HIGH-DOSE CORTICOSTEROID INHALERS FOR ASTHMA

HIGH-DOSE CORTICOSTEROID INHALERS FOR ASTHMA

23 HIGH-DOSE CORTICOSTEROID INHALERS FOR ASTHMA INHALED corticosteroids have become such a standard hard to realise that they in in UK the introduced...

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HIGH-DOSE CORTICOSTEROID INHALERS FOR ASTHMA INHALED corticosteroids have become such a standard hard to realise that they in in UK the introduced were only 1972, and 4 years later in whose In USA. the patients symptoms are not adequately controlled by sympathomimetic bronchodilators and sodium cromoglycate inhalations, inhaled corticosteroids can reduce or obviate the need for oral corticosteroid therapy. In the early evaluations a daily dose of about 400 g (8 puffs) of beclomethasone dipropionate (BDP) or betamethasone valerate was effective in most of the patients who responded;I higher doses of up to 1600 g did not seem to bring greater benefit and were associated with impaired adrenal responsiveness.2 This evidence, and the practical difficulties of taking over 30 puffs daily, led to lower doses becoming standard, although other work in small numbers of patients showed that some patients’did benefit from higher doses without adrenal suppression.The development of an inhaler delivering 250 g BDP per puff, and the appearance of new corticosteroid inhalers containing budesonide (50 g or 200 g per puff) has reawakened interest in high-dose inhaled corticosteroid therapy for asthma. Because the use of such treatments increases the cost of inhaled corticosteroid therapy as much as fourfold, we need to be reassured that high doses of inhaled corticosteroid are justified by improved control of asthma, a reduction in side-effects, or a lower net inhibition of adrenal function. Evidence of clinical benefit of high-dose BDP comes from a large study of a mixed group of patients, reported retrospectively.’ When 162 patients on long-term oral and standard-dose inhaled corticosteroid were started on highdose BDP, 27% were then able to stop oral steroids altogether, and 3907o could reduce their oral steroid dosage. Of a further 131 patients who did not require maintenance oral corticosteroids 65% showed much improved asthmatic control when changed from standard-dose to high-dose BDP. The same workers5showed that, of patients who had not previously been taking oral corticosteroids, 91% of those taking up to 1500 pg BDP daily retained normal adrenal responsiveness; among those on higher doses the percentage was lower. While there probably remains a need for a controlled prospective study with high-dose BDP, a trial of inhaled budesonide, 1600 J1g daily given via the 750 ml spacer extension (’Nebuhaler’) has been briefly reported.It showed significant improvements in peak expiratory flow recordings, a reduction of about 50% in oral corticosteroid requirements, and a reduction in the need for sympathomimetic bronchodilators. There does seem to be mounting evidence that many patients with more severe asthma requiring oral corticosteroids, or those inadequately controlled on standard-dose inhaled corticosteroid, can benefit from high-dose inhaled corticosteroid. In those who can avoid oral corticosteroids as a result, there will be the added benefit of maintained adrenal treatment for chronic asthma that it is

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Cooper BJ, Grant IWB Beclomethasone dipropionate aerosol in treatment of chronic asthma. Quart J Med 1977; 46: 295-308 2. Gaddie J, Petrie GR, Reid IW, Sinclair DJM, Skinner C, Palmer KNV. Aerosol beclomethasone dipropionate; a dose response study in chronic bronchial asthma Lancet 1973, ii: 280-81. JF, Clark TJH. Response of patients receiving high dose beclomethasone dipropionate Thorax 1974, 29: 571-73. 4 Smith MJ, Hodson ME. High-dose beclomethasone inhaler in thetreatment of asthma Lancet 1983, i. 265-69 5 Smith MJ, Hodson ME Effects of long-term inhaled high dose beclomethasone dipropionate on adrenal function. Thorax 1983, 38: 676-81. 6 Laursen LC, Taudorf E, Weeke B, Glennov C High-dose inhaled budesonide in treatment of severe steroid-dependent asthmatics Lancet 1983; ii. 1305

responsiveness, although those requiring to continue oral corticosteroids will not gain in this way. As for the possible benefits resulting from a reduction in major systemic corticosteroid side-effects, a prospective and long-term study would be required; but there are already hints that the less frequent dosing (two or three times daily) may result in

reduced incidence of oropharyngeal to candidiasis, the larynx may also be affected by a dysphonia caused by an adductor vocal cord deformity which can occur from inhaled corticosteroids:88 fortunately, this change, which may be a local steroid myopathy, is usually reversible on withdrawal of treatment. While less frequent dosing may bring advantages, most of the patients treated with high-dose inhaled corticosteroids with twice or three times daily dosing were in a stable state; in less stable asthma more frequent dosing may be necessary9and, as with all patients on inhaled corticosteroids, oral corticosteroid should be given for exacerbations. On existing evidence high-dose inhaled corticosteroids have a place in patients whose asthma is poorly controlled by standard doses, and in patients already on oral corticosteroids who may benefit from a reduction in oral dosage, or improvement in control, or both. It would be quite improper to prescribe one of these expensive high-dose inhalers without making sure that the patient’s inhaler technique is immaculate; and if, after training, there is still doubt, the use of the rather cumbersome 750 ml spacer extension may improve deposition in the airways and reduce oropharyngeal deposition.’"’" If there is good evidence of improved control and lowered oral steroid requirement, continuation of highdose inhaled corticosteroid will be fully justified, but it will be wise to find the minimum dose required to keep good control, by regular observation and measurements of peak expiratory flow. The new high-dose inhalers should reduce long-term systemic steroid side-effects, but a prospective trial is needed to prove the point and confirm that, as with standard doses, there are no long-term local effects on the airways. a

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DISCITIS AND THE ACUTE ABDOMEN IN CHILDHOOD ANY list of causes of acute abdominal pain in adults will include spinal lesions. Because acute spinal disease is rare among children, it does not readily come to mind in the differential diagnosis of the acute abdomen. Two papers, from Liverpool’ and Dublin,2 each record three patients with discitis in whom the presenting symptom was abdominal pain. If the diagnosis comes to mind there should be no difficulty, since the clinical features are very consistent. The children are irritable, their temperature is slightly raised, the Toogood JH, Baskerville J, Jennings B, Anderson J, Johansson S-A. Determinants of oropharyngeal complications during aerosol steroid treatment of chronic asthma. Am Rev Resp Dis 1982; 125: suppl P120 (abstr). 8. Williams AJ, Baghat MS, Stableforth DE, Cayton RM, Shenoi PM, Skinner C. Dysphonia caused by inhaled steroids; recognition of a characteristic laryngeal abnormality. Thorax 1983; 38: 813-21. 9. Toogood JH, Baskerville JC, Jennings B, Lefcoe NM, Johansson S-A. Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid, budesonide. J Allergy Clin Immunol 1982; 70: 288-98. 10. Newman SP, Moren F, Pavia D, Little F, Clarke SW. Deposition of pressurised suspension aerosols inhaled through extension devices. Am Rev Resp Dis 1981; 124: 7.

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Toogood JH, Baskerville J, Jennings B, Lefcoe NM, Johansson S-A. Use of spacers to facilitate inhaled corticosteroid therapy of asthma. Am Rev Resp Dis 1984; 129:

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Hensey OJ, Coad N, Carty HM, Sills JM. Juvenile discitis. Arch Dis Child 1983, 58:

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Leahy AL, Fogarty EE, Fitzgerald RJ, Regan BF. Discitis as a cause of abdominal pain in children. Surgery 1984; 95: 412-14.

723-30. 983-87.