Childhood Asthma Pathophysiology

Intro to AsthmaChronic inflammatory disease of conducting airwaysasthma-pathophysiology

  • Airflow obstruction, usually reversible (>12% increase in FEV1 15 mins after inhaled SABA)
  • Atopic (allergic hypersensitivity) or non-atopic (intrinsic)

Atopy – major risk factor; excessive IgE-mediated rxn; may also suffer from allergic sx’s

Non-atopic individuals have very low risk of developing asthma; these pts have negative skin tests to allergens & normal IgE concs; usually adult-onset

Allergens à house dust mites, cat/dog fur, cockroaches, grass/tree pollens, rodents, smoke

Exercise à hyperventilation, mast cell release, bronchoconstriction (EIA); recover w/in 30 mins; preventable w/ prior admin of beta-2 agonists/ICS

Drugs à Beta-blockers acutely worsen asthma (bronchoconstriction); aspirin may worsen

Pathogenesis

  • Pathology uniform in different types of asthma (Airway inflammation, hyper-responsiveness (AHR), & obstruct)
  • Inflammation affects all airway cells

à Leukotrienes! Prostaglandins! Cytokines! à Eosinophils! Mast cells! Lymphocytes! Etc!

– Mast cells, eosinophils, lymphocytes, and their associated products appear especially prominent in the airways of patients with asthma. Inflammatory events and associated alterations in airway smooth muscle function result in asthma symptoms, and structural changes within the epithelium, subepithelium, fibroblasts, and smooth muscle.

– Bronchial Hyper Responsiveness (BHR) – defining feature of asthma from exaggerated reversible airway obstruction due to smooth muscle contraction.

– Structural cells, particularly the epithelium, fibroblasts, smooth muscle, and endothelium, may contribute to inflammation or airway remodeling through elaboration of mediators and cytokines.

Management

  1. Decr Sx’s & exacerbations, avoid triggers; 2. Decrease med side effects; 3. Optimize lung function; 4. Pt education

Treatment of Asthma

ICS = inhaled corticosteroids, LABA = long acting β2 – agonists, OCS = Oral corticosteroids

Bronchodilators

  • Bronchodilators give rapid relief of symptoms mainly through relaxation of airway smooth muscle
    • β2-Agonists à relaxes smooth muscle and inhibits certain inflammatory cells (mast cells)
    • Anticholinergics à prevent nerve-induced bronchoconstriction and mucus secretion
    • Theophylline à inhibition of phosphodiesterases in airway smooth muscle cells; also anti-inflammatory effects through an unknown mechanism
  • Bronchodilator Therapy – β2-agonists most effective; rapid relief of sx’s
    • SABAs vs LABAs – SABAs 3-6 hours, take as needed for sx relief or prior to exercise; LABAs 12 hours
  • Doesn’t control underlying inflammation!

Controllers

  • Controllers inhibit the underlying inflammatory process
    • Inhaled Corticosteroids (ICS) à reduce eosinophils in airways and sputum, and numbers of activated T cells and surface mast cells in airway mucosa. These effects reduce inflammation and AHR.
    • Antileukotrienes à block cys-LT1 receptors
      • Cysteinyl-leukotrienes are potent bronchoconstrictors, cause microvascular leakage, and increase eosinophilic inflammation through the activation of cys-LT1-receptors.
    • Cromones à inhibit mast cell and sensory nerve activation, blocking trigger-induced asthma
    • Anti-IgE à blocking antibody that neutralizes circulating IgE without binding to cell-bound IgE and, thus, inhibits IgE mediated reactions
  • Controller Therapy – Inhaled corticosteroids (ICS) most effective
    • Reduce inflammatory cell #’s (eosinophils, lymphocytes, mast cells). Red in AHR, major goal of tx