Proton-Pump Inhibitor Use and the Risk for Community-Acquired Pneumonia

16 September 2008 | Volume 149 Issue 6 | Pages 391-398

Background: Recent studies suggest that proton-pump inhibitors (PPIs) may increase the risk for community-acquired pneumonia (CAP).

Objective: To examine the association between PPI use and CAP in adults followed in general practices in the United Kingdom.

Design: Nested case–control study.

Setting: The General Practice Research Database (1987 to 2002) in the United Kingdom.

Participants: Patients age 18 years or older with at least 6 months of initial pneumonia-free follow-up in the database. Case patients (n = 80 066) were defined as those who received an incident diagnosis of CAP. Control participants (n = 799 881) were selected by using incidence density sampling, matching on practice site, calendar period, and follow-up duration.

Measurements: Use of PPIs within 30 days before the index date. Adjusted odds ratios (ORs) were estimated by using conditional logistic regression, adjusting for potential confounders.

Results: Overall, current PPI use was not associated with an increased risk for CAP (adjusted OR, 1.02 [95% CI, 0.97 to 1.08]) or risk for CAP that required hospitalization (adjusted OR, 1.01 [CI, 0.91 to 1.12]). There was a strong increase in risk for CAP associated with current use of PPI therapy that was started within the previous 2 days (adjusted OR, 6.53 [CI, 3.95 to 10.80]), 7 days (adjusted OR, 3.79 [CI, 2.66 to 5.42]), and 14 days (adjusted OR, 3.21 [CI, 2.46 to 4.18]), but there was no statistically significant association for longer-term current PPI therapy. A separate matched case–control analysis, which included the 3 strongest confounders as additional matching factors, yielded similar results as the primary analysis (adjusted OR, 0.96 [CI, 0.91 to 1.02]).

Limitations: Adherence to PPI prescription was assumed to be 100%. No radiographic evidence was available to corroborate a diagnosis of CAP.

Conclusion: Proton-pump inhibitor therapy started within the past 30 days was associated with an increased risk for CAP, whereas longer-term current use was not.

Editors' Notes Context Some studies suggest that proton-pump inhibitors (PPIs) may increase risk for community-acquired pneumonia (CAP). Contribution This large, nested case–control study involving adults in general practices in the United Kingdom found that current, long-term PPI use was not associated with increased risk for CAP. Recently started PPI therapy was associated with increased risk: Adjusted odds ratios for PPI use started within 2, 7, and 14 days of CAP diagnosis were 6.5, 3.8, and 3.2, respectively. Implication Long-term PPI use is not associated with increased risk for CAP. The association between recently started PPIs and CAP risk is not clear but is not necessarily causal. —The Editors

 

Author and Article Information

From the University of Pennsylvania, Philadelphia, Pennsylvania.

Grant Support: By an Academic Development Fund by the Department of Medicine, University of Pennsylvania (Dr. Yang).

Potential Financial Conflicts of Interest: Consultancies: S. Hennessy (Wyeth), Y.X. Yang (AstraZeneca). Grants received: Y.X. Yang (AstraZeneca, GlaxoSmithKline).

Reproducible Research Statement: Study protocol: Available from Dr. Yang (e-mail, yangy{at}mail.med.upenn.edu). Statistical code and data set: Not available.

Requests for Single Reprints: Yu-Xiao Yang, MD, MSCE, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 722 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021; e-mail, yangy{at}mail.med.upenn.edu.

Current Author Addresses: Dr. Sarkar: Hospital of the University of Pennsylvania, 3400 Spruce Street, 100 Centrex, Philadelphia, PA 19104.

Dr. Hennessy: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 803 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021.

Dr. Yang: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 722 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021.

Author Contributions: Conception and design: M. Sarkar, S. Hennessy, Y.-X. Yang.

Analysis and interpretation of the data: M. Sarkar, S. Hennessy, Y.-X. Yang.

Drafting of the article: M. Sarkar, Y.-X. Yang.

Critical revision of the article for important intellectual content: M. Sarkar, S. Hennessy, Y.-X. Yang.

Final approval of the article: M. Sarkar, S. Hennessy, Y.-X. Yang.

Provision of study materials or patients: Y.-X. Yang.

Statistical expertise: Y.-X. Yang.

Obtaining of funding: Y.-X. Yang.

Administrative, technical, or logistic support: Y.-X. Yang.

Collection and assembly of data: Y.-X. Yang.

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