Up to the mid-1980s there was a fairly general consensus that the mast cell was central in the pathophysiology of asthma. In 1983 on the occasion of the Third International Symposium on Asthma, it was suggested that ‘perhaps asthma is no more than physical allergy of the mast cells of the lung’, the analogy being made with urticaria where it was established that allergic and non-allergic triggers could release histamine (and presumably other mediators) from mast cells, which in turn produced the urticarial lesion. Thus asthma, which was characterized clinically as intermittent airway narrowing, was believed to result, in atopic asthma, from intermittent type I (immediate-type hypersensitivity) reactions by IgE-dependent mast cell mediator release or by mast cell degranulation owing to physical or other stimuli in non-atopic (‘intrinsic’) asthma.
The hypothesis explained both atopic and non-atopic asthma, as well as the mode of action of drugs such as sodium cromoglycate, considered at that time to work principally through stabilization of mast cells. Set against the ‘leaky mast cell’ theory was the observation that corticosteroids, a mainstay in asthma treatment since the 1950s, had no effect on histamine release from dispersed mast cells from human lung tissue. Furthermore, agents such as antihistamines, which antagonize the effects of mast cell mediators, were shown to have little effect in asthma. In addition, the mast cell hypothesis did not explain why only a proportion of atopic subjects are asthmatic since mast cell degranulation might be expected to produce similar symptoms in any sensitized individual.
Most important was the realization that, even between acute attacks, the asthmatic airways were hyper-responsive to non-specific stimuli such as histamine even when the patient was asymptomatic, and thus the concept of asthma as a chronic inflammatory disease emerged. This was given greater currency by the application of fibre-optic bronchoscopy and the ability to study the inflammatory infiltrate in the airway mucosa of asthmatics. This advance in the early 1980s soon established that an eosinophilic and mononuclear cell infiltrate was a feature of asthmatic airways even in the absence of symptoms. By 1987, asthma definitions included eosinophilic airway hyper-responsiveness, airway inflammation and desquamative bronchial eosinophilia as charactersitics of the disease.
There were several reasons for turning to the T cell for clues as to what ‘drives’ the asthma process — not least of which being the exquisite sensitivity of T cells to the anti-proliferative action of corticosteroids (a drug that remains the mainstay of treatment of the disease). Also, at this time, there had been a considerable increase in understanding of the allergic response in terms of the essential role of T cells in both antibody-mediated as well as cell-mediated hypersensitivity reactions.
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