Stahl Mirjam, Joachim Cornelia, Kirsch Ines, Uselmann Tatjana, Yu Yin, Alfeis Nadine, Berger Christiane, Minso Rebecca, Rudolf Isa, Stolpe Cornelia, Bovermann Xenia, Liboschik Lena, Steinmetz Alena, Tennhardt Dunja, Dörfler Friederike, Röhmel Jobst, Unorji-Frank Klaudia, Rückes-Nilges Claudia, von Stoutz Bianca, Naehrlich Lutz, Kopp Matthias V, Dittrich Anna-Maria, Sommerburg Olaf, Mall Marcus A
Dept of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Dept of Pediatrics, University of Heidelberg, Heidelberg, Germany.
ERJ Open Res. 2020 Oct 26;6(4). doi: 10.1183/23120541.00408-2020. eCollection 2020 Oct.
Multiple-breath washout (MBW)-derived lung clearance index (LCI) detects early cystic fibrosis (CF) lung disease. LCI was used as an end-point in single- and multicentre settings at highly experienced MBW centres in preschool children. However, multicentre feasibility of MBW in children aged 2-6 years, including centres naïve to this technique, has not been determined systematically.
Following central training, 91 standardised nitrogen MBW investigations were performed in 74 awake preschool children (15 controls, 46 with CF, and 13 with other lung diseases), mean age 4.6±0.9 years at investigation, using a commercially available device across five centres in Germany (three experienced, two naïve to the performance in awake preschool children) with central data analysis. Each MBW investigation consisted of several measurements.
Overall success rate of MBW investigations was 82.4% ranging from 70.6% to 94.1% across study sites. The number of measurements per investigation was significantly different between sites ranging from 3.7 to 6.2 (p<0.01), while the mean number of successful measurements per investigation was comparable with 2.1 (range, 1.9 to 2.5; p=0.46). In children with CF, the LCI was increased (median 8.2, range, 6.7-15.5) compared to controls (median 7.3, range 6.5-8.3; p<0.01), and comparable to children with other lung diseases (median 7.9, range, 6.6-13.9; p=0.95).
This study demonstrates that multicentre MBW in awake preschool children is feasible, even in centres previously naïve, with central coordination to assure standardised training, quality control and supervision. Our results support the use of LCI as multicentre end-point in clinical trials in awake preschoolers with CF.
多次呼吸洗脱（MBW）衍生的肺清除指数（LCI）可检测早期囊性纤维化（CF）肺部疾病。在学龄前儿童中，LCI在经验丰富的MBW中心被用作单中心和多中心研究的终点。然而，MBW在2至6岁儿童中的多中心可行性，包括对该技术不熟悉的中心，尚未得到系统的确定。
经过集中培训后，使用市售设备在德国的五个中心（三个经验丰富，两个对清醒学龄前儿童的检测不熟悉）对74名清醒的学龄前儿童（15名对照，46名CF患儿，13名患有其他肺部疾病）进行了91次标准化的氮MBW检测，检测时平均年龄为4.6±0.9岁，并进行了集中数据分析。每次MBW检测包括多次测量。
MBW检测的总体成功率为82.4%，各研究地点的成功率在70.6%至94.1%之间。各检测点每次检测的测量次数差异显著，范围为3.7至6.2（p<0.01），而每次检测成功测量的平均次数相当，为2.1次（范围为1.9至2.5次；p=0.46）。与对照组（中位数7.3，范围6.5 - 8.3；p<0.01）相比，CF患儿的LCI升高（中位数8.2，范围6.7 - 15.5），与其他肺部疾病患儿相当（中位数7.9，范围6.6 - 13.9；p=0.95）。
本研究表明，即使在以前不熟悉的中心，通过集中协调以确保标准化培训、质量控制和监督，对清醒学龄前儿童进行多中心MBW检测是可行的。我们的结果支持将LCI用作清醒学龄前CF患儿临床试验的多中心终点。
