Emphysema and Bronchitis

Overview - Overlap in COPD

EMPHYSEMA

Four Types of Emphysema

1. Centriacinar (Centrilobular) Emphysema

• Most common type - constitutes >95% of clinically significant cases
• The central/proximal parts of the acinus (respiratory bronchioles) are destroyed; distal alveoli are spared
• Both emphysematous and normal airspaces coexist within the same acinus
• Distribution: upper lobes, especially apical segments
• Association: heavy cigarette smokers; commonly accompanied by chronic bronchitis
• In advanced disease, distal acinus also becomes involved, making it difficult to distinguish from panacinar emphysema

2. Panacinar (Panlobular) Emphysema

• Acini are uniformly enlarged from the respiratory bronchiole all the way to the terminal blind alveoli - the entire acinus is affected
• Distribution: lower lung zones and anterior lung margins; worst at the bases
• Association: alpha-1 antitrypsin (α1-AT) deficiency - exacerbated by smoking
• Less common than centriacinar emphysema

3. Distal Acinar (Paraseptal) Emphysema

• The proximal acinus is normal; the distal part (alveolar ducts and alveolar sacs) is predominantly involved
• Located near the pleura, along lobular connective tissue septa, and at margins of lobules adjacent to areas of fibrosis or atelectasis
• More severe in the upper half of the lungs
• Characteristically forms enlarged air spaces (0.5 mm to >2 cm), sometimes progressing to bullae
• Cause unknown; comes to attention most often in young adults who present with spontaneous pneumothorax

4. Irregular Emphysema

• Acinus is irregularly involved, almost invariably associated with scarring (e.g., post-inflammatory or post-traumatic fibrosis)
• Clinically the least significant type - generally asymptomatic
• The most common form found at autopsy when carefully examined

Key point: Only centriacinar and panacinar emphysema cause clinically significant airflow obstruction and are associated with COPD.

Histopathology of Emphysema

Pathogenesis of Emphysema

• Cigarette smoke recruits neutrophils and macrophages into the lung, which release elastase and other proteases
• These degrade the elastin matrix of alveolar walls
• Normally, α1-antitrypsin (produced by the liver) inhibits elastase - when α1-AT is deficient (or inactivated by smoking), unchecked protease activity destroys alveolar walls
• Oxidative stress from smoking also directly damages lung tissue and inactivates antiproteases

BRONCHITIS

Types

Acute Bronchitis

• Acute inflammation of the bronchi, usually due to viral infection (rhinovirus, adenovirus, influenza)
• Self-limiting; presents with cough, mucoid sputum, low-grade fever
• Resolves in 1-3 weeks; not associated with COPD
• Antibiotics are generally not indicated unless secondary bacterial infection is confirmed

Chronic Bronchitis

• Defined clinically (not anatomically): persistent productive cough for at least 3 consecutive months in at least 2 consecutive years, in the absence of any other identifiable cause
• Common in cigarette smokers and urban dwellers in heavily polluted cities

Pathogenesis

1. Mucus hypersecretion - the earliest and most characteristic feature
   • Enlargement of submucosal mucous glands in trachea and large bronchi
   • Increase in goblet cells in small airways
   • Driven by inflammatory mediators (histamine, IL-13) and acquired CFTR dysfunction from smoking (producing dehydrated, abnormal mucus)
2. Inflammation - neutrophils, lymphocytes, and macrophages infiltrate the airways; eosinophils are NOT seen (unlike asthma)
3. Infection - does not initiate chronic bronchitis, but maintains it and triggers acute exacerbations

Morphology

• Hyperemia, swelling, and edema of bronchial mucosa
• Heavy mucinous or mucopurulent secretions filling bronchi
• Enlargement of submucosal mucous glands - the hallmark finding
• Reid index (ratio of mucous gland thickness to bronchial wall thickness between epithelium and cartilage) is normally ≤0.4; elevated in chronic bronchitis, proportional to disease severity
• Goblet cell hyperplasia, smooth muscle hypertrophy, peribronchial fibrosis
• In severe cases: bronchiolitis obliterans (complete obliteration of bronchiolar lumen by fibrosis)

Consequences

• Small airway disease (chronic bronchiolitis) is the primary cause of airflow obstruction - NOT the large-airway mucus hypersecretion
• Progressive: can lead to hypoxemia, pulmonary hypertension, and cor pulmonale
• Some patients with chronic bronchitis develop asthmatic bronchitis (with bronchospasm and wheezing due to airway hyperresponsiveness)
• Chronic bronchitis frequently coexists with centriacinar emphysema in heavy smokers

Comparison Summary