Lansoprazole for Children With Poorly Controlled Asthma: A Randomized Controlled Trial

Abstract

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.

International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma

“…Gastro-oesophageal reflux (GOR) is present in 60-80% [15,23,120,141,144], but clinical trials with antireflux therapy generally show little to no effect on asthma control [145][146][147]. The role of ''silent'' GOR disease (GORD) as a cause of poor asthma control in general may be over-emphasised, but the child with gastrointestinal symptoms and problematic asthma should be evaluated and treated for GORD [147].…”

“…The role of ''silent'' GOR disease (GORD) as a cause of poor asthma control in general may be over-emphasised, but the child with gastrointestinal symptoms and problematic asthma should be evaluated and treated for GORD [147]. Although the impact of treatment of sinusitis and GORD on severe asthma is not yet clear, when these comorbidities are present, they should be treated as appropriate to improve these conditions.…”

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

“…A recent met-analysis of 26 studies reported 49% increase in the risk of community acquired pneumonia, which was at its highest during the first 30 days of PPI initiation [82]. Data also have shown associations between PPIs and increased upper respiratory tract infections and asthma exacerbation in pediatric population [83,95]. …”

Asthma and Gastroesophageal Reflux Disease in Children – Completing the Puzzle

“…7,8 Indeed, in a recent study in children with poorly controlled asthma, no gastrointestinal symptom differentiated those with and without GER identified by oesophageal pH monitoring. 9 Taken together, these findings emphasise that the prevalence of GERD in asthmatic children identified in studies that used symptom scores as inclusion criteria and/or endpoints is likely biased by the inability to differentiate symptoms of asthma from those of GER.…”