What are the differential diagnoses of cough, categorized by duration (acute, sub‑acute, chronic) and red‑flag features?

Differential Diagnoses of Cough by Duration and Red-Flag Features

The first step in evaluating any patient with cough is to classify it by duration—acute (<3 weeks), subacute (3-8 weeks), or chronic (>8 weeks)—as this immediately narrows the differential diagnosis and guides management. 1

Classification by Duration

Acute Cough (<3 weeks)

• Viral upper respiratory tract infection is the most common cause, typically self-limited and requiring only reassurance 2, 3
• Lower respiratory tract infection (bronchitis, pneumonia) should be considered if systemic symptoms or abnormal lung examination are present 1
• Pulmonary embolism must be excluded in patients with risk factors and acute dyspnea 1
• Acute exacerbation of underlying disease (asthma, COPD, heart failure) in patients with known conditions 1
• Environmental or occupational exposures should be assessed in all cases 1

Subacute Cough (3-8 weeks)

• Postinfectious cough is the most common cause, accounting for 48.4% of cases, and often resolves spontaneously without treatment 1, 4
• Bordetella pertussis should be included in the differential, particularly in endemic areas 2, 5
• Exacerbation of underlying asthma or COPD accounts for approximately 15.8% of subacute cough 1
• Upper airway cough syndrome (UACS) from rhinosinus conditions represents 33.2% of cases 1
• Nonasthmatic eosinophilic bronchitis (NAEB) is responsible for 5.4% of subacute cough 1
• Tuberculosis must be considered in endemic areas or high-risk populations even with normal chest radiographs 1

Chronic Cough (>8 weeks)

The "big four" causes account for >90% of chronic cough cases in nonsmokers with normal or near-normal chest radiographs: 1, 6, 2, 7

Upper Airway Cough Syndrome (UACS)

• Represents 18.6-81.8% of chronic cough cases 1, 8, 6
• Previously called postnasal drip syndrome 6, 3
• Encompasses various rhinosinus conditions including allergic rhinitis, vasomotor rhinitis, and chronic sinusitis 1, 8

Asthma (including cough-variant asthma)

• Accounts for 14.6-41.3% of chronic cough 1, 8
• Cough may be the sole manifestation without wheezing or dyspnea 8, 2
• Normal spirometry does not exclude asthma-related cough 8, 3
• Typically worsens at night, with cold air exposure, or with exercise 6

Gastroesophageal Reflux Disease (GERD)

• Implicated in 4.6-85.4% of chronic cough cases 1, 8
• Can occur without any gastrointestinal symptoms 8, 2
• Acid suppression alone is no longer recommended as sole therapy 1, 6

Nonasthmatic Eosinophilic Bronchitis (NAEB)

• Contributes to 6.4-17.2% of cases 1, 8, 6
• Characterized by eosinophilic airway inflammation without airway hyperresponsiveness or variable airflow obstruction 8, 9

Additional Important Causes

• Multiple simultaneous etiologies occur in up to 67% of patients, requiring combination therapy 1, 8, 6
• ACE inhibitor-induced cough resolves within a median of 26 days after discontinuation 8, 3
• Sitagliptin can cause cough and should be discontinued 1, 6
• Smoking-related chronic bronchitis typically resolves within 4 weeks of cessation 8, 6
• Atopic cough is more prevalent in Asian populations 1, 6
• Environmental and occupational exposures must be systematically evaluated 1, 8

Red-Flag Features Requiring Immediate Evaluation

Always screen for red flags as they indicate potentially life-threatening conditions that require urgent investigation before pursuing the standard algorithmic approach: 1, 8

Hemoptysis

• Mandates immediate evaluation for malignancy, tuberculosis, bronchiectasis, or pulmonary embolism 1, 8

High-Risk Smoking History

• Smoker >45 years with new cough, change in cough pattern, or coexisting voice disturbance 1, 8
• Adults aged 55-80 years with ≥30 pack-year smoking history who currently smoke or quit within past 15 years (lung cancer screening criteria) 1, 6

Respiratory Distress

• Prominent dyspnea, especially at rest or at night, suggests severe underlying cardiopulmonary disease 1, 6

Systemic Symptoms

• Fever suggests infection or inflammatory disease 1, 8
• Unintentional weight loss raises concern for malignancy, tuberculosis, or chronic infection 1, 8, 7
• Night sweats indicate possible tuberculosis or lymphoma 6

Other Red Flags

• Hoarseness may indicate laryngeal pathology or recurrent laryngeal nerve involvement 1
• Peripheral edema with weight gain suggests heart failure 1
• Trouble swallowing (dysphagia) when eating or drinking 1
• Vomiting associated with cough 1
• Recurrent pneumonia raises concern for structural lung disease, immunodeficiency, or aspiration 1, 7
• Abnormal respiratory examination or chest radiograph coinciding with cough duration 1
• History of cancer, tuberculosis, or immunosuppression 8

Common Pitfalls to Avoid

• Assuming a single etiology: Up to 40-67% of chronic cough patients have multiple simultaneous causes requiring combination therapy rather than sequential monotherapy 1, 8, 6, 9
• Failing to discontinue ACE inhibitors or sitagliptin before pursuing extensive workup, as these are common reversible causes 1, 8, 6, 9
• Relying on normal spirometry to exclude asthma: Cough-variant asthma frequently presents with normal pulmonary function tests, and methacholine challenge testing is required 8, 3
• Using acid suppression alone for GERD-related cough: Comprehensive management including lifestyle modifications, dietary changes, and potentially prokinetic agents is necessary 1, 8, 6
• Not quantifying cough severity: Validated cough severity tools or quality-of-life questionnaires should be used routinely to objectively assess treatment response 1, 8, 6, 9
• Inadequate treatment duration: Each empiric trial requires 4-6 weeks before declaring treatment failure 1, 8
• Abandoning partially effective therapies: When treating multiple etiologies, continue effective treatments while adding new ones for partial responders 8, 9