Cough

A cough is a protective mechanism that forcefully expels air from the lungs to clear secretions, foreign bodies, and irritants from the airway, and can be triggered by various conditions. A cough can be classified as acute, subacute, or chronic, in addition to productive (with sputum expectoration) or dry. The most common causes of acute cough are upper respiratory tract infections (URTIs), exacerbations of chronic conditions, and pneumonia. Subacute cough is often a sequela of a URTI (postinfectious cough) but can also be caused by upper airway cough syndrome (UACS) or pertussis. Common causes of chronic cough in adults include UACS, asthma, gastroesophageal reflux disease (GERD), nonasthmatic eosinophilic bronchitis (NAEB), and certain medications (e.g., ACE inhibitors, sitagliptin). The cause of an acute cough can often be determined clinically with a thorough medical history and physical examination. Chronic cough or the presence of red flag symptoms (including dyspnea, fever, hemoptysis, and weight loss) indicate that further investigation is required. Treatment depends on the underlying etiology and often includes symptomatic therapy.

See also “Dyspnea” and “Chest pain.”

• Cough: a protective mechanism that forcefully expels air from the lungs to clear secretions, foreign bodies, and irritants from the airway
• Upper airway cough syndrome (UACS): also known as postnasal drip ^[1][2]
  • The drainage of mucus down the back of the throat due to increased nasal mucus production; various causes, such as allergic rhinitis and chronic sinusitis
  • Symptoms include coughing, a feeling of obstruction in the throat, and throat clearing.
• Protracted bacterial bronchitis ^[1]
  • Chronic bacterial infection that causes a productive cough
  • Clinical diagnosis requires all of the following:
    • Daily cough for > 4 weeks
    • Resolution within 2–4 weeks of antibiotic treatment
    • Absence of alternate diagnosis

• Triggers: cough 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
  • Irritation of cough receptors in the nose, sinuses, upper and lower respiratory tract (see the triggers above)
  • Transmission along the afferent pathway via the internal laryngeal nerve of the vagus nerve (CN X) to the cough center in the medulla
  • Generation of efferent signal in the medulla and initiation of cough via the vagus, phrenic, and spinal motor nerves
• Mechanism of cough reflex: initiation of the cough reflex arc 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

References:^{[3][4][5][6][7][8]}

Cough is usually classified by duration.

• Adults and adolescents > 14 years of age ^[2]
  • Acute cough: < 3 weeks
  • Subacute cough: 3–8 weeks
  • Chronic cough: > 8 weeks
• Children and adolescents ≤ 14 years of age ^{[1][9][10][11]}
  • Acute cough: < 2 weeks
  • Subacute cough: 2–4 weeks
  • Chronic cough: at least daily cough for > 4 weeks ^[11][12][13]

In endemic areas, consider pulmonary tuberculosis in all patients with a cough of any duration. ^[2]

Consider pertussis in patients with risk factors, e.g., underimmunization and/or contact with an infected individual. ^[12]

Initial management ^[2][15]

• Conduct a thorough clinical evaluation for cough, and if possible, identify specific cough etiology.
  • Categorize cough by the duration of symptoms (see “Classification”).
  • Assess for red flags for cough.
  • Consider risk factors for tuberculosis and pertussis in all patients. ^[12]
  • In children, consider classic coughs based on cough quality, e.g., croup, whooping cough.
• Evaluate and treat life-threatening causes of cough immediately if present.
  • Consult specialist urgently (e.g., pulmonology and critical care for severe asthma exacerbation)
  • Consider hospital or critical care unit admission.
• Order routine diagnostic studies for chronic cough or if red flags for cough are present (see “Diagnostics”).

Subsequent management ^[2][15]

• If specific cough etiology is identified:
  • Order additional or confirmatory testing as directed by clinical suspicion (see “Diagnostics”).
  • Begin targeted therapy and consider adding symptomatic therapy as needed (see “Treatment”).
• If the cause remains uncertain after initial evaluation:
  • Follow the recommended approach for cough by duration (see “Acute and subacute cough” and “Chronic cough”).
  • Consider empiric symptomatic therapy (see “Treatment”).
  • Consider observation and follow-up vs. a trial of empiric therapy based on the duration of symptoms.
  • Consider expedited specialist referral (e.g., pulmonology) for:
    • Suspected serious underlying conditions
    • Chronic cough of unclear etiology

Acute and subacute cough is most commonly due to self-limiting viral illnesses. Routine diagnostic studies are typically unnecessary unless red flags for cough are present or required for specific suspected cough etiologies.

