New Meaning for the Term ‘Hacking’

Abstract & Commentary

By Barbara A. Phillips, MD, MSPH, Professor of Medicine, University of Kentucky; Director, Sleep Disorders Center, Samaritan Hospital, Lexington. Dr. Phillips serves on the speakers bureau for PotomaCME.

Synopsis: This meta-analysis did not convincingly demonstrate a positive effect of gastric acid-suppressing treatment in patients with chronic cough.

Source: Kahrilas PG, et al. Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease. Chest 2013;143:605-612.

This report is the result of a systematic review of the literature concerning the effects of acid-suppressing therapy on chronic cough. The authors specifically focused on whether the presence or absence of gastroesophageal reflux disease (GERD) affected the outcome of treatment. The investigators found nine studies that met their criteria; eight studied proton pump inhibitors (PPIs) and one assessed ranitidine. Only two of the nine trials demonstrated a statistically significant improvement in chronic cough with acid-suppressive therapy. The trials that demonstrated the greatest therapeutic gain to treatment were those that included patients with demonstrated esophageal acid exposure after 8 weeks of treatment. Lowest therapeutic gain was seen in those trials that looked at response after 12 weeks. Lowest of all was the trial that used ranitidine. Of note, the mean placebo response was about 14%; placebo response was less in those patients who had pathologic esophageal acid exposure than in those without.


Chronic cough is a prevalent and vexing problem, affecting up to one-third of U.S. and Western European adults.1,2 GERD is considered to be a significant factor in the etiology of chronic cough, despite lack of robust evidence to support this notion.2-4 In the accompanying editorial, Vaezi asserts that the reasons for this confusion are the unreliability of symptoms in patients who actually have GERD, lack of a gold standard for establishing GERD, and variable designs and outcome measures in studies attempting to address this issue.5 Vaezi reminds us that there are many factors associated with chronic cough, and notes, “Our enthusiasm for increasing the dose, frequency, and duration of therapy with PPIs in a group of patients who may have been misdiagnosed should be guarded because this is the main reason for increased health-care cost in this group of patients,” and adds that chronic cough has even been reported to improve with gabapentin treatment.6 Dr. Vaezi urges us to consider allergies, sinus disease, pulmonary disease (e.g., asthma), or other causes of chronic cough. To that list, I would add medications, especially the angiotensin converting enzyme (ACE) inhibitors.

One of the conundrums the investigators faced was to sort out how “cough” was defined. One big take-home message of this study is that the assessment of cough is not at all standardized. In the reports included in this analysis, assessment of cough included questionnaires, diaries, visual analog scales, and unspecified reports. This reflects that clinical approach to chronic cough; objective measurement of cough is rarely done in clinical practice. Like insomnia or pain, cough is patient-defined. As clinicians, our inclination is to attempt to address complaints that our patients bring us. However, given the fact that cough resolved with placebo (or time) in a significant number of carefully screened patients in the reports included here, and that physiologic consequences of chronic cough have not been convincingly demonstrated, aggressive evaluation and treatment may not always be warranted.


1. Schappert SM, Burt CW. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 2001-02. Vital Health Stat 2006;13:1-66.

2. Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet 2008;371:1364-1374.

3. Kahrilas PJ, et al. American Gastroenterological Association Institute technical review on the management of gastroesophageal reflux disease. Gastroenterology 2008; 135:1392-1413.

4. Irwin RS. Chronic cough due to gastroesophageal reflux disease: ACCP evidence-based clinical practice guidelines. Chest 2006;129(suppl 1):80S-94S.

5. Vaezi MF. Chronic cough and gastroesophageal reflux disease: How do we establish a causal link? Chest 2013; 143:587-589.

6. Ryan NM, et al. Gabapentin for refractory chronic cough: A randomised, double-blind, placebo-controlled trial. Lancet 2012;380:1583-1589.

7. Izzo JL Jr, Weir MR. Angiotensin-converting enzyme inhibitors. J Clin Hypertens 2011;13:667-675.