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Frequently asked questions about chronic cough

1. Why is there a higher prevalence of chronic cough in patients in their 50s, particularly women?

Studies have observed that chronic cough patients tend to be women with an average age in their 50s.1-3

Women with chronic cough have been observed to have a greater cough frequency and a more sensitive cough reflex compared to men.4,a

Currently, there are no published studies that identify why chronic cough may be more prevalent among certain age groups.

aA UK study to identify factors which predict objective cough frequency in 100 consecutive patients (65 women) presenting with chronic cough to a specialty cough clinic. Mean age was 55.8 years and median cough duration was 4 years. Patients completed various cough assessments, including ambulatory cough monitoring and cough reflex sensitivity. 86 patients completed 24-hour cough monitoring.4

2. What is chronic cough?

The American College of Chest Physicians (CHEST) Expert Cough Panel classifies cough in adults by duration.5

For adult patients, chronic cough is a cough that persists for >8 weeks.5

Cough as a medical problem can be evaluated by its duration, characteristics, severity, etiology, pathophysiology, or treatment response.6

Chronic cough is often associated with an underlying condition such as asthma, GERD, UACS (postnasal drop), and NAEB.5,7

In some cases, cough persists even after underlying conditions have been treated, or an underlying condition cannot be identified.8

3. Who is the intended audience of the CHEST guidelines?

The CHEST guidelines provide recommendations to aid clinical decisions-making for the diagnosis and management of cough across disciplines.9

The CHEST expert panel includes clinicians across disciplines and does not exclusively include pulmonologists.5

4. What is the difference between the mechanism of disease in a protective cough reflex vs a pathologic cough reflex, which can result in chronic cough?

The identification of anatomically and functionally distinct vagal afferent pathways known to regulate cough might suggest the existence of 2 types of cough—protective and pathologic.10-12

A-delta fibers are thought to play a critical role in mediating the protective cough reflex, which is needed to prevent aspiration and facilitate the clearance of foreign bodies, irritants, and excess secretions from the airways. These fibers are myelinated, faster conducting, and respond rapidly to mechanical stimulation or a rapid drop in airway pH.10,11

The pathologic cough response found in chronic cough is thought to arise from dysregulation of vagal sensory nerves, including C-fibers. C-fibers are unmyelinated, slower conducting, and can sense inhaled chemical stimuli and endogenous inflammatory molecules. 10-12

Watch a short video on the potential mechanisms of chronic cough to learn more. Watch now.

5. What can activate sensory receptors on vagal nerve C-fibers, resulting in cough?

In the pathologic cough response, a cough can be triggered by chemical irritants, inflammatory mediators, or signaling molecules which activate sensory receptors on vagal nerve C-fibers. Several receptors and ion channels may have a role in C-fiber activation, resulting in cough: NaV, TRPA1, TRPV1, P2X2/3, P2X3, and B2R.10,11

For example, acid from esophageal refluxate can activate TRPV1. Environmental irritants such as acrolein that is found in cigarette smoke can stimulate TRPA1. A signaling molecule such as extracellular ATP can bind purinergic receptors, such as P2X3, and each of these activated receptors may stimulate C fibers, triggering the cough reflex arc.10,11

These potential mechanisms of pathologic cough differ from the protective cough reflex, which is important for clearing the airways of inhaled particles.10

6. What is refractory chronic cough (RCC) and unexplained chronic cough (UCC)?

Refractory or unexplained chronic cough is a chronic cough that persists despite appropriate treatment of an underlying condition or for which no underlying condition has been identified despite a thorough clinical evaluation.8

Refractory chronic cough (RCC) and unexplained chronic cough (UCC) are not terms that are currently widely used as diagnoses. However, they may help define a subset of chronic cough patients that have been historically difficult to address.6

The terms refractory chronic cough and unexplained chronic cough are defined by the American College of Chest Physicians (CHEST) Expert Cough Panel guidelines.8

The variety of health care professional (HCP) specialists who evaluate patients with chronic cough, including pulmonologists, gastroenterologists, allergists, primary care physicians, and ENTs, may each use different terminology to define these conditions.6