A detailed history and physical examination are essential to help narrow down the possible causes of cough and guide initial investigations and management. ^[2][15]

History of present illness

• Duration of cough (weeks): Ascertaining the symptom duration is a recommended first step in evaluating adults presenting with cough (see “Classification”). ^[2][15]
• Other cough characteristics
  • Presence of sputum
    • Productive cough
    • Nonproductive cough
  • Onset
    • Sudden
    • Gradual
  • Quality: classic cough presentations in children ^[1][12]
    • Brassy or barking cough
    • Staccato cough (in infants)
    • Paroxysmal cough
    • Inspiratory whoop
• Aggravating factors
  • Symptom variation depending on the weather and/or season
  • Supine position
  • Exercise
  • Daytime or nighttime worsening of symptoms
• Associated symptoms
  • Viral symptoms, e.g., rhinorrhea, odynophagia, myalgia, fever
  • Allergic symptoms, e.g., itching or watery eyes, rhinorrhea, nasal congestion, throat clearing
  • Posttussive vomiting
  • Chest pain or heartburn

Cough exacerbated by exercise and at nighttime is characteristic of cough-variant asthma.

Coughing paroxysms, inspiratory whoop, and posttussive emesis are characteristic of pertussis. ^[16]

Other key historical features

• Comorbidities
  • Personal or family history of atopy
  • History of chronic disease
    • Cardiac conditions
    • Respiratory conditions
    • Immunodeficiency
    • Neurological or developmental impairment
• Vaccination status: absent or incomplete immunization, e.g., against Streptococcus pneumoniae, Haemophilus influenzae type b, pertussis, influenza
• Medication
  • ACE inhibitors ^[13]
  • Sitagliptin ^[2]
  • Beta blockers
• Exposures
  • Infectious contacts
  • Radiation sources
  • Lifetime tobacco smoke exposure
  • Occupational exposure to irritants, e.g., chemicals, organic or inorganic dust ^[17]
  • Travel history ^[18]
    • Travel to endemic areas
    • At-risk activities
    • Means of transportation

Red flags for cough ^[2][13]

These red flag features may indicate a life-threatening cause of cough and typically warrant rapid evaluation and treatment.

• Smoking history, in particular:
  • Current smokers > 45 years of age with a new or worsening cough and/or voice changes
  • Patients 55–80 years old with ≥ 30 pack-years who either currently smoke or quit smoking ≤ 15 years ago
• Symptoms
  • Fever
  • Weight loss
  • Severe dyspnea (especially at nighttime or when at rest)
  • Hoarseness
  • Weight gain with peripheral edema
  • Dysphagia
  • Vomiting
  • Hemoptysis ^[1]
  • Recurrent pneumonia
  • Excessive sputum production
• Physical examination
  • Abnormal pulmonary examination, e.g.,
    • Wheeze
    • Crackles
  • Abnormal cardiovascular examination, e.g., pulsus paradoxus

An abnormal screening chest x-ray in a patient with cough is also a red flag (see “Diagnostics”).

The following recommendations apply to adults and are consistent with the 2006 and 2018 CHEST guidelines on diagnosis and management of cough. ^[2][15]

• Suspected life-threatening causes of cough: Begin immediate empiric therapy and expedite targeted diagnostics and treatment.
• Suspected self-limiting infectious (e.g., URTI, acute bronchitis) or postinfectious cause: Consider conservative approach. ^[19][20]
• Suspected non-self-limiting infection (e.g., pneumonia, TB, pertussis): Confirm diagnosis and begin targeted therapy. ^[16]
• Newly diagnosed chronic condition or exacerbation thereof (e.g., UACS, asthma, GERD, NAEB, COPD, bronchiectasis): Begin targeted management.
• Suspected environmental or occupational lung disease: Limit exposure to the presumed trigger, refer to a specialist for targeted therapy. ^[15]
• Subacute cough of suspected noninfectious origin: See “Chronic cough.”
• Consider tailored symptomatic therapy and supportive care in all patients in addition to targeted therapy (see “Treatment”).
• Monitoring
  • Adults ^[2]
    • Routine follow-up 4–6 weeks after cough onset
    • Use validated cough severity and quality of life measurement tools if available.
  • Children: Reassess if cough becomes chronic, i.e., lasts ≥ 4 weeks. ^[12]

Diagnostic studies for acute or subacute cough are not routinely indicated in patients without red flags for cough. ^[2][13][15]

Postinfectious cough is the most common cause of subacute cough and often resolves without treatment. If it is interfering with the patient's sleep and/or daily activities, consider the use of antitussives.

