Pathophysiological mechanisms of asthma. Application of cell and molecular biology techniques.
Asthma is a common increasing and relapsing disease that is associated with genetic and environmental factors such as respiratory viruses and allergens. It causes significant morbidity and mortality. The changes occurring in the airways consist of a chronic eosinophilic and lymphocytic inflammation, together with epithelial and structural remodeling and proliferation, and altered matrix proteins, which underlie airway wall narrowing and bronchial hyperresponsiveness (BHR). Several inflammatory mediators released from inflammatory cells such as histamine and cysteinyl-leukotrienes induce bronchoconstriction, mucus production, plasma exudation, and BHR. Increased expression of T-helper 2 (Th2)-derived cytokines such as interleukin-4 and 5 (IL-4, 5) have been observed in the airway mucosa, and these may cause IgE production and terminal differentiation of eosinophils. Chemoattractant cytokines (chemokines) such as eotaxin may be responsible for the chemoattraction of eosinophils to the airways. The initiating events are unclear but may be genetically determined and may be linked to the development of a Th2-skewed allergen-specific immunological memory. The use of molecular biology techniques on tissues obtained from asthmatics is increasing our understanding of the pathophysiology of asthma. With the application of functional genomics and the ability to transfer or delete genes, important pathways underlying the cause if asthma will be unraveled. The important outcome of this is that new preventive and curative treatments may ensue.
Chung
K F
KF
National Heart & Lung Institute, Imperial College, Dovehouse St., London SW3 6LY, UK. f.chung@ic.ac.uk
Adcock
I M
IM
D000818:Animals; D001249:Asthma / Q000453:epidemiology / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D002908:Chronic Disease; D020732:Cytogenetic Analysis; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D008967:Molecular Biology; D014157:Transcription Factors / Q000378:metabolism
D016207:Cytokines; D014157:Transcription Factors