Chronic Obstructive Pulmonary Disease (COPD)

Definition & Epidemiology

Forms of COPD

1. Emphysema

• Defined by enlargement of air spaces distal to terminal bronchioles, caused by destruction of elastic support structures by proteases (particularly from neutrophils).
• Subtypes:
  • Centriacinar (most common): smoking-related; affects respiratory bronchioles
  • Panacinar: seen in alpha-1 antitrypsin (AAT) deficiency; affects entire acinus
• Classic presentation: increased chest volume ("barrel chest"), dyspnea, relatively normal blood oxygenation at rest - "pink puffer"
• Increased lung compliance and static lung hyperinflation

2. Chronic Bronchitis

• Defined clinically: persistent productive cough for at least 3 consecutive months in at least 2 consecutive years.
• Caused by mucus overproduction from hyperplasia of tracheal/large airway mucous glands AND small airway inflammation (chronic bronchiolitis).
• Histology: enlargement of mucus-secreting glands, goblet cell metaplasia, inflammation, bronchiolar wall fibrosis.
• Patients develop hypoxemia and hypercapnia - "blue bloater"
• Robbins & Kumar Basic Pathology

Pathogenesis

• Mucus dysfunction: Cigarette smoke causes MUC5AC concentration to increase ~10-fold and MUC5B ~3-fold in severe COPD. Mucus hyperconcentration leads to failure of mucociliary transport and adhesion to airway surfaces.
• Ciliary damage: Structural and functional changes in ciliated cells from cigarette smoke exposure.
• Airway obstruction: Small airway mucus occlusion correlates with degree of airflow obstruction even in emphysematous phenotypes.
• Impaired mucociliary clearance leads to persistent infection, particularly with Haemophilus influenzae.
• Fishman's Pulmonary Diseases and Disorders

Pathophysiology

Clinical Features

• Dyspnea (progressive, worse on exertion)
• Chronic cough with sputum production
• Barrel chest (air trapping, increased AP diameter)
• Wheezing and prolonged expiration
• Cyanosis (in severe/bronchitic type)
• Cor pulmonale in advanced disease (right heart failure from pulmonary hypertension)
• Reduced breath sounds, hyperresonance on percussion
• Use of accessory muscles of breathing

Diagnosis

• Spirometry (gold standard): Post-bronchodilator FEV1/FVC < 0.70
• GOLD Staging based on FEV1 (% predicted):
  • GOLD 1: Mild (FEV1 ≥ 80%)
  • GOLD 2: Moderate (50-79%)
  • GOLD 3: Severe (30-49%)
  • GOLD 4: Very Severe (<30%)
• Chest X-ray: hyperinflation, flattened diaphragms, increased AP diameter
• CT scan: detects emphysema and small airway disease
• ABG: assess oxygenation and ventilation in moderate-severe disease
• Alpha-1 antitrypsin level: screen patients <45 years or minimal smoking history

Management

Non-Pharmacologic

• Smoking cessation - the single most important intervention to slow disease progression
• Pulmonary rehabilitation: improves exercise tolerance and quality of life
• Long-term oxygen therapy (LTOT): indicated when resting PaO2 ≤55 mmHg (or ≤59 with cor pulmonale/polycythemia); one of the few treatments proven to improve mortality
• Influenza and pneumococcal vaccines
• Nutritional support; treat comorbidities (especially cardiovascular disease)

Pharmacologic Treatment

• High eosinophils (≥300 cells/µL): likely to benefit from ICS
• Low eosinophils (<100 cells/µL): minimal benefit, avoid ICS
• ICS use is associated with increased risk of bacterial pneumonia

• Roflumilast (PDE4 inhibitor): reduces exacerbation frequency in severe COPD with chronic bronchitis phenotype (FEV1 <50%, frequent exacerbations)
• Azithromycin (long-term, low-dose): reduces exacerbations, especially in ex-smokers
• Theophylline: largely fallen out of favor - recent RCT showed no benefit on exacerbation frequency
• Katzung's Basic and Clinical Pharmacology

COPD Exacerbations (AECOPD)

• Increased/intensified bronchodilators (SABA ± SAMA)
• Systemic corticosteroids: 5-day course (prednisone 40 mg/day)
• Antibiotics: routinely used (unlike asthma exacerbations) because bacterial infection frequently involved. Common pathogens: H. influenzae, Streptococcus pneumoniae, Moraxella catarrhalis. Agents: beta-lactams, doxycycline, azithromycin
• Controlled oxygen: target SpO2 88-92% (avoid over-oxygenation which can worsen hypercapnia)
• NIV (BiPAP): for hypercapnic respiratory failure (PaCO2 >45 mmHg with respiratory acidosis, pH <7.35)
• ICU and invasive ventilation for severe/refractory cases

Complications

• Cor pulmonale: pulmonary hypertension → right ventricular hypertrophy → right heart failure
• Secondary polycythemia: compensatory erythrocytosis from chronic hypoxemia
• Respiratory failure: hypoxic or hypercapnic
• Pneumothorax: bullae rupture
• Lung cancer: increased risk due to shared smoking etiology

Recent Evidence (PubMed 2024-2025)

Key Distinguishing Points: COPD vs Asthma