TORONTO — Treatment with a proton pump inhibitor did not improve asthma control in patients with poorly controlled asthma and minimal or no symptoms of gastroesophageal reflux, according to results from a large study presented at an international conference of the American Thoracic Society.
Gastroesophageal reflux disease (GERD) is a common problem in patients with asthma, with small studies reporting a prevalence of reflux in 32%–84% of asthmatics. Proton pump inhibitor (PPI) therapy is commonly added to therapy in asthma, adding to the overall cost of treatment, but the effect of suppression of gastric acid on asthma symptoms remains unclear, according to Dr. Mario Castro of Washington University School, St. Louis.
Uncertainty about the role of GERD in asthma derives from observations that about half of asthmatics without symptoms of GERD have been shown to have abnormal reflux and about half of asthmatics who have abnormal reflux shown on pH probe studies do not have symptoms of the disease, Dr. Castro explained. “GERD symptoms can mimic symptoms of asthma, and we wanted to know how to distinguish them and how best to treat them.”
Recent guidelines released by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health suggested that, even in the absence of GERD symptoms, consideration should be given to evaluation and possible treatment with PPI for patients with poorly controlled asthma. This was a consensus-based recommendation.
To gain additional data to strengthen the recommendation, the Study of Acid Reflux in Asthma (SARA) was undertaken with funding from the NHLBI and conducted by the American Lung Association's asthma clinical research centers, a national 20-center network dedicated to improving asthma care.
“SARA included only patients with minimal or no symptoms of GERD, because we felt that any patient with moderate or severe GERD should, by definition, be receiving a PPI—and, in this trial, there was the possibility that they would receive placebo,” Dr. Castro said.
Aside from determining whether PPI therapy could improve asthma symptoms in those patients, SARA also sought to determine whether ambulatory pH probe monitoring could identify patients with asymptomatic GERD who might benefit from suppression of gastric acid.
The study design called for a 2- to 8-week run-in period, during which patients underwent pH probe monitoring and, if not contraindicated, methacholine challenge testing. They then were randomized to receive esomeprazole, 40 mg/day, along with stable doses of inhaled corticosteroids (equivalent to at least 400 mg fluticasone/day) and long-acting β-agonists if needed.
Poorly controlled asthma was defined as two or more occasions of a 30% or greater decline in peak expiratory flow from baseline, the need for oral prednisone, the requirement for acute intervention (an emergency department visit), or the need for more than four puffs of rescue medication.
Another investigator, Dr. W. Gerald Teague of the pediatric asthma center at Emory University, Atlanta, described the participants' baseline characteristics. “A total of 412 patients were randomized, … data from 10 patients were lost in Hurricane Katrina.” Of those remaining, 199 received placebo and 203 received esomeprazole.
Overall, the groups were comparable. Mean age was 42 years, and 50% were white and 38% were black. In the placebo group, 28% were male and 20% were former smokers. In the esomeprazole group, 36% were male and 15% were former smokers. About half of the patients in both groups had required use of rescue medications during the previous year, and the same number had required courses of oral prednisone. Asthma control also was equivalent in the two groups, with a mean Asthma Control Questionnaire (ACQ) score of 1.9 in the placebo group and 1.8 in the PPI group.
Lung function also was comparable, with a forced expiratory volume in 1 second (FEV1) at 78% of predicted in the placebo group and 76% of predicted in the esomeprazole group. There were no differences in post-albuterol response, forced vital capacity, or bronchial hyperresponsiveness. On pH probe testing, 40% of patients in both groups were positive for GERD.
“We were surprised, but when baseline asthma characteristics were analyzed according to whether or not patients were positive for GERD on pH probe testing, there was very little effect,” Dr. Teague said. In both GERD and non-GERD groups, 80% had required rescue medicine, ACQ scores were 1.9, and Asthma Quality of Life scores were 4.6, he reported.
“Overall, we saw no treatment effect in either group,” Dr. John G. Mastronarde, a pulmonologist at Ohio State University Medical Center, Columbus, and director of the university's asthma center. The number of episodes of decrease in peak flow was 1.7/person per year in the placebo group and 2.1/person per year in the esomeprazole group. The number of episodes requiring urgent care was 0.7 in the placebo group and 0.6 in the esomeprazole group.