Emphysema Pathophysiology and Management
Emphysema is fundamentally characterized by permanent destructive enlargement of air spaces, destruction of alveolar walls, and loss of pulmonary elastic recoil, resulting in increased lung compliance, air trapping, and impaired gas exchange. 1
Pathophysiological Characteristics
Structural Changes
- Destruction of alveolar walls and supporting tissue 1, 2
- Enlargement of alveolar airspaces 3
- Loss of elastic recoil in lung tissue 1
- Reduction of total lung gas exchange area 3
Mechanical Consequences
- Increased lung compliance (lungs become more distensible) 1
- Hyperinflation with increased residual volume (RV) and total lung capacity (TLC) 1
- Air trapping due to collapse of small airways during expiration 1
- Increased work of breathing despite higher compliance due to mechanical inefficiency 1
- Dynamic hyperinflation during exercise 1
- Diaphragmatic flattening, leading to reduced pressure-generating capacity 1
Pulmonary Function Abnormalities
- Obstructive pattern with reduced FEV1 and FEV1/FVC ratio <70% 1
- Increased TLC, RV, and functional residual capacity (FRC) 1
- Markedly decreased diffusing capacity (DLCO) 1
- Reduced expiratory flow rates 1
Molecular and Cellular Mechanisms
Key Pathogenic Processes
- Protease/antiprotease imbalance leading to excessive tissue destruction 4, 5
- Increased oxidative stress damaging lung structures 4
- Impaired repair mechanisms of lung tissue 4, 5
- Alveolar epithelial cell injury and apoptosis 6, 5
- Dysfunction of mesenchymal cells critical for wound repair 6
- Cellular senescence contributing to failed tissue repair 5
Subtypes of Emphysema
- Centriacinar (Centrilobular) Emphysema: Predominantly affects respiratory bronchioles
- Panacinar Emphysema: Uniform destruction throughout the acinus
- Paraseptal Emphysema: Predominantly affects distal airway structures 1
Diagnostic Approach
Pulmonary Function Testing
- Spirometry showing FEV1 <80% predicted and FEV1/VC ratio <70% 1
- Measurement of static lung volumes showing increased TLC and RV 1
- Assessment of diffusing capacity (DLCO) which is typically reduced 1
Imaging
- CT scanning is more sensitive than plain radiography for detecting emphysema 1
- Chest radiography may show flattened diaphragm but is not reliable for mild disease 1
Management Options
Bronchoscopic and Surgical Interventions
- Lung volume reduction surgery (LVRS) can improve pulmonary function and exercise capacity in selected patients 2
- Endobronchial valves may provide benefits comparable to LVRS in appropriate candidates 2
- Endobronchial coils may benefit patients with severe hyperinflation and less parenchymal destruction 2
- Vapor thermal ablation and sclerosant agents are alternative approaches but have limitations due to unpredictable inflammatory responses 2
Pharmacological Approaches
- Current pharmacological treatments have limited effects, particularly in emphysematous COPD 2, 4
- Emerging therapeutic targets include:
Clinical Considerations and Pitfalls
- CT lung density measurement is the most sensitive endpoint for monitoring disease progression, followed by DLCO, FEV1, and RV 3
- Understanding the specific emphysema subtype is crucial for predicting disease progression and determining appropriate management strategies 1
- Emphysema should be recognized as a distinct clinical entity rather than simply as a COPD phenotype 4
- Disease progression is marked by declining FEV1 and vital capacity, increasing residual volume, and worsening ventilation-perfusion inequality 1
- Alpha-1 antitrypsin deficiency should be considered as a genetic cause of emphysema, especially in younger patients or those with minimal smoking history 4