A cough is a common respiratory symptom and has a protective function. It can be caused by a variety of different diseases and environmental factors, as Steve Titmarsh explains…

Acute cough following an upper respiratory tract infection (URTI), usually caused by a virus (common cold), is the most common respiratory symptom worldwide.¹ 

Cough is a reflex action that involves a network of events that is not completely understood but starts with activation of airway sensory nerves via cough receptors in the airways.^2,3 When stimulated, nerve signals from the cough receptors travel to the cough centre in the medulla in the brainstem stimulating the central respiratory generator. That in turn generates nerve signals through the vagus nerve to the intercostal muscles, abdominal wall, diaphragm and pelvic floor to produce the cough.⁴

“Cough is the most common symptom of several respiratory diseases. It is a defence mechanism of the body to clear the respiratory tract from foreign materials inhaled accidentally or produced internally by infections, with viruses being the main cause of acute cough in upper respiratory tract infections (URTIs),” said Edel Duffy, head of medical for VIVIO Junior Multivitamin.

“URTIs are very frequent in school children and they suffer from seven to 10 episodes per year. Children are almost four times more likely to experience URTI-associated acute cough than adults. Mucosal dehydration and mechanical stimuli, caused by pharyngeal dripping of viscous nasal mucus, viruses, bacteria, inflammatory mediators and irritant substances, play a decisive role in triggering the urge to cough and sustaining URTI-associated acute cough.

“In this regard, up to 85 per cent of the benefit of cough syrups depends on the physical and chemical effects of the syrup itself that exert a demulcent action, namely smoothing. A demulcent substance can form a soothing film over a mucous membrane, indirectly reducing pain and inflammation.”

What’s the point of coughing?

Cough provides a protective mechanism in response to airway irritation; it also helps keep the airway open.¹Coughing helps remove mucus, noxious substances and irritants from the larynx, trachea and bronchi.² It can be caused by mucosal inflammation that results from infection, for example (see Table 1). Postnasal drip, caused by excessive mucus production, may also induce coughing.¹

Other things that can cause a cough include exposure to irritants (such as tobacco smoke, pollutants, smells, aerosols, and dust), cold and/or dry air, and allergens (typically pollens for people with hay fever).¹ Cough caused by thermal, chemical or mechanical stimulation is also known as cough hypersensitivity syndrome.⁵ 

If a cough lasts more than eight days rhinosinusitis should be suspected. Adults may have 2–5 episodes of UTRI each year; school children can suffer from 7 to 10 episodes a year so they may cough for up to 140 days a year.¹

Table 1. Common causes of cough⁵

Types of cough

Generally, cough can be: ^6,7,8

• Acute, lasting <3 weeks
• Subacute, 3–8 weeks of symptoms
• Chronic, where symptoms last >8 weeks (4 weeks in children).

Acute cough associated with a cold or flu is usually self-limiting. A cough that persists or is accompanied by other symptoms may signal a more serious illness that requires medical attention. 

More serious symptoms or conditions in people with a cough that warrant referral for medical attention include:⁹

• Difficulty breathing (dyspnoea)
• Chest pain
• Coughing up blood (haemoptysis)
• Unintended sudden weight loss
• Persistent change in voice
• Swellings in neck
• Persistent fever
• Risk factors for tuberculosis or HIV infection.

Wet cough, dry cough

A wet or productive cough is one where people produce phlegm or sputum (mucus) that they cough up. Dry or non-productive cough, as the name suggests, is one where no mucus is produced.

Chronic productive cough has broadly the same causes as dry cough although some causes such as gastro-oesophageal reflux disease (GORD/GERD – see following section) are more likely to be associated with a dry cough.

Causes of chronic productive cough include bronchiectasis, defined as irreversible abnormal dilatation of the bronchi. Prevalence of the condition is higher among older people, peaking at age ≥70 years, and is more prevalent among women.

Bronchiectasis has numerous causes, including congenital, mycobacterium infection, panbronchiolitis, cystic fibrosis, ulcerative colitis, GORD/aspiration, rheumatoid arthritis, ciliary dysfunction, allergic bronchopulmonary aspergillosis, immune deficiency, post-infection or, as is the situation in a significant number of cases, the cause may be unknown.  

Chronic bronchitis is also associated with chronic cough – indeed the condition is defined as the presence of a chronic productive cough for more than three months in two successive years. Smoking is a major cause of chronic bronchitis.

