EFFICACY AND SAFETY OF LOW-DOSE TROLEANDOMYCIN THERAPY IN CHILDREN WITH SEVERE, STEROID-REQUIRING ASTHMA

Background: Troleandomycin (TAO), a macrolide antibiotic, was studied as an alternative treatment in 18 children with severe, steroid-requir ing asthma. Methods: In this investigation three treatment arms were u sed in randomized, double-blind, parallel fashion: combination TAO and methylprednisolone (MPn), combination TAO and prednisone, and MPn alo ne. Results: All groups tolerated a considerable reduction in glucocor ticoid dose over the 12 weeks of the study: 80% +/- 6% for TAO-MPn, 55 % +/- 8% for TAO-prednisone, and 44% +/- 14% for MPn alone. These redu ctions are all statistically significant (p < 0.05) within groups, and the differences between groups were statistically significant between the TAO-MPn and MPn alone groups. The concentration of methacholine r equired to induce a 20% decrease in forced expiratory volume in 1 seco nd and pulmonary function were not significantly improved in any treat ment group. Safety parameters including blood chemistry and hematology , adrenal function assessment, bone densitometry, and muscle strength testing, were not altered significantly. Two patients who received TAO had elevated liver enzyme levels; one required discontinuation of TAO and one experienced spontaneous resolution without intervention. Lack of statistically significant changes in the efficacy parameters were likely a result of small sample size and effects of the glucocorticoid dose taper. Conclusions: TAO is safe and may be a reasonable treatmen t alternative in a limited trial for patients who are unable to tolera te tapering of their glucocorticoid dosage. Therapy should be guided b y the goal of treatment, that is, glucocorticoid dose reduction or imp rovement of pulmonary function with appropriate monitoring of pulmonar y function and adverse effects.