Pathophysiology Airway hyper-reactivity (AHR) - the tendency for airways to narrow excessively in response to triggers that have little or no effect in normal individuals is integral to the diagnosis of asthma and appears to be related, although not exclusively, to airwayinflammation . Other factors likely to be impoant in the behaviour of airway smooth muscle include the degree of airway narrowing and neurogenic mechanisms. The relationship between atopy (the propensity to produce IgE) and asthma is well established and in many individuals there is a clear relationship between sensitisation and allergen exposure, as demonstrated by skin-prick reactivity or elevated serum-specific IgE. Common examples of allergens include house dust mites, pets such as cats and dogs, pests such as cockroaches, and fungi. Inhalation of an allergen into the airway is followed by an early and late-phase bronchoconstrictor response . Allergic mechanisms are also implicated in some cases of occupational asthma . In cases of aspirin-sensitive asthma, the ingestion of salicylates results in inhibition of the cyclo-oxygenase enzymes, preferentially shunting the metabolism of arachidonic acid through the lipoxygenase pathway with resultant production of the asthmogenic cysteinyl leukotrienes. In exercise-induced asthma, hyperventilation results in water loss from the pericellular lining fluid of the respiratory mucosa, which, in turn, triggers mediator release. Heat loss from the respiratory mucosa may also be impoant. In persistent asthma, a chronic and complex inflammatory response ensues, characterised by an influx of numerous inflammatory cells, the transformation and paicipation of airway structural cells, and the secretion of an array of cytokines, chemokines and growth factors. Examination of the inflammatory cell profile in induced sputum samples demonstrates that, although asthma is predominantly characterised by airway eosinophilia, neutrophilic inflammation predominates in some patients while in others scant inflammation is observed: so-called 'pauci- granulocytic' asthma. Ref Davidson edition23rd pg 568