Acid-Suppressive Drugs Linked to Increased Risk for Pneumonia

Laurie Barclay, MD

December 20, 2010

December 20, 2010 — Use of acid-suppressive drugs is linked to increased risk for pneumonia, according to the results of a systematic review and meta-analysis reported online December 20 in the Canadian Medical Association Journal.

"Several previous studies have shown that treatment with acid-suppressive drugs might be associated with an increased risk of respiratory tract infections and community-acquired pneumonia in adults and children," write Chun-Sick Eom, MD, from Seoul National University Hospital in Korea, and colleagues.

"However, the association between use of acid-suppressive drugs and risk of pneumonia has been inconsistent. Given the widespread use of proton pump inhibitors and histamine2-receptor antagonists, clarifying the potential impact of acid-suppressive therapy on the risk of pneumonia is of great importance to public health."

Two evaluators independently extracted data from studies identified through a search of MEDLINE (PubMed), Embase, and the Cochrane Library from inception to August 28, 2009. Pooled estimates of effect were calculated through random effects meta-analysis to account for heterogeneity. Of 31 studies identified, 5 were case-control studies, 3 were cohort studies, and 23 were randomized controlled trials.

Overall risk for pneumonia was higher in persons taking proton pump inhibitors (adjusted odds ratio, 1.27; 95% confidence interval [CI], 1.11 - 1.46; Higgins I 2 value, 90.5%) and in those taking histamine-2 receptor antagonists (adjusted odds ratio, 1.22; 95% CI, 1.09 - 1.36; Higgins I 2 value, 0.0%), based on a meta-analysis of the 8 observational studies. Use of histamine-2 receptor antagonists was also associated with an increased risk for hospital-acquired pneumonia (relative risk, 1.22; 95% CI, 1.01 - 1.48; Higgins I 2 value, 30.6%), based on a meta-analysis of the randomized controlled trials.

"Use of a proton pump inhibitor or histamine-2 receptor antagonist may be associated with an increased risk of both community- and hospital-acquired pneumonia," the study authors write. "Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk."

Limitations of this study include selection of only English-language publication observational studies, possible confounding by the presence of gastroesophageal reflux disease, and heterogeneity in study characteristics.

These findings suggest that 1 of every 200 inpatients treated with acid-suppressive drugs will develop pneumonia, which is even more clinically meaningful given that 40% to 70% of hospitalized patients receive these medications.

"Clinicians should carefully consider any decision to prescribe acid-suppressive drugs, especially for patients who are already at risk for pneumonia," the study authors conclude. "Since it is unnecessary to achieve an achlorhydric state in order to resolve symptoms, we recommend using the optimal effective dose of the drug necessary to achieve desired therapeutic goals."

The Basic Science Research Program of the National Research Foundation of Korea, which is funded by the Ministry of Education, Science, and Technology of the Korean government, supported this study. The study authors have disclosed no relevant financial relationships.

CMAJ. Published online December 20, 2010.

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