What is the differential diagnosis (diff dx) for a patient presenting with chronic cough?

Differential Diagnosis for Chronic Cough

Most Common Causes (The "Big Three")

In nonsmoking adults with chronic cough (>8 weeks) and normal chest X-ray who are not taking ACE inhibitors, focus your diagnostic approach on upper airway cough syndrome (UACS), asthma, and gastroesophageal reflux disease (GERD)—these three conditions account for 92-100% of cases, either alone or in combination. 1

Primary Differential Diagnosis

• Upper Airway Cough Syndrome (UACS) - previously called postnasal drip syndrome; most common single cause 1

  • Can be completely "silent" with no nasal symptoms 1
  • Due to rhinosinusitis, allergic rhinitis, vasomotor rhinitis, or other rhinosinus conditions 1

• Asthma - second most common cause 1

  • May present as "cough variant asthma" with cough as the only symptom 1
  • No wheezing or dyspnea required for diagnosis 1

• Gastroesophageal Reflux Disease (GERD) - third most common cause 1

  • Can be "silent GERD" without heartburn or regurgitation 1
  • Cough may be the sole manifestation 1

• Nonasthmatic Eosinophilic Bronchitis (NAEB) - increasingly recognized as important 1

  • Should be considered early in evaluation 1
  • Responds predictably to inhaled corticosteroids 2

Medication-Induced Causes

• ACE Inhibitor-Induced Cough 1

  • Can occur anytime within the first year of therapy 1
  • Median resolution time is 26 days after discontinuation (range: few days to 2 weeks) 1, 2
  • Stop the ACE inhibitor regardless of temporal relationship 1

• Other Drug-Induced Cough 1

  • Beta-blockers (may exacerbate asthma) 1
  • Consider therapeutic trial of withdrawing suspected medications 1

Smoking-Related

• Chronic Bronchitis/COPD 1
  • Usually productive cough 1
  • Majority resolve within 4 weeks of smoking cessation 1
  • May persist in severe COPD due to frequent exacerbations 1

Infectious Causes

• Tuberculosis 1

  • Consider in endemic areas or high-risk populations 1
  • Post-TB complications include bronchiectasis, endobronchial abnormalities, retained sutures 2
  • Biapical scarring pattern suggests prior TB 2

• Pertussis 3

  • Consider when cough lasts ≥2 weeks with paroxysms, post-tussive vomiting, or inspiratory whooping 3

• Fungal or Parasitic Infections 1

  • Consider in patients from endemic areas after ruling out common causes 1

• Opportunistic Infections in Immunocompromised 1

  • HIV patients with CD4+ <200 cells/μL: suspect Pneumocystis pneumonia, tuberculosis 1
  • Also consider in patients with fever, weight loss, or thrush 1

Uncommon but Important Causes

• Lower Airway Infection 1
• Congestive Heart Failure 1
• Bronchiectasis 2
• Sarcoidosis - can present with apical scarring 2
• Endobronchial Tumor 1, 2
• Airway Foreign Body - consider with abrupt onset 1
• Tracheobronchomalacia 2
• Airway Stenosis 2
• Broncholithiasis 2
• Thyroid Disease 1
• Neuromuscular Disorders 1
• Mediastinal Mass 1
• Habitual or Psychogenic Cough 1

Critical Diagnostic Principles

What NOT to Rely On

The character, timing, or productivity of the cough has NO diagnostic value—do not use these features to rule in or rule out any diagnosis. 1 Even significant sputum production in a nonsmoker with normal chest X-ray typically indicates UACS, asthma, or GERD 1.

Multiple Causes Are Common

• Up to 25% of patients have multiple contributing diagnoses 1
• All three common causes (UACS, asthma, GERD) must be considered in every patient regardless of symptoms 1

When to Consider Uncommon Causes

• Cough persists after treating common causes 1
• Red flags present: fever, weight loss, hemoptysis, recurrent pneumonia 1
• Proceed to chest CT scan and bronchoscopy if indicated 1, 2

Special Populations

• Peritoneal Dialysis Patients: increased prevalence of GERD, pulmonary edema, asthma exacerbated by beta-blockers, infection 1
• Immunocompromised: use same initial algorithm but expand differential based on immune defect type and severity 1

Diagnostic Approach Algorithm

1. History: ACE inhibitor use, smoking status, endemic area exposure, systemic symptoms (fever, sweats, weight loss), cancer/TB/AIDS history 1
2. Chest X-ray: obtain in most patients 1
3. If normal chest X-ray, nonsmoker, not on ACE inhibitor: sequentially evaluate/treat UACS → asthma → NAEB → GERD 1, 2
4. If persistent after empiric treatment: chest CT and consider bronchoscopy 1, 2
5. Idiopathic/unexplained cough is diagnosis of exclusion only after thorough evaluation and failed appropriate treatment 1