Phenotype specific treatment of asthma in childhood.
The term "asthma syndrome" encompasses a range of disorders, all characterised clinically by combinations of cough, wheeze and breathlessness. In older children, evidence of variable airway obstruction is manifest by change in peak flow over time or with treatment, reduction in peak flow on exercise, and a positive methacholine challenge. The underlying pathology includes combinations of bronchial hyperreactivity (BHR), airway inflammation and alterations in underlying baseline airway calibre or compliance. This is not merely of academic importance, but is fundamental to organizing appropriate treatment. In children with symptoms with viral colds and also between colds, and in particular if they are atopic, the underlying abnormality is likely to be T-cell driven, eosinophil-mediated airway inflammation. There is compelling evidence that early treatment with inhaled corticosteroids is essential if airway remodelling is to be avoided and optimum long-term lung function is to be achieved. The pathophysiology of wheezing with viral colds in the non-atopic infant is completely different; such infants have evidence of abnormal lung function soon after birth and before their first episode of viral wheeze, and no evidence of either bronchial hyperreactivity or airflow inflammation. Response to inhaled steroids is very poor. For most infants with wheeze, it is currently not possible to predict whether they will go on to the picture of established asthma. Post-bronchiolitic asthma syndrome also does not respond to inhaled steroids, because prolonged symptoms are likely due to abnormal pre-morbid airway function, albeit worsened by atopy. Phenotype-specific treatment is also important in older children who have severer asthma and do not respond to high dose inhaled steroids. We have delineated a group with marked BHR but no evidence of inflammation who respond to subcutaneous terbutaline, and a second group with steroid resistant inflammation who may do better with cyclosporin. A phenotype-specific treatment approach may also help to delineate which add on therapy (long-acting beta agonist, leukotriene receptor antagonist, theophylline) is best for children with moderate asthma not controlled by moderate dose (400 mcg/day) inhaled corticosteroids. Asthma is not one disease but many, and attention to delineating clinical phenotypes, rather than being obsessed with guidelines based on large heterogeneous groups, may allow rational individual treatment.
Imperial School of Medicine at National Heart and Lung Institute, Royal Brompton Hospital, UK. a.bush@rbh.nthames.nhs.uk
Andrew
A
Bush
D000328:Adult; D000367:Age Factors; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D002648:Child; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology; D010641:Phenotype; D012720:Severity of Illness Index