The use of inhaled corticosteroids in the treatment, of bronchial asthma with particular reference to beclomethasome dipropionate.

Abstract

The Problem : Corticosteroids may be necessary to control the symptoms of many patients with chronic bronchial asthma, their use, however, is frequently complicated by side effects, which are unpleasant for the patient and often worrying for the physician. Any measure, therefore, which would permit a useful anti-inflammatory effect of these drugs whilst minimising side effects would be of benefit to patients. It is for this reason that, for over twenty years, repeated attempts have been made with every corticosteroid as they have been introduced, to administer them directly onto the bronchial mucous membrane by inhalation in one form or another. These attempts have failed, probably because the steroids used have had potent systemic glucocorticoid effects following any route of administration. The use of inhaled beclomethasone-17,21-dipropionate, however, is in marked contrast to the earlier experiences with inhaled corticosteroids, because the symptoms of bronchial asthma are controlled without important. corticosteroid induced side effects. The aim of this thesis is twofold, first, to establish by simple means, the properties of beclomethasone-17, 21- dipropionate in in an attempt to discover, the reasons why this corticosteroid should be successful when given by inhalation whilst others were not, and secondly, to discover whether the regular use of an inhaled corticosteroid may be complicated by any side effects, peculiar to this route of administration. Summary of the Present Work : The use of corticosteroids in the treatment of bronchial asthma, and, the attempts to reduce side effects by clinical means, including the local, inhaled use of corticosteroids are reviewed. The work of steroid chemists aimed at producing compounds where there may be some separation of antiinflammatory from other glucocorticoid effects is outlined. The literature on inhaled beclomethasone-l7, 2l-dipropionate is reviewed and contrasted with the earlier studies on inhaled corticosteroids. The properties of beclomethasone-17,21-dipropionate in man are investigated. These original studies include an assessment of its topical anti-inflammatory potency on the skin; the effects following its administration by inhalation by mouth, intra-nasally and intravenously on the Hypothalamic-Pituitary-Adrenal (H. P. A. ) axis, together with an investigation of its absorption, and metabolic fate after oral and intravenous administration are described. The effects of beclomethasone-l7,2l0-dipropionate upon circulating white blood cells and fasting blood sugar levels have also been investigated. Particular attention has been paid to describing and reviewing the evidence in animals and in man concerned with potential toxic effects on the tissues of the respiratory tract. The incidence of bacterial infection in the lungs of patients treated with beclomethasone-17,21-dipropionate has also been investigated. Increased colonisation of the oro-phaxynx with candida albicans, and, less frequently, clinical candidiasis is a complication of treatment with beclomethasone-17,21-dipropionate. This, together with possible predisposing factors is assessed. It is concluded : one, that high topical activity together with lower systemic activity and metabolic inactivation of the swallowed portion of beclomethasone-17,2l-dipropionate are the likely reasons why this corticosteroid, in the doses employed, controls bronchial asthma in most patients without causing important glucocorticoid. side effects. And two, although no clinical or experimental evidence exists at present to suggest that this drug is exerting any deleterious effect on the tissues of the respiratory tract, this cannot be excluded and continued vigilance is necessary. Oro-pharyngeal candidiasis is a complication of this treatment, but, at present, the advantages to the patient of reduced or no oral dosage with corticosteroids, outweighs the disadvantages of candidiasis, because this does not occur invariably, it is frequently symptomless, easily treated and has only occurred superficially.