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 is a protective mechanism that forcefully expels air from the lungs to clear secretions, foreign bodies, and irritants from the airway.

• 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:^{[1][2][3][4][5][6]}

Cough is usually classified by duration.

• Adults and adolescents > 14 years of age ^[7]
  • Acute cough: < 3 weeks
  • Subacute cough: 3–8 weeks
  • Chronic cough: > 8 weeks
• Children and adolescents ≤ 14 years of age ^{[8][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. ^[7]

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

Initial management

• Evaluate for and treat life-threatening causes of cough immediately if present.
• Assess for red flags for cough.

Life-threatening causes of 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. ^[15]

Red flags for cough

These red flag features may indicate a life-threatening cause of cough and typically warrant rapid evaluation and treatment. ^[7][13]

• 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)
  • Weight gain with peripheral edema
  • Dysphagia, hoarseness, vomiting
  • Hemoptysis ^[8]
  • Recurrent pneumonia
  • Excessive sputum production
• Abnormal physical examination and/or abnormal imaging findings

An abnormal screening chest x-ray in a patient with cough is also a red flag.

A detailed history and physical examination are essential to help narrow down the possible causes of cough and guide initial investigations and management. ^[7][16]

Focused history

• Duration of cough (weeks): Ascertaining the symptom duration is a recommended first step in evaluating adults presenting with cough (see “Classification”). ^[7][16]
• Other cough characteristics
  • Presence of sputum
    • Productive cough
    • Nonproductive cough
  • Onset
    • Sudden
    • Gradual
  • Quality: classic cough presentations in children ^[8][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. ^[17]

Other key historical features

• Comorbidities
  • Smoking history
  • 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 ^[7]
  • Beta blockers
• Exposures
  • Infectious contacts
  • Radiation sources
  • Lifetime tobacco smoke exposure
  • Occupational exposure to irritants, e.g., chemicals, organic or inorganic dust ^[18]
  • Travel history ^[19]
    • Travel to endemic areas
    • At-risk activities
    • Means of transportation

Focused physical examination

• Pulmonary examination
• Cardiac examination

Diagnostic approach

• Confirm duration of cough as first step in narrowing the differential diagnosis (see “Classification”). ^[7][16]
• Conduct a thorough clinical evaluation for cough to identify specific cough etiology.
  • 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.
• Diagnostic evaluation depends on chronicity and the presence of red flags for cough:
  • Acute cough and subacute cough: Diagnostic studies are not routinely indicated (unless red flags for cough are present).
  • Chronic cough:
    • Obtain CXR (if not already performed). ^[7][12]
    • Perform sequential diagnostics and/or empiric treatment for the most common causes of chronic cough

Diagnostic studies for acute or subacute cough are not routinely indicated in patients without red flags for cough. ^[7][13][16]

Imaging ^[7]

Chest x-ray

• Indications:
  • Chronic cough
  • Suspected pneumonia or TB
  • Presence of red flags for cough (e.g., high risk of lung cancer).
  • As directed by clinical evaluation of cough
• Interpretation: If abnormal findings are identified, manage the patient based on the suspected underlying disease and consider further diagnostics as indicated. ^[7][12]

Additional imaging

• 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
• X-ray of paranasal sinuses: Consider in patients with UACS secondary to suspected sinusitis.

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

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

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 studies ^{[7][20][21][22][23]}

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

• Bronchoalveolar lavage (BAL): 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 include:
    • 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)
• Bronchoscopy
  • Consider if high suspicion for the following:
    • 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

Management ^[7][13][16]

• Diagnostic studies are not routinely indicated (unless red flags for cough are present).
• Consider differentiating between the following groups, based on clinical suspicion:
  • Life-threatening causes of cough and/or red flags for cough present: Identify and treat underlying cause immediately.
  • Infectious causes:
    • Self-limiting infectious (e.g., URTI, acute bronchitis) or postinfectious cause most likely: supportive care ^[24][25]
    • Non-self-limiting infection (e.g., pneumonia, TB, pertussis) most likely: Confirm diagnosis and begin targeted therapy. ^[17]
  • New onset or exacerbation of pre-existing condition: Identify and treat the underlying condition.
  • > 3 weeks duration and not post-infectious or due to pre-existing condition: Manage as chronic cough.

Diagnostic studies for acute or subacute cough are not routinely indicated in patients without red flags for cough. ^[7][13][16]

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.

Common causes of acute and subacute cough

Additional causes to consider

• Pneumonia
• Medication effect (e.g., sitagliptin, ACE-inhibitor)
• Environmental or occupational lung disease

Management

• Obtain CXR (if not already performed). ^[7][12]
• Perform sequential diagnostics and/or empiric treatment for the most common causes of chronic cough.
  • Consider the four most common etiologies and start empiric therapy for what is clinically most likely (see “Most common causes of chronic cough”). ^[16]
  • If suboptimal response after 4–6 weeks, proceed to the next condition. ^[7]
• 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”).

Common causes of chronic cough

Additional causes to consider

• Tuberculosis (in endemic areas and high-risk exposures)
• Medication effect (e.g., sitagliptin, ACE-inhibitor)
• New-onset COPD
• Interstitial lung disease
• Lung cancer

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

General principles

• All patients
  • Identify and treat the underlying cause.
  • Consider symptomatic therapy/supportive care.
  • Eliminate any known modifiable triggers, e.g.:
    • Smoking cessation
    • Potential offending medications (e.g., ACE inhibitors, NSAIDs, beta blockers).
    • Environmental and/or occupational exposures.
• Acute and subacute cough: See “Management of acute and subacute cough.”
• Chronic cough: See “Management of chronic cough.”

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

Symptomatic treatment for cough ^{[24][25][28][29]}

Expectorants

• Indication: : can be considered for productive coughs
• Mechanism of action
  • Increase bronchial fluid to reduce viscosity of mucus (no cough suppression)
  • The exact mechanism is unknown.
• 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)

• Indications
  • There is little evidence for the therapeutic effectiveness of cough suppressants. ^[24][25]
  • Can be considered for nocturnal dry cough ^[30]
• 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.

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)

Supportive care

• Rest and adequate hydration
• Avoid lung irritants, e.g., smoke, incense. ^[31][32]
• Nonpharmacological measures may be beneficial, e.g.: ^[14]
  • Nasal saline for nasal congestion
  • Honey ^[33][34][35]
  • A humidifier

Monitoring ^[7]

• Adults
  • Routine follow-up 4–6 weeks after treatment initiated
  • Use validated cough severity and quality of life measurement tools if available.
• Children: Reassess if acute cough becomes chronic, i.e., lasts ≥ 4 weeks. ^[12]

Specialist referral ^[7]

• Persistent symptoms despite treatment for most common causes
• Consider expedited specialist referral (e.g., pulmonology, ENT, GI) for:
  • Suspected serious underlying conditions
  • Chronic cough of unclear etiology

Refractory symptoms ^[7]

• If symptoms persist despite evaluation and treatment for the most common causes:
  • Reconsider the working diagnosis if treatment is unsuccessful.
  • Consider specialist referral, e.g., pulmonology, otolaryngology.
  • Consider further diagnostic testing for less common causes (see “Diagnostics”).