Dinakar C. Exhaled nitric oxide in the clinical management of asthma. Curr Allergy Asthma Rep. 2004 Nov; 4(6):454-9. Review.

Section of Allergy/Asthma/Immunology, Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA. cdinakar@cmh.edu.

Management of asthma has gradually evolved from the concept of controlling bronchial hyper responsiveness to focusing on control of inflammation. The awareness of airway remodeling, and the emergence of data suggesting irreversibility of some of these changes, despite standard-of-care pharmacotherapies such as inhaled steroids, has highlighted the need for early detection; effective diagnosis and treatment; monitoring responses and adhering to treatment; and predicting exacerbations. Pre-clinical intervention strategies targeted toward picking up early suggestions of asthma before irreversible airway changes occur may open the door to primary prevention approaches. Although invasive methods, such as bronchial biopsy, remain the gold standard to understanding and treating asthma, there is a preference for noninvasive techniques for reasons of convenience, ease of use, and patient comfort. In this article, recent data that support the use of exhaled nitric oxide as a noninvasive biomarker of inflammation in clinical practice are reviewed.

2.

Lemanske RF. Viral infections and asthma inception. J Allergy Clin Immunol. 2004 Nov; 114(5):1023-6. Review.

Departments of Pediatrics and Medicine, Division of Pediatric Allergy, Immunology, and Rheumatology, University of Wisconsin Medical School, 600 Highland Avenue, Madison, WI 53792, USA. rfl@medicine.wisc.edu.

Respiratory tract infections caused by viruses have been implicated in the pathogenesis of asthma. Of these respiratory pathogens, viruses have been demonstrated to be associated with asthma epidemiologically in at least 3 ways ( Fig 1 ). First, during infancy, certain viruses have been implicated in the inception of the asthmatic phenotype. Genetic susceptibility, particularly genes coding for a topic phenotypic characteristics, might differentiate, at least in part, those children who are destined to have persistent wheezing, asthma, or both later in childhood. Second, repeated exposure to infectious viruses in daycare centers or in households with multiple older siblings increases the number of respiratory infections, but in doing so, it might paradoxically reduce the long-term risk of allergies and asthma through either pre-existing or newly formed alterations in cytokine response profiles. Third, in patients with established asthma, particularly children, viral upper respiratory tract infections play a significant role in producing acute exacerbations of airway obstruction that might result in frequent outpatient visits or in hospitalizations. This review will highlight available data on respiratory syncytial virus infections and their relationship to asthma inception in childhood.

3.

Mehta SV, Parkin PC, Stephens D, Keogh KA, Schuh S. Oxygen saturation as a predictor of prolonged, frequent bronchodilator therapy in children with acute asthma.

Division of Pediatric Emergency Medicine, The Hospital for Sick Children, University of Toronto, Canada.

OBJECTIVES: To examine if the initial oxygen saturation (SaO2) in the Emergency Department is a useful predictor of prolonged frequent bronchodilator therapy (FBT) in children with acute asthma. STUDY DESIGN: Prospective cohort study of 273 children, 1 to 17 years of age, requiring systemic corticosteroids. Patients were categorized as needing FBT for >4 hours (n=166) versus >4 hours (n=107) and >12 hours (n=79) versus >12 hours (n=194). Multiple logistic regression determined the association between SaO2 and these outcomes. RESULTS: Baseline SaO2 remains a significant independent predictor of FBT for >4 hours (OR=0.81) and >12 hours (OR=0.84); 91% of patients with SaO2 of 90% to 91% had FBT >4 hours and 80% of patients with SaO2 of < or =89% had FBT >12 hours. Children with SaO2 of < or =91% are 14.7 and 12.0 times more likely to require FBT for >4 hours and >12 hours, respectively, than those with SaO2 of 98% to 100%. The interval likelihood ratios for FBT >4 hours were 12.3 for SaO2 of < or =89%, 6.5 for 90% to 91%, but only 1.8 for 92% to 93%. The likelihood ratios for FBT >12 hours decreased from 9.8 for SaO2 of < or =89% to 3.5 for SaO2 of 90% to 91%. CONCLUSIONS: SaO2 is a useful predictor of FBT >4 hours if it is < or =91% and of FBT >12 hours if it is < or =89%. J Pediatr. 2004 Nov;145(5):641-5. Erratum in: J Pediatr. 2004 Dec; 145(6):864.

