Chronic cough is a common problem otolaryngologists see in clinical practice, with a global estimate of 10% of people affected, many of whom experience it for more than 15 years, even after trying different treatments (ERJ Open Res. doi: 10.1183/23120541.00459-2024). Chronic cough in this latter case is referred to as refractory chronic cough.
Defined as lasting for longer than eight weeks in adults and four weeks in children, chronic cough requires a multidisciplinary approach, both in diagnosis and treatment, to adequately address a problem that can be a long and frustrating experience for patients.
As with all conditions, understanding the etiology of the cough is the first step, requiring a thorough history and physical examination of the patient. Over the years, the thinking on chronic cough has evolved. Until more recently, treatments were aimed at the underlying disease, of which the cough was considered a symptom, but this did not adequately treat the chronic cough, and patients were given unnecessary treatments. More recently, with a growing understanding of the distinct pathophysiology of chronic cough, many practitioners now recognize and argue that chronic cough is its own disease and should be considered as such to deliver appropriate care (ERJ Open Res. doi: 10.1183/23120541.00459-2024; Eur Respir Rev. doi: 10.1183/16000617.0127-2021).
Recent evidence (eBioMedicine. doi.org/10.1016/j.ebiom.2024.104976) also points to the neurogenic cough in some patients, with studies showing that patients with chronic cough have a cough hypersensitivity that may occur in brain circuits and may involve the mid regions of the brain, where ascending sensory signals are amplified or the efficacy of the central inhibitory control systems that usually filter sensory inputs is altered. Further evidence (Neurosci Biobehav Rev. doi: 10.1016/j.neubiorev.2023.105142) illustrates how the nervous system processes sensory information and interprets and integrates those signals from the body, including reflexes or urges exhibited in chronic cough.
All of this emerging evidence on the pathophysiology of chronic cough is helping researchers to better understand a condition that, for many patients and doctors, has sometimes been baffling, lacking a clear etiology. Historically, in adults and occasionally in teenagers, chronic cough is attributed to three main causes. However, emerging insights from pathoneurophysiology reveal that some patients may experience a type of chronic cough that is not caused by anatomical or functional issues, such as those related to the sinuses, but rather occurs due to dysfunction in the nervous system’s signaling to the brain.
Among the most critical factors to consider first when presented with a patient with a chronic cough is the age of the patient, as chronic cough in adults is different from that occurring in children. For all patients, an understanding of the etiology of chronic cough begins with a comprehensive clinical history, physical examination, and diagnostic testing as indicated, and ideally includes an interdisciplinary team, often involving a gastrointestinal specialist, a pulmonary specialist, an allergy specialist, and a speech–language pathology specialist. Once the etiology is understood and a diagnosis is made, several treatment options are available, and investigational solutions are in the pipeline.
Common Causes of Chronic Cough in Adults
Common causes of chronic cough in adult patients, which otolaryngologists consider first, are gastroesophageal acid reflux, cough variant asthma, and allergies. “There is still a large portion of patients who suffer from one of these conditions, which are primarily nonlaryngeal,” said Peak Woo, MD, an otolaryngologist in private practice in Manhattan and clinical professor in the department of otolaryngology at Icahn School of Medicine at Mount Sinai in New York, who adheres most often to the guidelines on refractory chronic cough published in CHEST (Chest. doi: 10.1378/chest.15-1496).
Understanding the etiology of the cough begins with a history of the pattern of the cough, such as whether it is a single cough or spasms of coughing, and whether the cough is productive or nonproductive. Dr. Woo will ask patients to point to the area of their body where the cough originates; patients often point to the throat, chest, or sternum.
After this initial assessment, he then conducts a physical examination, primarily to identify whether the cough is associated with an inflammation or if there is a movement the patient makes that suggests the organicity of the cough. If the examinations suggest the cough is caused by inflammation in the airway, he refers patients for further workup with a gastroenterologist (preferably one who specializes in the esophagus) for pH impedance and manometry tests to assess esophageal function. When patients have a totally negative workup for acid reflux but have inflammation, he’ll often refer them to a rhinologist to order a CT scan of the sinus and have them see an allergist and immunologist who will do further testing for things like immunoglobulin immunodeficiency. Sometimes he’ll refer patients to a pulmonologist, for example, if steroid treatment suggests a reactive airway component and the patient is not getting better.
