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Association Between Proton Pump Inhibitor Use and Risk of Asthma in Children

Educational Objective
To investigate the association between proton pump inhibitor (PPI) use and risk of asthma in children.
1 Credit CME
Key Points

Question  Is proton pump inhibitor (PPI) use associated with risk of asthma in children?

Findings  This propensity score–matched cohort study included 80 870 pairs of children who were and were not new users of PPIs. The incidence rate of asthma was 21.8 per 1000 person-years among those who initiated PPI use and 14.0 per 1000 person-years among those who did not; the hazard ratio increased by 57%.

Meaning  These findings suggest that asthma is one of several potential adverse events that should be considered when prescribing PPIs to children.


Importance  The use of proton pump inhibitors (PPIs) in children has increased substantially in recent years, concurrently with emerging concerns that these drugs may increase the risk of asthma. Whether PPI use in the broad pediatric population is associated with increased risk of asthma is not known.

Objective  To investigate the association between PPI use and risk of asthma in children.

Design, Setting, and Participants  This nationwide cohort study collected registry data in Sweden from January 1, 2007, to December 31, 2016. Children and adolescents 17 years or younger were matched by age and propensity score into 80 870 pairs of those who initiated PPI use and those who did not. Data were analyzed from February 1 to September 1, 2020.

Exposures  Initiation of PPI use.

Main Outcomes and Measures  The primary analysis examined the risk of incident asthma with a median follow-up to 3.0 (interquartile range, 2.1-3.0) years. Cox proportional hazards regression was used to estimate hazard ratios (HRs).

Results  Among the 80 870 pairs (63.0% girls; mean [SD] age, 12.9 [4.8] years), those who initiated PPI use had a higher incidence rate of asthma (21.8 events per 1000 person-years) compared with noninitiators (14.0 events per 1000 person-years), with an HR of 1.57 (95% CI, 1.49-1.64). The risk of asthma was significantly increased across all age groups and was highest for infants and toddlers with an HR of 1.83 (95% CI, 1.65-2.03) in the group younger than 6 months and 1.91 (95% CI, 1.65-2.22) in the group 6 months to younger than 2 years (P < .001 for interaction). The HRs for individual PPIs were 1.64 (95% CI, 1.50-1.79) for esomeprazole, 1.49 (95% CI, 1.25-1.78) for lansoprazole, 1.43 (95% CI, 1.35-1.51) for omeprazole, and 2.33 (95% CI, 1.30-4.18) for pantoprazole. In analyses of the timing of asthma onset after PPI initiation, the HRs were 1.62 (95% CI, 1.42-1.85) for 0 to 90 days, 1.73 (95% CI, 1.52-1.98) for 91 to 180 days, and 1.53 (95% CI, 1.45-1.62) for 181 days to end of follow-up. The association was consistent through all sensitivity analyses, including high-dimensional propensity score matching (HR, 1.48; 95% CI, 1.41-1.55).

Conclusions and Relevance  In this cohort study, initiation of PPI use compared with nonuse was associated with an increased risk of asthma in children. Proton pump inhibitors should be prescribed to children only when clearly indicated, weighing the potential benefit against potential harm.

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Article Information

Accepted for Publication: September 9, 2020.

Published Online: February 8, 2021. doi:10.1001/jamapediatrics.2020.5710

Corresponding Author: Yun-Han Wang, MSc, BPharm, Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Eugeniahemmet T2, 171 76 Stockholm, Sweden (yun-han.wang@ki.se).

Author Contributions: Ms Wang and Dr Pasternak had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Wang, Wintzell, Ludvigsson, Pasternak.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Wang.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Wang.

Obtained funding: Pasternak.

Administrative, technical, or material support: Pasternak.

Supervision: Pasternak.

Conflict of Interest Disclosures: Dr Ludvigsson coordinates, on behalf of the Swedish IBD quality register (SWIBREG), a study that has received funding from Janssen Global Services, LLC. Dr Svanström reported receiving consulting fees from Celgene Corporation and being employed by IQVIA outside of the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by the Swedish Research Council and Frimurare Barnhuset Foundation and an investigator grant from the Strategic Research Area Epidemiology program at Karolinska Institutet (Dr Pasternak).

Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
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  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

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