Etiology

All chronic cough begins as subacute, and differential diagnosis includes all causes of subacute cough. Postinfectious cough is the most common etiology of subacute cough.[6] Most cases will be self-limited. Once cough duration has exceeded 8 weeks, a systematic approach to elucidating cause and best treatment is needed.

Common etiologies

In most nonsmoking adults with a normal chest x-ray who do not take ACE inhibitors, chronic cough is caused by one or more of four conditions:[2][3]​​[7][8]​​

  • Upper airway cough syndrome (formerly postnasal drip syndrome)

  • Asthma

  • Gastroesophageal reflux disease

  • Nonasthmatic eosinophilic bronchitis.

More than one cause of chronic cough is often present. Truly idiopathic cough is rare and is a diagnosis of exclusion.[9][10]

Cough as a principal or sole symptom of asthma, known as cough-variant asthma, is present in a subgroup of patients. The cough may be productive and may be worse at night or with exercise.​ There may be absence of variable airflow limitation.[11]

These commonest causes account for most patients presenting to specialty clinics with chronic cough and should generally be considered first if there are no signs or symptoms pointing to alternative diagnoses.

Other common causes include the following.

  • ACE inhibitors: dry cough, typically associated with a tickling or scratching sensation in the throat. The reported incidence varies.[12] ACE inhibitor-induced cough is more frequent in women than men and is associated with increasing age.[13][14]

  • Postinfectious cough: postinfectious cough is the most common etiology of subacute cough.[6] A history typical for postinfectious cough should prompt watchful waiting and symptomatic therapy as necessary.

  • Chronic bronchitis: adult with a history of chronic productive cough lasting for more than 3 months of the year and for at least 2 consecutive years when other diagnoses have been ruled out.[15]​ Chronic bronchitis is one of the manifestations of chronic obstructive pulmonary disease. Predisposing factors include nicotine and marijuana smoking, second-hand exposure to nicotine smoke, and environmental exposure to toxins.[8]​​[16]​​

  • Bordetella pertussis: when local epidemiology indicates a high rate of pertussis infection, testing for Bordetella pertussis is recommended. If tests are supportive of pertussis, specific antimicrobial therapy is indicated.

Less common etiologies

Diagnoses to consider are those that impart cough through stimulation of airway mechanical and chemical receptors that feed into the vagus nerve, including afferent nerves located in the chest wall, diaphragm, esophagus, abdominal wall, and external auditory meatus.[8] Other potential causes therefore are:

  • Disorders that distort or irritate the airway (e.g., bronchiectasis, chronic suppurative lung disease, endobronchial tumors, granulomatous disease, foreign bodies)

  • Disorders of lung parenchyma (e.g., interstitial lung disease resulting from hypersensitivity pneumonitis, occupational/environmental exposure, or autoimmune diseases such as systemic lupus erythematosus)

  • Systemic diseases (e.g., rheumatoid arthritis, sarcoidosis) or autoimmune diseases such as systemic lupus erythematosus

  • Chronic vagal neuropathy (e.g., vitamin B12 neuropathy, diabetic neuropathy, herpes zoster infection, chemical irritant exposure)

  • Irritation of the external ear canal by an infection, wax, or hearing aids may produce cough, through a reflex mediated by Arnold's nerve

Obstructive sleep apnea may cause repeated drops in intrapleural pressure, resulting in episodes of nocturnal aspiration, throat irritation and cough.[17]

Oral-pharyngeal dysphagia that results in recurrent aspiration of foods and liquids may also cause cough. Patients with cough who report difficulty swallowing should be further evaluated for such etiology.

Zenker diverticulum can cause chronic cough, accompanied by dysphagia, regurgitation, aspiration, and weight loss.[18]

Bronchiolitis should also be considered, and may result from infection, or may be drug/toxin-related. Diffuse panbronchiolitis should be considered in patients from East Asia.​[19][20]

Neurologic conditions affecting the medulla oblongata or cerebellum may increase the cough reflex (e.g., brainstem space-occupying lesions, Tourette syndrome, neuromyelitis optica spectrum disorder, cerebellar neurodegenerative diseases).[21]

In areas of endemic infection with fungi or parasites, diagnostic evaluation for these should be undertaken when more common causes of cough have been ruled out. Slow enlargement of intrathoracic blood vessels, such as an aortic aneurysm, may cause chronic cough.[22]

People who work with their voice (e.g., teachers, call center operators, actors, singers, coaches) may experience chronic cough and hoarseness.[16]

Coronavirus disease 2019 (COVID-19) may be associated with long-term symptoms, most commonly cough, low grade fever, and fatigue, and/or organ dysfunction.[23] The definition and time frame of "postacute COVID-19 syndrome" or "long COVID" has not been universally determined. In the UK, "ongoing symptomatic COVID-19" has been defined as signs and symptoms of COVID-19 from 4-12 weeks. "Post-COVID-19 syndrome" is defined as signs and symptoms that develop during or after COVID-19 and continue for more than 12 weeks.[24] Incidence, natural history, and etiology data continue to emerge. See Coronavirus disease 2019 (COVID-19).

Chronic cough that persists in spite of therapeutic trials and is otherwise unexplained by extensive evaluations is labeled as refractory chronic cough or unexplained chronic cough. In the literature, it is also referred to as neurogenic cough, cough hypersensitivity syndrome, or somatic cough.[25][26]

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