Chronic Obstructive Pulmonary Disease (COPD)

Definition

The COPD Spectrum

Schematic overlap between chronic obstructive lung diseases - Robbins Basic Pathology

Epidemiology

• Affects >10% of U.S. adults over age 40; global prevalence ~175 million
• Third leading cause of death worldwide, responsible for ~3.2 million deaths/year
• Annual U.S. costs estimated at $50 billion (~$30B direct, ~20B indirect)
• 35-50% of heavy smokers develop COPD; ~80% of COPD is attributable to smoking
• Women appear more susceptible than men
• Robbins Basic Pathology, p. 447; Goldman-Cecil Medicine, p. 890

Risk Factors

Pathology

Emphysema Patterns

1. Centriacinar (centrilobular) - most common; involves central/proximal acini while distal alveoli are spared; upper-lobe predominant; caused by cigarette smoking (~20x more common than panacinar)
2. Panacinar (panlobular) - uniform enlargement from respiratory bronchiole to terminal alveoli; lower-lobe predominant; associated with AAT deficiency
3. Distal acinar (paraseptal) - affects acini distal to the respiratory bronchiole, near pleura; causes bullae; presents as spontaneous pneumothorax in young adults
4. Irregular - associated with scarring; usually clinically insignificant

Chronic Bronchitis Pathology

• Hypersecretion of mucus from enlarged Reid index (ratio of mucous gland to bronchial wall thickness) >0.4
• Goblet cell hyperplasia, squamous metaplasia, airway inflammation

Pathogenesis

Pathogenesis of emphysema - Robbins Basic Pathology

1. Inflammatory cells and mediators - neutrophils, macrophages, CD4+/CD8+ T cells release LTB4, IL-8, TNF-alpha
2. Protease-antiprotease imbalance - elastases (MMP, neutrophil elastase) exceed antiproteases (AAT), leading to connective tissue breakdown
3. Oxidative stress - reactive oxygen species from cigarette smoke and activated inflammatory cells cause increased apoptosis and cellular senescence

• Robbins Basic Pathology, p. 448

Clinical Features

Symptoms (progressive over years)

• Dyspnea on exertion (earliest complaint) progressing to rest
• Chronic productive cough (bronchitis component)
• Wheezing, chest tightness
• In advanced disease: breathlessness with basic ADLs

Physical Examination

• Early: often normal
• Later: prolonged expiratory phase, expiratory wheezing
• Hyperinflation signs: barrel chest, poor diaphragmatic excursion, hyperresonance
• Severe: accessory muscle use (sternocleidomastoid, scalenes), "tripod" posture, cyanosis
• Advanced: cachexia, weight loss (elevated TNF-alpha), cor pulmonale (right heart failure), peripheral edema

Important: Clubbing is NOT a feature of COPD - its presence should prompt evaluation for lung cancer or other causes. - Harrison's, p. 2298

"Pink Puffer" vs "Blue Bloater"

Diagnosis

Spirometry (mandatory)

• Post-bronchodilator FEV1/FVC < 0.70 confirms airflow obstruction
• GOLD spirometric grading (based on FEV1 % predicted):

Other investigations

• ABG: resting or exertional hypoxemia; hypercarbia in severe disease
• Chest X-ray: hyperinflation, flat diaphragms, increased AP diameter, bullae; ~25% show abnormalities during exacerbations (pneumonia, CHF, pneumothorax)
• CT chest: better assessment of emphysema distribution; detects pulmonary artery enlargement (predictor of exacerbations)
• DLCO: reduced in emphysema (reflects parenchymal destruction)
• Alpha-1 antitrypsin level: screen all patients with COPD, especially age <45 or minimal smoking history

Multidimensional Assessment

• mMRC dyspnea scale (0-4)
• CAT score (COPD Assessment Test, 0-40)

GOLD ABE Classification (2024 Updated)

Pharmacological Management

Bronchodilators (cornerstone of therapy)

• Albuterol (salbutamol), levalbuterol - PRN relief
• Available as MDI, DPI, nebulizer solution

• Ipratropium - also available combined with albuterol (soft mist inhaler)

• Salmeterol, formoterol, indacaterol - twice daily or once daily
• Never used as monotherapy in COPD (unlike asthma concerns)

• Tiotropium (gold standard LAMA), umeclidinium, aclidinium, glycopyrronium
• Reduce exacerbations, improve exercise tolerance, slow decline in FEV1

• Preferred in symptomatic patients and high-risk; greater efficacy than either alone

Inhaled Corticosteroids (ICS)

• Never used alone in COPD (unlike asthma) - used only as add-on to bronchodilators
• Indicated when eosinophil count ≥300/µL
• Reduce exacerbation frequency in selected patients
• Side effects: pneumonia risk, oral candidiasis, osteoporosis - Harrison's, p. 2299

Other Pharmacotherapy

• For severe COPD + chronic bronchitis + frequent exacerbations
• Modest benefit on airflow; side effects: nausea, diarrhea, weight loss

• Reduces exacerbation frequency in patients with recent exacerbation history
• Most effective in older, former smokers with milder COPD
• Risks: hearing loss, macrolide resistance; avoid with prolonged QTc

Non-Pharmacological

• Smoking cessation - single most effective intervention; slows FEV1 decline
• Pulmonary rehabilitation - improves exercise capacity and quality of life
• Influenza and pneumococcal vaccination - reduce exacerbations and hospitalizations
• LTOT (Long-term oxygen therapy) - resting SpO2 ≤88% (or ≤89% with cor pulmonale, polycythemia, PH); proven mortality benefit; must be used ≥15-18 hours/day
• Lung volume reduction surgery / bronchoscopic procedures - selected patients with upper-lobe predominant emphysema and low exercise capacity
• Lung transplantation - for very severe disease refractory to all other therapy

COPD Exacerbations

Precipitants

• Viral infections (rhinovirus, influenza) - cause >50% of exacerbations by PCR studies
• Bacterial infections (new strain acquisition)
• Air pollution, allergens, pulmonary embolism (incidence elevated in COPD), medication non-adherence

Assessment in Exacerbation

• Quantify change in dyspnea, sputum character, fever, wheezing
• Pulse oximetry; ABG if severe COPD, hypercarbia suspected, altered mental status
• CXR/CT: ~25% abnormal (pneumonia, CHF, pneumothorax)
• Spirometry is NOT helpful during exacerbations (unlike asthma)

Indications for Hospitalization

• Respiratory acidosis + hypercarbia (PaCO2 >45 mmHg)
• New or worsening hypoxemia
• Severe underlying COPD
• Significant comorbidities (CHF)
• Inability to manage at home

Treatment of Exacerbations

• Harrison's Principles of Internal Medicine 22E, p. 2302

Comorbidities

• Cardiovascular disease (most common cause of death in mild-moderate COPD)
• Lung cancer (shared risk factors; new clubbing in COPD should prompt workup)
• OSA-COPD overlap syndrome - higher risk of hypercapnia, hypoxemia, PH; diagnosed with sleep study (PSG preferred over HSAT in moderate-severe COPD)
• Osteoporosis, depression, anxiety, GERD
• Pulmonary hypertension and cor pulmonale (late complication; supplemental O2 is key treatment)

Prognosis

• Low FEV1, severe dyspnea (mMRC ≥3)
• Low 6-minute walk distance
• Low BMI / cachexia
• Frequent exacerbations
• Hypercapnia at rest
• Cor pulmonale / pulmonary hypertension