Making Sense of the Laboratory Diagnosis of Asthma

‍Introduction to Asthma

Asthma as a Global Health Concern

• Affects over 260 million people worldwide.
• Causes more than 450,000 deaths annually, most of which are preventable.
• Most common chronic disease in children.

Pathophysiology of Asthma

• Characterized by chronic airway inflammation, hyper-responsiveness, and variable airflow limitation.
• Triggered by viruses, allergens, irritants, and exercise.
• Symptoms include:
  • Wheezing.
  • Shortness of breath.
  • Chest tightness.
  • Coughing.
• Episodes are reversible with bronchodilators or corticosteroids.

Personalized Treatment Approach

• Asthma is now recognized as a heterogeneous disease with different molecular mechanisms.
• Classifying asthma based on endotypes enables a targeted approach to treatment.

Asthma treatment is shifting from a "one-size-fits-all" approach to precision medicine based on biomarkers.

What is Severe Asthma?

Definition of Severe Asthma

• Affects 5–10% of asthmatics.
• Requires high-dose inhaled corticosteroids (ICS) plus a second controller (e.g., LABA or systemic corticosteroids).
• Remains uncontrolled despite optimal therapy.
• Exacerbating factors must be corrected before diagnosing severe asthma.

📌 Severe asthma requires intensive monitoring and specialized treatment, including biologic therapies.

Endotypes and Phenotypes of Asthma

Asthma Classification Based on Molecular Pathways

• Asthma was previously classified by phenotype (observable clinical traits).
• Now categorized into endotypes based on underlying molecular mechanisms.

1. T2-High Asthma

• Most common form of asthma.
• Involves Th2 lymphocytes, IL-4, IL-5, and IL-13 cytokines.
• Driven by eosinophilic inflammation.

Atopic Asthma

• Early onset, well-defined, steroid-sensitive.
• Associated with allergic sensitization.
• Key biomarkers:
  • Elevated eosinophils (blood/sputum).
  • High FeNO.
  • Elevated total and specific IgE.

Late-Onset Eosinophilic Asthma

• Adult-onset, often severe, associated with nasal polyps.
• Key biomarkers:
  • Elevated eosinophils and FeNO.

Aspirin-Exacerbated Respiratory Disease (AERD)

• Adult-onset, triggered by NSAIDs.
• Key biomarker:
  • Urinary leukotriene E4 (LTE4).

2. Non-T2 (T2-Low) Asthma

• Less understood, may involve Th1/Th17 inflammation.
• Poor response to inhaled corticosteroids.

Neutrophilic Asthma

• Adult-onset, associated with smoking and obesity.
• Key biomarker:
  • Induced sputum neutrophil count >50%.

Identifying the asthma endotype is crucial for selecting the most effective treatment strategy.

Biomarkers of Asthma

Blood and Sputum Eosinophils

• Strongly associated with Type 2 inflammation.
• Eosinophil count >0.3 × 10⁹/L predicts exacerbation risk.
• Sputum eosinophils >2% indicate airway inflammation.

Fractional Exhaled Nitric Oxide (FeNO)

• Non-invasive marker of airway inflammation.
• Higher in T2-high asthma.
• Diagnostic cut-offs:
  • <25 ppb (adults) or <20 ppb (children) → Low likelihood of T2 asthma.
  • ≥50 ppb (adults) or ≥35 ppb (children) → Suggests eosinophilic inflammation.

Total and Specific IgE

• High total IgE correlates with asthma severity.
• Specific IgE identifies allergen triggers.

Using multiple biomarkers improves diagnostic accuracy and guides personalized treatment.

Using Biomarkers to Guide Asthma Management

Stepwise Approach to Asthma Treatment Based on Biomarkers

Step 1: Determine T2 Status

• T2-high asthma is defined by:
  • High FeNO.
  • Elevated blood eosinophils.
  • Allergic sensitization (specific IgE or skin prick test).

Step 2: Select Appropriate Treatment

• T2-high asthma:
  • ICS therapy.
  • Biologics (omalizumab, dupilumab, mepolizumab) if severe.
• T2-low asthma:
  • Consider alternative treatments (e.g., macrolides, bronchodilators).

Personalized asthma treatment improves symptom control and reduces exacerbations.

Asthma Monitoring with FeNO Testing

FeNO Testing Now Available at Selected Ampath Facilities

• Easy, non-invasive point-of-care test.
• Monitors airway inflammation and corticosteroid response.
• Factors that affect FeNO results:
  • Age, gender, smoking, food intake, infections, allergic rhinitis, asthma medications.

FeNO testing provides a convenient tool for diagnosing and managing asthma in clinical practice.

Key Takeaways for Clinicians

Asthma diagnosis and management should be guided by biomarkers.

Laboratory Evaluation of Asthma Includes:

1. Routine laboratory tests and Type 2 (T2) inflammation biomarkers.
2. Full blood count (FBC) with differential count: Helps confirm or exclude eosinophilia.
3. Sputum eosinophils: Persistently high levels despite high-dose corticosteroids are linked to more severe disease.
4. Total serum IgE: Determines eligibility for anti-IgE therapy.
5. Specific IgE: Identifies triggering allergens.
6. Fractional exhaled nitric oxide (FeNO): A non-invasive test used for diagnosis and monitoring.

T2-high asthma responds well to corticosteroids and biologics, while T2-low asthma requires alternative approaches.

Blood eosinophils, FeNO, and IgE testing help classify asthma endotypes.

FeNO testing is a valuable non-invasive tool for monitoring airway inflammation.

Personalized treatment improves patient outcomes and reduces asthma-related hospitalizations.

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Asthma classification based on biomarkers enables precision treatment.

Precision medicine is transforming asthma care by allowing targeted therapy based on molecular mechanisms.