• Guus A Westerhof, Jantina C de Groot, Marijke Amelink, Selma B de Nijs, Anneke Ten Brinke, Els J Weersink, and Elisabeth H Bel.
• Department of Respiratory Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. Electronic address: g.a.westerhof@amc.nl.
• Respir Med. 2016 Sep 1; 118: 122-127.

BackgroundPersistent eosinophilic airway inflammation is an important driver for asthma exacerbations in non-smokers with asthma. Whether eosinophilic inflammation is also a predictor of asthma exacerbations in (ex)smokers is not known.ObjectiveThe aim was to investigate factors associated with frequent exacerbations in never smokers and (ex)smokers with asthma.Methods(Ex)smoking (n = 83) and never smoking (n = 70) patients with uncontrolled asthma despite high dose asthma medication (GINA treatment step 4-5) were selected from a cohort of 571 adult-onset asthma patients. Clinical, functional and inflammatory parameters were used in multivariate logistic regression analyses to identify factors associated with frequent exacerbations (≥3 oral corticosteroid (OCS) bursts in the previous year).ResultsFrequent exacerbations in (ex)smokers were independently associated with ICS dose (OR 1.2, 95%CI: 1.1-1.3) and blood neutrophil count (OR 1.5, 95%CI: 1.2-2.1). In never smokers frequent exacerbations were independently associated with blood eosinophil count (OR 18.9, 95%CI: 1.8-202.1).Conclusion And Clinical RelevanceThis study shows that never smoking and (ex)smoking patients with severe asthma have different predictors of frequent exacerbations: higher blood neutrophils in (ex)smokers versus higher blood eosinophils in never smokers. This suggests that different types of systemic background inflammation play a role in the aetiology of exacerbations in these patients.Clinical Trial RegistrationNetherlands Trial Register: NTR2217, NTR1846 and NTR1838.Copyright © 2016 Elsevier Ltd. All rights reserved.

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