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The pathogenesis of chronic cough
Causes of chronic cough
The diagnosis of chronic cough
The diagnosis of chronic cough
References 
Further reading

Coughing is a natural defense mechanism that enables secretions produced in the bronchial tract and tree to be cleared to eliminate any inhaled foreign particles that may be physical or biochemical. In addition, it is a common respiratory reaction, or symptom, for diseases that are either easily identifiable or covert.

Chronic cough differs from acute cough, characterized as having a known cause that can be eliminated by managing the underlying cause. Chronic cough, however, cheap cefixime canbera is the only symptom, and there is no clear presence of a disease etiology. Chronic cough is characterized as a cough that lasts more than eight weeks. It can produce marked suffering for patients and present a diagnostic problem for clinicians when the disease is not apparent.

The pathogenesis of chronic cough

Ther all three phases of a cough. These consist of an inhalation phase which produces enough volume and pressure to produce an effective cough. The second phase is compression, characterized by increased pressure against the larynx because of a contraction of the chest wall, abdominal muscles, and diet. The final phase is expiratory, characterized by the opening of the glottis, which results in airflow.

Coughs can either be voluntary or involuntary. A voluntary cough is produced on demand (initiation) or can result in the suppression of a cough (inhibition). An involuntary cough, by contrast, is caused by the autonomic system and is produced by the stimulation of the vagal afferent nerves. Through simulation of the cough receptors in the airway and other regions of the upper body, impulses are generated, which travel through the vagus nerve to the medulla, which the higher cortical centers control.

Afferent signals (signals toward the effector muscles) are then transmitted down the phrenic (a mixed nerve carrying motor, sensory and sympathetic fibers. It is the only nerve that provides motor innervation to the diaphragm) and afferent nerves (any nerve that carries impulses from the central nervous system toward the periphery, such as a motor nerve to produce the response) to the muscles which control expiration to produce the cough.

A chronic cough may be stimulated by abnormalities of the cough relaxation and the sensitization of both the central and afferent components, which produce an exaggerated cough reflex sensitivity to stimuli that would otherwise not produce a cough (cough hypersensitivity syndrome).

Causes of chronic cough

There are several causes of chronic cough; however, the most prevalent are asthma, postnasal drip, and acid reflux. Postnasal drip refers to secretions produced in the nose dripping or flowing into the back of the throat from the nose. These secretions, which contain microbes and other bactericidal components, can irritate the throat, triggering a cough. This can occur in people who develop allergies, colds, rhinitis, and sinusitis.

Asthma is considered the second most frequent cause of chronic cough in adults but the leading cause in children. Alongside coughing, patients often experience shortness of breath and wheezing. Some patients with asthma have a comorbid condition, cough variant asthma, in which a cough is the only symptom presented.

Acid reflux occurs when stomach acid flows from the stomach into the esophagus. Many people with gastro-oesophageal reflux disease experience chronic cough due to acid reflux. Chronic cough also accompanies heartburn; however, people with gastro-oesophageal reflux disease may only have cough as their symptom. Coughing is worsened during or after eating, talking, and bending.

Other causes of chronic cough are varied but include respiratory tract infection, bacterial tracheobronchitis, or bacterial sinusitis after a viral upper respiratory tract infection. Approaching all bacterial tracheobronchitis patients experience a cough that produces sputum. In addition, patients may have sinus congestion which causes nasal secretions that drip or flow into the back of the throat.

Another cause of chronic cough is treatment with angiotensin-converting–enzyme (ACE) inhibitors. ACE inhibitors are favored by healthcare professionals as they produce highly efficacious effects in patients. However, a common side effect is persistent coughing which occurs in approaching 20% of people who take an ACE inhibitor to treat high blood pressure and heart failure. Although cough is a common side effect, several patients opt to continue with treatment if it is mild; coughs may also reduce in severity if switched to a different ACE inhibitor.

Several Less common causes of chronic cough include airborne environmental irritants, aspiration (the act of drawing something, such as a liquid or a foreign object, into the respiratory tract when taking a breath) during swallowing, heart failure; pertussis (whooping cough), lung cancer, infections, and other lung infections; and psychological disorders. Those that are common in smokers include tobacco smoke, lung cancer, and infections.

The diagnosis of chronic cough

the duration of a cough at presentation can help healthcare practitioners diagnose a chronic cough. This occurs in cases where the cough has persisted for over eight weeks. As chronic cough may be caused by several disorders, as outlined previously, healthcare practitioners must assess whether the patient has clinical features of these diseases.

In the case of upper airway cough syndrome caused by postnasal drip, assessment must consider additional symptoms such as frequent throat clearing, an unpleasant sensation in the throat, nasal congestion, and discharge. Other airway abnormalities are considered a key component and seasonal and occupational stimuli are risk factors in some patients. The patient may have visible mucus and a cobblestone appearance to their oropharyngeal wall and local upper airway structures on examination.

