Stockholm, Sweden—An increased risk of asthma should be considered as a potential adverse event when prescribing proton pump inhibitors (PPI) to children, according to a recent study.

The report in JAMA Pediatrics discusses the results of a propensity score–matched cohort study including 80,870 pairs of children who were and were not new users of PPIs. Results indicate that the incidence rate of asthma was 21.8 per 1,000 person-years among children who initiated PPI use and 14.0 per 1,000 person-years among those who did not. In other words, the hazard ratio increased by 57%.

“These findings suggest that asthma is one of several potential adverse events that should be considered when prescribing PPIs to children,” write researchers from the Karolinska Institutet in Sweden and Columbia University College of Physicians and Surgeons in New York.

“Proton pump inhibitors (PPIs) are first-line therapy for acid-related gastrointestinal tract disorders in children,” the authors explain. “The use of PPIs has increased substantially in the last decade. Off-label use and prolonged use are relatively common despite limited data supporting the safety of PPI use in children. Emerging observational data, primarily derived from studies of drug use in pregnancy, indicate that exposure to PPIs may be associated with subsequent development of asthma.”

Background information in the article points out that the increased use of PPIs in children has heightened concerns that the heartburn/acid reflux drugs might be linked to increased risk of asthma.

To explore that question, researchers conducted a nationwide cohort study that collected registry data in Sweden from January 1, 2007, to December 31, 2016, involving children and adolescents 17 years old and younger. Data were analyzed from February 1 to September 1, 2020.

The authors report that, among the more than 80,000 pairs—63% girls with a mean age of 12.9 years—those who initiated PPI use had a higher incidence rate of asthma (21.8 events per 1,000 person-years) compared with noninitiators (14.0 events per 1,000 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]),” according to the authors.

Hazard risks for individual PPIs were:
• 1.64 (95% CI, 1.50-1.79) for esomeprazole
• 1.49 (95% CI, 1.25-1.78) for lansoprazole
• 0.43 (95% CI, 1.35-1.51) for omeprazole
• 2.33 (95% CI, 1.30-4.18) for pantoprazole

In terms of the timing of asthma onset after PPI initiation, analysis found that hazard rations (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), researchers note.

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

Researchers point to dysbiosis and disturbance of the human microbiome as factors in provoking asthma flares, advising that PPIs have been reported to alter gut and lung microbiomes through inhibition of gastric acid secretion. They add, however, that little research has been done on the issue.

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