Use of acid suppressing drugs may be associated with a modestly increased risk of pneumonia, according to a systematic review and meta-analysis.

Evidence suggests that treatment with acid-suppressing drugs, histamine-2 receptor antagonists (H2RA) and proton-pump inhibitors (PPI), is associated with an increased risk of pneumonia. It is inconsistent, however, and the authors carried out this systematic review and meta-analysis to summarise the available evidence. They performed a comprehensive literature search for observational studies and randomised controlled trials that reported an estimate of effect for a potential association between the use of acid-suppressive drugs and the risk of pneumonia.

The initial search yielded 2,377 possible articles for observational studies and 8,513 possible articles for controlled trials; of these, there were 31 eligible studies, 5 case–control studies, 2 cohort studies and 23 randomized controlled trials, published between 1985 and 2009. Meta-analysis of the observational studies showed that the overall risk of pneumonia was higher among people using both PPI (adjusted odds ratio [OR] 1.27, 95% CI 1.11 to 1.46) and H2RA (adjusted OR 1.22; 95% CI 1.09 to 1.36). Controlled trial data were only available for H2RA, and these confirmed an increased risk of hospital-acquired pneumonia associated with treatment (relative risk 1.22; 95% CI 1.01 to 1.48). Sub-group analyses gave similar results by type of pneumonia and suggested a dose-response relationship. Sub-group analysis by duration of treatment found a decreasing risk with longer duration of treatment before the index date (diagnosis of pneumonia).

Based on their analysis, the authors conclude that use of acid-suppressing drugs is associated with an increased risk of pneumonia. Using previously published data, they estimate that if pneumonia occurs in about 20 patients per 1,000 admitted to hospital not taking acid-suppressing drugs, the rate will be about 24 to 25 per 1,000 in those taking these drugs. Given their widespread use, they suggest that the associated morbidity and mortality will potentially be significant. They discuss possible mechanisms for the effect and explanations for the decrease in risk with longer duration of use. Overall, they interpret their results to indicate that clinicians should consider carefully whether use of these drugs is necessary, and if it is, to use the minimum dose needed.