3.1 Asthma, COPD & Airway Diseases

Diagnostic Evaluation & Asthma Pathophysiology

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow obstruction, airway hyper-responsiveness, and bronchial wall remodeling. Symptoms include episodic dyspnoea, wheeze, chest tightness, and cough, typically worse at night or early morning.

Objective Spirometric Criteria

• Bronchodilator Reversibility (BDR): Post-bronchodilator spirometry following 400 µg inhaled salbutamol demonstrating an FEV1 increase of >12% and >200 mL relative to baseline confirms reversible airflow obstruction.
• Peak Expiratory Flow (PEF) Variability: Diurnal PEF variability calculated as (Highest PEF - Lowest PEF) / Mean PEF > 20% over a 2-week monitoring period.
• Fractional Ex exhaled Nitric Oxide (FeNO): FeNO ≥50 ppb in adults indicates eosinophilic airway inflammation driven by T-helper 2 (Th2) cytokines (IL-4, IL-5, IL-13).
• Airway Challenge Testing: Methacholine or histamine challenge testing revealing a Provocative Concentration causing a 20% drop in FEV1 (PC20) of <8 mg/mL establishes airway hyper-reactivity when baseline spirometry is normal.

Chronic Asthma Management (BTS/GINA Guidelines)

Under GINA 2024 guidance, management is divided into two tracks:

1. Track 1 (Preferred): Uses low-dose ICS-formoterol as the anti-inflammatory reliever across all steps (as-needed in Steps 1–2; maintenance and reliever therapy [MART] in Steps 3–5).
2. Track 2 (Alternative): Uses Short-Acting Beta-2 Agonists (SABA e.g., salbutamol) as reliever, paired with regular daily maintenance Inhaled Corticosteroid (ICS e.g., beclometasone, budesonide, fluticasone). Step-up therapy adds a Long-Acting Beta-2 Agonist (LABA e.g., salmeterol), Long-Acting Muscarinic Antagonist (LAMA e.g., tiotropium), or Leukotriene Receptor Antagonist (LTRA e.g., montelukast).

Exam Pearl: Biologic therapies targeting specific Th2 inflammatory pathways are indicated for severe refractory eosinophilic asthma:

• Anti-IL-5 / Anti-IL-5Rα: Mepolizumab, Reslizumab, Benralizumab (indicated if blood eosinophils ≥300 cells/µL).
• Anti-IL-4Rα: Dupilumab (inhibits IL-4 and IL-13 signaling).
• Anti-IgE: Omalizumab (indicated for severe allergic asthma with elevated serum IgE).

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Acute Severe & Life-Threatening Asthma: BTS Classification & Emergency Protocol

Acute asthma exacerbations require rapid clinical assessment and risk stratification based on British Thoracic Society (BTS) criteria.

Critical Clinical Warning: A normal or elevated PaCO2 (4.6–6.0 kPa or >6.0 kPa) in a patient with severe asthma who is tachypnoeic represents respiratory muscle fatigue and impending respiratory arrest! This is a medical emergency requiring immediate senior ITU escalation.

Stepwise Emergency Management Protocol

1. Oxygen Therapy: High-flow oxygen via non-rebreathe mask targeting SpO2 94–98%.
2. Inhaled Bronchodilators: Nebulised Salbutamol 5 mg driven by oxygen (6–8 L/min), repeated every 15–30 minutes, combined with nebulised Ipratropium bromide 0.5 mg 4–6 hourly.
3. Systemic Corticosteroids: Oral Prednisolone 40–50 mg daily (or IV Hydrocortisone 100 mg 6-hourly) continued for 5–7 days.
4. Intravenous Magnesium Sulphate: 1.2–2.0 g IV infusion over 20 minutes for patients with acute severe asthma not responding to initial inhaled therapy.
5. Intravenous Aminophylline / Salbutamol: Second-line IV bronchodilator infusions administered only in ITU/HDU settings with therapeutic drug monitoring.
6. Endotracheal Intubation & Mechanical Ventilation: Indicated for coma, respiratory arrest, worsening exhaustion with hypercapnia, or severe refractory acidosis.

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COPD Staging & Maintenance Pharmacotherapy (GOLD Guidelines)

Chronic Obstructive Pulmonary Disease (COPD) is characterized by persistent, non-reversible airflow limitation due to airway (obstructive bronchitis) and/or alveolar abnormalities (emphysema), primarily triggered by tobacco smoke or biomass exposure.

Diagnostic Spirometry

• A post-bronchodilator FEV1/FVC ratio <0.70 is mandatory to confirm persistent airflow obstruction.
• Severity of airflow limitation is graded by post-bronchodilator FEV1 % predicted:
  • GOLD 1 (Mild): FEV1 ≥80% predicted
  • GOLD 2 (Moderate): FEV1 50–79% predicted
  • GOLD 3 (Severe): FEV1 30–49% predicted
  • GOLD 4 (Very Severe): FEV1 <30% predicted

GOLD ABE Assessment & Treatment Scheme

Exacerbation history and symptom burden (evaluated via mMRC dyspnoea scale or CAT score) guide maintenance therapy:

• Group A (0–1 moderate exacerbations/year without hospital admission, mMRC 0–1): Initiate a single bronchodilator (LAMA or LABA).
• Group B (0–1 moderate exacerbations/year, mMRC ≥2): Initiate LAMA + LABA combination therapy.
• Group E (≥2 moderate exacerbations or ≥1 exacerbation leading to hospital admission): Initiate LAMA + LABA combination therapy. Add an Inhaled Corticosteroid (ICS) (triple therapy: LAMA + LABA + ICS) if blood eosinophil count is ≥300 cells/µL.