The following recommendations apply to adults and are consistent with the 2006 and 2018 CHEST guidelines on diagnosis and management of cough. ^[2][13][15]

• Follow the diagnostic and therapeutic approach for suspected causes of cough based on detailed clinical evaluation for cough.
• Obtain CXR as part of the routine evaluation (if not already performed). ^[2][12]
• Eliminate any known modifiable triggers , e.g.:
  • Recommend smoking cessation and avoiding second-hand smoke.
  • Stop or substitute offending medications (e.g., ACE inhibitors, NSAIDs, beta blockers).
  • Recommend avoiding environmental and/or occupational exposures.
• Focus the evaluation on the most common causes of chronic cough in adults and consider sequential diagnostics and/or empiric treatment. ^[15]
• Reassess 4–6 weeks after the treatment is initiated. ^[2]
• If symptoms persist despite evaluation and treatment for the most common causes:
  • Consult or refer to a specialist, e.g., pulmonology, otolaryngology.
  • Consider further diagnostic testing for less common causes (see “Diagnostics”).

In endemic areas, screen all patients with cough for tuberculosis regardless of cough duration. ^[12]

Also consider new-onset COPD, interstitial lung disease, and lung cancer, especially in patients with red flags for cough.

The following conditions should be considered in all adults who present with a cough accompanied by signs of respiratory distress, hemodynamic instability, and/or red flags for cough (see also “Dyspnea”):

• Severe asthma exacerbation or life-threatening asthma exacerbation
• Pneumonia with respiratory failure
• Severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD)
• Pulmonary embolism (PE)
• Acute heart failure (AHF)
• Foreign body aspiration (FBA)
• Acute inhalation injury
• Pneumothorax
• Acute pericarditis
• Acute chest syndrome
• Anaphylaxis
• Lung cancer

If the patient is unstable, follow the ABCDE approach and consider immediate oxygen therapy, airway management, and/or mechanical ventilation.

A large proportion of malignancies are first diagnosed following an emergency presentation of illness, more often in vulnerable and marginalized patients. Maintain a high index of suspicion for lung cancer in patients with red flags for cough and consider expedited referral for definitive diagnosis, staging, and treatment to prevent poor outcomes. ^[21]

Diagnostic studies for acute or subacute cough are not routinely indicated in patients without red flags for cough. ^[2][13][15]

Initial investigations ^{[2][22][23][24][25]}

• Chest x-ray
  • Obtain routinely for investigating chronic cough, suspected pneumonia, or suspected TB.
  • Obtain urgently if red flags for cough are present (e.g., high risk of lung cancer).
  • Otherwise, consider as directed by clinical evaluation of cough.
• Laboratory studies: Consider in patients with red flags for cough, signs of respiratory distress, suspected sepsis/bacteremia, or risk factors for specific infections.
  • CBC
  • ABG
  • Microbiology of respiratory infections
    • Cultures: e.g., sputum culture, blood culture
    • TB testing: e.g., tuberculin skin test, sputum examination for acid-fast bacilli
    • Pertussis testing: e.g., nasopharyngeal swab, deep nasopharyngeal aspirate, culture and/or PCR
    • Viral testing: e.g., nasopharyngeal PCR for influenza, RSV, COVID-19
• Pulmonary function tests: Consider based on clinical suspicion of chronic lung disease. ^[12]
  • Spirometry: 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 diseases
  • Single-breath diffusing capacity: to differentiate between intrapulmonary (e.g., interstitial lung disease) and extrapulmonary causes (e.g., pleural effusion) of restrictive lung disease

Additional investigations ^{[2][22][23][24][25]}

Consider the following on a case-by-case basis depending on clinical evaluation for cough, duration, and results of initial investigations.

• Imaging
  • X-ray of paranasal sinuses: Consider in patients with UACS secondary to suspected sinusitis.
  • Consider CT chest for:
    • Suspected bronchiectasis
    • Recurrent pneumonia
    • CXR findings suggestive of lung cancer (e.g., mass, hilar lymphadenopathy)
    • Inconclusive chest x-ray findings in patients with foreign body aspiration
• Endobronchial investigations
  • Bronchoalveolar lavage (BAL)
    • Description: A minimally invasive technique that is performed during flexible bronchoscopy in order to evaluate the immunologic, inflammatory, and infectious processes at the level of the alveoli in diffuse lung disease.
    • Indications
      • Inconclusive noninvasive diagnostic tests (e.g., in bronchiectasis, asbestosis)
      • Suspected infectious etiology in patients who are unable to expectorate sputum for examination (e.g., tuberculosis, PCP, histoplasmosis, aspergillosis)
  • Consider bronchoscopy for:
    • Foreign body aspiration
    • Lung cancer
    • Suspected tracheoesophageal fistula
• Others
  • BNP levels, ECG, and ECHO: e.g., for suspected heart failure
  • Endoscopy, 24-hour esophageal pH monitoring, and/or barium swallow: e.g., for suspected GERD/achalasia that is not responsive to a trial of PPIs
  • Assessment of environmental and occupational exposures

