Effect of salmeterol on allergen-induced airway inflammation in mild allergic asthma

Background A previous study suggested that the long-acting beta (2)-adrener gic agonist salmeterol (SM) had inhibitory effects on bronchial mucosal inf lammation 6 hours after allergen exposure. Objective To further evaluate the influence of SM on allergen-induced airwa y inflammation. Methods We studied, in a randomized, double-blind, cross-over trial, 16 mil d asthmatic patients who had a dual asthmatic response to allergen inhalati on. Subjects received 50 mug of SM or placebo (P), twice daily for 1 week e ach, separated by a 2-week wash-out period. At the end of each treatment pe riod, after withholding SM for 24 h, they had a methacholine inhalation tes t (medication was resumed after the test), followed 24 h later by an AC wit h the concentration of allergen that had induced a LAR at baseline. Airway inflammation was assessed 24 h after the AC by bronchoalveolar lavage (BAL) (n = 16) and bronchial biopsies (n = 13). Results As expected, SM improved baseline FEV1 and PC20 (P less than or equ al to 0.009) and decreased the allergen-induced early bronchoconstrictive r esponse. There were no significant differences in BAL cell counts after the two treatments. On bronchial biopsies, numbers (median, mm(2)) of submucos al CD45 (P: 43 +/- 23; SM: 161 +/- 43, P = 0.031), CD45Ro (P: 37 +/- 19; SM : 126 +/- 41, P = 0.047) and AA1 positive cells (P: 38 +/- 6, SM: 65 +/- 17 , P = 0.006) were significantly higher after SM than P treatment. The numbe rs of CD4 (P: 11 +/- 10; SM: 32 +/- 7, P = 0.085), HLA-DR (P: 65 +/- 30; SM : 116 +/- 36, P = 0.079) and EG2 positive cells (P: 25 +/- 15; SM: 38 +/- 2 6, P = 0.09) tended to increase with SM treatment. Conclusion In summary, compared to placebo, 1 week of regular use of SM is associated with an increase in bronchial inflammatory cells 24 h after AC. This is in keeping with the recommendation that salmeterol should only be u sed with an anti-inflammatory agent, particularly in the context of signifi cant allergen exposure.