3.2 COPD: Staging, Long-Term Management & Acute Exacerbations

3.2 COPD: Staging, Long-Term Management & Acute Exacerbations

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable lung condition characterized by persistent, usually progressive airflow limitation associated with an enhanced chronic inflammatory response in the airways and lung parenchyma to noxious particles or gases. Tobacco smoking accounts for over 80% of cases in high-income settings, alongside occupational dust and biomass fuel exposures.

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1. Pathophysiology and Clinical Diagnosis

COPD encompasses two distinct but frequently overlapping pathological processes:

1. Chronic Bronchitis: Clinically defined as a daily productive cough for at least 3 consecutive months in 2 successive years. Pathologically, it involves goblet cell hyperplasia, submucosal gland hypertrophy in large bronchi, and ciliary dysfunction.
2. Emphysema: Anatomically defined as abnormal, permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of alveolar walls without gross fibrosis. Centrilobular emphysema primarily affects the upper lung lobes in cigarette smokers, whereas panacinar emphysema affects the lower lung lobes and is classically associated with alpha-1 antitrypsin deficiency.

Clinical Presentation

• Exertional Dyspnoea: Progressive, persistent, and worsening with exercise.
• Chronic Cough: Often productive with clear or white mucoid sputum.
• Physical Signs: Wheezing, tachypnoea, hyperinflated "barrel chest" (increased anteroposterior diameter), pursed-lip breathing, intercostal indrawing, reduced cricosternal distance ($< 3\text{ finger breadths}$), and loss of cardiac dullness.

Diagnostic Spirometry

Diagnosis requires post-bronchodilator spirometry performed 15 minutes after inhaling 400 mcg salbutamol:

• Diagnostic Threshold: $\mathbf{\text{FEV}_1/\text{FVC} < 0.70}$ (a fixed, non-reversible ratio).
• The lack of significant reversibility differentiates COPD from asthma, although a subset of patients exhibits asthma-COPD overlap features.

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2. Severity Staging by Airflow Limitation

Once an obstructive ratio ($\text{FEV}_1/\text{FVC} < 0.70$) is confirmed, disease severity is graded based on the post-bronchodilator $\text{FEV}_1$ expressed as a percentage of predicted normal value:

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3. Disease-Modifying & Non-Pharmacological Management

Only two therapeutic interventions have been proven in randomized trials to reduce mortality in COPD:

1. Smoking Cessation: The single most effective intervention to halt accelerated annual decline in $\text{FEV}_1$. First-line pharmacotherapies include nicotine replacement therapy (NRT transdermal patch + oral gum/lozenge), varenicline (nicotinic receptor partial agonist), or bupropion.
2. Long-Term Oxygen Therapy (LTOT): Indicated for selected patients with severe chronic resting hypoxaemia.

Key Non-Pharmacological Interventions

• Pulmonary Rehabilitation: A multi-disciplinary programme combining physical exercise training, disease education, and nutritional advice. Proven to reduce hospital readmissions and improve quality of life. Strongly indicated for patients with a Medical Research Council (MRC) dyspnoea scale score $\ge 3$ or following a recent hospital admission for an acute exacerbation.
• Vaccinations: Annual inactivated influenza vaccination and pneumococcal vaccination (PCV20 or PPV23) to prevent infective exacerbations.
• Alpha-1 Antitrypsin Screening: Recommended by NICE for all patients diagnosed with COPD before age 50 or with minimal smoking history.

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4. Stepwise Inhaled Maintenance Therapy (NICE NG115)

Pharmacological treatment aims to reduce symptoms, decrease the frequency and severity of exacerbations, and improve exercise capacity.

Step 1: Initial Symptom Relief

• Short-acting beta-2 agonist (SABA, e.g., salbutamol) or short-acting muscarinic antagonist (SAMA, e.g., ipratropium) as needed for transient breathlessness.

Step 2: Maintenance Therapy for Persistent Symptoms / Exacerbations

Patients are stratified according to the presence or absence of asthmatic features or steroid responsiveness (NICE NG115: a previous secure diagnosis of asthma or atopy, a higher blood eosinophil count, substantial variation in $\text{FEV}_1$ over time (at least 400 mL) or substantial diurnal variation in PEF (at least 20%)). NICE gives no eosinophil cut-off; the international GOLD report uses $\ge 300\text{ cells/}\mu\text{L}$ as the level that most favours adding an ICS:

• Without Asthmatic Features: Prescribe a dual long-acting bronchodilator: LABA + LAMA (e.g., indacaterol/glycopyrronium, vilanterol/umeclidinium).
• With Asthmatic Features / Higher Eosinophils (GOLD: $\ge 300/\mu\text{L}$): Prescribe LABA + ICS (e.g., formoterol/budesonide, salmeterol/fluticasone).

Step 3: Triple Therapy

• If patients on LABA + LAMA experience subsequent exacerbations ($\ge 1$ hospital admission or $\ge 2$ moderate exacerbations per year), or patients on LABA + ICS have ongoing symptoms, escalate to Triple Therapy: LAMA + LABA + ICS.

