. Serial 5' deletion analysis of the reporter gene demonstrated that
the cis-regulatory element located at -119 to -80 is critical for anti-CD3 mAb-induced
IL-5 gene transcription.
CONCLUSIONS:
Our present findings provide a useful model reflecting IL-5 gene transcription
in human peripheral T cells in vivo, and clearly demonstrate that an interaction
with monocytes enhances IL-5 gene transcription. Copyright 2003 S. Karger AG,
Basel
7776.
Parikh SA, Cho SH, Oh CK. Preformed
enzymes in mast cell granules and their potential role in allergic rhinitis.Curr
Allergy Asthma Rep. 2003 May;3(3):266-72.
Mast
cells not only function as effector cells but also influence nearly every other
cell involved in causing allergic rhinitis. Mast cell-derived mediators such as
histamine, bradykinin, tryptase, and the arachidonic acid derivatives produce
the symptoms of the early-phase reaction of allergic rhinitis and also attract
and activate other leukocytes involved in the late-phase reaction. In addition,
activated mast cells are known to secrete a number of cytokines, both preformed
and newly synthesized, that can modulate T- and B-cell function, propagate the
early- and late-phase reactions, and contribute to tissue remodeling. Most
currently available therapies work by antagonizing the mediators secreted by
mast cells and other leukocytes. With the possible exception of immunotherapy,
these therapies do not provide long-term protection against allergic disorders.
Exciting new developments in gene-based therapies seem promising in both
reducing and reversing the development of allergic rhinitis.
7777.
Partridge MR, Dockrell M, Smith NM.
The use of complementary medicines by those with asthma. Respir Med. 2003
Apr;97(4):436-8.
Complementary
therapies attract considerable media attention and previous surveys of members
of an asthma patient organisation suggested that their use by those with asthma
was commonplace. This report concerns a study of a stratified cross section of
the asthma population designed to give a more representative insight into
current usage of complementary therapies. A sift questionnaire was used to
identify those with asthma and 785 of those so identified undertook a
semi-structured face-to-face interview. Only 6% of the study population were
current users of complementary therapies with use being more common amongst
those who expressed most concern regarding their current medication. Low use of
complementary therapies may well reflect satisfaction with current management
and suggests that previous surveys may have been unrepresentative of a more
balanced population of those with asthma.
7778.
Pierzchalska M, Szabo Z, Sanak M, Soja J, Szczeklik A.
Deficient prostaglandin E2 production by bronchial fibroblasts of
asthmatic patients, with special reference to aspirin-induced asthma. J Allergy
Clin Immunol. 2003 May;111(5):1041-8.
BACKGROUND:
Regulation of prostaglandin synthesis and the activation of human airway
fibroblasts associated with the remodeling of the bronchi play an important role
in asthma. OBJECTIVE: We sought to assess the cyclooxygenase pathways in airway
fibroblasts of patients with bronchial asthma. METHODS: Generation of
prostaglandin E(2) (PGE(2)) and pros-taglandin D(2) (PGD(2)) by bronchial
fibroblasts was measured by means of mass spectrometry in culture supernatants,
and cyclooxgenases expression was estimated by means of RT-PCR and
immunoblotting. The cells were isolated from 3 groups of subjects: nonasthmatic
patients (n = 10), patients with aspirin-tolerant asthma (ATA, n = 9), and
patients with aspirin-intolerant asthma (AIA, n = 7). RESULTS: The cytomix (LPS,
5 square g/mL; IL-1 square, 5 ng/mL; and TNF- square, 10 ng/mL; 18 hours)
stimulated the production of prostaglandins. Asthmatic patients were
characterized by low capacity to produce PGE(2) after cytomix stimulation. In
the nonasthmatic patient group the mean PGE(2) production was 32 +/- 33 ng/mL
(35-fold of the basic production), in the ATA group it was 16 +/- 18 ng/mL
(16-fold), and in the AIA group it was only 5.3 +/- 3.6 ng/mL (4-fold). The mean
concentration of PGD(2) for nonasthmatic patients, patients with ATA, and
patients with AIA was 0.18 +/- 0.16 ng/mL (4.7-fold of the basic production),
0.18 +/- 0.14 ng/mL (4.2-fold), and 0.235 +/- 0.19 ng/mL (1.9-fold),
respectively. The observed difference was not due to insufficient cyclooxygenase
2 expression because all groups had similar levels of its mRNA and protein. The
patients with AIA had low expression levels of cyclooxygenase 1 protein but not
of its mRNA. The PGE(2)/PGD(2) concentration ratio increased after cytomix
stimulation in all groups but was significantly less in patients with AIA than
in patients with ATA. CONCLUSIONS: Our results point to a deficient
PGE(2)production under proinflammatory conditions in asthmatic airways. This
could weaken local defensive mechanisms and promote cysteinyl leukotriene
overproduction.
