American Lung Association Study Designated as Editor’s Choice Article in Next Edition of the “Journal of the American Medical Association”

Treatment of symptomless acid reflux does not improve asthma in children

Washington, D.C. (January 24, 2012)

There is debate in the medical community over whether or not undetected gastroesophageal reflux (GER) —a condition caused by acid coming up from the stomach into the esophagus—could contribute to inadequate asthma control in children taking inhaled steroids. According to new research conducted by the American Lung Association Asthma Clinical Research Centers Network (ALA-ACRC)—published today in the Journal of the American Medical Association—adding prescription acid controllers to standard inhaled steroid treatment does not improve asthma symptoms or control in children.

“The use of proton pump inhibitors (PPIs) in children has increased dramatically to more than 2.5 million prescriptions per year,” said Janet T. Holbrook, M.P.H., Ph.D., co-director of the ALA-ACRC Data Coordinating Center at Johns Hopkins. “These drugs are commonly prescribed to patients without symptoms of GER who continue to have problems controlling their asthma while taking effective asthma medications. Therefore, it was important to evaluate whether PPIs are effective for treating asthma in children without the typical symptoms of acid reflux.”

The results of this study—which was co-funded by the American Lung Association and the National Heart, Lung and Blood Institute (NHLBI), a component of the National Institutes of Health—are considered to be the most comprehensive evaluation to date of the efficacy of prescription acid controllers to improve asthma symptoms and control among children. These results are similar to those found in a previous ALA-ACRC study, which examined the relationship between asthma and GER among adults. That study was published in the New England Journal of Medicine in 2009.

In the latest ALA-ACRC trial, 360 children aged 6-17 years with poorly controlled asthma and without symptoms of GER were randomly assigned to receive a daily dose of either lansoprazole—a class of drugs that suppresses the production of stomach acid—or an inactive placebo pill in addition to their inhaled steroid therapy.  Compared with placebo, children who received lansoprazole did not show signs of improved lung function or a decrease in asthma symptoms. However, children who took lansoprazole had an increased risk of adverse effects, notably sore throats and bronchitis.

Asthma and GER are common disorders in children and symptoms of GER such as “heartburn,” vomiting, and difficulty swallowing are frequently reported among children with asthma. Approximately 40 percent of participants in the ALA-ACRC trial were identified as having GER.

“Prescription acid control medications are costly; those with asthma can spend as much as $1.1 billion dollars per year,” said Norman H. Edelman, M.D., chief medical officer of the American Lung Association. “Knowing that silent acid reflux does not play a significant role in poor asthma control is the kind of practical research that is helpful immediately for both physicians and patients’ alike. Talk with your doctor before discontinuing any medication, as each patient’s specific needs will vary.”

Takeda Pharmaceuticals and GlaxoSmithKline provided the medication for the study.

The ACRC Network is an American Lung Association sponsored research program that conducts large scale clinical trials with the mission of advancing the care and treatment of people with asthma. The network, with a central data coordinating center and 18 clinical centers located across the country, is the largest nonprofit network of its kind. By placing numerous clinical centers nationwide, the ACRC Network is able to enroll large numbers of patients for clinical trials, thus ensuring relevant research findings can be interpreted with the highest level of scientific authority.

Abstract
Context  Asymptomatic gastroesophageal reflux (GER) is prevalent in children with asthma. Untreated GER has been postulated to be a cause of inadequate asthma control in children despite inhaled corticosteroid treatment, but it is not known whether treatment with proton pump inhibitors improves asthma control.

Objective To determine whether lansoprazole is effective in reducing asthma symptoms in children without overt GER.

Design, Setting and Participants The Study of Acid Reflux in Children with Asthma, a randomized, masked, placebo-controlled, parallel clinical trial that compared lansoprazole with placebo in children with poor asthma control who were receiving inhaled corticosteroid treatment. Three hundred six participants enrolled from April 2007 to September 2010 at 19 US academic clinical centers were followed up for 24 weeks. A subgroup had an esophageal pH study before randomization.

Intervention Participating children were randomly assigned to receive either lansoprazole, 15mg/d if weighing less than 30 kg or 30 mg/d if weighing 30 kg or more (n=149), or placebo (n=157).

Main Outcome Measures The primary outcome measure was change in Asthma Control Questionnaire (ACQ) score (range, 0-6; a 0.5-unit change is considered clinically meaningful). Secondary outcome measures included lung function measures, asthma-related quality of life, and episodes of poor asthma control.

Results The mean age was 11 years (SD, 3 years). The mean difference in change (lansoprazole minus placebo) in the ACQ score was 0.2 units (95% CI, 0.0-0.3 units). 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, 1.2; 95% CI, 0.9-1.5). 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 vs placebo was observed for any asthma outcome. Children treated with lansoprazole reported more respiratory infections (relative risk, 1.3 [95% CI, 1.1-1.6]).

Conclusion In this trial of children with poorly controlled asthma without symptoms of GER who were using inhaled corticosteroids, the addition of lansoprazole, compared with placebo, improved neither symptoms nor lung function but was associated with increased adverse events.

Norman H. Edelman, MD, disclosed stock ownership with Johnson & Johnson.

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