Kamada A K, Hill M R, Iklé D N, Brenner A M, Szefler S J
Ira J. and Jacqueline Neimark Laboratory for Clinical Pharmacology in Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
J Allergy Clin Immunol. 1993 Apr;91(4):873-82. doi: 10.1016/0091-6749(93)90345-g.
Troleandomycin (TAO), a macrolide antibiotic, was studied as an alternative treatment in 18 children with severe, steroid-requiring asthma.
In this investigation three treatment arms were used in randomized, double-blind, parallel fashion: combination TAO and methylprednisolone (MPn), combination TAO and prednisone, and MPn alone.
All groups tolerated a considerable reduction in glucocorticoid 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 reductions 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 required to induce a 20% decrease in forced expiratory volume in 1 second and pulmonary function were not significantly improved in any treatment 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.
TAO is safe and may be a reasonable treatment alternative in a limited trial for patients who are unable to tolerate tapering of their glucocorticoid dosage. Therapy should be guided by the goal of treatment, that is, glucocorticoid dose reduction or improvement of pulmonary function with appropriate monitoring of pulmonary function and adverse effects.
三乙酰竹桃霉素（TAO），一种大环内酯类抗生素，在18名患有严重、需使用类固醇的哮喘儿童中作为替代治疗方法进行了研究。
在本研究中，采用随机、双盲、平行方式设置了三个治疗组：TAO与甲泼尼龙（MPn）联合治疗组、TAO与泼尼松联合治疗组以及单独使用MPn治疗组。
在为期12周的研究中，所有组的糖皮质激素剂量均有显著降低：TAO - MPn组降低了80%±6%，TAO - 泼尼松组降低了55%±8%，单独使用MPn组降低了44%±14%。这些降低在组内均具有统计学意义（p < 0.05），且TAO - MPn组与单独使用MPn组之间的组间差异具有统计学意义。在任何治疗组中，诱导一秒用力呼气量降低20%所需的乙酰甲胆碱浓度及肺功能均未得到显著改善。包括血液化学和血液学、肾上腺功能评估、骨密度测定以及肌肉力量测试在内的安全性参数均未发生显著改变。两名接受TAO治疗的患者肝酶水平升高；一名患者需要停用TAO，另一名患者未经干预自行恢复。疗效参数缺乏统计学显著变化可能是由于样本量小以及糖皮质激素剂量逐渐减少的影响。
TAO是安全的，对于无法耐受糖皮质激素剂量逐渐减少的患者，在有限的试验中可能是一种合理的治疗选择。治疗应以治疗目标为指导，即减少糖皮质激素剂量或改善肺功能，并适当监测肺功能和不良反应。