7. What are the differences between patients with refractory compared to unexplained chronic cough?

Patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) often present similarly with common characteristics of cough hypersensitivity. The difference between them is whether they have an underlying etiology that’s been identified.5,8,13

According to the American College of Chest Physicians (CHEST) Expert Cough Panel guidelines, RCC is a chronic cough that persists despite a thorough investigation and appropriate treatment for an underlying condition. UCC is a chronic cough with no underlying etiology identified, despite a thorough diagnostic workup.5,8

Therefore, RCC patients will have an identified comorbid condition, such as asthma, GERD, UACS, or NAEB with a cough that persists after appropriate treatment, while UCC patients will not have any underlying etiology identified.5,8

8. How should I approach evaluating and managing a patient with chronic cough?

Evaluating the underlying causes of chronic cough can be challenging and may involve multiple specialists. However, the American College of Chest Physicians (CHEST) Expert Cough Panel guidelines provide a stepwise process to help manage patients with chronic cough.5,8

This includes taking a thorough medical history and physical exam to rule out red flags. Common causes of cough are also ruled out. This may be done through empiric therapeutic trials or using diagnostic testing. Further evaluation may by performed to rule out any less common causes that are suspected.5,8

If cough persists despite appropriate investigation and treatment for underlying conditions, consider referral to a cough clinic for investigation of refractory chronic cough or unexplained chronic cough.5,8

Patients with RCC and UCC have been observed to demonstrate symptoms of allotussia and hypertussia indicative of cough hypersensitivity. RCC/UCC may be described to patients in this context if they are exhibiting features of allotussia or hypertussia.13

9. Is there an ICD-10 code for refractory or unexplained chronic cough?

There is no specific ICD-10 code for refractory or unexplained chronic cough. However, an ICD-10 symptom code R05.3 Chronic Cough is available for use. This code includes persistent cough, refractory cough, and unexplained cough as examples of chronic cough. It expands upon the existing R05 Cough ICD-10 symptom code. 14,15

For Background Only: The structure of the ICD-10 symptom codes for cough are as follows14:

R05 Cough

Excludes1: paroxysmal cough due to Bordetella pertussis (A37.0-) smoker’s cough (J41.0)

Excludes2: cough with hemorrhage (R04.2)

R05.1 Acute cough

R05.2 Subacute cough

R05.3 Chronic cough

Persistent cough

Refractory cough

Unexplained cough

R05.4 Cough syncope

Code first syncope and collapse (R55)

R05.8 Other specified cough

R05.9 Cough, unspecified

GERD, gastroesophageal reflux disease; UACS, upper airway cough syndrome; NAEB, nonasthmatic eosinophilic bronchitis

References: 1. Morice AH et al. Eur Respir J. 2014;44:1149-1155. 2. Zeiger RS et al. Perm J. 2020;24:1-3. 3. Zeiger RS et al. J Allergy Clin Immunol Pract. 2021;9:1624-1637.e10. 4. Kelsall A et al. Thorax. 2009;64:393-398. 5. Irwin RS et al. Chest. 2018;153:196-209. 6. McGarvey L, Gibson PG. J Allergy Clin Immunol Pract. 2019;7:1711-1714 7. Mazzone SB et al. Lancet Respir Med. 2018;6:636-646. 8. Gibson P et al. Chest. 2016;149:27-44. 9. CHEST. Clinical pulmonary; guidelines and expert panel reports. Accessed July 27, 2022. 10. Mazzone SB, McGarvey L. Clin Pharmacol Ther. 2021;109:619-636. 11. Mazzone SB, Undem BJ. Physiol Rev. 2016;96:975-1024. 12. Canning BJ. Pulm Pharmacol Ther. 2011;24:295-299. 13. Sundar KM et al. ERJ Open Res. 2021;7:1-12. 14. Centers for Disease Control and Prevention. Accessed July 27, 2022. 15. Centers for Disease Control and Prevention. Accessed July 27, 2022.