Lansoprazole Therapy Ineffective for Poorly Controlled Asthma in Kids

A study on the use of the proton pump inhibitor (PPI) lansoprazole in children with poorly controlled asthma without overt gastroesophageal reflux (GER) disease found that acid suppression therapy did not have any benefit on symptom relief, lung function, airways reactivity, or quality of life. The PPI, however, was associated with increased adverse events [JAMA. 2012;307(4):373-381]. Untreated GER has been considered a possible cause of inadequate asthma control in children treated with inhaled corticosteroids, but PPIs have not been well studied with regard to their use for asymptomatic GER in children with refractory asthma. In the Study of Acid Reflux in Children with Asthma, researchers sought to determine whether lansoprazole was effective in reducing asthma symptoms in children without overt GER. The study was a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in 306 children with poor asthma control who were receiving inhaled corticosteroid treatment. The patients were enrolled from April 2007 to September 2010 at 19 US academic clinical centers and were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization. The children had a mean age of 11 years (range, 6-17 years), 50% were black, and all were using inhaled corticosteroids. Most of the participants required an intervention for asthma symptoms in the year before enrollment, and the mean Asthma Control Questionnaire (ACQ) at screening was high, at 1.6 for both the lansoprazole and placebo groups, which is consistent with poor asthma control. Children were randomly assigned in a 1:1 ratio to receive either lansoprazole 15 mg/day if weighing <30 kg or 30 mg/day if weighing ≥30 kg (n=149), or placebo (n=157). The primary end point was a change in ACQ score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary end points included lung function measures, asthma-related quality of life, and episodes of poor asthma control. The results showed that after randomization, the ACQ score decreased by less than the meaningful clinically important difference in both groups (lansoprazole, −0.1; 95% confidence interval [CI], −0.2 to 0.1 and placebo, −0.2; 95% CI, −0.4 to −0.1). There were no statistically significant differences in the mean difference in change for the secondary outcomes of forced expiratory volume in the first second (0.0 L; 95% CI, −0.1 to 0.1 L), asthma-related quality of life (−0.1; 95% CI, −0.3 to 0.1), or rate of episodes of poor asthma control (relative risk [RR], 1.2; 95% CI, 0.9-1.5). Additionally, among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In a subanalysis of 49 children with GER (n=29 in the lansoprazole group and n=20 in the placebo group), no treatment effect for lansoprazole versus placebo was observed for any asthma outcome. As for adverse events, the lansoprazole group experienced significantly more respiratory infections (RR, 1.3; 95% CI, 1.1-1.6), sore throats (RR, 1.3; 95% CI, 1.0-1.6), and episodes of bronchitis (RR, 2.2; 95% CI, 0.8-6.1). The treatment group also experienced more activity-related bone fractures (6 vs 1 in treatment vs placebo groups, respectively), although this difference did not reach significance. The findings also raise important questions about the adverse effects of lansoprazole in children and, along with concerning data on PPIs that have led to US Food and Drug Administration Advisory Board Reviews in the past 2 years, underscore the need for continued study of PPI safety in children, noted the researchers. In summary, the authors said, “The results of our study indicate that PPI treatment of children with poorly controlled asthma without symptomatic GER was not an effective therapy for asthma.” Limitations of the study include that the researchers did not conduct on-treatment pH probe studies to confirm acid suppression. Adherence to the study drug, although high by self-report, could have influenced the results.