Objectives

To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke.

Background

One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control.

Participants

Steroid-naive male and female subjects between the ages of 18 and 50 years with a history of asthma (28) were recruited. All were required to have prebronchodilator FEV1 values of 70 to 90% of predicted and heightened airway reactivity as indicated by 12% or greater reversibility after albuterol inhalation or by PC20 (provocative concentration causing a 20% fall in FEV1) methacholine of less than 8 mg/ml. Nonsmokers were required to have a total lifetime smoking history of less than 2 pack-years, and no smoking for at least 1 year. Subjects were enrolled as smokers if they were currently smoking 10 to 40 cigarettes/day, had a 2 to 15 pack-year smoking history, and a diffusing capacity of carbon monoxide (DlCO) of 80% of predicted or greater. To avoid inclusion of subjects with COPD, exclusion criteria included age older than 50, smoking history of greater than 15 pack-years, active smoking of more than 40 cigarettes/day, and DlCO less than 80% of predicted.

Design

In a multicenter, placebo-controlled, double-blind, doubledummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast.

Primary outcome was change in prebronchodilator FEV1 in smokers versus nonsmokers. Secondary outcomes included peak flow, PC20 methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV1, bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV1 (170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased A.M. peak flow in smokers (12.6 L/min, p = 0.002), but not in nonsmokers.

Conclusions

In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke.

Request Data

Please note that researchers must be registered on this site to submit a request, and you will be prompted to log in. If you are not registered on this site, you can do so via the Request button. Registration is quick, easy and free.