Purpose of the Study. To evaluate the effect of salmeterol on allergen-induced airway inflammation.
Study Population. Sixteen atopic patients with mild asthma (10 male, 6 female) >18 years (mean 25.2) old with diagnosis of asthma for at least 6 months. The subjects had stable asthma for at least 1 month and baseline forced expiratory volume in 1 second (FEV1) >70% (mean: 95%). Subjects had to have a late asthmatic response (LAR) to an allergen inhalation challenge, defined as a 15% decrease in FEV1 between 2 and 8 hours after challenge. Patients had to be off of oral or inhaled steroids and any other antiinflammatory medications for at least 1 month before the study.
Methods. The study was a randomized, double-blind, cross-over trial. The subjects underwent baseline allergen skin testing with titration to determine the specific allergen and dose to use for the inhalation challenge. Baseline FEV1 was performed and inhalation challenge was performed to document early asthmatic response (EAR) and LAR. After a 2-week run-in without medication other than rescue albuterol, the subjects underwent a saline challenge a day before randomization. Subjects were randomized to receive either salmeterol 50 μg daily or 1 week of inhaled placebo. They were also allowed to use rescue salbutamol and record the use on diary cards. A 2-week washout period separated the 2 cross-over treatment periods. Subjects recorded asthma symptoms and medication usage on diary cards and had spirometry and methacholine (Mch) challenges before and at the end of each treatment period 24 hours after holding the study medication. They also underwent bronchoalveolar lavage (BAL) and bronchial biopsies 24 hours after an allergen challenge. The allergen challenges were performed before the run-in period and each allergen challenge was preceded the day before by an Mch challenge. Salmeterol or placebo was given on the day of the challenge and bronchoscopy. Allergen challenges were performed with increasing allergen doses until the FEV1 dropped >15% or until the maximum dose was reached, and subjects had repeated spitrometry up to 8 hours postchallenge.
Results. All 16 subjects completed the study. The mean baseline Mch PC20 (Mch dose causing a 20% decrease in FEV1) was 1.53 ± 1.28. The mean percentage drop in FEV1 after allergen challenge for EAR was 28.7 ± 1.7% and for LAR was 24.6 ± 1.8%. Mean PC20 after placebo was 1.15 ± 1.34 and after salmeterol was 2.20 ± 1.31 (P = .009). Salmeterol significantly inhibited the decrease in FEV1 during EAR compared with placebo, but LAR was similar between the 2 groups. There was no significant difference in BAL macrophage, lymphocyte, neutrophil, and eosinophil counts 24 hours after allergen challenge in the 2 treatment groups. However, the salmeterol treated group showed an increase in a number of inflammatory cells on bronchial biopsies after allergen challenge compared with placebo.
Conclusion. This study found an increase in lung mast cells and total leukocyte counts from bronchial biopsies obtained 24 hours after allergen exposure from allergen sensitized asthmatics taking salmeterol regularly for 1 week versus those taking placebo.
Reviewer’s Comments. This study showed an increase in inflammatory cells from bronchial biopsy 24 hours after antigen challenge in asthmatic subjects taking salmeterol for 1 week as monotherapy, versus those taking placebo control. Although salmeterol can improve baseline spirometry and reduce airway responsiveness to allergen, this study suggests that when used alone, salmeterol may be associated with mild increased allergen-induced airway cellular responses. Others studies have found some conflicting effects of salmeterol on various inflammatory markers, both in the serum, BAL fluid, and bronchial biopsies. Compared with inhaled corticosteroids, when used as monotherapy, long-acting β-agonists have been associated with increased frequency of asthma exacerbations. These results support the concomitant use of inhaled corticosteroids with long-acting β-agonists.
- Copyright © 2002 by the American Academy of Pediatrics