What is the differential diagnosis (Ddx) for Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD)?

Differential Diagnosis for AECOPD

When evaluating a patient presenting with acute worsening of respiratory symptoms and known COPD, you must systematically exclude life-threatening mimics before confirming the diagnosis of AECOPD, as comorbidities commonly trigger or masquerade as exacerbations. 1

Critical Differential Diagnoses to Exclude

The following conditions must be actively ruled out in every patient presenting with suspected AECOPD, as they carry significant mortality risk and require distinct management:

Cardiovascular Causes

• Acute coronary syndrome - particularly important as cardiovascular disease commonly coexists with COPD 1, 2
• Acute decompensated heart failure/pulmonary edema - can present identically with dyspnea and may be triggered by the same infectious/inflammatory processes 1, 2
• Atrial fibrillation - may precipitate acute respiratory decompensation 2
• Pulmonary embolism - critical not to miss, especially in patients with reduced mobility or recent hospitalization 1, 2

Pulmonary Causes Beyond AECOPD

• Pneumonia - bacterial superinfection is common and changes antibiotic selection; chest radiography is essential to differentiate 1, 2
• Pneumothorax - particularly in patients with bullous emphysema 1, 2
• Lung cancer - may present with new or worsening respiratory symptoms 1, 2
• Upper airway obstruction - can mimic AECOPD presentation 1

Other Considerations

• Aspiration - especially in patients with reduced consciousness or swallowing difficulties 3
• Systemic arterial hypertension complications 2

Diagnostic Approach to Differentiate

Essential Investigations

• Chest radiography is mandatory to exclude pneumonia, pneumothorax, pulmonary edema, and lung cancer 2
• ECG and cardiac biomarkers when acute coronary syndrome or heart failure is suspected 1
• Sputum culture and sensitivity when purulent sputum is present, previous antibiotics failed, or in severe exacerbations requiring hospitalization 2

Clinical Features Suggesting True AECOPD

The diagnosis of AECOPD is supported by the classic triad of:

• Increased dyspnea (the key symptom) 1
• Increased sputum volume 1
• Increased sputum purulence 1

Additional supportive features include increased cough, increased wheeze, chest tightness, and fluid retention 1

Common Pitfalls to Avoid

The most critical error is assuming all acute respiratory worsening in COPD patients represents AECOPD. 1 In patients with multimorbidity (which is the norm in COPD), exacerbation of respiratory symptoms may be caused by decompensation of comorbidities without necessarily involving the airways and lung 4. This is particularly challenging because many comorbid conditions share clinical manifestations like fatigue and dyspnea with COPD 4.

Viral respiratory infections predispose to bacterial superinfection by interfering with mucociliary clearance and impairing bacterial killing, so the presence of viral infection does not exclude bacterial pneumonia 2. Molecular typing shows that acute exacerbations are often associated with new bacterial strains, supporting their causative role 2.

Systemic inflammation from infections/pollutants may cause acute respiratory symptoms through decompensation of concomitant chronic diseases (heart failure, thromboembolism) rather than direct airway involvement 4. This mechanistic understanding explains why cardiovascular complications are so common during what appears to be a "respiratory" exacerbation 2, 4.