Differential Diagnoses and Never-Miss Causes for Cough
Always screen immediately for red flags indicating life-threatening conditions: hemoptysis, pulmonary embolism, tuberculosis (especially in endemic areas or high-risk populations even with normal chest X-rays), pneumonia, and lung malignancy 1.
Never-Miss (Life-Threatening) Causes
The following conditions require immediate recognition and evaluation:
- Pulmonary embolism - acute onset with dyspnea and pleuritic chest pain
- Pneumonia/Lower respiratory tract infection - fever, productive cough, consolidation on exam
- Tuberculosis - must be considered even with normal chest radiographs in endemic areas or high-risk populations 1
- Lung malignancy - particularly in smokers with chronic cough; early detection offers the only possibility of cure 2
- Hemoptysis of any cause - requires immediate workup for malignancy, bronchiectasis, or diffuse alveolar hemorrhage
- Diffuse alveolar hemorrhage - presents with acute/subacute cough, hemoptysis, diffuse infiltrates, anemia, and hypoxemia; infectious causes in immunocompetent patients include influenza A (H1N1), Staphylococcus aureus, dengue, leptospirosis, and malaria 3
Differential Diagnoses by Duration
Acute Cough (<3 weeks)
- Viral upper respiratory tract infection (most common, self-limiting) 4
- Community-acquired pneumonia (most important differential) 4
- Lower respiratory tract infection
- Environmental/occupational exposures 1
Subacute Cough (3-8 weeks)
- Postinfectious cough (48.4% in prospective studies) 1
- Upper airway cough syndrome/UACS (33.2%) - formerly called postnasal drip syndrome 1
- Asthma exacerbations (15.8%) 1
- COPD exacerbations
- Bordetella pertussis - may occur in localized epidemics 5
- Nonasthmatic eosinophilic bronchitis/NAEB (5.4%) 1
Chronic Cough (>8 weeks)
The "big three" account for the vast majority of cases and should be the initial diagnostic focus 5:
Upper Airway Cough Syndrome (UACS) - from rhinosinus conditions; may be "silent" without other symptoms; voice hoarseness is an independent predictor 5, 6
Asthma/Cough Variant Asthma - may present as "silent asthma" with cough as the only symptom; predictors include female sex, tiredness, and hypersensitivity to irritants 5, 6
Gastroesophageal Reflux Disease (GERD) - may be "silent GERD" without typical reflux symptoms; patients typically have less severe cough and less hoarseness 5, 6
Important: Each of these may present alone or in combination, and may be clinically silent apart from cough itself 5.
Additional Chronic Cough Causes
- Nonasthmatic eosinophilic bronchitis (NAEB) - prevalence 13-33% in non-US series; characterized by eosinophilic infiltration, normal spirometry, lack of bronchial hyperresponsiveness; responds to inhaled corticosteroids; should be considered early as it's easily diagnosed with induced sputum eosinophil staining 5
- ACE inhibitor use - must be excluded in initial evaluation 5
- Bronchiectasis
- Interstitial lung diseases
- Endobronchial abnormalities (tumors, tuberculosis, sarcoidosis, retained sutures)
- Congestive heart failure
- Thyroid disease
- Neuromuscular disorders
- Mediastinal mass
- Habitual/psychogenic cough
Clinical Pitfalls
- Do not use cough character, timing, or sputum production to rule in or rule out specific diagnoses - these features are unreliable 5
- Never assume normal chest X-ray excludes TB in endemic areas or high-risk populations 1
- Always consider UACS, asthma, and GERD even when "silent" - each can present with cough as the only symptom 5
- NAEB is underdiagnosed in US studies despite being relatively common elsewhere; consider early if you have access to induced sputum eosinophil analysis 5
- Assess cough severity with validated tools (e.g., Leicester Cough Questionnaire, COAT) before and after treatment 1
- Follow up patients at 4-6 weeks after initial evaluation to ensure resolution 1