Acid Reflux Doubles COPD Exacerbations

JACKSONVILLE, Fla., Oct. 10 -- Acid reflux atop chronic obstructive pulmonary disease is associated with twice as many COPD exacerbations a year compared with patients without acid reflux, researchers here said.

Reflux patients also appeared to have more severe COPD exacerbations, reported Kenneth J. Vega, M.D., of the University of Florida here, and colleagues, in the October issue of Chest.

An acute COPD exacerbation was defined as worsening difficulty breathing, increasing volume of sputum, or purulent sputum in conjunction with physician-initiated use of corticosteroids or antibiotics, hospitalization, or emergency department visit during the previous year.

Participants in the study with gastroesophageal reflux disease symptoms had 3.2 exacerbations per year compared with 1.6 per year among those without reflux symptoms (P=0.02). This was despite similar lung capacity between groups and use of antireflux medications by most GERD patients. According to previous studies, COPD patients have an average of 2.4 to three acute exacerbations per year.

Compared with COPD patients without GERD, exacerbations in patients with weekly reflux symptoms required significantly more:

• Hospitalizations per year (P=0.007),
• Emergency room visits per year (P=0.005),
• Unscheduled clinic visits per year (P=0.01), and
• Antibiotic use per year (P=0.01).

More than a third of surveyed COPD patients had weekly reflux or heartburn symptoms and were classified as having GERD (37%). By comparison, an estimated 14% to 19% of the general U.S. adult population experience weekly gastroesophageal reflux symptoms.

Weekly reflux symptoms were significantly associated with the number of exacerbations per year even after controlling for age (P=0.004), severity of airflow obstruction (P=0.7), gender (P=0.36), and tobacco use (P=0.154).

While the study suggested that GERD is a possible predictor of the number of exacerbations a COPD patient will have, "this study was not designed to demonstrate causality," Dr. Vega and colleagues cautioned.

The study included 86 patients diagnosed with COPD by pulmonary function tests (FEV₁ to FVC ratio 70% or less) who completed a questionnaire of gastroesophageal reflux symptoms and COPD exacerbations.

The groups did not differ in gender, age, FEV₁ percentage of predicted, smoking status, body mass index, weekly alcoholic consumption, or weekly coffee consumption.

The average age was 67, 55% were men, and all had at least a 20 pack-year history of smoking. Individuals with respiratory disorders other than COPD, known esophageal disease, or current abuse of alcohol (defined as more than three drinks per day) were excluded.

The GERD plus COPD group averaged 1.56 more exacerbations (95% confidence interval 0.44 to 2.69) per year after adjusting for other factors (3.2/yr versus 1.6/yr, P

Interestingly, all but four of the 32 participants with symptomatic GERD were on antireflux therapy (16 proton pump inhibitors, 10 H₂-receptor antagonists, and 23 antacids). In a subanalysis of the patients receiving antireflux therapy, those with controlled or nonsymptomatic GERD on proton pump inhibitors averaged only 1.6 COPD exacerbations compared to 3.7 for the symptomatic GERD group receiving the same medication, a difference which did not reach statistical significance (P=0.09), and the study was not powered to show a difference.

"At this point, we cannot conclude that the use of antireflux therapy was or was not protective against exacerbation," the researchers wrote.

The eight smokers with GERD (25%) tended to have more frequent COPD exacerbations than the 10 non-GERD patients (18%) who smoked, but the difference was not significant (2.0 versus 1.6 per year, P=0.9).

The mechanism through which GERD increases exacerbations may be microaspiration of gastric contents or vagal nerve-induced bronchospasm from gastric acid irritation of the esophagus or both acting as airway irritants, Dr. Vega and colleagues postulated.

They said the study supports GERD as "a possible modifiable risk factor in exacerbations of COPD."