Anti-reflux therapy no help for most with chronic cough

Chronic Cough and Reflux: A Tangled Relationship

Although we're taught that gastroesophageal reflux disease (GERD) is a major cause of chronic cough, the truth may be more complicated, and confusing.

A meta-analysis by Peter Kahrilas et al in Chest examining trials of acid-suppressing treatments for chronic cough found no significant benefit of treatment in 7 of the 9 trials. And the two trials that were positive were crossover studies, with the benefit only seen in the arm getting placebo first (meaning they could easily have just gotten better over time, unrelated to treatment).

However, the meta-analysis suggests that patients with documented esophageal acid exposure may constitute a subgroup for whom acid-suppressing therapy is helpful.

When analyzing only the patients for whom esophageal acid exposure could be measured with pH probes, acid suppression therapy did reduce cough, a fairly robust finding across 7 studies (cough reduction of 12-36%, vs. 0-9% reduction in patients without high esophageal acid exposure).

Average placebo response to anti-acid therapy for chronic cough was about 14% overall. However, the response rate to placebo varied according to whether there was esophageal acid exposure. Across 5 study datasets:

• Chronic cough with normal esophageal pH:  24% improved with placebo.

• Chronic cough with pathologic esophageal acid exposure: 8.4% improved after receiving placebo.

Eight of the trials used proton pump inhibitors, and one used ranitidine; duration of therapy was 8-16 weeks.

The findings fly in the face of conventional wisdom and abundant observational data as highlighted in the ACCP's 2006 practice guideline on cough due to gastroesophageal reflux. If the key to relief of chronic cough with anti-acid therapy is having excess esophageal acid, though, any trial could be falsely negative with a small enough sample size and enough people with normal esophageal pH included.

A last wrinkle: chronic cough can probably cause reflux to occur just after a coughing episode. In these people, chronic cough and reflux coexist, but acid reduction won't be expected to improve the cough.

I applaud the ongoing research to better understand this frustrating and common problem that accounts for a huge number of outpatient pulmonology visits. Without new technology (acid breathalyzer?) though, it's hard to foresee a change to standard care with empiric anti-reflux therapy, owing to the inconvenience and cost of esophageal pH monitoring (compared to $40 for 3 months of omeprazole at generic pricing).

Peter Kahrilas, Colin Howden, Nesta Hughes, and Michael Molloy-Bland.  Response of Chronic Cough to Acid-Suppressive Therapy in Patients With Gastroesophageal Reflux Disease. Chest 2013; 143(3):605-612.