Pathophysiology of Asthma

                                      Asthma

The National Asthma Education and Prevention Program (NAEPP) defines asthma as a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. In susceptible individuals, inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing. These episodes are usually associated with airflow obstruction that is often reversible either spontaneously or with treatment.

PATHOPHYSIOLOGY

The major characteristics of asthma include a variable degree of:

• Airflow obstruction (related to bronchospasm, edema, and hypersecretion),
  
• Bronchial hyper responsiveness and
  
• Airway inflammation.
  

Early phase Allergic reaction
Inhaled allergens cause an early-phase allergic reaction characterized by activation of cells bearing allergen-specific immunoglobulin E (IgE) antibodies. There is rapid activation of airway mast cells and macrophages, which release pro-inflammatory mediators such as histamine and eicosanoids that induce contraction of airway smooth muscle, mucus secretion, vasodilation, and exudation of plasma in the airways. Plasma protein leakage induces a thickened, engorged, edematous airway wall and a narrowing of the airway lumen with reduced mucus clearance.

Late phase inflammatory reaction
The late-phase inflammatory reaction occurs 6 to 9 hours after allergen provocation and involves recruitment and activation of eosinophils, T lymphocytes, basophils, neutrophils, and macrophages.

• Eosinophils migrate to the airways and release inflammatory mediators (leukotrienes and granule proteins), cytotoxic mediators, and cytokines. The 5-lipoxygenase pathway of arachidonic acid metabolism is responsible for production of cysteinyl leukotrienes. Leukotrienes C4, D4, and E4 are released during inflammatory processes in the lung and produce bronchospasm, mucus secretion, microvascular permeability, and airway edema.
  

• T-lymphocyte activation leads to release of cytokines from type 2 T-helper (TH2) cells that mediate allergic inflammation (interleukin [IL]-4, IL-5, and IL-13). Conversely, type 1 T-helper (TH1) cells produce IL-2 and interferon-γ that are essential for cellular defense mechanisms. Allergic asthmatic inflammation may result from an imbalance between TH1 and TH2 cells.
  

• Mast cell degranulation in response to allergens results in release of mediators such as histamine; eosinophil, and neutrophil chemotactic factors leukotrienes C4, D4, and E4; prostaglandins; and platelet-activating factor (PAF). Histamine is capable of inducing smooth muscle constriction and bronchospasm and may play a role in mucosal edema and mucus secretion.
  

• Alveolar macrophages release a number of inflammatory mediators, including PAF and leukotrienes B4, C4, and D4. Production of neutrophil chemotactic factor and eosinophil chemotactic factor furthers the inflammatory process.

Neutrophils are also a source of mediators (PAFs, prostaglandins, thromboxanes, and leukotrienes) that contribute to BHR and airway inflammation.

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