4.

Barnes PJ.  New drugs for asthma. Nat Rev Drug Discov. 2004 Oct; 3(10):831-44. Review.

National Heart and Lung Institute, Imperial College Faculty of Medicine, Dovehouse Street, London SW3 6LY, UK. p.j.barnes@imperial.ac.uk

Asthma is a major and increasing global health problem and, despite major advances in therapy, many patients' symptoms are not adequately controlled. Treatment with combination inhalers, which contain a corticosteroid and long-acting beta (2) adrenoceptor agonist, is the most effective current therapy. There is therefore a search for new therapies, particularly safe and effective oral treatments and those that are more efficacious in severe asthma. New therapies in development include mediator antagonists and inhibitors of cytokines, although these therapies might be too specific to be very effective. New anti-inflammatory therapies include corticosteroids and inhibitors of phosphodiesterase-4, p38 mitogen-activated protein kinase and nuclear factor-kappa B. The prospects for a curative treatment are on the horizon.      

5.

Douwes J, Le Gros G, Gibson P, Pearce N. Can bacterial endotoxin exposure reverse atopy and atopic disease? J Allergy Clin Immunol. 2004 Nov; 114(5):1051-4.

Centre for Public Health Research, Massey University, Wellington Campus, Private Box 756, Wellington, New Zealand. J.douwes@massey.ac.nz

Studies have shown that endotoxin exposure in childhood is associated with a reduced risk of atopy and atopic asthma. It is commonly assumed that these effects only occur in early life. However, recent epidemiologic studies suggest that immune deviation might take place throughout life. Assuming that the immune system is not fixed after the first years of life, we hypothesize that endotoxin exposure might not only inhibit the development of atopic sensitization and disease at any time throughout life but might also reverse this process. This novel extension of the hygiene hypothesis is primarily based on the indirect evidence of several epidemiologic observations showing a reduction in atopy in adults highly exposed to endotoxin that is unlikely to be explained by protective effects alone. In addition, some animal studies demonstrated the potential of endotoxin to down regulate pre-existing airway eosinophilia and hyper reactivity. However, there is currently little direct evidence that endotoxin might reverse atopy and allergic diseases. Observational studies and randomized trials to test this hypothesis could ultimately lead to the development of novel treatments for atopic diseases, such as allergic asthma, hay fever, and eczema.

11343.    Araujo MI, Hoppe B, Medeiros M Jr, Alcantara L, Almeida MC, Schriefer A, Oliveira RR, Kruschewsky R, Figueiredo JP, Cruz AA, Carvalho EM. Impaired T helper 2 response to aeroallergen in helminth-infected patients with asthma. J Infect Dis. 2004 Nov 15;190(10):1797-803. 

11344. Latha GS, Vijaya Lakshmi V, Surekha Rani H, Murthy KJR. Use of gynandropsis pollen fractions to assess the effect of hyposensitization in patients of bronchial asthma. Indian Journal of Allergy Asthma and Immunology. 2004 Jan-Jun; 18(1): 25-31

11345.     Aroni R, Goeman D, Stewart K, Thien F, Sawyer S, Abramson M, Douglass J. Enhancing validity: what counts as an asthma attack? J Asthma. 2004 Oct;41(7):729-37.

11346.     Campos FL, da Silva-Junior FP, de Bruin VM, de Bruin PF. Melatonin improves sleep in asthma: a randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2004 Nov 1;170(9):947-51.

11347.     Chavannes N, Schermer T, Akkermans R, Jacobs JE, van de Graaf G, Bollen R, van Schayck O, Bottema B. Impact of spirometry on GPs' diagnostic differentiation and decision-making. Respir Med. 2004 Nov;98(11):1124-30.

