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SUPPLEMENT TO Journal of the association of physicians of india • MAY 2013 • VOL. 61
Combating Cough - Etiopathogenesis
Nishtha Singh*, Virendra Singh**
C
ough is a common protective mechanism and the most
common symptom of respiratory ailments. Cough is a
guarding mechanism that protects lungs from entry of any
harmful substance. By coughing, our body tries to expel any
irritant substance that reaches the respiratory tract. Apart from
acting as a normal physiological barrier, coughing is seen in
diseases of both respiratory and non-respiratory origin. Cough
favours equilibrium. Both its excess and deficit can be harmful for
the body. In its absence, aspiration can occur frequently. Airway
aspiration can lead to infection and pneumonia. While excessive
cough can lead to exhaustion, muscle pain, rib fracture, cough
syncope and other complications (Table 1).
The prevalence and aetiology of cough is governed by
multiple factors ranging from geographical location, history
of exposure to offender agents or drugs, seasonal variation,
concomitant respiratory and non-respiratory illnesses. In a
survey done by American Academy of Allergy, Asthma and
Immunology it was found that chronic cough was the chief
complaint in 20% to 40% new patients.1
What is the Mechanism of Cough?
Cough is a reflex induced modification of normal breathing
pattern.2 Cough reflex is a highly sequential and precisely
timed activation of respiratory muscles, larynx and parts of
brain. Muscles involved during coughing include diaphragm,
muscles of chest wall, cervical muscles, abdominal muscles
and laryngeal muscles. Cough is comprised of four phasesinspiratory, compressive, expulsive and ending with a restorative
inspiration.3 The initial inspiration is followed by a phase of
compressibility against a closed glottis, wherein the pressure
inside chest wall is stupendously increased. This is followed
by a forceful expiration. The phase of vigorous expiration is
responsible for the sound that is generated while coughing.
Table 1 : Potential Complications from Excessive Cough
Respiratory Complications
Pneumothorax
Subcutaneous emphysema
Pneumomediastinum
Pneumoperitoneum
Cardiovascular Complications
Cardiac dysrhythmias
Loss of consciousness
Subconjunctival haemorrhage
Central Nervous System Complications
Syncope
Headaches
Musculoskeletal Complications
Intercostal muscle pain
Rupture of rectus abdominis muscle
Cervical disc prolapsed
How Cough Reflex Works?
Like most reflexes the cough reflex is initiated at the receptor
level. These receptors are located in the pharynx, larynx, trachea,
airways up to terminal bronchiole and external auditory meatus.
Some receptors have also been found in pericardium, stomach
and diaphragm. But the most sensitive sites for provoking a
cough reflex are the areas of high turbulence where inhaled
air encounters resistance such as larynx, at the level of carina
and sites where bronchial branching occurs.2,4-8 The irritant
substances impinge on the mucosal lining of the above regions
and stimulate the receptors present on the surface.
The afferents to cough reflex are majorly carried by cranial
nerve X (Vagus nerve). In the medulla oblongata, all the afferent
impulses are integrated and interconnected in the nucleus of
tractus solitarius. This information is then relayed to nucleus
ambiguous and nucleus retroambiguus which in turn send
activating efferent signals to the various groups of muscles
involved in coughing (Table 2).
What can make us Cough?
Cough can be triggered by a variety of stimuli. Inflammatory
mediators, chemical substances (capsaicin), mechanical factors
(particulate matter in air) and psychological factors can trigger
cough.2,4,5
What are the Causes of Cough?
The causes of cough are categorized according to the duration.
Cough of less than three weeks period is called acute cough and
more than eight weeks duration is termed chronic cough. Cough
of intermediate duration (three to eight weeks) is called sub-acute
cough. The causes for cough differ in all the 3 categories.
Acute cough is caused due to conditions such as viral upper
respiratory infections, bacterial rhinosinusitis, allergic rhinitis,
pneumonia, congestive cardiac failure and exacerbation of
chronic obstructive pulmonary disease (COPD).
The cough that occurs due to rhinitis is usually self-limiting.
It occurs generally within first 2 days of acquisition of cold.9 The
cough of common cold may be associated with other symptoms
of postnasal drip. These include frequent throat clearing, throat
irritation, nasal obstruction and nasal discharge.
The other causes of acute cough such as pneumonia,
exacerbation of COPD, congestive cardiac failure are usually
associated with other specific symptoms of underlying disease.
Subacute cough is caused by post viral cough syndrome and
Bordetella Pertussis infection. Pertussis should be considered in
Table 2 : Cough Reflex
Sensory receptors: upper airways (hypopharynx, larynx) and lower
airways (trachea, bronchi, segmental bronchi), external auditory
meatus.
Stimulus: mechanical, chemical, thermal, inflammatory
Afferent nerve: Vagus (Cranial nerve X)
Center: Brain stem with cortical modulation
*
Efferent: Vagus (Cranial nerve X)
**
Muscles: glottis, larynx, diaphragm, chest wall and abdominal
Resident, Respiratory Medicine, JLN Medical College, Ajmer;
Professor and Head, Division of Allergy and Pulmonary Medicine,
SMS Medical College, Jaipur, Rajasthan.
