Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study

{ 'indexed': {'date-parts': [[2024, 7, 19]], 'date-time': '2024-07-19T00:15:46Z', 'timestamp': 1721348146688}, 'reference-count': 44, 'publisher': 'eLife Sciences Publications, Ltd', 'license': [ { 'start': { 'date-parts': [[2024, 7, 16]], 'date-time': '2024-07-16T00:00:00Z', 'timestamp': 1721088000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}, { 'start': { 'date-parts': [[2024, 7, 16]], 'date-time': '2024-07-16T00:00:00Z', 'timestamp': 1721088000000}, 'content-version': 'am', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}, { 'start': { 'date-parts': [[2024, 7, 16]], 'date-time': '2024-07-16T00:00:00Z', 'timestamp': 1721088000000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'http://creativecommons.org/licenses/by/4.0/'}], 'funder': [ { 'name': 'National Natural Science Foundation of China Regional Innovation and Development ' 'Joint Foundation', 'award': ['U23A20408']}, { 'DOI': '10.13039/501100001809', 'name': 'National Natural Science Foundation of China', 'doi-asserted-by': 'publisher', 'award': ['82171698']}, { 'DOI': '10.13039/501100001809', 'name': 'National Natural Science Foundation of China', 'doi-asserted-by': 'publisher', 'award': ['82170561']}, { 'DOI': '10.13039/501100001809', 'name': 'National Natural Science Foundation of China', 'doi-asserted-by': 'publisher', 'award': ['81300279']}, { 'DOI': '10.13039/501100001809', 'name': 'National Natural Science Foundation of China', 'doi-asserted-by': 'publisher', 'award': ['81741067']}, { 'DOI': '10.13039/501100001809', 'name': 'National Natural Science Foundation of China', 'doi-asserted-by': 'publisher', 'award': ['82100238']}, { 'name': 'Program for High-level Foreign Expert Introduction of China', 'award': ['G2022030047L']}, { 'name': 'Natural Science Foundation for Distinguished Young Scholar of Guangdong Province', 'award': ['2021B1515020003']}, { 'name': 'Guangzhou Basic and Applied Basic Research Scheme', 'award': ['Project for Pilot Voyage 2024A04J6573']}, { 'DOI': '10.13039/501100021171', 'name': 'Guangdong Basic and Applied Basic Research Foundation', 'doi-asserted-by': 'publisher', 'award': ['2022A1515012081']}, { 'name': 'Foreign Distinguished Teacher Program of Guangdong Science and Technology ' 'Department', 'award': ['KD0120220129']}, { 'name': 'Climbing Program of Introduced Talents and High-level Hospital Construction Project ' "of Guangdong Provincial People's Hospital", 'award': ['DFJH201923']}, { 'name': 'Climbing Program of Introduced Talents and High-level Hospital Construction Project ' "of Guangdong Provincial People's Hospital", 'award': ['DFJH201803']}, { 'name': 'Climbing Program of Introduced Talents and High-level Hospital Construction Project ' "of Guangdong Provincial People's Hospital", 'award': ['KJ012019099']}, { 'name': 'Climbing Program of Introduced Talents and High-level Hospital Construction Project ' "of Guangdong Provincial People's Hospital", 'award': ['KJ012021143']}, { 'name': 'Climbing Program of Introduced Talents and High-level Hospital Construction Project ' "of Guangdong Provincial People's Hospital", 'award': ['KY012021183']}, { 'DOI': '10.13039/100001947', 'name': 'American Society for Gastrointestinal Endoscopy', 'doi-asserted-by': 'publisher', 'award': ['VA Clinical Merit and ASGE clinical research funds']}], 'content-domain': {'domain': ['elifesciences.org'], 'crossmark-restriction': False}, 'abstract': '<jats:sec id="abs1"><jats:title>Background:</jats:title><jats:p>Adverse effects of proton ' 'pump inhibitors (PPIs) have raised wide concerns. The association of PPIs with influenza is ' 'unexplored, while that with pneumonia or COVID-19 remains controversial. Our study aims to ' 'evaluate whether PPI use increases the risks of these respiratory ' 'infections.</jats:p></jats:sec><jats:sec ' 'id="abs2"><jats:title>Methods:</jats:title><jats:p>The current study included 160,923 ' 'eligible participants at baseline who completed questionnaires on medication use, which ' 'included PPI or histamine-2 receptor antagonist (H2RA), from the UK Biobank. Cox proportional ' 'hazards regression and propensity score-matching analyses were used to estimate the hazard ' 'ratios (HRs) and 95% confidence intervals (CIs).</jats:p></jats:sec><jats:sec ' 'id="abs3"><jats:title>Results:</jats:title><jats:p>Comparisons with H2RA users were tested. ' 'PPI use was associated with increased risks of developing influenza (HR 1.32, 95% CI ' '1.12–1.56) and pneumonia (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.26–1.59). In ' 'contrast, the risk of COVID-19 infection was not significant with regular PPI use (HR 1.08, ' '95% CI 0.99–1.17), while the risks of severe COVID-19 (HR 1.19. 95% CI 1.11–1.27) and ' 'mortality (HR 1.37. 95% CI 1.29–1.46) were increased. However, when compared with H2RA users, ' 'PPI users were associated with a higher risk of influenza (HR 1.74, 95% CI 1.19–2.54), but ' 'the risks with pneumonia or COVID-19-related outcomes were not ' 'evident.</jats:p></jats:sec><jats:sec ' 'id="abs4"><jats:title>Conclusions:</jats:title><jats:p>PPI users are associated with ' 'increased risks of influenza, pneumonia, as well as COVID-19 severity and mortality compared ' 'to non-users, while the effects on pneumonia or COVID-19-related outcomes under PPI use were ' 'attenuated when compared to the use of H2RAs. Appropriate use of PPIs based on comprehensive ' 'evaluation is required.</jats:p></jats:sec><jats:sec ' 'id="abs5"><jats:title>Funding:</jats:title><jats:p>This work is supported by the National ' 'Natural Science Foundation of China (82171698, 82170561, 81300279, 81741067, 82100238), the ' 'Program for High-level Foreign Expert Introduction of China (G2022030047L), the Natural ' 'Science Foundation for Distinguished Young Scholars of Guangdong Province (2021B1515020003), ' 'the Guangdong Basic and Applied Basic Research Foundation (2022A1515012081), the Foreign ' 'Distinguished Teacher Program of Guangdong Science and Technology Department (KD0120220129), ' 'the Climbing Program of Introduced Talents and High-level Hospital Construction Project of ' 'Guangdong Provincial People’s Hospital (DFJH201923, DFJH201803, KJ012019099, KJ012021143, ' 'KY012021183), and in part by VA Clinical Merit and ASGE clinical research funds ' '(FWL).</jats:p></jats:sec>', 'DOI': '10.7554/elife.94973', 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