title: The 1992 Cournand Lecture. Asthma: past, present and future.
abstract: The association of asthma with the release of inflammatory mediators, through a mechanism that involves the immune system, has taken almost 100 years to evolve. While studies on lung tissue from patients who had died from asthma pointed to inflammation of the airways as a major lesion, clinicians have, until relatively recently, preferred to consider the disease more in terms of airways dysfunction rather than the cause(s) of this dysfunction. Bronchial mucosal biopsy and lavage has reaffirmed the view that asthma is a special type of airway inflammation involving mast cells and eosinophils which is orchestrated by T-lymphocytes of a Th2-like phenotype. Through cytokine release, these cells upregulate the function of mast cells and eosinophils. However, other factors are now considered important in the maintenance and chronicity of the inflammatory response both through tissue remodelling (e.g. fibrosis) and through the secretion of cytokines from epithelial, endothelial and constitutive mesenchymal cells. Evidence is accumulating that these events are genetically-linked although this is likely to involve multiple genes. Of special importance is the role of the environment both in the induction of allergen sensitised airways and the subsequent inflammatory response that follows. Included in these are intrauterine events, early life exposure to allergens, pollutants and viruses. If prevention of asthma is to be a future target for intervention, then future work should concentrate on those early genetic and environmental factors that initiate the inflammatory response rather than relying on strategies that attempt to reverse established disease.
authors.affiliation: University Medicine, Southampton General Hospital, UK.
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
mesh_terms: D001249:Asthma / Q000209:etiology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines