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This study analysed 364 683 patients from an established Dutch primary care database comprising full electronic patient records. Patients were described as exposed (n = 19 459) if they were prescribed acid suppression (proton pump inhibitor (PPI) or H2 receptor antagonist (H2RA)) and were followed until the development of pneumonia or the end of the study period. A total of 977 893 patient-years of data were obtained. The unadjusted relative risk of pneumonia in the exposed group was 4.5 (95% CI 3.8 to 5.1) compared with the non-exposed group. A nested case-control study using 475 patients and 4690 controls was performed to attempt to allow for confounding by indication. Adjusted relative risks for pneumonia in those currently using PPIs or H2RAs were 1.89 (95% CI 1.36 to 2.62) and 1.63 (95% CI 1.07 to 2.48), respectively. Interestingly, there appeared to be a dose-response relationship for those taking PPIs and their risk of pneumonia that was not apparent for H2RAs. The conclusion is that gastric acid suppression is associated with an increased risk of community acquired pneumonia.
The concept of gastric acid suppression and the development of pneumonia is longstanding and has biological plausibility. Evaluating the link using a randomised controlled trial is unlikely to be feasible. This study has flaws which the authors recognise: its observational nature, the definition of pneumonia, and that confounding variables are possible even with the nested case-control study. This paper will not alter prescribing habits as gastric acid suppression is effective and has an enviable safety record. It should remind us that few treatments are without side effects and that care is needed in high risk patients (elderly, those with pre-existing lung disease, and immunosuppression).