title: Frequency and time to onset of community-acquired respiratory tract infections in patients receiving esomeprazole: a retrospective analysis of patient-level data in placebo-controlled studies.
abstract: BACKGROUND
  Debate continues on whether a causal association exists between the use of proton pump inhibitors (PPIs) and the risk of respiratory tract infections, in particular pneumonia.
  
  
  OBJECTIVE
  To investigate the occurrence of community-acquired respiratory tract infections, including pneumonia, in patients receiving esomeprazole.
  
  
  METHODS
  A retrospective investigation of pooled data on adverse events related to respiratory tract infections, originally reported in 24 randomised, double-blind clinical studies, was conducted. The frequencies of respiratory tract infections and their relative risks were calculated retrospectively for the total patient population (9602 patients receiving esomeprazole and 5500 receiving placebo) and for sub-populations defined according to sex, age, esomeprazole dose, indication and geographical region. The cumulative frequency of first occurrence of events was calculated over 180 days.
  
  
  RESULTS
  Frequencies of respiratory tract infections were similar in patients receiving esomeprazole and in those receiving placebo (any respiratory tract infection or signs/symptoms potentially indicating an respiratory tract infection, 0.278 and 0.296 patients per patient-year; lower respiratory tract infections, 0.048 and 0.058 per patient-year; pneumonia, 0.006 and 0.009 per patient-year, respectively). The relative risk for any respiratory tract infection in patients receiving esomeprazole compared with placebo was 0.94 (95% CI, 0.86-1.04). For lower respiratory tract infections, the relative risk was 0.82 (95% CI, 0.65-1.03) and for pneumonia, 0.66 (95% CI, 0.36-1.22). Sub-analyses by demographics, dose and indication yielded similar results to the overall analysis. The occurrence of respiratory tract infections was evenly distributed over time and similar in the esomeprazole and placebo groups.
  
  
  CONCLUSIONS
  There is no causal association between treatment with esomeprazole and the occurrence of community-acquired respiratory tract infections, including pneumonia.
authors.affiliation: Patient Safety, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Estborn
authors.affiliation: Patient Safety, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Joelson
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D017714:Community-Acquired Infections / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064098:Esomeprazole / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000453:epidemiology; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D012141:Respiratory Tract Infections / Q000453:epidemiology*; D012189:Retrospective Studies; D012737:Sex Factors; D055815:Young Adult
chemical_list: D054328:Proton Pump Inhibitors; D064098:Esomeprazole