Context Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. It is not known whether treatment of GER with a proton-pump inhibitor (PPI) improves asthma control. Objective To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER. Design, Setting, and Patients A multicenter, randomized, masked, placebo controlled, parallel clinical trial comparing lansoprazole to placebo in children with poor asthma control on inhaled corticosteroid treatment conducted at 18 academic clinical centers. Participants were followed for 24 weeks. A subgroup had an esophageal pH study before randomization. Intervention Children received either lansoprazole (15 mg daily < 30 kg; 30 mg ≥ 30 kg) or placebo, 1:1 allocation ratio. Main outcome The primary outcome was the change in Asthma Control score (ACQ, range from 0 to 6). Secondary outcomes included lung function measures, asthma-related quality of life and acute episodes of poor asthma control. Results 306 children were enrolled from April 2011 to August 2010, the median age was 11. The mean change (95% confidence interval (CI)) in the ACQ score was −0.1 (−0.2, 0.1) and −0.2 (−0.4, −0.1) units for the lansoprazole and placebo groups, respectively (P=0.12). There were no detectable treatment differences in secondary outcomes (mean (95% CI) for FEV1(0.00 (−0.08, 0.08)), asthma quality of life (−0.1 (−0.4, 0.1) or episodes of poor asthma control, hazard ratio of 1.18 (95% CI 0.91, 1.53). Among the 115 children with esophageal pH studies, the prevalence of GER was 43%. In the subgroup with a positive pH study, no treatment effect for lansoprazole versus placebo was observed for any asthma outcome. Children treated with lansoprazole reported more upper respiratory infections (63% vs 49%, P=0.02), sore throats (52% vs 39%, P=0.02), and bronchitis (7% vs 2%, P=0.05). Conclusion Among children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, as compared to placebo, did not improve symptoms nor lung function but was associated with increased adverse events.

Lansoprazole-associated upper respiratory infections and ST in children are related in part to CYP2C19 haplotype. Our data suggest that lansoprazole-associated adverse events in children may be mitigated by adjusting the conventional dose in PMs. Additional studies are required to replicate our findings.

Current evidence does not support the routine use of anti-GERD medications in the treatment of poorly controlled asthma of childhood. However large controlled trials of children symptomatic of both GERD and asthma have not been conducted, and in this case the benefits of treatment, although unproven, might outweigh the risks.

The efficacy of proton pump inhibitor (PPI) medications is highly dependent on plasma concentrations, which varies considerably due to cytochrome P450 ( CYP2C19 ) genetic variation. We conducted a pragmatic, pilot study of CYP2C19 genotype‐guided pediatric dosing of PPI medications. Children aged 5–17 years old with gastric‐acid‐related conditions were randomized to receive either conventional dosing of a PPI or genotype‐guided dosing for a total of 12 weeks. Sixty children (30 in each arm) were enrolled and had comparable baseline characteristics. The mean daily omeprazole equivalent dose prescribed to participants across metabolizer phenotype groups was significantly different in the genotype‐guided dosing arm ( P < 0.001), but not in the conventional dosing arm. Prescribers waited for the genotype result before prescribing the PPI medication for 90% of the participants in the genotype‐guided dosing arm. The number of participants who reported an infection was marginally lower in genotype‐guided dosing vs. conventional dosing (20% vs. 44%; P = 0.07). Sinonasal symptoms were higher in the conventional dosing arm as compared with genotype‐guided dosing arm: (2.6 (2.0, 3.4) vs. 1.8 (1.0, 2.3), P = 0.031). CYP2C19 genotype‐guided PPI therapy is feasible in a clinical pediatric setting, well accepted by providers, resulted in differential PPI dosing, and may reduce PPI‐associated infections. A future large scale randomized clinical trial of CYP2C19 genotype‐guided pediatric dosing of PPI medications in children is warranted.

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