Long-Term Prophylaxis & Phosphodiesterase-4 Inhibitors

• Azithromycin: 250 mg 3 times weekly may be prescribed for non-smokers with frequent exacerbations despite optimal inhaler therapy. Baseline ECG (to exclude QTc prolongation) and liver function tests are essential.
• Roflumilast: Oral PDE-4 inhibitor indicated as add-on therapy in severe COPD (FEV1 <50%) associated with chronic bronchitis and frequent exacerbations.

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Acute Exacerbations of COPD (AECOPD) & Non-Invasive Ventilation (NIV)

An acute exacerbation is defined by acute worsening of dyspnoea, cough, and/or sputum purulence and volume, commonly triggered by viral (rhinovirus, influenza) or bacterial (H. influenzae, S. pneumoniae, M. catarrhalis, Pseudomonas) infections.

Controlled Oxygen & Pharmacotherapy

• Controlled Oxygen: Target SpO2 88–92% using a Venturi mask (24% or 28%) to prevent loss of hypoxic respiratory drive and severe hypercapnia resulting from ventilation-perfusion mismatching and Haldane effect.
• Bronchodilators: Nebulised Salbutamol 2.5–5 mg and Ipratropium 0.5 mg driven by compressed air (not pure O2, to prevent hypercapnia).
• Corticosteroids: Oral Prednisolone 30 mg PO daily for 5 days.
• Antibiotics: Prescribed when sputum purulence is present alongside increased dyspnoea or sputum volume. First-line choices include Amoxicillin 500 mg TDS, Doxycycline 200 mg stat then 100 mg OD, or Clarithromycin 500 mg BD for 5 days.

Non-Invasive Ventilation (NIV / BiPAP)

NIV provides bilevel positive airway pressure (BiPAP) and is the standard of care for acute decompensated type II respiratory failure.

• Indications: Acute hypercapnic respiratory failure with pH 7.25–7.35 and PaCO2 >6.0 kPa despite maximal medical therapy.
• Initial Settings: Inspiratory Positive Airway Pressure (IPAP) 10–12 cmH2O; Expiratory Positive Airway Pressure (EPAP) 4–5 cmH2O; titrated to achieve target SpO2 88–92% and resolve respiratory acidosis.
• Contraindications: Facial trauma/burns, fixed upper airway obstruction, severe vomiting, bowel obstruction, undrained pneumothorax, or inability to protect airway.

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Long-Term Oxygen Therapy (LTOT) & Alpha-1 Antitrypsin Deficiency

Long-Term Oxygen Therapy (LTOT) Criteria

LTOT improves survival in COPD patients with severe chronic hypoxaemia. Assessment must be performed in a stable state at least 5 weeks post-exacerbation on optimal medical therapy.

• Primary Indication: Resting room air PaO2 <7.3 kPa.
• Secondary Indication: Resting room air PaO2 between 7.3 and 8.0 kPa PLUS evidence of:
  1. Secondary polycythaemia (haematocrit >55%),
  2. Clinical or echocardiographic pulmonary hypertension, or
  3. Peripheral oedema / cor pulmonale.
• Operational Requirements: Administered via nasal cannulae for ≥15 hours per day (including overnight). Patients MUST be non-smokers due to catastrophic domestic fire risk.

Bronchiectasis

Bronchiectasis involves permanent abnormal dilation of the bronchi resulting from chronic inflammation and impaired mucociliary clearance.

• Diagnostic Gold Standard: High-Resolution CT (HRCT) demonstrating an internal bronchial diameter >1.0 times the diameter of the adjacent pulmonary artery (bronchoarterial ratio >1.0, "signet-ring sign") and failure of bronchial tapering toward the periphery.
• Microbiology & Management: Sputum colonisation with Pseudomonas aeruginosa portends accelerated FEV1 decline and increased hospitalisations. Treatment includes regular chest physiotherapy (active cycle of breathing techniques), hypertonic saline nebulisers (3–7%), and prompt antibiotic therapy (oral Ciprofloxacin 750 mg BD for P. aeruginosa).

Alpha-1 Antitrypsin (A1AT) Deficiency

• Genetics: Autosomal co-dominant disorder caused by mutations in the SERPINA1 gene on chromosome 14. Normal allele is PiM; severe deficiency phenotype is PiZZ (serum A1AT levels <11 µmol/L).
• Pathology: Lack of protective neutrophil elastase inhibition causes panacinar emphysema classically localized to the lower lobes of the lungs in young non-smokers (30–40 years).
• Extrapulmonary Manifestations: Accumulation of misfolded mutant protein in hepatocytes causes neonatal cholestasis, juvenile cirrhosis, and hepatocellular carcinoma.