title: Lung function decline and variable airway inflammatory pattern: longitudinal analysis of severe asthma.
abstract: BACKGROUND
  Eosinophilic airway inflammation measured by using induced sputum is an important treatment stratification tool in patients with severe asthma. In addition, sputum eosinophilia has been shown to be associated with severe exacerbations and airflow limitation.
  
  
  OBJECTIVE
  We sought to identify whether eosinophilic inflammation in sputum is associated with FEV₁ decrease in patients with severe asthma and whether we could identify subgroups of decrease behavior based on the variation of eosinophilic airway inflammation over time.
  
  
  METHODS
  Ninety-seven patients with severe asthma from the Glenfield Asthma Cohort were followed up with scheduled 3-month visits; the median duration of follow-up and number of visits was 6 years (interquartile range, 5.6-7.6 years) and 2.7 visits per year. Induced sputum was analyzed for eosinophilic inflammation at scheduled visits. Linear mixed-effects models were used to identify variables associated with lung function and overall decrease. In addition, using individual patients' mean and SD sputum eosinophil percentages over time, a 2-step cluster analysis was performed to identify patient clusters with different rates of decrease.
  
  
  RESULTS
  FEV₁ decrease was -25.7 mL/y in the overall population. Postbronchodilator FEV₁ was also dependent on exacerbations, age of onset, height, age, sex, and log10 sputum eosinophil percentages (P < .001). Three decrease patient clusters were identified: (1) noneosinophilic with low variation (mean decrease, -14.0 mL/y), (2) eosinophilic with high variation (mean decrease, -40.9 mL/y), and (3) hypereosinophilic with low variation (mean decrease in lung function, -19.2 mL/y).
  
  
  CONCLUSIONS
  The amplitude of sputum eosinophilia was associated with postbronchodilator FEV₁ in asthmatic patients. In contrast, high variability rather than the amplitude at baseline or over time of sputum eosinophils was associated with accelerated FEV₁ decrease.
authors.affiliation: Department of Health Sciences, University of Leicester, Leicester, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Newby
authors.affiliation: Department of Infection Immunity and Inflammation/Institute for Lung Health, University of Leicester/Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Joshua
authors.initials: J
authors.lastname: Agbetile
authors.affiliation: Department of Infection Immunity and Inflammation/Institute for Lung Health, University of Leicester/Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Beverley
authors.initials: B
authors.lastname: Hargadon
authors.affiliation: Department of Infection Immunity and Inflammation/Institute for Lung Health, University of Leicester/Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Will
authors.initials: W
authors.lastname: Monteiro
authors.affiliation: Department of Infection Immunity and Inflammation/Institute for Lung Health, University of Leicester/Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Green
authors.affiliation: Oxford University Hospitals, Oxford University, NDM Research Building, Oxford, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Pavord
authors.affiliation: Department of Infection Immunity and Inflammation/Institute for Lung Health, University of Leicester/Glenfield Hospital, Leicester, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Brightling
authors.affiliation: Department of Infection Immunity and Inflammation/Institute for Lung Health, University of Leicester/Glenfield Hospital, Leicester, United Kingdom. Electronic address: salman95@yahoo.com.
authors.forename: Salman
authors.initials: S
authors.lastname: Siddiqui
mesh_terms: D000328:Adult; D001249:Asthma / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D001993:Bronchodilator Agents / Q000627:therapeutic use; D004802:Eosinophilia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D008137:Longitudinal Studies; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry / Q000166:cytology
chemical_list: D001993:Bronchodilator Agents
keywords: Severe asthma; airway inflammation; eosinophilia; induced sputum; lung function decline