CHEST. 2003;123(3) 

In This Article

Chronic Cough

Cough remains one of the most common complaints motivating patients to seek medical attention in the United States. Fortunately, we have 25 years of evidenced-based research to help us evaluate and treat even the most perplexing cases. Utilizing a diagnostic protocol allows the cause of cough to be identified in 88 to 100% of patients, and with appropriate therapy there is resolution of cough in up to 98% of patients.[1] Several studies have supported the utility of the diagnostic protocol in patients with chronic persistent cough, not only in the academic tertiary care setting, but also in the community setting. Under the leadership of Dr. Richard Irwin, the American College of Chest Physicians (ACCP) developed an evidence-based consensus panel report[2] in which diagnostic algorithms and appropriate treatment regimens were presented that target the underlying cause of cough. By definition, chronic persistent cough is a cough lasting for > 8 weeks in a nonsmoking, immunocompetent patient who has a normal chest radiograph finding, is not receiving therapy with an angiotensin-converting enzyme inhibitor, and has not been exposed to an environmental irritant. In this setting, the three most common causes of cough are postnasal drip (frequency, 41 to 58%), cough-variant asthma (frequency, 24 to 59%), and gastroesophageal reflux (GER) [frequency, 21 to 41%]. Cough-variant asthma and rhinosinus diseases can be dealt with by appropriate evaluation and treatment. Another compounding factor is that in approximately 20% of patients cough is due to more than one cause, making careful, persistent follow-up and further evaluation a requirement to ensure cough resolution.

GER-related cough can be diagnosed easily if the cough patient has esophageal manifestations of GER. Six to ten percent of chronic cough patients have prominent esophageal GER symptoms. In these patients, GER should be treated aggressively. However, it may be clinically silent in 50 to 75% of cough patients. These patients do not have esophageal symptoms; however, they do have significant esophageal acid contact times or coughs that are temporally associated with esophageal acid events on esophageal pH testing.[3,4] The ACCP consensus report recommends esophageal pH testing, if available, in evaluating these patients and utilizing an empiric trial of medical reflux therapy when esophageal pH testing cannot be performed or is unavailable.[2]

In this issue of CHEST (see page 679), Poe and Kallay report on a practical approach for diagnosing and treating GER-related cough that was successfully utilized in their pulmonary specialty practice affiliated with a university. Using the anatomic diagnostic protocol in 214 patients, with cough resolution defining success, GER-related cough was present in 53 subjects (31%). As in previously reported trials, clinically silent GER was present in 24 of their subjects (43%). Another key finding is that an empiric trial of antireflux therapy successfully diagnosed and treated GER-related cough in 42 patients (79%). All of their GER subjects were instructed on lifestyle measures (ie, weight reduction, high-protein antire-flux diet, and elevation of head of bed) and were prescribed omeprazole, 40 mg, lansoprazole, 30 mg, or rabeprazole, 20 mg, to take each morning before breakfast. A prokinetic agent was added to the regimen if dysphagia was present or if initial therapy with a proton pump inhibitor was less successful than expected (18 subjects). If the empiric trial approach failed, then 24-h esophageal pH testing was employed in the nonresponders (12 subjects). Of these initial nonresponders, four eventually responded to therapy with high-dose proton pump inhibitors combined with a prokinetic agent, and two had success with surgical fundoplication. Poe and Kallay also noted that 4 weeks of therapy resulted in cough resolution in 86% of their responders, while 6 weeks of therapy resulted in cough resolution in 95% of their responders.

These data further support the use of an empiric antireflux trial in chronic persistent cough patients, even in those without esophageal GER symptoms. An appropriate approach would be to administer before breakfast a prokinetic agent in selected patients with dysphagia, utilizing a proton pump inhibitor, for 4 to 6 weeks, followed by esophageal pH testing in the nonresponders while the patients continue to receive antireflux therapy. This approach is not only practical for the practicing pulmonologist who does not routinely perform esophageal pH testing, but is also cost-effective. Ours et al[5] noted that an empiric trial of omeprazole, 40 mg twice daily, was threefold to fivefold less costly than esophageal pH testing at onset.

So, why use a proton pump inhibitor first? The use of therapy with (histamine 2) H2 antagonists is often unsuccessful in adequate acid suppression, and treatment may be prolonged before there is an impact on cough. Furthermore, of the 18 patients who were treated with an H2 antagonist prior to referral to Poe and Kallay, 17 had not achieved cough relief.

Also, who should be considered for an empiric trial? Obviously, patients with esophageal symptoms should be considered. However, a large number of patients have clinically "silent" GER. Irwin and Madison[6] have described the clinical profile of a patient with cough due to silent GER, as someone who is a nonsmoker, is not receiving an angiotensin-converting enzyme inhibitor, has not been exposed to environmental irritants, who has a normal or near-normal chest radiograph finding showing nothing more than stable inconsequential scarring, and in whom asthma, rhinosinus diseases, and eosinophilic bronchitis have been ruled out or have been adequately treated.[6] These patients also should be considered for an empiric trial.

Finally, 24-h esophageal pH testing should be performed in cough nonresponders. Treatment failures may be due to inadequate acid suppression (which would be picked up by esophageal pH testing) or may be due to nonacid reflux and/or failure to recognize and treat other conditions that could cause chronic cough. Irwin et al[7] reported eight subjects whose chronic cough did not respond to antireflux medical therapy despite esophageal pH testing showing minimal esophageal acid. Since fundoplication resulted in cough resolution in six subjects and in marked improvement in the remaining two subjects, their findings suggested that mediators other than acid may play a role. These medical nonresponders should be referred to a specialized center for further testing, which may include esophageal impedance monitoring (ie, monitoring of esophageal liquid and gas contents).

The experience of Poe and Kallay shows the ACCP consensus panel report on chronic persistent cough to be very useful, clinically. Second, GER is a common cause of chronic persistent cough. Third, an empiric antireflux trial of therapy utilizing a proton pump inhibitor before breakfast for 4 to 6 weeks is not only practical, but also may be cost-effective. Revising the algorithm for GER-related chronic cough to include an empiric trial in the consensus panel report should be considered. Twenty-four-hour esophageal pH testing should be reserved for the nonresponders to medical antireflux therapy. These patients are the "challenging" ones and should be evaluated much more carefully.

Susan M. Harding, MD, FCCP, Birmingham, AL

Dr. Harding is Associate Professor of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, and has been a consultant for Astra Zeneca LP.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Susan M. Harding, MD, FCCP, Division of Pulmonary, Allergy, and Critical Care Medicine, 1900 University Blvd, THT Rm 215, University of Alabama at Birmingham, Birmingham, AL 35294; E-mail: sharding@uab.edu.

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