Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study

Abstract

Summary Background Cough may be a manifestation of gastro-esophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain. Aim To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. Methods Subjects were non-smokers without history of asthma, with chronic cough for > 8 weeks. All subjects underwent a baseline 24 hr pH/impedance study, methacholine challenge test (MCT), and laryngoscopy. Subjects were randomized to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores, and change in laryngeal findings. Results 40 subjects were randomized (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8, vs. 5.9 in placebo, p = 0.3), or Fisman Cough Severity/Frequency scores. The proportion of patients who improved by >1 standard deviation on the CQLQ was 27.8% (5/18) and 31.8% (7/22) in the placebo and PPI groups respectively. Conclusions In subjects with chronic cough and rare or no heartburn, high-dose PPI did not improve cough-related quality of life or symptoms in this randomized controlled trial.

Unmet Needs in the Treatment of Gastroesophageal Reflux Disease

“…Two recent, double-blind, placebo-controlled trials in adult patients with chronic cough did not demonstrate that PPIs are more effective than placebo. 67,68 A recent metaanalysis of 5 randomized, placebo-controlled trials in adult patients with chronic cough did not find sufficient evidence in favor of PPI therapy. 69 Hoarseness has also been considered to be an important extraesophageal manifestation of GERD.…”

Treatment of Unexplained Chronic Cough

“…36 No benefits on cough severity or quality of life were observed, suggesting that there was no evidence that the chronic cough was due to acid reflux with GERD. Moreover, there were no serious adverse events, and no one was withdrawn from the study for safety.…”

“…Asthma was excluded by physician Idiopathic chronic cough 1 study 20,25 1 SR 32 Chronic cough of unknown etiology 3 studies 26,36,37 Chronic treatment-resistant cough 1 study 25 Intractable chronic cough 1 study 25 Postviral vagal neuropathy 1 study 22 SR ¼ systematic review.…”

Expert opinion on the cough hypersensitivity syndrome in respiratory medicine

“…A systematic review found no conclusive support for the use of PPIs in reflux cough [54]. More recently, two randomised controlled trials confirmed little or no effect of PPIs on chronic cough when compared with placebo (placebo, as is common in the trials of cough, having quite a marked effect over baseline) [55,56]. The authors of these trial reports [55,56] concluded that, given the evidence that PPIs may increase the likelihood of aspiration pneumonia [57], PPIs should not be routinely used in the treatment of a reflux cough, but should be reserved for patients exhibiting features of acid-related disease [58] or bronchospasm [59] in addition to cough.…”