Baker J W, Mellon M, Wald J, Welch M, Cruz-Rivera M, Walton-Bowen K
Kaiser Permanente, San Diego, California, USA.
Pediatrics. 1999 Feb;103(2):414-21. doi: 10.1542/peds.103.2.414.
Topical antiinflammatory medications such as inhaled corticosteroids are recommended for therapy of asthma, but no formulation suitable for administration to infants and young children is available in the United States.
This was a 12-week, multicenter, double-blind, randomized, parallel-group study comparing the efficacy and safety of four dosing regimens of bude-sonide inhalation suspension (BIS) or placebo in 480 asthmatic infants and children (64% boys), ages 6 months to 8 years, with moderate persistent asthma. Approximately 30% of children were previously on inhaled corticosteroids that were discontinued before the study. Active treatments were comprised of BIS 0.25 mg once daily (QD), 0.25 mg twice a day (BID), 0.5 mg BID, or 1.0 mg QD. Efficacy was assessed by twice daily recording at home of asthma symptom scores and use of rescue medication, and discontinuation from the study because of worsening asthma and/or a requirement for systemic steroids. Peak flow measurements were recorded twice daily on diary and spirometry was recorded at clinic visits for those children able to perform these tests. Safety was assessed by reported adverse events and by cortisol testing (adrenocorticotropic hormone stimulation) in a subset of patients.
Patients enrolled had an average duration of asthma of 34 months; the mean asthma symptom score was approximately 1.3 (scale of 0-3). All dosing regimens with BIS produced statistically significant improvement in various clinical efficacy measures for asthma control compared with placebo. The lowest dose used, 0.25 mg QD, was efficacious but with fewer efficacy parameters than seen with the other doses administered. Separation between active treatment and placebo in daytime and nighttime symptom scores were observed by week 2 of treatment for all BIS treatment regimens. A significant increase in peak flow measurement was observed in most active treatment groups compared with placebo in the subset of children able to do pulmonary function testing. All treatment groups showed numerical improvement in forced expiratory volume in 1 second but only the 0.5-mg BID dose was significantly different from placebo. Adverse events for the entire group and response to adrenocorticotropic hormone in a subgroup of children who underwent cortisol testing before and at the end of the treatment period were no different in budesonide-treated patients in comparison to placebo.
Results of this study demonstrate that BIS is effective and safe for infants and young children with moderate persistent asthma in a multiple dose range, and that QD dosing is an important option to be considered by the prescribing physician.
吸入性糖皮质激素等局部抗炎药物被推荐用于哮喘治疗，但在美国尚无适合婴幼儿使用的剂型。
这是一项为期12周的多中心、双盲、随机、平行组研究，比较了布地奈德吸入混悬液（BIS）四种给药方案或安慰剂在480例6个月至8岁中度持续性哮喘婴幼儿及儿童（64%为男孩）中的疗效和安全性。约30%的儿童此前使用过吸入性糖皮质激素，在研究前停药。活性治疗组包括每日一次（QD）给予0.25 mg BIS、每日两次（BID）给予0.25 mg BIS、每日两次给予0.5 mg BIS或每日一次给予1.0 mg BIS。通过在家中每日记录两次哮喘症状评分和急救药物使用情况，以及因哮喘恶化和/或需要全身使用类固醇而退出研究的情况来评估疗效。对于能够进行这些测试的儿童，每日在日记中记录两次峰值流量测量值，并在门诊就诊时记录肺活量测定值。通过报告的不良事件和对一部分患者进行皮质醇检测（促肾上腺皮质激素刺激试验）来评估安全性。
入组患者的哮喘平均病程为34个月；平均哮喘症状评分为约1.3（0 - 3分制）。与安慰剂相比，所有BIS给药方案在哮喘控制的各种临床疗效指标上均产生了统计学上显著的改善。使用的最低剂量，即每日一次0.25 mg，是有效的，但与其他给药剂量相比，疗效参数较少。在所有BIS治疗方案中，治疗第2周时观察到活性治疗组与安慰剂组在白天和夜间症状评分上的差异。在能够进行肺功能测试的儿童亚组中，与安慰剂相比，大多数活性治疗组的峰值流量测量值显著增加。所有治疗组在1秒用力呼气量方面均有数值上的改善，但只有每日两次给予0.5 mg剂量组与安慰剂组有显著差异。与安慰剂相比，布地奈德治疗患者的整个组的不良事件以及治疗期开始和结束前接受皮质醇检测的儿童亚组对促肾上腺皮质激素的反应无差异。
本研究结果表明，BIS在多个剂量范围内对中度持续性哮喘的婴幼儿及儿童有效且安全，每日一次给药是处方医生应考虑的重要选择。
