Chronic cough remains a persistent challenge for clinicians and patients, given the wide range of potential causes and confusion regarding symptoms, according to experts.
One of the key features of chronic cough is its duration of 8 weeks or longer, which makes the cough less likely to be associated with a cold or a respiratory infection, according to the American Lung Association. Symptoms associated with chronic cough vary and may include vomiting, muscle pain, urinary incontinence, tiredness, syncope, depression, and even rib fractures in some patients.
Diagnostic Dilemma
The most common causes of chronic cough include gastroesophageal reflux disease (GERD), asthma, and postnasal drip (also known as upper airway cough syndrome), said Sean Duffy, MD, an associate professor of pulmonary and critical care medicine at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.
“The initial history and physical exam remain the most important aspect of attempting to establish a cause in patients with chronic cough,” said Duffy.
Treatment trials are the most cost-effective way to establish a chronic cough diagnosis, but many patients’ trials are too short, said Duffy. “Many times, this is the result of patients’ expectations that the cough should improve quickly once on therapy,” he noted.
“A proper treatment trial with PPI [proton pump inhibitor] for GERD should last about 2 months, and a similar timeframe is necessary to determine response for patients on inhaled corticosteroids for suspected asthma,” Duffy said.
“Chronic cough is distinct from many other conditions in that it truly requires a multidisciplinary workup and treatment. Patients are typically seen and followed by multiple consultants in different subspecialties,” Duffy told Medscape Medical News.
Chronic cough’s multidisciplinary nature makes diagnosis more difficult, and patients often require evaluation by multiple subspecialists including ear, nose, and throat; gastroenterology; allergy; and pulmonology, which can delay diagnosis as patients wait for appointments, testing, and imaging, Duffy said. “While on treatment, some patients have a partial response with regard to their cough, but these patients may still have a significant impairment in their quality of life related to their chronic cough,” he said. “This underscores the fact that chronic cough can be multifactorial or even refractory to proper treatment,” he added.
Another distinguishing factor in chronic cough is the lack of a singular identifiable etiology, Duffy said.
Strategies for Severe Cases
Patients with a suspected etiology for chronic cough who do not respond to adequate treatment for one or more possible causes are considered to have refractory chronic cough (RCC), and patients whose chronic cough has no identifiable cause are deemed to have unexplained chronic cough (UCC), Duffy told Medscape Medical News. These patients tend to have persistent symptoms despite thorough workup and treatment, he said. “These patients are thought to have dysregulation of the neuromodulatory pathways resulting in hypertussia (excessive cough response) and allotussia (easily triggered cough response), which manifests in patients as an easily triggered cough that is very difficult to stop once it begins,” Duffy noted.
Currently, no on-label, approved medications exist for chronic cough, and the treatment protocol depends on the underlying cause, Duffy said.
Patients diagnosed with cough-variant asthma should be treated with guideline-based asthma therapy such as inhaled corticosteroids and long-acting bronchodilators. Those with upper airway cough syndrome may be prescribed intranasal steroids along with an antihistamine, Duffy said.
“Where available, patients may require referral to a chronic cough specialty clinic for additional workup and treatment,” Duffy told Medscape Medical News. Current guidelines suggest a trial of neuromodulator medication, along with speech and language therapy, for patients ultimately diagnosed with RCC or UCC, he said.
Clinicians should not presume that neuropsychologic symptoms are the causes of chronic cough, although all chronic cough patients are at risk for psychological symptoms as a complication of unresolved coughing, wrote Richard S. Irwin, MD, a professor at the University of Massachusetts Chan Medical School and pulmonologist at UMass Memorial Health, and J. Mark Madison, MD, of the University of Massachusetts Chan Medical School, Worcester, Massachusetts, in a recent review article on unexplained or refractory chronic cough in adults.
“Since depression and anxiety have been observed to abate or resolve when cough subsides, these psychological symptoms should always be considered and addressed,” the authors noted. However, “the mistaken assumption that chronic cough in a patient with depression or anxiety must necessarily have a neuropsychological cause may be a reason for the true cause of chronic cough remaining elusive and unexplained in some patients,” the authors noted.
