title: Predictors of frequent exacerbations in (ex)smoking and never smoking adults with severe asthma.
abstract: 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.
  
  
  
  The aim was to investigate factors associated with frequent exacerbations in never smokers and (ex)smokers with asthma.
  
  
  
  (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).
  
  
  
  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).
  
  
  
  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.
  
  
  
  Netherlands Trial Register: NTR2217, NTR1846 and NTR1838.
authors: Department of Respiratory Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. Electronic address: g.a.westerhof@amc.nl.
authors: Guus A
authors: GA
authors: Westerhof
authors: Department of Respiratory Medicine, Medical Centre Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, The Netherlands.
authors: Jantina C
authors: JC
authors: de Groot
authors: Department of Respiratory Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors: Marijke
authors: M
authors: Amelink
authors: Department of Respiratory Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors: Selma B
authors: SB
authors: de Nijs
authors: Department of Respiratory Medicine, Medical Centre Leeuwarden, Henri Dunantweg 2, 8934 AD, Leeuwarden, The Netherlands.
authors: Anneke
authors: A
authors: Ten Brinke
authors: Department of Respiratory Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors: Els J
authors: EJ
authors: Weersink
authors: Department of Respiratory Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors: Elisabeth H
authors: EH
authors: Bel
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009504:Neutrophils / Q000276:immunology; D011237:Predictive Value of Tests; D012137:Respiratory System / Q000276:immunology / Q000473:pathology; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology
chemical_list: D000305:Adrenal Cortex Hormones
keywords: Adult asthma; Exacerbation; Predictors; Severe asthma; Smokers