Causes and Treatments of Asthma

Asthma is a chronic disorder of airways categorized physiologically as a reversible airflow obstruction, and pathologically with bronchoconstriction, the narrowing of the airways in the lungs due to the constriction of the surrounding smooth muscle. Asthma affects children and adolescent worldwide, caused by environmental, host, genetic factors and a variety of potential triggers. The sign and symptoms of asthma include chest tightness, wheezing, coughing, and dyspnea. One of the symptomatic treatments involves relaxing lungs smooth muscle, most commonly with inhaled β2-agonists (salbutamol).

Figure 1 :The pathophysiology of asthma

In this process, the inflammatory response developed as patients exposed to allergens such as bacteria, dust or smoke that are trapped by the mucus. These allergens bind with receptors mast cell, dendritic cells and activated IgE-dependent response mechanism. This Mast cell triggers the march inflammatory cells including neutrophil and eosinophil. Activation of mast cell by allergens through IgE-dependent mechanism also releases mediators such as histamine, tryptase, leukotrienes, and prostaglandins. The Dentritic cell which are specialized macrophage like cells in the airway epithelium are triggered by allergen to promote TH2 cell differentiation with the help of mediators such as IL-12 and tumor necrosis factor a.

The presence of inflammatory mediators causes mucus hypersecretions which will then cause formation of mucous plug that will block the airway. This will trigger hyperplasia of sumucosal gland in large airways and increased number of epithelial goblet cells. The mediators involve in this process include IL-4 and IL-13.

Inflammatory mediators also cause vasodilation of the new vessels and causes microvascular plasma leak from the vessels to the airway causing oedema to the airway. This increases airway mucosal blood flow in asthma which increases vascular volume that contributes to airway narrowing. Microvascular leakage from postcapillary venules results in airway oedema and plasma exudation into airway lumen.

Mediators including histamine, prostaglandin D2 and leukotriene also cause contraction of airway smooth muscle thus causing bronchoconstriction. In asthmatic patient there would be hyperplasia and hypertrophy of airway smooth muscle stimulated by growth factors such as platelet-derived growth factors that are released from inflammatory cells.

Basement membrane is also thickened due to subepithelial fibrosis with deposition of types III and V collagen. It occurs due to eosinophilic infiltration by release of profibrotic mediators such as transforming growth factor β. This fibrosis contributes to irreversible narrowing of airways.

Inflammatory mediators may activate sensory nerves resulting in reflex cholinergic bronchoconstriction or release of inflammatory neuropeptides which further exacerbate asthma.