Similarly, Rebecca Howell, MD, associate professor, director of the US Health Swallowing Center, program director of the fellowship in laryngology, and division chief of laryngology in the department of otolaryngology–head and neck surgery at the University of Cincinnati in Ohio, first looks to see if the cough is more of a spastic type of cough or a single cough, like throat clearing. If it is the latter, she sees it as a sign of laryngeal irritation likely caused by postnasal drip, acid reflux, or asthma/allergy. She conducts both a functional exam (i.e., she has the patient simulate a cough to try to see what the cough is) and an anatomic exam (i.e., to rule out anything bad or scary). The most important finding on a laryngoscopy is the absence of anything else, she said. “Absence of any anatomic findings is really important,” she said, such as no masses, no cobblestoning (i.e., sign of inflammation), and no pooling of secretion or food in the throat (if so, then neurologic or swallowing conditions should be on the differential).
When nothing is abnormal anatomically, Dr. Howell said it is critical to make sure laryngopharyngeal movement is full. “Sometimes we look for asymmetry of the vocal cord motility, and this can guide treatments,” she said. “We also do different breathing strategies, such as simulating a paradoxical vocal fold motion with inhalation, sometimes deep breathing exercises, to ideally trigger or suppress the cough.”
Treatment for these common causes of cough is based on the underlying cause. Nikita Kohli, MD, assistant professor of surgery (otolaryngology) at the Yale School of Medicine in New Haven, Conn., cited a number of treatment choices. For chronic cough associated with rhinitis, she recommends nasal sprays and saline rinses. If related to chronic sinusitis, she may include antibiotics, steroids, and, potentially, sinus surgery in collaboration with a sinus surgeon. For reflux, she starts with diet and recommends patients avoid reflux triggers such as fatty foods, spicy foods, and caffeine, and she encourages them to keep a diary of potential reflux triggers. Medical therapy with antacids and/or alginates may also be prescribed for reflux. She also ensures that patients have had a cardiopulmonary workup for their cough.
Neurogenic Cough
Relatively recently, it has been recognized that, in some people, chronic cough is caused by a neural hypersensitivity or intrinsic nerve issue related to the larynx. Called neurogenic cough, the diagnosis is based on the exclusion of the other potential etiologies described above. “Once you decide the chronic cough is not one of the three common things, and patients are not responding to the usual therapies, we put them in this neuropathic bucket, and often patients have had this neuropathic cough for years,” said Dr. Howell. “Patients typically describe sensitivities to strong smells and temperature changes, and many will describe it as a spastic cough where they can’t catch their breath.”
Dr. Woo referred to this type of chronic cough as a cough that has a primary laryngeal source. He said you can see this in patients, for example, who had vocal cord paresis during COVID-19, and they couldn’t stop coughing. Another example is in patients with intensely inflamed vocal cords that could be irritating the mucosa to cause the cough. “Patients with inflammation at the vocal folds are less likely to have neurogenic cough,” he said. Checking for these things, he said, is how he triages patients.
Dr. Woo underscored that neurogenic cough is increasingly being referred to otolaryngologists by outside physicians, including specialists, as it is seen as an otolaryngologic issue. “We’re diagnosing more neurogenic cough than we did 10 years ago,” he said.
For patients with neurogenic chronic cough, different classes of neuromodulator therapies are used, typically for an initial trial period and, if successful, are used for a longer duration before tapering. Relatively new but increasingly used is the superior laryngeal nerve block, which has been shown to be safe and effective (Ann Otol Rhinol Laryngol. doi: 10.1177/00034894231194384; J Voice. doi.org/10.1016/j.jvoice.2025.01.004). Newer agents are also emerging that may alleviate chronic cough, but many of these are not yet approved by the U.S. Food and Drug Administration.
Dr. Kohli emphasized the burden of chronic cough on patients. “Many patients don’t think there are treatment options, and they struggle with this for years,” she said, adding that she sees patients who have had this for 10 to 20 years and think there are no more treatments for them.
“I let them know they do have options but that it will take time and work to find the right treatment, particularly for neurogenic chronic cough,” she said.
For patients with neurogenic chronic cough, she considers three treatment approaches. First is cough modulating therapy, in which the patient works with a speech–language pathologist on techniques to modulate the cough. Second, she offers medical therapy using neuromodulators such as gabapentin and amitriptyline. Lastly, she may offer a relatively new intervention with a nerve block in which a combination of lidocaine and a steroid is injected into the neck, targeting the superior laryngeal nerve. “All of these treatments have shown efficacy in improving neurogenic cough, and I try to offer a personalized treatment approach for each patient,” she said.
