Abstract
Background 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.
Methods 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.
Results 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).
Conclusion 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.
Abstract
MBW is feasible in awake preschool children with high success rates in a multicentre setting and LCI detects ventilation inhomogeneity in preschool children with CF. This supports LCI as an end-point in early intervention trials in preschool children with CF. https://bit.ly/3lD4wnj
Footnotes
This article has supplementary material available from openres.ersjournals.com.
Author contributions: M. Stahl and M.A. Mall conceived and designed the study. M. Stahl, C. Joachim, I. Kirsch, T. Uselmann, Y. Yu, N. Alfeis, C. Berger, R. Minso, I. Rudolf, C. Stolpe, X. Bovermann, L. Liboschik, A. Steinmetz, D. Tennhardt, F. Dörfler, J. Röhmel, K. Unorji-Frank, C. Rückes-Nilges, B. von Stoutz, L. Naehrlich, M.V. Kopp, A-M. Dittrich, O. Sommerburg and M.A. Mall acquired, analysed and interpreted the data. M. Stahl, C. Joachim, I. Kirsch, T. Uselmann, Y. Yu, N. Alfeis, C. Berger, R. Minso, I. Rudolf, C. Stolpe, X. Bovermann, L. Liboschik, A. Steinmetz, D. Tennhardt, F. Dörfler, J. Röhmel, K. Unorji-Frank, C. Rückes-Nilges, B. von Stoutz, L. Naehrlich, M.V. Kopp, A-M. Dittrich, O. Sommerburg and M.A. Mall wrote the manuscript or revised it critically for important intellectual content.
Conflict of interest: M. Stahl reports grants from Mukoviszidose eV, personal fees from Vertex Pharmaceuticals and grants from Christiane Herzog Foundation, during the conduct of the study.
Conflict of interest: C. Joachim has nothing to disclose.
Conflict of interest: I. Kirsch has nothing to disclose.
Conflict of interest: T. Uselmann has nothing to disclose.
Conflict of interest: Y. Yu has nothing to disclose.
Conflict of interest: N. Alfeis has nothing to disclose.
Conflict of interest: C. Berger has nothing to disclose.
Conflict of interest: R. Minso has nothing to disclose.
Conflict of interest: I. Rudolf has nothing to disclose.
Conflict of interest: C. Stolpe has nothing to disclose.
Conflict of interest: X. Bovermann has nothing to disclose.
Conflict of interest: L. Liboschik has nothing to disclose.
Conflict of interest: A. Steinmetz has nothing to disclose.
Conflict of interest: D. Tennhardt has nothing to disclose.
Conflict of interest: F. Dörfler has nothing to disclose.
Conflict of interest: J. Röhmel has nothing to disclose.
Conflict of interest: K. Unorji-Frank has nothing to disclose.
Conflict of interest: C. Rückes-Nilges has nothing to disclose.
Conflict of interest: B. von Stoutz has nothing to disclose.
Conflict of interest: L. Naehrlich reports that he has received institutional fees for site participation in clinical trials from Vertex Pharmaceuticals.
Conflict of interest: M.V. Kopp has nothing to disclose.
Conflict of interest: A-M. Dittrich has nothing to disclose.
Conflict of interest: O. Sommerburg has nothing to disclose.
Conflict of interest: M.A. Mall reports grants from the German Federal Ministry of Education and Research and the Einstein Foundation Berlin during the conduct of the study; advisory board, consultancy, lecture and clinical trial fees from Boehringer Ingelheim, advisory board and consultancy fees from Arrowhead Pharmaceuticals, advisory board, consultancy, lecture and clinical trial fees from Vertex Pharmaceuticals, advisory board and consultancy fees from Santhera, consultancy fees from Galapagos and Sterna Biologicals, advisory board and consultancy fees from Enterprise Therapeutics, and consultancy fees from Antabio, outside the submitted work.
Support statement: This work was supported in part by the German Ministry for Education and Research (grants 82DZL00401, 82DZL0040A1, 82DZL10106 and 82DZL10501), the Dietmar Hopp Foundation and the Mukoviszidose Förderverein Giessen e.V. M. Stahl was supported by the German Cystic Fibrosis Association Mukoviszidose e.V. (grant 15/01) and the Christiane Herzog Foundation (C-H-P 1803). M.A. Mall was supported by the Einstein Foundation Berlin (EP-2017-393). The funders had no role in study design, data collection or analysis, the decision to publish or preparation of the manuscript. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received June 20, 2020.
- Accepted August 17, 2020.
- Copyright ©ERS 2020
This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.