What is the differential diagnosis and management approach for a patient presenting with cough?

Differential Diagnosis for Cough

Classification by Duration

The differential diagnosis for cough is fundamentally organized by duration: acute (<3 weeks), subacute (3-8 weeks), or chronic (>8 weeks), with each category having distinct common causes that guide your diagnostic and therapeutic approach. 1

Acute Cough (<3 weeks)

The critical first step is distinguishing life-threatening from benign causes 2:

Life-threatening causes to rule out immediately:

• Pneumonia (look for tachypnea, tachycardia, dyspnea, abnormal lung findings) 2
• Pulmonary embolism 2
• Severe respiratory distress (markedly elevated respiratory rate, intercostal retractions, cyanosis, altered mental status) 1

Common benign causes:

• Viral upper respiratory infection/common cold (most frequent) 2
• Acute bronchitis 2
• Acute exacerbation of preexisting conditions (COPD, asthma, bronchiectasis) 2
• Environmental or occupational exposure to irritants (allergic or irritant-induced rhinitis) 2

Subacute Cough (3-8 weeks)

First determine if postinfectious or non-infectious 2:

Postinfectious causes:

• Upper airway cough syndrome (UACS) 2
• Transient bronchial hyperresponsiveness 2
• Asthma 2
• Pertussis (especially if paroxysms, post-tussive vomiting, or inspiratory whooping present) 3
• Acute exacerbation of chronic bronchitis 2

If non-infectious, approach as chronic cough 2

Chronic Cough (>8 weeks)

The four most common causes account for the vast majority of cases and frequently coexist, requiring sequential and additive treatment 2, 1:

1. Upper Airway Cough Syndrome (UACS) - previously called postnasal drip syndrome 2
2. Asthma (including cough-variant asthma) 2
3. Non-Asthmatic Eosinophilic Bronchitis (NAEB) 2
4. Gastroesophageal Reflux Disease (GERD) 2

Additional common causes:

• ACE inhibitor-induced cough (check medication history immediately) 2, 1
• Smoking-related chronic bronchitis (90-94% resolve within first year of cessation) 1
• COPD 4

Uncommon Causes to Consider After Common Causes Excluded

These should only be pursued after 4-6 weeks of appropriate empiric treatment for common causes has failed 2, 1:

• Bronchiectasis 2
• Occult interstitial lung disease 2
• Endobronchial tumor 2
• Sarcoidosis 2
• Suppurative lower airway infection 2
• Eosinophilic or lymphocytic bronchitis 2
• Non-acid reflux disease 2
• Swallowing disorder 2
• Congestive heart failure 2
• Drug-induced cough (beyond ACE inhibitors) 2
• Bronchogenic carcinoma 5
• Tuberculosis (especially in high-prevalence areas or immunocompromised patients) 1

Special Population Considerations

Immunocompromised patients:

• Use the same initial algorithm but expand differential based on immune defect type and severity 1, 6
• In HIV patients with CD4+ <200 cells/μL, suspect Pneumocystis pneumonia, tuberculosis, and opportunistic infections 1

Peritoneal dialysis patients:

• Consider GERD, ACE inhibitors, pulmonary edema, asthma exacerbated by β-blockers, and infection 3

Critical Pitfalls to Avoid

Do not rely on cough characteristics (timing, quality, sound) for diagnosis—they have minimal diagnostic value 2, 1

Do not treat only one cause—multiple etiologies coexist in the majority of chronic cough cases, requiring additive sequential therapy 2, 1

Do not label as "idiopathic" or "unexplained" until thorough diagnostic evaluation, appropriate treatment trials (4-6 weeks minimum), and specialist referral have been completed 2, 1

Do not forget to immediately discontinue ACE inhibitors if present—this is a common, easily reversible cause 2, 1

Do not overlook smoking cessation counseling—this alone resolves cough in the vast majority of smokers 2, 1