Multidisciplinary clinic specializes in chronic cough

Chronic cough — one lasting eight weeks or more — is one of the most common reasons adults seek medical treatment. Persistent severe coughing can be debilitating and profoundly affect work, relationships, sleep and quality of life.

Traditionally, chronic cough has been thought to result from three underlying triggers:

  • Gastroesophageal reflux disease (GERD)
  • Sinonasal disease (upper airway cough syndrome)
  • Asthma

Treating these conditions often improves symptoms, but a subset of patients with no apparent lung disease will continue to cough after treatment.

GERD has traditionally been thought to play the largest role in chronic cough and is included in most diagnostic and therapeutic algorithms for cough management. More recently, using ambulatory cough monitors, researchers at the University of Manchester in the U.K. have demonstrated a strong temporal association between gastroesophageal reflux events and coughing, even when patients had other associated conditions or normal levels of reflux. A 2010 study in Gastroenterology found that roughly half of 71 patients with chronic cough had a statistically significant association with reflux before cough and half had an association with reflux after it. Around one-third of patients had both.

Lesley A. Houghton, Ph.D., a researcher at Mayo Clinic's campus in Jacksonville, Florida, reports that two physiological mechanisms have been proposed to explain the association between GERD and chronic cough. The standard anatomical theory is that gastroesophageal reflux directly stimulates cough nerves in the larynx via laryngopharyngeal reflux and sometimes the bronchial tree via aspiration, with cough occurring as a protective mechanism. But because reflux is often normal in patients with chronic cough, a newer, increasingly accepted idea is that reflux causes cough via a sensitized neuronal pathway linking the esophagus to the airway — a pathway that appears inactive in healthy people.

Gastroenterologist Kenneth R. DeVault, M.D., who specializes in reflux and other gastroesophageal disorders at Mayo Clinic's campus in Florida, explains that neuronal cross-talk may be possible because the esophagus and respiratory tract share common embryological origins.

"Afferents from the esophagus and airways converge in the brain stem. In healthy people no cross-talk occurs, but in patients with chronic cough, the pathway becomes sensitized, allowing stimuli within the esophagus, such as reflux, to cause cough. But what causes this sensitization isn't known," he explains.

Another important and often overlooked cause of cough is nonacid reflux, says pulmonologist Augustine S. Lee, M.D., also of Mayo Clinic's campus in Florida. He explains: "Physicians often treat patients with chronic cough empirically with acid suppressants like proton pump inhibitors (PPIs) whether GERD is present or not. When the cough persists, it's assumed the patient doesn't have reflux cough. But empiric treatment of cough with PPIs may only help a subset of patients.

"The lack of efficacy of PPI in reflux-associated cough may occur because PPIs don't treat non-acid reflux or because of the neuronal link between reflux and cough. As a result, until we have more data to guide us, we have approached the issue of GERD and cough more systematically by precisely measuring the relationship between a patient’s cough with both acid and non-acid reflux obtained from an impedance-pH study."

Because patients aren't responding to PPIs, they get more and more referrals, from GI to pulmonologists and back again, with multiple procedures, diagnostic tests and empiric therapies, yet fail to get satisfactory relief, Dr. Lee says.

To help address the unmet clinical needs of chronic cough patients, Mayo Clinic's campus in Florida has established a chronic cough clinic — "something fairly novel in the U.S.," according to Dr. Houghton, formerly of the University of Manchester. "Both frustrated physicians and their patients are often thrilled to find such a clinic exists," she says.

Dr. Lee adds: "What makes us different from other centers is not just that we have a cough clinic at all, but that we also have the luxury of a multidisciplinary team to tackle this very difficult yet common condition. Cough can be a symptom of another disease — asthma, tumors, fibrosis, bronchiectasis — or medications, so we first perform a very comprehensive clinical evaluation to identify and treat any primary associated disorders. As a multidisciplinary practice, this may involve our colleagues in otolaryngology, speech pathology, allergy and gastroenterology as well as formal systematic testing for anatomic or functional abnormalities of the lungs, bronchial hyper-reactivity, formal reflux testing, and rhinoscopy."

Dr. DeVault notes, "After a comprehensive evaluation at our clinic, patients have complete reassurance that cough itself is the problem and not a sign of a separate, serious disease, which is a common fear among many who seek tertiary care, especially older patients."

Research

Researchers at Mayo's Florida campus are studying chronic cough in collaboration with the University of Manchester as well as pursuing their own investigations. They are currently recruiting patients for a pilot study evaluating possible predictors of respiratory hypersensitivity and how they relate to clinical subtypes of GERD.

The number of patients seeking evaluation has substantially increased since the cough clinic opened a year ago and continues to grow as awareness of the clinic increases among patients and referring doctors. Dr. Houghton says patients can receive a comprehensive evaluation for cough and a customized treatment plan based on currently available medications, but that Mayo, in collaboration with the University of Manchester also hopes to be involved in trials of agents that specifically target neuronal pathways.

Comprehensive, multidisciplinary evaluations for chronic cough are also available at Mayo Clinic campuses in Rochester, Minnesota and Scottsdale, Arizona.

For more information

Smith JA, et al. Acoustic cough — Reflux associations in chronic cough: Potential triggers and mechanisms. Gastroenterology. 2010;139:754.

Pilot Studies Evaluating Cough Reflex Sensitivity and Bronchial Hyper-Responsiveness: The Road to Cough and Wheeze in Patients With Gastroesophageal Reflux. ClinicalTrials.gov.