Randomized trial of allergen-induced asthmatic response in smokers andnon-smokers: effects of inhaled corticosteroids.

Abstract

It is thought that asthmatics who smoke cigarettes respond less well to inhaled corticosteroid (ICS) therapy than asthmatics who do not smoke. To evaluate the effects of smoking on allergen-induced airway responses in asthmatics treated with ICS. Randomized, double-blind, crossover study evaluating twice daily fluticasone propionate (FP) 100μg, FP 500μg and placebo, for 7days, on allergen-induced asthmatic responses in 18 non-smoking and 17 smoking atopic asthmatics (NCT01400906). At 1h post-morning dose on Day 6, forced expiratory volume in 1 sec (FEV1 ) was measured up to 10h post-challenge. Exhaled nitric oxide (eNO), induced sputum cell counts, and responsiveness to methacholine were assessed the following day. The late asthmatic response (LAR) was suppressed by FP in smokers and non-smokers; with placebo, the LAR was also attenuated in smokers versus non-smokers (adjusted mean minimum change in FEV1 (L) over 4-10h [95% CI] in non-smokers: placebo -1.01 [1.31, 0.70], FP 100μg -0.38 [0.54, 0.22], FP 500μg -0.35 [0.54-0.22]; and in smokers: placebo -0.63 [0.84, 0.43]; FP 100μg -0.44 [0.65, 0.23]; FP 500μg -0.46 [0.59-0.32]). The Early AR was suppressed by FP treatment in non-smokers, but was not impacted in smokers. The reduction in methacholine hyperresponsiveness after FP was greater in non-smokers (1.5- and twofold doubling dose difference from placebo after FP 100μg and FP 500μg) than smokers (1.0 and 1.3 difference, respectively). Allergen-induced increases in eNO and sputum eosinophils were lower in smokers than non-smokers and were suppressed in both groups by FP. Allergen-induced LARs were of a similar amplitude in both smoking and non-smoking atopic asthmatics at the end of ICS treatment, but attenuation of the LAR in smokers was only partly associated with ICS treatment. The marked attenuation of the LAR observed in smokers in the absence of ICS treatment is a novel observation.