Diagnosis, Diagnostics, Immunodiagnosis & Immunodiagnostics:




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3092.      Andre FE. The future of vaccines, immunisation concepts and practice.Vaccine.  19(17-19):2206-9, 2001 Mar 21.


      Vaccines have prevented more deaths, disability and suffering than any other medical discovery or intervention. Recent breakthroughs in immunology and genomics offer the prospect of the development of many new prophylactic and therapeutic vaccines not only against infectious diseases but also for use in conditions such as allergy, autoimmunity and carcinogenesis where malfunction of the immune system undoubtedly plays a role. These hopeful perspectives are however dimmed by several counterproductive societal trends that include the spreading-although unjustified-belief that vaccines are not safe and may even be unnecessary, escalating costs of vaccine research, development, production and control that are exacerbated by political pressure on selling prices and expensive lawsuits by 'victims' of vaccination who claim excessive compensation. Negative media coverage of vaccine issues is adversely affecting acceptance of vaccination. In spite of these negative trends, vaccines should have a bright future, because it is increasingly being realised that prevention is not only better than cure but it is often also more cost-effective. A better understanding of the dynamics of microbial transmission in populations is leading to more rational immunisation practices on a global scale that could lead to eradication of several pathogens. Attention is being given to making vaccines more user-friendly through the development of combined vaccines and the introduction of less invasive inoculation techniques.


3093.      Anhoej C.  Backer V.  Nolte H. Diagnostic evaluation of grass- and birch-allergic patients with oral allergy syndrome. Allergy.  56(6):548-52, 2001 Jun.


  BACKGROUND: Patients with birch and grass allergy often suffer from oral allergy symptoms when ingesting cross-reacting fresh fruits and vegetables. However, fruit and vegetable allergen extracts are often readily degradable or contain clinically irrelevant cross-reacting epitopes, resulting in diagnostic discrepancies when fruit and vegetable allergic reactions are evaluated. The risk of using nonstandardized fresh food extracts for skin testing may also be of concern. The objective was to compare and evaluate the clinical utility of selected recombinant grass and birch cross-reacting food allergens with fresh and commercial melon, hazelnut, and apple extracts. METHODS: Thirty-six grass- and or birch-allergic patients and 17 control subjects consented to participate in the study. All subjects were skin prick tested and had basophil histamine-release tests done with fresh fruits and various extracts of hazelnut, apple, and melon. The diagnosis of oral allergy syndrome was confirmed by oral challenges. In addition, histamine release to recombinant Bet v 1 and Bet v 2, and recombinant Phl p 1 and Phl p 2, Phl p 5 was performed. RESULTS: The skin prick test with fresh hazelnut, apple, and melon showed sensitivities of 0.97, 0.92, and 0.89, respectively. The corresponding specificities were 0.78, 0.72, and 0.82, respectively. In contrast, the histamine-release test with hazelnut, apple, and melon gave sensitivities of 0.87, 0.71, and 1.00, respectively. The corresponding specificities were 0.65, 0.93, and 0.43. The skin prick test showed excellent negative predictive value (> 90%). No added value of recombinant allergen testing was noted. Oral challenge did not result in severe systemic reactions, and no systemic reactions were observed with skin prick tests with fresh fruits. CONCLUSION: The skin prick test showed an almost optimal diagnostic value with a satisfactory sensitivity (> 89%) and excellent negative predictive value with fresh fruits. When the skin prick test with fresh nut and apple cannot be performed, histamine release is a diagnostic alternative. Histamine release with melon showed lack of specificity. This was probably due to extensive IgE cross-reactivity with pollen, since these patients also responded to recombinant Phl p 1 and Bet v 1. Skin testing and challenges with fresh fruits were safe.



3094.      Bhave SY. Approach to recurrent respiratory infections. Indian Journal of Pediatrics.  68 Suppl 2:S26-32, 2001 Apr.


  Rational approach to diagnosis and management of recurrent respiratory infections is needed, or else the child is subjected to unnecessary investigations and multiple drugs. Repeated respiratory symptoms do not mean a respiratory infection. A diagnosis of viral infection does not justify prescription of an antibiotic. Recurrent viral infections are part of the growing up process of any child. Giving antibiotics at every episode to cover "so-called superadded bacterial infections" will lead to "recurrent antibiotics" and adverse effects on growth. Systematic approach should be used to find the underlying cause. An otoscopic examination of a child should form part of a pediatric examination in all cases of respiratory infections. Antibiotics should be judiciously chosen depending on age, socioeconomic status, severity of infection and the type of organism expected and always given in adequate doses and proper duration. Treatment should be specific and symptomatic. Adequate drainage of the sinuses is an important adjuvant therapy. Use of cough syrups with various combinations should be avoided. Efforts should be made to diagnose and treat manifestations of hyperactive airway or allergy, role of CEA (cough equivalent asthma) and WLRI (Wheeze associated lower respiratory infections). Investigations are needed in recent lower respiratory infections and adverse effect on growth, school performance, abnormal physical findings. CBC, CRP, ESR, nasal smear, appropriate cultures, tests for TB, X-Rays, barium studies, milk scan, ultra sound, CT, MRI, bronchoscopy in selected cases.


3095.                     Boccara F.  Benhaiem-Sigaux N.  Cohen A. Acute myopericarditis after diphtheria, tetanus, and polio vaccination. Chest.  120(2):671-2, 2001 Aug.


  We report the first case of myopericarditis after triple vaccination against diphtheria, tetanus, and poliovirus in a young adult. He presented with fever, acute chest pain, and diffuse ST-segment elevation 2 days after vaccination. Two-dimensional echocardiography findings were normal. Endomyocardial biopsy showed interstitial edema with diapedesis of erythrocytes. Laboratory findings showed inflammatory syndrome and elevated circulating immune complexes. He recovered within a few days with high-dose aspirin treatment and was without complications at 3-month follow-up. We discuss the different hypotheses for infective or hypersensitivity myocarditis.


3096.                     Broide D.  Sriramarao P. Eosinophil trafficking to sites of allergic inflammation. [Review] [90 refs] Immunological Reviews.  179:163-72, 2001 Feb.


  Eosinophils play a prominent pro-inflammatory role in allergic inflammation. Studies utilizing flow chambers, intravital video-microscopy, and cytokine and adhesion molecule-deficient mice have provided important insight into the mechanisms of eosinophil trafficking in inflamed blood vessels and into tissues in vivo. While the bone marrow generation of eosinophils is finely regulated by interleukin (IL)-5, the trafficking of eosinophils into tissues is regulated by several cytokines, chemokines, and adhesion molecules with overlapping functions. Prospects for therapeutically inhibiting eosinophilic inflammation by inhibiting eosinophil adhesion to endothelium are dependent on an improved understanding of the relative importance of individual cytokines and adhesion molecules in regulating eosinophil adhesion to endothelium. Alternative strategies to inhibit eosinophilic inflammation include the use of immunostimulatory DNA sequences containing a CpG motif to act as a Th1 adjuvant to prevent Th2 responses associated with IL-5 and eosinophilia. Immunostimulatory DNA sequences do not induce eosinophil apoptosis, but function at the level of the bone marrow to inhibit the IL-5-induced bone marrow generation and release of eosinophils. [References: 90]


3097.                     Ghaemmaghami AM.  Robins A.  Gough L.  Sewell HF.  Shakib F. Human T cell subset commitment determined by the intrinsic property of antigen: the proteolytic activity of the major mite allergen Der p 1 conditions T cells to produce more IL-4 and less IFN-gamma. European Journal of Immunology.  31(4):1211-6, 2001 Apr.


  The house dust mite Dermatophagoides pteronyssinus allergen Der p 1 elicits IgE antibody responses in a significant proportion of patients suffering from dust mite allergy. We have recently shown that Der p 1 proteolytically cleaves a cell surface molecule involved in the homeostatic control of human IgE synthesis, namely the IL-2 receptor (CD25) on T cells. As a result, these T cells show markedly diminished proliferation and IFN-gamma secretion in response to stimulation by anti-CD3 antibody. However, these observations still leave open the important issue of whether CD25 cleavage, and the consequent suppression of IFN-gamma secretion, leads to enhanced IL-4 secretion, and whether such cytokine changes would be exhibited by both CD4 and CD8 T cells. Here we demonstrate for the first time that the proteolytic activity of Der p 1 biases human CD4 and CD8 T cells towards a type 2 cytokine profile. Our data provide compelling evidence for the role of the proteolytic activity of Der p 1 in creating a microenvironment conducive for IgE synthesis.



3098.                     Horner AA.  Van Uden JH.  Zubeldia JM.  Broide D.  Raz E. DNA-based immunotherapeutics for the treatment of allergic disease. [Review] [72 refs] Immunological Reviews.  179:102-18, 2001 Feb.


Allergic diseases are a growing health concern in industrialized countries. Despite a number of effective therapeutic options for the prevention and treatment of the pathophysiologic responses which characterize allergic diseases, the induction of true allergen desensitization remains an elusive therapeutic goal. Only immunotherapy (IT) has been shown to have any effect on the underlying hypersensitivities which mediate allergic reactions, and traditional protein-based allergen IT has a limited scope of efficacy However, a number of reagents collectively termed DNA-based immunotherapeutics have proven highly effective in both the prevention and reversal of Th2-mediated hypersensitivity states in mouse models of allergic disease. Four basic DNA-based immunotherapeutic modalities have been used for these studies. These include immunization with gene vaccines, allergen mixed with immunostimulatory oligodeoxynucleotide (ISS-ODN), and physical allergen-ISS-ODN conjugates (AIC), as well as immunomodulation with ISS-ODN alone. Results from many laboratories have generated guarded optimism that DNA-based immunotherapeutics may be effective for the reversal of allergic hypersensitivity states in humans, and several clinical trials have already been initiated. This review will focus on our present understanding of the biological activities of DNA-based immunotherapeutics and their application to the treatment of allergic diseases. [References: 72]


3099.                     Labidi AH.  Estes RC.  David HL.  Bollon AP. Mycobacterium recombinant vaccines. [Review] [105 refs] Tunisie Medicale.  79(2):65-81, 2001 Feb.


  Intracellular diseases are difficult to treat and constitute a major problem for modern medicine. In this type of diseases, a TH-1 immune response favors protection, while a TH-2 response is detrimental to the host. Current vaccines are using antigens to initiate an immune response regardless of its nature and its mechanism. New vaccines are designed to combine selected antigens with potent adjuvants to stimulate the appropriate pathway of the immune system and deliver a lasting protective immunity. The Mycobacterium recombinant vaccine system for treatment of intracellular diseases utilizes antigen delivery systems in the form of non pathogenic Mycobacterium strains, genetic transfer systems in the form of cloning and expression vectors, and related technologies to provide products containing non toxic immuno-regulating Mycobacterium adjuvants, non toxic immuno-stimulating exogenous antigens specific for a variety of diseases, and non toxic amounts of cytokines that boost the TH-1 pathway. The cloning and expression Mycobacterium vectors include both pAL5000-based extra-chromosomal and D29-based integrative vectors. [References: 105]


3100.                     Lebel B.  Messaad D.  Kvedariene V.  Rongier M.  Bousquet J.  Demoly P. Cysteinyl-leukotriene release test (CAST) in the diagnosis of immediate drug reactions. Allergy.  56(7):688-92, 2001 Jul.


  BACKGROUND: The diagnosis of allergic reactions to drugs is difficult. Most skin tests are not standardized, and in vitro tests are needed to avoid provocation tests. Cross-linking of IgE on basophils is known to cause the release of both cysteinyl leukotriene (Cys-LT) and histamine. We aimed to evaluate the diagnostic utility (sensitivity, specificity, and efficiency) of measurement of sulfidoleukotrienes in drug allergy. METHODS: We performed a prospective study in 55 patients with proven immediate adverse reactions to drugs (30 to beta-lactams, six to acetaminophen, and 19 to aspirin) and 64 drug-exposed nonallergic controls. Positive diagnosis was established by history, skin tests, and, if needed, oral provocation tests. Cys-LT release was determined after drug-allergen stimulation by the cellular antigen stimulation test (CAST(R)) technique. Histamine release was also assessed on the same samples by enzyme immunoassay. Spontaneous and anti-FcepsilonRIalpha-induced mediator release was also studied in all subjects. Sensitivity, specificity, and efficiency were calculated. RESULTS: Net Cys-LT release was over the maximal threshold given by the manufacturer in 19/55 patients and in 9/64 controls. Net histamine release was over 5% of total histamine content in 28/55 patients and 34/64 controls. The efficiency of both tests was low. CONCLUSION: Thus, in most cases, the in vitro Cys-LT test has little or no diagnostic utility and is not superior to histamine release.



3101.                     Luque I.  Leyva L.  Jose Torres M.  Rosal M.  Mayorga C.  Segura JM.  Blanca M.  Juarez C. In vitro T-cell responses to beta-lactam drugs in immediate and nonimmediate allergic reactions. Allergy.  56(7):611-8, 2001 Jul.


  BACKGROUND: beta-Lactam drugs may induce both cellular and humoral allergic reactions, and there is evidence that T cells play an important role in the pathogenesis of these reactions. The aim of this work was to assess the sensitivity and specificity of the lymphocyte transformation test (LTT) as an in vitro diagnostic tool, in patients with either an immediate or a nonimmediate reaction to penicillin G and/or amoxicillin. METHODS: Fifty patients with a well-documented history of allergic reactions to beta-lactams (31 immediate and 19 nonimmediate) were studied by means of skin tests (prick and intradermal), radioallergosorbent test (RAST), and, when necessary, controlled administration of the drug. Twenty-eight healthy subjects with good tolerance to penicillins served as controls. LTT was performed in all subjects. RESULTS: Skin tests were positive in 77.4% of the patients with immediate reactions and in 36.8% of those with nonimmediate reactions. The overall sensitivity of LTT in the allergic patients was 62%, but, when analyzed separately, sensitivity was 64.5% for the immediate group and 57.9% for the nonimmediate group. The LTT specificity was 92.8%. CONCLUSION: The LTT should be considered a useful in vitro diagnostic tool to identify subjects allergic to penicillins, especially patients with nonimmediate reactions where the LTT has a better diagnostic value than skin tests. Interestingly, positive T-cell proliferative responses can be observed 10 or more years after the occurrence of the reaction without further exposure to the drug.



3102.                     Nguyen MD.  Cinman N.  Yen J.  Horner AA. DNA-based vaccination for the treatment of food allergy. [Review] [19 refs] Allergy.  56 Suppl 67:127-30, 2001.


  At present, avoidance is the only therapeutic option available for individuals with food allergies. However, studies suggest that DNA-based vaccination might be an effective therapeutic option for the reversal of allergic hypersensitivities, including allergies to foods. Because severe anaphylactic reactions represent a life-threatening risk for individuals with food allergies, we and others have evaluated the effectiveness of DNA-based vaccination for the prevention of anaphylactic hypersensitivity in murine models. Our investigations demonstrated that primary gene and protein/immunostimulatory sequence oligodeoxynucleotide (ISS-ODN) vaccination of subsequently Th2-sensitized mice reduced the risk of death after anaphylactic challenge, significantly. In addition, gene and protein/ISS-ODN vaccination reduced post challenge plasma histamine levels. Analysis of the immune profiles of mice receiving DNA-based vaccines showed that both gene and protein/ISS-ODN vaccination effectively prevented the development of Th2-biased immune profiles after sensitization. In contrast, vaccination with protein alone, the experimental equivalent of the traditional protein-based immunotherapy (IT) reagents used in clinical practice provided no protection from anaphylaxis, nor did it prevent the development of a Th2-biased immune profile after allergen sensitization. These studies justify continued optimism in the potential of DNA-based vaccination for the desensitization of food allergic individuals. [References: 19]


3103.                     Nishiyama K.  Yao K.  Iguci Y.  Yamamoto K.  Suzuki T.  Sato K.  Okamoto M.  Majima M. Change in tissue kallikrein level in nasal wash after the administration of oxatomide in patients with nasal allergy. American Journal of Rhinology.  15(2):105-8, 2001 Mar-Apr.


  The tissue kallikrein level in the nasal wash was measured before and after 4-week administration of oxatomide (30 mg per day) in 9 patients with perennial allergy. It was found that tissue kallikrein level in the nasal wash obtained following provocation tests significantly decreased from 6.05 +/- 4.43 (10(-10) mol/hour/L) to 1.84 +/- 0.93 (10(-10) mol/hour/L) after the administration of oxatomide. Improvement in subjective symptoms was also observed in all patients after the administration. These results would indicate that kinin in the system is actively involved in the pathogenesis of nasal allergy.


3104.                     Sakaguchi M.  Miyazawa H.  Inouye S. Specific IgE and IgG to gelatin in children with systemic cutaneous reactions to Japanese encephalitis vaccines. Allergy.  56(6):536-9, 2001 Jun.


  BACKGROUND: Systemic allergic reactions to Japanese encephalitis (JE) vaccine that include urticaria, angioedema, and rash have been reported. In Japan, children who suffered from allergic immediate-type reactions to JE vaccine had antigelatin IgE in their sera. However, the immunologic mechanism of allergic nonimmediate-type reactions that consist of cutaneous signs appearing several hours or more after JE vaccination has not been defined. METHODS: Serum samples were taken from 28 children who showed allergic nonimmediate-type cutaneous reactions to JE vaccine. Furthermore, serum samples were taken from 10 children who showed allergic immediate-type reactions with cutaneous signs and/or respiratory symptoms to JE vaccine. We have defined an immediate-type reaction as one occurring within 1 h after vaccination. RESULTS: Of 10 children who showed immediate-type reactions, all had antigelatin IgE and IgG. Of 28 children who showed systemic nonimmediate-type reactions, one had antigelatin IgE and nine (32%) had antigelatin IgG. The child who had antigelatin IgE showed urticaria 2 h after JE vaccination. CONCLUSION: These results suggest that some children who showed allergic nonimmediate-type reactions to JE vaccine were sensitized to gelatin.


3105.                     Weller PF.  Plaut M.  Taggart V.  Trontell A. The relationship of asthma therapy and Churg-Strauss syndrome: NIH workshop summary report. Journal of Allergy & Clinical Immunology.  108(2):175-83, 2001 Aug.


  The Churg-Strauss syndrome (CSS) is a distinct form of vasculitis that is notable for its eosinophilia and frequent associations with asthma and sinusitis. Because there has been an increasing recognition that CSS can develop in patients with asthma and that CSS might be associated with specific asthma treatments, the National Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, the Office of Rare Diseases, National Institutes of Health, and the US Food and Drug Administration jointly sponsored a workshop to consider interrelationships among CSS, asthma, and asthma therapeutics and to assess what is known about underlying mechanisms of CSS. Issues related to the criteria for defining and diagnosing CSS were reviewed, including the contemporary understanding that diagnostic biopsies need only reveal eosinophilic perivascular infiltrates and that asthma need not be present when CSS develops. From published reports and reports to the US Food and Drug Administration, treatment of patients with asthma with any of 3 cysteinyl leukotriene receptor antagonists, a 5-lipoxygenase inhibitor, and inhaled corticosteroids has been associated with CSS development. It is unknown whether these agents were eliciting CSS. A variety of physiologic and study design issues might lead to the reported associations of these drugs with CSS. Because many asthma patients receiving these therapies were able to diminish their systemic corticosteroid therapy, it is possible that incipient CSS was unmasked by lessened steroid use. The underlying pathophysiologic mechanisms of CSS, however, are unknown, and there is no means of identifying which patients with asthma might be at risk for CSS. Accordingly, investigations with the goals of defining the underlying pathophysiologic processes of CSS and establishing the relationships of asthma and its therapies to CSS are needed.


3106.                     Werfel T. Skin manifestations in food allergy. [Review] [39 refs] Allergy.  56 Suppl 67:98-101, 2001.


  Skin manifestations represent the most often observed clinical symptoms in food allergy. Immediate symptoms are urticaria, angioedema and sudden erythema (flush). Delayed symptoms which can be observed are exanthema and exacerbation or worsening of eczema (most often atopic dermatitis). Since delayed symptoms are difficult to diagnose, oral provocation tests are often necessary for patients with a suspected late onset of symptoms upon food ingestion. There is evidence that besides specific IgE, specific T cells play a role in the deterioration of eczema in atopic dermatitis. Although urticarial skin lesions are most often observed upon oral provocation with a suspected food, the rate of IgE-mediated food allergy in acute or chronic urticaria is rather low. In some patients suffering from chronic urticaria, intolerance reactions are also suspected. Since no laboratory or skin tests are available yet for the identification of clinically relevant food additives causing urticaria, oral provocation tests are mandatory for these patients. [References: 39]


3107.                     Yman L. Standardization of in vitro methods. [Review] [44 refs] Allergy.  56 Suppl 67:70-4, 2001.


  IgE-antibody analysis is a major diagnostic procedure and a primary tool in allergological research. The determination of sensitization frequencies and antibody concentrations against allergens of defined sources provides critical information for the estimation of the relative importance of food and environment in clinical allergy. True quantitation is essential and requires assay designs providing allergen excess and mass unit calibration. Standardized and reproducible methods show geographic and culture dependent differences between patient populations and contribute to the quality of diagnosis and treatment of allergic disease. [References: 44]


3108.                     Yoshimura C.  Miyamasu M.  Nagase H.  Iikura M.  Yamaguchi M.  Kawanami O.  Morita Y.  Iwata T.  Yamamoto K.  Hirai K. Glucocorticoids induce basophil apoptosis.   Journal of Allergy & Clinical Immunology.  108(2):215-20, 2001 Aug.


  BACKGROUND: Induction of apoptosis represents an important mechanism by which glucocorticoids (GCCs) exert their anti-inflammatory properties. The effects of GCCs on apoptosis have been determined in various immune cells and found to vary among different cell types. On the other hand, the effects of GCCs on apoptosis of basophils, active participants in allergic inflammation, have remained obscure. OBJECTIVE: The objective of this study was to investigate the effects of GCCs on basophil apoptosis. METHODS: Basophils were highly purified (purity, >97%) by Percoll density gradient centrifugation followed by negative selection. Cell status was determined by their ability to bind annexin V and exclude propidium iodide. DNA fragmentation was determined by flow cytometry. RESULTS: Dexamethasone (DEX) significantly accelerated the decrease in live cells and increased the number of apoptotic cells in a time-dependent fashion. Light microscopy as well as DNA fragmentation assay confirmed the induction of apoptosis by DEX. A half-maximal effect was observed in a DEX concentration range from 10(-9) to 10(-8) mol/L. Sex steroids did not induce basophil apoptosis at all. DEX also induced basophil apoptosis in the presence of low doses of IL-3. CONCLUSION: GCCs exert potent apoptogenic effects on basophils. GCC-mediated apoptogenic effects on basophils might have implications with respect to the mechanism of action of this class of drugs in allergic disorders.


Arp 02


3763. Aberer W, Woltsche M, Woltsche-Kahr I, Kranke B. IgG antibodies typical for extrinsic allergic alveolitis--an inter-laboratory quality assessment. Eur J Med Res  2001 Nov 20;6(11):498-504

BACKGROUND: Determination of specific IgG antibodies is important for the diagnosis of extrinsic allergic alveolitis (EAA). Various evaluations have however shown, that current methodology lacks sufficient standardization in that the employment of different sources of extracts and techniques makes a comparison of data from one laboratory to another almost impossible. OBJECTIVE: The aim of this study is to establish an external quality control system and to analyse, what the explanations for the different outcomes from various laboratories might be. METHODS: In the past 4 years 5 sera from patients suffering from EAA or healthy controls were sent every 6 months to 11 different allergy laboratories in Austria. The determination of specific IgG antibodies against antigens that are typical for this disease were requested. Results were gained with the method routinely used in the respective laboratory, and then sent back to the reference center for statistical evaluation. Precipitating techniques were used in 8 laboratories during the first mailings, but were gradually exchanged by automated ELISA systems being employed in 8 laboratories in the last mailing. RESULTS: 1127 values were determined in 105 expectedly positive sera and 1003 in 94 negative samples. Of the 562 values obtained with precipitation techniques in positive sera, only 52.0% were reported to be positive, and the results varied considerably among laboratories and antigens. In contrast, 93.3% were positive with commercially available ELISA techniques, with 92.3% for the EnzyDex System and even 95.5% for the UniCAP System. Regarding the specificity however, 93.0% of the expected negative results were correct negative using precipitation methods, whereas merely 75.2% were negative with the EnzyDex System and only 22.5% using the UniCAP System. Moreover 35.8% of the results using this latter method were false-positive. CONCLUSIONS: The traditional precipitation techniques proved not only technically difficult to perform, but also unreliable, difficult to reproduce, insensitive and impractical in daily laboratory work. They suffer from that many draw backs, that their use in daily routine cannot be recommended any more. Automated ELISA systems seem to fulfill the criteria for a routine technique concerning handling, automation, and quality criteria like sensitivity quite well, but not for specificity. Both techniques urgently need external standardization in order to make the results comparable among the different systems and methods; the danger of potentially false-positive results, pretending sensitizations that might be clinically irrelevant in several cases, is high.


3764.         Airaghi L, Lorini M, Tedeschi A. The insulin analog aspart: a safe alternative in insulin allergy. Diabetes Care  2001 Nov;24(11):2000  No abstract

3765.         Armstrong JL, Lantz AB, Jerath RS, Meyer CF. Urticaria, angioedema, and an elevated eosinophil count in an adolescent. Ann Allergy Asthma Immunol  2001 Dec;87(6):457-60 No abstract

3766.         Axell T. Hypersensitivity of the oral mucosa: clinics and pathology. Acta Odontol Scand 2001 Oct;59(5):315-9 No abstract

3767.         Bahmer FA. Histamine reactivity of the skin. Allergy  2001 Dec;56(12):1228 No abstract

3768.         Barbaud A, Trechot P, Reichert-Penetrat S, Commun N, Schmutz JL. Relevance of skin tests with drugs in investigating cutaneous adverse drug reactions. Contact Dermatitis  2001 Nov;45(5):265-8

Abstract :Skin tests with drugs can be of value in investigating patients who have developed cutaneous adverse drug reactions (CADR), but their specificity and relevance remain to be determined. A false-positive result on skin testing can happen if it is not compared to results in control subjects. When performing intradermal tests (IDT), we have determined the lowest concentrations that induce false-positive results for many drugs, including betalactam antibiotics, cephalosporins, other antibiotics or non-steroidal anti-inflammatory drugs. Some drugs in their commercialized form contain sodium lauryl sulfate and can induce irritation when patch tested as such. When patch tested with colchicine at 10% in pet. or with a Cytotec pill (containing misoprostol) at 30% in pet.,respectively, 80% of the 29 and 9 of the 10 negative controls developed false-positive results. Lastly, positive results of patch tests with drugs can be related to contact allergy to one of the components of the commercialized form of the drug, without any relevance to the investigation of a CADR, as observed in 2 cases with iodine or avocado oil.

3769.           Barnes PJ. Molecular mechanisms of corticosteroids in allergic diseases. Allergy 2001 Oct;56(10):928-36 No abstract

3770.         Belhadjali H, Giordano-Labadie F, Bazex J. Contact dermatitis from vitamin C in a cosmetic anti-aging cream. Contact Dermatitis  2001 Nov;45(5):317 No abstract

3771.         Berardesca E, Barbareschi M, Veraldi S, Pimpinelli N. Evaluation of efficacy of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multicenter study. Contact Dermatitis  2001 Nov;45(5):280-5

Disturbances of skin barrier function occur in several skin diseases, e.g., atopic dermatitis (AD), irritant/allergic contact dermatitis (ICD, ACD). Skin barrier damage triggers the production of cytokines that stimulate lipogenesis which may also cause inflammatory processes. The aim of this study was to evaluate the efficacy of a topical skin lipid mixture in the treatment of ICD, ACD and AD. 580 consecutive patients suffering from ICD, ACD or AD were treated with a skin lipid mixture containing ceramide-3 and patented nanoparticles. Patients received the lipid mixture alone or in combination with topical corticosteroids until clearance or for 8 weeks. Both treatment groups statistically improved all parameters considered at week 4 and 8 as compared to baseline. Between the 2 treatment groups, there was a statistically significant difference in favour of combined therapy for (ICD, ACD, AD, respectively): erythema, pruritus and overall disease severity; erythema and pruritus; erythema, pruritus, fissuring and overall disease severity. No statistically significant difference was found for (ICD, ACD, AD, respectively): dryness, scaling and fissuring; scaling, fissuring and overall disease severity; dryness and scaling. Between the 2 ACD treatment groups, there was a statistically significant difference in favour of the skin lipid mixture for dryness. In conclusion, the study shows that balanced lipid mixtures are effective in improving barrier properties and the clinical condition of the skin in contact dermatitis.

3772.         Biagini RE, Krieg EF, Pinkerton LE, Hamilton RG. Administration-cleared serological assays for natural rubber latex-specific immunoglobulin E antibody. Clin Diagn Lab Immunol  2001 Nov;8(6):1145-9 

Receiver operating characteristics (ROC) analyses to evaluate and compare the diagnostic accuracy of Food and Drug Administration (510K)-cleared natural rubber latex (NRL)-specific immunoglobulin E (IgE) antibody immunoassays have not been performed using well-characterized skin-testing reagents. Sera were collected from 311 subjects (131 latex puncture skin test [PST] positive and 180 PST negative). All masked, coded sera were analyzed for latex-specific IgE antibodies in the Diagnostic Products Corporation microplate AlaSTAT, HYCOR HY-TEC RAST, and Pharmacia-Upjohn CAP System RAST FEIA (CAP). Diagnostic accuracy was evaluated using GraphRoc for Windows software to construct and analyze ROC curves in relation to the subjects' PST status and the results of the immunoassays. The ROC areas under the curve (AUCs) +/- standard error based on PST for the three diagnostic tests were 0.858 +/- 0.024, 0.869 +/- 0.024, and 0.924 +/- 0.017, respectively, for AlaSTAT, CAP, and HY-TEC. The HY-TEC system had a significantly greater AUC based on PST than those observed for AlaSTAT (P < 0.05) and CAP (P < 0.05) analyses. When the diagnostic tests were probed as to the cutoffs giving maximal diagnostic efficiency compared to PST, CAP and AlaSTAT yielded values of <0.35 kU of allergen IgE (kU(A))/liter and <0.35 kU/liter while the HY-TEC assay yielded 0.11 kU/liter. The diagnostic efficiencies based on PST in our cohort at these cutoffs were 87.1, 88.1, and 88.7%, respectively. The HY-TEC assay had a significantly greater AUC than CAP and AlaSTAT using PST as a diagnostic discriminator in our cohort. When the HY-TEC system was probed at its maximally efficient cutoff (0.11 kU/liter) versus HYCOR's recommended cutoff of 0.05 kU/liter, a loss of sensitivity of 8.4% was observed with a gain in specificity of 19.5%.

3773.         Bielory L, Gewirtz M, Hinrichs C, Lal P. Asthma and vasculitis: controversial association with leukotriene antagonists. Ann Allergy Asthma Immunol  2001 Oct;87(4):274-82 No abstract

3774.         Bircher AJ, Stern WB. Allergic contact dermatitis from "titanium" spectacle frames. Contact Dermatitis  2001 Oct;45(4):244-5 No abstract

3775.           Black AK. Unusual urticarias. J Dermatol  2001 Nov;28(11):632-4 No abstract

3776.         Blease K, Jakubzick C, Schuh JM, Joshi BH, Puri RK, Hogaboam CM. IL-13 fusion cytotoxin ameliorates chronic fungal-induced allergic airway disease in mice. J Immunol  2001 Dec 1;167(11):6583-92 No abstract

3777.         Boguniewicz M, Sampson H, Leung SB, Harbeck R, Leung DY. Effects of cefuroxime axetil on Staphylococcus aureus colonization and superantigen production in atopic dermatitis. J Allergy Clin Immunol  2001 Oct;108(4):651-2 No abstract

3778.           Bonamonte D, Mundo L, Daddabbo M, Foti C. Allergic contact dermatitis from Mentha spicata (spearmint). Contact Dermatitis  2001 Nov;45(5):298  No abstract

3779.         Breit S, Rueff F, Przybilla B. 'Deep impact' contact allergy after subcutaneous injection of local anesthetics. Contact Dermatitis  2001 Nov;45(5):296-7 No abstract

3780.         Bretsche PA, Ismail N, Menon JN, Power CA, Uzonna J, Wei G. Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections. Cell Mol Life Sci  2001 Nov;58(12-13):1879-96

Abstract : The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed.

3781.         Brown AF, McKinnon D, Chu K. Emergency department anaphylaxis: A review of 142 patients in a single year. J Allergy Clin Immunol 2001 Nov;108(5):861-6

BACKGROUND: There are few data on the incidence, clinical features, and management of patients with acute anaphylaxis presenting to the emergency department. We investigated all presentations to one department during the course of a year to improve current awareness of this medical emergency. OBJECTIVE: The purpose of the study was to describe the clinical features, management, and outcome of anaphylaxis presentations to a single Australian adult emergency department in a single year, 1998-1999. METHODS: This was a retrospective, case-based study of adult patients (>or=13 years of age) attending a single emergency department in Brisbane, Australia, during the year 1998-1999. The medical records of 304 patients satisfying the relevant discharge diagnostic codes were studied. We determined incidence, sex ratio, age, clinical features, management, disposal, asthma prevalence, and causes in patients presenting with acute allergic reactions and anaphylaxis. RESULTS: In all, 162 emergency department patients with acute allergic reactions and 142 emergency department patients with anaphylaxis, including 60 whose anaphylaxis was severe, were seen during the year, for an anaphylaxis presentation incidence of 1 in 439. One patient died; this gave a case fatality rate of 0.70%. Cutaneous features were present in 94% of the patients with anaphylaxis. Of those with severe anaphylaxis, 35% had dizziness/syncope before hospital presentation, 25% laryngeal edema, and 21.7% systolic hypotension on hospital presentation. A cause was recognized in 73% of the anaphylaxis cases; most commonly, the causative agent was a drug, insect venom, or food. Adrenaline was used in 57% of the severe cases before hospital presentation or in the hospital. The emergency department alone definitively cared for 94% of all patients, though only 43% severe anaphylaxis cases were referred for follow-up. CONCLUSION: The emergency department anaphylaxis presentation incidence of 1 in 439 cases is greater than previously recognized, though death remains rare. In three fourths of cases, a precipitant was identified, a fact that emphasizes the need for a detailed initial history. Definitive management in the emergency department alone is possible in most cases, provided that the appropriate use of adrenaline and the need for allergy clinic follow-up are appreciated.

3782.         Brusasco V, Crimi E. Methacholine provocation test for diagnosis of allergic respiratory diseases. Allergy  2001 Dec;56(12):1114-20  No abstract.

3783.         Buckley MG, Variend S, Walls AF. Elevated serum concentrations of beta-tryptase, but not alpha-tryptase, in Sudden Infant Death Syndrome (SIDS). An investigation of anaphylactic mechanisms. Clin Exp Allergy 2001 Nov;31(11):1696-704 

BACKGROUND: Sudden Infant Death Syndrome, (SIDS) or cot death, remains the most common category of post-perinatal death in the UK. By definition, the cause of death is unknown, but a long-standing theory is that some of these deaths could be the result of anaphylaxis. OBJECTIVE: To investigate the potential contribution of anaphylactic mechanisms to deaths in infancy by determining relative levels of alpha- and beta-tryptases and both total and allergen-specific IgE in sera from groups of infants whose deaths were attributed to SIDS or to other causes. METHODS: Serum samples were collected at the time of post-mortem examination from infants whose death was classed as SIDS (n = 40) and from a comparison group in which cause of death had been established (n = 32). Serum tryptase concentrations were measured with a radioimmunoassay with monoclonal antibody G5 which detects primarily beta-tryptase or an ELISA with antibody AA5 which has equal sensitivity for alpha- and beta-tryptases. Levels of total IgE and IgE specific for casein, beta-lactoglobulin, house dust mite and moulds were determined. RESULTS: Analysis of the results of the two assays for tryptase indicated that levels of the beta-like tryptase (the form secreted on anaphylactic degranulation) were significantly higher in serum from infants with SIDS compared with those whose death was explained. There was no evidence for an increase in serum levels of alpha-tryptase (the variant secreted constitutively from mast cells). Total levels of serum IgE did not differ between the two groups and, reflecting the low circulating IgE concentrations in infancy, an elevation in IgE specific for the panel of allergens was not detected. CONCLUSIONS: In a proportion of SIDS victims there may be increased serum levels of beta-like tryptase, a marker for anaphylaxis. The failure to detect an increase in alpha-tryptase would suggest that mast cell hyperplasia is not a feature of cot death. The nature of the inciting agents remains unclear, but anaphylaxis deserves serious consideration as a possible cause of sudden death in infancy.

3784.         Budinger L, Neuser N, Totzke U, Merk HF, Hertl M. Preferential usage of TCR-Vbeta17 by peripheral and cutaneous T cells in nickel-induced contact dermatitis. J Immunol  2001 Nov 15;167(10):6038-44 No abstract

3785.         Burk K, Melms A, Schulz JB, Dichgans J. Effectiveness of intravenous immunoglobin therapy in cerebellar ataxia associated with gluten sensitivity. Ann Neurol  2001 Dec;50(6):827-8 No abstract

3786.         Ciprandi G, Cosentino C, Milanese M, Mondino C, Canonica GW. Fexofenadine reduces nasal congestion in perennial allergic rhinitis. Allergy  2001 Nov;56(11):1068-70 No abstract

3787.         Clough GF, Boutsiouki P, Church MK. Comparison of the effects of levocetirizine and loratadine on histamine-induced wheal, flare, and itch in human skin. Allergy  2001 Oct;56(10):985-8 

BACKGROUND: This randomized, double-blind, crossover study compared the effects of the R-enantiomer of cetirizine, levocetirizine, with those of loratadine on the wheal, flare, and itch response to histamine in human skin. METHODS: Levocetirizine (5 mg), loratadine (10 mg), or placebo was taken orally 4 h before the intradermal injection of histamine (20 microl, 100 microM) or the control vehicle into the forearm skin of healthy volunteers. Flare areas were assessed by scanning laser Doppler imaging before and at 30-s intervals for a period of 9 min. Wheal areas were measured by planimetry at 10 min. Itch was scored every 30 s with a visual analogue scale. RESULTS: After placebo administration, the mean peak flare area was 23.01+/-1.94 cm(2), the wheal area 248+/-27 mm(2), and the cumulative itch score 28.8+/-4.6% (mean+/-SEM). Levocetirizine reduced the flare, wheal, and itch by 60%, 68%, and 91%, respectively (all P<0.001, Student's t-test for paired data). The effects of loratadine were variable and not statistically significant. CONCLUSION: Levocetirizine (5 mg) is a potent inhibitor of the effects of histamine in human skin with an efficacy that exceeded that of loratadine (10 mg) when single doses of the drugs were administered 4 h before the test.

3788.         Cohen D, Hatch KL, Maibach H, Pratt M. Clothes make the (wo)man: diagnosis and management of clothing dermatitis. Am J Contact Dermat  2001 Dec;12(4):229-31 No abstract.

3789.         Corazza M, Levratti A, Virgili A. Allergic contact dermatitis due to methyl glucose dioleate. Contact Dermatitis  2001 Nov;45(5):308 No abstract.

3790.         Decraene T, Goossens A. Contact allergy to atropine and other mydriatic agents in eye drops. Contact Dermatitis  2001 Nov;45(5):309-10 No abstract.

