Proton pump inhibitors therapy and the risk of pneumonia: a systematic review and meta‐analysis of randomized controlled trials and observational studies
- 22 February 2019
- journal article
- research article
- Published by Informa UK Limited in Environment, Development and Sustainability
- Vol. 18 (3), 163-172
- https://doi.org/10.1080/14740338.2019.1577820
Abstract
Objective: We aimed to summarize the current evidence regarding the risk of pneumonia associated with proton pump inhibitors (PPI) treatment. Methods: We searched PubMed, Embase, and CENTRAL from the 1970 through December 2017. We included both randomized controlled trials (RCTs) and observational studies. We used random-effect model to calculate the summary effect estimates and quantified the heterogeneity by I-2 statistics. Results: A total of 7,643,982 patients from 10 RCTs and 48 observational studies were included in this meta-analysis. The primary meta-analysis demonstrated PPIs use was significantly associated with increased risk of pneumonia, but the heterogeneity was high (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.30-1.57; I-2, 95.4%). The sensitivity analysis indicated PPIs were not statistically associated with increased risk of pneumonia among patients concomitantly taking nonsteroidal anti-inflammatory drugs (OR, 1.11; 95% CI, 0.94-1.31; I-2, 5.8%). The funnel plot demonstrated significant publication bias, especially for observational studies. Conclusions: The presence of significant between-study heterogeneity and publication bias raised concerns regarding the validity of the primary meta-analytic result. Protopathic bias, or reverse causality, may cause overestimated association. Studies that adopted a design to account for protopathic bias did not show a significant association between PPI use and risk of pneumonia.Keywords
Funding Information
- National Taiwan University Hospital (108-S4091)
- Taiwan National Ministry of Science and Technology (104-2314-B-002-039-MY3)
This publication has 93 references indexed in Scilit:
- Proton pump inhibitors and the risk of pneumonia: a comparison of cohort and self-controlled case series designsBMC Medical Research Methodology, 2013
- Increased Risk of Pneumonia Among Patients With Inflammatory Bowel DiseaseAmerican Journal Of Gastroenterology, 2013
- Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term non-steroidal anti-inflammatory drug (NSAID) therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trialThe Esophagus, 2012
- Lansoprazole for secondary prevention of gastric or duodenal ulcers associated with long-term low-dose aspirin therapy: results of a prospective, multicenter, double-blind, randomized, double-dummy, active-controlled trialThe Esophagus, 2011
- Use of proton pump inhibitors and H2 blockers and risk of pneumonia in older adults: a population-based case-control studyPharmacoepidemiology and Drug Safety, 2010
- Acid-Suppressive Medication Use and the Risk for Hospital-Acquired PneumoniaJAMA, 2009
- Observed association between antidepressant use and pneumonia risk was confounded by comorbidity measuresJournal of Clinical Epidemiology, 2007
- Use of Proton Pump Inhibitors and the Risk of Community-Acquired PneumoniaArchives of Internal Medicine, 2007
- Risk of Community-Acquired Pneumonia and Use of Gastric Acid–Suppressive DrugsJAMA, 2004
- Meta-analysis in clinical trialsControlled Clinical Trials, 1986