What causes exacerbation of Chronic Obstructive Pulmonary Disease (COPD)?

Causes of COPD Exacerbations

Respiratory viral infections are the most common trigger of COPD exacerbations, accounting for approximately one-third of episodes, followed closely by bacterial infections, with environmental factors and comorbidities also playing significant roles. 1, 2

Primary Infectious Triggers

Viral Pathogens

• Viral infections are the leading cause of acute exacerbations, with common culprits including rhinovirus, coronavirus, influenza B, and parainfluenza. 2
• These viral infections predispose airways to bacterial superinfection by interfering with mucociliary clearance, impairing bacterial killing by pulmonary macrophages, and increasing aspiration risk of bacteria-containing secretions. 2

Bacterial Pathogens

• Bacterial infections frequently trigger exacerbations, with the most common organisms being Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. 2
• Molecular typing demonstrates that acute exacerbations are often associated with acquisition of a new strain of a preexisting bacterial organism, supporting the causative role of bacteria. 2
• Increased sputum purulence indicates bacterial involvement, with purulent sputum containing increased bacterial load. 1

Environmental and Exposure-Related Triggers

• Air pollution and environmental pollutants can initiate and amplify exacerbation events. 1
• These exposures cause acute inflammation of the airways and lung superimposed on the chronic inflammation already present in COPD. 3

Comorbidity-Related Causes

Critical cardiovascular conditions can trigger or mimic COPD exacerbations and must be actively excluded:

• Acute heart decompensation/heart failure presents with identical dyspnea and may be triggered by the same infectious/inflammatory processes. 2, 4
• Pulmonary embolism is a critical diagnosis not to miss, especially in patients with reduced mobility or recent hospitalization. 2, 4
• Acute coronary syndrome, particularly in patients with coexisting cardiovascular disease, can precipitate acute respiratory decompensation. 2, 4
• Atrial fibrillation may precipitate acute respiratory symptoms. 2, 4
• Systemic arterial hypertension can contribute to exacerbation events. 2

Other Pulmonary Causes

• Pneumonia, particularly bacterial superinfection following viral infection, is common and changes management. 2, 4
• Pneumothorax, particularly in patients with bullous emphysema, can present as acute worsening. 2, 4
• Lung cancer may present with new or worsening respiratory symptoms. 2, 4

Pathophysiological Mechanisms

• Exacerbations are characterized by increased airway inflammation, greater mucus production, marked gas trapping, increased cough and wheeze, and increased sputum purulence and volume. 1, 2
• The acute inflammation caused by infections or pollutants is almost always associated with systemic inflammation, which may cause acute respiratory symptoms through decompensation of concomitant chronic diseases. 3

Risk Factors for Exacerbations

• History of previous exacerbations (≥1 moderate or severe exacerbation in the previous year) is a strong predictor of future events. 1
• Severe airflow limitation (FEV1 <33% predicted) increases exacerbation risk. 5
• Presence of bronchiectasis increases susceptibility. 5
• Chronic bronchitis phenotype is associated with increased exacerbation frequency. 1
• Non-adherence to maintenance therapy increases risk. 6

Common Diagnostic Pitfall

Do not assume all acute respiratory worsening in COPD patients represents a simple COPD exacerbation—comorbidities are common and can cause identical symptoms. 2, 4 Chest radiography is mandatory to exclude pneumonia, pneumothorax, pulmonary edema, and lung cancer. 2, 4 ECG and cardiac biomarkers are necessary when acute coronary syndrome or heart failure is suspected. 4 BNP/NT-proBNP is the most useful initial test to differentiate between heart failure and COPD exacerbation in patients with both conditions. 4