3791.         Dejobert Y, Delaporte E, Piette F, Thomas P. Vesicular eczema and systemic contact dermatitis from sorbic acid. Contact Dermatitis  2001 Nov;45(5):291 No abstract.

3792.         Ezughah FI, Murdoch SR, Finch TM. Occupational airborne allergic contact dermatitis from medium-density fibreboard containing phenol-formaldehyde resin-2 (PFR-2). Contact Dermatitis  2001 Oct;45(4):242 No abstract.

3793.         Ezughah FI, Murdoch SR, Finch TM. Occupational airborne allergic contact dermatitis from medium-density fibreboard containing phenol-formaldehyde resin-2 (PFR-2). Contact Dermatitis  2001 Oct;45(4):242 No abstract.

3794.         Field SK. Underlying mechanisms of respiratory symptoms with esophageal acid when there is no evidence of airway response. Am J Med  2001 Dec 3;111 Suppl 8A:37S-40S 

Although a strong association exists between gastroesophageal reflux (GER) and asthma, results of studies designed to maximize the likelihood of identifying that GER worsens pulmonary function in patients with asthma have been negative or inconclusive. Asthma symptoms worsen during symptomatic reflux episodes, and asthma symptom severity correlates with the severity of symptomatic reflux. Various reasons have been proposed to explain these findings. Discomfort associated with GER can cause reflux-associated respiratory symptoms even when pulmonary function is normal. New findings suggest that increases in minute ventilation rather than inhibition of diaphragm activity are responsible for the changes in respiratory sensation during acid perfusion of the esophagus in nonasthmatic subjects. These results may also pertain to asthmatic patients, because increasing minute ventilation can cause dyspnea and bronchospasm in this population. Treating GER, either medically or surgically, may improve asthma symptoms by preventing GER-induced changes in minute ventilation.

3795.         Francalanci S, Giorgini S, Ricci L, Sertoli A. Patch testing by additional series of allergens: results of further experiences. Am J Contact Dermat  2001 Dec;12(4):203-7

BACKGROUND: Patch testing with additional series (AS) of allergens may be a useful tool in diagnosing allergic contact dermatitis (ACD). OBJECTIVE: Aim of the study was to verify the usefulness, to check the reliability in clinical practice and to evaluate the economic costs of AS previously built up. METHODS: A total of 281 patients with suspicious ACD underwent patch test with the standard series (SS) and with one or more AS (51 among 71 built up). RESULTS: A total of 170 patients (60.5%) showed positive reactions to SS; 116 (41.3%) to AS. Among 582 nonstandard allergens used, 113 (19.4%) elicited 1 or more positive reactions: out of 10,916 patch tests carried out, 260 (2.4%) positive reactions were observed. The correlation between SS and AS indicated that 8.2% patients resulted SS-/AS+, 27.7% SS+/AS-, 32.7% SS+/AS+, 31.3% SS-/AS-. The most frequently used AS showed the following percentages of patients with 1 or more positive reactions: clothes 41.4%, building industry 51.8%, hairdressers 77.3%, textile industry 42.1%, shoes 36.8%. Positive reactions to the most frequently used nonstandard allergens resulted: propylene glycol 0.4%, cobalt chloride 12.6%, phenylmercuric nitrate 2.2%, p-aminophenol 4.5%. The approximate economic cost of patch testing with AS has been evaluated in 1.3 euro per single patch test. CONCLUSION: The cost of patch testing AS is not irrelevant, but it can be compensated by the advantages deriving from the increase of data concerning ACD etiology. A reduction in the number of allergens included in single AS should be performed. Cobalt chloride, taking into account the high percentage of positive reactions observed and its presence in a large number of AS, could be (re)introduced in the standard series. Copyright 2001 by W.B. Saunders Company

3796.         Friedman Ross L. Salmeterol and inhaled corticosteroids in pattients with persistent asthma JAMA  2001 Dec 26;286(24):3076; discussion 3077-8  No abastract

3797.         Ganglberger E, Barbara Sponer, Scholl I, Wiedermann U, Baumann S, Hafner C, Breiteneder H, Suter M, Boltz-Nitulescu G, Scheiner O, Jensen-Jarolim E. Monovalent fusion proteins of IgE mimotopes are safe for therapy of type I allergy. FASEB J  2001 Nov;15(13):2524-6 By screening phage display random peptide libraries with purified immunoglobulin E (IgE) from birch pollen-allergic patients, we previously defined peptides mimicking natural IgE epitopes (mimotopes) of the major birch pollen allergen Bet v 1. The present study aimed to define a monovalent carrier for the IgE mimotopes to induce protective antibodies directed to the IgE epitopes, suitable for mimotope-specific therapy. We expressed the selected mimotopes as fusion proteins together with streptococcal albumin binding protein (ABP). The fusion proteins were recognized specifically by anti-Bet v 1 human IgE, which demonstrated that the mimotopes fused to ABP resemble the natural IgE epitope. Bet v 1-specific IgG was induced by immunization of BALB/c mice with fusion proteins. These IgG antibodies could inhibit IgE binding to Bet v 1. Skin testing of Bet v 1 allergic mice showed that the ABP mimotope constructs did not elicit type I skin reactions, although they possess IgE binding structures. Our data suggest that IgE mimotopes are safe for epitope-specific immunotherapy of sensitized individuals, when presented in a monovalent form. Therefore, ABP-fused mimotopes are promising candidates for a new type of immunotherapy based on the precise induction of blocking antibodies.

3798.         Garvey LH, Roed-Petersen J, Husum B. Anaphylactic reactions in anaesthetised patients - four cases of chlorhexidine allergy. Acta Anaesthesiol Scand  2001 Nov;45(10):1290-4

Chlorhexidine is widely used all over the world in many different preparations. In Denmark chlorhexidine is the standard skin disinfectant used before surgery or invasive procedures and it is widely used in the general population in mouthwash or for disinfection of minor scratches etc. The potential for developing allergy to chlorhexidine is thus great, especially in surgical patients. We have identified four patients with serious allergic reactions in connection with surgery and general anaesthesia, who on subsequent skin testing tested positive for chlorhexidine. Symptoms appeared 20-40 min into the operation and all four patients required treatment with adrenaline. All four patients had a history of minor symptoms like rashes or faints in connection with previous surgery/invasive procedures. Allergy to chlorhexidine may be more prevalent in surgical patients and cases may have been overlooked due to the nature of reactions and lack of suspicion towards this substance.

3799.         Gauvreau GM, Parameswaran KN, Watson RM, O'Byrne PM. Inhaled leukotriene E(4), but not leukotriene D(4), increased airway inflammatory cells in subjects with atopic asthma. Am J Respir Crit Care Med 2001 Oct 15;164(8 Pt 1):1495-500 No abstract.

3800.         Gehring U, Bolte G, Borte M, Bischof W, Fahlbusch B, Wichmann HE, Heinrich J; LISA study group. Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood. Exposure to endotoxin decreases the risk of atopic eczema in infancy: a cohort study. J Allergy Clin Immunol 2001 Nov;108(5):847-54 No abstract.

3801.         Gu X, Beardslee T, Zeece M, Sarath G, Markwell J. Identification of IgE-binding proteins in soy lecithin. Int Arch Allergy Immunol  2001 Nov;126(3):218-25

BACKGROUND: Soy lecithin is widely used as an emulsifier in processed foods, pharmaceuticals and cosmetics. Soy lecithin is composed principally of phospholipids; however, it has also been shown to contain IgE-binding proteins, albeit at a low level. A few clinical cases involving allergic reactions to soy lecithin have been reported. The purpose of this investigation is to better characterize the IgE-binding proteins typically found in lecithin. METHODS: Soy lecithin proteins were isolated following solvent extraction of lipid components and then separated on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The separated lecithin proteins were immunoblotted with sera from soy-sensitive individuals to determine the pattern of IgE-binding proteins. The identity of IgE-reactive bands was determined from their N-terminal sequence. RESULTS: The level of protein in six lecithin samples obtained from commercial suppliers ranged from 100 to 1,400 ppm. Lecithin samples showed similar protein patterns when examined by SDS-PAGE. Immunoblotting with sera from soy-sensitive individuals showed IgE binding to bands corresponding to 7, 12, 20, 39 and 57 kD. N-terminal analysis of these IgE-binding bands resulted in sequences for 3 components. The 12-kD band was identified as a methionine-rich protein (MRP) and a member of the 2S albumin class of soy proteins. The 20-kD band was found to be soybean Kunitz trypsin inhibitor. The 39-kD band was matched to a soy protein with unknown function. CONCLUSIONS: Soy lecithin contains a number of IgE-binding proteins; thus, it might represent a source of hidden allergens. These allergens are a more significant concern for soy-allergic individuals consuming lecithin products as a health supplement. In addition, the MRP and the 39-kD protein identified in this study represent newly identified IgE-binding proteins. Copyright 2001 S. Karger AG, Basel

3802.      Gutgesell C, Fuchs T. Orally elicited allergic contact dermatitis to tetraethylthiuramdisulfide. Am J Contact Dermat  2001 Dec;12(4):235-6  No abstract.

3803.                     Harding SM. Gastroesophageal reflux, asthma, and mechanisms of interaction. Am J Med  2001 Dec 3;111 Suppl 8A:8S-12S

Gastroesophageal reflux (GER) is a potential trigger of asthma. The esophagus and lung interact through a variety of mechanisms. Esophageal acid-induced bronchoconstriction can be provoked by a vagally mediated reflex, whereby acid in the distal esophagus produces airway responses; by neural enhancement of bronchial reactivity, whereby esophageal acid augments airway hyperresponsiveness; or by microaspiration, in which small amounts of esophageal acid in the upper airway cause significant airway responses. Interestingly, even in the microaspiration model, the vagus nerve plays a significant role. Neurogenic inflammation in the lung may occur with either vagally mediated mechanisms or with microaspiration. The prevalence of reflux symptoms, esophagitis, and abnormal esophageal acid contact time is higher in patients with asthma than in control populations. Potential mechanisms, whereby asthma may predispose to the development of GER, include autonomic dysregulation, an increased pressure gradient differential between the thorax and the abdomen, a high prevalence of hiatal hernia, alterations in crural diaphragm function, and bronchodilator medication use. Further research will help define how the esophagus and lung interact.

3804.      Holdiness MR. Contact dermatitis to topical drugs for glaucoma. Am J Contact Dermat  2001 Dec;12(4):217-9

A review of the literature has identified 10 agents causing contact dermatitis among topically administered drugs for glaucoma. These agents include beta-blockers (timolol, befunolol, betaxolol, levobunolol, carteolol, metipranolol), a carbonic anhydrase inhibitor (dorzolamide), a parasympathomimetic (pilocarpine), and sympathomimetics (dipivefrin, apraclonidine). Patch testing has been documented in certain individuals as well as cross sensitization and reactivity. Systemic reactions to these topically applied medications have been briefly noted. Copyright 2001 by W.B. Saunders Company

3805.      Hossny E, Aboul-Magd M, Bakr S. Increased plasma eotaxin in atopic dermatitis and acute urticaria in infants and children. Allergy  2001 Oct;56(10):996-1002

BACKGROUND: The previously reported eotaxin overexpression in the lesional skin of atopic dermatitis (AD) led us to the assumption that circulating levels of eotaxin may be elevated too. We sought to investigate the plasma expression of eotaxin in children with skin allergy in relation to clinical activity and type of lesions. METHODS: Plasma eotaxin was assayed in 78 infants and children, of whom 16 had AD, 19 had acute urticaria (AU), and 43 were healthy matched subjects. Seven children in the group of AU were resampled for plasma eotaxin after clinical remission. RESULTS: The plasma eotaxin levels in AD (median=158 pg/ml, mean [SD]=168 [61] pg/ml) were significantly higher than the control values (median=60 pg/ml, mean [SD]=59.5 [18.5] pg/ml). Not only did patients with AU demonstrate elevated plasma eotaxin levels (median=126 pg/ml, mean [SD]=124 [33] pg/ml), but also a significant decline occurred on follow-up. The coexistence of angioedema with AU did not cause any further increase in plasma eotaxin expression. Plasma eotaxin levels were significantly higher in AD than in AU, probably reflecting the chronic nature of eczematous AD lesions. The plasma eotaxin levels did not correlate with serum total IgE, peripheral blood absolute eosinophil count, or age of the patients. However, there was a positive correlation between age and plasma eotaxin in the control group. CONCLUSION: Our findings imply that circulating levels of eotaxin increase in AD and during flares of AU, probably to serve in the recruitment and activation of eosinophils. It may also represent a biomarker of lesional activity.

3806.         Janefjord CK, Jenmalm MC. PHA-induced IL-12R beta(2) mRNA expression in atopic and non-atopic children. Clin Exp Allergy  2001 Oct;31(10):1493-500  No abstract

3807.         Jeffery PK. Remodeling in asthma and chronic obstructive lung disease. Am J Respir Crit Care Med  2001 Nov 15;164(10 Pt 2):S28-38

Asthma and chronic obstructive lung disease (COPD) are both inflammatory conditions of the lung associated with structural "remodeling" inappropriate to the maintenance of normal lung function. The clinically observed distinctions between asthma and COPD are reflected by differences in the remodeling process, the patterns of inflammatory cells and cytokines, and also the predominant anatomic site at which these alterations occur. In asthma the epithelium appears to be more fragile than that of COPD, the epithelial reticular basement membrane (RBM) is significantly thicker, there is marked enlargement of the mass of bronchial smooth muscle, and emphysema does not occur in the asthmatic nonsmoker. In COPD, there is epithelial mucous metaplasia, airway wall fibrosis, and inflammation associated with loss of surrounding alveolar attachments to the outer wall of small airways: bronchiolar smooth muscle is increased also. Emphysema is a feature of severe COPD: in spite of the destructive process, alveolar wall thickening and focal fibrosis may be detected. The hypertrophy of submucosal mucus-secreting glands is similar in extent in asthma and COPD. The number of bronchial vessels and the area of the wall occupied by them increase in severe corticosteroid-dependent asthma: it is likely that these increases also occur in severe COPD as they do in bronchiectasis. Pulmonary vasculature is remodeled in COPD. In asthma several of these structural alterations begin early in the disease process, even in the child. In COPD the changes begin later in life and the0 associated inflammatory response differs from that in asthma. The following synopsis defines and compares the key remodeling processes and proposes several hypotheses.

3808.         Jeon SH, Park JW, Lee BH. Characterization of human IgE and mouse IgG1 responses to allergens in three mosquito species by immunoblotting and ELISA. Int Arch Allergy Immunol  2001 Nov;126(3):206-12 

BACKGROUND: IgE-mediated allergic reactions caused by mosquito bites are a common problem all over the world. This study was undertaken to determine IgE levels in subjects, to elucidate human IgE and mouse IgG1 binding patterns and to investigate the cross-reactivity of salivary gland antigens with three mosquitoes. METHODS: Mosquito larvae of Aedes togoi, Culex tritaeniorhynchus and Culex pipiens pallens were collected and maintained in the laboratory. Salivary gland extracts (SGE) and whole-body extracts (WBE) were prepared from female mosquitoes of each species. Mosquito-specific IgE levels in 17 subjects were measured by ELISA. Polypeptide patterns were analyzed by SDS-PAGE. Immunoblotting was performed with sensitized human and immune mouse sera, and elucidated human IgE and mouse IgG1 binding patterns to SGE. For the determination of cross-reactivity to the three types of mosquitoes, ELISA inhibition tests were performed using sera from mice sensitized by biting of A. togoi. RESULTS: The 9 sera out of 12 with positive skin reactions to SGE of A. togoi by skin prick test showed significantly higher anti-mosquito SGE IgE levels than in those without skin reactions. Protein band patterns of the SGE and WBE of the three species were different from one another. Specific human IgE reacted to the protein in SGE of 30.5, 33, 37 and 57.5 kD from A. togoi, of 38, 43 an 68 kD from C. tritaeniorhynchus, and of 23, 33, 34, 43, 44, 60, 74 and 93 kD from C. pipiens pallens. There were specific mouse IgG1 reactions to the bands of 30.5, 33, 37 and 57.5 kD in the SGE of A. togoi. The ELISA inhibition studies disclosed almost no cross-reactivities between A. togoi, C. tritaeniorhynchus and C. pipiens pallens. CONCLUSIONS: Immunoblot analysis disclosed that allergenic proteins in the SGE of mosquitoes and their patterns were remarkably similar between human and mouse sera to the SGE of A. togoi. Species-shared allergens may not exist among the three mosquito species prevalent in Korea. Copyright 2001 S. Karger AG, Basel

3809.         Kanerva L, Estlander T, Petman L, Makinen-Kiljunen S. Occupational allergic contact urticaria to yucca (Yucca aloifolia), weeping fig (Ficus benjamina), and spathe flower (Spathiphyllum wallisii). Allergy  2001 Oct;56(10):1008-11 

BACKGROUND: Occupational contact urticaria (CU) from plants is often reported, but it is less often attributed to decorative houseplants. We present an atopic gardener and caretaker of plants who developed CU when occupationally exposed to weeping fig, spathe flower, and yucca. METHODS: Sensitization was evaluated by skin prick tests (SPT) and analyses for IgE antibodies. RESULTS: SPT were positive to all three plants, and IgE antibodies were found to weeping fig and spathe flower. SPT were also performed with several decorative houseplants in more than 600 patients. Positive SPT was found to weeping fig (12%), African milk tree (8.3%), yucca (5.8%), Chinese rose (4.7%), massangana (4.6%), bird's nest fern (3.2%), and spathe flower (3.2%). CONCLUSION: Our study indicates that SPT and tests for IgE antibody are useful in detecting occupational CU caused by houseplants.

3810.         Kaszuba SM, Baroody FM, deTineo M, Haney L, Blair C, Naclerio RM. Superiority of an intranasal corticosteroid compared with an oral antihistamine in the as-needed treatment of seasonal allergic rhinitis. Arch Intern Med  2001 Nov 26;161(21):2581-7 No abstract.

3811.         Kiehl P, Falkenberg K, Vogelbruch M, Kapp A. Tissue eosinophilia in acute and chronic atopic dermatitis: a morphometric approach using quantitative image analysis of immunostaining. Br J Dermatol  2001 Nov;145(5):720-9 No abstract

3812.         Kokkonen J, Haapalahti M, Laurila K, Karttunen TJ, Maki M. Cow's milk protein-sensitive enteropathy at school age. J Pediatr  2001 Dec;139(6):797-803 No abstract.

3813.         Kutting B, Weber B, Brehler R. Evaluation of a dipstick test (Allergodip-Latex) for in vitro diagnosis of natural rubber latex allergy. Int Arch Allergy Immunol  2001 Nov;126(3):226-30

BACKGROUND: IgE-mediated hypersensitivity to latex has been recognized as an increasing health problem with far-reaching consequences for patients, regarding both their occupational situation and safety in medical care. Therefore, a correct diagnosis of natural rubber latex (NRL) allergy is essential. The purpose of the study was to evaluate sensitivity and specificity of several established diagnostic methods for NRL allergy (in vitro assays and skin prick test) in relation to a new semiquantitative dipstick test (Allergodip-Latex, Allergopharma) as a screening test for NRL allergy. METHODS: Data obtained with quantitative assays including Pharmacia CAP System(FEIA), DPC-AlaSTAT and Magic Lite were compared with the dipstick test results in latex-sensitized (n = 151) and nonsensitized persons (n = 232). In addition these in vitro findings were related to clinical symptoms after exposure to latex and skin prick test results with a panel of different latex allergen extracts. RESULTS: When comparing sensitivity and specificity of all in vitro assays relative to skin prick test results the Pharmacia CAP System (FEIA) had the highest sensitivity in the range of 90%. Sensitivity of the other in vitro assays was in the range of 73.7-74.9%, specificity varied from 85.3 to 89.8%. A diagnostic standard was defined in terms of at least three corresponding test results out of all diagnostic methods (in vitro assays and skin prick test). The sensitivity and specificity of each diagnostic test were determined relative to this diagnostic standard. Hereby the Allergodip test results showed a sensitivity of 91% and a specificity of 93%. CONCLUSION: The dipstick test results are in line with the data of the other in vitro assays. In contrast to other in vitro assays the dipstick test requires no further laboratory equipment and is easy to perform. Copyright 2001 S. Karger AG, Basel

3814.         Kvitko E. Occupational contact dermatitis in the tanning industry. Contact Dermatitis  2001 Oct;45(4):256  No abstract.

3815.         Lin RY, Trivino MR, Curry A, Pesola GR, Knight RJ, Lee HS, Bakalchuk L, Tenenbaum C, Westfal RE. Interleukin 6 and C-reactive protein levels in patients with acute allergic reactions: an emergency department-based study. Ann Allergy Asthma Immunol  2001 Nov;87(5):412-6

BACKGROUND: Elevations of interleukin 6 (IL-6) have been described in drug-induced anaphylaxis. Although IL-6 is well known to stimulate an acute phase response, profiling acute phase protein levels, such as C-reactive protein (CRP), has, to our knowledge, never been performed in patients with acute allergic reactions. OBJECTIVE: To examine the pattern of IL-6 and CRP levels in patients with acute allergic reactions and to relate these to relevant clinical and laboratory parameters. METHODS: Plasma CRP and serum IL-6 levels were determined in 85 adult emergency department patients. These patients had been previously studied with questionnaires, physical examinations, and histamine/tryptase levels. Clinical and historical features were related to CRP and IL-6 levels. CRP and IL-6 levels were also examined for relationships with histamine and tryptase levels. RESULTS: CRP and IL-6 levels were significantly correlated with one another in the study patients (Spearman p = 0.36, P =0.0008). Similar to histamine levels, IL-6 levels were significantly correlated with the extent of erythema manifested by the study patients. The extent of erythema was independently predicted by both IL-6 and histamine levels. Histamine levels were negatively correlated with CRP levels (Spearman p = -0.32, P = 0.003). Unlike histamine levels, IL-6 and CRP did not show significant relationships with the extent or presence of urticaria/angioedema or the presence of wheezing. IL-6 levels were correlated with the duration of symptoms before serologic sampling. An inverse correlation was observed between IL-6 levels and mean arterial blood pressure. Multivariate modeling showed significant independent effects from mean arterial pressure, duration of symptoms, erythema extent, and age in predicting IL-6 levels. Tryptase levels were higher in patients whose IL-6 levels were >20 pg/mL. CONCLUSIONS: CRP and IL-6 levels are not simple surrogate markers for histamine or tryptase release by mast cells or basophils in acute allergic reactions. Increasing IL-6 levels relate to greater erythema extent, lower mean arterial blood pressure, and a longer duration of symptoms. It would be interesting to speculate that CRP and IL-6 increases characterize a late-phase response in immediate hypersensitivity reactions. In this perspective, the inverse relationship between CRP and histamine levels could be explained. As histamine levels are waning, CRP levels are increasing. Timed studies for histamine and CRP/IL-6 levels in allergic reactions are necessary to confirm this hypothesis.

3816.         Linden A. Role of interleukin-17 and the neutrophil in asthma. Int Arch Allergy Immunol  2001 Nov;126(3):179-84 

Recent clinical evidence shows that acute, severe exacerbations of asthma are associated with recruitment and activation of neutrophils in the airways. There is also experimental evidence from rodents that T-lymphocytes are involved in the recruitment of neutrophils following allergen challenge in sensitised airways. This review addresses the potential role of neutrophils and the cytokine interleukin-17 (IL-17) in severe asthma. IL-17 is produced and released as a free protein from T-lymphocytes of the memory (CD45RO+) subset. Evidence from rats in vivo suggests that IL-17 can recruit and activate neutrophils in the airways; the recruitment is mediated by the rat correlate to the neutrophil chemoattractant interleukin-8 (IL-8) macrophage inflammatory protein-2 (MIP-2). Endogenous peptidases modulate neutrophil recruitment by acting on NK-1 receptors in rat airways in vivo. Human bronchial epithelial cells in vitro respond to stimulation with IL-17 by increasing the production and release of the human neutrophil chemoattractant IL-8. This release of IL-8 is functionally significant; it causes neutrophil chemotaxis in vitro. Furthermore, this IL-8 release is sensitive to a glucocorticoid and is potentiated by the pro-inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha) in vitro. In addition, IL-17 stimulates human bronchial epithelial cells in vitro to release the neutrophil-activating factor IL-6. This effect of IL-17 on IL-6, and IL-8 is in part mediated via mitogen-activated protein kinases. In conclusion, as indicated in rat airways in vivo and in human bronchial epithelial cells in vitro, IL-17 may constitute a link between the activation of certain T-lymphocytes and mobilisation of neutrophils in the airways, via induced release of C-X-C chemokines and tachykinins. Further studies are required to answer the question whether free, soluble IL-17 protein plays this role in the airways of patients with severe asthma. Copyright 2001 S. Karger AG, Basel

3817.         Liutu M, Kalimo K, Uksila J, Savolainen J. Extraction of IgE-binding components of Helicobacter pylori by immunoblotting analysis in chronic urticaria patients. Int Arch Allergy Immunol  2001 Nov;126(3):213-7

BACKGROUND: An association between Helicobacter pylori and chronic urticaria has been suspected previously. An IgE-mediated pathway might be a possible link between H. pylori infection and chronic urticaria, and therefore we wanted to prepare an optimal H. pylori antigen to detect H. pylori-specific IgE antibodies in chronic urticaria patients. METHODS: H. pylori antigen extracts were prepared in different ways to find the optimal antigen extract to be used in the assays. Immunoblotting was used to detect IgE-binding bands. The results were applied in an H. pylori RAST assay for specific H. pylori IgE antibodies in patient sera. RESULTS: In immunoblotting, the largest number of IgE-stained bands were visualized in the washing fluids and sonicated extracts, while strong heating and denaturing treatments destroyed the epitopes for IgE binding, suggesting that they belonged to the flagellar structures of H. pylori. However, in H. pylori-specific RAST analysis, specific IgE was found only in 1 of 25 H. pylori-infected patients. CONCLUSIONS: Our findings suggest that although IgE-binding epitopes were found in H. pylori, H. pylori-specific IgE antibodies are not common in chronic urticaria, and the clinical significance of the IgE response is unclear. Copyright 2001 S. Karger AG, Basel

3818.         Lu CY, Sun CC. Localized erythema-multiforme-like contact dermatitis from rubber gloves. Contact Dermatitis  2001 Nov;45(5):311-2  No abstract

3819.           MacLean JA, Eidelman FJ. The genetics of atopy and atopic eczema. Arch Dermatol 2001 Nov;137(11):1474-6 No abstract

3820.         Magnaval JF, Berry A, Fabre R, Morassin B. Eosinophil cationic protein as a possible marker of active human Toxocara infection. Allergy  2001 Nov;56(11):1096-9

BACKGROUND: Human toxocariasis is a common, worldwide helminthozoonosis that may elicit syndromes including various allergy symptoms. The diagnosis relies upon specific serology. However, this parasitosis is often self-limiting, and many subjects have residual antibodies, thus making differential diagnosis quite difficult when blood eosinophilia, a commonly accepted criterion of active helminthiasis due to tissue-dwelling parasites, is lacking. METHODS AND RESULTS: We present a patient with chronic irritant cough displaying negative allergologic screening, normal blood eosinophilia, but positive toxocariasis immunodiagnosis. Therefore, this case presented the fortuitous association of an unexplained allergic picture with residual anti-Toxocara antibodies. In an attempt to distinguish between active and past toxocaral infection, the subject's level of eosinophil cationic protein (ECP) was assessed and then compared to those of four control groups, namely, healthy volunteers, subjects presenting anti-Toxocara residual antibodies, patients with various helminthiases, and patients with active toxocaral disease. Since the patient's ECP level was found to be sharply elevated, we hypothesized that viable Toxocara larvae were still present in the tissues, and the patient was given anthelmintic therapy. At the control checkup, the cough had waned and the ECP level had decreased to below the mean value observed in both healthy subjects and in subjects with past toxocaral infections. CONCLUSIONS: These data suggest, first, that patients presenting unexplained allergic syndromes should be checked for helminthiases, even if blood eosinophilia is lacking, and, second, in such subjects displaying positive toxocariasis immunodiagnosis, ECP assessment would be a useful marker to distinguish between active and past toxocaral disease.

3821.         Mallol J, Aguirre V, Rhem R, Rodriguez J, Dolovich M. Therapeutic equivalence of three metered-dose inhalers containing salbutamol (Albuterol) in protecting against methacholine-induced bronchoconstriction in children with asthma. Pediatr Pulmonol  2001 Dec;32(6):447-52

Many pharmaceutical companies sell salbutamol in metered-dose inhalers (MDI) for the treatment of asthma. However, the therapeutic equivalence of the more recently released generic products has not been compared with the original patented product in children. Twenty children with mild to moderate asthma, presently asymptomatic and with normal lung function, were randomly allocated to receive 200 microg of inhaled salbutamol (Albuterol) from three MDIs prepared by different manufacturers: the original Glaxo product and two generic products. The three drug formulations and placebo were given 10 min before a methacholine challenge test to determine the degree of protection provided against methacholine-induced bronchoconstriction (MIB) by each salbutamol aerosol. Tests were performed on 4 consecutive days. Doubling concentrations of methacholine were inhaled until the forced expired volume in 1 sec (FEV(1)) decreased by 20% from its baseline value. Compared to placebo, all patients increased significantly the provocation concentration that decreased FEV(1) by 20% (PC(20)) by more than one doubling concentration after inhaling each of the three salbutamol aerosols. The effectiveness was not significantly different between medications (P = 0.8). There was a small but significant difference among MDIs in aerosol particle size and total and fine-particle dose released per actuation. However, no relation was found between aerosol particle size or released dose and the protective effect. This study shows that the three tested brands of salbutamol MDI protected asthmatic children equally from MIB. When prescribing these salbutamol MDIs to prevent symptoms triggered by nonspecific stimuli in asthmatic children, the selection may be based on cost-benefit criteria. Copyright 2001 Wiley-Liss, Inc.

3822.         Mancuso G, Berdondini RM. Allergic contact blepharoconjunctivitis from dorzolamide. Contact Dermatitis  2001 Oct;45(4):243  No abstract.

3823.         May JR. Allergic rhinitis: nothing to sniffle at. J Am Pharm Assoc (Wash)  2001 Nov-Dec;41(6):891-2  No abstract.

3824.         Mayo PR. Effect of passive smoking on theophylline clearance in children. Ther Drug Monit  2001 Oct;23(5):503-5 No abstract.

The author investigated the effects of passive tobacco smoking on the metabolism of theophylline in a pediatric population. In a retrospective analysis of 201 children admitted to a pediatric unit for asthma, 31 were identified with an acute exacerbation of asthma of noninfectious origin in which environmental exposure to tobacco smoke could be established. The parents were known smokers with a minimum 1-pack-per-day habit. An age-and gender-matched control population of children was then identified who had an acute exacerbation of asthma without any environmental exposure to tobacco smoke. In addition, the patients in both groups received the same dose of intravenous aminophylline for a minimum of 48 hours to ensure steady-state conditions. Total body clearance of theophylline was significantly elevated in the children exposed to environmental tobacco smoke (1.36 +/- 0.09 vs. 0.90 +/- 0.04 mL/min per kg, p < 0.0001). Steady-state serum levels were significantly lower in the passive smoking group (55.3 +/- 2.8 vs. 73.2 +/- 3.3 p < 0.00001) for those receiving nearly identical intravenous doses. The length of hospital stay was longer in the group exposed to passive smoke (4.4 +/- 2.6 vs. 2.9 +/- 1.3 days, p < 0.05). The clearance of theophylline is greater in asthmatic children exposed to passive tobacco smoke than in asthmatic children not exposed to passive tobacco smoke. These findings suggest that passive smoking may increase the clearance of other drugs metabolized in a manner similar to theophylline.

3825.         McNally NJ, Williams HC, Phillips DR. Atopic eczema and the home environment. Br J Dermatol  2001 Nov;145(5):730-6 

BACKGROUND: There is strong evidence to suggest that the prevalence of atopic eczema is increasing in developed countries. Environmental factors have been implicated in the disease. OBJECTIVES: This descriptive case-control study sheds light on the possible association between atopic eczema in school children and various home environmental factors, and generates hypotheses for further studies. METHODS: The study uses data on reported atopic eczema symptoms collected via a cross-sectional parental postal survey (n = 1350) in Nottingham, U.K. Estimates of the risk of reported eczema associated with various home environmental factors were calculated by means of odds ratios (OR), along with population attributable risk percentages. RESULTS: The study showed statistically significant associations between atopic eczema symptoms and dampness in the home [OR 1.40; 95% confidence interval (CI) 1.00-1.97], the use of a radiator to heat the child's bedroom (OR 1.50; 95% CI 1.05-2.16) and the use of synthetic pillows (OR 1.51; 95% CI 1.01-2.28). Frequent vacuuming in the home was associated with a decreased prevalence of atopic eczema (OR 0.74; 95% CI 0.58-0.94). The associations with dampness in the home, synthetic pillows and frequency of vacuuming were not altered significantly after adjustment for age, sex and socio-economic status. Population attributable risk percentages for the use of a radiator and synthetic pillows indicate that although the relative risk estimates for these factors may be small, the population impact of these factors is considerable (26% and 28%, respectively), owing to the high prevalence of exposure to these factors among this group of school children. CONCLUSIONS: Further research is needed to confirm these associations and additional research is needed to see whether they might be causative. Practical public health advice about the importance of controlling the home environment may then be targeted at families with atopic eczema.

3826.         McPherson A, Glazebrook C, Smyth A. Double click for health: the role of multimedia in asthma education. Arch Dis Child  2001 Dec;85(6):447-9  No abstract.

3827.         Mehta SS, Reddy BS. Pattern of cosmetic sensitivity in Indian patients. Contact Dermatitis  2001 Nov;45(5):292-3 No abstract.

3828.         Menzies-Gow A, Robinson DS. Eosinophil chemokines and chemokine receptors: their role in eosinophil accumulation and activation in asthma and potential as therapeutic targets. J Asthma  2001 Dec;38(8):605-13 No abstract.

3829.           Merrill W. Hypersensitivity pneumonitis: just think of it! Chest  2001 Oct;120(4):1055-7 No abstract.

3830.           Miller FG, Shorr AF. Salmeterol and inhaled corticosteroids in patients with persistent asthma. JAMA  2001 Dec 26;286(24):3075-6; discussion 3077-8 No abstract.

3831.         Miracco C, Lalinga AV, Sbano P, Rubegni P, Romano C. Delayed skin reaction to Red Sea coral injury showing superficial granulomas and atypical CD30+ lymphocytes: report of a case. Br J Dermatol  2001 Nov;145(5):849-51 No abstract.

3832.         Mita H, Hasegawa M, Saito H, Akiyama K. Levels of cysteinyl leukotriene receptor mRNA in human peripheral leucocytes: significantly higher expression of cysteinyl leukotriene receptor 2 mRNA in eosinophils. Clin Exp Allergy  2001 Nov;31(11):1714-23

BACKGROUND: Cysteinyl leukotrienes (CysLTs) have been implicated as important contributors in the pathophysiology of asthma and their biological effects are mediated by at least two distinct G-protein-coupled receptors. cDNA sequences of cysteinyl leukotriene receptor 1 (CysLTR1) and cysteinyl leukotriene receptor 2 (CysLTR2) have recently been elucidated.OBJECTIVES: Our aim is to explore gene expression and the comparative expression of CysLTR1 mRNA and CysLTR2 mRNA in human peripheral blood leucocytes. METHODS: Gene expression of CysLTR1 and CysLTR2 mRNAs in human peripheral blood eosinophils, neutrophils, monocytes and T lymphocytes has been measured by competitive reverse transcription-polymerase chain reactions using RNA or DNA competitors. RESULTS: (a) When cellular levels of CysLTR1 mRNA were normalized to those of G3PDH mRNA, the relative concentration of CysLTR1 mRNA in eosinophils (43.8 +/- 37.2, n = 29) was significantly higher than that in neutrophils (18.7 +/- 23.3, n = 11), monocytes (0.93 +/- 1.1, n = 10) and T lymphocytes (3.4 +/- 2.4, n = 11). (b) When measured using each DNA competitor, mRNAs for both types of CysLTR coexisted in each type of leucocyte. The ratio of CysLTR1 mRNA to CysLTR2 mRNA was significantly lower in eosinophils (0.65 +/- 0.42, n = 12) than in neutrophils (6.9 +/- 4.9, n = 12), monocytes (1.8 +/- 0.9, n = 10) and T lymphocytes (4.5 +/- 5.7, n = 10). (c) Human umbilical vein endothelial cells expressed CysLTR2 mRNA, but not CysLTR1 mRNA. CONCLUSION: These studies reveal that CysLTR1 mRNA and, in particular, CysLTR2 mRNA are abundantly expressed at high levels in eosinophils, raising the possibility that CysLTR2 may have an important physiological role in eosinophils and a CysLTR2 antagonist may be a good target for preventing signal transduction by CysLTs in eosinophils.

3833.         Moneret-Vautrin DA, Kanny G, Morisset M, Flabbee J, Guenard L, Beaudouin E, Parisot L. Food anaphylaxis in schools: evaluation of the management plan and the efficiency of the emergency kit. Allergy 2001 Nov;56(11):1071-6 

BACKGROUND: Children with severe food allergies can benefit from a personalized care project (PCP) in schools. The usefulness of the PCP and the residual risk of allergic emergencies are poorly appreciated. The objective was to evaluate the efficiency of the management plan and the training in the use of the emergency kit. METHODS: A telephone survey using a detailed questionnaire was performed in 45 families whose children had been previously referred to the department. The distribution of disorders was as follows: asthma, 37.7%; atopic dermatitis and asthma, 28.8%; atopic dermatitis, 15.5%; angioedema and urticaria, 13.3%; and anaphylactic shock, 4.2%. Food allergy had been diagnosed in the 45 children by past history, and double-blind or single-blind, placebo-controlled food challenges (DBPCFCs, or SBPCFCs) with evidence of specific IgE. Exactly 75.5% of the children had peanut allergy. Multiple food allergies characterized 46.8% of the subjects. They had benefited from a strict elimination diet and a protocol for emergency care including a ready-to-use intramuscular epinephrine injection. A PCP had been requested by the School Public Health Service. RESULTS: Thirty-nine PCPs were implemented (86.5% of the requests). They represented 63% of the PCPs for food allergy in the eastern region of France: one per 5800 school-age children. The retrospective period of evaluation was 25 months on average. The types of meals were very diverse, and medically acceptable in 83% of cases. The place where the emergency kit was stored in the school varied. Forty reactions occurred in 33% of the children (5/6 times in the absence of a PCP), asthma in 28%, shock in 1%, and immediate skin reactions in 11%. Reactions occurred at home in 78% of the subjects, and in school in 22% of the subjects. The cause of the reactions was not specifically known in 63% of cases. Twenty-seven percent of the reactions were linked to the ingestion of food allergens. In 10% of subjects, the reaction was due to a modification of ingredients by the food industry. CONCLUSIONS: The frequency of respiratory symptoms during oral challenge tests was confirmed by the frequency of asthmatic reactions within the follow-up period. The role of hidden allergens and of misleading labeling validates the need for PCPs in the case of peanut and tree nut allergies, past history of severe reactions, multiple food allergies, reactions to a low dose in DBPCFCs, and asthmatic reactions to foods. This study provides encouraging data on the usefulness of PCPs and confirms the need for thorough instruction and training of the school staff in dealing with allergic emergencies. Addition of a beta-agonist spray to the emergency kit is suggested.

