Guest Editorial

Drugs 15: 1-2 (1978) © ADIS Press 1978

Aerosol Bronchodilators in Preventive Treatment of Asthma Ann J. Woolcock Department of Medicine. University of Sydney. Sydney

Over the last few years, with the introduction of new drugs, the approach to the treatment of asthma has changed, with increasing emphasis being placed on preventing attacks rather than on treating wheezing episodes. The asthmatic has excessive 'twitchiness' of his airways . The cause of this 'twitchiness', called bronchial hyper-reactivity, is not known but the airways narrow excessively in response to a number of stimuli including mediators from mast cells (released by allergens in allergic people), exercise, infections, cold air, strong smells, and emotional upsets. In general, asthmatics who have very severe bronchial hyper-reactivity have severe asthma clinically, while those with less severe hyper-reactivity have only occasional attacks. These mild asthmatics respond well to almost any bronchodilator and their management is not a problem. Severe asthmatics , i.e. those having symptoms requiring medication every day, pose a greater problem. These patients, if they do not take medication and if the provoking agent is not removed, develop severe narrowing of the airways with mucosal oedema, thickening of the bronchial wall, infiltration with cells, and often increased mucous secretion. These changes, which probably occur throughout the large and the small airways, are less easily reversed with sympathomimetic bronchodilator drugs alone and require corticosteroid therapy.

There are a number of reasons for keeping the airways of severe asthmatics fully dilated and for preventing the occurrence of attacks. Firstly, it is known that many patients with severe asthma have residual airways obstruction between attacks [I]and that some of them develop permanent and increasing airways obstruction over a period of years. Secondly, if mediators are released, they will cause less narrowing and less symptoms if acting on normal rather than narrowed airways. Thirdly, it is known that constant exposure to mediators (as in the polIen season in the case of many allergic asthmatics) increases the level of bronchial hyper-reactivity, making the airways more 'twitchy ' [2] and thus allowing stimuli to produce attacks more easily. It is possible that if the airways have long periods without stimulation by mediators, the overall degree of bronchial reactivity decreases. This is the most likely reason for children 'growing out' of their asthma . A recent article by Anderson et al. [3] (see summary Drugs 14: 155, 1977) reports the results of a study of exercise-induced asthma in which aerosol and oral forms of bronchodilator were given prior to the exercise. Both forms of the drugs resulted in similar levels of bronchodilatation, but only the aerosol form of the drug fully prevented the exercise-induced attack. The explanation for this difference between the methods of administration, which is now well documented in exercise-induced attacks for the ~2-

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Aerosol Bronchodilators in Asthma

adrenoceptor stimulant bronchodilators, is not known. Presumably, the aerosol affects something in the lumen or mucosa which the oral drug does not (at least in the dosage given). Mast cells are found throughout the bronchial tree and some are known to be superficial, perhaps even in the lumen . Mast cells are involved in a ~2-adrenoceptor response and when these are so stimulated (in this study by salbutamol), there is less mediator released when an antigen-antibody reaction occurs at the cell surface [41. It is possible that exercise-induced asthma is related in some way to mediator release from mast cells in the upper part of the airway and this release is prevented by the bronchodilator as an aerosol. The importance of the findings of Anderson et al. [31 lies in the fact that they have demonstrated a preventive as well as a relieving role for aerosol bronchodilators in the treatment of asthma. Although not well documented, it seems likely that aerosol bronchodilators also protect against allergen-induced attacks . It therefore makes sense to treat severe asthmatics with regular aerosol bronchodilator therapy throughout the 24 hour period (4 or 5 times a day) to prevent attacks , at least when exercise and/or allergens are the documented provoking factors in that patient . Experience shows that in many instances this is enough to prevent almost all attacks and to keep the airways fully dilated. Measurements of lung function such as vital capacity (VC), I second forced expiratory volume (FEV), or peak expiratory flow rate (PEFR) are mandatory to document the normal airway function . Sodium cromoglycate is also known to block exercise- and allergen-induced asthma [51 and in many allergic asthmatics (particularly children and young adults) it is effective alone. Most severe asthmatics, however, are best controlled by sodium cromoglycate plus a long-acting aerosol bronchodilator. Beclomethasone dipropionate inhaler is needed if these 2 drugs do not keep the lung function normal and the patient free from attacks . There has been considerable experience with these drugs in Australasia. Of the ~2-adrenoceptor stimulant bronchodilators, orciprenaline has been in use

since 1962 and the newer long-acting bronchodilators such as salbutamol, terbutaline, fenoterol or hexoprenaline are not substantially different in duration, effect or side-effects [61. They cause slight tachycardia and skeletal tremor but these effects are usually seen only when the oral form is used; the aerosol forms have almost no side-effects. Sodium cromoglycate and beclomethasone dipropionate inhalers have been used for a shorter period of time but no major harm long-term side-effects have been demonstrated. In view of the low dose used in the inhaled forms of these 3 types of drug, and their apparent safety and efficacy in preventing attacks, the severe asthmatic is likely to be better off taking regular medication by inhalation than having continued attacks which, unless treated vigorously, in the long-term probably lead to permanent airways obstruction [7).

References I . Rub infeld. A.R . and Pain . M.e. : Perception of asthma. Lancet I: 882-884 (1976) . 2. Howell , J .B.L.: Asthma: A clinical view . Identification of asthma. CIBA Foundation Study Group 38 : 151-159 (197 I). 3. Anderson. S.A .: Searle. P.R.: Bandler, L.: Theobald. G. and Lindsay , D.A.: Inhaled and oral salbutamol in exercise-induced asthma. American Review of Respiratory Disease 114: 493-500 (1976) . 4. Kaliner, M. and Austin . K.F .: Immunologic release of chemical mediators from human tissues . Annual Review of Pharmacology 15: 177-189 (J 975). 5. Godfrey. S.: The effect of disodium cromoglycate on asthma induced by exercise: in Proceedings of the VII International Congress of Allergology, Florence . Italy. pp.35-40 (Edizioni , CEPI . Roma 1970). 6. Leifer. K.N. and Wittig. H.J. : The beta-2 sympathomimetic aerosols in the treatment of asthma. Annals of Allergy 35: 69-80 (1975) . 7. Woolcock. Ann J .: Inhaled drugs in the prevention of asthma. American Review of Respiratory Diseases 115: 191-194 (977).

Author's address: Prof. Ann J. Woo/cock , Department of Medicine. University of Sydney . Sydney . NSW 2006 (Australia).

Aerosol bronchodilators in preventive treatment of asthma.

Guest Editorial Drugs 15: 1-2 (1978) © ADIS Press 1978 Aerosol Bronchodilators in Preventive Treatment of Asthma Ann J. Woolcock Department of Medic...
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