Cough

A cough is a forceful expulsion of air from the lungs that helps to clear secretions, foreign bodies, and irritants from the airway. It may be classified as acute (< 3 weeks), subacute (3–8 weeks), or chronic (> 8 weeks), as well as productive (with sputum/mucus expectoration) or dry. Upper respiratory tract infections (URI) and acute bronchitis are the most common causes of acute cough. Subacute cough is often a sequela of a URI (postinfectious cough) but can also be due to chronic bronchitis or pneumonia. Chronic cough is often caused by rhinitis/sinusitis (upper airway cough syndrome), asthma, GERD, and ACE inhibitors. A thorough medical history and physical examination often suffice to diagnose the etiology of cough. Chronic cough or the presence of associated red flag symptoms (dyspnea, fever, hemoptysis, weight loss) are indications for further investigation. Sputum culture, chest x-ray/CT scan, and pulmonary function tests are useful diagnostic tests in the evaluation of cough, but are not routinely indicated. Treatment of cough depends on the underlying etiology.

• Definition: a forceful expulsion of air from the lungs that helps to clear secretions, foreign bodies, and irritants from the airway
• May be voluntary or a reflex to airway irritants/triggers
  • Mechanical
    • Inhaled/aspirated solid or particulate matter (e.g., smoke, dust)
    • Mucus
  • Chemical
    • Gastric acid (GERD)
    • Inflammatory mediators: bradykinin, prostaglandin E2
  • Thermal: cold air
• Cough reflex arc
  1. Irritation of cough receptors in the nose, sinuses, and upper and lower respiratory tracts (see the triggers above)
  2. Transmission along the afferent pathway via the vagus nerve (CN X) to the cough center in the medulla
  3. Generation of efferent signal in the medulla and initiation of cough via the vagus, phrenic, and spinal motor nerves
• Mechanism of cough reflex
  • Irritation of cough receptors → initiation of the cough reflex arc, which leads to:
    • Rapid inspiration, closure of the epiglottis and vocal cords (which traps inhaled air in the lungs), and contraction of the diaphragm, expiratory, and abdominal muscles → rapid increase of intrathoracic pressure
    • A sudden opening of the vocal cords and forceful expulsion of air from the lungs

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History

• Onset and duration of cough
  • Acute: cough lasting < 3 weeks
  • Subacute: cough lasting 3–8 weeks
  • Chronic: cough lasting > 8 weeks in adults; > 4 weeks in children
• Characteristics of the cough
  • Quality
    • Productive (cough with production of phlegm/mucus): pneumonia , bronchitis , bronchiectasis , pulmonary edema , tuberculosis
    • Nonproductive (dry cough): asthma, interstitial lung disease, viral pneumonia (e.g., adenovirus. RSV, influenza virus)
  • Timing
    • Nocturnal cough: asthma ; upper airway cough syndrome (UACS) ; GERD
    • Seasonal/geographical variation: allergy/irritant-induced cough (e.g., asthma, hypersensitivity pneumonitis, UACS due to allergic rhinitis/sinusitis, acute bronchitis)
• Risk factors
  • History of smoking (pack years)
  • Occupational history (e.g., pneumoconiosis, hypersensitivity pneumonitis)
  • Medication history (E.g., ACE inhibitors, β blockers, aspirin can induce dry cough and/or bronchoconstriction.)
  • History of allergies
  • History of contact with an individual who has TB
• Associated symptoms
  • URI: rhinorrhea, odynophagia, myalgia, fever: suggestive of URI
  • Allergic origin: itching and watering of eyes, rhinorrhea, pruritus
  • Cough-variant asthma: exacerbation of cough with activity
  • GERD (3^rd most common cause of chronic cough) : heartburn or reflux
  • Red flag symptoms:
    • Systemic symptoms: persistent fever (pneumonia, TB); night sweats, weight loss (TB, lung cancer)
    • Dyspnea (asthma, congestive heart failure, COPD, interstitial lung disease)
    • Hemoptysis (TB, lung cancer); copious sputum production (bronchiectasis)
    • Severe thoracic pain/pleurisy (pneumonia, TB, pulmonary embolism)
    • Change in character of a chronic cough (esp. in a smoker's cough)
    • History of contact with TB and/or HIV

Clinical examination:

• See pulmonary examination

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• An acute cough is often a clinical diagnosis (diagnostic tests are not routinely indicated in this case).
• Patients with chronic cough and/or red flag symptoms (see “Approach” above) require further assessment.

Laboratory tests

• Complete blood count: indicated in patients with chronic cough/red flag symptoms if an infective etiology (e.g., neutrophilic leukocytosis in pneumonia, lymphocytosis in TB) or allergic etiology (e.g., eosinophilia in asthma) is suspected
• Tuberculin skin test: patients with suspected TB
• Sputum examination
  • Sputum culture: suspected bacterial pneumonia, TB
  • Sputum examination for acid-fast bacilli: suspected TB
• Nasopharyngeal swab/deep nasopharyngeal aspirate culture and PCR for pertussis: indicated in patients with subacute/chronic cough, esp. if associated with an inspiratory whoop and/or post-tussive vomiting
• Blood culture: suspected pneumonia
• Arterial blood gas analysis: patients with dyspnea and those with suspected life-threatening causes of acute cough
• Bronchoalveolar lavage
  • Inconclusive non-invasive diagnostic tests (e.g., in bronchiectasis, asbestosis, bronchioloalveolar carcinoma)
  • Suspected infectious etiology in patients who are unable to expectorate sputum for examination (e.g., tuberculosis, PCP, histoplasmosis, aspergillosis)

