Background: Gastrointestinal and respiratory symptoms of gastroesophageal reflux disease (GERD) are commonly reported in children with asthma, and it has been postulated that untreated GERD may worsen asthma control. Although some evidence suggests that proton pump inhibitor (PPI) use improves asthma control in adults with symptomatic GERD, more research is needed to determine the role of PPI use in children with asthma and asymptomatic GERD. Despite inconsistent evidence, children with poorly controlled asthma have been increasingly prescribed PPIs in the hopes of improving asthma symptoms. Writing for the American Lung Association Asthma Clinical Research Centers, Holbrook and colleagues conducted a double-blind placebo-controlled study to determine whether PPI use is effective for the treatment of poorly controlled asthma in children.
The Study: The Study of Acid Reflux in Children With Asthma was conducted at 19 centers in the United States. Children between six and 17 years of age were included in the study if their asthma was categorized as poorly controlled despite adequate use of inhaled corticosteroids. Poor asthma control was defined as any one of the following criteria: using short-acting beta agonists two or more times per week; having more than one nocturnal asthma episode per week; or having two or more emergency department visits, unscheduled physician visits, hospital admissions, or courses of prednisone therapy in the previous year. Children were excluded if they had symptomatic GERD, a history of PPI use, antireflux surgery or tracheoesophageal fistula repair, a history of neonatal respiratory distress or premature birth (before 33 weeks’ gestation), or forced expiratory volume in one second of less than 60 percent of the predicted value. The primary outcome was improvement in the Asthma Control Questionnaire (ACQ) at 24 weeks. This scale ranges from 0 to 6, with higher values indicating worse asthma control; patients with ACQ scores of 0.75 or less have well-controlled asthma, whereas those with scores of 1.5 or greater are considered to have inadequately controlled asthma. A 0.5-point change in the scale reflects meaningful clinical improvement.
Participants were randomized to receive weight-based dosing of lansoprazole (Prevacid) or placebo for six months. Before randomization, 152 participants underwent esophageal pH testing. Of the 115 children who had adequate results for interpretation, 49 (43 percent) had abnormal esophageal acid exposure indicative of GERD. There were no differences in gastrointestinal symptoms between those in the normal and abnormal pH groups.
Results: Of the 2,453 children screened, 157 were randomized to placebo and 149 to lansoprazole. The mean ACQ score at baseline was 1.6 for both groups, indicating poor control. At 24 weeks, there was no significant change in ACQ scores in either group (–0.1 for the lansoprazole group and –0.2 for the placebo group). Subanalysis of the children with asymptomatic GERD revealed no effects from lansoprazole use. Compared with placebo, lansoprazole use was associated with a statistically significant increase in upper respiratory tract infections, sore throats, and bronchitis.
Conclusion: Lansoprazole use does not improve asthma symptoms in children with asymptomatic GERD, even in those with pH-probe–documented acid reflux.