Respiratory Medicine
High Evidence

Asthma (Chronic Management)

Updated 2026-01-05
5 min read

Asthma (Chronic Management)

1. Overview

Chronic Asthma is a heterogeneous respiratory disease characterised by chronic airway inflammation and bronchial hyper-responsiveness. It is clinically defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity, together with variable expiratory airflow limitation. [1]

Adult-onset asthma often differs significantly from pediatric "atopic" asthma, frequently presenting as non-atopic, eosinophilic, or obesity-related phenotypes. The 2020-2024 paradigm shift, led by GINA (Global Initiative for Asthma), has moved away from SABA monotherapy in favour of Inhaled Corticosteroid (ICS)-containing regimens for all adults, even those with "mild" symptoms. [2]

The modern management goals are two-fold: Symptom Control (minimising day-to-day impact) and Risk Reduction (preventing exacerbations, fixed obstruction, and medication side-effects). For the ~5-10% of patients with "Severe Asthma," the advent of Biologic Therapies targeting specific cytokines (IL-4, IL-5, IL-13, TSLP) has redefined the limits of disease control. [3]

2. Epidemiology

The Global Burden

  • Prevalence: Approximately 300 million people globally. In the UK, 1 in 12 adults are treated for asthma.
  • The "At-Risk" Phenotypes:
    • Early-onset Atopic: Classic Th2-driven; associated with the "Allergic March" (eczema, hayfever).
    • Late-onset Eosinophilic: Often non-atopic; associated with nasal polyps and aspirin sensitivity (Samter's Triad).
    • Obesity-related: Typically non-eosinophilic; poor response to ICS. [4]

Mortality and Preventability

The NRAD (National Review of Asthma Deaths) report highlighted that 2/3 of asthma deaths are preventable. Key risk factors for death include over-reliance on SABA (> 12 canisters/year) and under-use of ICS. [5]

3. Aetiology & Pathophysiology

⚠️ THE 7-STEP MOLECULAR MECHANISM (T2-High Cascade)

  1. Epithelial Barrier Breach: Environmental triggers (pollens, viruses, smoke) damage the airway epithelium, breaching the tight junctions.
  2. Alarmin Release: Damaged epithelial cells release "Alarmins": TSLP (Thymic Stromal Lymphopoietin), IL-25, and IL-33.
  3. Th2 Priming: Alarmins activate dendritic cells and Type 2 Innate Lymphoid Cells (ILC2s). Dendritic cells present antigens to naive T-cells, driving Th2 cell differentiation.
  4. Cytokine Orchestration: Th2 cells and ILC2s produce the "Big Three" cytokines:
    • IL-4: Stimulates B-cell class switching to produce IgE.
    • IL-5: Critical for Eosinophil maturation and survival in the bone marrow and airway.
    • IL-13: Drives Mucus Hypersecretion and Bronchial Hyper-responsiveness (BHR).
  5. Mast Cell Degranulation: IgE binds to FcεRI receptors on mast cells. Allergen cross-linking triggers the release of Histamine and Leukotrienes, causing acute bronchoconstriction.
  6. Eosinophilic Destruction: Eosinophils release Major Basic Protein (MBP) and Eosinophil Peroxidase, which strip the airway epithelium, exposing underlying nerves and causing hypersensitivity.
  7. Airway Remodelling: Chronic inflammation stimulates fibroblasts via TGF-β, leading to subepithelial fibrosis, smooth muscle hypertrophy, and goblet cell hyperplasia. This leads to fixed airflow obstruction. [6, 7]

4. Clinical Presentation

Symptom Dynamics

  • Variability: Symptoms are typically worse at night or in the early morning.
  • Triggers: Cold air, exercise, viral infections, or allergens.
  • Cough-Variant Asthma: Presenting solely with a persistent dry cough, often misdiagnosed as reflux or ACEi side-effect.

Physical Examination

  1. Expiratory Wheeze: Polyphonic and widespread. (Note: A "silent chest" is a medical emergency).
  2. Atopic Features: Inspect for nasal polyps, allergic shiners, or flexural eczema.
  3. Hyperinflation: In chronic severe cases, an increased AP diameter of the chest.

5. Investigations

Confirming Variability (The Diagnostic Triad)

  1. Spirometry: FEV1/FVC ratio less than 0.7 indicates obstruction.
  2. Reversibility: An increase in FEV1 of > 12% AND > 200 mL after 400mcg Salbutamol.
  3. Peak Flow Variability: Diurnal variation > 20% over 2 weeks.

Phenotyping (T2-High Biomarkers)

  • FeNO (Fractional Exhaled Nitric Oxide): > 25 ppb suggests eosinophilic airway inflammation and ICS responsiveness.
  • Blood Eosinophils: > 0.3 x 10^9/L (or > 300 cells/µL) indicates a high risk of exacerbations and eligibility for biologics. [8]
  • Methacholine Challenge: Used if spirometry is normal but clinical suspicion is high (high NPV).

