KEYSTONE, Colo. – Physicians would do well to add habituation, neuropathic triggers, and laryngopharyngeal reflux to the list of factors they assess when tracing the origins of a cough that has persisted for longer than 8 weeks, advised a Colorado pulmonary specialist.
The usually recognized initiators of chronic refractory cough include asthma, upper airway cough syndrome (postnasal drip), and gastroesophageal reflux disease. But looking beyond these common culprits and analyzing combined etiologic factors on a case-by-case basis may be necessary, emphasized Dr. Ronald C. Balkissoon of the division of pulmonary and critical care medicine at National Jewish Health in Denver.
"Most people who have chronic cough have at least two or more underlying problems that are contributing to it," Dr. Balkissoon said at a meeting on allergy and respiratory diseases, sponsored by National Jewish Health. "Often [physicians] will just try to treat one issue like acid reflux and it doesn’t work, so they presume that’s not part of the problem. But you really have to have a multidisciplinary approach and consider all the relative contributing factors."
An especially underappreciated complication is laryngopharyngeal reflux (LPR), he said. Physicians using both classic pH probes or impedance probes often shortchange their diagnoses by missing clues, in large part because LPR is not specific in its presentation. The role LPR plays can be obfuscated by the presence of supraglottic edema or erythema, glottic abnormalities, epiglottic malformations, and lingual tonsillar hypertrophy, among other factors.
Moreover, the cobblestoning of epithelial tissue, an obvious sign of LPR, is not exclusive to that disease. It is also seen in cases where chronic cough derives mostly from a postnasal drip. Bronchoscopy will often reveal a transformation of tissue from normal columnar epithelium into squamous epithelium, even when the reflux is nonacidic, but beyond that, finding the proper context for tissue changes such as cobblestoning and ruling out non-LPR origins can be a challenge.
Chronic cough has a detrimental effect on the lives of many, with almost 30 million clinical visits reported annually in the United States. Females demonstrate a higher cough reflex sensitivity than do males, and the condition is driven by several additional originating factors that range from ACE inhibitor use to chronic bronchitis and bronchiectasis.
The learned and neuropathic origins of persistent cough stand as additional elements that may be more important in the big picture than many clinicians realize.
"Habituation, I think, is a very, very big part of what happens to people who have chronic cough," Dr. Balkissoon said. "They may have postnasal drainage issues. They may have gastroesophageal reflux disease issues and even ongoing asthma, but by the time they develop this cough that’s been going on for 15 or 25 years, there’s clearly habituation."
At another level, neuropathic manifestations of chronic cough are due to the irritant receptors that thrive in the lungs and throat. These include nociceptive C fibers, G protein, transient receptor potential vanilloid 1, and transient receptor potential A1.
The jury is still out on newer receptor antagonists, as well as surgical procedures such as fundoplication and other nonpharmacologic management approaches. But a diagnosis that acknowledges the likelihood of a more complex group of reasons for chronic cough may be the most logical way to seek better-tailored therapies.
"Most of the people who have chronic cough really have the common etiologies, but understanding that they’re often in combination and they have one or more reasons for it being refractory is the most important point," Dr. Balkissoon said.
Dr. Balkissoon disclosed speaking on behalf of AstraZeneca, Boehringer Ingelheim, Genentech, GlaxoSmithKline, and Novartis.