title: Risk of pneumonia with inhaled corticosteroid versus long-acting bronchodilator regimens in chronic obstructive pulmonary disease: a new-user cohort study.
abstract: BACKGROUND
  Observational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs.
  
  
  OBJECTIVE
  To estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.
  
  
  METHODS
  Pneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding.
  
  
  METHODS
  United Kingdom electronic medical records with linked hospitalization and mortality data (2002-2010). New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up.
  
  
  RESULTS
  severe pneumonia (primary) and any pneumonia (secondary).
  
  
  RESULTS
  Following adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83). Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use. There was an apparent dose-related effect, with greater risk at higher daily doses of ICS. There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.
  
  
  CONCLUSIONS
  The results of this new-user cohort study are consistent with published findings; ICS were associated with a 20-50% increased risk of pneumonia in COPD, which reduced with exposure time. This risk must be weighed against the benefits when prescribing ICS to patients with COPD.
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: Rachael L
authors.initials: RL
authors.lastname: DiSantostefano
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: Tim
authors.initials: T
authors.lastname: Sampson
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: Hoa Van
authors.initials: HV
authors.lastname: Le
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Hinds
authors.affiliation: Worldwide Epidemiology, GlaxoSmithKline, Research Triangle Park, North Carolina, United States of America.
authors.forename: Kourtney J
authors.initials: KJ
authors.lastname: Davis
authors.affiliation: Salford Royal NHS Foundation Trust and Manchester University, Manchester, United Kingdom.
authors.forename: Nawar Diar
authors.initials: ND
authors.lastname: Bakerly
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000150:complications*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D012306:Risk
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D001993:Bronchodilator Agents