DENVER—Historically, smokers have been excluded from most studies of inhaled corticosteroids (ICS) for asthma because investigators feared that positive smoking status would confound the results. Therefore, not much is known about how smoking influences the effectiveness of ICS in asthma patients.

That will change in a year or so, when Stephen C. Lazarus, MD, and colleagues expect to complete the Smoking Modulates Outcomes of Glucocorticoid Therapy in Asthma (SMOG) study, an investigation designed specifically to compare smoking and nonsmoking asthma patients before and after ICS therapy. “The study grew out of the surprising and somewhat depressing realization that about 10% to 30% of patients with asthma smoke,” remarked Dr. Lazarus, a Professor of Pulmonary and Critical Care Medicine at the University of California in San Francisco, at the annual meeting of the American Academy of Allergy, Asthma and Immunology in Denver.[1]

Preliminary results for the first 60 patients in the study support data from recent smaller investigations hinting that smoking may blunt the response to ICS in asthma patients.[2] Indeed, after eight weeks of ICS treatment, smokers had a lower peak expiratory flow, more asthma symptoms, and poorer quality of life scores than did their nonsmoking counterparts.

As part of the study’s crossover design, patients received another eight weeks of therapy with the leukotriene receptor antagonist montelukast. Smoking reduced that drug’s effectiveness, too.

SMOG: INCLUSION CRITERIA AND TREATMENT

To be included in the double-blind placebo-controlled study, patients must be between ages 18 and 50, have a history of asthma, and have a forced expiratory volume in one second (FEV1) of 70% to 80% of predicted. They must also show a 20% drop in FEV1 when challenged with less than 8 mg/mL of methacholine, or they must experience a 12% FEV1 increase after receiving albuterol.

Smokers participating in the study must smoke at least 10 cigarettes daily, with a limit of 40 per day during the past year. They must also have a cumulative smoking history of five to 15 pack-years. The investigators are attempting to exclude patients with occult chronic obstructive pulmonary disease, as this would obviously confound their results.

The principal outcome is a change in FEV1 after ICS use. Patients are initially randomized to either 320 mg of inhaled beclomethasone twice daily or 10 mg of montelukast once daily (at night). When the first treatment interval is complete, patients switch to the opposite therapy after a washout period.

WELL-MATCHED GROUPS

In the preliminary analysis, the smokers had a mean cumulative pack-year history of 7.25, which was reflected by their cotinine levels. In contrast, cotinine measurements among the nonsmokers indicated a complete lack of cigarette use, as well as minimal secondhand smoke exposure.

Smokers and nonsmokers were well matched for age (about 28 years, on average), sex, and other standard demographics, as well as for asthma duration (more than 10 years in most cases). They were also well matched for sputum eosinophil and neutrophil counts and for FEV1 (both absolute and as a percentage of predicted); however, the lung function measurements tended to be slightly lower among smokers.

Importantly, diffusing capacity was no different between smokers and nonsmokers, Dr. Lazarus pointed out. Furthermore, the two groups had identical responses to bronchodilators and methacholine.

Despite these similarities, smokers and nonsmokers had highly significant differences in peak flow, asthma symptoms, and asthma quality of life after both ICS and montelukast treatment. No difference was observed in the absolute or relative proportions of sputum epithelial cells, macrophages, eosinophils, or neutrophils. Surprisingly, smokers had far fewer sputum lymphocytes after treatment, although the significance of this finding is unknown. Dr. Lazarus remarked that “it will be interesting [to see] if this correlates with any of the outcomes, again in keeping with the idea that there is something different about the inflammation in smokers than … in the rest of the population.”

—Timothy Begany