The chronic productive cough in people with the disease is a result of overproduction and hypersecretion of mucus from goblet cells and reduced clearance mechanisms in the airways. Mucus overproduction is a reaction to exposure to inflammatory agents such as cigarette smoke, and viral or bacterial infection, for example.¹⁰

Chronic dry cough may be the main initial symptom in asthma; indeed it may be the only symptom in cough-variant asthma. The causes are not entirely clear but may well involve increased amounts of inflammatory mediators such as bradykinin, tachykinin or prostaglandins sensitising cough receptors, or constricted smooth muscle stimulating cough mechanoreceptors. Mucus hypersecretion and chronic bacterial infection are implicated. Eosinophilic bronchitis and immunodeficiency can also cause chronic dry cough.^10,11

Night-time cough

The causes of nocturnal cough are similar to other types of cough and include respiratory causes such as postnasal drip, following infection, and asthma. Environmental factors such as smoking (active and passive) may be the culprit, or it may be due to angiotensin-converting enzyme inhibitors (ACEIs). 

Lung disease can also be the cause of coughing at night. However, the majority (90 per cent) of cases are the result of cough variant asthma, GORD or upper airway cough syndrome.²

If a person with a nocturnal cough has clear sputum the likely cause is a hypersensitivity mechanism. Coloured mucus indicates sinusitis or bronchiectasis if tuberculosis has been ruled out.

A non-productive cough or dry cough signals a potential adverse drug reaction (eg ACEI) and a cough that improves after taking an antihistamine is likely to be upper airway cough syndrome.²

Chronic cough

Chronic cough may be associated with a range of diseases, including asthma, GORD or lung disease (for example bronchitis, bronchiectasis, chronic obstructive pulmonary disease, interstitial lung disease, pulmonary tuberculosis, obstructive speel apnoea, carcinoma, heart failure, foreign body aspiration).¹²

European guidelines categorise chronic cough into several types (or phenotypes):  Asthmatic cough/eosinophilic bronchitis; reflux cough; postnasal drip syndrome/upper airways cough syndrome, and iatrogenic cough.⁸ 

Eosinophilic inflammation may be a good biomarker of asthmatic cough and may help treatment decisions. It can be measured using sputum eosinophilia. However, the technique is not available everywhere and needs specialist interpretation, so a less accurate method involving measuring exhaled nitric oxide may be preferable but is not without its critics.⁸ 

The role of reflux in chronic cough remains controversial. It is thought that non-acid reflux – liquid and gaseous – may also be a factor as proton pump inhibitors have only a small benefit in patients with reflux cough. Also, cough associated with reflux is perhaps the result of an inflammatory response following aspiration of gastrointestinal tract contents.⁸

Postnasal drip syndrome, or upper airways cough syndrome, which describes a range of signs and symptoms, including post-nasal drip syndrome, rhinitis and rhinosinusitis, may be a trigger for cough hypersensitivity but the details of its mechanism of action are as yet unclear.⁸ 

Drug-induced or iatrogenic cough is seen with ACEIs. About 10 per cent of people taking ACEIs are affected, and cough is thought to be caused by an increased cough reflex sensitivity in susceptible individuals. Typically, people complain of a persistent dry cough with a tickle in the throat. 

The increased cough sensitivity may be due to an accumulation of bradykinin, an inflammatory mediator, which has been found to sensitise the cough reflex in animals. ACEIs prevent the breakdown of bradykinin by ACE, resulting in an accumulation of the peptide.¹³

Whooping cough

Also known as pertussis, whooping cough is caused by Bordetella pertussis and is highly infectious. The bacterium produces pertussis toxin, along with other substances, which are thought to be the cause of the disease. 

The term whooping is descriptive of the sound made by children who have the disease resulting from sharp intakes of breath during bouts of coughing. A cough may persist for up to three months after infection and is sometimes called the 100-day cough.¹⁴

Vaccination has significantly reduced the incidence of whooping cough. However, since a peak in 2011–12 rates have remained higher than in previous years, which may be due to a combination of factors such as B. pertussis becoming more virulent, waning herd immunity or incomplete booster vaccination and less effective acellular vaccines (as compared with previously used whole-cell formulations) as well as greater surveillance and higher awareness leading to increased reporting of the infection.¹⁴

Covid-associated cough

Persistent cough is one of the three classic symptoms of Covid-19 infection, the other two being fever and loss of a sense of smell.¹⁵ However, a recent survey of 17,500 patients in the UK found that 58 per cent reported a sore throat, 49 per cent a headache and 40 per cent a cough with no phlegm, while 37 per cent reported a cough with phlegm.¹⁶

In contrast around a quarter (26 per cent) of children with Covid-19 infection have a cough.¹⁵ Covid-associated cough can persist for weeks or months after infection as part of a group of symptoms such as fatigue, cognitive impairment, dyspnoea or pain, termed long Covid or post-Covid syndrome.