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SUPPLEMENT TO Journal of the association of physicians of india • MAY 2013 • VOL. 61
the differential diagnosis, particularly if there is a “whooping”
sound characteristic of the cough, often associated with vomiting.
Chronic cough is most commonly caused by cough variant
asthma, postnasal drip (rhinosinusitis), gastro-esophageal reflux
disease (GERD), associated with use of angiotensin coverting
enzyme (ACE) inhibitor medication, post infectious cough and
non asthmatic eosinophilic bronchitis (NAEB).10-12
The three leading causes of cough in an immunocompetent
and non-smoking adult with a normal chest radiograph who is
not on ACE inhibitor medicine are - post nasal drip, cough variant
asthma and gastro-esophageal reflux disease. Occasionally more
than one of the above conditions is present concomitantly and
therefore treatment for all the ailments needs to be done.
Upper Airway Cough Syndrome
(UACS)
Postnasal Drip is also Called as postnasal drip has been cited
as the most common cause of chronic cough.12-13 Patients with
postnasal drip usually present with frequent throat clearing and
sensation of nasal secretions at the back of throat. They may also
complain of hoarseness of voice, nasal congestion and blockage.
Oro-nasal examination may reveal a mucosa with ‘cobblestone’
pattern and mucoid secretions. CT scan of sinuses often shows
mucosal thickening or sinus haziness with air-fluid levels.
Cough Variant Asthma
Asthma is characterized by cardinal symptoms of episodic
breathlessness, cough and wheezing. However, in some patients,
a phenotype of asthma is seen, which is known as cough variant
asthma. The principle symptom in these patients is cough
which may or may not be associated with other symptoms. It is
predominantly seen in children. The cough occurs more at night
and may even be absent during day. In these patients spirometry
and diurnal variability of peak flow are normal. The diagnosis
is made in such situations by demonstration of bronchial hyper
responsiveness, sputum eosinophilia and by measurement of
exhaled nitric oxide.14,15 A negative methacholine challenge test
excludes the diagnosis of cough variant asthma while its positive
predictive value is between 60 to 80%. Exhaled nitric oxide (eNO)
test more than 35 has sensitivity of 95% and specificity of 80%
in diagnosing the same.
amount of reflux becomes higher it is associated with symptoms
of GERD. Important symptoms of GERD include cough, throat
clearing, globus sensation in the throat and hoarseness of voice.
Sometimes symptoms of heart burn or indigestion are absent.
Cough is induced due to chemical stimulation of laryngeal and
pharyngeal receptors by gastric contents.
Other Causes of Cough
ACE medication use is associated with cough in many
patients. However, angiotensin II receptor blocker drugs are
not associated with cough. Smoking is also associated with
cough and the cough reduces when smoking is stopped. Patients
with obstructive sleep apnea, bronchiectasis, pneumoconiosis,
interstitial lung disease and with bronchogenic carcinoma also
sometimes manifest with cough as a predominant symptom.
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The mechanism of cough in asthmatics can be explained by
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mediators such as bradykinin, tachykinin, or prostaglandins
in asthmatic patients may sensitize the cough receptors and
cause a labile cough reflex.16 Two, the bronchial smooth muscle
constriction evident in patients with asthma may stimulate
cough receptors through mechanical deformation. Therefore,
beta-adrenergic agonists may provide relief in such cases.17
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Non asthmatic eosinophilic bronchitis (NAEB) also presents
in similar way. The patients present with cough and sputum
eosinophilia. But the similarity ends here, as these patients show
normal indices in lung function shown by spirometry and airway
hyper-responsiveness.18
15. Gibson PG, Fujimura M, Niimi A. Eosinophilic bronchitis: clinical
manifestations and implications for treatment. Thorax 2002;57:17882.
Gastro-esophageal Reflux Disease
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The stomach content may regurgitate into the esophagus and
it is called reflux. A small amount of reflux every day is usually
not associated with the disease. However when frequency and
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timing, and complications of chronic cough in diagnosing its cause.
Arch Intern Med 1996;156:997-1003.
14. Corrao WM, Braman SS, Irwin RS. Chronic cough as the sole
presenting manifestation of bronchial asthma. N Engl J Med
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responsiveness and cough in asthma and chronic obstructive
pulmonary disease. Thorax 2000;55:643-649.
17. Fujimura M, Kamio Y, Hashimoto T, Matsuda T. Cough receptor
sensitivity and bronchial responsiveness in patients with only
chronic non-productive cough: Effect of bronchodilator therapy. J
Asthma 1994;31:463-472.
18. Gibson PG, Dolovich J, Denburg J, Ramsdale EH, Hargreave FE.
Chronic cough: eosinophilic bronchitis without asthma. Lancet
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