3834.         Morali T, Yilmaz A, Erkan F, Akkaya E, Ece F, Baran R. Efficacy of inhaled budesonide and oral theophylline in asthmatic subjects. J Asthma  2001 Dec;38(8):673-9 

The aim of present study was to evaluate clinical, functional, and anti-inflammatory effects of inhaled budesonide and oral theophylline treatments in patients with mild to moderate asthma. The study included 38 patients. After a 10-day run-in period, the patients were randomly assigned into two groups. Group 1 received inhaled budesonide (Pulmicort Turbuhaler) 800 microg/day for 4 weeks. Group 2 received oral theophylline (Talotren tablets, 200 mg twice daily) for 4 weeks. Inhaled budesonide therapy was accompanied by a significant decrease in serum interleukin (IL)-5 levels (p < 0.0005) and blood, sputum, and nasal eosinophil counts (p < 0.005). It produced a significant reduction in daytime (p < 0.01) and nighttime (p < 0.005) symptom scores and an increase in morning (p < 0.005) and evening (p < 0.05) peak expiratory flow (PEF) and forced expiratory volume in I sec (FEV1) values (p < 0.01). Theophylline therapy was associated with a significant decrease in blood (p < 0.02) and nasal (p < 0.01) eosinophil counts and serum IL-5 levels (p < 0.01). It resulted in significant improvements in daytime and nighttime symptom scores (p < 0.05), and morning PEF and FEV1 values (p < 0.05). These changes were more significant in group I than in group 2. There was no statistically significant difference between the two groups with respect to post-treatment values. Our results confirm the role of inhaled corticosteroids in the treatment of asthma and are consistent with the recommendation that theophylline exerts an anti-inflammatory effect. Further studies should be conducted to determine long-term benefits of theophylline.

3835.         Mowad CM. Cocamidopropyl betaine allergy. Am J Contact Dermat  2001 Dec;12(4):223-4 

Cocamidopropyl betaine (CAPB) is a surfactant, and reports of allergic contact dermatitis to this chemical have been reported in the literature. Although most commonly found in rinse-off products, the chemical nonetheless has been shown to induce allergy. The actual component responsible for allergic reaction may be the final compound itself, CAPB, or one of the substances used in its synthesis that may be present as an impurity. Allergy to CAPB is most commonly seen in a head and neck distribution, although other patterns have been identified. Copyright 2001 by W.B. Saunders Company

3836.         Nayak AS, Schenkel E. Desloratadine reduces nasal congestion in patients with intermittent allergic rhinitis. Allergy  2001 Nov;56(11):1077-80  No abstract.

3837.         Nentwich I, Michkova E, Nevoral J, Urbanek R, Szepfalusi Z. Cow's milk-specific cellular and humoral immune responses and atopy skin symptoms in infants from atopic families fed a partially (pHF) or extensively (eHF) hydrolyzed infant formula. Allergy  2001 Dec;56(12):1144-56

BACKGROUND: Hydrolyzed milk formulas are recommended to feed infants at high risk of atopy if breast-feeding is not possible. We studied the specific cellular and humoral immune response to cow's milk proteins and occurrence of atopic dermatitis under different feeding regimens: two hydrolyzed infant milk formulas (partially [pHF] and extensively hydrolyzed [eHF]) and under exclusive breast-feeding (BF). METHODS: Seventy-two infants from families with atopic symptoms were randomized in the pHF and eHF groups, respectively. At 6 and 12 months of age, peripheral blood mononuclear cell proliferation along with specific IgG and IgE to cow's milk proteins was determined in infants fed pHF or eHF, respectively, and those who had not yet received any formula at 6 months of age (BF). Cases of atopic dermatitis were recorded throughout the first 12 months of life, and their severity was evaluated with SCORAD points. RESULTS: A significantly decreased proliferation to cow's milk caseins was found in the pHF group compared to the exclusively breast-fed group. Medians of stimulation indexes for CAS at 6 months were as follows: pHF 1.18; n=24; BF 1.70; n=24 (P=0.033, Mann-Whitney U-test). Higher levels of plasma IgG antibodies to BCAS were found in infants fed pHF than in those fed eHF at 12 months. Optical density (OD): (25th percentile; median; 75th percentile): pHF: 0.00; 0.14; 0.38; n=30; eHF: 0.00; 0.03; 0.14; n=28; P=0,089, Mann-Whitney U-test. Cow's milk-specific IgE was detected at 6 months as follows: BF: 3 of 24; eHF: 2 of 21; pHF: 0 of 23. The number of cases of atopic dermatitis and their severity did not differ among the groups during the first 12 months. CONCLUSIONS: Feeding pHF appears to suppress cow's milk-specific cellular responses and stimulate specific IgG production. Specific IgE sensitization can occur also with breast-feeding.

3838.         Neva FA, Gam AA, Maxwell C, Pelletier LL. Skin test antigens for immediate hypersensitivity prepared from infective larvae of Strongyloides stercoralis. Am J Trop Med Hyg  2001 Nov;65(5):567-72

More rapid and simplified diagnostic procedures are needed for the diagnosis of strongyloidiasis. One approach is the use of an immediate hypersensitivity skin test that would reliably identify infected people. Accordingly, somatic and excretion/secretion (E/S) antigens were prepared from filariform larvae of Strongyloides stercoralis and were treated to remove possible adventitious agents. By use of a quantitative method for measurement of skin reactions, several preparations of the 2 antigens were tested in uninfected controls and in various groups of patients. Doses of 0.35 microg of E/S and 4 microg of somatic antigens elicited positive skin tests in 82-100% of infected people, depending on clinical status. A lower frequency of positive skin tests was found in strongyloidiasis patients also infected with human T-cell lymphotropic virus type 1. Cross-reactions, especially to somatic antigens, were frequently found in patients with filarial infections. Despite these limitations and the need for further study of specificity, these results provide a basis for future development of a diagnostic skin test antigen for strongyloidiasis.

3839.         Nilsson S, Bergstrand L, Erikson U, Johansson J, Smedby O, Walldius G. Allergic reactions at repeat femoral angiography with ioxaglate. Acta Radiol  2001 Nov;42(6):608-11 

PURPOSE: To study the occurrence of allergy-like reactions at angiography, repeated several times, and, secondly, to evaluate the effect of prophylactic treatment in individuals who had earlier experienced such reactions. MATERIAL AND METHODS: One hundred and fifty-seven patients with hypercholesterolaemia, participating in the Probucol Quantitative Regression Swedish Trial (PQRST), underwent aortofemoral angiography with ioxaglate (Hexabrix) repeated annually for 3 years. Allergic reactions to the contrast medium were recorded. At the following angiographies, all patients who had earlier experienced such reactions were treated prophylactically with steroids and antihistamine. RESULTS: Allergic reactions were observed in 35 patients. Twelve reacted only year 0, 3 only year 1, 5 only year 2 and 6 only year 3. Eight patients had at least one reaction also when treated prophylactically. It was significantly (p<0.05) more common to react at year 0 but not at year 1 than to react at year 1 but not at year 0. At years 1, 2 and 3 the frequency of reactions was significantly greater in the group given prophylactic treatment than in the group without any earlier reaction at all: 8/20 versus 3/137, 4/23 versus 6/134, and 6/29 versus 6/128, respectively. CONCLUSION: Some individuals had an increased risk of an allergy-like reaction to the contrast agent. Prophylactic treatment reduced the risk of renewed reactions, but not to the same level as for those without earlier reaction. Nevertheless, individuals who have had earlier reactions can be investigated in the future, with prophylactic treatment.

3840.         Noell CA, Roland PS, Mabry RL, Shoup AG. Inhalant allergy and Meniere's disease: Use of electrocochleography and intranasal allergen challenge as investigational tools. Otolaryngol Head Neck Surg  2001 Oct;125(4):346-50

INTRODUCTION: In an earlier study, we demonstrated the feasibility of using electrocochleography (ECoG) to document changes in inner ear function objectively after intranasal challenge of patients with inhalant allergy (with no prior immunotherapy) and Meniere's disease, using the antigen to which they were most sensitive. OBJECTIVE: We expand on this earlier study and continue to investigate the feasibility of this model in a subset of patients with inhalant allergy and Meniere's disease after immunotherapy. STUDY DESIGN: Prospective study of 11 patients identified with both Meniere's disease and inhalant allergy in the practices of 2 neurotologists at our institution. Patients underwent a baseline ECoG, followed by intranasal challenge with the allergen to which they were most sensitive. This was followed by a second ECoG. RESULTS: Six of 11 patients had at least 1 year of immunotherapy (group 1), and 5 of 11 had had 0 to 6 months of immunotherapy (group 2). Four of 6 group 1 patients had a >15% increase in SP/AP ratio after immunotherapy. In group 2, 2 patients increased the SP/AP in at least 1 ear. No patient with a normal ECoG experienced vestibular symptoms after allergen challenge, whereas 2 of group 1 and 2 of group 2 had vestibular symptoms with abnormal ECoGs. CONCLUSION: This protocol is a useful tool for investigating the relationship of inhalant allergy and Meniere's disease, but needs a larger group of patients and further study to draw valid statistical conclusions.

3841.         Nolles G, Hoekstra MO, Schouten JP, Gerritsen J, Kauffman HF.Prevalence of immunoglobulin E for fungi in atopic children. Clin Exp Allergy  2001 Oct;31(10):1564-70 

BACKGROUND: The prevalence of sensitization to fungi in young atopic patients in relation to age and clinical importance is largely unknown. OBJECTIVE: The aim of this study was to investigate the prevalence of sensitization to different fungi in atopic children in relation to age and other aeroallergens. METHODS: A total of 137 atopic children (male 62%, female 38%; mean age 5 years and 9 months, range 5 months-14 years) were studied. Sera of all patients were routinely tested for total IgE and specific IgE against aeroallergens and milk. Positive sera were also tested for IgE against Alternaria alternata, Aspergillus fumigatus, Cladosporium herbarum and Penicillium chrysogenum, using the Pharmacia Enzyme CAP procedure. RESULTS: In this study in atopic children total IgE showed a significant linear relation with age, whereas specific IgE against outdoor fungi, indoor fungi and house dust mite showed significant non-linearity with age. Prevalence of specific IgE for Cladosporium ranked first, followed closely by Aspergillus and Alternaria. Calculation of the sensitization of indoor and outdoor fungi showed maximum prevalence at 7.8 years, followed by lower values at higher ages. A similar significant relation was also found for Alternaria, while this relation was not significant for the other individual fungi. Specific IgE for indoor and outdoor fungi was associated with the presence of specific IgE for aeroallergen and milk. We found that all children aged 4 years and older showed IgE for house dust mite that did not decline with increasing age. CONCLUSIONS: Sensitization to fungi is prevalent in childhood, with an age-dependent distribution reaching maximum values at 7.7-7.8 years, followed by a decline for all fungal sensitization with increasing age. The importance and relative contribution of fungal sensitization to airway disease, compared with the other allergens, remains to be established.

3842.         Nolte H, Backer V, Porsbjerg C. Environmental factors as a cause for the increase in allergic disease. Ann Allergy Asthma Immunol  2001 Dec;87(6 Suppl 3):7-11 

LEARNING OBJECTIVES: To be able to understand the interaction among genetic factors, environmental exposure to allergens, and nonspecific adjuvant factors contributing to the increase in atopic diseases in developed countries. DATA SOURCES: Peer-reviewed literature identified by searching medical databases. STUDY SELECTION: Careful review of epidemiologic cross-sectional, sequential, and longitudinal population studies and, when appropriate, intervention studies. The criteria used to accept a study reporting environmental factors influencing the prevalence of allergic diseases were adopted from the report published by the US Department of Health and Education in 1964 (Hill AB, Principles of Medical Statistics, 9th Ed. New York: Oxford University Press, 1971, p. 323) RESULTS: There is ample evidence that specific environmental factors may cause sensitization and development of allergic symptoms and disease in susceptible individuals. It is unclear when and how long a sufficient exposure will result in clinical symptoms related to the immunoglobulin E-sensitizing agents. CONCLUSIONS: Environmental factors play an important role for the development and manifestation of allergic conditions in genetically predisposed subjects. It is well documented that increased exposure to indoor allergens and selected outdoor allergens (eg, grass pollen and molds) and smoking are important risk factors for development of asthma and allergic sensitization. The importance of other environmental factors is less clear and which environmental factors that cause the increase in prevalence of allergic disease is still unknown.

3843.         Nyan OA, Walraven GE, Banya WA, Milligan P, Van Der Sande M, Ceesay SM, Del Prete G, McAdam KP. Atopy, intestinal helminth infection and total serum IgE in rural and urban adult Gambian communities. Clin Exp Allergy 2001 Nov;31(11):1672-8 

BACKGROUND: The rarity of atopy in traditional societies has been attributed to high parasite-driven blocking IgE concentrations. Information is lacking on the relationship between atopy, IgE and intestinal helminth infection in African populations. OBJECTIVE: To determine the prevalence of atopy and intestinal helminth infection and to relate these to wheeze history and serum total IgE in a community sample of adults from an urban (Banjul) and a rural (Farafenni) area of the Gambia. METHODS: Six hundred and ninety-three adults were interviewed about respiratory symptoms using a modified version of the IUTLD questionnaire, and had skin prick testing using four allergens. Stools were examined after formol-ether concentration. Total serum IgE concentration was measured in a subset of participants. RESULTS: The prevalence of atopy (mean weal diameter > or = 3 mm) in the urban and rural area was 35.3% and 22.5% (P = 0.05); D. pteronyssinus and Mold mix being the common sensitizing allergens. Prevalence of wheeze in the previous 12 months was 4.4% and 3.5% for the urban and rural areas, respectively. Wheezing was not significantly associated with atopy. Seventeen per cent of urban and 8.2% of rural subjects had helminths detected in stools. There was an inverse association between atopy and intestinal helminth infection; 7% of atopic subjects had helminths, compared to 13% of non-atopic subjects (unadjusted odds ratio 0.51, 95%CI 0.24-1.1, P = 0.09; adjusted odds ratio 0.37, 95%CI 0.15-0.92, P = 0.03). Non-atopics had total serum IgE concentrations about 2.5 times the upper limit of the reference range in non-atopic Western populations. Geometric mean total serum IgE concentration was significantly higher among atopic subjects (570 IU/mL, IQR 91-833) than non-atopic subjects (259 IU/mL, IQR 274-1303) (P < 0.001). IgE concentration was not associated with the presence of helminth infection. CONCLUSION: Further studies are needed to clarify why asthma is still relatively uncommon in spite of the prevalence of atopy in Gambian adults. Our data are also compatible with the idea that atopy might protect against helminth infection.

3844.         Oehlschlager S, Reece P, Brown A, Hughson E, Hird H, Chisholm J, Atkinson H, Meredith C, Pumphrey R, Wilson P, Sunderland J. Food allergy--towards predictive testing for novel foods. Food Addit Contam  2001 Dec;18(12):1099-107 

The risks associated with IgE-mediated food allergy highlight the need for methods to screen for potential food allergens. Clinical and immunological tests are available for the diagnosis of food allergy to known food allergens, but this does not extend to the evaluation, or prediction of allergenicity in novel foods. This category, includes foods produced using novel processes genetically modified (GM) foods, and foods that might be used as alternatives to traditional foods. Through the collation and analysis of the protein sequences of known allergens and their epitopes, it is possible to identify related groups which correlate with observed clinical cross-reactivities. 3-D modelling extends the use of sequence data and can be used to display eptiopes on the surface of a molecule. Experimental models support sequence analysis and 3-D modelling. Observed cross-reactivities can be examined by Western blots prepared from native 2-D gels of a whole food preparation (e.g. hazelnut, peanut), and common proteins identified. IgEs to novel proteins can be raised in Brown Norway rat (a high IgE responder strain) and the proteins tested in simulated digest to determine epitope stability. Using the CSL serum bank, epitope binding can be examined through the ability of an allergen to cross-link the high affinity IgE receptor and thereby release mediators using in vitro cell-based models. This range of methods, in combination with data mining, provides a variety of screening options for testing the potential of a novel food to be allergenic, which does not involve prior exposure to the consumer.

3845.         Ou LS, Kuo ML, Huang JL. Anaphylaxis to riboflavin (vitamin B2). Ann Allergy Asthma Immunol  2001 Nov;87(5):430-3 

BACKGROUND: Vitamin supplements are used more commonly in normal healthy subjects than in patients with vitamin deficiency. Thiamine (vitamin B,) is the vitamin that most frequently induces allergic reactions. To the best of our knowledge, no case of anaphylaxis to riboflavin (vitamin B2) has thus far been reported in the literature. OBJECTIVE: We describe a previously healthy 15-year-old boy in whom anaphylaxis developed several times after he drank one soft drink or took a single multivitamin tablet. This study was done to determine which of the many components found in the soft drink and vitamin tablet caused the anaphylactic reaction. METHODS: In an outpatient clinic with the availability of complete resuscitative procedures, we performed single-blind prick skin tests and intradermal skin tests on the patient with various pure vitamin components of the soft drink and the multivitamin tablet. Physiologic saline and histamine were used for negative and positive controls, respectively. RESULTS: Riboflavin, a component of both the soft drink and the vitamin tablet, produced positive reactions on intradermal skin tests in the patient. Positive reactions were not present in the normal control subjects. CONCLUSIONS: Riboflavin is a previously unreported cause of anaphylaxis. Free-form riboflavin may potentially be associated with an anaphylactic reaction. It is a vitamin widely used in many patients with chronic disease and in healthy subjects. Vitamin B2 must be considered as a cause of anaphylaxis.

3846.         Pacor ML, Di Lorenzo G, Corrocher R. Efficacy of leukotriene receptor antagonist in chronic urticaria. A double-blind, placebo-controlled comparison of treatment with montelukast and cetirizine in patients with chronic urticaria with intolerance to food additive and/or acetylsalicylic acid. Clin Exp Allergy  2001 Oct;31(10):1607-14 

BACKGROUND: The cause and pathogenesis of chronic urticaria are still poorly understood. IgE-independent reactions, are common in adult patients with chronic urticaria, who have daily spontaneous occurrence of weals. H(1)-receptor antagonists (antihistamines) are the major class of therapeutic agents used in the management of urticaria and angioedema. Nevertheless, chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone. It has been postulated that mediators other than histamine, such as kinins, prostaglandin and leukotrienes, may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines. In this study, which was randomized double-blind, placebo-controlled, we compare the clinical efficacy and safety of montelukast (MT) 10 mg given once a day and cetirizine (CET) 10 mg given once a day with placebo (PLA), in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid (ASA) and/or food additives. PATIENTS AND METHODS: A group of 51 patients, ranging in age from 15 to 71 years, with chronic urticaria and positive challenge to food additives and/or ASA, participated in this study for a period of 4 weeks, starting from a 3-day run-in. The assessment of the efficacy was based on scores of daily urticaria symptoms. RESULTS: MT significantly increased the percentage of symptom-free days for hive and itch. Analysis of frequency distribution of urticaria scores for each symptom gave similar results (MT vs. CET and MT vs. PLA, P < 0.001). The interference with sleep due to their skin condition was also lower in the group treated with MT (P < 0.001). In addition, the median number of days without the rescue medication was significantly higher in the MT group (24 days) than both the CET and the PLA groups (18 days, P < 0.001, and 20 days, P < 0.001, respectively). Finally, a low incidence of adverse events was observed in this study. CONCLUSION: The results of this comparative study demonstrate that montelukast orally administered once a day is very effective for the treatment of cutaneous symptoms in patients with chronic urticaria due to food additives and/or ASA.

3847.         Palczynski C, Walusiak J, Ruta U, Gorski P. Occupational asthma and rhinitis due to glutaraldehyde: changes in nasal lavage fluid after specific inhalatory challenge test. Allergy  2001 Dec;56(12):1186-91 

BACKGROUNDd: Glutaraldehyde (GA) is a known respiratory sensitizers, and some studies have reported occupational asthma in exposed workers. Specific changes in nasal lavage fluid (NLF) induced by high-molecular-weight allergen provocation in sensitized subjects were described previously. The purpose of this study was to evaluate the changes in cytogram, protein content, eosinophil cationic protein (ECP), and mast-cell tryptase concentrations in NLF after GA inhalation challenge in patients with a positive history of GA-induced asthma and late or dual asthmatic response due to exposure to low-level GA. METHODS: A single-blind, placebo-controlled study was performed on 11 health workers with occupational asthma and rhinitis due to GA. The control groups comprised 10 atopic subjects with perennial asthma and rhinitis and 10 healthy ones. A "nasal pool" technique was used to evaluate the examined parameters in nasal washings before and 30 min, 4 h, and 24 h after the inhalatory provocation with GA and placebo. RESULTS: There was a significant increase in eosinophil number and percentage, and albumin, ECP, and tryptase concentrations in NLF from patients with occupational asthma and rhinitis when compared to controls. CONCLUSIONS: The results indicate the immunologic mechanism of GA-induced asthma and the applicability of the "nasal pool" technique as the diagnostic procedure in GA-induced airway allergy.

3848.         Palma-Carlos AG, Spinola-Santos A, Ferreira MB, Santos MC, Palma-Carlos ML. Immunotherapy in allergic rhinitis. Allerg Immunol (Paris)  2001 Oct;33(8):323-6

Allergen specific immunotherapy (IT) represents a cornerstone of allergic rhinitis treatment and his efficacy has been confirmed, through open and double blind trials and meta-analysis. In the last few years non invasive routs for IT (oromucosal, nasal) were developed gained general acceptation mainly in children and were validated by WHO. The efficacy of IT could be markers, the pattern of specific antibody response or by the effect on sequential nasal challenges. We have evaluated the effect of IT in allergic rhinitis by different methods. Nasal IT decreased mean symptoms and pharmacological scores as well as in seasonal as in perennial rhinitis. The same decrease has been observed after oromucosal IT. The effect of IT in allergic inflammation has been confirmed by a decrease in the level of soluble adhesion molecule sVCAM-1 which is related to eosinophilic inflammation but not statistically for sICAM-1. We have also evaluated the immunoblotting pattern or specific IgE after oromucosal IT for house dust mites. For D. pteronyssinus in 4 patients the bands intensity decreased and in 3 patients the bands decreased and in 10 disappeared. IT decreases tryptase and ECP in nasal lavage after sequential nasal challenges. Therefore IT decreases clinical scores, inflammation markers, specific IgE immunoblotting bands and response to allergen challenge. These different results confirm his efficacy and usefulness in allergic rhinitis.

3849.         Parnia S, Frew AJ. Is diesel the cause for the increase in allergic disease? Ann Allergy Asthma Immunol  2001 Dec;87(6 Suppl 3):18-23 

LEARNING OBJECTIVES: The purpose of this review is to objectively critique available data regarding the role of diesel exhaust particles (DEPs) in allergic disease. Readers of this review should understand the ways in which diesel particulates can affect human airways and the extent of the scientific data which are currently available. DATA SOURCES: Data were obtained from published studies and reviews. STUDY SELECTION: The specific reviewed studies selected for this review met the following criteria: human and animal in vivo, in vitro, and pulmonary dosimetry studies, as well as epidemiologic studies to examine the role of DEPs and particulates on the airways. RESULTS: The results of the published studies show that although DEPs may play a role in the increased levels of allergic disorders through a number of immunologic mechanisms, it remains to be proven whether it is responsible for the recent rise in the prevalence of asthma and other allergic disorders. CONCLUSIONS: Further studies in humans are needed to elucidate the mechanisms by which DEPs may be responsible for the increased prevalence of allergic disorders.

3850.         Patel L, Wales JK, Kibirige MS, Massarano AA, Couriel JM, Clayton PE. Symptomatic adrenal insufficiency during inhaled corticosteroid treatment. Arch Dis Child  2001 Oct;85(4):330-4 

Symptomatic adrenal insufficiency, presenting as hypoglycaemia or poor weight gain, may occur on withdrawal of corticosteroid treatment but has not previously been reported during inhaled corticosteroid treatment. This case series illustrates the occurrence of clinically significant adrenal insufficiency in asthmatic children while patients were on inhaled corticosteroid treatment and the unexpected modes of presentation. General practitioners and paediatricians need to be aware that this unusual but acute serious complication may occur in patients treated with inhaled corticosteroids.

3851.         Raj Kumar:: Allergic bronchopulmonary aspergillosis with aspergilloma mimicking pulmonary tuberculosis. Indian J Tuberc 2000, 47(2), 103-5. (013253). July 1,  2001. No abstract.

3852.         Rak S, Heinrich C, Jacobsen L, Scheynius A, Venge P.  A double-blinded, comparative study of the effects of short preseason specific immunotherapy and topical steroids in patients with allergic rhinoconjunctivitis and asthma. J Allergy Clin Immunol  2001 Dec;108(6):921-8

BACKGROUND: Both specific immunotherapy (SIT) and nasal steroid (NS) have been shown to effectively reduce symptoms of allergic rhinitis. Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies, few comparative studies have been performed. OBJECTIVE: The purpose of this study was to compare the effects of preseason SIT with a standardized allergen extract and NS in seasonal allergic disease (rhinoconjunctivitis and asthma). METHODS: We examined 41 patients allergic to birch pollen, 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma; they were treated in a randomized, double-blinded comparative study with birch SIT and NS (budesonide 400 microg daily). Bronchial hyperresponsiveness was measured before and during the season. Changes in eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity (ECA) in peripheral blood were investigated. RESULTS: Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season (P = .03 and P = .04, respectively). Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients (P = .01). In the NS-treated patients, bronchial hyperresponsiveness increased significantly during the season (P = .0001); however, SIT treatment prevented seasonal PC(20) increase in the asthmatic patients. Measurement of blood eosinophils, eosinophil cationic protein, and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients. CONCLUSION: Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis; however, the 2 therapies were equivalent in terms of the need for rescue medication. SIT prevented seasonal increase in bronchial hyperresponsiveness, eosinophil number, eosinophil cationic protein, and eosinophil chemotactic activity only in asthmatic patients. The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma.

3853.         Ravenscroft J, Goulden V, Wilkinson M. Systemic allergic contact dermatitis to 8-methoxypsoralen (8-MOP). J Am Acad Dermatol  2001 Dec;45(6 Suppl):S218-9

Photochemotherapy with psoralens and UVA (PUVA) is widely used in the treatment of psoriasis and many other skin conditions. Cutaneous adverse reactions to 8-methoxypsoralen (8-MOP) appear to be rare and may be difficult to distinguish from phototoxicity or UV-induced polymorphic light eruption. We describe a patient who had a systemic allergic contact dermatitis to 8-MOP develop during her second course of PUVA treatment for psoriasis.

3854.         Rebollo S, Sanchez P, Vega JM, Sedano E, Sanchis ME, Asensio T, Callejo A. Hypersensitivity syndrome from isoniazid with positive patch test. Contact Dermatitis  2001 Nov;45(5):306  No abstract.

3855.         Reche M, Pascual CY, Vicente J, Caballero T, Martin-Munoz F, Sanchez S, Martin-Esteban M. Tomato allergy in children and young adults: cross-reactivity with latex and potato. Allergy  2001 Dec;56(12):1197-201

BACKGROUND: Several studies have shown that allergy to natural rubber latex is associated with cross-reactivity to certain foods such as tomato and potato. The objective was to investigate the clinical and immunologic differences between a group of patients with clinical allergy to tomato and latex and another which had only clinical allergy to tomato. We also aimed to assess, in vitro, the relationship of tomato and latex allergens, which could explain the cross-reactivity. METHODS: Forty patients with histories of adverse reactions to tomato and IgE-mediated hypersensitivity were enrolled in the study. Tomato, latex, and potato components were analyzed by SDS-PAGE immunoblotting. CAP and immunoblot inhibition were used to study allergen cross-reactivity. RESULTS: Patients from group A had a mean age of 13.2 years, and in group B the mean age was 21.7 years. In group B, 9/10 patients belonged to the latex-fruits syndrome. All patients of both groups tolerated potato. Immunoblotting patterns obtained with patients' sera from pool A showed IgE-binding bands to tomato ranging from 44 to 46 kDa and a triple band at 67 kDa. For latex, there was a strong binding at 44 kDa, and potato showed a strong band of 44 kDa and a 67-kDa triple band. In pool B, the binding to the band of 44 kDa in latex and tomato was more intense than in pool A. In pool A, immunoblot inhibition with potato allergen showed an intense inhibition of the three allergens (potato, latex, and tomato); with latex, inhibition was partial and with tomato, a complete inhibition of tomato and latex was observed, and a partial inhibition of potato. In pool B, the inhibition pattern followed a similar tendency to pool A. The CAP inhibition confirmed the high rate of cross-reactivity between tomato, potato, and latex. CONCLUSIONS: In our study, tomato, potato, and latex showed a common band of 44-46 kDa probably corresponding to patatin. This protein could be implicated in the high cross-reactivity between tomato, latex, and potato observed in the immunoblot and CAP inhibition.

3856.         Renstrom A, Karlsson AS, Malmberg P, Larsson PH, van Hage-Hamsten M. Working with male rodents may increase risk of allergy to laboratory animals. Allergy  2001 Oct;56(10):964-70 

BACKGROUND: Our aim was to study the risk of laboratory animal allergy (LAA) among research staff working in laboratories separate from the animal confinement area. The roles of atopy and exposure intensity in LAA were studied with special regard to exposure to male rodents, who excrete higher levels of urinary allergens than female rodents. METHODS: Eighty rodent-exposed subjects gave blood samples for the analysis of total IgE, Phadiatop, and specific IgE against rat (RUA) and mouse urinary allergens (MUA), and answered questionnaires. Air samples were collected for RUA and MUA aeroallergen measurement in both laboratories and animal confinement facilities. RESULTS: Twenty percent of the subjects had IgE >0.35 kU/l to RUA and/or MUA, and 32% had experienced animal work-related symptoms, although 90% of aeroallergen samples from the research department laboratories were below the detection limit (<0.26 ng RUA per m(3) and <0.8 ng MUA per m(3)). Atopy (positive Phadiatop), total IgE >100 kU/l, other allergies (especially to other animals), or more than 4 years of exposure significantly increased laboratory animal sensitization and symptoms. Working with mainly male rodents gave odds ratios (95% CI) of 3.8 (0.97-15) for sensitization and 4.4 (1.4-14) for symptoms. Subjects with both exposure to mainly male rodents and atopy or elevated total IgE had a 10-fold higher frequency of sensitization than exposed subjects with neither risk factor. CONCLUSION: A majority of subjects with a combination of exposure to mainly male rodents and atopy or elevated total IgE developed sensitization to and symptoms from laboratory animals. Current low exposure seems to maintain the presence of specific IgE. Further measures must be undertaken to provide a safe workplace for laboratory animal workers.

3857.         Rhodes HL, Sporik R, Thomas P, Holgate ST, Cogswell JJ. Early life risk factors for adult asthma: a birth cohort study of subjects at risk. J Allergy Clin Immunol 2001 Nov;108(5):720-5 

BACKGROUND: Prediction of adult asthma is important, and early prevention strategies should be targeted at those most at risk. Identifying high-risk children at an early age, however, is currently difficult. OBJECTIVE: We sought to determine those factors present in early life that predict an increased risk of adult asthma. METHODS: A prospective cohort study of subjects at risk of asthma and atopy was undertaken in Poole, England. One hundred babies of atopic parents were recruited at birth. During the first 5 years of life, subjects were recalled annually, all respiratory events were reported, and skin prick tests and total serum IgE measurements were performed. At 11 and 22 years, bronchial hyperresponsiveness was also measured. Seventy-three subjects were followed up at 5 years, 67 at 11 years, and 63 at 22 years. RESULTS: Twenty-three (37%) adult subjects reported wheezing within the previous 12 months. Fifteen (25%) of these subjects showed signs of bronchial hyperresponsiveness and were regarded as asthmatic. Wheezing before the age of 2 years occurred in 28% and was not significantly related to adult asthma (odds ratio, 0.3; 95% CI, 0.03-1.7; P =.19). A positive skin prick test response to hen's egg, cow's milk, or both in the first year was independently predictive of adult asthma (odds ratio, 10.7; 95% CI, 2.1-55.1; P = .001; sensitivity, 57%; specificity, 89%). CONCLUSION: Prediction of adult asthma remains difficult. In this study of subjects at risk of atopy, skin sensitivity to hen's egg or cow's milk in the first year was predictive of adult asthma.

3858.         Riediker M, Monn C, Koller T, Stahel WA, Wuthrich B. Air pollutants enhance rhinoconjunctivitis symptoms in pollen-allergic individuals. Ann Allergy Asthma Immunol  2001 Oct;87(4):311-8 

BACKGROUND: Little is know about the relation of airborne pollen allergens to nasal and ocular symptoms in combination with air pollutants. OBJECTIVE: The hypothesis was that air pollutants exacerbate allergic symptoms of the nose and eyes during the pollen season. In addition, the use of allergen measurements instead of pollen counts should be tested. METHODS: Fifteen pollen-allergic, nonsmoking subjects with weak reactivity of the airways recorded rhinoconjunctival symptoms and medication every morning and evening throughout the pollen season. Symptoms were compared with air pollutants (nitrogen oxide [NOx], particulate matter smaller than 10 microm, and ozone) and birch and grass pollen counts or, alternatively, to airborne birch and grass allergens determined using ELISA-techniques. A multiple linear regression model was used which controlled for autocorrelation of the residuals of the time series (Cochrane-Orcutt approach). This model was applied to each subject individually, followed by calculations of summary scores for the group. RESULTS: Air pollution levels were moderate, often meeting air quality standards. Effect estimates (increase of score with 10-fold increase of concentration) were NOx = 1.06, P < 0.01; ozone = 1.59, P < 0.01; and pollen = 0.48, P < 0.001. Using allergen concentrations instead of pollen counts resulted in similar effect estimates. Using particulate matter smaller than 10 microm instead of NOx gave comparable but less consistent results. CONCLUSIONS: Symptoms were related to moderate levels of pollutants, suggesting that rhinoconjunctival tissue is very sensitive to irritant stimuli during an ongoing allergic inflammation, and that susceptibility toward allergens might be increased in areas with increased levels of air pollutants. Allergen measurements seem equally usable as pollen counts to investigate rhinoconjunctivitis.

3859.         Ring J, Eberlein-Koenig B, Behrendt H. Environmental pollution and allergy. Ann Allergy Asthma Immunol  2001 Dec;87(6 Suppl 3):2-6

OBJECTIVES: Among the theories supporting the increase of allergic diseases in modern western countries during the last several decades is the concept that environmental pollutants may play a vital role. Reading this article will enable the reader to recognize the effect of different types of environmental pollution on the development, modulation, and persistence of allergic reactions. DATA SOURCES: Data sources include references to relevant articles and texts. To characterize the influence of environmental pollutants on allergic reactions (allergotoxicology), epidemiologic, clinical, and experimental data are considered. RESULTS: The investigations show that air pollution patterns differ with respect to their effect upon allergies. Classical air pollution (type I) with high sulfur dioxide and dust particles seems not to be associated with allergic disease in humans. However, type II pollution characterized by elevation of oxides of nitrogen (NOx), ozone (O3), tobacco smoke, fine and ultrafine particulate matter, and diesel exhaust particles seems to enhance allergic disease. CONCLUSIONS: The data suggest that environmental pollution can act at different levels and by complex interactions both outside and inside the individual and influence allergic diseases.

3860.         Ring J, Kramer U, Schafer T, Behrendt H. Why are allergies increasing? Curr Opin Immunol  2001 Dec;13(6):701-8 

The incidence of atopic allergy is increasing in certain 'Western' countries but this remains unexplained. Various hypotheses with differing amounts of evidence and/or relevance have been assessed, including increased awareness of the diseases, improved diagnostics, genetic susceptibility, psycho-socialinfluences, allergen exposure, decreased immune-system stimulation, underlying disease, anti-allergic therapy and pollution.

3861.         Rose EA, Schwartz K. Is a 2-day course of oral dexamethasone more effective than 5 days of oral prednisone in improving symptoms and preventing relapse in children with acute asthma? J Fam Pract  2001 Nov;50(11):993 No abstract.

3862.         Rosenberg HF, Domachowske JB. Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens. J Leukoc Biol  2001 Nov;70(5):691-8

Eosinophils remain among the most enigmatic of cells, as our appreciation of their detrimental activities--e.g., asthma and allergic disease—far outweighs our understanding of their beneficial effects. Among the major secretory effector proteins of eosinophils are the ribonucleases eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in primates and their orthologs, the eosinophil-associated ribonucleases (EARs) in rodents. The rapid diversification observed among these ribonucleases suggested that the ultimate target(s) might be similarly efficient at generating sequence diversity while maintaining an unalterable susceptibility to ribonucleolytic cleavage. This has prompted us to consider a role for these proteins and by extension, for eosinophils, in host defense against single-stranded RNA virus pathogens. We detail our studies of the antiviral activity of eosinophils and eosinophil ribonucleases against respiratory syncytial virus (RSV) in vitro and the related, natural rodent pathogen, pneumonia virus of mice (PVM), in vivo, and consider the possibility that antiviral host defense and the dysregulated responses leading to asthma represent opposing sides of an eosinophil-mediated double-edged sword.

3863.         Rudin A, Macaubas C, Wee C, Holt BJ, Slya PD, Holt PG. "Bystander" amplification of PBMC cytokine responses to seasonal allergen in polysensitized atopic children. Allergy 2001 Nov;56(11):1042-8 

BACKGROUND: Atopic children show increased expression and production of the Th2-associated cytokines IL-4, IL-5, IL-13, and IL-9 from PBMCs after stimulation with allergen, but it has previously not been clearly determined whether the Th2-cytokine production is restricted to the inhalant allergen the child is sensitized to, and whether perennial or seasonal allergens induce different cytokine responses. Our purpose was to determine whether in vitro Th2 cytokine production is specific to the sensitizing allergen, and to compare the cytokine responses to a perennial and a seasonal allergen in monosensitized and polysensitized children. METHODS: Using semiquantitative RT-PCR, we analyzed the expression of the cytokines IL-4, IL-5, IL-13, IL-9, IL-10, and IFN-gamma after stimulation of PBMCs with house-dust-mite (HDM) or ryegrass allergen. The cells were sampled from groups of 6-year-old children sensitized to either HDM (n=20) or ryegrass (n=24), or to both allergens (n=20), as well as from a nonatopic group (n=20). RESULTS: After stimulation with HDM allergen, PBMCs from children sensitized only to HDM expressed increased mRNA levels of the Th2 cytokines, but not of IL-10 and IFN-gamma, whereas ryegrass stimulation did not result in increased cytokine expression. PBMCs from children sensitized to HDM and ryegrass expressed increased Th2 cytokines after stimulation with either of the two allergens. In contrast, PBMCs from children sensitized only to ryegrass did not express increased levels after stimulation with either of the allergens. CONCLUSIONS: The expression of Th2 cytokines after in vitro stimulation of PBMCs from atopic children is specific to the sensitizing allergen, indicating that atopic status per se does not affect the type of T-cell response. In addition, T cells specific to seasonal allergens circulate in the blood out of season only if the child is concomitantly sensitized to a perennial allergen.

