Asthma: Inflammation and Endotypes

Asthma

• Asthma is a chronic respiratory disease characterized by:
  • Inflammation
  • Reversible expiratory airflow obstruction
  • Airway hyper-responsiveness
  • Airway remodeling

Inflammation

• Persistent inflammation is the root cause of all asthma symptoms.
• Asthma is a heterogeneous disease, meaning it presents differently in different people.
• Different endotypes, phenotypes, and responses to treatment are seen.

Asthma Endotypes

• Endotypes describe the inflammatory processes driving the disease in different patient groups.
• Proposed endotypes for asthma include:
  • Allergic eosinophilic asthma
  • Non-allergic eosinophilic asthma
  • Neutrophilic asthma
  • Paucigranulocytic asthma
  • Mixed granulocytic asthma

Asthma Phenotypes

• Phenotypes describe clinical manifestations seen in different patient groups.
• Five phenotypes have been proposed:
  • Early symptom predominant
  • Obese, non-eosinophilic
  • Benign asthma
  • Inflammation predominant
  • Discordant inflammation

Response to Treatment

• Corticosteroid insensitivity: Failure to improve FEV1 by at least 15% from baseline after 10-14 days of oral prednisolone 40 mg daily treatment.
• Irresponsiveness to beta-2 agonists: Patients not responding to inhalers for unknown reasons.

Expiratory Airflow Obstruction

• Difficulty exhaling normally, due to ongoing inflammation causing mediator release, bronchoconstriction, increase in airway smooth muscle mass, and insufficient exhalation.
• Assessed by spirometry, measuring FEV1/FVC ratio (<70%), reduced FEV1 (defines severity), and normal or reduced FVC.
• Reversible in asthma (unlike COPD). Improved after bronchodilator administration (12% or 200ml increase in FEV1).

Clinical Presentation

• Symptoms include:
  • Cough
  • Wheezing (decreased breath sounds in severe cases)
  • Chest tightness
  • Shortness of breath

Treatment of Asthma

• Conventional Therapy:
  • Reliever Medications: Short-acting bronchodilators (beta-2 agonists) for airway dilation.
  • Controller Medications: Anti-inflammatory agents (corticosteroids) and long-acting bronchodilators (beta-2 agonists) to reduce inflammation and manage symptoms.

Treatment for Acute Asthma (Exacerbation)

• Goal: Relieve symptoms and return patients to baseline lung function.
• Inhaled Bronchodilators: MDI or nebulizer-administered beta-2 agonists or anticholinergics. Heliox (helium and oxygen mixture) may be added for enhanced delivery to distal airways.
• Systemic Corticosteroids: Prednisone, prednisolone, or methylprednisolone (higher doses for severe cases). Dosage dependent on severity (40-60 mg once a day), duration of treatment (3-5 days for children, 5-7 days for adults).
• Subcutaneous Epinephrine: 1 mg/mL (1:1000) solution; may be preferred to epinephrine for children (although no longer widely used)
• Antibiotics: Only if a bacterial infection is suspected.
• Magnesium Sulfate : Airway smooth muscle relaxant; use controversial due to lack of confirmed safety and efficacy. Administered IV, bolus, or infusion.

PFT Revision

• Obstructive Disorders: Low FEV1/FVC ratio, low FEV1, normal TLC.
• Restrictive Disorders: Normal FEV1/FVC ratio, low TLC.
• Mixed Disorders: Low FEV1/FVC ratio, low TLC (but FVC may be low due to hyperinflation).