title: Prediction of Long-Term Benefits of Inhaled Steroids by Phenotypic Markers in Moderate-to-Severe COPD: A Randomized Controlled Trial.
abstract: BACKGROUND
  The decline in lung function can be reduced by long-term inhaled corticosteroid (ICS) treatment in subsets of patients with chronic obstructive pulmonary disease (COPD). We aimed to identify which clinical, physiological and non-invasive inflammatory characteristics predict the benefits of ICS on lung function decline in COPD.
  
  
  METHODS
  Analysis was performed in 50 steroid-naive compliant patients with moderate to severe COPD (postbronchodilator forced expiratory volume in one second (FEV1), 30-80% of predicted, compatible with GOLD stages II-III), age 45-75 years, >10 packyears smoking and without asthma. Patients were treated with fluticasone propionate (500 μg bid) or placebo for 2.5 years. Postbronchodilator FEV1, dyspnea and health status were measured every 3 months; lung volumes, airway hyperresponsiveness (PC20), and induced sputum at 0, 6 and 30 months. A linear mixed effect model was used for analysis of this hypothesis generating study.
  
  
  RESULTS
  Significant predictors of attenuated FEV1-decline by fluticasone treatment compared to placebo were: fewer packyears smoking, preserved diffusion capacity, limited hyperinflation and lower inflammatory cell counts in induced sputum (p<0.04).
  
  
  CONCLUSIONS
  Long-term benefits of ICS on lung function decline in patients with moderate-to-severe COPD are most pronounced in patients with fewer packyears, and less severe emphysema and inflammation. These data generate novel hypotheses on phenotype-driven therapy in COPD.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00158847.
authors.affiliation: Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jiska B
authors.initials: JB
authors.lastname: Snoeck-Stroband
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Therese S
authors.initials: TS
authors.lastname: Lapperre
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
authors.affiliation: Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Henk A
authors.initials: HA
authors.lastname: Thiadens
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands.
authors.forename: Nick H T
authors.initials: NH
authors.lastname: Ten Hacken
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands.
authors.forename: Huib A M
authors.initials: HA
authors.lastname: Kerstjens
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pulmonology, Groningen, The Netherlands.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pathology, Groningen, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.affiliation: Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Jacob K
authors.initials: JK
authors.lastname: Sont
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000368:Aged; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D000068298:Fluticasone / Q000627:therapeutic use; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015990:Placebo Effect; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D013147:Spirometry; D013183:Sputum; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D001993:Bronchodilator Agents; D000068298:Fluticasone