3864.         Sakaguchi M, Inouye S. Anaphylaxis to gelatin-containing rectal suppositories. J Allergy Clin Immunol  2001 Dec;108(6):1033-4 

BACKGROUND: Some children--though the number is few-have been sensitized with gelatin. OBJECTIVE: To investigate the relationship between the presence of antigelatin IgE and anaphylaxis to gelatin-containing rectal suppository, we measured antigelatin IgE in the sera of the children with anaphylaxis. METHODS: Ten children showed systemic allergic reactions, including anaphylaxis, to a chloral hydrate rectal suppository containing gelatin (231 mg/dose) that had been used as a sedative. These children's clinical histories and serum samples were submitted from physicians to the National Institute of Infectious Diseases during a 2-year period from 1996 to 1997. RESULTS: Of the 10 children, 5 showed apparent anaphylaxis, including hypotension and/or cyanosis, along with urticaria or wheezing; 2 showed both urticaria and wheezing without hypotension or cyanosis; the other 3 showed only urticaria. All of the children had antigelatin IgE (mean value +/- SD, 7.9 +/- 8.4 Ua/mL). As a control, samples from 250 randomly selected children had no antigelatin IgE. These findings suggest that the 10 children's systemic allergic reactions to this suppository were caused by the gelatin component. CONCLUSION: Gelatin-containing suppositories must be used with the same caution as gelatin-containing vaccines and other medications.

3865.         Sampson HA. Use of food-challenge tests in children. Lancet  2001 Dec 1;358(9296):1832-3 No abstract.

3866.         Sasseville D. Exacerbation of allergic contact dermatitis from amcinonide triggered by patch testing. Contact Dermatitis  2001 Oct;45(4):232-3  No abstract.

3867.         Schappi GF, Konrad V, Imhof D, Etter R, Wuthrich B. Hidden peanut allergens detected in various foods: findings and legal measures. Allergy  2001 Dec;56(12):1216-20 

BACKGROUND: Undeclared allergens in foodstuffs represent a major health problem for sensitized persons. Until recently, most food control authorities were not in the position to monitor hidden allergens and to take legal measures against their presence in foodstuffs. METHODS: In this study, we employed human sera-based immunoassay techniques, enabling semiquantitative detection and identification of peanut allergens in a variety of foodstuffs. RESULTS: This study showed the presence of undeclared allergens in products belonging to various food categories, such as cereals, cookies, cakes, and snacks. The detection limit for peanut contamination was in most instances less than 50 mg peanut material per kg, i.e., less than about 5 mg peanut allergens per kg. We legally objected to products with more than one part per thousand or 1000 mg/kg of peanut contamination. CONCLUSIONS: In most cases, food producers, confronted with our results, were able to detect and eliminate the sources of the contamination. They implemented measures to prevent the presence of hidden peanut allergens in their products, increasing food safety for sensitized persons and overall food quality.

3868.         Schellenberg RR, Isserow SH. Anaphylactoid reaction to a cyclooxygenase-2 inhibitor in a patient who had a reaction to a cyclooxygenase-1 inhibitor. N Engl J Med  2001 Dec 20;345(25):1856 No abstract.

3869.         Schlievert PM. Use of intravenous immunoglobulin in the treatment of staphylococcal and streptococcal toxic shock syndromes and related illnesses. J Allergy Clin Immunol  2001 Oct;108(4 Suppl):S107-10 

Pyrogenic toxin superantigens comprise a large family of exotoxins made by Staphylococcus aureus and group A streptococci. These toxins include toxic shock syndrome toxin-1, the staphylococcal enterotoxins, and the streptococcal pyrogenic exotoxins (synonyms: scarlet fever toxins and erythrogenic toxins), all of which have the ability to cause toxic shock syndromes and related illnesses. These toxins have a similar three-dimensional structure that allows them to interact with relatively invariant regions of major histocompatibility complex class II molecules on the surface of antigen-presenting cells and with certain variable regions of the T-cell receptor-beta chain. The consequence of these interactions (and other immunobiological properties of the toxins) is the exaggerated release of bioactive cytokines. The latter molecules are responsible for the clinical signs of illness associated with these toxins.

3870.         Schulman ES. Development of a monoclonal anti-immunoglobulin E antibody (omalizumab) for the treatment of allergic respiratory disorders. Am J Respir Crit Care Med  2001 Oct 15;164(8 Pt 2):S6-11 

Immunoglobulin E (IgE) mediates many of the inflammatory processes that underlie the symptoms of asthma and other allergic respiratory disorders. Recently, a recombinant, humanized, monoclonal antibody (mAb) that binds to and neutralizes IgE has been developed for the treatment of these disorders. Preclinical and clinical studies have shown that this mAb, directed against IgE and known as omalizumab, inhibits the binding of IgE to its receptors on effector cells, reduces IgE synthesis by B cells in response to allergen exposure, decreases the expression of IgE receptors, and attenuates both immediate and delayed inflammatory airway responses following exposure to inhaled allergen. Omalizumab is nonanaphylactogenic, and clinical experience to date suggests that omalizumab is safe and well tolerated by patients. These results suggest that specific inhibition of IgE may be an important new therapeutic option for the treatment of asthma and related disorders.

3871.         Scott MB, Ellis MH, Cruz-Rivera M, Fitzpatrick S, Smith JA. Once-daily budesonide inhalation suspension in infants and children < 4 and > or = 4 years of age with persistent asthma. Ann Allergy Asthma Immunol  2001 Dec;87(6):488-95

BACKGROUND: Budesonide inhalation suspension (Pulmicort Respules; AstraZeneca LP, Wilmington, DE), a nebulized corticosteroid, was developed for use in infants and young children with persistent asthma. OBJECTIVE: To compare the efficacy and safety of once-daily budesonide inhalation suspension in children < 4 years of age and in those > or = 4 years of age with persistent asthma. METHODS: A retrospective analysis stratified by age group was performed on data from two randomized, double-blind, placebo-controlled, parallel-group studies that evaluated the efficacy and safety of budesonide inhalation suspension 0.25 mg, 0.5 mg, or 1.0 mg once daily for 12 weeks in children 6 months to 8 years of age with persistent asthma. Clinical assessments included nighttime and daytime asthma symptoms, breakthrough medication use, adverse events, and hypothalamic-pituitary-adrenal-axis function. RESULTS: In both randomized studies, budesonide inhalation suspension demonstrated statistically significant improvement in nighttime and daytime asthma symptom scores compared with placebo. In the retrospective analysis of pooled data from these studies, the efficacy of budesonide was maintained when children were stratified by age group. Clinical improvements from baseline in nighttime and daytime asthma symptom scores were observed in both age groups at all budesonide inhalation suspension dose levels. No significant differences were observed between age groups in breakthrough medication use in any of the treatment groups. No differences were observed in the incidence of adverse events between the two age groups, and significant (P < 0.01) effect on hypothalamic-pituitary-adrenal-axis function was apparent only in children < 4 years of age at the 0.25-mg dose level. CONCLUSIONS: Once-daily budesonide inhalation suspension is effective in the treatment of persistent asthma in children aged < 4 and > or = 4 years of age.

3872.         Sharland CE. Suspected latex allergies. SADJ  2001 Oct;56(10):452-3 No abstract.

3873.         Shida K, Koizumi H, Shiratori I, Matsumoto M, Kikkawa S, Tsuji S, Begum NA, Fukumori Y, Toyoshima K, Seya T. High serum levels of additional IL-18 forms may be reciprocally correlated with IgE levels in patients with atopic dermatitis. Immunol Lett  2001 Dec 3;79(3):169-75  

We established an ELISA system for determination of as yet unidentified species of interleukin 18 (IL-18), named IL-18 type 2, in human serum. Serum IL-18 levels and their effect on IgE levels were examined in 18 patients with atopic dermatitis (AD) with no other allergic symptoms. Three of these patients showed high IL-18 type 2 concentrations (25-100 ng/ml) in their blood serum, and this IL-18 type 2 was detectable only with our established ELISA system. In contrast, the level of the conventional form of IL-18 (type 1) was found to be 50-400 pg/ml in all patients by the commercially available ELISA. The levels of type 1 IL-18 showed no correlation with those of type 2 and approximately 2-fold higher in AD patients than in normal subjects. IL-12 p40 and IgE levels were correlated in the patients with no IL-18 type 2, and interestingly, relatively low IgE concentrations were detected in the three IL-18 type 2-positive patients. They showed considerable levels of IL-12 p40 unlike normal subjects. The IFNgamma-inducing activity of IL-18 type 2 was >100-fold less potent by weight ratio than that of a recombinant 'active' IL-18 preparation, even after the treatment with Caspase 1. Although the relationship between AD and serum IgE levels is not clear cut, IL-18 type 2 appears to play some roles in the Th2-polarization involving IgE production in association with immune responses occurring in local inflammatory milieu such as atopic lesions.

3874.         Silvestre JF, Carnero L, Ramon R, Albares MP, Botella R. Allergic contact dermatitis from apraclonidine in eyedrops. Contact Dermatitis 2001 Oct;45(4):251 No abstract.

3875.         Smith KJ, Rosario-Collazo J, Skelton H. Delayed cutaneous hypersensitivity reactions to hirudin. Arch Pathol Lab Med  2001 Dec;125(12):1585-7 

Hirudin is one of the new synthetic antithrombin agents, which is most commonly used in patients with type II heparin-induced thrombocytopenia and in patients with hypersensitivity reactions to unfractionated heparin as well as low-molecular-weight heparins. Hirudin is comparable to heparin as an antithrombotic agent and also has been studied as a primary treatment in patients who experienced acute myocardial infarctions. We describe a patient with a history of type II heparin-induced thrombocytopenia who was placed on intravenous hirudin therapy. After extravasation of the intravenous hirudin site, the patient developed a delayed hypersensitivity reaction that histologically showed an epithelioid granulomatous infiltrate. Although rare reports of hypersensitivity reactions to hirudin have been published, these reactions have not been well characterized and the histopathologic changes have not been described.

3876.         Smurthwaite L, Walker SN, Wilson DR, Birch DS, Merrett TG, Durham SR, Gould HJ. Persistent IgE synthesis in the nasal mucosa of hay fever patients. Eur J Immunol  2001 Dec;31(12):3422-31 

The location of IgE synthesis has been a longstanding controversy, with previous evidence favoring either the mucosa or lymphoid tissue in the region of allergen entry. The evidence for IgE synthesis in mucosal tissues has always been circumstantial. We have developed a novel explant culture system, using ELISA and radioactive amino acid incorporation, to measure de novo IgE protein synthesis in the nasal mucosa of hay fever patients. Surprisingly, IgE synthesis continues between seasons in the explants from grass pollen-sensitive patients and a higher proportion of this IgE compared to serum IgE is allergen specific. Persistent IgE synthesis may ensure the expression of immediate hypersensitivity in the mucosa and promote rapid amplification of the allergic response in the local lymphoid tissue on allergen provocation. Our work demonstrates definitively for the first time that the local mucosa is a site of ongoing IgE synthesis.

3877.         Strachan DP, Wong HJ, Spector TD. Concordance and interrelationship of atopic diseases and markers of allergic sensitization among adult female twins. J Allergy Clin Immunol  2001 Dec;108(6):901-7 

BACKGROUND: Previous twin studies of asthma and allergy implicate both genetic and environmental factors in disease risk, but few have related the occurrence of clinical disease to objective markers of allergic sensitization in twins. OBJECTIVE: We sought to investigate the concordance and interrelationships of self-reported allergic disease and total and aeroallergen-specific IgE levels within pairs of British adult female twins. METHODS: Three hundred forty monozygotic and 533 dizygotic pairs, aged 18 to 72 years, completed questionnaires about allergic disease. Of these, 282 monozygotic and 270 dizygotic pairs were tested for total IgE and specific IgE to Der p 1, mixed grass pollen, and cat dander by means of fluoroimmunoassay. RESULTS: Concordance rates for all variables were higher for monozygotic than for dizygotic twins, significantly (P < .05) so for hay fever, eczema, and specific IgE positivity but not (P > .05) for self-reported asthma or allergies. Within-pair correlations of log-transformed IgE were 0.59 for monozygotic twins and 0.29 for dizygotic twins, implying heritability of 60%. Within both monozygotic and dizygotic pairs discordant for hay fever or reported allergies, the affected twin had significantly higher total and specific IgE levels. Within pairs who were doubly discordant for 3 allergic diseases, associations between diseases were of similar strength for monozygotic and dizygotic pairs. CONCLUSIONS: These results confirm that genetic factors influence susceptibility to aeroallergen sensitization and clinical allergic disease. However, genetically identical twins are often discordant in their expression of atopy, suggesting a substantial modifying role for environmental factors.

3878.         Streit M, Braathen LR. Contact dermatitis: clinics and pathology. Acta Odontol Scand  2001 Oct;59(5):309-14


Contact dermatitis or eczema is a polymorphic inflammation of the skin. It occurs at the site of contact with irritating or antigenic substances. In the acute phase there is occurrence of itching erythema, papules, and vesicles, whereas in the chronic phase there is dryness, hyperkeratosis, and sometimes fissures. Contact dermatitis can be divided into irritant and allergic types. Allergic contact dermatitis is a type-IV T-cell-mediated reaction occurring in a sensitized individual after contact with the antigen/allergen. Such antigens are usually low molecular weight substances (MW approximately 500), called haptens; 3000 contact allergens are known. The diagnosis of contact allergy is made on the basis of the history, clinical findings, and a positive epicutancous test result. Allergic, but not irritative, contact dermatitis can spread beyond the area of contact to other body parts. Eczematous lesions are characterized by a mononuclear infiltrate consisting mainly of T cells in the dermis and epidermis, together with an intercellular epidermal edema that is. spongiosis. In allergic contact dermatitis, skin-applied antigen is taken up by epidermal Langerhans cells and transported with the afferent lymph to the regional lymph nodes. Here, naive T lymphocytes are sensitized to become antigen-specific effector T cells, which then leave the lymph node, enter the circulation, and are recruited to the skin by means of specific cell surface molecules, to form the infiltrates. Cytokines released by infiltrating T cells eventually cause keratinocyte apoptosis.


3879.         Tai YS, Liu BY, Wang JT, Sun A, Kwan HW, Chiang CP. Oral administration of milk from cows immunized with human intestinal bacteria leads to significant improvements of symptoms and signs in patients with oral submucous fibrosis. J Oral Pathol Med  2001 Nov;30(10):618-25

BACKGROUND: Previous studies have shown that the local and systemic upregulation of fibrogenic cytokines and downregulation of antifibrotic cytokine are central to the pathogenesis of oral submucous fibrosis (OSF). The milk from cows immunized with human intestinal bacteria (immune milk) contains an anti-inflammatory component that may suppress the inflammatory reaction and modulate cytokine production. Therefore, it was decided to test whether immune milk may have some beneficial effects on controlling the symptoms and signs in OSF patients. METHODS: In this preliminary study, 26 OSF patients who received immune milk treatment (45 g of immune milk powder twice a day) for 3 months and oral habit intervention were included in the experimental group. Another 20 OSF patients who received only oral habit intervention served as the control group. RESULTS: We found that the interincisor distance was significantly improved (> or =3 mm of the baseline measurement) in 18 of the 26 (69.2%) OSF patients in the experimental group at exit. However, in the control group none of the OSF patients had an increase in interincisor distance greater than 2 mm. In addition, disappearance or significant improvement of symptoms at exit was observed in 80% (16/20) of the patients with intolerance to spicy foods (P < 0.001) and 72.2% (13/18) of the patients with xerostomia (P < 0.005) in the experimental group, compared with 17.6% (3/17) of the patients with improvement of intolerance to spicy foods and 15.4% (2/13) of the patients with improvement of xerostomia in the control group. Partial regression of concomitant oral leukoplakia or erythroplakia (judged from the size reduction of the lesions) at exit was noted in 71.4% (5/7) of the patients in the experimental group (P < 0.05), compared with none (0/5) of the patients with improvement in the control group. CONCLUSION: We conclude that oral administration of immune milk leads to significant improvements of symptoms and signs in OSF patients.


3880.         Thami GP, Kaur S, Kanwar AJ. Allergic contact dermatitis to henna. Allergy  2001 Oct;56(10):1013-4 No abstract.

3881.         Thawani V R, Gharpure K J, Balani N D, Paranjpe B D: Penicillin allergic deaths: the phobia leading to disuse. Indian J clin Pract 2001, 11(9), 52-4. (017451) Sept 1, 2023 No abstract.

3882.         Trautmann A, Akdis M, Brocker EB, Blaser K, Akdis CA. New insights into the role of T cells in atopic dermatitis and allergic contact dermatitis. Trends Immunol 2001 Oct;22(10):530-2 No abstract.

3883.         Trautmann A, Akdis M, Schmid-Grendelmeier P, Disch R, Brocker EB, Blaser K, Akdis CA. Targeting keratinocyte apoptosis in the treatment of atopic dermatitis and allergic contact dermatitis. J Allergy Clin Immunol 2001 Nov;108(5):839-46

BACKGROUND: Activation and skin-selective homing of T cells and effector functions in the skin represent sequential events in the pathogenesis of atopic dermatitis and allergic contact dermatitis. OBJECTIVE: T cell-mediated keratinocyte apoptosis plays a key pathogenetic role in the formation of eczematous dermatitis. IFN-gamma released from activated T cells upregulates Fas on ke-ratinocytes, which renders them susceptible to apoptosis. The lethal hit is given to keratinocytes by means of Fas ligand expressed on the T-cell surface or released to the inflammatory microenvironment. We sought to investigate whether drugs used for the treatment of eczematous disorders interfere with this pathogenic pathway. METHODS: T cell-mediated, Fas-induced keratinocyte apoptosis in a keratinocyte-T cell coculture system serves as an in vitro model of eczematous dermatitis. We tested, in this model, whether immunomodulatory agents (dexamethasone, cyclosporine A, rapamycine, tacrolimus/FK506, intravenous immunoglobulin [IVIG], and theophylline) are able to inhibit apoptosis of keratinocytes. Additionally, skin biopsy specimens from patients with untreated and successfully treated eczematous dermatitis were evaluated for keratinocyte apoptosis. RESULTS: Dexamethasone, cyclosporine A, FK506, rapamycine, and IVIG are inhibitors of keratinocyte apoptosis induced by activated T cells. This effect is mediated by 2 major mechanisms directed on T cells or keratinocytes. T-cell activation was mainly inhibited by dexamethasone, FK506, cyclosporine A, and rapamycine. Interestingly, high-dose dexamethasone and IVIG directly inhibited Fas-mediated keratinocyte apoptosis. In vivo keratinocyte apoptosis was significantly reduced after successful topical treatment of eczematous lesions. CONCLUSION: These results demonstrate mechanisms of action of current treatment approaches and provide a future for more focused therapeutic applications.

3884.         Turjanmaa K. Community management of severe allergies must be integrated and comprehensive, and must consist of more than just epinephrine. Allergy  2001 Nov;56(11):1023-5 No abstract.

3885.         Tzaneva S, Seeber A, Schwaiger M, Honigsmann H, Tanew A. High-dose versus medium-dose UVA1 phototherapy for patients with severe generalized atopic dermatitis. J Am Acad Dermatol  2001 Oct;45(4):503-7 No abstract.

3886.         van der Meer JB, Schuttelaar ML, Toth GG, Kardaun SH, Beerthuizen G, de Jong MC, Jonkman MF, Nieuwenhuis P. Successful dexamethasone pulse therapy in a toxic epidermal necrolysis (TEN) patient featuring recurrent TEN to oxazepam. Clin Exp Dermatol  2001 Nov;26(8):654-6

A 62-year-old female patient is described who developed toxic epidermal necrolysis (TEN) after medication with phenytoin and oxazepam. Initially phenytoin was discontinued and dexamethasone pulse therapy (1.5 mg/kg on 3 consecutive days) was initiated on the tenth day of skin disease. This resulted in clinical improvement. Histologically re-epithelialization could be demonstrated below the necrotic epidermis. However, on the eighteenth day of skin disease (10 days after discontinuation of phenytoin and 8 days after the start of dexamethasone pulse therapy), a histologically verified rebound-TEN developed with a detachment of 95%. Oxazepam was stopped and a second series of dexamethasone pulse therapy was given. Re-epithelialization began within 24 h of the start of the second series of dexamethasone pulse therapy, and continued to almost complete recovery within 1 week.


3887.         Vila L, Beyer K, Jarvinen KM, Chatchatee P, Bardina L, Sampson HA. Role of conformational and linear epitopes in the achievement of tolerance in cow's milk allergy. Clin Exp Allergy  2001 Oct;31(10):1599-606

BACKGROUND: Cow's milk (CM) is one of the leading causes of food allergy in children. However, approximately 85% of milk-allergic children become clinically tolerant to CM within the first 3 years of life. The mechanisms involved in the achievement of tolerance remain unknown. OBJECTIVE: To study whether IgE antibodies from children with persistent cow's milk allergy (CMA) differ from children who become clinically tolerant in their ability to recognize linear and conformational epitopes of alpha(s1)- and beta-casein. METHODS: Thirty-six milk-allergic children were included in the study: 11 of the children became clinically tolerant, and 25 had persistent CMA. Blood was obtained from all patients during the time they showed clinical reactions to milk challenge. Six non-milk-allergic children served as controls. Specific IgE antibodies against linear (denatured) as well as conformational (native) milk proteins were determined by probing dot-blots with patients' sera. In addition, selected decapeptides from alpha(s1)- and beta-casein, previously found to be suggestive of persistent CMA, were synthesized on a cellulose-derivatized membrane and probed with individual sera from 10 patients who outgrew CMA and from 10 patients with persistent CMA. RESULTS: Analysis of immunodot-blots showed that, in comparison to tolerant patients, milk-allergic children with persistent symptoms had a significantly higher ratio of specific IgE antibodies to linearized than to native alpha- and beta-casein (P < 0.005 and P < 0.02, respectively). Comparing the selected decapeptides, six of the 10 patients with persistent allergy recognized the peptide corresponding to amino acids 69-78 from alpha(s1)-casein while none of the patients who outgrew CMA had IgE binding to this epitope. CONCLUSION: Patients with persistent milk allergy possess higher detectable levels of IgE antibodies to linear epitopes from alpha(s1)- and beta-casein than children who have achieved tolerance. Specific IgE binding to particular linear epitopes in alpha(s1)-casein may be a predictive factor for persistence of CMA.

3888.         Vissers M, Doekes G, Heederik D. Exposure to wheat allergen and fungal alpha amylase in the homes of bakers. Clin Exp Allergy  2001 Oct;31(10):1577-82

BACKGROUND: Few data are available on exposure to occupational allergens in dwellings occupied by inhabitants with occupational exposure to allergens. In small bakeries working and living often takes place in the same building. It is possible that allergens from the bakery can be transported into the homes of the bakers, via the clothes or shoes of the baker. OBJECTIVE: The aims of this study were to investigate exposure to occupational allergens, wheat and fungal alpha-amylase in the homes of bakers, and evaluate potential determinants of exposure. Sensitization in family members to occupational allergens was investigated in a small preliminary survey. METHODS: Floor dust samples were collected in the homes of 34 bakers. Levels of wheat and fungal alpha-amylase allergens were determined in an extract of the dust samples. Blood samples were collected from bakers and their family members to determine the prevalence of sensitization to occupational allergens. RESULTS: The concentration of wheat and alpha-amylase allergens ranged from 38.9 to 172.4 microgeq/m(2) (GM), to 10.5-76.7 ngeq/m(2) (GM). Higher levels of dust and allergens were measured when the house could be reached directly through the bakery, and in houses with textile floor covers. Higher concentrations were also measured when bakers brought their work clothes and shoes into the house and when textiles from the bakery were laundered at home. Some family members appeared to be sensitized to wheat flour and alpha-amylase, but it cannot be excluded that they became sensitized because of their incidental presence in the bakery. CONCLUSIONS: Occupational allergens can be found in house dust from the homes of bakers and levels are associated with hygienic behaviour and distance to the bakery.

3889.         von Mutius E. Pro: the increase in asthma can be ascribed to cleanliness. Am J Respir Crit Care Med  2001 Oct 1;164(7):1106-7; discussion 1108-9 No abstract.

3890.         Walker WA. Cow's milk protein-sensitive enteropathy at school age: a new entity or a spectrum of mucosal immune responses with age. J Pediatr  2001 Dec;139(6):765-6 No abstract.

3891.         Weiss KS. Anaphylactic reaction to ondansetron. Arch Intern Med  2001 Oct 8;161(18):2263  No abstract.

3892.         Wictorin A, Hansson C. Allergic contact dermatitis from a bismuth compound in an eye ointment. Contact Dermatitis  2001 Nov;45(5):318  No abstract.

3893.         Wong CS, Beck MH. Allergic contact dermatitis from triclosan in antibacterial handwashes. Contact Dermatitis  2001 Nov;45(5):307 No abstract.

3894.         Yadav S P S, Chandra R: Fluticasone propionate – a new steriod nasal spray for management of allergic rhinits. Indian J clin Pract 2001, 11(12), 23-4. (016545) Aug 16, 2001.

Corticosteroids are the most effective medication available for the treatment of allergic rhinitis. They are frequently used intranasally, because intranasal corticosteroids have their action on both early as well as late phase of allergic reaction. On the other hand, oral steroids have an unacceptable risk of slide effects and have no effect on the early phase reaction.


3895.         Yesudian PD, King CM. Allergic contact dermatitis from stearyl alcohol in Efudix cream. Contact Dermatitis  2001 Nov;45(5):313-4 No abstract.

3896.         Zollner TM, Spengler K, Podda M, Ergezinger K, Kaufmann R, Boehncke WH. The Western blot is a highly sensitive and efficient technique in diagnosing allergy to wasp venom. Clin Exp Allergy  2001 Nov;31(11):1754-61


BACKGROUND: Diagnosis of allergy to wasp venom and decision to perform immunotherapy are based on the patient's history, along with skin and in vitro tests. OBJECTIVE: Given the high prevalence of specific IgE also in non-allergic individuals, we evaluated the sensitivity and specificity of Western blots as a possible alternative to serum analyses of venom-specific IgE. METHODS: Skin prick and/or intracutaneous tests were performed in 30 patients with allergy to wasp venom (generalized reaction following sting) along with serum analysis of venom-specific IgE (AlaSTAT microplate) and Western blots. Western blots were subsequently scanned and evaluated qualitatively and semiquantitatively by means of densitometry. Bands were scored 'positive' in cases of signal intensities beyond the mean plus 3 standard deviations of control sera. Twenty newborns (age 2-7 days) and 30 adults without systemic or increased local reactions to hymenoptera stings served as controls. RESULTS: Western blot sensitivity reached 100% in the samples studied and was thus superior to the sensitivities of serum analysis of venom-specific IgE using AlaSTAT microplate assay (90%) and skin tests (87%). The sensitivity of detection of a phospholipase A1 and antigen 5-specific band was higher compared with a hyaluronidase-specific band (97%, 97% and 86%, respectively). Twenty-four out of twenty-nine (83%) patients exhibited specific IgE antibodies against at least three distinct allergens. With regard to the specificities, skin tests as well as AlaSTAT microplate assays were comparable (90% and 93%, respectively), whereas the specificity of the Western blots was 70% if the appearance of any single band was regarded as a positive result. However, when analysing the appearance of a specific band for antigen 5 or hyaluronidase the specificity and overall diagnostic value increased markedly, making it the most efficient test (specificity 97% and 100%, efficiency 96.8% and 93.2%, respectively). CONCLUSION: As allergy to wasp venom is a severe and potentially life threatening disease, false-negative test results need to be minimized. Therefore, the superiority of the Western blot with regard to sensitivity, specificity and overall efficiency makes this technique a valuable tool for its diagnosis.


July 2002

4421.  Aalberse RC, Schuurman J. IgG4 breaking the rules. Immunology. 2002 Jan;105(1):9-19. Review.


Immunoglobulin G4 (IgG4) antibodies have been known for some time to be functionally monovalent. Recently, the structural basis for this monovalency has been elucidated: the in vivo exchange of IgG half-molecules (one H-plus one L-chain) among IgG4. This process results in bispecific antibodies that in most situations will behave as functionally monovalent antibodies. The structural basis for the abnormal behaviour of IgG4 seems to be largely the result of a single amino acid change relative to human IgG1: the change of a proline in core hinge of IgG1 to serine. This results in a marked shift in the equilibrium between interchain disulphide bridges and intrachain disulphide  ridges, which for IgG4 results in 25-75% absence of a covalent interaction between the H-chains. Because of strong non-covalent interactions between the CH3 domains (and possibly also between the CH1 domain and the trans-CH2 domain) IgG4 is a stable four-chain molecule and does not easily exchange half-molecules under standard physiological conditions in vitro. We postulate that the exchange is catalysed in vivo by protein disulphide isomerase (PDI) and/or FcRn (the major histocompatibility complex (MHC)-related Fc receptor) during transit of IgG4 in the endosomal pathway in endothelial cells. Because IgG4 is predominantly expressed under conditions of chronic antigen exposure, the biological relevance of this exchange of half-molecules is that it generates antibodies that are unable to form large immune complexes and therefore have a low potential for inducing immune inflammation. In contrast to monovalent immunoglobulin fragments, these scrambled immunoglobulins have a normal half-life. The significance of the ensuing bispecificity needs further evaluation, because this will be relevant only in situations where high IgG4 responses are found to two unrelated antigens that happen to be present in the body at the same time and place. In this context the significance of IgG4 autoreactivity might have to be re-evaluated. The main function of IgG4, however, is presumably to interfere with immune inflammation induced by complement-fixing antibodies, or, in the case of helminth infection or allergy, by IgE antibodies.


4422.   Abraham WM. Tryptase: potential role in airway inflammation and remodeling. Am J Physiol Lung Cell Mol Physiol. 2002 Feb;282(2):L193-6. Review. No abstract.

4423.   Aldrich TK. Pink puffers vs blue bloaters in asthma too? Chest. 2002 Feb;121(2):313-5.  No abstract.

4424.   Baki A, Orhan F. The effect of loratadine in exercise-induced asthma. Arch Dis Child. 2002 Jan;86(1):38-9.


AIMS: To assess the effect of loratadine in exercise induced asthma. METHODS: Randomised, double blind, placebo controlled study of 10 mg oral loratadine, once daily for three days in 11 children. At the end of the treatment period FEV(1) was measured, and patients were exercised on a treadmill. FEV(1) measurements were repeated at intervals after exercise. RESULTS: Loratadine significantly reduced the decrease in FEV(1) after exercise at two, five, 10, 15, and 30 minutes, compared with placebo (p < 0.05). However, the mean decrease in FEV(1) at five minutes was more than 15% of baseline in the loratadine group. CONCLUSIONS: Loratadine reduces, but does not prevent, exercise induced asthma in children.

4425.   Barnes PJ. Cytokine modulators as novel therapies for asthma. Annu Rev Pharmacol Toxicol. 2002;42:81-98. Review.


Cytokines play a critical role in orchestrating and perpetuating inflammation in asthmatic airways and several specific cytokine and chemokine inhibitors are now in development for the treatment of asthma. Inhibition of IL-4 with soluble IL-4 receptors has shown promising early results in asthma. Anti-IL-5 antibody is very effective at inhibiting peripheral blood and airway eosinophils but does not appear to be effective in symptomatic asthma. Inhibitory cytokines, such as IL-10, interferons, and IL-12 are less promising because systemic delivery produces intolerable side effects. Inhibition of TNF-alpha may be useful in severe asthma. Many chemokines are involved in the inflammatory response of asthma, and small-molecule inhibitors of chemokine receptors are in development. CCR3 antagonists are now in clinical development for the treatment of asthma. Because so many cytokines are involved in asthma, drugs that inhibit the synthesis of multiple cytokines may prove to be more useful. Several such classes of drug are now in clinical development, and the risk of side effects with these nonspecific inhibitors may be reduced by the inhaled route of delivery.


4426.   Bartunkova J, Kolarova I, Sediva A, Holzelova E.  Antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, and specific IgE to food allergens in children with inflammatory bowel diseases. Clin Immunol. 2002 Feb;102(2):162-8.


Differential diagnosis between ulcerative colitis (UC) and Crohn's disease (CD) is difficult in the initial phases in pediatric patients with inflammatory bowel diseases (IBD). This study was performed to determine the significance of anti-neutrophil cytoplasmic antibodies (ANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) in IBD. ANCA were specified with regard to their antigenic specifity, significance to the diagnosis, and correlation of titer with the disease activity. The occurrence of food allergy was questioned, too. Serum samples from 44 children with UC (n = 23) or CD (n = 21) and from disease-control children (coeliac disease, n = 21) were analyzed for IgG ANCA, ANCA target antigens, IgA and IgG ASCA, and IgE to food allergens. Results show that ANCA occur more frequently in UC than in CD and disease-control (74, 24, and 10%, respectively). The presence of ANCA does not reflect disease activity. Antigenic specificity does not differ in any group. IgA-ASCA are found more often in patients with CD (76% versus 17% in UC). The testing for both ANCA and ASCA enabled clear-cut differential diagnosis between UC and CD based on the high specificity (ANCA+ ASCA- 92.5% for UC, ANCA- ASCA+ 93.2% for CD). Specific IgE to food allergens were found in 8.7, 14.3, and 23.8% of patients with UC, CD, and coeliac disease, respectively. We conclude that combined testing of ANCA and ASCA represents a valuable tool in the differential diagnosis between UC and CD in pediatric patients, minimizing invasive diagnostic procedures. Monitoring of ANCA, its specificity, and titer determination does not bring more information. Testing for specific IgE to food allergens may be considered in individual patients. Copyright 2001 Elsevier Science (USA).


4427.   Becker AB, Chan-Yeung M. Primary prevention of asthma. Curr Opin Pulm Med. 2002 Jan;8(1):16-24. Review.


There has been a dramatic increase in the prevalence of asthma over the last quarter century, particularly in the industrialized world. Although our understanding of asthma continues to improve, there is no cure for the disease. Primary prevention of asthma is the focus of this review. Asthma is a disease with multiple gene-environment interactions. Candidate genes for asthma are considered, and potential interaction between one of those genes, CD14, and an environmental factor, endotoxin, is reviewed as it relates to the hygiene hypothesis. Environmental risk factors for asthma including allergens, pollutants, infectious factors, and dietary modifications are considered, particularly their potential for primary prevention of asthma. Ongoing cohort studies including the Canadian Allergy and Asthma Prevention Study, the Manchester Allergy and Asthma Study, the Children's Asthma Prevention Study from Australia, and the Prevention and Incidence of Asthma and Mite Allergy Study from the Netherlands are briefly reviewed. A more definitive understanding of genetic background and environmental triggers and their interactions is required before any specific approach to the primary prevention of asthma can be championed aggressively.


4428.   Bhullar N, Folzenlogen DD.  Henoch-Schonlein purpura: upper respiratory tract infection or drug induced? Arch Intern Med. 2002 Jan 28;162(2):222-3.  No abstract.

4429.   Browne GJ, Trieu L, Van Asperen P. Randomized, double-blind, placebo-controlled trial of intravenous salbutamol and nebulized ipratropium bromide in early management of severe acute asthma inchildren presenting to an emergency department.Crit Care Med. 2002 Feb;30(2):448-53.


BACKGROUND: In acute severe asthma, treatment must be initiated early to reverse the pathophysiology that may render airways less responsive to bronchodilation. The addition of nebulized ipratropium bromide to initial emergency department therapy improves pulmonary function, but it is unclear whether this approach results in earlier hospital discharge. The early use of bolus intravenous salbutamol has also been shown to improve outcome, including earlier discharge. We therefore assessed the relative benefits of intravenous salbutamol and nebulized ipratropium bromide in the early management of acute severe asthma in children by a double-blind, randomized, controlled trial. METHODS: This study was undertaken at a tertiary children's hospital, The Children's Hospital at Westmead, The Royal Alexandra Hospital for Children, Westmead, Sydney, Australia. Only children with severe acute asthma as determined by the National Asthma Campaign guidelines criteria and pulmonary index were included. All children received initial nebulized salbutamol therapy (2.5-5 mg salbutamol in 4 mL of normal saline depending on age) at initial emergency department presentation. If asthma remained severe 20 mins later, an intravenous cannula was inserted and intravenous methylprednisolone (1 mg/kg) was administered to all children receiving nebulized salbutamol every 20 mins. Children were then randomized to one of three groups: intravenous salbutamol (15 microg/kg as a single bolus over 10 mins), ipratropium bromide (250 microg), or intravenous salbutamol plus ipratropium bromide. All observers were blinded to treatment groups. Children were randomly assigned to receive a single-dose intravenous bolus of either saline or salbutamol and either nebulized saline or ipratropium bromide determined by a number generated randomly in the hospital pharmacy. The primary outcomes were recovery time and discharge time of each group. Respiratory and hemodynamic monitoring were continuous during the first 2 hrs of the study and then children were monitored clinically for 24 hrs. RESULTS: A total of 55 children with acute severe asthma were entered into the study over an 18-month period. The three groups were similar demographically, with a mean age of 5.9 yrs, and mean duration of attack of 19.6 hrs. No side effects or treatment intolerance were reported. Children in the groups that received intravenous salbutamol had a significant reduction in recovery time to achieving second hourly inhaled salbutamol (p =.008) compared with those administered inhaled bronchodilator alone. The addition of ipratropium bromide to intravenous salbutamol provided no significant further benefit in terms of nebulizer therapy (intravenous salbutamol compared with intravenous salbutamol plus ipratropium bromide). Children administered intravenous salbutamol ceased supplemental oxygen therapy earlier than those administered ipratropium alone at 12 hrs post-randomization (p =.0003). Children administered intravenous salbutamol could be discharged from the hospital 28 hrs earlier than those administered ipratropium bromide (p =.013). CONCLUSION: Children administered intravenous salbutamol for severe acute asthma showed a more rapid recovery time, which resulted in earlier discharge from the hospital than those administered inhaled ipratropium bromide. There was no additional benefit obtained by combining ipratropium bromide and intravenous salbutamol administration.

4430.   Cameron I. "Help me breathe." Finding the right way to respond. Can Fam Physician. 2002 Feb;48:263-4.  No abstract.

4431.   Colice GL. Categorizing asthma severity and monitoring control of chronic asthma. Curr Opin Pulm Med. 2002 Jan;8(1):4-8. Review.


Asthma is a distressing disease, affecting up to 8% of the US population and causing considerable morbidity. Effective management of asthma requires accurate categorization of asthma severity and effective methods for monitoring the activity of the disease with treatment. Currently, symptoms, lung function, and requirements for corticosteroid treatment are the most accepted factors used for asthma severity categorization. Measures of airway hyperresponsiveness, particularly the use of methacholine, may provide additional information regarding the duration of asthma. Assessing airway inflammation using either sputum eosinophilia or exhaled nitric oxide levels has added little to clinical methods for determining asthma severity, but may be useful in monitoring the activity of the disease.

4432.   Davenport PW. What caused the screech, whamity, bang, and thump? Am J Respir Crit Care Med. 2002 Jan 1;165(1):2-3. No abstract.

4433.   Dixon JK. Kids need clean air: air pollution and children's health. Fam Community Health. 2002 Jan;24(4):9-26. Review.


Air pollution affects children's health in many ways, including reduced lung function, increased morbidity, increased use of health care services, and infant mortality. Information on the relationship of air pollution and children's health is discussed, with a focus on the diversity of research methods used to understand this relationship. Decisions affecting air quality ultimately are made through political and social processes. Health care and health promotion practitioners who are concerned about the health of children should provide leadership for advocacy to promote environmental health in our communities.

4434.   Donnelly LE, Barnes PJ. Expression and regulation of inducible nitric oxide synthase from human primary airway epithelial cells. Am J Respir Cell Mol Biol. 2002 Jan;26(1):144-51.