It is postulated that the virus interacts in some way with the airway vagus nerve and neuroinflammation has some role to play in starting the cough. Cough that occurs in long Covid is different from a cough that happens after a cold or the flu in that it usually occurs alongside other conditions such as fatigue, difficult or laboured breathing (dyspnoea) or pain. So its cause is likely to be multifactorial and may share some of the mechanisms of the other symptoms it tends to occur with.¹⁷

Conclusion

Cough is common and protects airways from irritant and noxious substances.¹ There are numerous causes of cough, and in some cases it signals more serious disease.⁹ A greater understanding of the underlying mechanisms causing cough may lead to improvements in the way symptoms are managed.^8,18,19

References

1. Murgia V, Manti S, Licari A, et al. Upper Respiratory Tract Infection-Associated Acute Cough and the Urge to Cough: New Insights for Clinical Practice. Pediatr Allergy Immunol Pulmonol 2020;33:3–11.
2. Singh DP, Jamil RT, Mahajan K. Nocturnal Cough. StatPearls[Internet] (www.ncbi.nlm.nih.gov/books/NBK532273; accessed September 2022).
3. Nasra J, Belvisi MG. Modulation of sensory nerve function and the cough reflex: understanding disease pathogenesis. Pharmacol Ther 2009;124(3):354–75.
4. Kaplan AG. Chronic Cough in Adults: Make the Diagnosis and Make a Difference. Pulm Ther 2019;5(1):11–21.
5. Clinical Knowledge Summaries. Cough: What causes it? (https://cks.nice.org.uk/topics/cough/background-information/causes; accessed September 2022).
6. Speich B, Thomer A, Aghlmandi S, et al. Treatments for subacute cough in primary care: systematic review and meta-analyses of randomised clinical trials. Br J Gen Pract 2018;68:e694–e702.
7. Irwin RS, French CL, Chang AB, Altman KW; CHEST Expert Cough Panel*. Classification of Cough as a Symptom in Adults and Management Algorithms: CHEST Guideline and Expert Panel Report. Chest. 2018;153(1):196–209.
8. Morice AH, Millqvist E, Bieksiene K, et al. ERS guidelines on the diagnosis and treatment of chronic cough in adults and children. Eur Respir J 2020;55(1):1901136.
9. NHS inform. Cough (www.nhsinform.scot/illnesses-and-conditions/lungs-and-airways/cough; accessed September 2022).
10. Martin MJ, Harrison TW. Causes of chronic productive cough: An approach to management. Resp Med 2015;109:1105–13.
11. Mahashur A. Chronic dry cough: Diagnostic and management approaches. Lung India 2015;32(1):44–9.
12. Clinical Knowledge Summaries. Cough: How do I diagnose the cause of cough? (https://cks.nice.org.uk/topics/cough/diagnosis/diagnosis; accessed September 2022).
13. Shim JS, Song WJ, Morice AH. Drug-Induced Cough. Physiol Res 2020;69(Suppl 1):S81-S92.
14. Clinical Knowledge Summaries. Whooping cough: What is it? (https://cks.nice.org.uk/topics/whooping-cough/background-information/definition; accessed September 2022).
15. ZOE Health Study. Symptom series: Persistent cough (https://health-study.joinzoe.com/post/is-a-persistent-cough-a-symptom-of-covid-19; accessed September 2022).
16. Ellis R. Sore Throat, Cough Now Top COVID Symptoms: U.K. Study (www.webmd.com/lung/news/20220715/sore-throat-cough-top-covid-symptoms-uk-study; accessed September 2022).
17. Song WJ, Hui CKM, Hull JH, et al. Confronting COVID-19-associated cough and the post-COVID syndrome: role of viral neurotropism, neuroinflammation, and neuroimmune responses. Lancet Respir Med 2021;9(5):533-44.
18. McGarvey L, Dupont L, Birring SS, et al. New understanding in the treatment of cough (NEUROCOUGH) ERS Clinical Research Collaboration: improving care and treatment for patients with cough. Eur Respir J 2019;53(5):1900787.
19. National Institute for Health and Care Research. First new cough treatment in 50 years as trials show significant reduction in symptoms (www.nihr.ac.uk/news/first-new-cough-treatment-in-50-years-as-trials-show-significant-reduction-in-symptoms/24200; accessed September 2022).