7779.
Regner KR, Riegert-Johnson L, Volcheck GW.
Serial measurement of serum tryptase in angiotensin-converting enzyme
inhibitor-associated angioedema. Mayo Clin Proc. 2003 May;78(5):655-6. No
abstract
7780.
Saarne T, Kaiser L, Rasool O, Huecas S, van Hage-Hamsten M, Gafvelin G.
Cloning and characterisation of two IgE-binding proteins, homologous to
tropomyosin and alpha-tubulin, from the mite Lepidoglyphus destructor. Int Arch
Allergy Immunol. 2003 Apr;130(4):258-65.
BACKGROUND:
The dust mite Lepidoglyphus destructor is a major source of mite allergy in
European rural environments, but it also causes allergy in urban populations
around the world. We have previously cloned, sequenced and expressed several
allergens from L. destructor (Lep d 2, Lep d 5, Lep d 7 and Lep d 13). The aim
of this study was to identify and clone additional allergens from L. destructor,
and to evaluate their IgE-binding reactivities. METHODS: PCR and screening with
sera from L. destructor-sensitised individuals were used to isolate new clones
from a phage display L. destructor cDNA library. The complete coding sequences
of the clones were determined and expressed as His(6)-tagged recombinant
proteins in Escherichia coli. The recombinant proteins were analysed by SDS-PAGE,
immunoblotting and mass spectrometry. RESULTS: Two new clones, showing homology
to tropomyosin and alpha-tubulin in several species, were isolated from the
phage display L. destructor cDNA library. Due to its homology to group 10 dust
mite allergens, the tropomyosin clone was named Lep d 10. The
IgE-binding
frequencies of the recombinant Lep d 10 and alpha-tubulin were 13% (18/136) and
12% (11/95), respectively, among subjects with IgE reactivity to mites and/or
crustaceans. CONCLUSIONS: Two new allergens from L. destructor have been
identified and can now be added to the repertoire of recombinant L. destructor
allergens. In addition, both these allergens belong to highly conserved protein
families and may be important for evaluation of allergenic cross-reactivity.
7781.
Sternberg EM. Introduction. Neuroendocrine and neural factors in
autoimmune, inflammatory, infectious, and allergic disease: a summary of the
conference. Ann N Y Acad Sci. 2003 May;992:xi-xii. No
abstract.
7782.
Taha R, Hamid Q, Cameron L, Olivenstein R.
T helper type 2 cytokine receptors and associated transcription factors
GATA-3, c-MAF, and signal transducer and activator of transcription factor-6 in
induced sputum of atopic asthmatic patients. Chest. 2003 Jun;123(6):2074-82.
BACKGROUND:
It is well-known that the expression of T helper (Th) type 2
cytokines
such as interleukin (IL)-4 and IL-5, and their receptors, is up-regulated within
the airways of allergic asthmatic patients. Furthermore, higher numbers of cells
producing GATA-3, c-MAF, and signal transducer and activator of transcription
factor (STAT)-6, which are transcription factors
(TFs) that
are implicated in the regulation and signaling of the Th2 cytokines, have been
observed in bronchial biopsy specimens from asthmatic patients but not in those
of healthy control subjects. METHODS: We examined whether these mediators also
can be detected in induced sputum. Immunoreactivity for IL-4Ralpha, IL-5Ralpha,
GATA-3, c-MAF, and STAT-6 was investigated in samples of induced sputum from
asthmatic patients (n = 8) and healthy control subjects (n = 8). RESULTS: Our
results showed that the numbers of cells expressing IL-4 receptor alpha (Ralpha)
and IL-5Ralpha were higher in samples from asthmatic patients compared to those
of control subjects (p < 0.01). More cells exhibiting GATA-3, c-MAF, and
STAT-6 immunoreactivity also were found in asthmatic patients vs those in
control subjects (p < 0.005). Furthermore, the expression of STAT-6 and
IL-4Ralpha, GATA-3 and IL-5Ralpha, and c-MAF with both IL-4Ralpha and IL-5Ralpha
was correlated (p < 0.05). CONCLUSIONS: This study demonstrated that induced
sputum provides sufficient sensitivity for examining the pathways of cytokine
signaling, cytokine receptor signaling, and intracellular signaling.
Furthermore, these data show correlations between the expression of Th2 cytokine
receptors and associated TFs in the human lung, which has not been documented
previously.
7783.
Taylor AJ. HLA phenotype and
exposure in development of occupational asthma. Ann Allergy Asthma Immunol. 2003
May;90(5 Suppl 2):24-7.
OBJECTIVE:
To review relevant scientific literature to understand the contribution of
exposure to the risk of developing occupational asthma and whether HLA class 2
molecules contribute to individual susceptibility to sensitization and asthma
caused by low-molecular-weight chemicals. STUDY SELECTION: The author's expert
opinion was used to select relevant articles
based on
systematic reviews of relevant literature. RESULTS: Studies during the past
decade have shown that intensity of exposure is an important determinant of
asthma induced by inhaled respiratory sensitizers, both proteins and
low-molecular-weight chemicals. There is evidence that HLA class 2 alleles
contribute to the risk of sensitization and asthma caused by
low-molecular-weight chemical sensitizers. HLA-DR3 is associated with an
increased
risk of developing specific IgE to trimellic anhydride (TMA) and complex
platinum salts such as ammonium hexachloroplate (ACP). In those exposed to ACP
and possibly also to TMA, risk is greater in those who have experienced lower
intensity of exposure. CONCLUSIONS: Exposure intensity is an important
determinant of sensitization and asthma caused by respiratory sensitizers. HLA
class 2 alleles contribute to individual susceptibility to low-molecular-weight
chemicals. For some chemicals, the contribution of HLA class 2 alleles is
greater in those less exposed at work to the relevant chemical.
7784.
Tsukahara H, Shibata R, Ohshima Y, Todoroki Y, Sato S, Ohta N, Hiraoka M,
Yoshida A, Nishima S, Mayumi M. Oxidative
stress and altered antioxidant defenses in children with acute exacerbation of
atopic dermatitis. Life Sci. 2003 Apr 18;72(22):2509-16.
The
underlying mechanisms of skin inflammation in atopic dermatitis (AD) are not
completely understood. The purpose of the present study was to examine the
involvement of oxidative stress and antioxidant defenses in children with acute
exacerbation of AD. We studied 13 children who were hospitalized for acute
exacerbation of AD with purulent skin infection by Staphylococcal aureus (age,
1.5 to 10.0 years), and 28 age-matched healthy subjects (controls). Urine
samples obtained from the patients on admission, on 2nd and 7th-9th hospital
days, as well as from the controls were analyzed for 8-hydroxy-2'-deoxyguanosine
(8-OHdG) (a marker of oxidative DNA damage), acrolein-lysine adducts (a marker
of lipid peroxidation), bilirubin oxidative metabolites (BOM) (a marker of
antioxidant activity of bilirubin under oxidative stress) and nitrite/nitrate (NO(x)(-))
(a marker of endogenous nitric oxide production). Of these, urinary
concentrations of 8-OHdG, acrolein-lysine adducts and BOM, but not NO(x)(-),
were significantly higher in AD children on admission than those in control
subjects. Response to treatment was associated with significant falls in the
concentrations of 8-OHdG and acrolein-lysine adducts. Urinary concentrations of
acrolein-lysine adducts, but not 8-OHdG, were still significantly higher in AD
patients on the 7th-9th hospital day relative to the control. Urinary BOM
remained almost constant and significantly high in AD children during
hospitalization. Our findings indicate that oxidative stress and altered
antioxidant defenses are involved in the pathophysiology of acute exacerbation
of AD, and that suppression of oxidative stress might be a potentially useful
strategy for the treatment of AD.
Vaccines :
7785.
Casadevall A, Pirofski LA. Exploiting the redundancy in the immune
system: vaccines can mediate protection by eliciting 'unnatural' immunity. J Exp
Med. 2003 Jun 2;197(11):1401-4. No abstract.
Therapy:
7786.
Anand MK, Nelson HS, Dreskin SC.
A possible role for cyclooxygenase 2 inhibitors in the treatment of
chronic urticaria. J Allergy Clin Immunol. 2003 May;111(5):1133-6. No
abstract.
7787.
Bork K, Hardt J, Schicketanz KH, Ressel N.
Clinical studies of sudden upper airway obstruction in patients with
hereditary angioedema due to C1 esterase inhibitor deficiency. Arch Intern Med.
2003 May 26;163(10):1229-35.
BACKGROUND:
Hereditary angioedema due to C1 esterase inhibitor deficiency is clinically
characterized by recurrent and self-limiting skin, intestinal, and laryngeal
edema. Asphyxiation by laryngeal edema is the main cause of death among patients
who die of hereditary angioedema. This study describes the age at which
laryngeal edema first occurs, the time between onset and full development, and
the effectiveness of therapy and prophylaxis. METHODS: Information on 123
patients with hereditary angioedema was obtained from medical histories and
reports by the general practitioners, emergency physicians, and hospitals
involved. RESULTS: Sixty-one patients (49.6%) experienced a total of 596
laryngeal edema episodes. The ratio of laryngeal edema episodes to skin
swellings and abdominal pain attacks was approximately 1:70:54 in patients who
had laryngeal edema. The mean (SD) age at the first laryngeal edema was 26.2
(15.3) years. Nearly 80% of the laryngeal edemas occurred between the ages of 11
and 45 years. The mean interval between onset and maximum development of
laryngeal edema was 8.3 hours. A total of 342 laryngeal edemas cleared
spontaneously without treatment, and 208 laryngeal edemas were successfully
treated with
C1 esterase inhibitor concentrate. Despite long-term prophylactic treatment with
danazol, 6 patients developed subsequent laryngeal edemas. CONCLUSIONS:
Laryngeal edema may occur at any age, although young adults are at greatest
risk. In adults, the interval between onset of symptoms and acute risk of
asphyxiation is usually long enough to allow for use of appropriate emergency
procedures. To prevent a fatal outcome, it is essential to instruct patients and
their relatives about the first signs of laryngeal edemas and the necessary
procedures to follow.
7788.
Calder PC. Polyunsaturated
fatty acids and cytokine profiles: a clue to the changing prevalence of atopy?
Clin Exp Allergy. 2003 Apr;33(4):412-5.
No abstract
7789.
Korniewicz DM, El-Masri MM, Broyles JM, Martin CD, O'Connell KP. A laboratory-based study to assess the performance of
surgical gloves. AORN J. 2003 Apr;77(4):772-9.
The
inherent tear resistance and elasticity of latex and the touch sensitivity it
provides has made it the traditional material of choice for surgical gloves,
protecting both health care workers and patients from the transmission of
bloodborne infections. Although increased incidence of latex allergy has led to
increased use of nonlatex surgical gloves, the effectiveness of these gloves as
a barrier to infection has not been examined thoroughly. This laboratory-based
study compared the performance of latex and nonlatex surgical gloves in a
simulated stress protocol. The propensity of surgical gloves to fail was
dependent on glove material, manufacturer, and stress. Nonlatex neoprene and
nitrile gloves were comparable to latex and can provide a good alternative to
latex for allergic patients and health care workers. In this study, isoprene was
found to be inferior to latex and other nonlatex materials. The presence or
absence of
glove powder had no significant influence on the probability of glove failure.
