November 2005 World Medical Journal Review

Reviewed by Richard F. Lockey, M.D., Editor-In-Chief

1. OUTCOME OF ASTHMA AND WHEEZING IN THE TUCSON CHILDREN'S RESPIRATORY STUDY
In a previous study (1995), four phenotypes were identified characterizing preschool age wheeze. They include: No wheeze from birth to age 6 yr (never wheeze), wheezing lower respiratory illness (LRI) before age 3 yr only (transient early wheeze), wheeze at age 6 yr only (late-onset wheeze), and wheezing LRI before age 3 yr and wheeze at age 6 yr (persistent wheeze). The prevalence of atopy and wheeze by age 16 was similar for never and transient early wheezers and for persistent and late-onset wheezers. Both transient early and persistent wheezers had significantly lower FEF 25-75, FEV1, and FEV1:FVC ratio through age 16 compared to never wheezers. Late-onset wheezers had lung function similar to those of never wheezers through age 16. There were no significant changes in lung function in any of the four phenotypes, relative to their peers, from age 6 to 16 yr. The authors conclude that wheezing prevalence levels of lung function are established by age 6 and do not change significantly by age 16. Editor's comment: Loss of lung function in childhood asthma appears to occur during the first 6 years of life. Morgan WJ, et al. Am J Respir Crit Care Med 2005; 172: 1253.

2. ASPIRIN SENSITIVITY AND SEVERITY OF ASTHMA
These researchers investigated the role of aspirin exacerbated respiratory disease (AERD) as a risk factor for developing irreversible airway obstruction. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) is a multi-centered observational study with patients having severe or difficult-to-treat asthma. Subjects with AERD vs. those with non-aspirin-sensitive asthma had significantly lower mean post-bronchodilator percent predicted FEV1, more severe asthma by physician assessment, a higher rate of intubation, have had a steroid burst during the previous three months and required high-dose inhaled corticosteroids. AERD patients have more severe asthma and possible remodeling of the lower airways. Editor's comment: The AERD phenotype is a more severe form of asthma. Mascia K, et al. J Allergy Clin Immunol 2005; 116: 970.

3.  RISK FACTORS OF FREQUENT EXACERBATONS IN DIFFICULT-TO-TREAT ASTHMA
Clinical and environmental factors potentially associated with asthma exacerbations were investigated on 136 subjects with difficult-to-treat asthma. Those with more than three severe exacerbations (n = 39) in the previous year were compared with those with one exacerbation per year (n = 24). Severe nasal sinus disease [adjusted odds ratio (OR) 3.7], gastro-oesophageal reflux (OR 4.9), recurrent respiratory infections (OR 6.9), psychological dysfunctioning (OR 10.8) and obstructive sleep apnea (OR 3.4) were associated with frequent exacerbations. Severe chronic sinus disease and psychological dysfunctioning were independently associated (OR 5.5 and 11.7, respectively). All patients with frequent exacerbations had one of these five, while 52% showed three or more. Co-morbid factors which exacerbate asthma are easy to detect and are treatable. Editor's comment: Appropriate recognition and treatment of illnesses commonly associated with asthma are essential for good outcomes. ten Brinke A, et al. Eur Respir J 2005; 26: 812

4. SEVERE FOOD-ALLERGIC REACTIONS IN 13 MILLION CHILDREN FROM THE UNITED KINGDOM ( UK ) AND IRELAND , 1998-2000.
Food allergic reactions resulted in 0.89 hospital admissions per 100,000 children per year. Main allergens were peanut (21%), tree nuts (16%), cow's milk (10%) and egg (7%). Fifty-eight cases were severe. Three were fatal and six near fatal, and eight of nine of these had asthma and developed life-threatening asthma with their food-allergic reaction. Three near-fatal cases received excess intravenous epinephrine. Seven of the 171 non-severe and 6/58 severe cases might have had a worse outcome if epinephrine auto-injectors had been unavailable. Six of the severe cases might have benefited if auto-injectors were prescribed. The authors conclude that asthma is a strong risk for severe food allergic reactions. Editor's comment: Food allergy in asthmatics is a particularly worrisome problem. Colver AF, et al. Acta Paediatrica 2005; 94: 689. Online abstract not available

5. A QUESTIONNAIRE-BASED SURVEY OF ANAPHYLACTIC REACTIONS IN CHILDREN IN GERMANY
Pediatricians in Germany were asked by the questionnaire to report anaphylaxis in infants and children less than 12 years over the previous 12 months. Severity of symptoms was classified grades I-IV. One hundred and three cases were evaluated with a median age of 12 years, 58% of whom were boys. Most reactions occurred in the home, with foods the most common causative agent, 57%; insect stings, 13%; and immunotherapy, 12%. Peanuts and tree nuts were the most frequent allergens among foods. Cardiovascular involvement occurred in 24% of cases without fatalities. Twenty percent received epinephrine, 8% intravenously. The authors conclude that doctors are uncertain about diagnosing anaphylaxis, the patients are under treated, the physicians need additional guidelines and training about anaphylaxis and families need self-management programs. Editor's comment: All physicians must understand how to recognize and treat anaphylaxis, the main theme for the 2006 AAAAI meeting in Miami. Mehl A, et al. Allergy 2005; 60: 1140.

