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• W2189138974 abstract "The international guidelines on asthma management, published in 1992 [1], suggest that inhaled anti-inflammatory therapy should be initiated in mild-to-moderate asthma when, among other criteria, the patient has chronic symptoms that require almost daily use of a shortacting inhaled β2-agonist. The recommendations for primary therapy are the inhaled corticosteroids, sodium cromoglycate or nedocromil sodium, but which drug should be used first is left to individual choice, apart from a recommendation that all children should begin with a trial of sodium cromoglycate. A workshop was held in June 1993 in Grindelwald, Switzerland, to review the risks and benefits of inhaled anti-inflammatory therapy for asthma, that might be considered in arriving at that choice. Safety Dukes recounted the results of his review of World Health Organization and manufacturer's clinical safety data on sodium cromoglycate and nedocromil sodium. Despite its availability for over 20 yrs, sodium cromoglycate has not been associated with serious side-effects and remains one of the safest drugs ever developed. Nedocromil sodium is newer but appears to be following this tradition of safety [2]. The most common complaint with nedocromil sodium is a bitter taste experienced by 10‐15% of patients. The potential systemic sideeffects of inhaled corticosteroids on growth, bone metabolism, the hypothalamo-pituitary-adrenal (HPA) axis and skin were discussed separately at the workshop. Pedersen and Wolthers reviewed their studies on the effects of budesonide and beclomethasone dipropionate (BDP) on short-term growth using knemometry, a technique which accurately measures lower leg growth over a period of weeks. Significant reductions in growth velocity were only evident during treatment with budesonide 800 µg·day -1 , and BDP 400 µg·day 1 . The extent to which short-term studies can be extrapolated to predict final height attained is not known, since growth naturally proceeds in lulls and spurts, and at times stops altogether; but, they may be a fairly reliable predictor. Pedersen also described a long-term follow-up over approximately 4 yrs and results to date are similar to those of the knemometry studies. Doull described a study [3] in which his group measured actual height over a period of 6 months during treatment with BDP, 400 µg·day -1 , in children with mild asthma, and found a highly significant reduction in growth which had not caught up in the 5 months following discontinuation of treatment. Pedersen concluded that in the short-term (weeks) and intermediate-term (months), budesonide at doses of ≤400 µg·day -1 via Nebuhaler does not have an adverse effect on growth; whereas BDP 400 µg·day -1 via Diskhaler does have a significant effect upon growth velocity. At present there are no good prospective studies evaluating longterm growth and the effect on final growth outcome, but uncontrolled asthma has a detrimental effect on growth, and this is probably the most important factor in choosing anti-inflammatory therapy. Pedersen and other speakers stressed the importance of defining the particular corticosteroid and the delivery system, since the degree of systemic absorption depends on the pharmacokinetic properties of the drug and on the delivery device. The difference in the effect on growth between the same dose of BDP delivered via Diskhaler and budesonide via Nebuhaler may reflect differences in the amounts of drug delivered to the lung and that which is swallowed, as well as the drugs' relative bioavailabilities from the lungs and intestines. Any unchanged drug absorbed from the lungs is not subject to first-pass hepatic metabolism. For example, delivery via Turbuhaler has a higher clinical effect because it delivers more drug to the lungs, but also a higher systemic effect since more drug is absorbed at this site [4]. However, systemic absorption arising from the drug deposited in the mouth can be reduced by mouth washing. Toogood reviewed the effects of inhaled corticosteroids on bone metabolism, most of the studies being with BDP and budesonide, and largely the latter. At high doses, both drugs may decrease serum levels of osteocalcin; budesonide, may inhibit procollagen production and BDP may increase urinary hydroxyproline output. These changes are subtle and their significance is unclear, although inhibition of dehydroepiandrosterone production by either drug may be important to postmenopausal asthmatic women, who depend critically upon androgen production from the adrenal cortex for their ability to biosynthesize oestrogen to restrain osteoclast activity and" @default.
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