Predictors of frequent exacerbations in (ex)smoking and never smoking adults with severe asthma

Abstract Background Persistent 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. Objective The 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). Results Frequent 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 relevance This 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 registration Netherlands Trial Register: NTR2217, NTR1846 and NTR1838.