title: Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting β2 agonist: observational matched cohort study (PATHOS).
abstract: OBJECTIVE
  To investigate the occurrence of pneumonia and pneumonia related events in patients with chronic obstructive pulmonary disease (COPD) treated with two different fixed combinations of inhaled corticosteroid/long acting β2 agonist.
  
  
  METHODS
  Observational retrospective pairwise cohort study matched (1:1) for propensity score.
  
  
  METHODS
  Primary care medical records data linked to Swedish hospital, drug, and cause of death registry data for years 1999-2009.
  
  
  METHODS
  Patients with COPD diagnosed by a physician and prescriptions of either budesonide/formoterol or fluticasone/salmeterol.
  
  
  METHODS
  Yearly pneumonia event rates, admission to hospital related to pneumonia, and mortality.
  
  
  RESULTS
  9893 patients were eligible for matching (2738 in the fluticasone/salmeterol group; 7155 in the budesonide/formoterol group), yielding two matched cohorts of 2734 patients each. In these patients, 2115 (39%) had at least one recorded episode of pneumonia during the study period, with 2746 episodes recorded during 19,170 patient years of follow up. Compared with budesonide/formoterol, rate of pneumonia and admission to hospital were higher in patients treated with fluticasone/salmeterol: rate ratio 1.73 (95% confidence interval 1.57 to 1.90; P<0.001) and 1.74 (1.56 to 1.94; P<0.001), respectively. The pneumonia event rate per 100 patient years for fluticasone/salmeterol versus budesonide/formoterol was 11.0 (10.4 to 11.8) versus 6.4 (6.0 to 6.9) and the rate of admission to hospital was 7.4 (6.9 to 8.0) versus 4.3 (3.9 to 4.6). The mean duration of admissions related to pneumonia was similar for both groups, but mortality related to pneumonia was higher in the fluticasone/salmeterol group (97 deaths) than in the budesonide/formoterol group (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003). All cause mortality did not differ between the treatments (1.08, 0.93 to 1.14; P=0.59).
  
  
  CONCLUSIONS
  There is an intra-class difference between fixed combinations of inhaled corticosteroid/long acting β2 agonist with regard to the risk of pneumonia and pneumonia related events in the treatment of patients with COPD.
  
  
  BACKGROUND
  Clinical Trials.gov NCT01146392.
authors.affiliation: Department of Medical Sciences, Respiratory Medicine, Uppsala University, Uppsala, Sweden. christer.janson@medsci.uu.se
authors.forename: Christer
authors.initials: C
authors.lastname: Janson
authors.forename: Kjell
authors.initials: K
authors.lastname: Larsson
authors.forename: Karin H
authors.initials: KH
authors.lastname: Lisspers
authors.forename: Björn
authors.initials: B
authors.lastname: Ställberg
authors.forename: Georgios
authors.initials: G
authors.lastname: Stratelis
authors.forename: Helena
authors.initials: H
authors.lastname: Goike
authors.forename: Leif
authors.initials: L
authors.lastname: Jörgensen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Johansson
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D000420:Albuterol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000730:Androstadienes / Q000009:adverse effects* / Q000627:therapeutic use; D019819:Budesonide / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D004983:Ethanolamines / Q000009:adverse effects* / Q000627:therapeutic use; D000068298:Fluticasone; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D011014:Pneumonia / Q000139:chemically induced* / Q000401:mortality*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality*; D000068299:Salmeterol Xinafoate
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D004983:Ethanolamines; D005938:Glucocorticoids; D019819:Budesonide; D000068299:Salmeterol Xinafoate; D000068298:Fluticasone; D000420:Albuterol; D000068759:Formoterol Fumarate