Elevated levels of exhaled nitric oxide are seen in inflammatory airway diseases such as asthma, but the cellular source remains unknown. This study investigated whether human airway epithelial cells express inducible nitric oxide synthase (iNOS). Human bronchial epithelial cells stimulated with 50 ng/ml interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma express iNOS mRNA, protein and increased nitrite in the cell culture media, which was inhibited by the selective iNOS inhibitor 1400W. Cells derived from subjects with asthma produced less nitrite than cells from normal subjects (6.59 +/- 0.99 microM nitrite, n = 15 versus 3.89 +/- 0.42 microM nitrite, n = 20; P < 0.05). This was not attributed to steroid treatment of subjects with asthma because there was no difference in the amount of nitrite released from steroid-naive and steroid-treated cells (3.51 +/- 0.46 versus 4.27 +/- 0.7 microM nitrite, n = 10). Neither dexamethasone nor budesonide inhibited iNOS mRNA induction, protein expression, or nitrite accumulation. The cells were not steroid insensitive because steroids inhibited GM-CSF release. Therefore, although these cells express iNOS under inflammatory conditions, they do not appear to be regulated directly by glucocorticosteroids.

4435.   Dorhofer DM, Sigmon ST. Physiological and psychological reactivity in women with asthma: the effects of anxiety and menstrual cycle phase. Behav Res Ther. 2002 Jan;40(1):3-17.


The relation between menstrual cycle timing, panic attacks, and diagnosis of asthma was explored in this study. Women with or without asthma and with or without a history of panic attacks engaged in a psychophysiological task during either the intermenstrual or premenstrual cycle phase and completed self-report measures of menstrual symptoms and attitudes, general psychological symptoms, and attitudes toward illness. No significant differences were identified for psychological or psychophysiological measures with menstrual cycle phase as a factor. However, women with both asthma and a history of panic attacks reported more general psychological distress than women in the other groups, and more state anxiety than controls. Women in the asthma, asthma and panic, and panic groups reported higher anxiety sensitivity than the control group. After listening to asthma-related scenes, women with asthma exhibited a decrease in peak expiratory air flow, and women with asthma and panic exhibited increased skin conductance response magnitude. Implications for the role of anxiety in

lung function are discussed, as well as directions for future research with asthma and anxiety populations.


4436.   Douma WR, Kerstjens HA, de Gooijer A, Overbeek SE, Koeter GH, Postma DS. Initial improvements in lung function and bronchial hyperresponsiveness are maintained during 5 years of treatment with inhaled beclomethasone dipropionate and terbutaline. Chest. 2002 Jan;121(1):151-7.


OBJECTIVES: Treatment with inhaled corticosteroids reduces bronchial hyperresponsiveness and relieves airways obstruction in patients with asthma. Up to now, it is unknown whether initial improvements are maintained over a long period of time. Therefore, we assessed whether initial improvements in FEV(1), provocative concentration of histamine causing a 20% fall in FEV(1) (PC(20)), and peak expiratory flow (PEF) persist with a constant dose of inhaled corticosteroids. Furthermore, we investigated whether FEV(1), PC(20), PEF indexes, and symptom scores improve after increasing the dose of inhaled corticosteroids in patients who did not respond sufficiently to treatment with beclomethasone dipropionate (BDP), 800 microg/d. METHODS: Sixty-eight patients with bronchial hyperresponsiveness and airways obstruction completed a previous study on 3 years of treatment with terbutaline, 500 microg qid, and BDP, 200 microg qid. Fifty-eight of these patients participated in the current extension of another 2.5 years of follow-up. Every 6 months, FEV(1) and PC(20) were measured. Five patients dropped out of the study, one for pulmonary reasons. Forty-four patients continued treatment with BDP, 800 microg/d (BDP-800 group), and 9 patients received a higher dose of BDP (500 microg tid; BDP-1,500 group) after the first 3 years because of a rapid decline in FEV(1) (> 50 mL/yr) despite BDP treatment during the previous study period. RESULTS: After the initial improvement, the mean slope of individual regression lines for FEV(1), PC(20), and morning PEF were - 28 mL/yr, - 0.01 doubling concentrations per year, and 0.6 L/min/yr, respectively, in the BDP-800 group. In the BDP-1,500 group, there were no statistically significant improvements in FEV(1), PC(20), PEF indexes, and symptom scores after increasing the dose of BDP. CONCLUSIONS: We conclude that initial improvements in FEV(1), PC(20), and PEF are well preserved over 5 years in patients with obstructive airways diseases who are treated with terbutaline and BDP. In the patients who responded sufficiently to 800 microg/d of BDP, there was no accelerated decline in FEV(1) compared with the general population. Increasing the dose of BDP in a small group of patients with an accelerated fall in FEV(1) (initially treated with a moderate dose of BDP) resulted in no significant improvement in FEV(1), PC(20), PEF indexes, and symptom scores.

4437.   Douwes J, Pearce N, Heederik D. Does environmental endotoxin exposure prevent asthma? Thorax. 2002 Jan;57(1):86-90. Review.


The evidence as to whether exposure to environmental airborne endotoxin plays a protective or an inducing role in the development of asthma is reviewed. Studies of endotoxin and atopy, endotoxin and asthma, and farming and asthma are considered and, in each instance, a distinction is made between evidence of primary causation and evidence of secondary causation. It is concluded that, although it is plausible that bacterial endotoxin may protect against the development of asthma, there is considerable reason for caution regarding this hypothesis.


4438.   Ernst P. Pesticide exposure and asthma. Am J Respir Crit Care Med. 2002 Mar 1;165(5):563-4. No abstract.

4439.   Frenkel M, Hermoni D. Effects of homeopathic intervention on medication consumption in atopic and allergic disorders. Altern Ther Health Med. 202 Jan-Feb;8(1):76-9.


CONTEXT: Allergies are the most common immunologic diseases among the general population. Increasing evidence suggests that the incidence of allergic disorders is rising dramatically. Conventional medicine provides only limited relief and does not offer a complete cure to this health problem. Consequently, patients seek additional approaches and therapies to integrate into their healthcare. Homeopathy is one of the leading complementary modalities used to treat this health problem. OBJECTIVE: This preliminary study assessed the effect of integrating homeopathic treatment in allergic diseases on conventional medication consumption in a health maintenance organization. DESIGN: Retrospective outcome study designed as a before-after trial. SETTING: Patients were studied in a complementary medicine clinic affiliated with an Israeli health maintenance organization. PARTICIPANTS: Forty-eight patients were treated for allergic diseases with homeopathic remedies and conventional medications. MAIN OUTCOME MEASURES: A computerized medication chart for each patient was evaluated for conventional medication consumption 3 months before and 3 months after the homeopathic intervention. Each patient served as his or her own control. RESULTS: Fifty-six percent of patients in this study reduced their use of conventional medication following the homeopathic intervention. Patients who used conventional medications for their allergic disorders reduced their medication expense by an average of 60%, with an average savings of $24 per patient in the 3-month period following the homeopathic intervention. CONCLUSIONS: This retrospective outcome study demonstrates cost savings for an Israeli health maintenance organization. The homeopathic intervention led to a modest but significant reduction in the use of medications commonly used to treat allergic conditions and their complications. Larger controlled studies are needed to verify these findings.


4440.   Frew AJ.  Asthma biomarkers and drug trials. J Allergy Clin Immunol. 2002 Feb;109(2):210-3.  No abstract.

4441.   Fritz SB, Singer AM, Revan VB, Baker JR Jr.  Bioterrorism: relevance to allergy and immunology in clinical practice. J Allergy Clin Immunol. 2002 Feb;109(2):214-28. Review.


It has become clear in recent months that the threat of bioterrorism is very real. All physicians need to be aware of the presenting signs and symptoms of the most likely agents. Allergists and immunologists care for a unique population of patients with several alterations of their immune system that might change the expected course of illnesses from biologic terror agents. In this review, we discuss specific bioterrorism agents, focusing on their presentation, pathogenesis, and immunology. In addition, we describe how these illnesses might differ in the population of patients followed by allergists and immunologists.


4442.   Fuji Y, Shima M, Ando M, Adachi M, Tsunetoshi Y. Effect of air pollution and environmental tobacco smoke on serum hyaluronate concentrations in school children. Occup Environ Med. 2002 Feb;59(2):124-8.


OBJECTIVES: To evaluate serum hyaluronate concentrations relative to air pollution, environmental tobacco smoke (ETS), and respiratory health in Japanese school children. METHODS: Respiratory symptoms and serum IgE concentrations were examined in 1037 school children living in four communities in Japan with differing levels of air pollution. Serum hyaluronate concentrations were assayed in 230 children, consisting of all the children who had symptoms of either asthma or wheeze (65 and 50 subjects, respectively) and normal controls adjusted for sex, school grade, and school without these symptoms (115 subjects). RESULTS: Although serum hyaluronate concentrations did not differ for either asthma or wheeze, the concentrations were significantly higher in children living in communities with higher levels of air pollution. Children with asthma or wheeze and those with serum IgE concentrations of 250 IU/ml or above showed differences in hyaluronate concentrations that related to the degree of air pollution in the communities. In children with higher serum IgE concentrations, the hyaluronate concentrations among subjects exposed to ETS were significantly higher than among those without exposure to ETS. CONCLUSIONS: The present results suggest that serum hyaluronate concentration is related to the degree of air pollution and exposure to ETS. Children with asthma or wheeze and children with higher IgE concentrations are considered to be more susceptible to environmental factors.

4443.   Griffith OW. Glutaminase and the control of airway pH: yet another problem for the asthmatic lung? Am J Respir Crit Care Med. 2002 Jan 1;165(1):1-2. Review. No abstract.

4444.   Hadjikoumi I, Loader P, Bracken M, Milner AD. Bronchodilator therapy and hyperactivity in preschool children. Arch Dis Child. 2002 Mar;86(3):202-3.


The common report of parents of asthmatic children that inhaled/nebulised salbutamol causes overactive behaviour was investigated. Nineteen children were assessed in a standardised setting before and after the administration of nebulised salbutamol and placebo. Neither parental report nor observer ratings suggested any significant increase in the child's level of activity.

4445.   Hastie AT, Kraft WK, Nyce KB, Zangrilli JG, Musani AI, Fish JE, Peters SP.Asthmatic epithelial cell proliferation and stimulation of collagen production: human asthmatic epithelial cells stimulate collagen type III production by human lung myofibroblasts after segmental allergen challenge. Am J Respir Crit Care Med. 2002 Jan 15;165(2):266-72.


Epithelial injury and subepithelial collagen deposition are characteristic of asthma. We hypothesized that epithelial cell proliferation increases after airway injury in asthmatics, that epithelial cells stimulate lung myofibroblast collagen production, and that both processes are modulated by allergen-recruited inflammatory cells. Epithelial cells obtained at baseline, 1 d, and 1 and 2 wk after endobronchial allergen challenge from asthmatics and nonasthmatics were placed in culture, with and without bronchoalveolar lavage cells obtained from the same segment. Epithelial cell proliferation and collagen synthesis by human lung myofibroblasts stimulated with culture medium from these epithelial cells were determined. Epithelial proliferation increased (108 +/- 50% above baseline, p = 0.01 for d, and p = 0.004 for group x day interaction) 1 wk postchallenge in cells from asthmatics, but not from nonasthmatics, and required bronchoalveolar lavage cell coculture. Culture medium from epithelium harvested from asthmatics, but not from nonasthmatics, at 1 to 2 wk postchallenge stimulated collagen type III production 50% to 70% (p = 0.043 for clinical group, p = 0.012 for day, and p = 0.022 for group x day interaction), but not collagen type I. This effect was independent of an acute eosinophilic response. We conclude that epithelial cells from asthmatics, but not from nonasthmatics, are stimulated to proliferate after allergen challenge, and over 1 to 2 wk postchallenge, stimulate collagen type III synthesis by lung myofibroblasts. Epithelial cell proliferation appears dependent upon infiltrating inflammatory cells, but stimulation of collagen type III does not.

4446.   Hawrylowicz C, Richards D, Loke TK, Corrigan C, Lee T. A defect in corticosteroid-induced IL-10 production in T lymphocytes from corticosteroid-resistant asthmatic patients. J Allergy Clin Immunol. 2002 Feb;109(2):369-70. No abstract.

4447.   Hogman M, Holmkvist T, Wegener T, Emtner M, Andersson M, Hedenstrom H, Merilainen P. Extended NO analysis applied to patients with COPD, allergic asthma and allergic rhinitis. Respir Med. 2002 Jan;96(1):24-30.


The recommended method to measure exhaled nitric oxide (NO) cannot reveal the source of NO production. We applied a model based on the classical Fick's first law of diffusion to partition NO in the lungs. The aim was to develop a simple and robust solution algorithm with a data quality control feature, and apply it to patients with known alterations in exhaled NO. Subjects with allergic rhinitis, allergic asthma, chronic obstructive pulmonary disease (COPD) smokers and controls were investigated. NO was measured at three expiratory flow rates. An iteration method was developed to partition NO. The airway tissue content of NO was increased in asthma, 144 +/- 80 ppb (P = 0.04) and decreased in smokers, 56 +/- 36 ppb (P = 0.02). There was no difference between subjects with rhinitis, 98 +/- 40 ppb and controls, 98 +/- 44 ppb. The airway transfer rate was increased in allergic asthma and allergic rhinitis, 12 +/- 4 vs. 12 +/- 5 ml sec(-1), compared to controls, 8 +/- 2 ml sec(-1) (P < 0.001). The alveolar levels were no different from controls, 2 +/- 1 ppb. In COPD the alveolar levels were increased, 4 +/- 2 ppb (P < 0.001). Extended NO analysis reveals from where in the respiratory system NO is generated. Hence, this new test can be added to the tools the physician has for the diagnosis and treatment of patients with respiratory disorders.


4448.   Jacoby DB. Virus-induced asthma attacks. JAMA. 2002 Feb 13;287(6):755-61.


Viral respiratory tract infections are a common cause of asthma attacks. Study of this phenomenon has revealed multiple mechanisms and contributed to understanding of the increase in airway inflammation and bronchoconstriction observed in this context. Changes in the neural control of the airways contribute to bronchoconstriction, which is reflected in an increased efficacy of anticholinergic medications during acute asthma attacks. The ability to prevent or treat viral respiratory tract infections is currently limited. However, as more effective antiviral treatments and vaccines become available, such therapies are likely to be effective in patients with asthma. Clinical management of this problem is illustrated in this article by the case of a 40-year-old woman with history of mild asthma who was admitted to an intensive care unit with severe bronchospasm and an upper respiratory tract infection.


4449.   Kelly HW, Bisgaard H. Leukotriene modifiers.Pediatrics. 2002 Jan;109(1):170-1. No abstract.

4450.   Kilpi T, Kero J, Jokinen J, Syrjanen R, Takala AK, Hovi T, Isolauri E. Common respiratory infections early in life may reduce the risk of atopic dermatitis. Clin Infect Dis. 2002 Mar 1;34(5):620-6. No abstract.

4451.   Klemola T, Vanto T, Juntunen-Backman K, Kalimo K, Korpela R, Varjonen E. Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cow's milk allergy: a prospective, randomized study with a follow-up to the age of 2 years. J Pediatr. 2002 Feb;140(2):219-24.


OBJECTIVES: We conducted a prospective, randomized study to evaluate the cumulative incidence of allergy or other adverse reactions to soy formula and to extensively hydrolyzed formula up to the age of 2 years in infants with confirmed cow's milk allergy. STUDY DESIGN: Infants (n = 170) with documented cow's milk allergy were randomly assigned to receive either a soy formula or an extensively hydrolyzed formula. If it was suspected that the formula caused symptoms, a double-blind, placebo-controlled challenge (DBPCFC) with the formula was performed. The children were followed to the age of 2 years, and soy-specific immunoglobulin E antibodies were measured at the time of diagnosis and at the ages of 1 and 2 years. RESULTS: An adverse reaction to the formula was confirmed by challenge in 8 patients (10%; 95% confidence interval, 4.4%-18.8%) randomly assigned to soy formula and in 2 patients (2.2%; 95% confidence interval, 0.3% to 7.8%) randomly assigned to extensively hydrolyzed formula. Adverse reactions to soy were similar in IgE-associated and non-IgE-associated cow's milk allergy (11% and 9%, respectively). IgE to soy was detected in only 2 infants with an adverse reaction to soy. Adverse reactions to soy formula were more common in younger (<6 months) than in older (6 to 12 months) infants (5 of 20 vs 3 of 60, respectively, P =.01). CONCLUSIONS: Soy formula was well tolerated by most infants with IgE-associated and non-IgE-associated cow's milk allergy. Development of IgE-associated allergy to soy was rare. Soy formula can be recommended as a first-choice alternative for infants >or=6 months of age with cow's milk allergy.

4452.   Krishna MT, Salvi SS. BCG vaccination and prevention of allergic disease. Pediatrics. 2002 Feb;109(2):346-7. No abstract.

4453.   Lilly CM, Churg A, Lazarovich M, Pauwels R, Hendeles L, Rosenwasser LJ, Ledford D, Wechsler ME.  Asthma therapies and Churg-Strauss syndrome. J Allergy Clin Immunol. 2002 Jan;109(1):S1-19.


The pulmonary vasculitides are a group of rare but serious disorders that require early recognition, accurate diagnosis, and effective therapy. Churg-Strauss syndrome (CSS) is classified as small vessel vasculitis. Four different definitions for the diagnosis of CSS have been developed: (1) the pathologic criteria put forth by Churg and Strauss, (2) the criteria based on clinical grounds from Lanham and colleagues, (3) the criteria based on clinical grounds from the American College of Rheumatology, and (4) the criteria from the Chapel Hill Consensus Conference, which closely concur with the Churg and Strauss definition. It is apparent that cessation, diminution, or even a switch from low-dose systemic to inhaled corticosteroid therapy can precipitate the appearance of CSS. The term forme fruste has been used to indicate that the signs and symptoms of CSS were (inadvertently) suppressed by cortico-steroids. The clinical risk factors for CSS are moderately severe or severe asthma, chronic sinusitis, or reductions in systemic corticosteroid therapy. Differential diagnosis, treatment, and ongoing monitoring of CSS therapeutic responses are reviewed. The introduction of leukotriene modifiers and high-potency inhaled corticosteroids have allowed control of asthma symptoms, which results in avoidance or reduction in oral corticosteroid use. The advent of these agents has been associated with reports of CSS appearing in patients with asthma. The available data regarding the association of CSS and antiasthma agents are most consistent with the unmasking of a previously contained pathologic condition (forme-fruste CSS) or disease that progresses because systemic corticosteroids were avoided. Early recognition and immunosuppressive therapy are the keystones of successful treatment of this rare disorder.

4454.   Lin YC, Su HJ, Hsiue TR, Lee CH, Chen CW, Guo YL. Levels of house dust mite-specific IgE and cockroach-specific IgE and their association with lower pulmonary function in Taiwanese children. Chest. 2002 Feb;121(2):347-53.


OBJECTIVE: Sensitization to an aeroallergen is known to diminish pulmonary function in young children and adults; however, it remains unclear whether it produces similar effects in adolescents. This study, therefore, examined the relationship between serum allergen-specific IgE levels and pulmonary function in adolescents. DESIGN: Middle-school children were invited for a physician's evaluation and pulmonary function test when not experiencing an asthma attack and for the determination of serum levels of specific IgE to common allergens. SETTING: National Cheng Kung University Hospital, Taiwan. SUBJECTS: Middle-school children in southern Taiwan, who had completed both a nationally administered Chinese version of the International Study of Asthma and Allergies in Childhood questionnaire and a pulmonary function test in October 1996. RESULTS: Forty-two then currently asthmatic children, 38 children with asthma in remission (no reported attack for > 12 months), and 69 children without asthma completed the study. Children with asthma had a significantly lower adjusted forced expiratory flow between 25% and 75% of FVC (FEF(25-75%)) and FEV(1)/FVC than children without asthma. A greater percentage of children with asthma were more sensitized to Dermatophagoides pteronyssinus (Der p), Dermatophagoides farinae (Der f), and German cockroach but not cat dander or dog dander. Children with asthma with Der f-specific IgE > 100 IU/mL, or cockroach-specific IgE > 0.7 IU/mL showed lower pulmonary function. No such association was found in children without asthma. CONCLUSION: Our findings suggest that sensitization to Der f and German cockroach was a critical factor for the lower pulmonary function observed in middle-school children with asthma.


4455.   Loukides S, Bouros D, Papatheodorou G, Panagou P, Siafakas NM.  The relationships among hydrogen peroxide in expired breath condensate, airway inflammation, and asthma severity. Chest. 2002 Feb;121(2):338-46.


STUDY OBJECTIVE: To investigate which cells are the main source of hydrogen peroxide (H(2)O(2)) production in stable patients with asthma and the associations among H(2)O(2) levels, airway inflammation, and disease severity. SETTING: Inpatient respiratory unit and outpatient clinic in tertiary-care hospital. PATIENTS: Fifty stable asthmatic patients with disease severity ranging from mild to moderate. METHODS: H(2)O(2) was measured in expired breath condensate and was correlated with variables expressing both asthma severity (ie, FEV(1) percent predicted, peak expiratory flow rate [PEFR] variability, symptom score, and histamine airways responsiveness) and airway inflammation (ie, differential cell counts from induced sputum and levels of eosinophil cationic protein [ECP]). RESULTS: The mean (95% confidence interval [CI]) concentration of H(2)O(2) was significantly elevated in patients with asthma compared to that in control subjects (mean, 0.67 microM [95% CI, 0.56 to 0.77 microM] vs 0.2 microM [95% CI, 0.16 to 0.24 microM]; p < 0.0001). The difference was primarily due to the elevation of H(2)O(2) in patients with moderate asthma whose expired breath H(2)O(2) level of 0.95 microM (95% CI, 0.76 to 1.12 microM) was significantly higher from that of patients with mild-persistent and mild-intermittent asthma (mean, 0.59 microM [95% CI, 0.47 to 0.7 microM] and 0.27 [95% CI, 0.23 to 0.32 microM], respectively; p < 0.0001). H(2)O(2) concentration was positively related to sputum eosinophilia as well as to ECP concentration. A similar correlation was found between H(2)O(2) and neutrophils in patients with moderate asthma. A positive correlation was observed between H(2)O(2) level, symptom score, and PEFR variability. H(2)O(2) level was negatively related to FEV(1) percent predicted. Further analysis showed that only patients with moderate asthma who were not receiving inhaled steroids were found to have a strong relationship with the variables tested. CONCLUSIONS: Eosinophils are the predominate cells that generate H(2)O(2) in all forms of the disease, while neutrophils might be responsible for the highest levels that are observed in the more severe forms of the disease. The role of H(2)O(2) concentration in predicting the severity of the disease as well as in the inflammatory process is limited and depends on the use of inhaled steroid therapy and the classification of the severity of the disease.


4456.      Loza MJ, Peters SP, Zangrilli JG, Perussia B. Distinction between IL-13+ and IFN-gamma+ natural killer cells and regulation of their pool size by IL-4. Eur J Immunol. 2002 Feb;32(2):413-23.


The hypothesis that distinct subsets of NK cells produce type 2 and type 1 cytokines in resting naive lymphocytes was tested analyzing cytokine production at the single-cell level. Two non-overlapping IL-13+ and IFN-gamma+ subsets were identified in adult and neonatal NK cells. IL-2 maintained their relative proportion. Accumulation of the former was induced by IL-4, but not IL-13, and inhibited by IL-12; that of the latter was induced by IL-12 and inhibited by IL-4 and IL-13. IL-4 induced preferential proliferation of the pre-existing peripheral IL-13+ cells, whereas IL-12 had minimal effect on proliferation of the IFN-gamma+ NK cells. The IL-13+ cells (CD161+ only) are phenotypically distinct from the IFN-gamma+ ones (CD56+) before and after culture under any condition analyzed, and produce IL-13 in response to NK-sensitive target cells and PMA+Ca(2+) ionophore, whereas also FcgammaRIIIA and IL-2+IL-12 stimulate IFN-gamma production. These data define the existence and regulation of two distinct resting peripheral NK cell subsets producing type 1 and type 2 cytokines, and suggest possible roles for IL-13+ NK cells in allergy.


4457.   Martinez FD. Development of wheezing disorders and asthma in preschool children. Pediatrics. 2002 Feb;109(2 Suppl):362-7. Review.


Recent longitudinal studies have shed light on the pathogenesis and progression of asthma. The patterns of expression of childhood asthma that persist into adult life have been explored. Distinct asthma phenotypes (transient wheezing, nonatopic wheezing, and atopy-associated asthma) have been identified. Defining which children are at risk for persistent asthma could allow for better management and, potentially, for reduced morbidity and mortality.

4458.   McConnell R, Berhane K, Gilliland F, London SJ, Islam T, Gauderman WJ, Avol E, Margolis HG, Peters JM. Asthma in exercising children exposed to ozone: a cohort study. Lancet. 2002 Feb 2;359(9304):386-91.


BACKGROUND: Little is known about the effect of exposure to air pollution during exercise or time spent outdoors on the development of asthma. We investigated the relation between newly-diagnosed asthma and team sports in a cohort of children exposed to different concentrations and mixtures of air pollutants. METHODS: 3535 children with no history of asthma were recruited from schools in 12 communities in southern California and were followed up for up to 5 years. 265 children reported a new diagnosis of asthma during follow-up. We assessed risk of asthma in children playing team sports at study entry in six communities with high daytime ozone concentrations, six with lower concentrations, and in communities with high or low concentrations of nitrogen dioxide, particulate matter, and inorganic-acid vapour. FINDINGS: In communities with high ozone concentrations, the relative risk of developing asthma in children playing three or more sports was 3.3 (95% CI 1.9-5.8), compared with children playing no sports. Sports had no effect in areas of low ozone concentration (0.8, 0.4-1.6). Time spent outside was associated with a higher incidence of asthma in areas of high ozone (1.4, 1.0-2.1), but not in areas of low ozone. Exposure to pollutants other than ozone did not alter the effect of team sports. INTERPRETATION: Incidence of new diagnoses of asthma is associated with heavy exercise in communities with high concentrations of ozone, thus, air pollution and outdoor exercise could contribute to the development of asthma in children.

4459.   McKeever TM, Lewis SA, Smith C, Collins J, Heatlie H, Frischer M, Hubbard R. Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database. J Allergy Clin Immunol. 2002 Jan;109(1):43-50.


BACKGROUND: It has been suggested that the rise in prevalence of allergic disease in westernized countries is due in part to a decrease in exposure to infections and an increase in the use of antibiotics early in life. OBJECTIVE: The purpose of this investigation was to quantify the relationships between (1) exposure to personal infections, infections in siblings, and use of antibiotics in early life and (2) the incidence of allergic disease. METHODS: Using the West Midlands section of the UK General Practice Research Database, we established a historical birth cohort of children (N = 29,238). For each child, we identified all personal infections and infections in siblings and determined the use of antibiotics in early life; we also noted incident diagnoses of asthma, eczema, and hay fever. The data were analyzed through use of Cox regression. RESULTS: There was no clear protective effect of exposure to either personal infections or infections in siblings with respect to the incidence of allergic disease. Antibiotic exposure was associated with an increased risk of developing allergic disease in a dose-related manner: having 4 or more courses of antibiotics in the first year of life was associated with an increased incidence of asthma (hazard ratio [HR], 3.13; 95% CI, 2.75-3.57), eczema (HR, 1.48; 95% CI, 1.31-1.68), and hay fever (HR, 2.12; 95% CI, 1.68-2.66). However, adjusting for consulting behavior reduced these effects (adjusted HR [95% CI]: asthma, 1.99 [1.72-2.31]; eczema, 1.01 [0.88-1.17]; hay fever, 1.14 [0.88-1.47]). CONCLUSIONS: We found no evidence that exposure to infections reduced the incidence of allergic disease, and infections did not explain the previous findings of a strong birth order effect in this cohort. The use of antibiotics might be associated with early diagnoses of allergic disease.

4460.   Moira CY, Ferguson A, Dimich-Ward H, Watson W, Manfreda J, Becker A. Effectiveness of and compliance to intervention measures in reducing house dust and cat allergen levels. Ann Allergy Asthma Immunol. 2002 Jan;88(1):52-8.


BACKGROUND: Allergic sensitization is a major risk factor in asthma. OBJECTIVE: To evaluate the effectiveness of and compliance to intervention measures in reducing levels of house-dust mite and cat allergen in the context of a randomized, controlled study in the primary prevention of asthma. METHODS: A total of 545 high-risk families were recruited prenatally and randomly assigned into the intervention group (n = 278) and the control group (n = 267). Intervention measures were instituted before birth of the infants and maintained for 12 months afterward in the intervention group and the control group received the usual care from their family physician. Dust samples were collected at six sites in the homes before birth and at specific intervals up to 24 months after birth for analysis of allergens. At 24 months, there were 244 families in the intervention group and 228 in the control group available for followup examination. RESULTS: House-dust mite avoidance measures, consisting of encasement of mattresses, pillows, and duvets, and hot-water washing of bedding were effective in reducing mite allergen in parents' mattresses to one-third from baseline, significantly lower than the control group, even at 24 months. The use of an acaricide did not reduce mite allergen levels in carpets and upholstered furniture. Seventeen intervention families gave up their cats but six families acquired a new one over a period of 24 months, similar to control families. Cat allergen levels decreased in all sites in the homes of those who removed the cat, similar in both groups. CONCLUSIONS: House-dust mite avoidance measures were effective in reducing house-dust mite allergen in mattresses, but not on floors. Reduction in cat allergen levels were evident for those families who got rid of their cats, but the advice to remove pets was not adhered to by most families.


4461.   Moller C, Dreborg S, Ferdousi HA, Halken S, Host A, Jacobsen L, Koivikko A, Koller DY, Niggemann B, Norberg LA, Urbanek R, Valovirta E, Wahn U.  Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study). J Allergy Clin Immunol. 2002 Feb;109(2):251-6.


BACKGROUND: Children with allergic rhinitis are likely to develop asthma. OBJECTIVE: The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis. METHODS: From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean age, 10.7 years) with grass and/or birch pollen allergy but without any other clinically important allergy were randomized either to receive specific immunotherapy for 3 years or to an open control group. All subjects had moderate to severe hay fever symptoms, but at inclusion none reported asthma with need of daily treatment. Symptomatic treatment was limited to loratadine, levocabastine, sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by peak flow. Methacholine bronchial provocation tests were carried out during the season(s) and during the winter. RESULTS: Before the start of immunotherapy, 20% of the children had mild asthma symptoms during the pollen season(s). Among those without asthma, the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P <.05). Methacholine bronchial provocation test results improved significant in the active group (P <.05). CONCLUSION: Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis.


4462.   Orr WC. Sleep-related breathing disorders: is it all about apnea? Chest. 2002 Jan;121(1):8-11. No abstract.

4463.   Paredi P, Kharitonov SA, Barnes PJ. Faster rise of exhaled breath temperature in asthma: a novel marker of airway inflammation? Am J Respir Crit Care Med. 2002 Jan 15;165(2):181-4.


In asthma there is increased vascularity of the airway mucosa, altering heat loss in the airways. We hypothesized that as a result of these inflammatory changes, asthmatic patients would have elevated rates of the exhaled air temperature increase (Deltae degrees T). We measured Deltae degrees T in 18 asthmatic subjects (mean age +/- SEM, 38 +/- 8 yr; 9 male, FEV(1) 74 +/- 10%) and 16 normal volunteers (mean age +/- SEM, 33 +/- 3 yr) and compared it with exhaled nitric oxide (NO) as a marker of inflammation. Deltae degrees T was measured during a flow- and pressure-controlled single exhalation with a fast response (1 ms) thermometer. The end-expiratory plateau temperature was similar in asthmatic compared with normal subjects (35.75 +/- 0.6 degrees C and 34.45 +/- 0.8 degrees C, p > 0.05). However, Deltae degrees T was greater in asthmatic subjects (8.17 +/- 0.83 degrees C/s and 4.12 +/- 0.41 degrees C/s, p < 0.01) and correlated with NO (r = 0.65, p = 0.034). Deltae degrees T was increased in normal subjects (from 4.28 +/- 0.8 degrees C/s to 7.60 +/- 0.5 degrees C/s, p < 0.01) but not in asthmatic patients (from 8.28 +/- 0.41 degrees C/s to 8.80 +/- 0.41 degrees C/s, p > 0.05) after the inhalation of albuterol, indicating that Deltae degrees T may reflect bronchial blood flow. Asthmatic subjects have elevated Deltae degrees T. This may represent a novel, noninvasive means of measuring airway blood flow and inflammation in asthma.

4464.   Pelaia G, Gallelli L, Vatrella A, Grembiale RD, Maselli R, De Sarro GB, Marsico SA. Potential role of potassium channel openers in the treatment of asthma and chronic obstructive pulmonary disease. Life Sci. 2002 Jan 18;70(9):977-90. Review.


Airway smooth muscle (ASM) cells express various types of potassium (K+) channels which play a key role in determining the resting membrane potential, a relative electrical stability and the responsiveness to both contractile and relaxant agents. In addition, K+ channels are also involved in modulation of neurotransmitter release from airway nerves. The most important K+ channels identified in airways include large and small Ca2+-activated, delayed-rectifier, and ATP-sensitive channels. These K+ channels are structurally and functionally different, thus playing distinct roles in airway electrophysiology and pharmacology. Many in vitro and in vivo studies, performed in both animals and humans, have shown that K+ channel openers are able to induce hyperpolarization of ASM cells, bronchodilation, suppression of airway hyperresponsiveness (AHR), and inhibition of neural reflexes. Therefore, airway K+ channels represent a suitable pharmacological target for the development of new effective therapeutic options in the treatment of asthma and chronic obstructive pulmonary disease (COPD).


4465.   Rhodes HL, Thomas P, Sporik R, Holgate ST, Cogswell JJ. A birth cohort study of subjects at risk of atopy: twenty-two-year follow-up of wheeze and atopic status. Am J Respir Crit Care Med. 2002 Jan 15;165(2):176-80.


This study describes the natural history of atopic and wheezy disorders from birth to adult life in a cohort at risk of atopy. One hundred subjects born in Poole, England, were selected at birth in 1976 on the basis that at least one parent was atopic. Subjects were examined annually in the preschool years, and at the ages of 11 and 22 yr. Skin prick tests and total serum immunoglobulin E (IgE) were performed at each visit, and at 11 and 22 yr, bronchial hyperresponsiveness (BHR) to inhaled histamine was measured. Sixty-three subjects remained on follow-up at 22 yr. The annual prevalence of both wheeze and atopy increased with age. Twenty-five percent of adults showed both wheeze and BHR (asthma). Remission of wheeze was common in subjects younger than 5 yr of age and likely if wheezing occurred on less than two occasions, but wheeze at 11 yr was likely to persist. Sixty percent of the adult subjects with asthma developed sensitivity to common allergens by the age of 2 yr and were showing BHR by mid-childhood. Sensitization to dietary allergens occurred in infancy and waned after early childhood but predicted the early sensitization to inhalant allergens. In conclusion, adults with asthma can begin wheezing at any age but tend to sensitize early and have abnormal airway characteristics by the age of 11 yr.

4466.   Schapowal A. Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis. BMJ. 2002 Jan 19;324(7330):144-6.


OBJECTIVES: To compare the efficacy and tolerability of butterbur (Petasites hybridus) with cetirizine in patients with seasonal allergic rhinitis (hay fever). DESIGN: Randomised, double blind, parallel group comparison. SETTING: Four outpatient general medicine and allergy clinics in Switzerland and Germany. PARTICIPANTS: 131 patients were screened for seasonal allergic rhinitis and 125 patients were randomised (butterbur 61; cetirizine 64). INTERVENTIONS: Butterbur (carbon dioxide extract tablets, ZE 339) one tablet, four times daily, or cetirizine, one tablet in the evening, both given for two consecutive weeks. MAIN OUTCOME MEASURES: Scores on SF-36 questionnaire and clinical global impression scale. RESULTS: Improvement in SF-36 score was similar in the two treatment groups for all items tested hierarchically. Butterbur and cetirizine were also similarly effective with regard to global improvement scores on the clinical global impression scale (median score 3 in both groups). Both treatments were well tolerated. In the cetirizine group, two thirds (8/12) of reported adverse events were associated with sedative effects (drowsiness and fatigue) despite the drug being considered a non-sedating antihistamine. CONCLUSIONS: The effects of butterbur are similar to those of cetirizine in patients with seasonal allergic rhinitis when evaluated blindly by patients and doctors. Butterbur should be considered for treating seasonal allergic rhinitis when the sedative effects of antihistamines need to be avoided.


4467.   Singh D, Arora V, Sobti PC. Chronic/recurrent cough in rural children in Ludhiana, Punjab. Indian Pediatr. 2002 Jan;39(1):23-9.


OBJECTIVE: To determine the prevalence, age distribution and common causes of chronic/recurrent cough in rural children. DESIGN: Prospective study. SETTING: Pediatric population in five villages of Dehlon Block of Ludhiana, Punjab. METHODS: 2275 children in the age group of 1 to 15 years were screened by house to house survey for chronic/recurrent cough using defined criteria. A detailed work up of selected cases was carried out. Underlying etiology was determined using clinical and laboratory parameters. Five hundred children in the study population formed the control group. Variables associated with chronic/recurrent cough were analyzed in cases and controls. RESULTS: Twenty four children were diagnosed with chronic/recurrent cough showing a prevalence rate of 1.06 percent. The most common cause was bronchial asthma (66.7 percent) followed by postnasal drip syndrome (25 percent). Family history of allergy/asthma was noted in 11 (45.8 percent) children as compared to 52 (10.4 percent) in the control group (p < 0.01). Family history of smoking was recorded in 16.7 percent of cases in contrast to 6.4 percent in controls (p = 0.05). There was no significant association with overcrowding, pets and kind of cooking fuel used. CONCLUSIONS: The most common cause of chronic/recurrent cough was bronchial asthma. There was a significant association with family history of allergy/asthma and smoking.

4468.   Stelmach I, Jerzynska J, Kuna P. A randomized, double-blind trial of the effect of treatment with montelukast on bronchial hyperresponsiveness and serum eosinophilic cationic protein (ECP), soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion molecule 1 (sICAM-1) in children with asthma. J Allergy Clin Immunol. 2002 Feb;109(2):257-63.


BACKGROUND: Anti-inflammatory properties of leukotriene modifiers and their effect on bronchial hyperresponsiveness have not been studied in children with asthma. OBJECTIVE: The primary objective of this study was to determine the changes in serum levels of inflammatory mediators, clinical efficacy, and bronchial hyperresponsiveness after treatment with montelukast. METHODS: In this double-blind, randomized, placebo-controlled trial, 39 children with mild-to-moderate atopic asthma were randomly allocated to receive montelukast or placebo for 6 weeks. Main outcome measures were changes in serum concentrations of soluble interleukin 2 receptor (sIL-2R), IL-4, and soluble intercellular adhesion molecule 1 (sICAM-1); peripheral blood eosinophil count; and eosinophilic cationic protein (ECP). Asthma severity score, FEV(1), and bronchial hyperreactivity (BHR) for histamine were secondary end points. RESULTS: Compared to placebo, serum concentrations of IL-4, sICAM-1, and ECP and eosinophil blood counts significantly decreased after 6 weeks of treatment with montelukast. Montelukast significantly improved asthma control and FEV(1). Montelukast resulted in within-group significant decrease in levels of serum sIL-2R (611 vs. 483 pg/mL), IL-4 (0.123 vs 0.102 pg/mL), sICAM-1 (280 vs. 244 ng/mL), and ECP (74 vs. 59 microg/mL) and in eosinophil blood counts (349 vs. 310 cells/mm(3)). Mean FEV(1) value changed from 85% of predicted to 95% (P <.001) and for histamine (PC(20)H) from 2.8 mg/mL to 3.8 mg/mL (P <.001) after treatment with montelukast. There was no significant difference between montelukast and placebo recipients in the serum concentrations of sIL-2R and PC(20)H after treatment. CONCLUSION: Montelukast provides clinical benefit to patients with chronic asthma and decreases bronchial hyperresponsiveness. Montelukast caused a statistically significant decrease of serum concentrations in cytokine, ICAM-1, and ECP and peripheral blood eosinophil counts over the 6-week treatment period. This observation raises the possibility that leukotriene receptor antagonists, such as montelukast, may have effects on parameters of asthmatic inflammation.

