Some Pathophysiology

The bronchi become hyperreactive as a result of a persistent inflammatory process in response to a number of stimuli that include biological agents,

7 A man with severe hay fever who received at least one depot injection of corticosteroid each year for eleven years developed avascular necrosis of both femoral heads, an uncommon but serious complication of exposure to corticosteroid. Nasser SMS, Ewan P W 2001 British Medical Journal 322: 1589.

e.g. allergens, viruses and environmental chemicals, e.g. ozone and glutaraldehyde. Inflammatory mediators are liberated from mast cells, eosinophils, neutrophils, monocytes and macrophages. Some mediators such as histamine are preformed and their release causes an immediate bronchial reaction. Others are formed after activation of cells and produce more sustained bronchoconstriction; these include metabolites of arachidonic acid from both the cyclo-oxygenase, e.g. prostaglandin D2 and lipoxygenase, e.g. cysteinyl-leukotrienes C4 and D4, pathways. In addition platelet activating factor (PAF) is being increasingly recognised as an important mediator (see p. 280).

The relative importance of many of the mediators is not precisely defined but they interact to produce mucosal oedema, mucus secretion and damage to the ciliated epithelium. Breaching of the protective epithelial barrier allows hyperreactivity to be maintained by bronchoconstrictor substances or by local axon reflexes through exposed nerve fibres. Wheezing and breathlessness result. The bronchial changes also obstruct access of inhaled drug to the periphery, which is why they can fail to give full relief.

Asthma, like many of the common chronic disorders (hypertension, diabetes mellitus), is a polygenic disorder and already genetic loci linked to either increased production of IgE or bronchial hyperreactivity have been reported in some families with an increased incidence of asthma.

Early in an attack there is hyperventilation so that Pa02 is maintained and PaC02 is lowered but with increasing airways obstruction the Pa02 declines and PaCOz rises, signifying a serious asthmatic episode.

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