We read with interest the recent open labeled investigation with etanercept as add‐on therapy in 15 patients with chronic severe asthma by Howarth and colleagues.1 In these patients treatment with etanercept (25 mg administered subcutaneously twice a week for a period of 12 weeks) was associated with a substantial improvement in asthma symptoms, lung function, and bronchial hyperresponsiveness (BHR). The clinical improvement was measured by means of the Juniper asthma control questionnaire (ACQ) score; during treatment with etanercept the ACQ score fell considerably from a mean (range) of 26 (9–32) to 11 (4–27).
The most common adverse effects during treatment were respiratory tract infections (58.8%) and asthma exacerbations (52.9%). Ten of the 15 patients presented with respiratory tract infections associated with worsening of asthma control. The majority of asthma exacerbations are caused by acute respiratory viral infections, of which rhinoviruses are by far the most frequent,2,3 but other respiratory pathogens are also important.4,5 Immunosuppression induced by the inhibition of TNFα is likely to be the cause of the observed high incidence of respiratory infections in these patients; in man, anti‐TNFα treatments have been implicated in increased susceptibility to pneumococcal infection.6
Symptoms due to asthma exacerbations in patients with respiratory infections are likely to severely compromise the quality of life of patients with severe chronic asthma. It was therefore surprising to see that the improvement in the ACQ score after etanercept occurred despite the reported high frequency in respiratory tract infections and asthma exacerbations. Perhaps the substantial improvement in asthma symptoms observed in these patients was merely due to increasing the dose of rescue medications used to manage worsening in asthma control. This may explain why etanercept failed to attenuate pulmonary eosinophilia and to reduce BHR to methacholine in a recent randomised, double blind, placebo controlled trial of patients with a mild form of the disease in whom asthmatic exacerbations were never reported.7 It is therefore important to take into account the overall increase in rescue medications used to control asthma exacerbations as a secondary measure along with the ACQ score.
References
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