New insights to combat chronic refractory cough: Canadian Thoracic Society meeting

Toronto - Chronic refractory cough (CRC) is still a challenge, but improved understanding of the underlying causes and upcoming new treatments are giving doctors better tools to help patients. The most common symptom doctors see in ambulatory primary setting is cough, according to Dr. Stephen Field, clinical professor of medicine at the University of Calgary. He gave an overview of the topic at the recent virtual annual meeting of the Canadian Thoracic Society. “In a paper we published in 2009, we found the average duration of cough in patients who presented to our clinic was 5.5 years,” he said. Chronic cough is defined as persistent cough that lasts for eight weeks or longer. Up to 40% of referrals to respiratory specialists are for chronic cough. A cough study recently published in EJR Open Research from the Canadian Longitudinal Study on Aging (CLSA) researchers found that among 29,972 participants, 15.8% experienced cough for "most days" during the last 12 months, and 17.6% at a three-year follow-up. Prevalence increased with smoking, age, male gender and lung disease. Chronic cough rarely is dangerous but should be taken seriously because it can have dramatic impacts on a person’s quality of life. People with persistent chronic cough can face sleep disturbance from coughing, stress incontinence when they cough, job loss or an inability to get hired, and more. “Some will cough to the point where they pass out—cough syncope—meaning it’s not safe for them to drive a car or operate machinery. Some people have fractured ribs from coughing, and some cough to the point where they vomit,” he told The Medical Post in an interview. On the bright side, there are treatment approaches that help resolve chronic cough in upwards of 70% of patients. And there are promising approaches for the remaining 30% who have CRC. To start, doctors need to take a detailed history, exam the patients, and order a chest X-ray if the cough has persisted for more than four weeks. Pulmonary function testing is often helpful. It’s important to first rule out serious conditions such as tuberculosis, lung cancer, chronic bronchitis or other serious conditions. “It depends on how the patient presents,” Dr. Field said. Issues such as gastroesophageal reflux, asthma, sinus issues, medications, occupational exposure to irritants or other manageable factors could be the cause. Still, “these patients need appropriate follow-up. If one thing doesn’t work try something else. Most of these patients will respond.” But what should be done with the remaining 30% of patients who are refractory or unresponsive? “They used to be dismissed as having a psychogenic or habit cough. We now realize that there are features suggesting an underlying neuropathic disorder,” he said. There are two key approaches that can help many of these patients. Indeed, about half of CRC patients respond to speech therapy techniques and breathing exercises. And others will improve symptomatically with medications used for neuropathic pain such as gabapentin and pregabalin. While gabapentin (pregabalin was still under study) is recommended for some patients in the 2016 guidelines on unexplained CRC from the American College of Chest Physicians (ACCP), this would be an off-label use. CRC as a neuropathy The argument for CRC being a neuropathy is compelling. “With neuropathic pain, people experience pins and needles or paresthesia. Patients with chronic cough get pharyngeal paresthesia—they get this tickle sensation in the back of their throat which is an equivalent sort of thing, that triggers them to cough,” he said. People with neuropathic pain experience hyperalgesia, where a very mild trigger will cause severe pain. A parallel is seen in CRC patients. For example, a little bit of cigarette smoke exposure that wouldn’t bother most people will trigger an intense coughing fit that will last several minutes. Allodynia is common in neuropathic pain. A parallel in CRC is allotussia where “things that don’t normally cause cough will cause cough in these people like laughing or temperature changes,” he said. Studies show about 50% of these otherwise hard-to-treat CRC patients improve with speech pathology approaches which include education, vocal hygiene, cough suppressant strategies and psychoeducational counseling. The strategies include avoiding triggers (such as fumes), and cough suppressant strategies which include techniques to prevent coughing fits. “Some patients will have a slight sensation in their throat, think there is something there and make an effort to clear their throat. That just causes more irritation and becomes part of a cycle. They can learn to control that by doing things such as having a sip of water or sucking on a hard candy,” Dr. Field said. Other breathing techniques can help too. For the half of that 30% who don’t respond to these approaches, the AACP guidelines suggest a trial with gabapentin. “There is some controversy over exactly what these neuromodulators do. Some studies show they improve patient quality of life, and perception of cough severity but may not decrease cough frequency. We think they may actually not actually affect cough but patient perception of cough severity,” Dr. Field said. A metanalysis in Otolaryngology Head and Neck Surgery of studies of pregabalin, gabapentin and amitriptyline found cough severity was generally reduced in these patients after neuromodulator treatment. There are also promising new medications in the pipeline, neuromodulators which specifically block purinergic receptors in the vagus nerve. Sensory receptors in the pharynx, larynx and airways transmit information to brain via vagal afferents to initiate cough. Preliminary studies show these medications actually reduce the frequency of cough. The downside is that these drugs commonly cause dysgeusia as a side effect, sometimes leading to a complete loss of taste. As studies continue, doctors may see new medications for CRC in the next few years, Dr. Field said.

New insights to combat chronic refractory cough: Canadian Thoracic Society meeting

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