Proton-Pump Inhibitor Use and the Risk for Community-Acquired Pneumonia
- Monika Sarkar, MD;
- Sean Hennessy, PharmD, PhD; and
- Yu-Xiao Yang, MD, MSCE
Abstract
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.
Article and Author Information
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Grant Support: By an Academic Development Fund by the Department of Medicine, University of Pennsylvania (Dr. Yang).
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Potential Financial Conflicts of Interest: Consultancies: S. Hennessy (Wyeth), Y.X. Yang (AstraZeneca). Grants received: Y.X. Yang (AstraZeneca, GlaxoSmithKline).
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Reproducible Research Statement: Study protocol: Available from Dr. Yang (e-mail, yangy{at}mail.med.upenn.edu). Statistical code and data set: Not available.
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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.
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Current Author Addresses: Dr. Sarkar: Hospital of the University of Pennsylvania, 3400 Spruce Street, 100 Centrex, Philadelphia, PA 19104.
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Dr. Hennessy: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 803 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021.
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Dr. Yang: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 722 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104-6021.
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Author Contributions: Conception and design: M. Sarkar, S. Hennessy, Y.-X. Yang.
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Analysis and interpretation of the data: M. Sarkar, S. Hennessy, Y.-X. Yang.
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Drafting of the article: M. Sarkar, Y.-X. Yang.
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Critical revision of the article for important intellectual content: M. Sarkar, S. Hennessy, Y.-X. Yang.
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Final approval of the article: M. Sarkar, S. Hennessy, Y.-X. Yang.
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Provision of study materials or patients: Y.-X. Yang.
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Statistical expertise: Y.-X. Yang.
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Obtaining of funding: Y.-X. Yang.
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Administrative, technical, or logistic support: Y.-X. Yang.
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Collection and assembly of data: Y.-X. Yang.
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