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Pharmacotherapy for Lower Respiratory Conditions: Asthma & COPD

Pharmacotherapy for Lower Respiratory Conditions: Asthma & COPD Series Overview

  • Part 1: Pharmacology for Asthma & COPD.
  • Part 2: Treatment Guidelines for Asthma & COPD.
  • Part 3: Clinical Case Studies and Application.

Global Strategy for Asthma Management and Prevention (GINA)

  • Asthma Definition: Chronic lung disease with airflow limitation and airway hyperresponsiveness triggered by external stimuli, leading to inflammation and symptoms like wheezing, coughing, and shortness of breath.
  • Asthma Management Goals:
    • Long-Term Control: Minimal symptoms, no sleep disturbances, unrestricted physical activity, minimal rescue inhaler use, near-normal lung function, patient satisfaction.
    • Risk Minimization: Prevent exacerbations, stable lung function, no maintenance oral steroids, reduce emergency visits/hospitalizations, prevent long-term lung damage, optimal treatment with minimal side effects.
    • Prevent Mortality: Morbidity/mortality largely preventable; consider expert consultation for severe/difficult-to-treat asthma.
  • Key Definitions:
    • Reliever (Rescue): As-needed (PRN) relief, prevents exercise-induced bronchoconstriction.
    • Controller (Maintenance): Reduces inflammation, controls symptoms, mitigates exacerbations.
    • Maintenance-and-Reliever Therapy (MART): Daily controller plus PRN reliever from same inhaler.
    • Anti-inflammatory Reliever (AIR): Reduces inflammation quickly during acute exacerbations/trigger exposure.
  • Overview of Drugs for Asthma Maintenance:
    • Bronchodilators: Short-Acting \beta2-Adrenergic Agonists (SABAs), Long-Acting \beta2-Adrenergic Agonists (LABAs), Long-Acting Muscarinic Antagonists (LAMAs).
    • Anti-Inflammatory Agents: Inhaled Glucocorticoids (ICS), Systemic Glucocorticoids, Leukotriene Inhibitors.
    • Principle: All asthma patients should receive ICS-containing therapy; always prescribe ICS with a SABA.
    • Key Combination: ICS-formoterol is the ONLY ICS-LABA usable as AIR (e.g., Symbicort, Fostair).
  • GINA Main Tracks Based on Reliever Medication:
    • Track 1 (Preferred, Simple): Reliever = PRN ICS-formoterol.
      • Steps 1-2: PRN ICS-formoterol.
      • Step 3: Maintenance Daily ICS-formoterol.
      • Step 5: LAMA.
    • Track 2 (Alternative, Controlled): Reliever = PRN ICS + SABA or PRN SABA.
      • Step 1: PRN ICS + SABA.
      • Step 2: Maintenance Daily ICS (+SABA).
      • Step 3: ICS-LABA^* (+SABA).
      • Step 5: LAMA (+SABA).
      • Note: Ensure compliance with daily ICS before prescribing SABA alone.
  • GINA Treatment Initiation (Adults & Adolescents \geq 12 years):
    • Step 1: As-needed low dose ICS-formoterol or low dose ICS with SABA.
    • Step 2: Daily low dose ICS + as-needed SABA.
    • Step 3: Low dose ICS-LABA + as-needed SABA or medium dose ICS-formoterol MART.
    • Step 4: Medium dose ICS-formoterol MART or medium/high dose ICS-LABA + as-needed SABA.
    • Assess, Adjust, Review before stepping up.
  • GINA Treatment Initiation (Children 6-11 years):
    • Step 1: Low dose ICS whenever SABA taken.
    • Step 2: Daily low dose ICS.
    • Step 3: Low dose ICS-LABA, or medium dose ICS, or very low dose ICS-formoterol MART.
    • Reliever: As-needed SABA (or ICS-formoterol reliever in MART).
  • GINA Treatment Initiation (Children \leq 5 years):
    • Step 1: Consider intermittent short course ICS at onset of viral illness for infrequent viral wheezing.
    • Step 2: Daily low dose ICS or Daily Leukotriene Receptor Antagonist (LTRA).
    • Step 3: Double 'low dose' ICS or low dose ICS + LTRA; consider specialist referral.
    • Reliever: As-needed Short-Acting \beta_2-agonist.

Global Initiative for Chronic Obstructive Lung Disease (GOLD)

  • COPD Definition: Chronic lung disease characterized by small airway obstruction, persistent airflow limitations, and reduction in expiratory flow rate.
  • Key Focus Areas: Personalized treatment based on symptom severity and exacerbation risk; pharmacological and non-pharmacological therapies.
  • Goals: Reduce symptoms, improve quality of life, slow disease progression.
  • Overview of Drugs:
    • Bronchodilators: SABAs, LABAs, Short-Acting Muscarinic Antagonists (SAMAs), Long-Acting Muscarinic Antagonists (LAMAs).
    • Anti-Inflammatory Agents: ICS, Systemic Glucocorticoids, Phosphodiesterase-4 Inhibitors.
    • Principle: Inhaled bronchodilators are central to symptom management in COPD.
  • GOLD Initial Pharmacological Treatment (Figure 3.7):
    • Group A (mMRC 0-1, CAT < 10, 0-1 moderate exacerbations): A bronchodilator.
    • Group B (mMRC \geq 2, CAT \geq 10, 0-1 moderate exacerbations): LABA +\ LAMA^* .
    • Group E (\geq 2 moderate exacerbations or \geq 1 leading to hospitalization): LABA +\ LAMA^* .
      • Consider LABA+LAMA+ICS^* if blood eosinophils (eos) \geq 300.
      • Note: Single inhaler therapy may improve adherence.
  • GOLD Follow-up Pharmacological Treatment (Figure 3.9):
    • For Dyspnea: Escalation from LABA or LAMA to LABA+LAMA.
    • For Exacerbations:
      • If blood eos \geq 100: LABA+LAMA+ICS.
      • If blood eos \geq 300: LABA+LAMA+ICS (stronger recommendation).
      • If blood eos \geq 100 and FEV_1 < 50\% & chronic bronchitis: Roflumilast.
      • Consider Azithromycin (preferentially in former smokers).
      • Note: Consider ICS de-escalation if pneumonia/side-effects; de-escalation is more likely associated with exacerbations if blood eos \geq 300.
  • Bronchodilators in Stable COPD: Inhaled preferred over oral; single combined inhaler improves adherence.
    • SAMA + SABA (PRN or daily): Superior to monotherapy, improves lung function/symptoms.
    • LABA + LAMA: More effective than using either alone, significantly improves \text{FEV}_1 and symptoms; reduces exacerbation rates.
    • LAMA Alone: Most effective with severe disease.
  • Anti-inflammatory Therapy in Stable COPD:
    • LABA + LAMA + ICS: More effective than ICS +\ LAMA; preferred over ICS + LABA, LABA + LAMA, or LAMA monotherapy; reduces mortality in frequent/severe exacerbations.
    • ICS + LABA: Improves lung function, reduces exacerbations; use ICS if comorbid asthma; increased pneumonia risk (evaluate eosinophil levels).
    • Additional: Roflumilast (PDE4 inhibitor), long-term antibiotic therapy.
    • Systemic Corticosteroids: No benefit in stable COPD.
  • Medications to Manage Severe Exacerbation:
    • Inhaled Bronchodilators + SABA and Antimuscarinic: Increase dosage/frequency of SABAs; combine SABA + SAMA/LAMA; switch to LABA once stable.
    • Systemic Corticosteroids: Improve lung function/oxygenation; shorten recovery/hospitalization; max 5-day treatment plan.