2.1 Asthma & COPD Maintenance

Section 2.1: Asthma & COPD Maintenance

1. Pathophysiology and Clinical Differentiation

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are the two most common chronic airway diseases encountered in general practice. While both feature airway obstruction, their pathophysiology, patient profiles, and clinical courses differ significantly.

• Asthma is a heterogeneous, chronic inflammatory disease of the airways characterized by variable expiratory airflow limitation and bronchial hyperresponsiveness. The inflammation is typically driven by type 2 helper T-cells (Th2), mast cells, and eosinophils. Airflow obstruction is primarily caused by smooth muscle bronchoconstriction and is characteristically reversible, either spontaneously or with bronchodilators.
• COPD is a common, preventable, and treatable disease characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities, typically caused by significant exposure to noxious particles or gases (most commonly tobacco smoke). The underlying inflammatory cascade is driven by neutrophils, macrophages, and CD8+ T-lymphocytes, leading to small-airway narrowing (obstructive bronchiolitis) and parenchymal destruction (emphysema). In contrast to asthma, the airflow limitation in COPD is progressive and largely irreversible.

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2. Asthma Maintenance and Step-Up Therapy (GINA Guidelines)

The Global Initiative for Asthma (GINA) guidelines outline a symptom-control and risk-reduction framework. A critical paradigm shift in recent years is the recommendation against SABA-only treatment for Step 1 asthma. Monotherapy with short-acting beta2-agonists (SABA) is associated with an increased risk of severe, life-threatening exacerbations and death due to a lack of anti-inflammatory coverage.

GINA divides maintenance therapy into two tracks:

• Track 1 (Preferred): Uses low-dose ICS-formoterol as both the controller and the preferred reliever across all steps. Formoterol is a long-acting beta2-agonist (LABA) with a rapid onset of action (similar to albuterol), making it suitable for quick relief, while the co-formulated inhaled corticosteroid (ICS) ensures that anti-inflammatory therapy is delivered whenever reliever therapy is used.
• Track 2 (Alternative): Uses a SABA as the reliever, with a daily scheduled controller (ICS or ICS-LABA). If using Track 2, patient adherence to the daily controller must be closely monitored, as patients often overuse the SABA reliever and neglect the controller.

GINA Step-Up Algorithm (Track 1)

1. Step 1 and 2: As-needed low-dose ICS-formoterol alone. No daily scheduled controller is required.
2. Step 3: Daily low-dose maintenance ICS-formoterol plus as-needed low-dose ICS-formoterol as the reliever (Single Maintenance and Reliever Therapy - SMART).
3. Step 4: Daily medium-dose maintenance ICS-formoterol plus as-needed low-dose ICS-formoterol as the reliever.
4. Step 5: Daily high-dose maintenance ICS-LABA plus add-on therapies. This includes adding a long-acting muscarinic antagonist (LAMA; e.g., tiotropium) and referring the patient for phenotypic evaluation. Biologic therapies targeting specific inflammatory pathways (e.g., anti-IgE like omalizumab, anti-IL5/5R like mepolizumab or benralizumab, or anti-IL4R like dupilumab) are considered here.

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3. COPD Maintenance and Patient Classification (GOLD Guidelines)

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines direct COPD management.

Diagnostic Criteria and Grading

A diagnosis of COPD must be confirmed by spirometry showing a post-bronchodilator FEV1/FVC ratio < 0.70. The severity of airflow limitation is graded based on the post-bronchodilator FEV1 % predicted (GOLD 1 to 4):

• 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

The GOLD ABE Assessment Tool

Patients are categorized into Groups A, B, or E based on their symptom burden (measured by the Modified Medical Research Council [mMRC] dyspnea scale or COPD Assessment Test [CAT] score) and their history of exacerbations:

• Group A: Low symptom burden (mMRC 0-1 or CAT < 10) and low risk (0-1 moderate exacerbations in the past year, not leading to hospital admission).
  • Therapy: A single bronchodilator (SABA, LABA, or LAMA) as needed or scheduled.
• Group B: High symptom burden (mMRC ≥ 2 or CAT ≥ 10) and low risk (0-1 moderate exacerbations, no hospitalizations).
  • Therapy: Dual long-acting bronchodilator combination (LABA + LAMA) is preferred over monotherapy for initial treatment.
• Group E: High exacerbation risk (≥ 2 moderate exacerbations or ≥ 1 exacerbation leading to hospital admission in the past year) regardless of symptom burden.
  • Therapy: Initial maintenance therapy is LABA + LAMA.

The Role of Blood Eosinophils and Inhaled Corticosteroids (ICS)

Unlike in asthma, ICS is not a first-line monotherapy in COPD due to an increased risk of pneumonia. In COPD, ICS is added to LABA+LAMA (triple therapy) based on blood eosinophil counts (EOS):

• EOS ≥ 300 cells/µL: Strongly recommends initiating triple therapy (LABA+LAMA+ICS) to prevent exacerbations.
• EOS < 100 cells/µL: ICS should be avoided, as it provides no clinical benefit and increases pneumonia risk.
• EOS 100-300 cells/µL: Consider adding ICS if the patient has recurrent moderate-to-severe exacerbations despite dual bronchodilation.

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4. Acute Exacerbations: Risk and Management

Exacerbations are defined as acute worsening of respiratory symptoms that require additional therapy.

Asthma Exacerbations

An acute severe asthma flare presents with tachypnea (RR > 30), tachycardia (HR > 120), accessory muscle use, and a Peak Expiratory Flow (PEF) < 50% of predicted. A "silent chest" (no wheezing due to minimal airflow) is a life-threatening sign indicating imminent respiratory failure.

• Oxygen Therapy: Deliver supplemental oxygen to maintain target oxygen saturation of 93-95%.
• Bronchodilators: High-dose inhaled SABA (albuterol 2.5-5 mg) every 20 minutes or continuously via nebulizer. Add ipratropium bromide (SAMA) for moderate-to-severe exacerbations.
• Corticosteroids: Early administration of systemic corticosteroids (e.g., oral prednisolone 40-50 mg daily for 5-7 days or IV hydrocortisone 100 mg).
• Refractory Cases: A single dose of IV magnesium sulfate (2 g infused over 20 minutes) can be administered for patients who do not respond to initial therapy.

COPD Exacerbations

Defined by increases in dyspnea, sputum volume, and/or sputum purulence.

• Oxygen Therapy: Controlled oxygen therapy must target a saturation of 88-92% (utilizing a Venturi mask). High-flow oxygen is contraindicated, as it can worsen ventilation-perfusion (V/Q) mismatch and suppress the patient's hypoxic drive, leading to acute hypercapnic respiratory failure.
• Bronchodilators: SABA (albuterol) and SAMA (ipratropium) via nebulizer or spacer.
• Corticosteroids: Oral prednisone (40 mg daily for 5 days) is standard. IV steroids offer no benefit over oral unless the patient cannot swallow.
• Antibiotics: Indicated if the patient has all three cardinal symptoms (dyspnea, sputum volume, purulence), has two symptoms if one is increased purulence, or requires mechanical ventilation. Target duration is 5 days.
• Non-Invasive Positive Pressure Ventilation (NIPPV): Indicated for patients with respiratory acidosis (pH < 7.35, PaCO2 > 45 mmHg, or RR > 25 bpm). NIPPV reduces intubation rates, hospital stay, and mortality.