Approach

• Treat specific underlying cough etiologies.
• Evaluate the patient's response with routine follow-up.
• Reconsider the working diagnosis if treatment is unsuccessful.
• Consider supportive measures and symptomatic treatment, e.g., in acute viral cough.
• Consider referral to a specialist such as pulmonology or otolaryngology if chronic cough fails to improve or recurs despite adequate treatment.

Antibiotics are not recommended for the routine treatment of cough unless there is a proven indication, e.g., in pneumonia or acute bacterial sinusitis.

Supportive measures

• Recommend rest and adequate hydration.
• Advise patients to avoid lung irritants, e.g., smoke, incense. ^[26][27]
• Nonpharmacological measures may be beneficial, e.g.: ^[14]
  • Nasal saline for nasal congestion
  • Honey ^[28][29][30]
  • A humidifier

Symptomatic treatment for cough ^{[19][20][31][32]}

• Expectorants
  • Mechanism of action
    • Increase bronchial fluid to reduce viscosity of mucus (no cough suppression)
    • The exact mechanism is unknown.
  • Indication: can be considered for productive coughs
    • Guaifenesin (immediate release or extended release )
      • Side effects include nausea and headache
      • Symptoms of overdose include vomiting, altered mental status (due to depression of the central nervous system)
    • Potassium iodide
      • Side effects include nausea, vomiting, salivary gland swelling and tenderness
      • Symptoms of overdose include Jod-Basedow phenomenon, Wolff-Chaikoff effect, hyperkalemia
• Cough suppressants (antitussives)
  • There is little evidence for the therapeutic effectiveness of cough suppressants. ^[19][20]
  • Can be considered for nocturnal dry cough ^[33]
  • Centrally acting: suppress the cough reflex arc at the level of the central nervous system (see “Opioids“ for more information)
    • Dextromethorphan (immediate release or extended release )
      • Side effects include constipation, nausea, dizziness
      • Symptoms of overdose include hallucinations, altered mental status
    • Codeine (off-label)
      • Side effects include, nausea, vomiting, constipation, dizziness, sedation, palpitations, pruritus
      • Symptoms of overdose: see opioid intoxication
  • Peripherally acting: suppress peripheral triggers of the cough reflex arc by anesthetizing respiratory stretch receptors
  • Benzonatate
    • A local anesthetic with cough suppressing properties which is administered as capsules
    • Side effects: e.g., nausea, dizziness, headache, altered mental status
    • Symptoms of overdose: visual disturbances, tremor, seizures

Antitussive medications decrease coughing and, therefore, should only be used in nonproductive cough, as coughing promotes the expectoration of mucus. Antitussives are not indicated in productive coughs or coughs caused by an infection.

Avoid prescribing opioids as antitussive medication in patients with risk factors for or a history of substance use disorders.

Symptomatic treatment for specific types of cough

• Mucolytics: e.g., N-acetylcysteine
  • Liquefy mucus by reducing the disulfide bonds of mucoproteins.
  • Indications include:
    • Hyperviscous chronic bronchopulmonary diseases (e.g., COPD, cystic fibrosis)
    • Acetaminophen overdose (antidote): acetylcysteine restores depleted hepatic glutathione
    • Prophylaxis of contrast agent nephropathy
• Chest physiotherapy
  • Loosens and mobilizes airway mucus through physical percussion, vibrations, and postural drainage
  • May be beneficial for patients with ineffective cough (e.g., neuromuscular disorders) and/or bronchopulmonary diseases with increased sputum viscosity (e.g., cystic fibrosis, bronchiectasis, pneumonia)

Treatment of associated symptoms

• Antihistamines: Consider if an allergic component is suspected, e.g., in allergic rhinitis.
• Bronchodilators (e.g., beta agonists): indicated for the treatment of asthma and COPD
• Steroids
  • Intranasal or inhaled steroids: used in allergic rhinitis, asthma, and NAEB
  • Systemic steroids: used in patients with acute inflammation and/or edema, e.g., in anaphylaxis, AECOPD, acute asthma exacerbation, croup
• Decongestants (e.g., oxymetazoline , pseudoephedrine ): may be used to treat nasal congestion ^[34]
• NSAIDs: may be used to treat myalgia, headache, and fever