Montelukast and Theophylline: No Use or Some Use in Persistent Asthma?

Abstract

The recent study by the American Lung Association Asthma Clinical Research Centers suggests that prescribing montelukast or theophylline for symptomatic patients with asthma, irrespective of existing treatment, confers little further benefit (1). However, before extrapolating their findings into everyday clinical practice it is important to consider several points regarding the validity of the study. First, between 21 and 26% of randomized patients were not using regular inhaled corticosteroids, while the vast majority of these alarmingly appeared to be maintained on long-acting 2-agonists as monotherapy. Second, since the mean prebronchodilator FEV1 in the symptomatic patients with asthma enrolled was between 78 and 80% predicted, it would appear reasonable to consider that inhaled corticosteroids—a fundamental component in all but the mildest of asthma—should have been instituted in “real life” before consideration of montelukast or theophylline. Third, at the end of the 24-week study, as many as 40% of individuals failed to adhere to randomized treatment. Fourth, the spectrum of asthma severity appears to have varied considerably in the study, presumably with patients with an FEV1 of 50% of predicted up to normal values. Moreover, while some patients were receiving no treatment prior to study entry, up to 40%were receiving combined inhaled corticosteroid and long-acting 2-agonist preparations. Finally, the authors failed to evaluate effects on underlying airway inflammation or airway hyperresponsiveness, which are undoubtedly integral pathophysiological components of the underlying syndrome of asthma. In view of shortcomings such as inappropriate maintenance therapy during the study, patient heterogeneity, and failure to evaluate inflammatory biomarkers, it may be understandable that the authors failed to demonstrate any benefit with the addition of montelukast or theophylline. Moreover, these factors may also explain why the current findings appear to contradict those of others, in terms of beneficial effects of add-on montelukast in the correct clinical setting across a spectrum of asthma phenotypes (2).