Proton Pump Inhibitor Use Tied To Childhood Asthma

Children who use proton pump inhibitors (PPIs) may be at increased risk of developing asthma, a Swedish study suggests.

Researchers examined registry data on children and adolescents up to 17 years old who were matched 1:1 into 80,870 pairs including one youth who used PPIs and one of similar age and propensity score who didn't use PPIs. After a median follow-up of 3.0 years, youth who used PPIs were significantly more likely to be diagnosed with asthma (hazard ratio 1.57).

"This potential association has been reported in a few previous observational studies of PPI exposure in pregnancy and infancy," said lead study author Yun-Han Wang of the Karolinska Institute in Stockholm.

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"One hypothesized underlying mechanism linking PPIs to asthma is that PPIs may alter gut and lung microbiomes through inhibition of gastric acid secretion, subsequently leading to asthma through immune dysregulation," Wang said by email.

However, it's also possible that gastroesophageal reflux disease, one potential indication for PPI use, is also a potential risk factor for asthma, Wang said. One shortcoming of the current analysis is that PPIs are often prescribed off-label, and researchers lacked data on the reason for PPI usage in the study population.

Age did appear to influence the magnitude of the asthma risk associated with PPIs, particularly among infants younger than 6 months (HR 1.83) and toddlers ranging in age from 6 to 24 months (HR 1.91).

The risk also varied within the class of drugs, with a larger increased risk seen with pantoprazole (HR 2.33), followed by esomeprazole (HR 1.64), lansoprazole (HR 1.49), and omeprazole (HR 1.43).

Asthma appeared most likely to surface within 91 to 180 days after PPI initiation (HR 1.73). By contrast, the risk was lower for the first 90 days (HR 1.62) and after 180 days (HR 1.53).

Overall, incidence rate of asthma was 21.8 per 1,000 person-years among those who initiated PPI use and 14.0 per 1,000 person-years among those who did not, the study team reports in JAMA Pediatrics.

One limitation of the study is that researchers lacked data on asthma cases diagnosed in primary care, which might include a substantial number of milder asthma cases where a specialist consult wasn't required, the authors note. Researchers also relied on prescription data to determine PPI usage, and it's possible some children with filled prescriptions didn't actually use the drugs.

Even so, the study results add to a strong body of evidence suggesting that PPIs are a risk factor for allergic disease and infections, said Dr. Yvan Vandenplas of the University Ziekenhuis in Brussels. These drugs most likely contribute to asthma because they block gastric acidity, changing the gut and pulmonary microbiome, Dr. Vandenplas, who wasn't involved in the study, said by email.

Clinicians should use PPIs only when indicated, Dr. Vandenplas added.

"PPI are great drugs to treat erosive esophagitis - whenever acid is causing problems," Dr. Vandenplas said. "But, they have adverse effects so the message is: use PPIs when they are needed, and do not use them when they are not needed."

—Lisa Rapaport

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