6. EFFECTS OF 24 WEEKS OF LANSOPRAZOLE ON ASTHMA IN PATIENTS WITH GERD SYMPTOMS
This multi-center, double-blind, randomized, placebo-controlled trial of 206 subjects with moderate-to-severe persistent asthma with reflux symptoms determined whether lansoprazole, 30 mg bid vs. placebo, improves asthma control. The primary outcome was daily asthma symptoms by diary and secondary outcomes, rescue albuterol use, daily AM and PM peak expiratory flow, FEV1, FVC, asthma quality of life score, investigator-assessed symptoms, exacerbations and oral corticosteroid-treated exacerbations. Such treatment did not improve asthma symptoms as assessed by the participant or the investigator, pulmonary functions, or reduce albuterol use. However, it did reduce asthma exacerbations and improve quality of life. Editor's comment: Treatment of GERD is also important for good asthma outcomes. Littner MR, et al. Chest 2005; 128: 1128.

7. ENDOSCOPIC SINUS SURGERY FOR SINUSITIS IN PATIENTS WITH BRONCHIAL ASTHMA
This is a prospective analysis of 88 subjects, with (28) or without (60) bronchial asthma, who had chronic sinusitis and endoscopic sinus surgery (ESS). Patients with asthma were assessed before and after to determine whether asthma improved with first-time ESS. The sinus surgical outcomes were significantly worse in the asthma group, especially the endonasal findings and medication scores. However, asthma patients showed improvement in symptoms, peak flow and medication scores. Editor's comment: Appropriate treatment of sinusitis is essential to control asthma. Dejima K, et al. Int Arch Allergy Immunol 2005; 138: 97.

8. COST-EFFECTIVENESS OF HOME-BASED ENVIRONMENTAL INTERVENTION
This Inner-City Asthma Study is a randomized trial involving home and environmental allergen and irritant remediation among children aged 6 through 11 years with moderate-to-severe asthma. The intervention, which costs $1,469 per family, led to statistically significant reductions in symptom days, unscheduled clinic visits and use of ß-agonist. There was an additional cost of $27.57 per additional symptom free day over the year of intervention and year of follow-up. The authors conclude that intervention is cost-effective when the purpose is to reduce asthma symptoms days and the associated cost. Editor's comment: Environmental controls are helpful for children with asthma. Kattan M, et al. J Allergy Clin Immunol 2005; 116: 1058.

9. ANNUAL INCREASE IN BODY MASS INDEX (BMI) IN CHILDREN WITH ASTHMA ON HIGHER DOSES OF INHALED GLUCOCORTICOSTEROIDS (IGC)
The Tayside Children's Asthma Database (Scotland, U.K.) was used to determine if children taking (IGC) at doses of < 200 µg/ day and > 400 µg/ day for approximately 12 months had a significantly greater annual change in BMI. There was a greater annual increase in BMI in children on the high-dose (0.5 kg/m²/year; n = 100) compared to those on the low-dose (0.1 kg/m²/year; n = 98) (P = .0003). The authors call for additional studies to confirm this observation. Editor's comment: Perhaps this could be dose-related or the more severe asthmatics are less active. Jani M, et al. J Pediatr 2005; 147: 549.

10. "THE SCIENCE OF COPD: OPPORTUNITIES FOR COMBINATION THERAPY"
A review on COPD in the Proceedings of the American Thoracic Society. There are sections on "Issues in Combination Therapy for COPD", "Targeting G-Protein-coupled Receptors in COPD", "Drug Pathways and Their Interactions in COPD Therapy", "COPD as a Multicomponent Disease" and "Opportunities for Combination Therapy in COPD". Editor's comment: An excellent review about the science and treatment of COPD. Proc Am Thorac Soc, 2005; 2: 257-394.

11. A PROPOSED CLASSIFICATION OF AIRWAY DISEASE BASED ON PATHOGENESIS
The authors of this article attempt to define a new taxonomy for airway disease which more closely reflects the spectrum of phenotypes that are encompassed within the term airway inflammatory disease. It takes into consideration disordered physiology and cell biology that characterizes these conditions with the hopes that this new classification will closely define both the etiology and response to treatment. Diseases included in this classification are: Viral wheeze in children, chronic cough, eosinophilic bronchitis, obliterative bronchiolitis, COPD, emphysema, non-smoking fixed obstruction, bronchiectasis, cystic fibrosis, ABPA, asthma, infective bacterial asthma and hyperventilation syndrome. Editor's comment: The authors are to be congratulated for illustrating the overlapping relationships between syndromes characterized by disordered airway function. Wardlaw AJ, et al. Clin Exp Allergy 2005; 35: 1254.

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