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A Population-Based Case-Control Study

Sinem Ezgi Gulmez, MD, PhD; Anette Holm, MD, PhD; Henrik Frederiksen, MD, PhD; Thøger Gorm Jensen, MD, PhD; Court Pedersen, DMSC; Jesper Hallas, DMSC

Arch Intern Med. 2007;167(9):950-955.

Background  Recently, the use of proton pump inhibitors (PPIs) has been associated with an increased risk of pneumonia. We aimed to confirm this association and to identify the risk factors.

Methods  We conducted a population-based case-control study using data from the County of Funen, Denmark. Cases (n = 7642) were defined as all patients with a first-discharge diagnosis of community-acquired pneumonia from a hospital during 2000 through 2004. We also selected 34 176 control subjects, who were frequency matched to the cases by age and sex. Data on the use of PPIs and other drugs, on microbiological samples, on x-ray examination findings, and on comorbid conditions were extracted from local registries. Confounders were controlled by logistic regression.

Results  The adjusted odds ratio (OR) associating current use of PPIs with community-acquired pneumonia was 1.5 (95% confidence interval [CI], 1.3-1.7). No association was found with histamine₂-receptor antagonists (OR, 1.10; 95% CI, 0.8-1.3) or with past use of PPIs (OR, 1.2; 95% CI, 0.9-1.6). Recent initiation of treatment with PPIs (0-7 days before index date) showed a particularly strong association with community-acquired pneumonia (OR, 5.0; 95% 2.1-11.7), while the risk decreased with treatment that was started a long time ago (OR, 1.3; 95% CI, 1.2-1.4). Subgroup analyses revealed high ORs for users younger than 40 years (OR, 2.3; 95% CI, 1.3-4.0). No dose-response effect could be demonstrated.

Conclusion  The use of PPIs, especially when recently begun, is associated with an increased risk of community-acquired pneumonia.

Author Affiliations: Research Unit of Clinical Pharmacology, Faculty of Health Sciences, Institute of Public Health, University of Southern Denmark, Odense (Drs Gulmez, Frederiksen, and Hallas); and Departments of Infectious Medicine (Drs Holm, Pedersen, and Hallas) and Clinical Microbiology (Drs Holm and Jensen), Odense University Hospital.

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