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Original Investigation
February 8, 2021

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

Author Affiliations
  • 1Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  • 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 3Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
  • 4Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, United Kingdom
  • 5Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York
  • 6Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
JAMA Pediatr. 2021;175(4):394-403. doi:10.1001/jamapediatrics.2020.5710
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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