Background information respiration | Pathophysiology | Overview

Mechanisms of acute and chronic inflammation in asthma

Airway inflammation and remodelling

Airway inflammation and airway remodelling are the two parts of the pathological process in asthma development. Although discriminated entities they are influenced and maintained by mutual molecular processes e.g. certain mediator release.

Airway inflammation is characterised by an increased number of activated eosinophils, mast cells, macrophages and T-lymphocytes in the airway mucosa and lumen. Inflammation in asthma is extremely complex in origin, regulation and outcome.

Airway biopsies of subjects with extrinsic asthma manifested through IgE-dependent mechanisms as well as with intrinsic asthma show T-helper cell subtype 2 to be primarily involved. The cytokines – IL-4, IL-5, IL-9, IL-13 and IL-16 – secreted by this subtype stimulate IgE synthesis in B-lymphocytes and activate mast cells, basophils and eosinophils. In response to stimulation these cells release mediators of inflammation like histamine, prostaglandins or leukotrienes resulting in bronchial hyperresponsiveness and airway obstruction.

Inflammation in asthma predominantly affects central and peripheral conducting airways and occurs both inside and outside the smooth muscle layer. Besides immunological processes predominantly triggered by specific antigen-response the bronchial epithelium exposed to injury or stress (e.g. viruses, irritants) also appears to induce a microenvironment that facilitates eosinophilic inflammation.

Airway remodelling is a complex process resulting in altered airways structure. This process involves dedifferentiation, migration and maturation of structural cells. Thickening of the lamina reticularis occurs early in the development of asthma and appears to be pathognomonic for the disease. This increase in density results from interstitial collagen and fibronectin deposition produced by activated myofibroblasts, which derive from attenuated fibroblasts.

Additionally activated myofibroblasts synthesise various growth factors, chemokines and cytokines promoting proliferation of smooth muscle cells and increase of microvascular permeability. Deposition of molecules like complex proteoglycans in the extracellular matrix (ECM), which is directly correlated with disease duration, appears to be another factor involved in airway remodelling. Proteoglycans may provide a reservoir for cytokines and growth factors, bind water causing tissue swelling, serve as ligands for cell adhesion molecules on inflammatory cells and promote leukocyte mediator release.

Literature:

Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma. From bronchoconstriction to airways inflammation and remodelling. 2000. Am J Respir Crit Care Med , 161: 1720-1745

O'Byrne P. GINA Executive Commitee. Global strategy for asthma management and prevention. 2004. National Institutes of Health. Publication No 02-3659

Roman J. Extracellular matrix and lung inflammation. 1996. Immunol Res , 15: 163-178

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