Dr. Woo also uses these three approaches to treat neurogenic chronic cough. For medical treatment, he places them into three main drug groups: He uses tramadol, gabapentin or pregabalin, and amitriptyline or naratriptan. “Each of these groups of drugs works differently on the central nervous system and reduces sensitivity to cough,” he said, adding that he’ll first try the drugs for a one- to two-month trial and, if successful, will extend to three to five months and then taper.
In his own practice, he is using nerve blockers instead of medical therapy, given the side effects of medical therapy. “We’re doing office-based superior laryngeal blocks using steroid and Novocain,” he said. “You give the block, and it breaks the coughing cycle.” He cited work by C. Blake Simpson (Ann Otol Rhinol Laryngol. doi: 10.1177/00034894231194384) that shows that in-office superior laryngeal nerve blocks are quick and well-tolerated, with positive short-term outcomes.
Although Dr. Howell used to prescribe one treatment at a time, she said that she now tends to give patients multiple treatments at once, such as combining cough behavioral therapy with medical therapy, given the length of time some patients have had to cope with chronic cough and the strong motivation to get it resolved sooner rather than later. She emphasized that before she starts a neuropathic medication or offers a superior laryngeal nerve block, she makes certain that the patient has had some kind of GI and pulmonary screening. “The patient should at least have some pulmonary function tests within the past year and a chest X-ray that are all normal prior to initiating these adjuvant therapies that are for recalcitrant patients,” she said.
Chronic Cough in Infants, Children, and Teenagers
The presentation of chronic cough in children differs from that seen in adults. Ian N. Jacobs, MD, MLA, the medical director of the Center for Pediatric Airway Disorders, endowed chair in pediatric otolaryngology and pediatric airway disorders at the Children’s Hospital of Philadelphia, and professor of otolaryngology–head and neck surgery at the Perelman School of Medicine at the University of Pennsylvania, both in Philadelphia, said that chronic cough can be a challenging condition to treat, and often the etiology remains elusive. “We search for the etiology and try to come up with a rational treatment plan,” he said.
As in the initial workup done in adults, conducting a comprehensive history is important to know how long the cough has been going on, its nature, and what exacerbates it (i.e., strenuous activity, cold air, or nasal drainage). Dr. Jacobs emphasized that involving multiple specialists, such as gastroenterologists and pulmonologists, is sometimes critical for the overall assessment.
“From the get-go, you want to differentiate a dry from a productive chronic cough, and the age of the patient matters tremendously,” he said. “In an infant, a cough may indicate a congenital airway problem like subglottic stenosis, tracheomalacia, vocal cord paralysis, or lower airway pathology, and in these cases, you may involve an airway and pulmonary specialist who will perform a microlaryngoscopy and bronchoscopy to examine the airway.”
Chronic cough in an older child or teenager is a totally different story, he said. In the older patient, a dry habitual cough could indicate a reactive airway in which something is inflaming the airway and is exacerbated by, for example, cold air or exercise. “In this case, I would think of cough variant asthma,” he said, adding that he’d refer this patient to a pulmonologist. “I have a low threshold for involving a pulmonologist or gastroenterologist in some of these workups,” he said.
If the cough in a teenager is productive, with lots of postnasal drip, for example, he would consider an allergy evaluation or sinus workup with nasal endoscopy or imaging and would then treat accordingly, he said. In cases of seasonal or non-seasonal allergic rhinitis, he would consult an allergist.
For a dry cough, he treats with inhaled steroids or a bronchodilator and again refers the patient to a pulmonologist. If the cough is productive and may indicate sinusitis, he treats the patient with maximal medical therapy that includes steroids, Flonase, Nasonex, or saline.
Another category of chronic cough he sees in kids is a habitual cough, or a cough that indicates a nervous tic. “You want to first rule out all the organic causes of chronic cough before diagnosing habitual cough or nervous cough,” he said. Once diagnosed, he said that some kids respond well to cough suppressants.
For these kids, he often sees stress as the underlying issue—maybe related to school or family issues. “You have to be honest with them and ask them what is going on in their lives to try to see if any stressors can be dealt with,” he said, noting that he saw an increase in habitual cough, particularly during the COVID-19 pandemic, with increased use of social media. “The most important part of chronic cough treatment involves identifying the underlying cause,” he said.
Mary Beth Nierengarten is a freelance medical writer based in Minnesota.
Leave a Reply