Physicians may also assess whether the patient has clinical features of:

• ACE inhibitor-induced cough — suggested by coughing bouts and the patient-perception of airway irritation having arisen within hours to months of the first dose
• Asthma – suggested by breathlessness, wheezing, exacerbated symptoms at night or in the morning, or with exercise and exposure to allergens. In addition, the healthcare professional may observe that the peak expiratory flow rate is reduced during an episode
• Gastro-oesophageal reflux disease — suggested by a cough that is worse during or after eating, with talking, and with bending

To rule out these conditions, the healthcare professional may examine systemic signs, which include observation of fever, weight loss, clubbing in the hands, or lymphadenopathy. In addition, the healthcare professional may look for upper airway signs, for example, hoarseness and nasal speech, vocal chest signs, changes to peak exploratory flow rate, and changes in the cardiovascular system.

In the absence of any 'red flag' symptoms in the initial examination, smokers may be subject to initial investigation chest X-ray (CXR) and spirometry. Smokers are advised to stop smoking. For non-smokers taking an ACE inhibitor, this may be replaced or stopped. ACE inhibitor-induced cough improves within four weeks with cessation; if not, physicians may consider CXR and spirometry.

If the cause of the cough can still not be identified, the patient may be subject to further investment, which includes blood tests as well as the assessment for other contributing factors such as reflux disease, rhinitis, and other occupation-related factors. The physician may treat these or eliminate the cause for a limited period to observe the response in the patient. In the absence of a diagnosis, further investigations may be conducted in secondary care, including echocardiogram, bronchoscopy, radiology, and high-resolution CT scans.

Treatment of chronic cough

If the underlying cause of the chronic cough cannot be managed, symptomatic treatment may begin. Regarding pharmacokinetics treatment, various drugs partially suppress coughing, although the cough reflex is difficult to prevent using pharmacological methods. In addition, evidence for the efficacy of antitussive drugs (medicines that suppress coughing, also known as cough suppressants) is lacking, with no effective treatments capable of controlling the cough response within an acceptable therapeutic ratio.

The use of antitussive drugs is useful when no identifiable cause can be found and in cases where sleep is disturbed. However, some antitussive drugs may cause sputum retention, and this may cause further harm in patients with chronic bronchitis or bronchiectasis.

A stronger antitussive may be an effective drug but can cause dependence. Alongside these, sedating antihistamines often present as the primary cough suppressant in many cough preparations on sale. Strong opioids at higher doses are occasionally used for severe, distressing coughs seen in palliative care.

Mucolytics, compounds that reduce mucus' viscosity, are also prescribed to aid expectoration by reducing the viscosity of sputum produced. This is especially effective in patients with chronic obstructive pulmonary disorder and chronic productive cough as they can reduce the exacerbations. Alongside mucolytic therapy, steam inhalation with postural drainage can be used in patients with bronchial stasis and some cases of chronic bronchitis.

Demulcents –substances that relieve irritation of the mucous membranes in the mouth by forming a protective film – are purported to relieve a dry irritating chronic cough and can be prepared using household substances such as honey glycerol or syrup. They are typically short-acting, however, relieving bouts of coughing for less than 30 minutes. These preparations have limited to no side effects/ contraindications and are relatively inexpensive to the patient.

Expectorant compounds promote the expulsion of the secretions made in the bronchi; however, there is limited evidence to suggest that there are effective drugs that can facilitate this. Both expectorant and demulcents are considered to be mucoactive agents, which are classes of chemical agents that aid in the clearance of either sputum or mucus from the lungs, trachea, and bronchi. Alongside expectorants and mucolytics, are mucokinetics can increase the transportability of mucus and mucoregulators, which can suppress the underlying mechanism of mucus hypersecretion. These may be used to alleviate coughing.

References

• Morice AH, McGarvey L, Pavord I; Protocol for the evaluation of chronic cough in an adult. Thorax 200661(suppl_1):i1-i24.
• Morice AH, McGarvey L, Pavord I; Protocol for the evaluation of chronic cough in an adult Part 2. Thorax 2006.
• Gibson P, Wang G, McGarvey L, Vertigan AE, et al. CHEST Expert Cough Panel. Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report. Chest. 2016;149(1):27-44. doi: 10.1378/chest.15-1496.
• McCrory DC, Coeytaux RR, Yancy WS et al. Assessment and Management of Chronic Cough [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Jan. Report No.: 13-EHC032-EF.
• Pavord ID, Chung KF. Management of chronic cough. The Lancet. 2008;371(9621):1375-84. doi: 10.1016/S0140-6736(08)60596-6.
• Barraclough K. Chronic cough in adults. BMJ. 2009;338:b1218. doi: 10.1136/bmj.b1218.

Further Reading

• All Chronic Cough Content

Written by

Hidaya Aliouche

Hidaya is a science communications enthusiast who has recently graduated and is embarking on a career in the science and medical copywriting. She has a B.Sc. in Biochemistry from The University of Manchester. She is passionate about writing and is particularly interested in microbiology, immunology, and biochemistry.