Pathophysiology

There are 2 major elements in the pathophysiology: inflammation and airway hyper-responsiveness (AHR). The large and the small airways with diameters <2 micrometres are the sites of inflammation and airway obstruction. [32]

Airway inflammation occurs secondary to a complex interaction of inflammatory cells, mediators, and other cells and tissues in the airway. An initial trigger leads to the release of inflammatory mediators, which leads to the consequent activation and migration of other inflammatory cells. The inflammatory reaction is a T-helper type 2 (Th2) lymphocytic response. Th2 inflammation is characterised by the presence of CD4+ lymphocytes that secrete interleukin (IL)-4, IL-5, and IL-13, the chemokine eotaxin, TNF-alpha, [33] and the leukotriene LTB4, a product of the lipoxygenase pathway, as well as mast cell tryptase. This Th2 response is important in the initiation and prolongation of the inflammatory cascade.

Other WBCs involved are eosinophils, basophils and mast cells, macrophages, invariant NK T cells, [34] and in near-fatal or status asthmaticus, neutrophils are important. [17] These cells move to the airway, causing changes in the epithelium, airway tone, and related autonomic neural control and hyper-secretion of mucus, mucociliary function alteration and increased smooth muscle responsiveness. Pathological studies of fatal asthma show severe hyper-inflation, mucous plugging with the mucus-containing mucins (proteins that are present in the blood). [17] Tissue biopsies show the deposition of eosinophil granular proteins throughout the lung tissue and damage of the epithelium mediated by those proteins. Denudation of the basal layer by epithelial cell sloughing produces clumps of cells in the sputum referred to as Creola bodies. There is also subbasement membrane deposition of collagen often referred to as thickened basement membrane, which is considered another hallmark.

Products of the inflammatory response induce smooth muscle contraction and consequent AHR. There appears to be at least 2 different kinds of AHR, a baseline fixed and an episodic variable element. [35] The underlying fixed AHR is possibly related to airway remodelling, whereas the variable AHR reflects the action of the inflammatory mediators, and are distinguished by direct and indirect bronchial challenges, respectively. Finally, airway smooth muscle in asthmatics is increased in mass, likely as a result of hypertrophy and hyperplasia, which in vitro studies display as having increased contractility. [35]