7790.
Lim AY, Chambers DC, Ayres JG, Stableforth DE, Honeybourne D.
Exhaled nitric oxide in cystic fibrosis patients with allergic
bronchopulmonary aspergillosis. Respir Med. 2003 Apr;97(4):331-6.
Exhaled
nitric oxide (NO) is thought to be a marker of asthmatic inflammation. Levels in
cystic fibrosis (CF) are generally low. This study aimed to measure exhaled NO
in CF patients at high risk of developing ABPA and patients at low risk. We
studied nine patients at high risk of developing ABPA and 36 at low risk. The
two groups were similar in age and spirometry. All patients in the high-risk
group were taking oral or inhaled glucocorticoids, compared to 56% in the
low-risk group (P=0.02). The exhaled NO levels were lower in the high-risk group
than in the low-risk group (2.0 vs. 3.6 ppb), mean difference (95% CI) 1.6 (-3.6
to 0.4) ppb, P=0.001. On subgroup analysis of patients on oral glucocorticoids,
the exhaled NO levels were significantly lower in patients with a high risk of
developing ABPA (n=7) than patients with a low risk (n=8) (P=0.011). The number
of patients who were on inhaled, but not oral glucocorticoids was too small to
analyse usefully. Exhaled NO levels were lower in CF patients with a high risk
of developing ABPA and on glucocorticoids. This may be because oral
glucocorticoids exert a greater effect on exhaled NO than inhaled
glucocorticoids. Alternatively, inducible nitric oxide synthase may be
down-regulated by Aspergillus toxin.
7791.
McCarthy M. Researchers call
for more research into asthma in Latin America. Lancet. 2003 May
24;361(9371):1797. No abstract.
7792.
Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D.
Incidence of serious side effects from first-line antituberculosis drugs
among patients treated for active tuberculosis. Am J Respir Crit Care Med. 2003
Jun 1;167(11):1472-7. Epub 2003 Jan 31.
Major
adverse reactions to antituberculosis drugs can cause significant morbidity, and
compromise treatment regimens for tuberculosis (TB). Among patients treated for
active TB we estimated the incidence, and risk factors, of major side effects
from first-line anti-TB drugs. Side effects, resulting in modification or
discontinuation of therapy, or hospitalization, were attributed on the basis of
resolution after withdrawal, and/or recurrence with rechallenge. Among 430
patients treated between 1990 and 1999, the incidence of all major adverse
effects was 1.48 per 100 person-months of exposure (95% confidence interval [95%
CI], 1.31 to 1.61) for pyrazinamide, compared with 0.49 (95% CI, 0.42 to 0.55)
for isoniazid, 0.43 (95% CI, 0.37 to 0.49) for rifampin, and 0.07 (95% CI, 0.04
to 0.10) for ethambutol. Occurrence of any major side effect was associated with
female sex (adjusted hazard ratio, 2.5; 95% CI, 1.3 to 4.7), age over 60 years
(adjusted hazard ratio, 2.9; 95% CI, 1.3 to 6.3), birthplace in Asia (adjusted
hazard ratio, 2.5; 95% CI, 1.3 to 5.0), and human immunodeficiency
virus-positive status (adjusted hazard ratio, 3.8; 95% CI, 1.05 to 13.4).
Pyrazinamide-associated adverse events were associated with age over 60 years
(adjusted hazard ratio, 2.6; 95% CI, 1.01 to 6.6) and birthplace in Asia
(adjusted hazard ratio, 3.4; 95% CI, 1.4 to 8.3), whereas rifampin-associated
adverse events were associated with age over 60 years (adjusted hazard ratio,
3.9; 95% CI, 1.02 to 14.9) and human immunodeficiency virus-positive status
(adjusted hazard ratio, 8.0; 95% CI, 1.5 to 43). The incidence of pyrazinamide-induced
hepatotoxicity and rash during treatment for active TB was substantially higher
than with the other first-line anti-TB drugs, and higher than previously
recognized.