MONTELUKAST OR AZITHROMYCIN FOR REDUCTION OF INHALED CORTICOSTEROIDS IN CHILD

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。持续性哮喘患者需要中到大剂量的吸入皮质类固醇(ICS)，即使与长效支气管扩张剂激动剂(LABA)联合使用以维持控制，ICS副作用的风险也很高。这些副作用包括生长速度减慢和对肾上腺功能的影响。这些和其他数据鼓励临床医生寻找方法来减轻患者的类固醇负担。在这里，我们研究了两种药物，大环内酯类(Mac)和白三烯受体拮抗剂(LTRA)在此类患者中的类固醇节省效果。Mac在加强哮喘治疗方面的作用已经有很长的历史了。20世纪50年代和60年代，由于发现了肝脏毒性和药物代谢相互作用，最初使用曲兰霉素的研究停止了。随着副作用更少的新型抗生素的引入，以及Mac对弥漫性毛细支气管炎和囊性纤维化的治疗已经确立，Mac的使用在治疗哮喘的医疗机构中重新出现，研究表明这些药物的抗炎活性，而不仅仅是它们的抗细菌特性。另一类可能具有类固醇节省作用的药物是白三烯受体拮抗剂(LTRA)。在低剂量ICS中加入孟鲁司特改善了呼吸道炎症和肺功能的标记物，同时减少了β-激动剂的使用、病情恶化和血嗜酸性粒细胞计数(62，63)。在临床实践中，孟鲁司特甚至被添加到中等剂量的ICS中，以试图避免使用更高剂量的ICS。白三烯受体拮抗剂(LTRA)减少ICS剂量的能力已经在需要中到高剂量ICS以维持哮喘控制的成年人中使用孟鲁司特进行了研究，发现是有效的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Patients with persistent asthma requiring moderate to high dose inhaled corticosteroid (ICS) even when given in combination with long acting bronchodilator agonist (LABA) to maintain control are at high risk for side effects from the ICS. These side effects include decreases in growth velocity and an impact on adrenal function. These and other data have encouraged clinicians to seek ways to reduce the steroid burden in their patients. Here we study the steroid sparing effectiveness of two medications, a macrolide (Mac) and a leukotriene receptor antagonist (LTRA) in such patients. A role of Mac in augmenting the treatment for asthma has had a long history. Initial investigations in the 1950s and 1960s using troleandomycin were stopped with discovery of liver toxicity and drug metabolism interactions. Use of Mac has reappeared in the therapeutic armamentarium for asthma as newer forms of the antibiotic class with fewer side effects have been introduced and as treatment with Mac for diffuse panbronchiolitis and cystic fibrosis was established, and studies demonstrating anti-inflammatory activities of the drugs rather than simply their anti-bacterial properties. Another drug class with possible steroid sparing effects is leukotriene receptor antagonist (LTRA). Addition of montelukast to low dose ICS improved both markers of airway inflammation and pulmonary function, while reducing beta agonist use, exacerbations, and blood eosinophil counts (62, 63). In clinical practice, montelukast is added even to moderate dose ICS in an attempt to avoid use of higher doses of ICS. The capacity of leukotriene receptor antagonist (LTRA) to allow a decrease in ICS dosing has been studied using montelukast in adults requiring moderate to high doses of ICS to maintain asthma control and found to be effective.