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5. Long-Term Oxygen Therapy (LTOT)

Long-term oxygen therapy increases survival and improves haemodynamics in selected patients with severe resting chronic arterial hypoxaemia.

Eligibility Criteria

Assessment must occur when the patient is clinically stable on optimal treatment (British Thoracic Society home oxygen guidance: not within 8 weeks of an exacerbation), using two arterial blood gas measurements at least 3 weeks apart (NICE NG115):

1. Absolute Threshold: Resting $\mathbf{\text{PaO}_2 < 7.3\text{ kPa}}$ ($< 55\text{ mmHg}$) on room air.
2. Relative Threshold: Resting $\mathbf{\text{PaO}_2\text{ between } 7.3\text{ and } 8.0\text{ kPa}}$ ($55\text{--}60\text{ mmHg}$) in the presence of any of the following:
   • Secondary polycythaemia (haematocrit $\ge 55\%$).
   • Clinical or echocardiographic evidence of pulmonary hypertension.
   • Peripheral oedema suggestive of cor pulmonale.

Strict Requirements for Prescription

• Must be administered for at least 15 hours per day, including overnight hours (continuous 24-hour use provides greater survival benefit).
• The patient must be a confirmed non-smoker (verified by carbon monoxide breath testing) due to the catastrophic risk of facial burns, home fires, and explosive flash injury.

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6. Acute Exacerbation of COPD (AECOPD)

An acute exacerbation is defined as a sustained worsening of the patient's respiratory symptoms beyond normal day-to-day variations that leads to a change in medication.

Cardinal Symptoms (Anthonisen Criteria)

1. Worsening dyspnoea.
2. Increased sputum volume.
3. Increased sputum purulence (green/yellow colour due to myeloperoxidase from neutrophils).

Emergency Management Protocol

1. Controlled Oxygen Therapy:

   • Administer controlled oxygen via a $24\%$ or $28\%$ Venturi mask.
   • Target Oxygen Saturation: $\mathbf{88\text{--}92\%}$.
   • Pathophysiological Rationale: Excessive oxygen delivery suppresses hypoxic drive in chronic CO2 retainers, reverses compensatory hypoxic pulmonary vasoconstriction leading to increased dead-space ventilation (V/Q mismatch), and unloads CO2 from deoxygenated haemoglobin (the Haldane effect), causing severe acute hypercapnic respiratory acidosis and CO2 narcosis.

2. Nebulised Bronchodilators:

   • Salbutamol $2.5\text{--}5\text{ mg}$ and ipratropium bromide $0.5\text{ mg}$.
   • Crucial Safety Rule: Nebulisers in COPD must be driven by compressed air, not high-flow oxygen, to prevent hypercapnia. Supplemental oxygen should be delivered simultaneously via nasal cannulae at $1\text{--}2\text{ L/min}$ to maintain saturations at $88\text{--}92\%$.

3. Systemic Corticosteroids:

   • Oral prednisolone $30\text{ mg}$ once daily for 5 days.
   • Short courses are equivalent to prolonged regimens and minimize steroid-induced myopathy, osteoporosis, and hyperglycaemia.

4. Antimicrobial Therapy:

   • Prescribed when sputum is purulent or when all three cardinal Anthonisen symptoms are present.
   • First-line oral choices: Amoxicillin $500\text{ mg}$ TDS, Doxycycline $200\text{ mg}$ stat then $100\text{ mg}$ OD, or Clarithromycin $500\text{ mg}$ BD for 5 days.

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7. Non-Invasive Ventilation (NIV / BiPAP)

Non-invasive positive pressure ventilation (BiPAP) delivers pressurized gas via a tight-fitting facial or nasal mask, decreasing work of breathing, improving alveolar ventilation, and reversing respiratory acidosis.

Indications for NIV

• Acute hypercapnic respiratory failure secondary to COPD exacerbation with:
  • Arterial blood gas showing $\text{pH} < 7.35$ and $\text{PaCO}_2 > 6.5\text{ kPa}$ (BTS/ICS 2016 acute hypercapnic respiratory failure guideline).
  • Persisting despite up to 60 minutes of optimal medical therapy (controlled oxygen, nebulisers, systemic steroids, antibiotics if indicated).
  • Severe acidosis (pH below 7.26) does not by itself rule out NIV, but it should then be delivered in a high-dependency setting with a clear plan for intubation if it fails.

Technical Settings & Goals

• Inspiratory Positive Airway Pressure (IPAP): BTS/ICS suggests starting at about $15\text{ cmH}_2\text{O}$ and increasing to $20\text{--}30\text{ cmH}_2\text{O}$ within 10–30 minutes as tolerated to improve ventilation and clear CO2.
• Expiratory Positive Airway Pressure (EPAP): Typically $3\text{--}5\text{ cmH}_2\text{O}$ to recruit collapsed alveoli and counteract intrinsic PEEP.
• Repeat ABG at 1 hour after initiating NIV; an improving pH and falling $\text{PaCO}_2$ confirms efficacy.