Imaging

• Chest x-ray
  • Suspected pneumonia or TB
  • Chronic cough with abnormal physical examination findings or prolonged history of nicotine abuse
  • Red flag symptoms
• X-ray of paranasal sinuses: patients with UACS secondary to suspected sinusitis
• Chest CT scan
  • Suspected bronchiectasis (diagnostic test)
  • Recurrent pneumonia
  • Chest x-ray findings suggestive of lung cancer (e.g., mass, hilar lymphadenopathy)
  • Inconclusive chest x-ray findings in patients with foreign body aspiration
• Bronchoscopy
  • Foreign body aspiration
  • Lung cancer
  • Suspected tracheoesophageal fistula

Pulmonary function tests

• Spirometry: indicated to differentiate between obstructive lung disease (e.g., asthma, COPD) and restrictive lung disease (e.g., interstitial lung disease)
• Bronchial challenge test (metacholine challenge test; bronchodilator reversibility test): to differentiate asthma from other obstructive lung disease
• Single-breath diffusing capacity: to differentiate between intrapulmonary (e.g., interstitial lung disease) and extrapulmonary causes (e.g., pleural effusion) of restrictive lung disease

Miscellaneous

• BNP levels, ECG, and ECHO: patients with cough due to suspected heart failure
• Endoscopy, 24-hour esophageal pH monitoring, and/or barium swallow: patients with chronic cough suspected to be due to GERD/achalasia that is not responsive to a trial of PPIs

Close history taking and physical examination are sufficient to diagnose the cause of an acute cough without red flag symptoms! In chronic cough and cough with red flag symptoms, thoracic x-ray and pulmonary function testing should be considered at an early stageReferences:^{[12][17][18][19][20]}

Acute cough

• Non-life-threatening acute cough (URI, acute bronchitis):
  • Nonpharmacological treatment
    • Honey
    • Menthol (vapors)
    • Hydration, lozenges, and humidifiers
  • NSAIDs: for myalgia, headaches, fever
  • Antibiotics: usually not recommended
  • Hypersensitivity pneumonitis: antigen avoidance with/without glucocorticoid therapy
• Life-threatening acute cough
  • Inhalation injury: secure airway (endotracheal intubation/tracheostomy) ; administer high-flow oxygen; administer aerosolized bronchodilators and N-acetylcysteine with/without heparin; chest physiotherapy
  • Treat the underlying cause: See congestive heart failure, pulmonary embolism, asthma, COPD, and acute pericarditis.
• In children: See “treatment” of croup and bronchiolitis.

Subacute cough

• Post-infectious cough
  • Often resolves spontaneously (no treatment needed)
  • Cough interfering with sleep/daily activities: antitussives (see below), inhaled bronchodilators, oral/inhaled corticosteroids
• Suspected pertussis: early administration of macrolide antibiotics
• See "treatment" of pneumonia and COPD.

Chronic cough

• Stop inciting or aggravating factor(s)
  • Cessation of smoking
  • Stop/substitute ACE-inhibitors
• Chronic cough with no abnormal physical examination findings and no history of ACE-inhibitor use:
  • Empirical trial of treatment with first-generation antihistamines (e.g., dimetindene, diphenhydramine) → improvement of symptoms within 2 weeks → diagnostic of UACS; treat the underlying cause (see "treatment" of allergic rhinitis and sinusitis)
  • No/partial improvement with antihistamines
    • → Empirical trial of inhaled bronchodilators or corticosteroids → symptomatic improvement → diagnostic of cough-variant asthma → See "treatment" of asthma (bronchodilators, corticosteroids, leukotriene receptor antagonists).
    • → Empirical trial of proton pump inhibitors and anti-reflux lifestyle modification (see "treatment" of GERD) → symptomatic improvement → continue PPIs for 8–12 weeks
• Treat the underlying cause

Symptomatic treatment of a cough

• Productive cough
  • Drugs to decrease the viscosity of mucus and enhance mucociliary clearance (no cough suppression)
    • Expectorants (e.g., guaifenesin)
      • Loosen mucus by increasing the fluid content of bronchial secretions via an unknown mechanism
      • Should be taken with sufficient amount of water for the best effect
    • Mucolytics (e.g., N-acetylcysteine)
      • Decrease the viscosity of mucus by disrupting disulfide bonds of mucus glycoproteins
      • Used in patients with viscous mucus in chronic bronchopulmonary diseases (e.g., cystic fibrosis, COPD)
      • Also used as an antidote in acetaminophen poisoning
  • Chest physiotherapy
    • Chest percussion/vibration may be used with postural drainage to mobilize and enhance the clearance of mucus from the airway.
    • Indicated in patients with thick mucus and/or ineffective cough (e.g., cystic fibrosis, bronchiectasis, pneumonia)
• Non-productive cough: cough suppressants (antitussive medications)
  • Centrally acting cough suppressants
    • Examples: dextromethorphan, codeine
    • See opioids for more information
  • Peripherally acting cough suppressants (e.g., benzonatate)

Antitussive medications decrease coughing, which is important for the expectoration of mucus! They are not usually indicated if an infection is the cause of cough.

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