Case 7.3 – COPD

Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable and treatable disease that is characterised by persistent respiratory symptoms and airflow limitation.

Key Features:

• The airflow limitation is due to airway and/or alveolar abnormalities
• Usually caused by significant exposure to noxious particles or gases
• The most common respiratory symptoms include dyspnoea, cough and/or sputum production
• These symptoms may be under-reported by patients

Pathophysiology:

• COPD encompasses two main conditions:
  • Chronic Bronchitis: Clinically defined as chronic productive cough for 3 months in each of 2 successive years (when other causes of chronic cough have been excluded)
  • Emphysema: Pathologically defined as permanent destructive enlargement of the air spaces distal to the terminal bronchioles
• Most patients have features of both conditions
• Characterised by chronic inflammation throughout the airways, parenchyma, and pulmonary vasculature

Risk Factors:

• Cigarette smoking: The most important risk factor (accounts for 80-90% of COPD)
• Occupational exposures: Dust, chemicals, and fumes
• Indoor air pollution: Biomass fuel used for cooking and heating in poorly ventilated dwellings
• Outdoor air pollution: Though less important than smoking
• Genetic factors: Alpha-1 antitrypsin deficiency (rare)
• Age: Usually develops in middle age
• Childhood factors: Low birth weight, respiratory infections

Natural History:

• Progressive disease that worsens over time
• Rate of decline accelerated by continued smoking
• Punctuated by exacerbations
• Associated with significant comorbidity

The modified Medical Research Council (mMRC) dyspnoea scale is a simple and validated tool used to assess the degree of breathlessness related to activities.

Modified MRC Dyspnoea Scale:

• Grade 0: I only get breathless with strenuous exercise
• Grade 1: I get short of breath when hurrying on level ground or walking up a slight hill
• Grade 2: On level ground, I walk slower than people of the same age because of breathlessness, or I have to stop for breath when walking at my own pace
• Grade 3: I stop for breath after walking about 100 metres or after a few minutes on level ground
• Grade 4: I am too breathless to leave the house or I am breathless when dressing

Clinical Utility:

• Simple and quick to administer
• Correlates well with other measures of health status
• Predicts mortality in COPD
• Used in conjunction with spirometry and exacerbation history to guide treatment
• Grades 0-1 usually indicate mild symptoms
• Grades 2-4 indicate more significant symptoms requiring more intensive treatment

In This Case:

Min Lai scores a 3 on the mMRC scale, meaning she stops for breath after walking about 100 metres or after a few minutes on level ground. This indicates significant breathlessness affecting her daily activities and suggests moderate to severe COPD.

Further History:

Respiratory History:

• Smoking history: Quantify in pack-years (packs per day × years smoked)
• Cough: Duration, frequency, character, productive vs dry
• Sputum: Volume, colour, consistency, haemoptysis
• Breathlessness: Onset, progression, precipitating factors, exercise tolerance
• Wheeze: Frequency, triggers
• Chest tightness
• Exacerbations: Frequency, severity, hospitalisations, need for ventilation
• Diurnal variation: Symptoms worse at particular times of day

Occupational and Environmental History:

• Occupational exposures to dust, fumes, chemicals
• Exposure to biomass fuels
• Passive smoking exposure

Past Medical History:

• Childhood respiratory problems, asthma
• Previous tuberculosis or other lung disease
• Cardiovascular disease
• Osteoporosis
• Depression and anxiety

Family History:

• COPD in family members
• Alpha-1 antitrypsin deficiency
• Other respiratory diseases

Impact on Daily Life:

• Ability to perform activities of daily living
• Sleep disturbance
• Impact on work
• Psychological impact (anxiety, depression)
• Social isolation

Physical Examination:

General Inspection:

• Respiratory distress, use of accessory muscles
• Pursed-lip breathing
• Barrel-shaped chest (hyperinflation)
• Cachexia (advanced disease)
• Peripheral oedema (cor pulmonale)
• Cyanosis
• Nicotine staining of fingers

Respiratory Examination:

• Inspection: Increased AP diameter, reduced chest expansion
• Palpation: Reduced chest expansion, decreased tactile fremitus
• Percussion: Hyperresonance (emphysema)
• Auscultation:
  • Decreased breath sounds
  • Prolonged expiratory phase
  • Wheeze (particularly on expiration or forced expiration)
  • Coarse crackles (if bronchitis predominant)

Cardiovascular Examination:

• Signs of cor pulmonale: elevated JVP, right ventricular heave, loud P2, tricuspid regurgitation
• Peripheral oedema

Other:

• BMI (cachexia or obesity)
• Oxygen saturation
• Blood pressure, heart rate, respiratory rate

Note: In early COPD, physical examination may be normal. Examination findings become more apparent as disease progresses.

