PURPOSE OF THE STUDY.
To study the efficacy of proton pump inhibitor (PPI) therapy over 24 weeks in reducing symptoms in asthmatic children without symptomatic gastroesophageal reflux (GER) who had poor asthma control.
Subjects were between 6 and 17 years old with physician-diagnosed asthma and “labile airways function” defined as (1) 12% or greater increase in postbronchodilator forced expiratory volume in 1 second (FEV1), (2) methacholine PC20 less than 16 mg/mL, or (3) positive exercise challenge with a 20% or greater decrease in FEV1.
This is a multicenter, randomized, double-masked, placebo-controlled parallel clinical trial in children with asthma. All subjects were on stable doses of inhaled corticosteroids and had poor asthma control defined by study specific criteria. Subjects were excluded if they self-reported any symptoms of GER requiring treatment with a PPI or other reflux medication. The primary outcome was change in asthma control questionnaire score at the 24-week visit. Secondary outcomes included rate of acute episodes of poor asthma control, change in Asthma Symptom Utility Index, change in Asthma Control Test, change in asthma-specific quality of life for children score, methacholine PC20, spirometry, FeNO, gastrointestinal symptoms, and nocturnal awakenings. Esophageal pH studies were performed before randomization in a subset. Participating children were randomly assigned to receive lansoprazole dosed by weight.
One hundred forty-nine children were randomized to lansoprazole therapy and 157 were randomized to placebo. Mean age at randomization was 11 years in both groups. More than 88% of participants completed the study. Of 115, 49 (43%) 24-hour pH probe studies demonstrated abnormal esophageal acid exposure. Gastrointestinal symptom scores were not different between patients with normal versus abnormal pH studies. No differences were seen in initial prebronchodilator FEV1 or forced vital capacity in those with normal or abnormal pH studies. At week 24 of therapy, mean Asthma Control Questionnaire score had decreased by <0.5 (the predetermined clinically important difference) in both groups and was not statistically different between the 2 groups (P = .12). There were no statistically significant treatment effects for any of the secondary outcome measurements. In a subanalysis of the children with abnormal pH probe studies (n = 49), there was no significant effect of lansoprazole treatment for 24 weeks on any of the study outcomes. Adverse event monitoring showed treatment with lansoprazole was associated with statistically greater prevalence of upper respiratory tract infection, sore throat, and bronchitis. Activity-related bone fractures were seen in 6 of 149 lansoprazole-treated subjects and 1 of 157 placebo-treated children (P = .06).
In children 6 to 17 years old with mild or moderate persistent asthma on inhaled corticosteroids, without GER symptoms, abnormal pH probe diagnostic of GER disease is present in 43%. Yet 24-week treatment with lansoprazole had no significant effect on measures of asthma control, quality of life, lung function, or bronchial responsiveness compared with placebo in the total group and in the subgroup of patients with abnormal pH probe studies. Increased adverse events, upper respiratory tract infection , sore throat, and bronchitis were seen in the lansoprazole-treated subjects. Activity-related bone fractures were slightly increased in the lansoprazole-treated subjects.
The same investigators have shown similar results in adults. This study contributes to the questioning of the true association between asthma and GER disease in children and adults and potential overuse of PPI therapy in patients without symptomatic GER. These data were obtained in asthmatic children without symptomatic GER and may not be comparable in children with active GER symptoms. Impedance monitoring was not done and the results cannot be extrapolated to the possible effect of non–acid reflux on asthma control. Increased fracture risk has been reported in adults on long-term PPI therapy. This is the first large study to suggest possible association in children, although specific cause-and-effect was not investigated.
- Copyright © 2012 by the American Academy of Pediatrics