Asthma is a reversible chronic airways condition characterized by airway obstruction, bronchial hyperresponsiveness and chronic inflammation. Exposure to triggers causes an inflammatory cascade and symptoms, such as wheeze, dyspnoea, and cough. It is the most common medical condition in children, affecting 1 in 10 to varying degree. Peaks in prevalence occur at 10 and 59 years of age, with a tendency towards those of an atopic (hypersensitive allergic/ genetic predisposition) nature. In asthma, there is a swing in balance between two opposing T- helper (Th) cell populations towards persistent and excessive T- helper cell type 2 (Th2) dominated immune responses. Th1 cells are involved in response to infection, while Th2 cells are responsible for cytokine production (e.g. IL- 4, IL- 5, IL- 6, IL- 9, and IL- 13) that are involved in allergic reaction, which may explain the overproduction of IgE, the presence of eosinophils and airway hyperresponsiveness. In the case of inhaled allergens, lung- based dendritic antigen- presenting cells ultimately stimulate Th2 cell production from naive Th0 cells (Figure 3.1). Aspirin and other NSAIDs can also initiate asthma symptoms, although this appears to be non- IgE dependant. Other dominant cells seen in asthma include mast cells and eosinophils. Mast cells, when activated by inhaled antigen, release bronchoconstrictive factors like histamine, cysteinyl-leukotrienes, prostaglandin D<sup>2</sup>, and eosinophil chemotactic factor. Mast cells in the airway may be sensitive to osmotic changes, thus account for exercise- induced asthma. The production of IL- 5 from activated Th2 and mast cells causes differentiation of eosinophils, which then migrate to the lung tissue, where they adhere to surface proteins like vascular- cell adhesion molecule 1 (VCAM- 1) and intercellular adhesion molecule 1 (ICAM- 1). Upon activation, these release pro- inflammatory cytokines like leukotrienes and granule proteins, which injure airway tissues. Additionally, eosinophil life is prolonged by the presence of IL- 4 and granulocyte- macrophage colony-stimulating factor (GM- CSF). Collectively, the persistence and presence of eosinophils may potentiate chronic inflammatory changes and this correlates closely with the clinical severity of disease. The overall cellular balance shift (Th2 dominance, mast cells, and eosinophils) and presence of an inflammatory stimulus results in bronchoconstriction (mainly via IgE- dependant release of mediators from mast cells constricting smooth muscle cells), airway oedema (through inflammation, mucus hypersecretion, and smooth muscle hypertrophy and hyperplasia), and airway hyperresponsiveness (through inflammation, dysfunctional neuroregulation, and structural changes).
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