4469.   Stevens CA, Wesseldine LJ, Couriel JM, Dyer AJ, Osman LM, Silverman M.  Parental education and guided self-management of asthma and wheezing in the pre-school child: a randomised controlled trial. Thorax. 2002 Jan;57(1):39-44.


BACKGROUND: The effects on morbidity were examined of providing an educational intervention and a written guided self-management plan to the parents of pre-school children following a recent attendance at hospital for asthma or wheeze. METHODS: A prospective, randomised, partially blinded, controlled trial was designed at two secondary care centres. Over a 13 month period 200 children aged 18 months to 5 years at the time of admission to a children's ward or attendance at an accident and emergency department or children's (emergency) assessment unit (A&E/CAU) with a primary diagnosis of acute severe asthma or wheezing were recruited. 101 children were randomised into the control group and received usual care and 99 were assigned to the intervention group and received: (1) a pre-school asthma booklet; (2) a written guided self-management plan; and (3) two 20 minute structured educational sessions between a specialist respiratory nurse and the parent(s) and child. Subjects were assessed at 3, 6, and 12 months. The main outcomes were GP consultation rates, hospital re-admissions, and attendances at A&E/CAU. Secondary outcomes included disability score, caregivers' quality of life, and parental knowledge of asthma. RESULTS: There were no statistically significant differences between the two groups during the 12 month follow up period for any of the main or secondary outcome measures. CONCLUSIONS: These results do not support the hypothesis that the introduction of an educational package and a written guided self-management plan to the parents of pre-school children with asthma who had recently attended hospital for troublesome asthma or wheeze reduces morbidity over the subsequent 12 months.

4470.   Suri JC, Sen MK, Chakrabarti S, Mehta C. Vocal cord dysfunction presenting as refractory asthma. Indian J Chest Dis Allied Sci. 2002 Jan-Mar;44(1):49-52.


Vocal cord dysfunction is a rare variety of upper airway obstruction characterized by typical laryngoscopic features and may mimic an acute asthma attack. The case presented in this report pertains to a 15-year-old girl who had repeated acute episodes of dyspnoea and wheezing and remained non-responsive to corticosteroids and inhaled bronchodilators requiring endotracheal intubations for adequate control. Laryngoscopic findings were consistent with vocal cord dysfunction. She was treated with a tracheostomy and psychological support.

4471.   Timonen KL, Pekkanen J, Tiittanen P, Salonen RO. Effects of air pollution on changes in lung function induced by exercise in children with chronic respiratory symptoms. Occup Environ Med. 2002 Feb;59(2):129-34.


OBJECTIVE: To investigate how daily variations in ambient air pollution, especially in particles, during the cold of winter affect repeated measurements of baseline lung function and exercise induced bronchial responsiveness among primary school children with chronic respiratory symptoms. METHODS: During alternate school weeks (maximum five) from February to April 1994, 33 children took part in exercise challenge tests (n=141 tests). The exercise challenges were conducted outdoors in a school yard in the centre of Kuopio, Finland. Spirometric lung functions were measured indoors before the exercise, and 3 and 10 minutes after. Daily mean concentrations of PM(10), black smoke (BS), NO(2), CO, SO(2), and particle size and numbers were monitored at a nearby fixed monitoring site. RESULTS: Daily variations in ambient air pollution were not associated with enhanced bronchial responsiveness. However, increased concentrations of BS, PM(10), particle numbers, NO(2), and CO were consistently associated with an impairment of baseline lung functions. The reductions in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV(1)) were 0.5% and 0.6%, respectively, for each 10 microg/m(3) increase in BS (lag 2). CONCLUSION: Particles derived from combustion affect baseline lung function rather than bronchial responsiveness among children with chronic respiratory symptoms.

4472.   Tinghino R, Twardosz A, Barletta B, Puggioni EM, Iacovacci P, Butteroni C, Afferni C, Mari A, Hayek B, Di Felice G, Focke M, Westritschnig K, Valenta R, Pini C.  Molecular, structural, and immunologic relationships between different families of recombinant calcium-binding pollen allergens. J Allergy Clin Immunol. 2002 Feb;109(2):314-20.


BACKGROUND: Calcium-binding plant allergens can be grouped in different families according to the number of calcium-binding domains (EF hands). OBJECTIVE: We sought to identify pollens containing crossreactive calcium-binding allergens and to investigate structural and immunologic similarities of members belonging to different families of calcium-binding allergens. METHODS: By means of multiple sequence alignment and molecular modeling, we searched for structural similarities among pollen allergens with 2 (Phl p 7, timothy grass; Aln g 4, alder), 3 (Bet v 3, birch) and 4 EF hands (Jun o 4, prickly juniper). Purified recombinant Aln g 4 and Jun o 4 were used to determine the prevalence of IgE recognition in 210 patients sensitized to different pollens and to search, by means of ELISA competition, for the presence of cross-reactive epitopes in pollens from 16 unrelated plant species. IgE cross-reactivity among the allergen families was studied with purified rPhl p 7, rAln g 4, rBet v 3, and rJun o 4 and 2 synthetic peptides comprising the N-terminal and C-terminal EF hands of Phl p 7 by means of ELISA competition. RESULTS: Structural similarities were found by using molecular modeling among the allergens with 2, 3, and 4 EF hands. Pollens from 16 unrelated plants contained Aln g 4- and Jun o 4-related epitopes. Twenty-two percent of the patients with multiple pollen sensitization reacted to at least one of the calcium-binding allergens. A hierarchy of IgE cross-reactivity (rPhl p7 > rAln g 4 > rJun o 4 > rBet v 3) could be established that identified rPhl p 7 as the EF-hand allergen containing most IgE epitopes in the population studied. CONCLUSION: The demonstration that members of different families of calcium-binding plant allergens share similarities suggests that it may be possible to use representative molecules for the diagnosis and therapy of allergies to EF-hand allergens.

4473.   Toda M, Tulic MK, Levitt RC, Hamid Q.  A calcium-activated chloride channel (HCLCA1) is strongly related to IL-9 expression and mucus production in bronchial epithelium of patients with asthma. J Allergy Clin Immunol. 2002 Feb;109(2):246-50.


BACKGROUND: One of the cardinal features of airway remodeling in asthma is mucus gland hyperplasia and mucus overproduction and hypersecretion. Recently, a calcium-activated chloride channel, HCLCA1, was described that is upregulated by IL-9 and thought to regulate the expression of soluble gel-forming mucins, such as MUC5A/C, a critical component of mucus in the airways. OBJECTIVE: We sought to examine the expression of HCLCA1 in bronchial biopsy specimens of asthmatic subjects compared with those of control subjects and to demonstrate its relationship with IL-9, IL-9 receptor (IL-9R), and markers of mucus production. METHODS: Bronchial biopsy specimens from asthmatic (n = 9) and control (n = 10) subjects were stained with periodic acid-Schiff to identify mucus glycoconjugates. IL-9- and IL-9R-positive cells were identified with immunocytochemistry, and HCLCA1 expression was detected by means of in situ hybridization with cRNA probes. RESULTS: We demonstrate significant increases in IL-9 (P <.001) and IL-9R (P <.05) immunoreactivity, as well as increased expression of HCLCA1 mRNA (P <.001), in the epithelium of asthmatic patients compared with that found in control subjects. There was also an increase in the number of mucusproducing cells in biopsy specimens from asthmatic subjects (P <.001). HCLCA1 mRNA was strongly and selectively colocalized with periodic acid-Schiff and IL-9R-positive epithelial cells. In particular, a strong positive correlation was observed between HCLCA1 mRNA expression and IL-9-positive (r = 0.69, P < 0.01) or IL9R-positive (r = 0.79, P <.01) cells. CONCLUSION: An upregulation of HCLCA1 in the IL-9- responsive mucus-producing epithelium of asthmatic subjects compared with that seen in control subjects supports the hypothesis that this channel may be responsible, in part, for the overproduction of mucus in asthmatic subjects. These preliminary findings suggest the inhibition of HCLCA1 may be an important new therapeutic approach to control mucus overproduction in chronic airway disorders.

4474.   Van der Wouden JC, Bueving HJ, Bernsen RM. Influenza vaccine and asthma.  J Pediatr. 2002 Feb;140(2):278-9.  No abstract.

4475.   Venis S. Transcription factor shown to have a role in triggering asthma. Lancet. 2002 Jan 12;359(9301):138. No abstract.

4476.   Vercelli D. The functional genomics of CD14 and its role in IgE responses: an integrated view. J Allergy Clin Immunol. 2002 Jan;109(1):14-21. No abstract.

4477.   Wachholz PA, Nouri-Aria KT, Wilson DR, Walker SM, Verhoef A, Till SJ, Durham SR. Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1:Th2 cytokine ratios. Immunology. 2002 Jan;105(1):56-62.


Grass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood. We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after immunotherapy. In a double-blind trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of immunotherapy. Placebo-treated patients showed a seasonal increase in CD3(+) T cells (P = 0.02) and in interleukin-5 (IL-5) mRNA(+) cells (P = 0.03) and no change in interferon-gamma (IFN-gamma ) mRNA(+) cells (P = 0.2) in the nasal mucosa. In contrast, in the immunotherapy-treated group, there were no changes in the number of CD3(+) T cells (P = 0.3) and IL-5 mRNA+ cells (P = 0.2) but a significant increase in the number of IFN-gamma mRNA(+) cells (P = 0.03). Furthermore, clinical improvement in the immunotherapy-treated group was accompanied by a seasonal increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P = 0.03). In contrast, there were no significant changes in peripheral T-cell proliferative responses or cytokine production for IFN-gamma or IL-5 in response to grass pollen either within or between the two treatment groups. We conclude that successful grass pollen immunotherapy was associated with an increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these changes were not reflected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment.

4478.   Weber RW. Atopic persons sensitive to cat dander. Ann Allergy Asthma Immunol. 2002 Jan;88(1):A4.  No abstract.

4479.   Woods RK, Thien F. Polyunsaturated fats and asthma. Thorax. 2002 Jan;57(1):94. No abstract.

4480.   Zanen P. PC(20) adenosine 5'-monophosphate is more closely associated with airway inflammation in asthma than PC(20) methacholine. Am J Respir Crit Care Med. 2002 Mar 1;165(5):730.  No abstract.



Oct 2002

5045.   Adams RJ, Fuhlbrigge AL, Finkelstein JA, Weiss ST. Intranasal steroids and the risk  of emergency department visits for asthma. J Allergy Clin Immunol. 2002 Apr;109(4):636-42.
BACKGROUND: In patients with asthma, treatment for associated conditions, such as rhinitis, is recommended. It is unknown whether this treatment can reduce the risk for emergency department (ED) visits for asthma. OBJECTIVES: We sought to determine whether treatment with intranasal steroids or prescription antihistamines in persons with asthma is associated with a reduced risk for ED visits caused by asthma. METHODS: We performed a retrospective cohort study of members of a managed care organization aged greater than 5 years who were identified during the period of October 1991 to September 1994 as having a diagnosis of asthma by using a computerized medical record system. The main outcome measure was an ED visit for asthma. RESULTS: Of the 13,844 eligible persons, 1031 (7.4%) had an ED visit for asthma. The overall relative risk (RR) for an ED visit among those who received intranasal corticosteroids, adjusted for age, sex, frequency of orally inhaled corticosteroid and beta-agonist dispensing, amount and type of ambulatory care for asthma, and diagnosis of an upper airways condition (rhinitis, sinusitis, or otitis media), was 0.7 (95% confidence interval [CI], 0.59-0.94). For those receiving prescription antihistamines, the risk was indeterminate (RR, 0.9; 95% CI, 0.78-1.11). When different rates of dispensing for intranasal steroids were examined, a reduced risk was seen in ED visits in those with greater than 0 to 1 (RR, 0.7; 95% CI, 0.57-0.99) and greater than 3 (RR, 0.5; 95% CI, 0.23-1.05) dispensed prescriptions per year. CONCLUSIONS: Treatment of nasal conditions, particularly with intranasal steroids, confers significant protection against exacerbations of asthma leading to ED visits for asthma. These results support the use of intranasal steroids by individuals with asthma and upper airways conditions.

5046.   Agarwal S, Gawkrodger DJ. Occupational allergic contact dermatitis to silver and colophonium in a jeweler. Am J Contact Dermat. 2002 Jun;13(2):74.


The aim of this study was to determine any occupationally relevant allergic contact sensitizations in hand dermatitis in a jeweler. Patch test with European Standard, vehicle, medicaments, and metal series (Finn chambers on Scanpor) was performed. Readings were taken on day 2 and day 4. Allergic positive reaction to colophonium 20% pet and silver nitrate 0.5% aq was detected. The contact sensitivities to silver and colophonium seem to be occupationally relevant in this case. Copyright 2002, Elsevier Science (USA). All rights reserved.

5047.   Al-Mobeireek A, Alamoudi O. Allergic bronchopulmonary aspergillosis mimicking pulmonary tuberculosis. Saudi Med J. 2002 Apr;23(4):476; discussion 476.  No abstract.

5048.   Amirav I, Newhouse MT. Treatment failures in children with asthma due to inappropriate use of Turbuhaler. J Pediatr. 2002 Apr;140(4):483. No abstract.

5049.   Baima B, Sticherling M. How specific is the TUNEL reaction? An account of a histochemical study on human skin. Am J Dermatopathol. 2002 Apr;24(2):130-4.


The TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) technique has been described as sensitive method of labeling apoptotic nuclei in tissues, which preferentially stains apoptotic strand breaks. In the current study, three commercially available TUNEL kits for paraffin-embedded and cryostat tissues were tested to optimize this method for the studies on human skin. The investigation included normal skin (n = 10), atopic eczema (n = 4), basal cell carcinoma (n = 5), and lupus erythematosus (LE) (n = 31) sections. Additionally, the expression of certain apoptotic markers (Fas antigen and Bcl-2 protein) was studied immunohistologically on normal and LE skin. During TUNEL labeling according to the manufacturers' protocols, abnormally high background and nonspecific staining were found in all skin sections. The manipulation with the pretreatment time and, in particular, the introduction of an additional step (terminating the labeling reaction by inhibiting the terminal deoxynucleotidyl transferase activity) in two kits led to a remarkable improvement in their performance. The conclusions are that it is generally difficult to establish a functionally specific TUNEL technique for skin sections and that the choice of a kit is absolutely crucial for obtaining reliable results. Considering the extent to which the apoptosis research has been carried out recently, it is advisable to remain critical in evaluating the results. Further, it is necessary to combine the TUNEL technique with the investigation of other apoptotic markers.

5050.   Bassiri S, Cohen DE. Bilateral palmar dermatitis. Am J Contact Dermat. 2002 Jun;13(2):75-6.  No abstract.

5051.   Beigelman-Aubry C, Capderou A, Grenier PA, Straus C, Becquemin MH, Similowski T, Zelter M.  Mild intermittent asthma: CT assessment of bronchial cross-sectional area and lung attenuation at controlled lung volume. Radiology. 2002 Apr;223(1):181-7.


PURPOSE: To evaluate, with thin-section computed tomography (CT), changes in bronchial cross-sectional area and lung attenuation induced by bronchial stimulation in patients with mild intermittent asthma, at a given lung volume monitored with pneumotachography. MATERIALS AND METHODS: Twelve patients with mild intermittent asthma who were nonsmokers (National Institutes of Health staging) and six nonsmoking healthy volunteers, age and sex ratio-matched, were examined by using helical thin-collimation CT at the level of basal bronchi at 65% of total lung capacity. Three sets of acquisitions were obtained: at baseline and after inhalation of methacholine and then salbutamol. Cross-sectional areas of bronchi greater than 4 mm(2) were segmented and calculated from CT images. Lung attenuation was measured in the anterior, lateral, and posterior areas of the right lung parenchyma. Gas trapping was evaluated by using thin-section CT at residual volume in six of the patients with asthma. Statistical analysis included two factors repeated-measurement analysis of variance and Mann-Whitney and Kruskal-Wallis nonparametric tests. RESULTS: Bronchial cross-sectional areas and lung attenuation did not vary significantly compared with baseline values following bronchial challenge in healthy volunteers or patients with asthma. However, in patients with asthma, bronchial cross-sectional areas were significantly smaller than in healthy volunteers, except after inhalation of salbutamol. Lung attenuation and anteroposterior attenuation gradient were significantly higher in patients with asthma than in healthy patients (P <.001). Air-trapping scores were significantly higher after methacholine challenge. CONCLUSION: Helical thin-collimation CT at controlled lung volume and at full expiration associated with bronchial challenge may help evaluate bronchoreactivity and inflammation in mild intermittent asthma.

5052.   Bensch GW, Nelson HS, Borish LC. Evaluation of cytokines in nasal secretions after nasal antigen challenge: lack of influence of antihistamines. Ann Allergy Asthma Immunol. 2002 May;88(5):457-62.


BACKGROUND: Previous studies of inflammation in allergic rhinitis using nasal irrication have been unsatisfactory because of 1) poor reproducibility; 2) the tendency of irrigation to overdilute mediators; and 3) the failure of this technique to evaluate interstitial concentrations of relevant mediators. For this study we used filter paper as a matrix to collect nasal secretions in patients undergoing nasal antigen challenge. OBJECTIVE: To evaluate inflammatory mediators of allergen-induced rhinitis during a clinical trial of fexofenadine. METHODS: Subjects evaluated at a referral medical center were placed on traditional dosing of fexofenadine at 60 mg, twice daily, or placebo in a double-blind, crossover fashion for 1 week before the nasal challenge. Nasal challenge was performed with nasal insufflation of either 1,000 AU timothy or 0.1 mL ragweed (1:100 wt/vol) extract outside the pollen season. Nasal secretions were collected at baseline and then at 2, 4, and 6 hours after nasal challenge. Secretions were evaluated for expression of the cellular adhesion molecule-1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-10, macrophage inflammatory protein (MIP)-1alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) using commercially available enzyme-linked immunoadsorbent assay kits. Patients' symptom scores were evaluated during the nasal challenge. RESULTS: Significantly (P < 0.05) increased peak levels of TNF-alpha, IL-4, IL-10, and MIP-1alpha were detected after antigen challenge as compared with baseline levels. There was a nonsignificant trend toward an increase in GM-CSF after antigen challenge (P = 0.07). There was no difference in the peak levels of TNF-alpha, IL-4, IL-10, MIP-1alpha, or GM-CSF measured when patients were on fexofenadine versus placebo. Finally, there were no significant differences in patients' symptom scores during antigen challenge when subjects were on fexofenadine versus placebo. CONCLUSIONS: Collection of nasal secretions using a filter paper matrix provides a reproducible model for accurately detecting and evaluating changes in cytokine levels after nasal challenge. Cytokine levels tend to peak 3 to 4 hours after antigen challenge. Standard doses of fexofenadine do not seem to have a mitigating effect on the production of these cytokines. Symptoms of allergic rhinitis using this type of antigen challenge did not differ from treatment with fexofenadine versus placebo.

5053.   Bonnans C, Vachier I, Chavis C, Godard P, Bousquet J, Chanez P. Lipoxins are potential endogenous antiinflammatory mediators in asthma. Am J Respir Crit Care Med. 2002 Jun 1;165(11):1531-5.


Lipoxins, endogenous eicosanoids biosynthetized in vivo at inflammation sites, are potential antiinflammatory mediators. Subjects with severe asthma present chronic inflammation of the airways despite long-term treatment with oral glucocorticoids. Therefore it is of interest to investigate the potential antiinflammatory effects of lipoxin A4 (LXA4) and lipoxin B4 (LXB4) that could attenuate chronic inflammation. In a first time, we detected interleukin (IL)-8 and LXA4 in supernatants of induced sputum. IL-8 was heightened in severe asthma (p = 0.001), whereas high concentrations of lipoxin A4 were present in mild asthma (p = 0.001). We then studied the effects of LXA4 on IL-8 released in vitro. Nanomolar concentrations of LXA4 and LXB4 inhibited the IL-8 released by peripheral blood mononuclear cells from the two groups of patients with asthma: a maximal inhibition of 29.4% (p < 0.01) was observed for patients with mild asthma, and 41.5% inhibition (p < 0.001) for patients with severe asthma at 1 nM and 100 nM LXA4 concentrations, respectively. Polymerase chain reaction analysis indicated that peripheral blood mononuclear cells from patients with asthma expressed the LXA4 receptor mRNA. Moreover, pertussis toxin reversed LXA4- and LXB4-inhibited IL-8 release. These findings suggest that lipoxins have potential antiinflammatory action in asthma.


5054.   Borish L.  Endothelin-1: a useful marker for asthmatic inflammation? Ann Allergy Asthma Immunol. 2002 Apr;88(4):345-6. No abstract.

5055.   Borrish L. Sinusitis and asthma: entering the realm of evidence-based medicine. J Allergy Clin Immunol. 2002 Apr;109(4):606-8. No abstract.

5056.   Burford JC.  Sensitivity to UV-cured inks used in bank notes. Australas J Dermatol. 2002 May;43(2):153-4. No abstract.

5057.   Buzzetti R, D'Amico R, Addis A. New drug treatment for asthma: clinical versus statistical significance. J Pediatr. 2002 Apr;140(4):484; discussion 484-5.  No abstract.

5058.   Cainelli F, Vento S.  BCG efficacy and tuberculin skin testing. Lancet. 2002 Apr 27;359(9316):1521-2.  No abstract.

5059.   Caress AL, Luker K, Beaver K, Woodcock A. Adherence to peak flow monitoring. Information provided by meters should be part of self management plan. BMJ. 2002 May 11;324(7346):1157; discussion 1157. No abstract.

5060.   Chan E, Zhan C, Homer CJ. Health care use and costs for children with attention-deficit/hyperactivity disorder: national estimates from the medical expenditure panel survey. Arch Pediatr Adolesc Med. 2002 May;156(5):504-11.


CONTEXT: Although attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent chronic condition of childhood, little is known about patterns of health care use and associated expenditures. OBJECTIVE: To compare health care use and costs among children with ADHD, children with asthma, and the general pediatric population. DESIGN AND SETTING: The 1996 Medical Expenditure Panel Survey, a nationally representative household survey. PARTICIPANTS: All 5439 children aged 5 to 20 years from the 1996 Medical Expenditure Panel Survey were included in this analysis. Children who had ADHD, asthma, or neither (general population) were identified from International Classification of Diseases, Ninth Revision, Clinical Modification codes and prescription records. MAIN OUTCOME MEASURES: Mean health care use (outpatient visits, emergency department visits, hospital stays, home health visit days, and prescriptions) and associated expenditures. RESULTS: We identified 165 children with ADHD, 322 with asthma, and 4952 with neither diagnosis. Children with ADHD had significantly higher mean total health care costs ($1151) compared with children with asthma ($1091; P<.05) and the general population ($712; P<.001). After adjusting for age, sex, race, household income, access to care, parent education, and marital status, excess total costs were $479 for children with ADHD (P<.001) and $437 for children with asthma (P<.01). CONCLUSIONS: Overall costs of care for children with ADHD are comparable to costs for children with asthma and significantly greater than for the general pediatric population. Specific types of health care use and the sources of expenditures differ between children with ADHD and children with asthma. Because much ADHD-related care occurs within school and mental health settings, these figures likely underestimate the true costs of caring for children with this condition.

5061.   Chhabra SK, Bhatnagar S. Comparison of bronchodilator responsiveness in asthma and chronic obstructive pulmonary disease. Indian J Chest Dis Allied Sci. 2002 Apr-Jun;44(2):91-7.


While asthmatics are known to have a greater response to bronchodilators than patients of chronic obstructive pulmonary disease (COPD), whether the pattern of response also differs has not been explored. Forced vital capacity (FVC) and forced expiratory volume in 1st second (FEV1) were measured before and 20 minutes after inhalation of 200 microg salbutamol in patients of bronchial asthma (n=133) and (COPD) (n=116). Three types of responses (defined as > or = 12% and 200 ml increase in FEV1 or FVC) were identified: increase in (i) only FVC (FVC response), (ii) only FEV1 (FEV1 response), and, (iii) both FVC and FEV1 (double response). The mean +/- SEM absolute increase in FEV1 was significantly greater in asthmatics (307+/-17ml) as compared to 120+/-12 ml in COPD patients (p<0.0001). On the other hand, the increase in FVC was not different in the two groups (296+/-22 ml and 230+/-24 ml, respectively, p>0.05). The proportion of subjects showing a > or = 200 ml increase in FEV1 was greater among asthmatics as compared to COPD (p<0.0001) but the proportions showing a > or = 200 ml in FVC were similar (p>0.05). All the three types of responses were observed in asthmatics with a double response being the commonest. In COPD, an FVC response was the predominant response while the FEV1 response was rare. Multinomial logistic regression revealed that younger subjects (below 45 years) were more likely to have a double or exclusive FEV1 response. Greater severity of obstruction was associated with higher odds for each of the three responses, the odds being especially very high for an exclusive FEV1 response. The odds for a double response and an exclusive FEV1 response were significantly increased in asthmatics as compared to COPD. For FVC response, age category and disease were not significant determinants. It was concluded that bronchodilator responsiveness in asthma and COPD differs not only quantitatively but also in the pattern.

5062.   Creticos P, Knobil K, Edwards LD, Rickard KA, Dorinsky P.  Loss of response to treatment with leukotriene receptor antagonists but not inhaled corticosteroids in patients over 50 years of age. Ann Allergy Asthma Immunol. 2002 Apr;88(4):401-9.


BACKGROUND: There are limited published data describing the relative efficacy of available treatment options in younger versus older patients with persistent asthma. OBJECTIVE: To compare the efficacy of fluticasone propionate (FP) and zafirlukast (Z) in younger (12 to 49 years of age) versus older (50 years and older) patients with asthma. METHODS: A retrospective analysis of five randomized, double-blind, double-dummy studies 4 to 12 weeks in duration of 1,742 patients <50 years of age and 243 patients aged 50 years or older. Interventions were inhaled fluticasone propionate (FP) 88 microg, oral Z 20 mg, or placebo twice daily. RESULTS: Treatment with FP resulted in significantly greater improvements than Z in all efficacy measurements (except for nighttime awakenings) regardless of age. In older patients, treatment with FP significantly increased pulmonary function compared with Z: FEV (FP= +0.19 L; placebo = -0.34 L; Z = -0.06 L); AM peak expiratory flow rate [PEFR] (FP = +25 L/minute; placebo = -18 L/minute; Z = +4 L/minute); PM PEFR (FP = +24 L/minute; placebo = -24 L/minute; Z = +5 L/minute; P < or = 0.023; for all comparisons). Compared with Z, treatment with FP in older patients also resulted in significantly greater increases in the percentage of symptom-free days (25% vs 13%) and rescue-free days (35% vs 17%); and significantly greater reductions in albuterol use (-1.6 vs -0.3 puffs/day) and the percentage of patients with exacerbations (2.7% vs 14.3%; P < or = 0.031). CONCLUSIONS: Regardless of age, treatment with FP in patients with asthma significantly improved pulmonary function and overall asthma control. In contrast, treatment with Z in older patients with asthma resulted in small improvements in asthma symptoms, whereas lung function improved minimally or not at all, and exacerbations increased. These data suggest that FP effectively controls inflammation in older patients, whereas Z may mask inflammation and may not provide the level of bronchodilatory or anti-inflammatory activity needed for effective asthma control in older patients.

5063.   Criado RF, Criado PR, Malaman F, Ensina LF, Vasconcellos C, Aun WT, Mello JF, Pires MC.  Nonoccupational allergic contact dermatitis to cashew nut simulating photosensitivity eczema. Am J Contact Dermat. 2002 Jun;13(2):85-6.  No abstract.

5064.   Davies P. Industry funding in medical education. Lancet. 2002 Jun 1;359(9321):1949-50. No abstract.

5065.   de la Sierra A, Giner V, Bragulat E, Coca A. Lack of correlation between two methods for the assessment of salt sensitivity in essential hypertension. J Hum Hypertens. 2002 Apr;16(4):255-60.


The existence of a heterogeneous blood pressure (BP) response to salt

intake, a phenomenon known as salt sensitivity, has increasingly become a subject of clinical hypertension research, and has important clinical and prognostic implications. However, two different methodologies are currently used to diagnose salt sensitivity. The aim of the present study was to compare the BP response to intravenous sodium load and depletion on the one hand, and to changes in dietary salt intake on the other, in order to assess salt sensitivity in a group of essential hypertensive patients. Twenty-nine essential hypertensives underwent two different procedures separated by 1 month: a dietary test consisting of a 2-week period of low (20 mmol/day) and high (260 mmol/day) salt intakes, and an intravenous test consisting of a 2 litre saline load over a 4-h period, followed by 1 day of low (20 mmol) salt intake and furosemide (40 mg/8 h orally) administration. BP was registered at the end of every period using 24-h ambulatory BP monitoring. In the whole group of hypertensive patients studied, both low salt intake and furosemide administration significantly (P < 0.01) decreased mean BP. Correlation coefficients of BP changes obtained using the two methodologies were between 0.3 and 0.4. Moreover, coefficients of agreement between the oral and the intravenous tests, using several cut points for BP changes, were systematically below 0.5, thus indicating a misclassification of salt sensitivity greater than 50%, depending on the method used. None of the cut points for BP changes during furosemide administration showed a good combination of sensitivity and specificity compared with changes in response to low dietary salt. The present results indicate that the diagnosis of salt-sensitive hypertension should be based on the BP response to changes in dietary salt intake, while BP response to saline and furosemide administration leads to a systematic misclassification of more than 50% of patients, even using different cutpoints for changes in BP.


5066.   DiMango EA, Lubetsky H, Austin JH. Assessment of bronchial wall thickening on posteroanterior chest radiographs in acute asthma. J Asthma. 2002 May;39(3):255-61.


A central bronchus that is readily visible end-on in approximately 50% of normal frontal chest radiographs is the bronchus to the anterior segment of either upper lobe. Bronchial wall thickening, or "cuffing," is considered to be a radiographic sign of an asthmatic exacerbation and is cited as a useful sign in a number of leading textbooks; however, to the authors' knowledge, no prior chest radiographic study has quantitatively assessed this specific sign in a population of asthmatics suffering an acute exacerbation. Posterior chest radiographs were reviewed retrospectively for 51 nonasthmatic, nonsmoking control subjects and for 45 adult asthmatic subjects during an acute exacerbation of moderate to severe asthma. Readers were blinded as to whether the radiograph was from an asthmatic or control subject. If visible end-on, the bronchus to the anterior segment of either upper lobe was assessed by measuring the diameter of the lumen and the thickness of the bronchial wall. At least one clearly defined bronchus to the anterior segment of an upper lobe was visible end-on in 22 patients (43%) in the control group and in 21 patients (47%) in the asthma group (p = NS). Mean wall thickness was 0.7 +/- 0.1 mm in the control group and 0.8 +/- 0.1 mm in the asthma group (p = 0.04). Lumen/wall thickness was 3.1 +/- 0.2 (SEM) in the control group and 2.5 +/- 0.2 in the asthma group (p = 0.055). The presence of bronchial wall thickness does not reliably distinguish radiographs of acutely asthmatic from normal individuals.


5067.   Duarte I, Lazzarini R, Bedrikow R. Excited skin syndrome: study of 39 patients. Am J Contact Dermat. 2002 Jun;13(2):59-65.


BACKGROUND: Excited skin syndrome (ESS) is an adverse reaction obtained when carrying out epicutaneous patch tests, characterized by multiple positive test results, associated with one or more strongly positive tests, which are not all reproduced when the patient is tested afterward. OBJECTIVE: The aim of this study was (1) to determine the frequency of ESS in patients submitted to patch testing, (2) to confirm the influence of the evolution time of the primary dermatosis with ESS induction, (3) to determine differences among patients according the rate of positive test loss, and (4) to compare the number of positive tests for each substance between the first test, when all allergens in the test battery were applied, and the second test, when only the allergens with positive tests on the first occasion were applied at a greater distance from one another. METHODS: Epicutaneous tests were carried out in 630 patients with a suspected diagnosis of allergic contact dermatitis. Patients presenting 2 or more positive test results were considered to have ESS and were submitted to a second patch test. RESULTS AND CONCLUSIONS: ESS developed in 39 of the 630 patients tested, corresponding to a frequency of 6.2%. Analysis of data found a longer duration of the primary dermatitis in patients who in whom ESS developed compared with those who did not. Parabens, fragrance mix, and thimerosal had more positive patch test reactions using standard application techniques relative to the retest procedure, which placed the substances at a greater distance from one another, suggesting that, in addition to the factors previously reported to influence the reduction of ESS, the position of the allergens in the testing procedure also should be considered. Copyright 2002, Elsevier Science (USA). All rights reserved.


5068.   Ekici A, Ekici M, Erdemoglu AK. Effect of azithromycin on the severity of bronchial hyperresponsiveness in patients with mild asthma. J Asthma. 2002 Apr;39(2):181-5.

The effect of azithromycin on bronchial hyperresponsiveness was measured in a group of 11 patients with mild asthma. Azithromycin 250 mg orally was administered intermittently to all the patients twice a week for eight weeks. The only other treatment was inhaled beta2 agonist, when required. A histamine inhalation test was performed at the beginning and at the fourth and the eighth week of the study. The mean PC20 values increased significantly over the initial value at the eighth week after the administration of azithromycin (p < 0.05) but mean values for FEV1 and FEV1 percent predicted did not differ significantly. These results suggested that eight weeks of intermittent, low-dose administration of azithromycin in patients with mild asthma might reduce the severity of bronchial hyperresponsiveness.

5069.   El-Gamal Y, Hossny E, Awwad K, Mabrouk R, Boseila N. Plasma endothelin-1 immunoreactivity in asthmatic children. Ann Allergy Asthma Immunol. 2002 Apr;88(4):370-3.


BACKGROUND: Endothelin-1 (ET-1) has been formerly demonstrated to have potent vasocontractile as well as bronchoconstrictor effects in vitro. This followup study was aimed to evaluate the possible changes in ET-1 levels in the plasma of asthmatic children, according to disease activity and severity. METHODS: Plasma ET-1 was estimated by enzyme-linked immunoadsorbent assay in 30 asthmatic patients (6 to 12 years old) during and after remission of an acute attack. Thirty age- and sex-matched healthy children were included as a control group. RESULTS: Plasma ET-1 immunoreactivity was significantly increased in the asthmatic children during the attacks (17.2+/-6.9 pg/mL) in comparison to the levels during quiescence of symptoms (0.9+/-1.13 pg/mL). Further, both values were significantly higher than the control value (0.22+/-0.29 pg/mL). The severity of attacks as judged clinically and by peak expiratory flow rate measurement did not influence the plasma endothelin status; neither did the family history of atopy nor the absolute eosinophil count. However, serum total IgE levels could be positively correlated to the plasma endothelin concentrations measured after remission of the asthmatic attacks (P < 0.05). CONCLUSIONS: Our findings reinforce the concept that ET-1 may be implicated in the pathogenesis of bronchoconstriction. This may encourage further studies on the value of ET-1 antagonism among alternative therapeutic modalities of childhood asthma.


5070.   Faul JL, Demers EA, Burke CM, Poulter LW. Alterations in airway inflammation and lung function during corticosteroid therapy for atopic asthma. Chest. 2002 May;121(5):1414-20.


INTRODUCTION: Although corticosteroid therapy for asthma improves lung function and reduces airway inflammation, the relation between these two events is unclear. This article investigates associations between changes in bronchial inflammation and lung function during high-dose inhaled corticosteroid therapy for asthma. METHODS: Nine subjects with atopic asthma received high-dose inhaled fluticasone propionate (FP), 2,000 microg/d for 8 weeks. Fiberoptic bronchoscopy with endobronchial biopsies, spirometry, and histamine provocation challenge were performed on each subject at baseline, after 2 weeks, and again after 8 weeks of therapy. Spearman rank correlation coefficients between changes in parameters of bronchial inflammation and lung function were computed. RESULTS: As expected, significant down-regulation of airway inflammation and improvements in lung function were observed after both short-term and long-term therapy with high-dose inhaled FP. During corticosteroid therapy, changes in lymphocyte and macrophage numbers in bronchial biopsy specimens were closely correlated. Changes in EG1+ eosinophils were associated with changes in EG2+ eosinophils after 8 weeks of therapy. Although changes in airway inflammation and changes in lung function were not closely associated after 2 weeks of therapy, changes in eosinophils (EG1) in bronchial biopsy specimens correlated with changes in bronchodilator response (r = 0.77, p = 0.016) after 8 weeks of therapy. CONCLUSION: In patients with atopic asthma, changes in bronchial eosinophils and lung function during steroid therapy are closely related but do not occur simultaneously.


5071.   Field SK. Asthma and gastroesophageal reflux: another piece in the puzzle? Chest. 2002 Apr;121(4):1024-7. No abstract.

5072.   Freishtat RJ, Goepp JG. Episodic stridor with latex nipple use in a 2-month-old infant. Ann Emerg Med. 2002 Apr;39(4):441-3.


Latex allergy in the pediatric population is most commonly identified in patients who have undergone multiple operations for neural tube defects or exstrophic genitourinary anomalies. However, there are a significant number of children who, without the usual risk factors, clinically and/or serologically appear to be latex allergic. There is sporadic information in the medical literature regarding reactions to latex allergens in household items, especially in patients younger than 1 year old. Several recent reports even support the existence of reactions to latex pacifiers. We report a case of an atopic 2-month-old infant who experienced the previously unreported reaction of repeated stridor on exposure to a latex nipple while feeding. It is important that clinicians recognize stridor as a potential reaction to latex in infants.

5073.   Gendel SM.  Where do we go from here? A discussion summary. Ann N Y Acad Sci. 2002 May;964:197-200.  No abstract.

5074.   Govindarao D. Studies on immuno modulation by honey on induction of allergen-specific immune response in murine system. Department of Biochemistry, Andhra University; Waltair, 2001. No abstract.

5075.   Greaves MW, Hussein SH. Drug-induced urticaria and angioedema: pathomechanisms and frequencies in a developing country and in developed countries. Int Arch Allergy Immunol. 2002 May;128(1):1-7. Review.


A careful drug history should be obtained from all patients with acute or chronic urticaria/angioedema, especially in the elderly. Although strictly comparable data are lacking, drug-induced urticaria appears to be more common in developed countries than in Malaysia, at least in a Hospital setting. Culprit drugs include antibiotics, analgesics and contrast media. Pseudoallergic drug-induced urticaria mimicks true allergic urticaria, but without an evident immunological basis, and is at least as common as the allergic type. In Malaysia, and in many other countries compulsory, ingredient labelling of 'traditional' medicines would do much to reduce the frequency of drug-induced urticaria. Copyright 2002 S. Karger AG, Basel


5076.   Groneberg DA, Eynott PR, Lim S, Oates T, Wu R, Carlstedt I, Roberts P, McCann B, Nicholson AG, Harrison BD, Chung KF. Expression of respiratory mucins in fatal status asthmaticus and mild asthma. Histopathology. 2002 Apr;40(4):367-73.