Long-Term Management Is Multifaceted
For long-term care, patients diagnosed with chronic cough may be managed by a variety of subspecialists depending on the cause, Duffy said. Whenever possible, patients with RCC or UCC should be seen by a chronic cough specialist for continued follow-up, he said.
However, a patient with chronic cough related to GERD should be managed by a gastroenterologist, a patient with upper airway cough syndrome may be managed by an allergist or otolaryngologist, and patients with asthma or underlying lung disease should certainly be followed by a pulmonologist long-term, said Duffy.
Some specific therapies favorably affect chronic cough caused by known factors such as asthma, non–asthmatic eosinophilic bronchitis, upper airway cough syndrome, GERD, and bronchiectasis, said Irwin in an interview.
However, treatment options for unexplained or refractory chronic cough caused by an overactive cough reflex are limited, he said.
“Effective pharmacologic antagonists of receptors on the overactive vagus nerve without serious adverse effects would be highly desirable for these patients,” Irwin told Medscape Medical News. “For these patients, antagonists of receptors on the vagus nerve have been or are being explored to downregulate the vagus nerve, although none have yet been approved for clinical use in the United States,” he noted. Current management and treatment options for these patients include multimodal speech therapy and pharmacologic neuromodulation, said Irwin, who also served as the lead author on the current CHEST guideline on classifying cough in adults.
Considerations in Children
Chronic cough in children is distinct from chronic cough in adults in several ways, notably duration and cause, said Julie Marchant, MD, a pediatric respiratory physician and associate professor at the Queensland University of Technology, Brisbane, Australia, in an interview. A chronic cough for children lasts more than 4 weeks vs 8 weeks for adults. “This is because in children most URTI [upper respiratory tract infection] symptoms have resolved by 3 weeks,” she said. Also, other significant conditions can be missed in children initially presenting with chronic cough, such as a foreign body trapped in the airway, she noted.
Children, especially preschool children, typically have many upper respiratory tract viral illnesses each year, which can mean 5-8 illnesses in a year-long period, said Marchant. “Differentiating between back-to-back URTIs and a true chronic cough is one of the challenges doctors face, especially in primary care,” she said.
To help, ask parents the last time their child had a day without a wet cough, Marchant advised. A child may not be able to cough in the office, but parents can record it on their phones for the next visit, she said.
“In children, a cause for the chronic cough should be investigated, diagnosed, and treated using the algorithmic pathways which have been shown to improve management and outcomes,” Marchant told Medscape Medical News.
The common causes of chronic cough in children are not the same as in adults, Marchant said. For example, GERD and upper airway cough syndrome, while common in adults, are not common cough causes in children.
A chest x-ray should be performed for all children with a chronic daily cough lasting more than 4 weeks if they have not yet been x-rayed, Marchant said. If the chest x-ray is normal, the most likely diagnoses are protracted bacterial bronchitis for cases of wet cough or asthma or postinfectious cough in cases of dry cough, she added.
Signs of a more serious underlying cause of chronic cough in children that will need further investigation and referral include symptoms that began in infancy or early childhood; coughing or choking when feeding; symptoms beginning after a choking episode; weight loss; fever and local chest signs; dry cough, contact history, and paroxysms in unvaccinated children; wet cough that fails to respond to 4 weeks of antibiotics or recurs; and crepitations (crackles) in the lungs, said Marchant.
More detailed algorithms for managing chronic cough in children were updated in CHEST in 2020, she said.
Knowledge Gaps in Prevention and Treatment
“Research into primary prevention of conditions such as bronchiectasis, which is a significant and important cause of chronic wet cough in children, is an important next step,” Marchant told Medscape Medical News. Other research needs include alternative treatments for chronic wet cough, such as mucolytics and anti-inflammatory therapies, as well as studies to explore why some children are at greater risk for chronic wet cough, including examination of airway pathobiologic pathways that put children at risk, she said. Looking ahead, “the development of noninvasive markers of airway infection and inflammation in children is an important future step,” Marchant added.
Duffy disclosed consultant relationships with Merck and with Bellus Health (now GSK). Irwin disclosed royalties as a codeveloper of a cough quality-of-life questionnaire and honoraria for reviewing back translations of the questionnaire. Marchant disclosed serving as co-author of two UpToDate chapters on chronic cough management and causes in children.