Abstract
Background With the increased use of acid suppressants, significant potential complications such as community-acquired pneumonia (CAP) are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and CAP. Our main objective was to evaluate the risk of CAP in children using acid suppressants (proton pump inhibitors (PPIs) and/or histamine-2 receptor antagonists (H2RAs)).
Methods We performed a cohort study using data from the UK Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to four unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of CAP. The cohort consisted of 84 868 exposed and 325 329 unexposed children.
Results Current use of PPIs and H2RAs was associated with an increased risk of CAP (adjusted hazard ratio 2.05 (95% CI 1.90–2.22) and 1.80 (95% CI 1.67–1.94), respectively). The risk was even greater in patients with respiratory disease. Long-term use (≥211 days) of PPIs and H2RAs led to a significantly greater risk of CAP compared with short-term use (<31 days). After cessation of therapy, the risk remained increased for the following 7 months.
Conclusion The use of acid suppressants in children was associated with a doubled risk of CAP. This risk increased with chronic use and respiratory disease, and remained increased after discontinuation of therapy.
Abstract
In this large cohort study, the use of acid suppressants in children, both PPIs and H2RAs, was associated with a doubled risk of CAP. This risk increased with chronic use and respiratory disease, and remained increased after discontinuation of therapy. https://bit.ly/3suT7s3
Footnotes
Author contributions: L.J.T.M. van der Sande, Q. Jöbsis, F. de Vries, E. Dompeling, E.M.W. van de Garde, J.J.M. Coremans and J.H.M. Driessen designed the study. J.H.M. Driessen, F. de Vries and L.J.T.M. van der Sande were responsible for the data extraction. L.J.T.M. van der Sande, Q. Jöbsis, M.A.G.E. Bannier, F. de Vries, E. Dompeling and J.H.M. Driessen wrote the paper. L.J.T.M. van der Sande and Q. Jöbsis performed a systematic review of the literature on this subject. All authors critically revised the article and approved the final version.
The protocol for this study was approved by the Independent Scientific Advisory Committee (ISAC) for Medicines and Healthcare products Regulatory Agency (MHRA) Database research (protocol 18_107). Clinical Practice Research Datalink (CPRD) GOLD data for this study have been sublicensed from the MHRA by Utrecht University and are subject to an agreement that does not allow further sharing with others. However, CPRD GOLD data, either for original or replication studies, are available from the licensor to any team of researchers who meet appropriate qualifications, subject to a priori scientific approval of the study protocol by the ISAC and the availability of a sublicensing agreement. Data dictionaries of exposures and outcomes are available for auditing purposes.
Conflict of interest: L.J.T.M. van der Sande has nothing to disclose.
Conflict of interest: Q. Jöbsis has nothing to disclose.
Conflict of interest: M.A.G.E. Bannier has nothing to disclose.
Conflict of interest: E.M.W. van de Garde has nothing to disclose.
Conflict of interest: J.J.M. Coremans has nothing to disclose.
Conflict of interest: F. de Vries is supervisor to two PhD students who are employed by F. Hoffmann La Roche Ltd (Basel, Switzerland and Welwyn Garden City, UK); the topics of the studies are not related to the current manuscript and no fees or reimbursements have been received for this.
Conflict of interest: E. Dompeling has nothing to disclose.
Conflict of interest: J.H.M. Driessen has nothing to disclose.
- Received August 21, 2020.
- Accepted February 21, 2021.
- Copyright ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org