AIMS: The airways of patients with asthma are characterized by chronic inflammatory changes comprising mainly T-cells and eosinophils, and airway remodelling with goblet cell metaplasia and submucosal gland hyperplasia. Mucus hypersecretion is often a marked feature, particularly in status asthmaticus. The matrix of airway sputum consists of high molecular glycoproteins and mucins. In this study, the expression and distribution of the major gel-forming mucins MUC5AC and MUC5B were studied in fatal status asthmaticus tissues and bronchial biopsies of mild asthmatic patients. The effect of inhaled corticosteroids on the expression of these mucins was also investigated. METHODS AND RESULTS: Polyclonal antibodies specific for MUC5AC and MUC5B, and a monoclonal antibody for MUC5B were used to stain lung tissues and airway mucosal biopsies obtained from patients who died of status asthmaticus (n=5) and from mild asthmatics (n=4), respectively. Immunohistochemistry for MUC5AC revealed abundant staining of goblet cells situated in the epithelial surface lining and glandular ducts of tissues from patients with fatal asthma. MUC5B immunoreactivity was restricted to mucous cells of submucosal glands and to epithelial cells. In mild asthmatics, large amounts of MUC5B, but not MUC5AC, positive extracellular mucus was found in the airway lumen as plugs, adjacent to the epithelial lining and in the necks of glandular secretory ducts of mild asthmatics. The distribution of MUC5AC and MUC5B in bronchial biopsies of mild asthmatics was similar before and after inhaled steroid treatment. CONCLUSIONS: The expression of MUC5AC and MUC5B shares a similar distribution to normal airways in different states of asthma. The distribution is not affected by topical corticosteroid therapy.


5077.   Hammerman SI, Becker JM, Rogers J, Quedenfeld TC, D'Alonzo GE Jr. Asthma screening of high school athletes: identifying the undiagnosed and poorly controlled. Ann Allergy Asthma Immunol. 2002 Apr;88(4):380-4.


BACKGROUND: It is believed that there are many high school-age athletes who have undiagnosed asthma or exercise-induced asthma (EIA). The screening of these athletes for EIA will allow them to be identified and treated. OBJECTIVES: 1) To obtain reliable peak expiratory flow rate (PEFR) measurements and administer questionnaires to high school-age athletes to evaluate their asthma risk. 2) To identify high-risk athletes for having EIA or asthma by a free run challenge test. 3) To evaluate whether an athlete's present asthma control is adequate. 4) To evaluate these tools for their value as screening tools for asthma or EIA. METHODS: Eight hundred one student athletes from 10 suburban Pittsburgh schools were screened for more than 18 months for asthma as part of their preparticipation sports physicals. The screening included all athletes from all high school sports. The athletes were given a brief questionnaire, had PEFR measured, and then participated in a free running exercise challenge. RESULTS: Forty-six of 801 athletes had asthma or EIA, Of the remaining 755 athletes, 49 athletes were identified as having undiagnosed asthma. In the previously unrecognized athletes with EIA, the positive and negative predictive value of the questionnaire was 42% and 97%, respectively. Eighty-five percent (39 of 46) of the known asthmatic athletes, using their recommended medication, failed their free running test by a >15% drop of their PEFR. CONCLUSIONS: The free running test is a good test for identifying and assessing the athlete with EIA. The PEFR meter is not a good screening tool for EIA in the high school athlete. A questionnaire may be a good negative screening tool, but further development is needed before it can be used for widespread screening.


5078.   Hunter CJ, Brightling CE, Woltmann G, Wardlaw AJ, Pavord ID. A comparison of the validity of different diagnostic tests in adults with asthma. Chest. 2002 Apr;121(4):1051-7.


STUDY OBJECTIVES: Diagnosing asthma is not always easy, and there are times when objective tests can be helpful. The extent to which these tests alter the probability of asthma depends on how much more commonly the test result is positive in subjects with asthma compared to healthy subjects and particularly subjects with conditions that are commonly confused with asthma. We set out to compare the sensitivity and specificity of different tests in this setting. DESIGN: Single-center, cross-sectional, observational study. SETTING: Teaching hospital. PATIENTS: Twenty-one healthy control subjects, 69 patients with asthma, and 20 subjects referred to the hospital with a diagnosis of asthma who were found to have alternative explanations for their symptoms (i.e., pseudoasthma). INTERVENTIONS: We measured methacholine airway responsiveness, the maximum within-day peak expiratory flow amplitude mean percentage (derived from twice-daily readings for > 2 weeks), the FEV(1)/FVC ratio, the percentage change in FEV(1) 10 min after the administration of 200 microg inhaled albuterol, and the differential eosinophil count in blood and induced sputum. We derived normal ranges (from the 95% upper or lower limit for healthy subjects), sensitivity, and specificity (ie, the percentage of subjects with pseudoasthma who had negative test results). RESULTS: Most tests were less specific when the reference population was composed of subjects with conditions that can be confused with asthma. Methacholine airway responsiveness and the sputum differential eosinophil count were the most sensitive (91% and 72%, respectively) and specific (90% and 80%, respectively) tests. CONCLUSION: We conclude that methacholine airway responsiveness and the sputum differential eosinophil count are the most useful objective tests in patients with mild asthma.


5079.   Incorvaia C, Asero R, Bertelli G, Pilone R, Nitti F.  Efficacy of a questionnaire for allergy. Allergy. 2002 Apr;57(4):367-8.  No abstract.

5080.   Keeler GJ, Dvonch T, Yip FY, Parker EA, Isreal BA, Marsik FJ, Morishita M, Barres JA, Robins TG, Brakefield-Caldwell W, Sam M. Assessment of personal and community-level exposures to particulate matter among children with asthma in Detroit, Michigan, as part of Community Action Against Asthma (CAAA). Environ Health Perspect. 2002 Apr;110 Suppl 2:173-81.


We report on the research conducted by the Community Action Against Asthma (CAAA) in Detroit, Michigan, to evaluate personal and community-level exposures to particulate matter (PM) among children with asthma living in an urban environment. CAAA is a community-based participatory research collaboration among academia, health agencies, and community-based organizations. CAAA investigates the effects of environmental exposures on the residents of Detroit through a participatory process that engages participants from the affected communities in all aspects of the design and conduct of the research; disseminates the results to all parties involved; and uses the research results to design, in collaboration with all partners, interventions to reduce the identified environmental exposures. The CAAA PM exposure assessment includes four seasonal measurement campaigns each year that are conducted for a 2-week duration each season. In each seasonal measurement period, daily ambient measurements of PM2.5 and PM10 (particulate matter with a mass median aerodynamic diameter less than 2.5 microm and 10 microm, respectively) are collected at two elementary schools in the eastside and southwest communities of Detroit. Concurrently, indoor measurements of PM2.5 and PM10 are made at the schools as well as inside the homes of a subset of 20 children with asthma. Daily personal exposure measurements of PM10 are also collected for these 20 children with asthma. Results from the first five seasonal assessment periods reveal that mean personal PM10 (68.4 39.2 microg/m(3)) and indoor home PM10 (52.2 30.6 microg/m(3)) exposures are significantly greater (p < 0.05) than the outdoor PM10 concentrations (25.8 11.8 microg/m(3)). The same was also found for PM2.5 (indoor PM2.5 = 34.4 21.7 microg/m(3); outdoor PM2.5 = 15.6 8.2 microg/m(3)). In addition, significant differences (p < 0.05) in community-level exposure to both PM10 and PM2.5 are observed between the two Detroit communities (southwest PM10 = 28.9 14.4 microg/m(3)), PM2.5 = 17.0 9.3 microg/m(3); eastside PM10 = 23.8 12.1 microg/m(3), PM2.5 = 15.5 9.0 microg/m(3). The increased levels in the southwest Detroit community are likely due to the proximity to heavy industrial pollutant point sources and interstate motorways. Trace element characterization of filter samples collected over the 2-year period will allow a more complete assessment of the PM components. When combined with other project measures, including concurrent seasonal twice-daily peak expiratory flow and forced expiratory volume at 1 sec and daily asthma symptom and medication dairies for 300 children with asthma living in the two Detroit communities, these data will allow not only investigations into the sources of PM in the Detroit airshed with regard to PM exposure assessment but also the role of air pollutants in exacerbation of childhood asthma.


5081.   Konig P. Irreversible airway obstruction in childhood asthma? A clinician's viewpoint. Pediatr Pulmonol. 2002 Apr;33(4):307-10.


Even though childhood asthma is assumed to comprise reversible airway obstruction, some children develop irreversible airway obstruction (not reversed by a bronchodilator or corticosteroids); this may be due to inflammation that has caused remodeling. Lately, it has been claimed that in the absence of treatment with inhaled corticosteroids, most patients will develop progressive irreversible obstruction. Several studies culminating with the Childhood Asthma Management Program (CAMP) study, which was the first randomized placebo-controlled prospective long-term study designed to test for irreversible obstruction, did not show the development of such progressive irreversible obstruction. Nevertheless, deterioration in pulmonary function does occur in some patients, probably due to inadequate anti-inflammatory treatment, and possibly also due to maintenance adrenergic treatment. Most previous studies concentrated on forced expiratory volume in 1 sec (FEV(1)), a test assessing mostly large airway obstruction. More studies are needed to investigate the presence of small airway obstruction. Copyright 2002 Wiley-Liss, Inc.


5082.   Kress JP, Noth I, Gehlbach BK, Barman N, Pohlman AS, Miller A, Morgan S, Hall JB.  The utility of albuterol nebulized with heliox during acute asthma exacerbations. Am J Respir Crit Care Med. 2002 May 1;165(9):1317-21.


Heliox improves lung deposition of inhaled particles when compared with air or oxygen inhalation. We studied the spirometric effects of albuterol nebulized with heliox during emergency room visits for asthma exacerbations. Forty-five patients were randomized to receive albuterol nebulized with oxygen (control) versus heliox (n = 22 control and 23 heliox subjects). At baseline, demographics, outpatient asthma medications, vital signs, oxygen saturation, and forced expiratory volume in one second were not different between the two groups. Three consecutive albuterol treatments were given to each group. The heliox group had a significantly higher heart rate after albuterol nebulization compared with the control group. Following albuterol Treatment 1, the median change in forced expiratory volume in one second was 14.6% in the control group and 32.4% in the heliox group (p = 0.007). After Treatment 2, the results were 22.7% versus 51.5%, respectively (p = 0.007). After Treatment 3, the results were 26.6% versus 65.1%, respectively (p = 0.016). We conclude that during acute asthma exacerbations, albuterol nebulized with heliox leads to a more significant improvement in spirometry when compared with albuterol nebulized with oxygen. This is likely due to the low-density gas improving albuterol deposition in the distal airways.

5083.   Kumar N, Singh N, Locham KK, Garg R, Sarwal D. Clinical evaluation of acute respiratory distress and chest wheezing in infants. Indian Pediatr. 2002 May;39(5):478-83. No abstract.

5084.   Lieu TA, Lozano P, Finkelstein JA, Chi FW, Jensvold NG, Capra AM, Quesenberry CP, Selby JV, Farber HJ.  Racial/ethnic variation in asthma status and management practices among children in managed medicaid. Pediatrics. 2002 May;109(5):857-65.


OBJECTIVE: Racial/ethnic disparities in hospitalization rates among children with asthma have been documented but are not well-understood. Medicaid programs, which serve many minority children, have markedly increased their use of managed care in recent years. It is unknown whether racial/ethnic disparities in health care use or other processes of care exist in managed Medicaid populations. This study of Medicaid-insured children with asthma in 5 managed care organizations aimed to 1) compare parent-reported health status and asthma care processes among black, Latino, and white children and 2) test the hypothesis that racial/ethnic variations in processes of asthma care exist after adjusting for socioeconomic status and asthma status. METHODS: This cross-sectional study collected data via telephone interviews with parents and computerized records for Medicaid-insured children with asthma in 5 managed care organizations in California, Washington, and Massachusetts. The American Academy of Pediatrics (AAP) Children's Health Survey for Asthma was used to measure parent-reported asthma status. We used multivariate models to evaluate associations between race/ethnicity and asthma status while controlling for other sociodemographic variables. We evaluated racial/ethnic variations in selected processes of asthma care while controlling for other demographic variables and asthma status. RESULTS: The response rate was 63%. Of the 1658 children in the respondent group, 38% were black, 19% were Latino, and 31% were white. Black children had worse asthma status than white children on the basis of the AAP asthma physical and emotional health scores, symptom-days, and school days missed in the past 2 weeks. Latino children had equivalent AAP scores but missed more school days than white children. On the basis of the AAP asthma physical health score, the black-white disparity persisted after adjusting for other sociodemographic variables. After adjusting for sociodemographic variables and asthma status, black and Latino children were less likely to be using inhaled antiinflammatory medication than white children (relative risk for blacks: 0.69; relative risk for Latinos: 0.58). They were more likely to have home nebulizers. Other processes of asthma care, including ratings of providers and asthma care, use of written management plans, use of preventive visits and specialists, and having no pets or smokers at home, were equal or better for minority children compared with white children. CONCLUSIONS: Black and Latino children had worse asthma status and less use of preventive asthma medications than white children within the same managed Medicaid populations. Most other processes of asthma care seemed to be equal or better for minorities in the populations that we studied. Increasing the use of preventive medications is a natural focus for reducing racial disparities in asthma.


5085.   Little SA, MacLeod KJ, Chalmers GW, Love JG, McSharry C, Thomson NC.  Association of forced expiratory volume with disease duration and sputum neutrophils in chronic asthma. Am J Med. 2002 Apr 15;112(6):446-52.


Some patients with chronic asthma develop irreversible airflow obstruction. Our aim was to assess whether reported duration of asthma and induced sputum cell counts were associated with pulmonary function in patients with asthma who did not smoke.Maximal forced expiratory volume in the first second (FEV(1)) was determined following a steroid trial (oral prednisolone, 30 mg/d [n = 92 patients]; or inhaled fluticasone, 2000 microg/d [n = 5]; for 2 weeks) and 2.5 mg of nebulized albuterol. Asthma history was recorded with duration from first diagnosis. All subjects were nonsmokers, or were to have stopped smoking > or =5 years previously and smoked < or =5 pack-years (n = 12). Induced sputum was obtained from 59 subjects for analysis of airway cell counts.Maximal FEV(1) was inversely associated with asthma duration (r = -0.47, P <0.0001), age (r =-0.40, P <0.0001), and the proportion of sputum neutrophils (r(s) = -0.50, P =0.00004). After adjusting for age, both duration of disease and sputum neutrophils were independently associated with maximal FEV(1). Neutrophil activation, as measured by sputum myeloperoxidase levels, was positively associated with the proportion of sputum neutrophils (r(s) = 0.45, P = 0.0004) and inversely associated with maximal FEV(1) (r(s) = -0.59, P <0.0001). Long disease duration may be a predisposing factor for the development of irreversible airflow obstruction in patients with chronic asthma. The negative associations of sputum neutrophil count and activation with maximal FEV(1) suggest that neutrophils may be involved in the pathophysiology of irreversible airflow obstruction in asthma.


5086.   Malmstrom K, Peszek I, Al Botto, Lu S, Enright PL, Reiss TF.  Quality assurance of asthma clinical trials. Control Clin Trials. 2002 Apr;23(2):143-56.


Accuracy and repeatability of spirometry measurements are essential to obtain reliable efficacy data in randomized asthma clinical trials. We report our experience with a centralized spirometry quality assurance program that we implemented in our phase III asthma trials. Six asthma trials of 4 to 21 weeks in duration were conducted at 232 clinical centers in 31 countries. Approximately 23,100 prebronchodilator and 13,700 postbronchodilator spirometry tests were collected from 2523 adult and 336 pediatric asthmatic patients. The program used a standard spirometer (the Renaissance spirometry system) with maneuver quality messages and automated quality grading of the spirometry tests. Each clinical center transmitted spirometry data weekly to a central database, where uniform monitoring of data quality was performed and feedback was provided in weekly quality reports. Seventy-nine percent of all patients performed spirometry sessions with quality that either met or exceeded American Thoracic Society standards and improved over time. Good-quality spirometry was associated with (1) less severe asthma; (2) active treatment; (3) infrequent nocturnal awakenings; (4) age above 15 years; and (5) low body weight. Maneuver-induced bronchospasm was rare. Good-quality spirometry was observed in multicenter asthma clinical trials that employed a standard spirometer and continuous monitoring. Both within- and between-patient variability decreased. Spirometry quality improved with time as study participants and technicians gained experience.

5087.   Marinkovich VA. Mild asthma. N Engl J Med. 2002 Apr 25;346(17):1335-6; discussion 1335-6. No abstract.

5088.   McConnell R, Berhane K, Gilliland F, Islam T, Gauderman WJ, London SJ, Avol E, Rappaport EB, Margolis HG, Peters JM.  Indoor risk factors for asthma in a prospective study of adolescents. Epidemiology. 2002 May;13(3):288-95.


BACKGROUND: The risk of asthma associated with pets and other indoor exposures has been examined in both cross-sectional and prospective studies of younger children. However, there has been little investigation of the effect of the indoor environment on incident asthma in adolescents. METHODS: Risk factors for the development of asthma were examined in a cohort of 3535 Southern California school children with no history of asthma at 1993 entry into the study, who were followed for up to 5 years. Newly diagnosed cases of asthma were identified by yearly interview report. A total of 265 children reported a new diagnosis of asthma during the follow-up period; 163 of these had reported no history of wheeze at baseline. The risk associated with indoor exposures assessed by questionnaire at entry into the study was examined using Cox proportional hazards models. RESULTS: In children with no history of wheezing, an increased risk of developing asthma was associated with a humidifier (relative risk [RR]  1.7; 95% confidence interval [CI] = 1.2-2.4), any pet (RR = 1.6; 95% CI = 1.0-2.5), or specifically a dog (RR = 1.4; 95% CI = 1.0-2.0) in the home. An estimated 32% of new asthma cases could be attributed to pets. CONCLUSIONS: We conclude that furry pets are a common and potentially remediable risk factor for new onset asthma in adolescents. Our results suggest that a humidifier in the home may contribute to the onset of asthma in this age group.

5089.   Meltzer EO, Lockey RF, Friedman BF, Kalberg C, Goode-Sellers S, Srebro, Edwards L, Rickard K. Efficacy and safety of low-dose fluticasone propionate compared with montelukast for maintenance treatment of persistent asthma. Mayo Clin Proc. 2002 May;77(5):437-45.


OBJECTIVE: To compare the long-term effects of an inhaled corticosteroid with those of a leukotriene modifier on measures of clinical efficacy, subject preference, and safety in patients with persistent asthma. PATIENTS AND METHODS: Between November 17, 1998, and May 26, 2000, we conducted a multicenter, randomized, double-blind, double-dummy, parallel-group study of patients aged 15 years or older with persistent asthma. The patients were symptomatic while taking short-acting beta2-agonists alone and were treated with fluticasone propionate (88 microg [2 puffs of 44 microg] twice daily) or montelukast (10 mg/d) for 24 weeks. Measures of pulmonary function, asthma symptoms, albuterol use, nighttime awakenings, physician assessments of efficacy, patient satisfaction, asthma-related quality of life, and safety were evaluated. RESULTS: A total of 522 patients were randomized to receive fluticasone or montelukast, and 395 patients completed the study. At end point, treatment with fluticasone significantly improved pulmonary function, asthma symptom scores, the percentage of symptom-free days, rescue albuterol use, and the number of nighttime awakenings due to asthma when compared with montelukast (P< or = .002, each comparison). Significantly more patients were satisfied with fluticasone therapy (83%) compared with montelukast therapy (66%) (P<.001), and fluticasone therapy was rated as effective by a significantly greater portion of physicians (67%) than was montelukast therapy (54%) (P<.001). Treatment with fluticasone significantly improved asthma-related quality-of-life measures compared with montelukast (P< or =.01). The incidence of asthma exacerbations was similar in the fluticasone (19 patients, 7%) and montelukast (21 patients, 8%) treatment groups, although slightly more patients in the montelukast group were withdrawn from the study because of asthma exacerbations (6% vs 4%, respectively). CONCLUSION: Long-term treatment with a low dose of inhaled fluticasone is more effective than oral montelukast as first-line maintenance therapy for the treatment of persistent asthma.

5090.   Miller FG, Shorr AF. Ethical assessment of industry-sponsored clinical trials: a case analysis. Chest. 2002 Apr;121(4):1337-42.


The rapid growth of clinical trials sponsored by the pharmaceutical industry and conducted by community physicians raises concerns about the scientific quality of this research and the adequacy of protections for research participants. In this article, we present an in-depth ethical analysis of a recent industry-sponsored placebo-controlled study for treatment of asthma. The ethical analysis uses a proposed ethical framework for evaluating clinical research focusing on seven ethical requirements: (1) scientific value, (2) scientific validity, (3) fair subject selection, (4) favorable risk/benefit ratio, (5) independent review, (6) informed consent, and (7) respect for enrolled subjects.

5091.   Nahm DH, Lee YE, Yim EJ, Park HS, Yim H, Kang Y, Kim JK. Identification of cytokeratin 18 as a bronchial epithelial autoantigen associated with nonallergic asthma. Am J Respir Crit Care Med. 2002 Jun 1;165(11):1536-9.


The allergic response to common environmental agents (allergens) has been regarded as an important mechanism in the development of airway inflammation of patients with asthma. However, allergic sensitization cannot be detected in a significant number of adult patients with asthma. The etiologic mechanism responsible for nonallergic asthma has not yet been identified. The idea of a possible involvement of autoimmunity in the pathogenesis of nonallergic asthma has been proposed by earlier studies. To test for the possible presence of an autoimmune response to bronchial epithelial cell antigens in nonallergic asthma, we examined circulating autoantibodies to cultured human bronchial epithelial cells (BEAS-2B) in sera from patients with nonallergic asthma by immunoblot analysis. IgG autoantibodies to the 49-kD bronchial epithelial cell antigen were detected in 10 of 23 patients with nonallergic asthma (43%), 3 of 27 patients with allergic asthma (11%), 2 of 20 patients with systemic lupus erythematosus (10%), and 3 of 34 healthy volunteers (9%) (p < 0.005). The 49-kD auto-antigen was purified and identified as cytokeratin 18 by amino acid sequencing. In this study, we identified cytokeratin 18 as a bronchial epithelial autoantigen associated with nonallergic asthma. Further studies are needed to determine the significance of autoimmunity in nonallergic asthma.


5092.   Ortega AN, Huertas SE, Canino G, Ramirez R, Rubio-Stipec M. Childhood asthma, chronic illness, and psychiatric disorders. J Nerv Ment Dis. 2002 May;190(5):275-81.


Asthma is a serious and vexing problem for many children and their families. Asthma, like most syndromes, has many symptoms and potential causes and effects. Studies have shown that pediatric asthma is associated with psychiatric disorders, but the specificity and temporality of these relations is not well known. This study examined the associations between any and specific psychiatric disorders and both childhood asthma and other childhood chronic illnesses. The study used the Methods for the Epidemiology of Child and Adolescent Mental Disorders data, a four-site, community-based study of 1,285 pairs of youths and caretakers. Psychiatric disorders were assessed using the Diagnostic Interview Schedule for Children (DISC 2.3). Methods for the Epidemiology of Child and Adolescent Mental Disorders was also used to assess individual characteristics, parental reports of asthma, and other chronic illnesses. Asthma and 'other' chronic illnesses were associated with different psychiatric disorders. In particular, having a history of asthma was associated with having an anxiety disorder, after adjustment for potential confounding, but was not associated with having an affective disorder. Having a chronic illness other than asthma or cancer was associated with having any affective disorder and dysthymia but not anxiety disorder. These results call for more mechanistic research that explores the specific relations between childhood anxiety disorder and asthma and between affective disorder and other pediatric chronic illnesses.


5093.   Ortega HG, Weissman DN, Carter DL, Banks D. Use of specific inhalation challenge in the evaluation of workers at risk for occupational asthma: a survey of pulmonary, allergy, and occupational medicine residency training programs in the United States and Canada. Chest. 2002 Apr;121(4):1323-8.


STUDY OBJECTIVES: To document the current practice of occupational asthma (OA) diagnosis and use of specific inhalation challenge (SIC). DESIGN, SETTING, AND PARTICIPANTS: A survey evaluating the current practice of SIC was mailed to 259 residency training programs in adult pulmonary diseases, allergy and immunology, and occupational medicine accredited in the United States and Canada during the year 2000. RESULTS: Forty-six percent (123 of 259 programs) participated. Ninety-two programs reported that patients with OA were seen during the previous year, 15 programs reported that SIC had been performed, and 10 programs reported that patients had been referred to other sites for SIC. A total of 259 patients underwent SIC. No unexpected adverse reactions were reported. Forty-one programs reported that they had been willing to undertake SIC but were unable to do so. The most common barriers cited were lack of availability of SIC within the evaluating institution, inability to locate a site for referral, concerns about reimbursement, and lack of an appropriate diagnostic reagent for use in SIC. Seventy-four programs indicated that SIC was useful, and 34 programs included training in the use of SIC was part of the residency curriculum. CONCLUSION: Although SIC is considered the "gold standard" for objective documentation of OA, the test is performed in only a few institutions in the United States and Canada. Many institutions indicate that SIC is not available, even when desired for patient management. Only a minority of participating residency training programs include SIC as a formal part of the training curriculum.

5094.   Ortona E, Vaccari S, Margutti P, Delunardo F, Rigano R, Profumo E, Buttari B, Rasool O, Teggi A, Siracusano A. Immunological characterization of Echinococcus granulosus cyclophilin, an allergen reactive with IgE and IgG4 from patients with cystic echinococcosis. Clin Exp Immunol. 2002 Apr;128(1):124-30.


By immunological screening of a cDNA library derived from protoscoleces of Echinococcus granulosus with IgE from patients with cystic echinococcosis (CE) and allergic manifestations, we isolated a protein identical to E. granulosus cyclophilin. The protein, named EA21, has close homology with Malassezia furfur cyclophilin allergen (Mal f 6) and with human cyclophilin. Using immunoblotting (IB) with a polyclonal antibody specific to EA21, we identified E. granulosus cyclophilin both in protoscoleces and in sheep hydatid fluid. Of the 58 sera from patients with CE, 29 (50%) were IgE positive to EA21, whereas, despite the high sequence homology, none were IgE positive to Mal f 6 or human cyclophilin. Only 26 of the 58 patients (45%) had IgG specific to EA21, whereas all patients (100%) had IgG specific to Mal f 6 and human cyclophilin. IB analysis showed that serum IgE-binding reactivity to EA21 differed significantly in patients with and without allergic reactions (20 of 25, 80% versus nine of 33, 27%; P < 10(-4)). Conversely, five of the 25 patients who had CE-related allergic manifestations (20%) and 21 of the 33 who did not (63%) had specific IgG4 (P = 10(-3)) and total IgG to EA21. EA21 induced a proliferative response in 15 of 19 (79%) patients' PBMC regardless of the allergic manifestations, but it induced no IL-4 production. Overall, these findings suggest that E. granulosus cyclophilin is a conserved, constitutive, parasite protein that does not cross-react with cyclophilins from other organisms and is involved in the allergic symptoms related to CE.


5095.   Packham S. Outcomes of adults with respiratory disease treated by specialists and generalists. Arch Intern Med. 2002 Jun 10;162(11):1313; discussion 1313-4. No abstract.

5096.   Sampson HA. Clinical practice. Peanut allergy. N Engl J Med. 2002 Apr 25;346(17):1294-9. No abstract.

5097.   Shahid SK, Kharitonov SA, Wilson NM, Bush A, Barnes PJ. Increased interleukin-4 and decreased interferon-gamma in exhaled breath condensate of children with asthma. Am J Respir Crit Care Med. 2002 May 1;165(9):1290-3.


Exhaled breath condensate analysis for noninvasive quantification of airway inflammation in asthma is a potentially useful research tool in children. There is an imbalance between T-helper (Th)-2 cells, which secrete interleukin (IL)-4, and Th1 cells, which secrete interferon (IFN)-gamma, in asthma. We measured concentrations of IL-4 and IFN-gamma in breath condensates of 37 children (11 normal, 12 steroid-naive, and 14 steroid-treated children with asthma). Exhaled IFN-gamma was significantly lower in steroid-naive and steroid-treated children with asthma compared with normal control subjects (3.7 +/- 0.2 versus 5.1 +/- 0.4 pg/ml, p < 0.01 and 4.1 versus 5.1 pg/ml, p < 0.05). By contrast, mean exhaled IL-4 was elevated in asthma (53.7 +/- 4.2 pg/ml) compared with normal children (35.7 +/- 6.2 pg/ml, p < 0.05) and concentrations were lower with steroid treatment (37.5 +/- 5.6 pg/ml, p < 0.05). Exhaled IL-4 was significantly lower in children with asthma on more than 600 microg inhaled steroid/day. The IL-4/IFN-gamma ratio was significantly greater in children with asthma compared with control children and the children with asthma on inhaled steroid therapy. We have shown for the first time that IFN-gamma and IL-4 can be assayed in exhaled breath condensate and shows an increased ratio of IL-4/IFN-gamma, consistent with predominance of Th2 cells in airways of children with asthma. Exhaled breath condensate analysis may have a useful role in studying allergic inflammation in childhood asthma.

5098.   Shapira MY, Berkman N, Ben-David G, Avital A, Bardach E, Breuer R. Short-term acupuncture therapy is of no benefit in patients with moderate persistent asthma. Chest. 2002 May;121(5):1396-400.


STUDY OBJECTIVES: Acupuncture traditionally has been used to treat asthma. Nevertheless, only a few controlled studies have been performed to determine the efficacy of this treatment. Our study aimed to determine the efficacy of acupuncture in patients with moderate persistent asthma. METHODS: Twenty-three patients with moderate persistent asthma who had been treated only with inhaled beta(2)-agonists were randomly assigned to receive four sessions of real acupuncture (RA) or sham acupuncture (SA) in a blinded manner. After a washout period of 3 weeks, the patients were crossed over. Monitoring included FEV(1), methacholine challenge, daily peak flow (PF) variability, and the keeping of an asthma diary. RESULTS: Twenty of 23 patients completed the study. There was no significant change in FEV(1) following treatment. The mean (+/- SE) FEV(1) values before and after the RA were 73 +/- 4% and 73 +/- 3%, respectively (not significant [NS]). FEV(1) values before and after SA were 70 +/- 3% and 70 +/- 3%, respectively (NS). There was also no change in provocative methacholine concentration causing a 20% fall in FEV(1) (PC(20)) before and after treatment. The mean PC(20) values before and after RA were 0.92 +/- 0.42 mg/mL and 1.16 +/- 0.51 mg/mL, respectively (p = 0.71), while the PC(20) values before and after SA were 1.47 +/- 0.83 mg/mL and 1.11 +/- 0.79 mg/mL, respectively (p = 0.59). There was no change in the mean PF variability before and after the RA (1.6 +/- 3.1% and 1.8 +/- 2.3%, respectively [NS]). The PF variability before and after SA were 3.6 +/- 2.8% and 2.8 +/- 3.4%, respectively (NS). No significant difference was demonstrated for symptom scores or for the use of beta(2)-agonist inhalers (RA, 6.7 +/- 3.4; SA, 8.1 +/- 3.6; p = 0.58). CONCLUSION: In patients with moderate persistent asthma, a short course of acupuncture treatment resulted in no change in lung functions, bronchial hyperreactivity, or patient symptoms.

5099.   Sicherer SH. Clinical update on peanut allergy. Ann Allergy Asthma Immunol. 2002 Apr;88(4):350-61; quiz 361-2, 394. Review.


BACKGROUND: Peanut allergy is common, potentially severe, and there has been a recent surge in clinical investigation of this important food allergen. OBJECTIVE: To provide the reader with a clinically oriented update on peanut allergy. DATA SOURCES: English language articles were selected from PubMed searches (search terms: peanut allergy, food allergy, anaphylaxis) and selected abstracts with a bias toward recent (3 years) studies judged to have immediate, practical clinical implications. RESULTS: Peanut allergy is an increasing problem in western diets that include this food. Both genetic and environmental factors influences the expression of this allergy. The at-risk subject is an atopic individual, with heightened risk for those with atopic dermatitis and/or other food allergies. The allergy is long-lived for most, may increase slightly in severity over time, but approximately 20% of young children will develop tolerance. Parameters that may identify the subset likely to achieve tolerance have been identified. Several large studies have determined laboratory parameters (skin tests, peanut-specific serum immunoglobulin E concentrations) with excellent predictive value (>95%) to diagnose current clinical reactivity or tolerance, although oral food challenges are necessary for a definitive diagnosis. Numerous practical lessons concerning management (avoidance, treatment, and prevention) have been identified. CONCLUSIONS: Recent studies provide the clinician with an armament of improved diagnostic and treatment modalities for peanut allergy. Studies are underway that are likely to provide more definitive therapies in the near future.


5100.   Singh B. Acropalynological studies at Jabalpur with special emphasis on allergenic pollens. Department of Botany, Rani Durgawati Vishwavidyalaya, Jabalpur ; 2001. No Abstract.

5101.   Steven K, Morrison J, Drummond N. Lay versus professional motivation for asthma treatment: a cross-sectional, qualitative study in a single Glasgow general practice. Fam Pract. 2002 Apr;19(2):172-7.


OBJECTIVE: Our aim was to identify the factors which motivate patient self-management in asthma and to compare the results with the factors which appear to have motivated the content of the British Thoracic Society (BTS) clinical guidelines for chronic asthma in adults. METHOD: We conducted a cross-sectional, qualitative survey of asthma patients from a single general practice list in Glasgow, Scotland. Twenty-three adult asthma patients on at least step 2 of the BTS guidelines were selected from the practice asthma register. RESULTS: Only seven of the 23 subjects had asthma treatment goals. People with asthma are motivated by the effect of the illness on self-image, the experience of symptoms, the value of life experiences affected, the perceived consequences of asthma, their acceptance of the diagnosis and their attitude towards medication. Asthma is largely viewed as unproblematic. CONCLUSIONS: The BTS guidelines appear to be motivated by a desire to heighten professional awareness about the disease. Patient goals and preferences for asthma treatment are largely unrecognized by the guidelines. A concordant model of disease management, involving the explicit acknowledgement of patient goals by professionals, alongside their own goals for treatment, may improve adherence to treatment perceived by patients as relevant and achievable.

5102.   Szczeklik A, Nizankowska E, Mastalerz L, Szabo Z. Analgesics and asthma. Am J Ther. 2002 May-Jun;9(3):233-43. Review.


The incidence of asthma is increasing throughout the world, which presents both public health and economic concerns. It is widely recognized that in some adult patients with asthma, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase (COX)-1 exacerbate the condition. This is a distinct clinical syndrome called aspirin-induced asthma (AIA). The disease develops according to a characteristic pattern of symptoms. Persistent eosinophilic rhinosinusitis precedes development of nasal polyposis, aspirin hypersensitivity, and asthma. There is no in vitro test, and diagnosis can only be established by provocation tests with aspirin. At the biochemical level, AIA is characterized by a chronic overproduction of cysteinyl leukotrienes. The key enzyme, leukotriene C4 synthase, is overexpressed in bronchi, and its messenger RNA is upregulated in peripheral blood eosinophils. This can be partly related to the genetic polymorphism of the enzyme. The disease runs a protracted course, even if COX-1 inhibitors are avoided. The course of AIA is often severe, and at least half of the patients need systemic corticosteroids to control their asthma. To prevent life-threatening reactions, patients with AIA should avoid aspirin and other analgesics that inhibit COX-1. The incidence of cross-sensitivity to paracetamol in AIA patients is low and, when a reaction does occur, the symptoms experienced are shorter and milder than if the reactions were evoked by an NSAID. Rapidly growing evidence indicates that highly specific COX-2 inhibitors, known as coxibs, are well tolerated and can be safely used by AIA patients.


5103.   Talini D, Benvenuti A, Carrara M, Vaghetti E, Martin LB, Paggiaro PL. Diagnosis of flour-induced occupational asthma in a cross-sectional study. Respir Med. 2002 Apr;96(4):236-43.


The diagnosis of occupational asthma is usually performed in epidemiology using a combination of symptoms and bronchial hyperresponsiveness, while in a clinical setting the 'gold standard' for the diagnosis of occupational asthma is the specific bronchial challenge test in the laboratory The aim of this study was to detect new cases of flour-induced occupational asthma (OA) in a group of workers exposed to grain and/or flour dust, by means of a step-by-step approach, as used in a clinical setting. In an epidemiological study, III millers and 186 bakers were examined by means of questionnaire, pulmonary function tests and skin-prick tests (SPT) to common allergens and to wheat flour dust extracts. From the whole sample, 82 subjects who showed asthma-like symptoms in the questionnaire and/or low forced expiratory volume in 1 sec (FEV1) were selected. Selected subjects underwent methacholine challenge test, and hyperreactive subjects underwent specific bronchial challenge with flour dust in the laboratory. Sixty-two of the selected subjects performed the methacholine challenge test, and 22 (33 8%) were hyperreactive (PD20 FEV1 <1 mg of methacholine). Fifteen of 22 hyperreactive subjects underwent specific bronchial challenge test (s BCT) with flour dust; a positive response was elicited in six subjects. These subjects can be diagnosed as having flour-induced occupational asthma. Atopy and skin sensitivity to flour was partially related to the response to flour bronchial challenge. Bronchial hyperreactivity can be observed in a small percentage of subjects with asthma-like symptoms and/or low FEV1, and a positive response to s BCTwas observed in a subgroup of hyperreactive subjects.Therefore, using these selection criteria, a diagnosis of flour-induced OA, as commonly performed in a clinical setting, can be performed in few previously undiagnosed subjects.This approach could be relevant for an early diagnosis ofoccupational asthma.


5104.   van Steekelenburg J, Clement PA, Beel MH. Comparison of five new antihistamines (H1-receptor antagonists) in patients with allergic rhinitis using nasal provocation studies and skin tests. Allergy. 2002 Apr;57(4):346-50.


BACKGROUND: It was the aim of the authors to compare all of the latest second-generation antihistamines and to see if there were significant differences in their efficacy. It is important for ENT specialists to know if these differences exist, as it is for general practitioners trying to choose between these drugs. METHODS: In 12 confirmed grass pollen allergic patients the authors performed nasal smears to asses eosinophilia, histamine/grass pollen skin tests, and grass pollen nasal provocation tests. All tests were performed before and after administration of one of five different antihistamines (cetirizine, loratadine, ebastine, fexofenadine, mizolastine) or placebo. The order of administration of antihistamines and placebo was randomised, and patients were not aware of which drug they were given. A decrease in nasal eosinophilia (nasal smear), or nasal or skin reactivity (provocation tests) was looked for. RESULTS: A significant decrease in nasal eosinophilia was observed for all antihistamines but not for placebo. For the grass pollen nasal provocation tests, the decrease was significant for nasal blockage and sneezing; for rhinorrhea there was an insignificant decrease that was true for all antihistamines. A significant reduction in histamine/grass pollen skin test reactivity was also observed for all antihistamines, during an 8 h observation period. A significant difference in efficacy between the different antihistamines could not be found with any of the tests performed. CONCLUSIONS: For the newer nonsedating H1-antagonists there appears to be no clinically relevant differences in activities--at least not in our study. Preference of the patient may be the most important factor in making a choice between these drugs.

5105.   Wood RA. Skin testing: making the most of every prick. Ann Allergy Asthma Immunol. 2002 Apr;88(4):347-9.  No abstract.

