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Proton Pump Inhibitors No Help for Kids' Asthma
Gastroesophageal reflux (GER) is a mysterious co-conspirator with asthma. Many people with uncontrolled asthma have reflux (either symptomatic by history, or asymptomatic and detected on esophageal pH studies). Randomized trials in adults suggest that treating symptomatic GERD (gastroesophageal reflux DISEASE) improves asthma, but treating asymptomatic GER does not [ref1, ref2, ref3]. Nevertheless, many adults and children with uncontrolled asthma without GERD symptoms are prescribed proton pump inhibitors empirically by physicians.
A new study in children published in JAMA suggests this rule-of-thumb in adults (reflux with symptoms worsens asthma; reflux without symptoms does not) may apply in children, as well. Worse, empiric PPIs seemed to increase children's risk for upper respiratory infections and bronchitis.
Janet Holbrook of Johns Hopkins and her co-investigators randomized 306 children (age ~11) with uncontrolled asthma despite inhaled corticosteroids to receive lansoprazole (a proton pump inhibitor) or placebo for 24 weeks. Children were enrolled and randomized without regard to reflux symptoms.
At 24 week followup, there were no significant differences between groups in Asthma Control Questionnaire scores, FEV1, or number of episodes of poor asthma control.
A subgroup of 115 children received esophageal pH probes as part of the study design; 43% had gastroesophageal reflux. However, among these children there were also no differences in outcomes for those treated with lansoprazole vs. placebo.
More children taking lansoprazole reported mild respiratory infections (colds and bronchitis), with a relative risk of 1.3; pneumonias occurred infrequently without differences between groups.
There were no stat.significant differences in the rate of bone fractures between groups, but 6 children taking lansoprazole had fractures, while only 1 taking placebo did (p=0.06).
The study was sponsored by the American Lung Association, with no contribution from Pharma other than the generous donation of lansoprazole (Takeda) and albuterol (GlaxoSmithKline).
Clinical Takeaway: Proton pump inhibitors are routinely prescribed to children and adults with uncontrolled asthma who lack symptoms of gastroesophageal reflux disease, but this practice should probably stop. Evidence from randomized trials in adults shows that the strategy doesn't improve their asthma, and this randomized trial suggests empiric GER treatment doesn't help asthmatic children, either. PPIs have an acceptable risk-benefit profile when there's a clear indication for their use, but growing evidence suggests that (like any medicine) they're not safe to prescribe indiscriminately.
Holbrook JT et al. Lansoprazole for Children With Poorly Controlled Asthma. A Randomized Controlled Trial. JAMA 2012;307(4):373-380.