The predominance of heartburn among asthma sufferers led many specialists to suspect that acid reflux could be a trigger for the coughing, wheezing and breathlessness of asthma. In fact, it has become standard practice to prescribe heartburn medication to people with poorly controlled asthma, even if they don’t have overt acid reflux symptoms.
But a new study of adults with inadequate asthma control without significant heartburn shows that heartburn medication does not help control their asthma symptoms. The study, conducted by the American Lung Association’s Asthma Clinical Research Centers at 20 U.S. sites, is the most comprehensive to date. It demonstrated that participants who took esomeprazole (Nexium) had as many asthma episodes as participants who were given an inactive pill, or placebo. The findings will appear April 9, 2009, in the New England Journal of Medicine.
“This study goes against the idea that mild or silent acid reflux contributes to uncontrolled asthma,” says Mario Castro, M.D., a Washington University pulmonary specialist at Barnes-Jewish Hospital who led the study in St. Louis. “It establishes that heartburn medications are not indicated for adults with uncontrolled asthma when they have mild or no symptoms of acid reflux.”
However, Castro says prescription heartburn medication is still indicated for those with severe heartburn and poorly controlled asthma because it might improve asthma control in some of these patients.
The practice of prescribing heartburn medication to patients with poorly controlled asthma was a product of common sense — not only did asthma patients often suffer from heartburn, doctors had evidence that stomach acid traveling up the esophagus could get into the lungs and cause coughing. In addition, studies in laboratory animals showed that if the lower esophagus is exposed to acid, it could send nerve signals that loop back to the lungs and cause airway constriction.
But, past investigations into the potential benefit of heartburn medication for asthma control were inconclusive, showing either no effect or a small benefit.
The current study enrolled 412 patients who had poorly controlled asthma despite being treated with inhaled corticosteroids. But they had either no or very mild acid reflux symptoms. Each participant was randomly assigned to receive either 80 milligrams of esomeprazole or a placebo daily. Then for 24 weeks, they kept a daily record of their asthma symptoms. Every four weeks their lung function was tested, and they completed asthma questionnaires.
In both the placebo and treatment groups, episodes of poor asthma control occurred with similar frequency. Occurrences of an urgent care visit for an asthma attack; a reduction in lung function; a course of corticosteroids, which reduce inflammation; or increased use of bronchodilators, which relax the airway muscles, did not differ significantly between the treatment and placebo groups. Night awakening due to asthma occurred on one or more occasions in about half of the participants, and the rate did not differ significantly between the two groups.
“Despite using four-times the typical dose of the heartburn medication, we achieved no improvement in asthma symptoms, control or exacerbation rates,” says Castro, also professor of medicine and pediatrics in the Division of Pulmonary and Critical Care Medicine.
Although the participants were mostly free of heartburn symptoms, when the researchers measured acid reflux using probes placed in the esophagus for 24 hours, they found that about 40 percent of the study participants had some acid reflux. But even the participants with measureable acid reflux did not achieve greater control of their asthma when they received esomeprazole.
The multicenter network is currently conducting a parallel study in children ages 6 to 17 who have poorly controlled asthma and no heartburn. Called SARCA (Studying Acid Reflux in Children with Asthma), the investigation will try to determine whether heartburn medication can help control asthma in younger patients.
“Acid reflux is fairly common in children,” Castro says. “And we know that a finding in adults doesn’t necessarily apply to children, so we feel it’s important to evaluate whether acid suppression in children with uncontrolled asthma is effective.”
Those interested in the SARCA trial can call the Volunteer for Health line at (866) 362-5656 or visit the web site at vfh.wustl.edu.
Mastronarde JG, Anthonisen NR, Castro M, Holbrook JT, Leone FT, Teague WG, Wise RA. Efficacy of esomeprazole for treatment of poorly controlled asthma. New England Journal of Medicine. April 9, 2009.
Funding from the National Heart, Lung, and Blood Institute and the American Lung Association supported this research. The study drug and placebo were supplied by AstraZeneca. Castro reports receiving lecture fees from AstraZeneca.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.