Essential Investigations:

1. Spirometry (Mandatory for Diagnosis):

• Confirms the presence of airflow limitation
• Diagnostic criteria: Post-bronchodilator FEV₁/FVC < 0.70 confirms persistent airflow limitation
• Severity assessment: Based on FEV₁ % predicted:
  • GOLD 1 (Mild): FEV₁ ≥ 80% predicted
  • GOLD 2 (Moderate): 50% ≤ FEV₁ < 80% predicted
  • GOLD 3 (Severe): 30% ≤ FEV₁ < 50% predicted
  • GOLD 4 (Very Severe): FEV₁ < 30% predicted
• Should be performed when patient is clinically stable
• Unlike asthma, shows limited reversibility to bronchodilators

2. Chest X-ray:

• Usually normal in mild to moderate COPD
• May show hyperinflation (flattened hemidiaphragms, increased retrosternal space)
• Bullae (large air spaces)
• Attenuated peripheral vascular markings
• Useful to exclude alternative diagnoses (lung cancer, tuberculosis, pulmonary fibrosis)
• May show complications (pneumothorax, pneumonia)

3. Pulse Oximetry:

• Assess oxygenation
• If SpO₂ < 92%, perform arterial blood gas

Additional Investigations (Selected Cases):

4. Arterial Blood Gas:

• Indicated if: FEV₁ < 50% predicted, SpO₂ < 92%, signs of respiratory failure or cor pulmonale
• Assesses hypoxemia and hypercapnia
• Guides need for long-term oxygen therapy

5. Full Blood Count:

• Exclude anaemia (worsens breathlessness)
• Polycythaemia (chronic hypoxia)
• Raised eosinophils may indicate asthma-COPD overlap or predict response to ICS

6. Alpha-1 Antitrypsin Level:

• If COPD develops at young age (< 45 years)
• Minimal smoking history
• Family history of early-onset COPD or liver disease
• Lower lobe predominant emphysema

7. CT Chest (High Resolution):

• Not routinely required for diagnosis
• Useful if considering surgical interventions (bullectomy, lung volume reduction surgery)
• Suspected bronchiectasis or interstitial lung disease
• Investigation of haemoptysis or weight loss (exclude malignancy)
• Can quantify emphysema distribution and severity

8. Sputum Culture:

• During acute exacerbations
• If recurrent infections
• Exclude tuberculosis in high-risk patients

9. ECG and Echocardiography:

• If suspected cor pulmonale or coexistent heart disease
• ECG may show: right axis deviation, right ventricular hypertrophy, P pulmonale, right bundle branch block
• Echo assesses right ventricular function and pulmonary hypertension

10. Exercise Tests:

• 6-minute walk test: Simple assessment of functional capacity
• Cardiopulmonary exercise testing: Detailed assessment in selected patients
• Useful for assessing disability, prognosis, and response to interventions

Assessment of Symptom Burden:

• CAT (COPD Assessment Test): Validated questionnaire to quantify impact of COPD
• mMRC dyspnoea scale

The pathophysiology of COPD involves chronic inflammation, structural changes, and progressive airflow limitation.

1. Chronic Inflammation:

• Trigger: Inhalation of noxious particles and gases (primarily cigarette smoke)
• Inflammatory response:
  • Abnormal inflammatory response in genetically susceptible individuals
  • Involves neutrophils, macrophages, and CD8+ T lymphocytes
  • Release of inflammatory mediators (cytokines, chemokines)
  • Protease-antiprotease imbalance
  • Oxidative stress
• Inflammation affects the entire respiratory system: airways, parenchyma, and pulmonary vasculature
• Inflammation persists even after smoking cessation

2. Airway Changes (Chronic Bronchitis Component):

• Large airways (central airways):
  • Mucous gland hyperplasia and goblet cell metaplasia
  • Increased mucus production
  • Ciliary dysfunction
  • Chronic productive cough
• Small airways (< 2mm diameter):
  • Primary site of airflow obstruction
  • Airway wall thickening due to inflammation and fibrosis
  • Smooth muscle hypertrophy
  • Mucus plugging
  • Loss of alveolar attachments (reduced elastic recoil)
  • Progressive narrowing and obliteration

3. Parenchymal Changes (Emphysema Component):

• Alveolar destruction:
  • Permanent enlargement of airspaces distal to terminal bronchioles
  • Destruction of alveolar walls without obvious fibrosis
  • Loss of elastic recoil
• Types of emphysema:
  • Centrilobular: Affects respiratory bronchioles, upper lobes, smoking-related
  • Panlobular: Affects entire acinus, lower lobes, alpha-1 antitrypsin deficiency
  • Paraseptal: Distal acinus, subpleural, associated with spontaneous pneumothorax
• Mechanisms:
  • Protease-antiprotease imbalance (excess proteases destroy elastin)
  • Apoptosis of alveolar cells
  • Loss of capillary bed

4. Vascular Changes:

• Thickening of vessel walls (intimal hyperplasia, smooth muscle hypertrophy)
• Loss of capillaries in alveolar walls
• Endothelial dysfunction
• Results in pulmonary hypertension in advanced disease