6. Management: The GINA 2024 Tracks

Track 1: Preferred (The MART/SMART Strategy)

Uses Low-dose ICS-Formoterol as both the daily controller and the reliever.

  • Rationale: Ensures the patient receives a burst of anti-inflammatory steroid every time they use their reliever, preventing the "SABA-only" risk.
  • Evidence: The SYGMA and MANDALA trials. [9]

Track 2: Alternative (Standard Step-Up)

ICS maintenance with SABA as needed.

  • Step 1-2: Low-dose ICS taken whenever SABA is used.
  • Step 3: Low-dose ICS-LABA maintenance.
  • Step 4: Medium-dose ICS-LABA.

Severe Asthma (Step 5)

Refer to specialist for Biological Therapy:

  • Omalizumab: Anti-IgE (Allergic phenotype).
  • Mepolizumab/Benralizumab: Anti-IL5 (Eosinophilic phenotype).
  • Dupilumab: Anti-IL4/IL13 (Atopic/Eosinophilic).
  • Tezepelumab: Anti-TSLP (The "broad-spectrum" biologic). [10]

7. Complications

  1. Fixed Airflow Obstruction: Permanent remodelling mimicking COPD.
  2. Iatrogenic Cushing's: From repeated oral steroid bursts (Osteoporosis, Diabetes, Cataracts).
  3. ABPA (Allergic Bronchopulmonary Aspergillosis): Hypersensitivity to Aspergillus; characterised by "finger-in-glove" opacities and high IgE.

8. Evidence: Landmark Trials

TrialYearPopulationInterventionResult
SYGMA 1 & 22018Mild AsthmaPRN ICS-Formoterol↓ 64% Exacerbations vs. SABA alone.
MANDALA2022Mod-SeverePRN Albuterol-Bud↓ 24% Exacerbations vs. SABA alone.
NAVIGATOR2021Severe AsthmaTezepelumabSignificant ↓ in all-comers (T2 high and low).
DiRECT2018Obese AsthmaWeight LossImproved control and reduced inflammation.

9. Single Best Answer (SBA) Questions

Question 1

A 30-year-old female with asthma uses a low-dose ICS-LABA (Track 1 MART). She is using her inhaler 5 times a week for symptoms and has woken up twice this month with a wheeze. What is the next best step?

  • A) Add Montelukast
  • B) Increase to high-dose ICS-LABA
  • C) Increase to medium-dose ICS-LABA MART
  • D) Add Tiotropium
  • E) Switch to Track 2
  • Answer: C. Per GINA Track 1, the next step for a patient uncontrolled on low-dose MART is to increase the maintenance dose to medium-dose MART.

Question 2

Which cytokine is the primary target for the monoclonal antibody Benralizumab?

  • A) IL-4
  • B) IL-5 Receptor alpha
  • C) IL-13
  • D) TSLP
  • E) IgE
  • Answer: B. Mepolizumab targets IL-5 directly, whereas Benralizumab targets the IL-5 receptor alpha, leading to near-total depletion of eosinophils via ADCC.

10. Viva Scenario: The "SABA Over-user"

Examiner: "Your patient is requesting their 15th Salbutamol inhaler this year. They say their asthma is 'fine' but they like to have it 'just in case.' What is your management?"

Candidate:

  1. Risk Assessment: I would identify this patient as being at high risk of asthma death (NRAD criteria).
  2. Education: I would explain that over-reliance on SABA actually increases airway inflammation and downregulates the receptors, making the inhaler less effective during a real emergency.
  3. Management Shift: I would move the patient to Track 1 (MART) with ICS-Formoterol, so they get anti-inflammatory treatment with every puff.
  4. Investigation: I would check their inhaler technique and check FeNO to see if they have significant untreated eosinophilic inflammation.

11. Patient Explanation

"Asthma is not just a problem of your airways getting tight; it's a problem of 'twitchiness' caused by underlying swelling. Think of it like a sensitive alarm system. If we only use the 'blue' inhaler, we are just silencing the alarm for a few hours while the fire (inflammation) continues to burn. This can eventually lead to permanent scarring. The 'preventer' or 'MART' inhaler acts like a sprinkler system that stays on all the time to keep the fire out. You must use it even when you feel 100% well to keep your lungs healthy for the future."

12. References

  1. Global Initiative for Asthma (GINA). 2024 Global Strategy for Asthma Management and Prevention. GINA
  2. O'Byrne PM, et al. Inhaled Combined Budesonide-Formoterol as Needed in Mild Asthma (SYGMA). N Engl J Med. 2018. [PMID: 29768147]
  3. Menzies-Gow E, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma (NAVIGATOR). N Engl J Med. 2021. [PMID: 33979488]
  4. Papi A, et al. Inhaled Albuterol-Budesonide for As-Needed Use in Asthma (MANDALA). N Engl J Med. 2022. [PMID: 35569462]
  5. Royal College of Physicians. Why asthma still kills: The National Review of Asthma Deaths (NRAD). 2014. RCP

Last Updated: 2026-01-05 | MedVellum Editorial Team