肺清除指数作为囊性纤维化幼儿临床试验的结局指标。一项使用吸入高渗盐水的初步研究。
Lung clearance index as an outcome measure for clinical trials in young children with cystic fibrosis. A pilot study using inhaled hypertonic saline.
机构信息
Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, 555 University Avenue, Ontario, Canada.
出版信息
Am J Respir Crit Care Med. 2013 Aug 15;188(4):456-60. doi: 10.1164/rccm.201302-0219OC.
RATIONALE
Lung clearance index (LCI), measured by multiple breath washout (MBW), is a noninvasive measure of ventilation inhomogeneity that holds promise as an objective physiologic endpoint for clinical trials in infants and preschool children with cystic fibrosis (CF).
OBJECTIVES
To study the feasibility of using LCI to assess treatment effect outcomes in CF trials of infants and preschoolers.
METHODS
The Infant Study of Inhaled Saline trial was a multicenter, randomized, controlled trial of hypertonic (7%) versus isotonic (0.9%) saline inhaled twice daily for 48 weeks in children with CF under 6 years of age. LCI measurements were performed in a single-center pilot substudy at baseline and 48 weeks using a respiratory mass spectrometer and sulfur hexafluoride as the tracer gas. LCI measurements were standardized using published normative data (zLCI) to account for height-related changes in LCI during early childhood. A generalized estimating equation model with an interaction between treatment group and test occasion was used to estimate a treatment effect.
MEASUREMENTS AND MAIN RESULTS
A total of 27 participants were randomized; 25 participants, aged (median [range]) 2.6 (0.34-4.95) years, had acceptable baseline and follow-up LCI measures. On average, LCI decreased in the hypertonic saline group (n = 12) by 1.19 z-scores units (95% confidence interval [CI] = -2.46 to 0.06), and remained stable in the isotonic saline group (n = 13) at 0.81 (95% CI = -0.40 to 2.02). A significant treatment effect was observed for zLCI (2.01; 95% CI = 0.26 to 3.76; P = 0.025).
CONCLUSIONS
MBW testing is feasible in an interventional study in infants and preschool children with CF. These pilot findings support the development of MBW and LCI as an objective outcome measure in interventional trials in young children with CF, and provide estimates for sample size calculations for future studies.
原理
通过多呼吸冲洗（MBW）测量的肺清除指数（LCI）是一种非侵入性的通气不均匀性测量方法，有望成为囊性纤维化（CF）婴儿和学龄前儿童临床试验的客观生理终点。
目的
研究使用 LCI 评估 CF 婴儿和学龄前儿童临床试验治疗效果的可行性。
方法
婴儿盐水吸入试验是一项多中心、随机、对照试验，比较 6 岁以下 CF 儿童每日两次吸入高渗（7%）与等渗（0.9%）盐水 48 周。在一个单中心的试点子研究中，使用呼吸质谱仪和六氟化硫作为示踪气体，在基线和 48 周时进行 LCI 测量。使用发表的正常数据（zLCI）对 LCI 测量进行标准化，以解释儿童早期 LCI 与身高相关的变化。使用具有治疗组和测试时间交互作用的广义估计方程模型来估计治疗效果。
测量和主要结果
共有 27 名参与者被随机分配；25 名参与者（年龄中位数[范围]）为 2.6（0.34-4.95）岁，有可接受的基线和随访 LCI 测量值。平均而言，高渗盐水组（n = 12）的 LCI 降低了 1.19 z 分数单位（95%置信区间[CI] = -2.46 至 0.06），等渗盐水组（n = 13）的 LCI 保持稳定在 0.81（95% CI = -0.40 至 2.02）。zLCI 观察到显著的治疗效果（2.01；95% CI = 0.26 至 3.76；P = 0.025）。
结论
MBW 测试在 CF 婴儿和学龄前儿童的干预性研究中是可行的。这些初步研究结果支持将 MBW 和 LCI 作为 CF 幼儿干预性试验的客观结局测量方法的发展，并为未来研究提供了样本量计算的估计值。
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