5. Consequences of Pathological Changes:

• Airflow limitation:
  • Small airway narrowing and obliteration (major component)
  • Loss of elastic recoil (emphysema)
  • Increased airway resistance
  • Predominantly affects expiration
• Gas trapping and hyperinflation:
  • Incomplete expiration
  • Dynamic hyperinflation (worsens during exercise)
  • Increased work of breathing
  • Flattened diaphragm with reduced mechanical efficiency
• Gas exchange abnormalities:
  • Ventilation-perfusion (V/Q) mismatch
  • Hypoxemia
  • Hypercapnia (in advanced disease)
• Mucus hypersecretion:
  • Chronic productive cough
  • Predisposition to infection
• Pulmonary hypertension and cor pulmonale:
  • Vascular changes
  • Hypoxic vasoconstriction
  • Loss of capillary bed
  • Right ventricular dysfunction

6. Systemic Effects:

• Weight loss and cachexia
• Skeletal muscle dysfunction
• Osteoporosis
• Cardiovascular disease
• Depression and anxiety
• Increased risk of lung cancer

The pathological changes in COPD are largely irreversible, but progression can be slowed (particularly by smoking cessation) and symptoms can be managed with appropriate therapy.

Management of stable COPD aims to reduce symptoms, decrease frequency and severity of exacerbations, and improve exercise tolerance and health status.

1. Non-Pharmacological Management:

Smoking Cessation:

• THE MOST IMPORTANT INTERVENTION
• Only intervention proven to slow decline in lung function
• Offer support, counselling, and pharmacotherapy (nicotine replacement, varenicline, bupropion)
• Should be addressed at every clinical encounter

Pulmonary Rehabilitation:

• Comprehensive program including exercise training, education, and behavioural change
• Improves dyspnoea, exercise capacity, and quality of life
• Reduces hospitalizations
• Indicated for patients with mMRC ≥ 1 or symptomatic patients

Vaccinations:

• Influenza vaccine: Annually
• Pneumococcal vaccine: Once, with revaccination after 5 years in high-risk patients
• COVID-19 vaccine: As per current guidelines

Nutrition:

• Nutritional support for patients who are underweight
• Weight reduction for obese patients

2. Pharmacological Management (Stepwise Approach):

Initial Treatment (All Patients):

• Short-acting bronchodilators (as needed):
  • Short-acting β2-agonist (SABA): Salbutamol
  • Short-acting muscarinic antagonist (SAMA): Ipratropium
  • Use as needed for symptom relief

Further Treatment Based on GOLD Classification:

Treatment escalation depends on symptom burden (mMRC or CAT score) and exacerbation history.

Group B (More Symptoms, Few Exacerbations):

• Long-acting bronchodilator monotherapy:
  • LABA (e.g., salmeterol, formoterol) OR
  • LAMA (e.g., tiotropium, glycopyrronium)
• LAMA may be preferred as first choice

If inadequate control:

• Dual long-acting bronchodilator therapy (LABA + LAMA)
• More effective than monotherapy for symptoms and lung function
• Examples: Umeclidinium/vilanterol, tiotropium/olodaterol

Group E (Frequent Exacerbations):

• LAMA monotherapy (preferred initial treatment)
• More effective than LABA at preventing exacerbations

If further exacerbations:

• LABA + LAMA

If still having exacerbations on LABA + LAMA:

• Consider blood eosinophil count:
  • Eosinophils ≥ 300 cells/μL: Add ICS (triple therapy: LABA + LAMA + ICS)
  • Eosinophils < 300 cells/μL: Continue LABA + LAMA, consider alternative approaches
• Triple therapy examples: Fluticasone furoate/umeclidinium/vilanterol

Additional Therapies:

• Chronic oral corticosteroids: NOT recommended due to significant side effects
• Oral theophylline: May be considered if inadequate response to other bronchodilators; narrow therapeutic window
• Oral phosphodiesterase-4 inhibitor (roflumilast): In severe COPD with chronic bronchitis and frequent exacerbations despite triple therapy
• Mucolytics: Limited evidence; may reduce exacerbations in selected patients not on ICS
• Prophylactic antibiotics (azithromycin): May reduce exacerbations in selected patients with frequent exacerbations

3. Oxygen Therapy:

• Long-term oxygen therapy (LTOT):
  • Indicated if: PaO₂ ≤ 7.3 kPa (55 mmHg) OR PaO₂ 7.3-8.0 kPa (55-60 mmHg) with evidence of cor pulmonale or polycythaemia
  • Must be used for ≥ 15 hours per day to improve survival
  • Assess when patient is stable (at least 4 weeks after exacerbation)
  • Repeat assessment after 3 months
• Ambulatory oxygen: For patients who desaturate on exercise

4. Surgical and Interventional Approaches:

• Lung volume reduction surgery: Selected patients with upper lobe predominant emphysema
• Bullectomy: If large bulla compressing surrounding lung
• Lung transplantation: Highly selected patients with very severe COPD
• Endobronchial valves: In selected patients with severe emphysema

5. Management of Comorbidities:

• Cardiovascular disease
• Osteoporosis
• Depression and anxiety
• Gastroesophageal reflux
• Lung cancer screening in high-risk patients

6. Monitoring and Follow-up:

• Regular review of symptoms, exacerbation frequency
• Spirometry annually or when clinically indicated
• Assess inhaler technique at every visit
• Reinforce smoking cessation
• Address patient concerns and optimize self-management