Confounding in the Association of Proton Pump Inhibitor Use With Risk of Community-Acquired Pneumonia
Use of proton pump inhibitors (PPIs) is associated with community-acquired pneumonia (CAP), an association which may be confounded by unobserved patient and prescriber characteristics.
We assessed for confounding in the association between PPI use and CAP by using a ‘falsification approach,’ which estimated whether PPI use is also implausibly associated with other common medical conditions for which no known pathophysiologic link exists.
Retrospective claims-based cohort study.
Six private U.S. health plans.
Individuals who filled at least one prescription for a PPI (N = 26,436) and those who never did (N = 28,054) over 11 years.
Multivariate linear regression of the association between a filled prescription for a PPI and a diagnosis of CAP in each 3-month quarter. In falsification analyses, we tested for implausible associations between PPI use in each quarter and rates of osteoarthritis, chest pain, urinary tract infection (UTI), deep venous thrombosis (DVT), skin infection, and rheumatoid arthritis. Independent variables included an indicator for whether a prescription for a PPI was filled in a given quarter, and quarterly indicators for various co-morbidities, age, income, geographic location, and marital status.
Compared to nonusers, those ever using a PPI had higher adjusted rates of CAP in quarters in which no prescription was filled (68 vs. 61 cases per 10,000 persons, p < 0.001). Similar associations were noted for all conditions (e.g. chest pain, 336 vs. 282 cases, p < 0.001; UTI, 151 vs. 139 cases, p < 0.001). Among those ever using a PPI, quarters in which a prescription was filled were associated with higher adjusted rates of CAP (111 vs. 68 cases per 10,000, p < 0.001) and all other conditions (e.g. chest pain, 597 vs. 336 cases, p < 0.001; UTI, 186 vs. 151 cases, p < 0.001), compared to quarters in which no prescription was filled.
PPI use is associated with CAP, but also implausibly associated with common medical conditions. Observed associations between PPI use and CAP may be confounded.
KEY WORDSproton pump inhibitors pneumonia falsification testing
All authors were involved in the study design and concept, interpretation of results and editing of manuscript. Drs. Jena and Sun analysed the data set and wrote the initial manuscript draft. Dr. Jena obtained ethical approval for the project. Dr. Goldman obtained funding. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.
National Institute on Aging. The design, conduct, analysis, interpretation, and presentation of the data are the responsibility of the investigators, with no involvement from the funding sources.
Conflict of Interest
The authors declare that they do not have a conflict of interest.
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