title: Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis.
abstract: OBJECTIVE
  Previous observational studies suggest that the use of proton pump inhibitors (PPIs) may increase the risk of hospitalisation for community-acquired pneumonia (HCAP). However, the potential presence of confounding and protopathic biases limits the conclusions that can be drawn from these studies. Our objective was, therefore, to examine the risk of HCAP with PPIs prescribed prophylactically in new users of non-steroidal anti-inflammatory drugs (NSAIDs).
  
  
  METHODS
  We formed eight restricted cohorts of new users of NSAIDs, aged ≥40 years, using a common protocol in eight databases (Alberta, Saskatchewan, Manitoba, Ontario, Quebec, Nova Scotia, US MarketScan and the UK's General Practice Research Database (GPRD)). This specific patient population was studied to minimise bias due to unmeasured confounders. High-dimensional propensity scores were used to estimate site-specific adjusted ORs (aORs) for HCAP at 6 months in PPI patients compared with unexposed patients. Fixed-effects meta-analytic models were used to estimate overall effects across databases.
  
  
  RESULTS
  Of the 4,238,504 new users of NSAIDs, 2.3% also started a PPI. The cumulative 6-month incidence of HCAP was 0.17% among patients prescribed PPIs and 0.12% in unexposed patients. After adjustment, PPIs were not associated with an increased risk of HCAP (aOR=1.05; 95% CI 0.89 to 1.25). Histamine-2 receptor antagonists yielded similar results (aOR=0.95, 95% CI 0.75 to 1.21).
  
  
  CONCLUSIONS
  Our study does not support the proposition of a pharmacological effect of gastric acid suppressors on the risk of HCAP.
authors.affiliation: Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, McGill University, , Montreal, Quebec, Canada.
authors.forename: Kristian B
authors.initials: KB
authors.lastname: Filion
authors.forename: Dan
authors.initials: D
authors.lastname: Chateau
authors.forename: Laura E
authors.initials: LE
authors.lastname: Targownik
authors.forename: Andrea
authors.initials: A
authors.lastname: Gershon
authors.forename: Madeleine
authors.initials: M
authors.lastname: Durand
authors.forename: Hala
authors.initials: H
authors.lastname: Tamim
authors.forename: Gary F
authors.initials: GF
authors.lastname: Teare
authors.forename: Pietro
authors.initials: P
authors.lastname: Ravani
authors.forename: Pierre
authors.initials: P
authors.lastname: Ernst
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dormuth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D005764:Gastroesophageal Reflux / Q000150:complications / Q000188:drug therapy; D006635:Histamine H2 Antagonists / Q000009:adverse effects; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000139:chemically induced* / Q000453:epidemiology / Q000209:etiology; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors
keywords: Epidemiology; Gastroesophageal Reflux Disease; Meta-Analysis; Proton Pump Inhibition