Risk of Community-Acquired Pneumonia with Outpatient Proton-Pump Inhibitor Therapy: A Systematic Review and Meta-Analysis

Abstract

BackgroundProton-pump inhibitors (PPIs) are among the most frequently prescribed medications. Community-acquired pneumonia (CAP) is a common cause of morbidity, mortality and healthcare spending. Some studies suggest an increased risk of CAP among PPI users. We conducted a systematic review and meta-analysis to determine the association between outpatient PPI therapy and risk of CAP in adults.MethodsWe conducted systematic searches of MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Scopus and Web of Science on February 3, 2014. Case-control studies, case-crossover, cohort studies and randomized controlled trials reporting outpatient PPI exposure and CAP diagnosis for patients ≥18 years old were eligible. Our primary outcome was the association between CAP and PPI therapy. A secondary outcome examined the risk of hospitalization for CAP and subgroup analyses evaluated the association between PPI use and CAP among patients of different age groups, by different PPI doses, and by different durations of PPI therapy.ResultsSystematic review of 33 studies was performed, of which 26 studies were included in the meta-analysis. These 26 studies included 226,769 cases of CAP among 6,351,656 participants. We observed a pooled risk of CAP with ambulatory PPI therapy of 1.49 (95% CI 1.16, 1.92; I2 99.2%). This risk was increased during the first month of therapy (OR 2.10; 95% CI 1.39, 3.16), regardless of PPI dose or patient age. PPI therapy also increased risk for hospitalization for CAP (OR 1.61; 95% CI: 1.12, 2.31).DiscussionOutpatient PPI use is associated with a 1.5-fold increased risk of CAP, with the highest risk within the first 30 days after initiation of therapy. Providers should be aware of this risk when considering PPI use, especially in cases where alternative regimens may be available or the benefits of PPI use are uncertain.

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

“…Respiratory infections such as community acquired pneumonia have been also linked to PPI use. A recent met-analysis of 26 studies reported 49% increase in the risk of community acquired pneumonia, which was at its highest during the first 30 days of PPI initiation [82]. Data also have shown associations between PPIs and increased upper respiratory tract infections and asthma exacerbation in pediatric population [83,95].…”

Asthma and Gastroesophageal Reflux Disease in Children – Completing the Puzzle

“…30 If asymptomatic reflux is suspected, treatment with PPIs is unlikely to ameliorate the symptoms of asthma; if symptomatic reflux is found, a three-month therapeutic trial with PPIs may be reasonable, but if there is no response, the drug should be immediately interrupted. There is a concerning increase in pneumonia 31 and in activity-related bone fractures 32 in children treated with PPIs that calls for a warning in the use of these medications.…”

PPIs and hypomagnesaemia: more common than we thought?

“…[1][2][3][4] Over the last decade, our knowledge of these potential harms has expanded and although some reviewers have concluded that associations may be explained by confounding, 5 other work supports the legitimacy of the earlier safety signals. [6][7][8][9][10] Studies have also emerged more recently reporting other possible serious consequences of PPI use, such as an association with myocardial infarction (MI) and dementia. 11,12 However, further research in these areas is required, to inform our understanding and consequently clarify whether there is a need for us to change PPI prescribing practices.…”