Obstructive Lung Disorders

• Module 4 covers fully integrated responses to learning objectives on obstructive pulmonary diseases

COPD Risk Factors

• Tobacco smoking is the primary risk factor in high-income countries
• Occupational exposure to dust, vapors, fumes, and chemicals is a risk factor
• Indoor air pollution from biomass fuels is a risk factor
• Outdoor air pollution is a risk factor
• Recurrent respiratory infections are a risk factor
• Aging increases the risk
• α1-antitrypsin deficiency is a rare genetic cause of early-onset emphysema

COPD Pathophysiology

• COPD is a progressive, inflammatory lung disease characterized by persistent airflow limitation
• COPD involves chronic bronchitis and emphysema, which often overlap
• Key features include airflow limitation, ventilation/perfusion mismatch leading to hypoxia and hypercapnia, loss of lung elasticity, and increased airway resistance
• These features lead to increased work of breathing, dyspnea, and eventually cor pulmonale

Emphysema Pathophysiology

• Destruction of alveolar walls leads to permanent enlargement of gas-exchange airways
• Loss of elastic recoil leads to airway collapse during expiration and air trapping
• Protease-antiprotease imbalance results in increased enzyme activity from neutrophils/macrophages, which destroy elastin
• Reduced surface area for gas exchange leads to hypoxemia
• Can lead to CO₂ retention and respiratory acidosis

Chronic Bronchitis Pathophysiology

• Hpersecretion of mucus and chronic productive cough occur for ≥3 months/year for 2+ years
• Inspired irritants such as smoke can lead to chronic inflammation, goblet cell hyperplasia, and thick mucus
• Impaired ciliary function leads to mucus retention and infection
• Airway narrowing, wall edema, smooth muscle hypertrophy, and fibrosis lead to airflow limitation

COPD Symptoms

• Chronic productive cough
• Shortness of breath (dyspnea)
• Wheezing
• Exercise intolerance
• Barrel chest (in emphysema)
• Pursed-lip breathing and tripod positioning
• Accessory muscle use in advanced cases
• Frequent infections, fatigue, and weight loss in later stages
• Hypoxemia and hypercapnia

Emphysema vs. Chronic Bronchitis

• Emphysema is defined by permanent enlargement and destruction of alveolar walls versus chronic bronchitis involves chronic mucus-producing cough for ≥3 months/year for 2 years
• Emphysema is caused by smoking and α1-antitrypsin deficiency versus chronic bronchitis is caused by to smoking, pollution, and repeated infections
• Emphysema involves Th1, neutrophil & macrophage driven inflammation versus chronic bronchitis involves Th1, macrophage & cytotoxic T cell driven inflammation
• Emphysema has minimal mucus production versus chronic bronchitis has marked increased mucus (goblet cell & gland hyperplasia)
• Emphysema has airflow limitation due to alveolar destruction and decreased elastic recoil versus chronic bronchitis has airflow limitation due to airway narrowing, wall edema, and mucus buildup
• Emphysema symptoms are dyspnea, minimal cough, barrel chest, and pursed-lip breathing versus chronic bronchitis symptoms are productive cough, cyanosis, and frequent infections
• Emphysema features blood gas findings of mild hypoxia early, hypercapnia in late disease versus chronic bronchitis features hypoxia and hypercapnia more commonly early on
• Emphysema has less risk of cor pulmonale versus chronic bronchitis has a higher risk

Asthma Pathophysiology

• Asthma is a chronic inflammatory airway disorder with variable airflow limitation, bronchial hyperresponsiveness, and airway remodeling
• Allergen exposure is processed by antigen-presenting cells (APCs)
• APCs activate Th2 lymphocytes, releasing IL-4, IL-5, and IL-13
• ILs stimulate B cells to produce IgE, which binds to mast cells
• Subsequent allergen exposure leads to mast cell degranulation
• The early phase involves histamine and leukotrienes, leading to bronchoconstriction, mucus secretion, and edema
• The late phase (4-8 hours later) sees eosinophils and neutrophils infiltrate, leading to sustained inflammation and hyperresponsiveness
• Chronic inflammation leads to airway remodeling, including smooth muscle hypertrophy, goblet cell hyperplasia, and subepithelial fibrosis

Asthma Symptoms

• Wheezing
• Dyspnea, especially with exertion
• Chest tightness
• Coughing, especially at night or early morning
• Decreased peak expiratory flow (PEF)
• Symptoms worsen with allergens, infections, exercise, cold air, and irritants
• Severe attacks may show use of accessory muscles and fatigue
• Air trapping, hypercapnia, and hypoxemia
• Risk of respiratory acidosis and failure in extreme cases

Obstructive Respiratory Diseases Summary

• Emphysema Definition: Alveolar wall destruction + airspace enlargement
• Chronic Bronchitis Definition: Productive cough ≥3 mo/year x 2 years
• Asthma Definition: Reversible airway inflammation & bronchoconstriction
• Emphysema Cause: Smoking, α1-antitrypsin deficiency
• Chronic Bronchitis Cause: Smoking, pollution, repeated infections
• Asthma Cause: Allergens, viral infections, irritants, stress
• Emphysema Inflammation Type: Th1 → macrophages & neutrophils
• Chronic Bronchitis Inflammation Type: Th1 → macrophages & cytotoxic T-cells
• Asthma Inflammation Type: Th2 → eosinophils, mast cells, IgE
• Emphysema Mucus: Minimal
• Chronic Bronchitis Mucus: Excessive (thick, chronic)
• Asthma Mucus: Increased (esp. during flare-ups)
• Emphysema Structural Changes: Alveolar wall loss,↓ elasticity, air trapping
• Chronic Bronchitis Structural Changes: Goblet cell hyperplasia, fibrosis, squamous metaplasia
• Asthma Structural Changes: Airway remodeling (SM hypertrophy, fibrosis, ↑ goblet cells)
• Emphysema Airflow Limitation: Due to loss of elastic recoil
• Chronic Bronchitis Airflow Limitation: Due to airway narrowing + mucus
• Asthma Airflow Limitation: Due to bronchospasm + inflammation
• Emphysema Key Symptoms: - Dyspnea- Barrel chest- Pursed-lip breathing
• Chronic Bronchitis Key Symptoms: - Productive cough- Cyanosis- Wheezing
• Asthma Symptoms: - Wheezing- SOB- Cough
• Emphysema Blood Gases: ↓ O₂ (later), ↑ CO₂ (retention) → acidosis
• Chronic Bronchitis Blood Gases: ↓ O₂ + ↑ CO₂ early on
• Asthma Blood Gases: ↓ O₂ (hypoxia), possible ↑ CO₂ in severe attacks
• Emphysema Cor PulmonaleRisk: Less common
• Chronic Bronchitis Cor Pulmonale Risk: More common
• Asthma Cor Pulmonale Risk: Possible if poorly controlled
• Emphysema Reversibility: Irreversible
• Chronic Bronchitis Reversibility: Irreversible
• Asthma Reversibility: Reversible (especially early)
• Emphysema Genetic Link: α1-antitrypsin deficiency
• Chronic Bronchitis Genetic Link: No major known link
• Asthma Genetic Link: Often linked to atopy, allergy, family history