6. Bronchial asthma – pathogenesis, clinical features, asthma severity scoring , diagnosis

Essay 6- Bronchial asthma- pathogenesis, clinical features, asthma severity scoring, diagnosis

• Definition
• Chronic inflammatory disorder of the airways that causes episodes of airway obstruction, bronchial hyper-responsiveness and airway inflammation
• Obstruction is reversible
• Defined by the history of respiratory symptoms such as wheeze, SOB, chest tightness and cough that vary in intensity and vary over time
• Risk factors
• Genetic predisposition- defects in chromosomes 5 and 11, atopy, bronchial hyper-reactivity
• Environment- exposure to allergens and chemicals, viral and bacterial infections, smoking, psychosomatic influence
• Triggers of asthma attacks
• Bronchospastic- depends on existing level of airway responsiveness.
• Examples are cold air, exercise, emotional upset, exposure to bronchial irritants (cigarette smoke)
• Inflammatory- exert effects through inflammatory response. They inflame and prime the airways so they are hyper-responsive to allergic and non-allergic stimuli
• Types of asthma
• TH2 asthma
• Caused by bronchial hyperresponsiveness
• As allergen enters system, it is engulfed by Maf that release IL 4,5,13
• IL-4 promotes B cell differentiation into plasma cells
• IL-5 and IL-13 recruit Eo
• IgE antibodies are produced which bind to Fc receptor of Eo or Neu and causes degranulation and release of histamine (causes bronchospasm)
• Occurs in children, adolescents
• Better prognosis
• Easier to manage
• Non TH2 asthma
• Triggered by smoking, exercise, obesity
• Comprised of TH1 (CD8+ T Ly) and Th-17
• IL 1,6 and TNF alpha are released that promote Neu recruitement
• Neu release Leukotrienes (B4,C4,D4)
• One of their roles (specifically, leukotriene D4) is to trigger contractions in the smooth muscles lining the bronchioles
• Has a late onset
• Poor prognosis
• Pathogenesis
• Acute phase response
• Results in immediate bronchoconstriction on exposure to inhaled antigen or irritant
• Symptoms develop in 10-20 mins
• There is release of chemical mediators from Ig-E coated mast cells
• Mediator release results in opening of mucosal intercellular junctions and enhancement of antigen movement

• Late phase response
• Develops 4-8 hours after exposure to asthmatic trigger
• Involves inflammation and increased airway responsiveness that prolongs attack
• Reaches maximum within a few hours
• Trigger causes release of inflammatory mediators from mast cells, macrophages and epithelial cells
• These substances induce migration and activation of other inflammatory cells (Ba,Neu,Eo) which then produce epithelial injury and edema
• There is also change in mucociliary function and reduced clearance of respiratory tract secretions

• Symptoms
• Wheezing
• Breathlessness
• Chest tightness
• Cough that often is worse at night and in the early morning.
• These episodes usually are reversible either spontaneously or with treatment
• Airways narrow because of bronchospasm, edema of the bronchial mucosa, and mucus plugging