11348.     Crabbe H, Barber A, Bayford R, Hamilton R, Jarrett D, Machin N. The use of a European telemedicine system to examine the effects of pollutants and allergens on asthmatic respiratory health. Sci Total Environ. 2004 Dec 1;334-335:417-26.

11349.     Dik N, Tate RB, Manfreda J, Anthonisen NR. Risk of physician-diagnosed asthma in the first 6 years of life. Chest. 2004 Oct;126(4):1147-53.

11350.     Dinakar C. Exhaled nitric oxide in the clinical management of asthma. Curr Allergy Asthma Rep. 2004 Nov;4(6):454-9. Review.

11351.     Guy ES, Kirumaki A, Hanania NA. Acute asthma in pregnancy. Crit Care Clin. 2004 Oct;20(4):731-45, x. Review.

11352.     Lemanske RF. Viral infections and asthma inception. J Allergy Clin Immunol. 2004 Nov;114(5):1023-6. Review.

11353.     Magnan A. Tools to assess (and achieve?) long-term asthma control. Respir Med. 2004 Oct;98 Suppl B:S16-21. Review.

11354.     Majima Y. Clinical implications of the immunomodulatory effects of macrolides on sinusitis. Am J Med. 2004 Nov 8;117 Suppl 9A:20S-25S. Review.

11355.     Mehta SV, Parkin PC, Stephens D, Keogh KA, Schuh S. Oxygen saturation as a predictor of prolonged, frequent bronchodilator therapy in children with acute asthma. J Pediatr. 2004 Nov;145(5):641-5. Erratum in: J Pediatr. 2004 Dec;145(6):864.

11356.     Peat JK, Mihrshahi S, Kemp AS, Marks GB, Tovey ER, Webb K, Mellis CM, Leeder SR. Three-year outcomes of dietary fatty acid modification and house dust mite reduction in the Childhood Asthma Prevention Study. J Allergy Clin Immunol. 2004 Oct;114(4):807-13.

11357.     Ruffin R. Peak expiratory flow (PEF) monitoring. Thorax. 2004 Nov;59(11):913-4.

11358.     Schaub B, von Mutius E. The marketing of asthma and allergies. Lancet. 2004 Oct 16;364(9443):1389-90.

11359.     Steinshamn S, Sandsund M, Sue-Chu M, Bjermer L. Effects of montelukast and salmeterol on physical performance and exercise economy in adult asthmatics with exercise-induced bronchoconstriction. Chest. 2004 Oct;126(4):1154-60.

11360.     Virchow JC. Guidelines versus clinical practice--which therapy and which device? Respir Med. 2004 Oct;98 Suppl B:S28-34. Review.

11361.     Babu KS, Davies DE, Holgate ST. Role of tumor necrosis factor alpha in asthma. Immunol    Allergy Clin North Am. 2004 Nov;24(4):583-97, v-vi. Review.

11362.     Barnes PJ. New drugs for asthma. Nat Rev Drug Discov. 2004 Oct;3(10):831-44. Review.

11363.     Kay AB, Klion AD. Anti-interleukin-5 therapy for asthma and hypereosinophilic syndrome. Immunol Allergy Clin North Am. 2004 Nov;24(4):645-66, vii. Review.

11364.     London SJ, Promislow JH. Breastfeeding and asthma in adolescents.Am J Public Health. 2004 Nov;94(11):1843;.

11365.   Sandberg S, Jarvenpaa S, Penttinen A, Paton JY, McCann DC. Asthma exacerbations in children immediately following stressful life events: a Cox's hierarchical regression.Thorax. 2004 Dec;59(12):1046-51.

11366.  Sun YC, Chu HW. Do neutrophils actively participate in airway inflammation and remodeling in asthma? Chin Med J (Engl). 2004 Nov;117(11):1739-42.

11367.     Douwes J, Le Gros G, Gibson P, Pearce N. Can bacterial endotoxin exposure reverse atopy and atopic disease? J Allergy Clin Immunol. 2004 Nov;114(5):1051-4.