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Normative data for multiple breath washout outcomes in school-aged Caucasian children

Pinelopi Anagnostopoulou, Philipp Latzin, Renee Jensen, Mirjam Stahl, Alana Harper, Sophie Yammine, Jakob Usemann, Rachel E. Foong, Ben Spycher, Graham L. Hall, Florian Singer, Sanja Stanojevic, Marcus Mall, Felix Ratjen, Kathryn A. Ramsey
European Respiratory Journal 2019; DOI: 10.1183/13993003.01302-2019
Pinelopi Anagnostopoulou
1Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland
2Insitute of Anatomy, University of Bern, Bern, Switzerland
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  • ORCID record for Pinelopi Anagnostopoulou
Philipp Latzin
1Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland
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Renee Jensen
3Division of Respiratory Medicine, The Hospital for Sick Children and Translational Medicine, SickKids Research Institute, University of Toronto, Toronto, Canada
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Mirjam Stahl
4Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany
5Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
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Alana Harper
6Telethon Kids Institute, Perth, Western Australia, Australia
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Sophie Yammine
1Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland
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Jakob Usemann
1Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland
9School of Physiotherapy and Exercise Science, Curtin University, Perth, Western Australia, Australia
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Rachel E. Foong
6Telethon Kids Institute, Perth, Western Australia, Australia
9School of Physiotherapy and Exercise Science, Curtin University, Perth, Western Australia, Australia
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Ben Spycher
8Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
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Graham L. Hall
6Telethon Kids Institute, Perth, Western Australia, Australia
9School of Physiotherapy and Exercise Science, Curtin University, Perth, Western Australia, Australia
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Florian Singer
1Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland
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Sanja Stanojevic
3Division of Respiratory Medicine, The Hospital for Sick Children and Translational Medicine, SickKids Research Institute, University of Toronto, Toronto, Canada
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Marcus Mall
4Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany
5Division of Pediatric Pulmonology and Allergy and Cystic Fibrosis Center, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany
10Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany
11Berlin Institute of Health (BIH), Berlin, Germany
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Felix Ratjen
3Division of Respiratory Medicine, The Hospital for Sick Children and Translational Medicine, SickKids Research Institute, University of Toronto, Toronto, Canada
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  • For correspondence: felix.ratjen@sickkids.ca
Kathryn A. Ramsey
1Division of Respiratory Medicine, Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland
6Telethon Kids Institute, Perth, Western Australia, Australia
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Abstract

Background The nitrogen multiple breath washout (N2MBW) technique is increasingly used to assess the degree of ventilation inhomogeneity in school-aged children with lung disease. However, reference values for healthy children are currently not available. The aim of this study was to generate reference values for N2MBW outcomes in a cohort of healthy Caucasian school-aged children.

Methods N2MBW data from healthy Caucasian school-age children between 6 and 18 years were collected from four experienced centers. Measurements were performed using an ultrasonic flowmeter (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) and were analyzed with commercial software (Spiroware, 3.2.1, Eco Medics AG). Normative values and upper limits of normal were generated for lung clearance index at 2.5% (LCI2.5%) and at 5% (LCI5%), moment ratios (M1/M0 and M2/M0), and a prediction equation generated for functional residual capacity (FRC).

Results Four hundred and eighty five trials from 180 healthy Caucasian children aged from 6 to 18 years were used for analysis. While LCI increased with age, this increase was negligible (0.04 units/year for LCI2.5%) and therefore fixed upper limits of normal were defined for this age group. These limits were 7.91 for LCI2.5%, 5.73 for LCI5%, 1.75 for M1/M0, and 6.15 for M2/M0 respectively. Height and weight were found to be independent predictors of FRC.

Conclusion We report reference values for N2MBW outcomes measured on a commercially available ultrasonic flowmeter device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) in healthy school-aged children to allow accurate interpretation of ventilation distribution outcomes and FRC in children with lung disease.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Anagnostopoulou has nothing to disclose.

Conflict of interest: Dr. Latzin reports personal fees from Gilead, personal fees from Novartis, personal fees from Polyphor, personal fees from Santhera, personal fees from Schwabe, personal fees from Vertex, personal fees from Vifor, personal fees from Zambon, grants from Vertex, outside the submitted work.

Conflict of interest: R. Jensen has nothing to disclose.

Conflict of interest: Dr. Stahl reports personal fees from Vertex Pharmaceuticals, outside the submitted work.

Conflict of interest: Dr. Harper has nothing to disclose.

Conflict of interest: Dr. Yammine has nothing to disclose.

Conflict of interest: Dr. Usemann has nothing to disclose.

Conflict of interest: Dr. Foong has nothing to disclose.

Conflict of interest: Dr. Spycher has nothing to disclose.

Conflict of interest: Dr. Hall reports grants from NHMRC, Australia and USA CF Foundation, and non-financial support from ndd, during the conduct of the study.

Conflict of interest: Dr. Singer reports personal fees from Vertex, personal fees from Novartis, outside the submitted work.

Conflict of interest: Dr. Stanojevic has nothing to disclose.

Conflict of interest: Dr. Mall reports grants from German Federal Ministry of Education and Research , grants from Einstein Foundation Berlin, during the conduct of the study; personal fees from Boehringer Ingelheim, personal fees from Vertex Pharmaceuticals, outside the submitted work.

Conflict of interest: Dr. Ratjen reports grants and personal fees from Vertex, personal fees from Novartis, personal fees from Bayer, personal fees from Roche, personal fees from Genetech, outside the submitted work.

Conflict of interest: Dr. Ramsey has nothing to disclose.

  • Received July 2, 2019.
  • Accepted December 10, 2019.
  • Copyright ©ERS 2019
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Normative data for multiple breath washout outcomes in school-aged Caucasian children
Pinelopi Anagnostopoulou, Philipp Latzin, Renee Jensen, Mirjam Stahl, Alana Harper, Sophie Yammine, Jakob Usemann, Rachel E. Foong, Ben Spycher, Graham L. Hall, Florian Singer, Sanja Stanojevic, Marcus Mall, Felix Ratjen, Kathryn A. Ramsey
European Respiratory Journal Jan 2019, 1901302; DOI: 10.1183/13993003.01302-2019

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Normative data for multiple breath washout outcomes in school-aged Caucasian children
Pinelopi Anagnostopoulou, Philipp Latzin, Renee Jensen, Mirjam Stahl, Alana Harper, Sophie Yammine, Jakob Usemann, Rachel E. Foong, Ben Spycher, Graham L. Hall, Florian Singer, Sanja Stanojevic, Marcus Mall, Felix Ratjen, Kathryn A. Ramsey
European Respiratory Journal Jan 2019, 1901302; DOI: 10.1183/13993003.01302-2019
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