5106.   Woodruff PG, Fahy JV. A role for neutrophils in asthma? Am J Med. 2002 Apr 15;112(6):498-500. No abstract.

5107.   Yawn BP, Wollan P, Kurland M, Scanlon P. A longitudinal study of the prevalence of asthma in a community population of school-age children. J Pediatr. 2002 May;140(5):576-81.


OBJECTIVE: Using a unique county-wide resource that links all health care providers' medical records to assess current and "ever" prevalence of physician-diagnosed asthma. To describe the age and sex rates and temporal trends in new asthma diagnoses and associations with race and socio-economic status. STUDY DESIGN: A longitudinal retrospective evaluation of a population-based cohort of school children using linked medical and school records. RESULTS: Overall, 17.6% of children in grades kindergarten through 12 had a physician diagnosis of asthma and 12.9% had an asthma-related visit within the past 2 years. An additional 19.7% had visits for reactive airway disease or recurrent wheezing or bronchospasm with no diagnosis of asthma. Children provided with free and reduced-cost lunches had lower cumulative and incident asthma rates from birth through their current school age. Race was not related to rates of physician-diagnosed asthma. There was a significant temporal increase in rates of new asthma diagnoses. CONCLUSIONS: In this community, 1 in 3 children have had a physician-documented recurrent wheezing-type illness, and 1 in 6 were diagnosed with asthma. Diagnoses rates were directly related to socioeconomic status.


5108.   Zaas D, Brock M, Yang S, Sylvester JT.  An uncommon mimic of an acute asthma exacerbation. Chest. 2002 May;121(5):1707-9.


Foreign body aspiration in adults has a variety of clinical presentations and often goes unrecognized. We describe the case of a patient who experienced crack cocaine aspiration and presented with symptoms of an acute asthma exacerbation requiring mechanical ventilation until the eventual diagnosis and bronchoscopic removal of the foreign body.



5109.      Akpinarli A, Guc D, Kalayci O, Yigitbas E, Ozon A. Increased interleukin-4 and decreased interferon gamma production in children with asthma: function of atopy or asthma? J Asthma. 2002 Apr;39(2):159-65.


Both atopy and asthma are claimed to be associated with a Th-2 cytokine pattern. We sought to determine the contribution of atopy and asthma to the observed Th-2/Th-1 imbalance in these conditions. Of 60 children aged 6-16 years that were included in the study, 13 were nonatopic nonasthmatic, 15 atopic nonasthmatic, 14 nonatopic asthmatic, and 18 atopic asthmatic. Atopic children had positive skin prick tests to grass pollens only. All children were studied after an asymptomatic and drug-free period of at least three months. Total IgE was measured in serum. Peripheral blood mononuclear cells were cultured and stimulated in vitro with phytohemagglutinin and interferongamma (IFN-gamma) and interleukin-4 (IL-4) measured in the supernatants. Total IgE was significantly higher in atopic asthmatics compared to nonatopic asthmatics (p = 0.004), and nonatopic nonasthmatics (p = 0.001), but was not different from atopic nonasthmatics (p >0.05). On the other hand, IL-4 was significantly elevated in atopic asthmatics and in nonatopic asthmatics compared to nonatopic nonasthmatics (p = 0.037 and p = 0.009, respectively). Although atopic asthmatics had lower IFN-gamma values than nonatopic asthmatics, the difference did not reach statistical significance. No correlation was detected between any two parameters. Our results suggest that both atopy and asthma contribute to the increased levels of IL-4 and that, whereas nonatopic asthma is associated with increases in both IL-4 and IFN-gamma release by mononuclear cells, only atopic asthma is characterized by a Th-2 type cytokine dominance.


5110.   Arvidsson MB, Lowhagen O, Rak S. Effect of 2-year placebo-controlled immunotherapy on airway symptoms and medication in patients with birch pollen allergy. J Allergy Clin Immunol. 2002 May;109(5):777-83.


BACKGROUND: Birch pollen is a common allergen in northern, central, and eastern Europe. Earlier studies of specific immunotherapy using birch pollen extract were not placebo-controlled or were only preseasonal. Long-term, placebo-controlled studies with subcutaneously administered standardized birch pollen extract are lacking. OBJECTIVE: The aim of this study was to evaluate the effect of immunotherapy with birch pollen extract on airway symptoms and use of medication in adult birch pollen-allergic patients in a double-blind, placebo-controlled trial. METHODS: Forty-nine patients with histories of birch pollen allergy from the upper and lower airways, positive skin prick test and conjunctival provocation test results, and in vitro specific IgE to birch pollen (Betula verrucosa ) extract were included. Immunotherapy with birch pollen extract was given during 2 consecutive years in a double-blind, randomized, placebo-controlled study. Clinical symptom scores from the upper and lower airways and use of rescue medication were registered throughout the pollen season. RESULTS: Forty-six patients reached the maintenance dose and were maintained on that dose during the 2-year study. The median symptom scores during the 1997 and 1998 seasons were 1.3 and 2.6, respectively, in the specific immunotherapy group and 2.1 and 4.3, respectively, in the placebo group. The differences between the groups were significant (P =.05 in 1997 and P =.005 in 1998). The placebo group used significantly more rescue medication during both seasons than the specific immunotherapy group (P =.004 for 1997 and P =.004 for 1998). CONCLUSION: Specific immunotherapy with birch pollen extract is an effective and safe treatment for reducing clinical allergy symptoms and medication use in birch pollen-allergic patients during the pollen season.


5111.   Babu KS, Holgate ST. Newer therapies for asthma: a focus on anti-IgE. Indian J Chest Dis Allied Sci. 2002 Apr-Jun;44(2):107-15. Review.


The prevalence of asthma and other allergic disorders has been on the increase not only in the western world but also in the developing countries. This increasing prevalence has lead research into the discovery and development of various new therapeutic strategies. The improved understanding about the pathophysiology of asthma has prompted the developments of novel molecules to tackle this problem. These include newer phosphodiesterase inhibitors, cytokine modulation strategies, allergen immunotherapy, and anti-IgE. Immunoglobulin E plays a major role in airway inflammation in asthma. Omalizumab, a novel humanised monoclonal antibody directed against the high affinity FcepsilonRI portion of the IgE has shown a lot of promise in the control of asthma symptoms and as a steroid sparing agent in the management of allergic asthma. This new molecule has an excellent safety profile and could play an important role in the management of patients with severe asthma. This review gives a brief overview of the newer therapies under investigation with special reference to omalizumab in the treatment of allergic asthma.


5112.   Barnetson RS, Rogers M. Childhood atopic eczema. BMJ. 2002 Jun 8;324(7350):1376-9. Review.  No abstract.

5113.   Beasley R. The burden of asthma with specific reference to the United States. J Allergy Clin Immunol. 2002 May;109(5 Suppl):S482-9. Review.


During the second half of the 20th century, the increasing prevalence, morbidity, economic burden, and, in some countries, mortality from asthma have generated worldwide concern. The prevalence in the United States and other English-speaking countries is higher than that in most other countries, but worldwide variations cannot be explained by current knowledge of recognized risk or protective factors. According to hospital admission rates, asthma morbidity rates have also risen throughout the world during the past 40 years. These trends are likely due to many different factors, including an increase in the prevalence of severe asthma. Asthma mortality rates gradually declined in the United States during the 1960s and 1970s but have exhibited a substantial, progressive increase during the past 20 years. This trend stands in contrast to those in most other western countries, where asthma mortality rates have generally been decreasing during the 1990s. In both western and developing countries, the considerable economic burden of asthma disproportionately affects individuals with severe disease. This observation illustrates the potential for reducing the costs associated with asthma through management approaches that have been proven to reduce morbidity and mortality.


5114.   Black J. The role of mast cells in the pathophysiology of asthma. N Engl J Med. 2002 May 30;346(22):1742-3.  No abstract.

5115.   Bohadana AB, Hannhart B, Teculescu DB. Nocturnal worsening of asthma and sleep-disordered breathing. J Asthma. 2002 Apr;39(2):85-100. Review.


Asthma has a tendency, to destabilize and get worse at night, probably due to a nocturnal increase in airiway inflammation and bronchial responsiveness. Nocturnal airway narrowing in asthma is often associated with sleep disorders, such as episodes of nocturnal and early morning awakening, difficulty in maintaining sleep, and day time sleepiness. On the other hand, an association has been documented between nocturnal sleep-disordered breathing and asthma. This review highlights the causes of nocturnal worsening of asthma and examines the evidence pointing toward a causal relationship between nocturnal asthma and sleep-disordered breathing.

5116.   Bonnin AJ.  Mild asthma. N Engl J Med. 2002 Apr 25;346(17):1335-6; discussion 1335-6.  No abstract.

5117.   Burks W. Current understanding of food allergy. Ann N Y Acad Sci. 2002 May;964:1-12. Review.


IgE-mediated hypersensitivity reactions account for the majority of well-documented food allergy reactions, but non-IgE-mediated immune mechanisms do cause some hypersensitivity disorders. A variety of gastrointestinal, cutaneous, respiratory, and generalized symptoms and syndromes have been associated with IgE-mediated food allergy. The diagnostic approach to adverse food reactions begins with a careful medical history and physical examination. Laboratory studies may then be used appropriately in the evaluation. Once the diagnosis of food allergy is established, the only proven therapy is the strict elimination of the food from the patient's diet. Studies in both children and adults indicate that symptomatic reactivity to food allergens is often lost over time, except possibly reactions to peanuts, tree nuts, and seafood.

5118.   Chen JT, Krieger N, Van Den Eeden SK, Quesenberry CP. Different slopes for different folks: socioeconomic and racial/ethnic disparities in asthma and hay fever among 173,859 U.S. men and women. Environ Health Perspect. 2002 Apr;110 Suppl 2:211-6.


Although allergic diseases such as asthma and hay fever are a major cause of morbidity in industrialized countries, most studies have focused on patterns of prevalence among children and adolescents, with relatively few studies on variations in prevalence by race/ethnicity and socioeconomic position among adults. Our study examined racial/ethnic and socioeconomic patterns in the prevalence of asthma overall, asthma with hay fever, asthma without hay fever, and hay fever overall, in a population of 173,859 women and men in a large prepaid health plan in northern California. Using education as a measure of socioeconomic position, we found evidence of a positive gradient for asthma with hay fever with increasing level of education but an inverse gradient for asthma without hay fever. Hay fever was also strongly associated with education. Compared with their White counterparts, Black women and men were more likely to report asthma without hay fever, and Black women were less likely to have asthma with hay fever. Asian men were also more likely to report asthma with hay fever, and Asian women and men were much more likely to have hay fever. Racial/ethnic disparities in prevalence of allergic diseases were largely independent of education. We discuss implications for understanding these social inequalities in allergic disease risk in relation to possible differences in exposure to allergens and determinants of immunologic susceptibility and suggest directions for future research.

5119.   Chiaverini L. Asthma, particulates, and diesel exhaust. Med Health R I. 2002 Apr;85(4):140-2.  No abstract.

5120.   Cinquetti M, Micelli S, Voltolina C, Zoppi G. The pattern of gastroesophageal reflux in asthmatic children. J Asthma. 2002 Apr;39(2):135-42.


The association between gastroesophageal reflux (GER) and asthma is not fortuitous. The objective of our study was to test a group of children with asthma by, 24 hr gastroesophageal pH monitoring and to relate the results to the patients medical history and clinical data. We studied 77 children aged from 39 to 170 months suffering from particularly recurrent and/or therapy resistant asthma. Medical history data were collected for each patient and included: severity and characteristics of respiratory symptoms, presence, if any of allergy; presence, if any, of GER-related symptoms; and presence, if any, of esophagitis-related symptoms. Esophageal pH was measured by 24 hr computerized monitoring of the main measures in all patients. Forty-seven children were also examined by gastroesophageal endoscopy. The prevalence of GER was 61% on the basis of the reflux index (cutoff: 4.2%). Gastroesophageal reflux in these asthmatic children was characterized mainly by short-lasting daytime episodes. The patients tended to present GER mainly associated with vomiting but not with signs and symptoms of esophagitis. The short-lasting nature of the reflux episodes demonstrates good esophageal clearance. The time of onset of respiratory symptoms (day/night) was not associated with any particular type of GER, the severity of which tends to be proportional to the seriousness of the asthma. No correlation was found between GER and allergy. No statistically significant differences were found in clinical or medical history findings between patients with pathologic and nonpathologic GER.


5121.   Cook N, Freeman S. Photosensitive dermatitis due to sunscreen allergy in a child. Australas J Dermatol. 2002 May;43(2):133-5. No abstract.

5122.   Drake AJ, Howells RJ, Shield JP, Prendiville A, Ward PS, Crowne EC. Symptomatic adrenal insufficiency presenting with hypoglycaemia in children with asthma receiving high dose inhaled fluticasone propionate. BMJ. 2002 May 4;324(7345):1081-2.  No abstract.

5123.   Eng PA, Reinhold M, Gnehm HP. Long-term efficacy of preseasonal grass pollen immunotherapy in children. Allergy. 2002 Apr;57(4):306-12.


BACKGROUND: In a previous controlled study we demonstrated that preseasonal grass pollen immunotherapy for three years was effective in children. In the current study we examined the same group of patients to see if there is still a benefit six years after discontinuation of treatment. METHODS: Thirteen of 14 patients with previous specific immunotherapy (SIT) and 10 out of 14 patients of the control group were prospectively followed during the grass pollen season. Outcome measures were seasonal symptom scores for eyes, nose and chest, the use of symptomatic medication and visual analog scale. Objective measures included skin prick test reactivity to seasonal and perennial allergens and conjunctival provocation testing. RESULTS: During the 13 week observation time scores for overall hayfever symptoms (P < 0.004) and individual symptoms for eyes (P <0.02), nose (P < 0.04) and chest (P < 0.01) as well as combined symptom and medication scores (P < 0.002) remained lower in the group with previous SIT. Only 23% of patients with previous pollen-asthma who had received SIT experienced pollen-associated lower respiratory tract symptoms compared to 70% in the control group (P < 0.05). There was no significant difference in the use of pharmacological treatment during the pollen season except for asthma medication. The average visual analog scale was lower in the post-SIT group (P <0.05). Six years after cessation of SIT the immediate skin response to grass pollen remained decreased compared to the reaction of the controls (P < 0.01). There was also a tendency for higher allergen concentration to provoke a conjunctival response in the post-SIT group but without reaching statistical significance. Eight years after commencement of SIT, 61% of the initially pollen-monosensitized children had developed new sensitization to perennial allergens compared to 100% in the control group (P < 0.05). CONCLUSIONS: There is still a significant clinical benefit six years after discontinuation of preseasonal grass pollen immunotherapy in childhood. SIT in children with pollen-allergy reduces onset of new sensitization and therefore has the potential to modify the natural course of allergic disease.


5124.   Faul JL, Demers EA, Burke CM, Poulter LW. Alterations in airway inflammation and lung function during corticosteroid therapy for atopic asthma. Chest. 2002 May;121(5):1414-20.


INTRODUCTION: Although corticosteroid therapy for asthma improves lung function and reduces airway inflammation, the relation between these two events is unclear. This article investigates associations between changes in bronchial inflammation and lung function during high-dose inhaled corticosteroid therapy for asthma. METHODS: Nine subjects with atopic asthma received high-dose inhaled fluticasone propionate (FP), 2,000 microg/d for 8 weeks. Fiberoptic bronchoscopy with endobronchial biopsies, spirometry, and histamine provocation challenge were performed on each subject at baseline, after 2 weeks, and again after 8 weeks of therapy. Spearman rank correlation coefficients between changes in parameters of bronchial inflammation and lung function were computed. RESULTS: As expected, significant down-regulation of airway inflammation and improvements in lung function were observed after both short-term and long-term therapy with high-dose inhaled FP. During corticosteroid therapy, changes in lymphocyte and macrophage numbers in bronchial biopsy specimens were closely correlated. Changes in EG1+ eosinophils were associated with changes in EG2+ eosinophils after 8 weeks of therapy. Although changes in airway inflammation and changes in lung function were not closely associated after 2 weeks of therapy, changes in eosinophils (EG1) in bronchial biopsy specimens correlated with changes in bronchodilator response (r = 0.77, p = 0.016) after 8 weeks of therapy. CONCLUSION: In patients with atopic asthma, changes in bronchial eosinophils and lung function during steroid therapy are closely related but do not occur simultaneously.

5125.   Field SK. Asthma and gastroesophageal reflux: another piece in the puzzle? Chest. 2002 Apr;121(4):1024-7.  No abstract.

5126.   Gerlini G, Prignano F, Pimpinelli N. Acute leucocytoclastic vasculitis and aquagenic pruritus long preceding polycythemia rubra vera. Eur J Dermatol. 2002 May-Jun;12(3):270-1. No abstract.

5127.   Gern JE. Rhinovirus respiratory infections and asthma. Am J Med. 2002 Apr 22;112 Suppl 6A:19S-27S. Review.


Viral infections, particularly respiratory illnesses caused by rhinovirus, are the most common cause of asthma exacerbations in children and contribute in large part to asthma morbidity in adults. Epidemiologic studies and increasingly sophisticated viral detection methodologies have helped to define the role of rhinovirus as a potential causative agent in asthma exacerbations. Rhinovirus-induced lung disease is multifaceted and can be characterized in terms of a variety of physiologic, immunologic, and viral processes. The precise direct and indirect mechanisms of viral contribution to exacerbations must still be elucidated. Understanding them will have an impact on the design of future treatment modalities.


5128.   Goodman B.  Immunology. Drink your shots. Sci Am. 2002 Apr;286(4):26. No abstract.

5129.   Grammer LC, Harris KE, Yarnold PR.  Effect of respiratory protective devices on development of antibody and occupational asthma to an acid anhydride. Chest. 2002 Apr;121(4):1317-22.


STUDY OBJECTIVES: To determine whether the use of respiratory protective equipment would reduce the incidence of occupational asthma due to exposure to hexahydrophthalic anhydride (HHPA). DESIGN: Prospective cohort study. SETTING: A facility that makes an epoxy resin product requiring HHPA for its manufacture. PARTICIPANTS: Sixty-six individuals newly hired at a facility that makes an epoxy resin product requiring HHPA for its manufacture. INTERVENTION: Employees who wished to use respiratory protective equipment could choose from three types of masks: dust mask, half-face organic vapor respirator, or full-face organic vapor respirator. MEASUREMENTS: Workers were evaluated annually for development of positive antibody to HHPA and occupational, immunologic respiratory disease, including occupational asthma. RESULTS: With use of respiratory protective equipment, the rate of developing an occupational immunologic respiratory disease was reduced from approximately 10 to 2% per year. Occupational asthma developed in only three individuals, and they were all in the higher exposure category. Statistically, one respirator was not superior to the others. CONCLUSION: Respiratory protective equipment can reduce the incidence of occupational immunologic respiratory disease, including occupational asthma, in employees exposed to HHPA.


5130.   Hallett R, Haapanen LA, Teuber SS. Food allergies and kissing. N Engl J Med. 2002 Jun 6;346(23):1833-4.  No abstract.

5131.   Huynh NT, Commens CA. Scrubbing for cutaneous procedures can be hazardous. Australas J Dermatol. 2002 May;43(2):102-4.


Office-based minor cutaneous surgery is a service provided by many medical practitioners. In New South Wales, Australia, it is a legal requirement for practitioners to surgically scrub before donning sterile gloves for all forms of invasive surgery, including minor cutaneous procedures. Frequent scrubbing causes altered skin barrier function, irritant dermatitis and a potential risk of latex sensitization. These adverse effects are associated with significant morbidity and cost. Better tolerated alternatives, including alcohol-based hand rubs, should be considered in preference to traditional surgical scrubs in order to reduce these occupational risks for minor proceduralists. Well-controlled, prospective studies should explore what extent of hand washing is necessary for donning sterile gloves for minor cutaneous surgery.

5132.   Jensen CS, Lisby S, Baadsgaard O, Volund A, Menne T. Decrease in nickel sensitization in a Danish schoolgirl population with ears pierced after implementation of a nickel-exposure regulation. Br J Dermatol. 2002 Apr;146(4):636-42.


BACKGROUND: To reduce the skin nickel exposure of the population, the Danish Ministry of Environment issued a regulation that was implemented in 1992, and the European Union countries have recently adopted an expanded regulation. OBJECTIVES: The aim of our combined patch testing and questionnaire investigation of girls in public schools and high schools/production schools was to evaluate whether the regulation has had an impact on the prevalence of nickel sensitization. METHODS: To find a group of girls with ears pierced mainly after implementation of the nickel-exposure regulation in Denmark, girls were recruited from the fifth and sixth grade in 12 public schools (the public school group). After the public school level almost all girls from a public school population continue their education in high schools or other schools such as production schools or technical schools. Therefore, to find girls demographically similar to the public school girls but older, and with ears pierced before implementation of the regulation, girls from seven high schools and two production schools were recruited (the high school group). Four hundred and twenty-seven girls in the public school group (mean age 12.4 years, range 10-14) and 534 in the high school group (mean age 18.8 years, range 17-22) participated. All participants filled out a questionnaire concerning ear piercing, use of oral braces and former patch testing for nickel sensitivity. Three hundred and five girls (71.4%) in the public school group and 275 (51.5%) in the high school group were patch tested or had been tested previously and the results of these tests were included in the study. The relation between the frequency of nickel sensitization and the various factors that might influence the prevalence of nickel sensitization was evaluated by multivariate logistic regression analysis. The investigation was conducted from March 1999 to March 2000. RESULTS: The study showed that both increasing age and having ears pierced before 1992 enhanced the prevalence of nickel sensitization. We found that 17.1% of the girls in the high school group demonstrated a positive patch test reaction to nickel. In contrast, the prevalence of nickel sensitization in the public school group was only 3.9%. Comparing girls with and without pierced ears, the prevalence of nickel sensitization was significantly higher in girls with ears pierced before, but not after, 1992 (odds ratio 3.34 and 1.20, respectively). Only in the high school group was there a tendency that wearing oral braces before ear piercing had a protective effect on nickel sensitization, but this did not reach statistical significance. CONCLUSIONS: As we found an effect of ear piercing before but not after 1992, this study strongly suggests that implementation of the nickel-exposure regulation in 1992 in Denmark has had the intended effect of protecting the female population from becoming allergic to nickel.

5133.   Jones CA, Holloway JA, Popplewell EJ, Diaper ND, Holloway JW, Vance GH, Warner JA, Warner JO.  Reduced soluble CD14 levels in amniotic fluid and breast milk are associated with the subsequent development of atopy, eczema, or both. J Allergy Clin Immunol. 2002 May;109(5):858-66.


BACKGROUND: Exposure to various microbial products in early life reduces the risk of atopy. Such exposure induces downregulation of T(H)2 allergy-biased responses by means of pattern recognition molecules, such as CD14, an LPS receptor. OBJECTIVE: We sought to determine whether infant and maternal levels of soluble CD14 (sCD14) are associated with the atopic outcomes of infants. METHODS: Levels of sCD14 in plasma, amniotic fluid, and breast milk were measured with a specific ELISA in different cohorts. Expression of toll-like receptors in the fetal gut was examined by using RT-PCR. RESULTS: Soluble CD14 levels increased during fetal development and postnatally, attaining adult levels by around 4 months of age, with an overshoot of adult levels from 6 months of age. There was no difference in plasma sCD14 levels at birth of children with a high compared with those with a low risk of development of atopy. Amniotic fluid sCD14 levels at midgestation (16-17 weeks) were significantly lower when the child was subsequently atopic (P <.05). Soluble CD14 levels in breast milk collected 3 months postpartum were significantly lower in children with eczema at 6 months of age, irrespective of whether they were atopic (P =.003). Transcripts for toll-like receptor 4, which would enable transmembrane signaling for LPS/sCD14 complexes, were expressed within fetal gut and skin. CONCLUSION: Exposure to reduced levels of sCD14 in the fetal and neonatal gastrointestinal tract is associated with the development of atopy, eczema, or both. Thus the exogenous supply of sCD14 might influence immunologic reactivity both locally and systemically in early life and thereby influence disease outcome.


5134.   Kolbe J, Fergusson W, Vamos M, Garrett J. Case-control study of severe life threatening asthma (SLTA) in adults: psychological factors. Thorax. 2002 Apr;57(4):317-22.


BACKGROUND: Severe life threatening asthma (SLTA) is important in its own right and as a proxy for asthma death. In order to target hospital based intervention strategies to those most likely to benefit, risk factors for SLTA among those admitted to hospital need to be identified. Adverse psychological factors are purported risk factors for asthma death and SLTA /near fatal asthma. A study was undertaken to determine whether, in comparison with patients admitted to hospital with acute asthma, those with SLTA have specific adverse psychological factors. METHODS: A case-control study was undertaken. Cases (n=77) were admitted to the intensive care unit with SLTA (mean (SD) pH 7.17 (0.15), PaCO(2) 10.7 (5.0) kPa). Controls (n=239) were admitted to general wards with acute asthma and were matched only by date of index attack. An interviewer administered questionnaire was undertaken 24-48 hours after admission. A random sample of community based asthmatics was recruited to provide normative data on asthmatics for comparison with cases and hospital controls. RESULTS: The risk of SLTA increased with age (OR 1.04/year, 95% CI 1.01 to 1.07) and was less for women (OR 0.36, 95% CI 0.20 to 0.68). These variables were controlled for in all further analyses. There was a high prevalence of psychological disorder in both cases and matched controls, but there was no difference in prevalence of caseness for anxiety or depression, total (or individual) life events in last 12 months, availability of general or disease specific social support, nor in any of the domains of the Attitudes and Beliefs about Asthma Questionnaire (emotional (mal) adjustment, doctor-patient relationship, stigma, self-efficacy). Cases (SLTA) were less likely to have had previous emotional counselling (25% v. 35%, p<0.05). However, when comparison was made with a community based group of asthmatic patients, those admitted to hospital with acute asthma (SLTA and hospital controls) had a higher prevalence of anxiety and depression, higher total life events, and higher prevalence of certain specific life events. CONCLUSIONS: There was considerable psychological morbidity generally (and anxiety specifically) in those admitted with acute asthma. Specific adverse psychological factors were not risk factors for SLTA, when comparison was made with those admitted to hospital with acute asthma, but adverse psychological factors were a risk factor for hospitalisation for acute asthma (including SLTA). Psychological risk factors for adverse events in asthma are dependent both on the type of event under study and the comparison group used.


5135.   Konig P. Irreversible airway obstruction in childhood asthma? A clinician's viewpoint. Pediatr Pulmonol. 2002 Apr;33(4):307-10.


Even though childhood asthma is assumed to comprise reversible airway obstruction, some children develop irreversible airway obstruction (not reversed by a bronchodilator or corticosteroids); this may be due to inflammation that has caused remodeling. Lately, it has been claimed that in the absence of treatment with inhaled corticosteroids, most patients will develop progressive irreversible obstruction. Several studies culminating with the Childhood Asthma Management Program (CAMP) study, which was the first randomized placebo-controlled prospective long-term study designed to test for irreversible obstruction, did not show the development of such progressive irreversible obstruction. Nevertheless, deterioration in pulmonary function does occur in some patients, probably due to inadequate anti-inflammatory treatment, and possibly also due to maintenance adrenergic treatment. Most previous studies concentrated on forced expiratory volume in 1 sec (FEV(1)), a test assessing mostly large airway obstruction. More studies are needed to investigate the presence of small airway obstruction. Copyright 2002 Wiley-Liss, Inc.


5136.   Lawrence DA. Psychologic stress and asthma: neuropeptide involvement. Environ Health Perspect. 2002 May;110(5):A230-1; discussion A231. No abstract.

5137.   Macdougall CF, Cant AJ, Colver AF. How dangerous is food allergy in childhood? The incidence of severe and fatal allergic reactions across the UK and Ireland. Arch Dis Child. 2002 Apr;86(4):236-9.


AIMS: To discover the incidence of fatal and severe allergic reactions to food in a large population of children. METHODS: A retrospective search for fatalities in children 0-15 years from 1990 to February 1998, primarily of death certification at offices of national statistics. A prospective survey of fatal and severe reactions from March 1998 to February 2000, primarily through the British Paediatric Surveillance Unit. MAIN OUTCOME MEASURES: were deaths and severe reactions. A case was deemed severe if one or more of the following criteria was met: cardiorespiratory arrest; need for inotropic support; fluid bolus >20 ml/kg; more than one dose of epinephrine; more than one dose of nebulised bronchodilator. A case was deemed near fatal if intubation was necessary. RESULTS: The UK under 16 population is 13 million. Over the past 10 years, eight children died (incidence of 0.006 deaths per 100 000 children 0-15 years per year). Milk caused four of the deaths. No child under 13 died from peanut allergy. Two children died despite receiving early epinephrine before admission to hospital; one child with a mild food allergic reaction died from epinephrine overdose. Over the past two years, there were six near fatal reactions (none caused by peanut) and 49 severe ones (10 caused by peanut), yielding incidences of 0.02 and 0.19 per 100 000 children 0-15 years per year respectively. Coexisting asthma is more strongly associated with a severe reaction than the severity of previous reactions. CONCLUSIONS: If 5% of the child population have food allergy, the risk that a food allergic child will die from a food allergic reaction is about 1 in 800 000 per year. The food allergic child with asthma may be at higher risk. Prescribing an epinephrine autoinjector requires a careful balance of advantages and disadvantages.

5138.   Mendell MJ, Fisk WJ, Petersen MR, Hines CJ, Dong M, Faulkner D, Deddens JA, Ruder AM, Sullivan D, Boeniger MF.  Indoor particles and symptoms among office workers: results from a double-blind cross-over study. Epidemiology. 2002 May;13(3):296-304.


BACKGROUND: We studied the effects of removing small airborne particles in an office building without unusual contaminant sources or occupant complaints. METHODS: We conducted a double-blind crossover study of enhanced particle filtration in an office building in the Midwest United States in 1993. We replaced standard particle filters, in separate ventilation systems on two floors, with highly efficient filters on alternate floors weekly over 4 weeks. Repeated-measures models were used to analyze data from weekly worker questionnaires and multiple environmental measurements. RESULTS: Bioaerosol concentrations were low. Enhanced filtration reduced concentrations of the smallest airborne particles by 94%. This reduction was not associated with reduced symptoms among the 396 respondents, but three performance-related mental states improved; for example, the confusion scale decreased (-3.7%; 95% confidence limits (CL) = -6.5, -0.9). Most environmental dissatisfaction variables also improved; eg, "stuffy" air, -5.3% (95% CL = -10.3, -0.4). Cooler temperatures within the recommended comfort range were associated with remarkably large improvement in most outcomes; for example, chest tightness decreased -23.4% (95% CL = -38.1, -8.7) for every 1 degrees C decrease. CONCLUSIONS: Benefits of enhanced filtration require assessment in buildings with higher particulate contaminant levels in studies controlling for temperature effects. Benefits from lower indoor temperatures need confirmation.

5139.   Park HS, Frew AJ. Genetic markers for occupational asthma. J Allergy Clin Immunol. 2002 May;109(5):774-6. Review. No abstract.

5140.   Plaud B, Donati F, Debaene B. Anaphylaxis during anaesthesia. Br J Anaesth. 2002 Apr;88(4):604-5; discussion 605-6. No abstract.

5141.   Rauh VA, Chew GR, Garfinkel RS. Deteriorated housing contributes to high cockroach allergen levels in inner-city households. Environ Health Perspect. 2002 Apr;110 Suppl 2:323-7.


The high prevalence of childhood asthma in low-income, inner-city populations is not fully understood but has been at least partly attributed to the disproportionate exposures associated with socioeconomic disadvantage. The contribution of indoor allergens to asthma is well documented, but links between socioeconomic disadvantage and indoor allergen levels are not clear. We investigated levels of cockroach allergens (Bla g 2) in a sample of 132 Dominican or African American low-income households with young children in northern Manhattan in New York City (40% were receiving public assistance) to determine whether the distribution of allergens is a function of housing deterioration. Deterioration was measured by the presence and number of physical housing problems (holes in the ceilings and walls, water damage, etc.). More than 50% of the sample had two or more types of housing dilapidation, and 67% of the sample reported cockroach sightings in their homes. Samples of dust were collected from kitchen and bedroom surfaces. We hypothesized that the greater the dilapidation, the higher the allergen levels, independent of income, sociocultural factors, and pest-control methods. In addition, we hypothesized that the homes of families characterized by frequent moves (23.5%) would have higher allergen levels than more stable families. Results showed significant positive associations between housing deterioration and allergen levels in kitchens, after adjusting for income and ethnicity, with independent effects of residential stability (p< 0.05). Bedroom allergen levels were associated with housing instability (p < 0.01) and ethnicity (p< 0.01). Findings demonstrated that indoor household allergen levels are related to degree of household disrepair, after adjusting for individual family attributes, suggesting that social-structural aspects of housing may be appropriate targets for public health interventions designed to reduce allergen exposure.


5142.   Ravenna F, Caramori G, Panella GL, Papi A, Benea G, Adcock IM, Barnes PJ, Ciaccia A. An unusual case of congenital short trachea with very long bronchi mimicking bronchial asthma. Thorax. 2002 Apr;57(4):372-3.


Case reports of a short trachea with early branching of the main bronchi are uncommon. The case is presented of a 64 year old woman with upper airway obstruction due to this anatomical abnormality which caused breathlessness and wheezing that was misdiagnosed (and treated) as bronchial asthma for many years.


5143.   Sicherer SH. Clinical update on peanut allergy. Ann Allergy Asthma Immunol. 2002 Apr;88(4):350-61; quiz 361-2, 394. Review.


BACKGROUND: Peanut allergy is common, potentially severe, and there has been a recent surge in clinical investigation of this important food allergen. OBJECTIVE: To provide the reader with a clinically oriented update on peanut allergy. DATA SOURCES: English language articles were selected from PubMed searches (search terms: peanut allergy, food allergy, anaphylaxis) and selected abstracts with a bias toward recent (3 years) studies judged to have immediate, practical clinical implications. RESULTS: Peanut allergy is an increasing problem in western diets that include this food. Both genetic and environmental factors influences the expression of this allergy. The at-risk subject is an atopic individual, with heightened risk for those with atopic dermatitis and/or other food allergies. The allergy is long-lived for most, may increase slightly in severity over time, but approximately 20% of young children will develop tolerance. Parameters that may identify the subset likely to achieve tolerance have been identified. Several large studies have determined laboratory parameters (skin tests, peanut-specific serum immunoglobulin E concentrations) with excellent predictive value (>95%) to diagnose current clinical reactivity or tolerance, although oral food challenges are necessary for a definitive diagnosis. Numerous practical lessons concerning management (avoidance, treatment, and prevention) have been identified. CONCLUSIONS: Recent studies provide the clinician with an armament of improved diagnostic and treatment modalities for peanut allergy. Studies are underway that are likely to provide more definitive therapies in the near future.


5144.   Stephenson J.  Scientists find some genes a bad omen for anti-HIV drug. JAMA. 2002 Apr 3;287(13):1637.  No abstract.

5145.   Uehara M, Sugiura H, Tanaka K. Rarity of hypertension in adult patients with atopic dermatitis. Br J Dermatol. 2002 Apr;146(4):631-5.


BACKGROUND: Patients with atopic dermatitis show a tendency for vasoconstriction of the small vessels in the skin. As peripheral vasoconstriction contributes to the cause of hypertension, it is natural to suppose that blood pressures might be on the high side in adult patients with atopic dermatitis. In the literature, however, there was little information on the subject. OBJECTIVES: To study the incidence of hypertension in adult patients with atopic dermatitis. PATIENTS/METHODS: Blood pressure was measured in 521 adult patients with active atopic dermatitis (235 males; 286 females) aged 30-59 years, and 87 adults with "healed" atopic dermatitis (26 males; 61 females) aged 34-52 years. The blood pressures were classified as definite hypertension, borderline hypertension or normal blood pressure. RESULTS: In those patients aged 30-39 years with active atopic dermatitis, the incidence of definite hypertension in the male patients and the female patients was 1.1% and 1.6%, respectively. The incidence remained almost at a plateau for the 30-39-year-old age group through to the 50-59-year-old age group, in both the male and female patients. There was no difference in the incidence of definite hypertension between patients with severe dermatitis and patients with mild dermatitis. Adult patients with "healed" atopic dermatitis also showed a low incidence of definite hypertension. CONCLUSIONS: These findings indicate that hypertension is rare in adult patients with atopic dermatitis. It is most probable that the rarity of hypertension is a primary feature of the disease.

5146.   Varner AE. The increase in allergic respiratory diseases: survival of the fittest? Chest. 2002 Apr;121(4):1308-16. Review.


The prevalence of allergic respiratory diseases, asthma and allergic rhinoconjunctivitis, has increased since the advent of industrialization. The inverse relationship between the number of infections early in life and atopy has been interpreted as the "hygiene hypothesis." That is, many infections early in life promote the development of T helper type 1 cytokines, while fewer infections early in life favor the development of T helper type 2 (Th2) cytokines and atopy. An alternate interpretation of the same data, that atopy is protective against infections early in life, is rarely considered. With epidemiologic, historical, and immunologic data, I suggest that human evolution has favored individuals with an atopic predisposition. Th2 immune responses promote parity, and ensure successful pregnancy and term birth; provide the infant protection against infections and the inflammation induced by common  pathogens in the first years of life until the immune system matures; and protect young adults exposed to viral respiratory pathogens. These traits are of particular value with the advent of industrialization, especially so in the era prior to the development of antibiotics. This theory contradicts the assumption that there is no biological or evolutionary advantage for allergic disease to exist in humans and has significant implications for our current and future treatments of allergic diseases.


5147.   Woodruff PG, Fahy JV. A role for neutrophils in asthma? Am J Med. 2002 Apr 15;112(6):498-500.  No abstract.


Vaccines :


5148.      Smits AJ, Hak E, Stalman WA, van Essen GA, Hoes AW, Verheij TJ. Clinical effectiveness of conventional influenza vaccination in asthmatic children. Epidemiol Infect. 2002 Apr;128(2):205-11.


Influenza immunization rates among young asthmatics remain unsatisfactory due to persistent concern about the impact of influenza and the benefits of the vaccine. We assessed the effectiveness of the conventional inactivated trivalent sub-unit influenza vaccine in reducing acute respiratory disease in asthmatic children. We conducted a two-season retrospective cohort study covering the 1995-6 and 1996-7 influenza outbreaks in 22 computerized primary care practices in The Netherlands. In total, 349 patients aged between 0 and 12 years meeting clinical asthma-criteria were included; 14 children were lost to follow-up in the second season. The occurrence of physician-diagnosed acute respiratory disease episodes including influenza-like illness, pneumonia. bronchitis, bronchiolitis, asthma exacerbation and acute otitis media in vaccinated and unvaccinated children were compared after adjustments for age, prior health care and medication use. The occurrence of acute respiratory disease in unvaccinated children was 28% and 24% in the 1995-6 and 1996-7 season, respectively, and was highest in children under 6 years of age (43%). The overall pooled clinical vaccine effectiveness was 27% (95% confidence interval -7 to 51%, P = 0.11) after adjustments. A statistically higher vaccine protectiveness of 55% (95% CI 20-75%, P = 0.01) was observed among asthmatics under 6 years of age compared with -5% in older children (95% CI -81 to 39%). The occurrence of acute respiratory disease among asthmatic children during influenza epidemics is very high, notably in the youngest. Influenza vaccination may reduce morbidity in asthmatic infants and pre-school children. However, larger, preferably experimental, studies are needed to establish the benefits of vaccination, notably in older asthmatic children.


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