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Original research
Multiple breath washout (MBW) testing using sulfur hexafluoride: reference values and influence of anthropometric parameters
  1. Frederik Trinkmann1,2,3,
  2. Máté Maros3,4,
  3. Katharina Roth1,
  4. Arne Hermanns1,
  5. Julia Schäfer1,
  6. Joshua Gawlitza5,
  7. Joachim Saur1,
  8. Ibrahim Akin1,6,
  9. Martin Borggrefe1,6,
  10. Felix J F Herth2,
  11. Thomas Ganslandt3
  1. 1 1st Department of Medicine, University Medical Centre Mannheim, Mannheim, Baden-Württemberg, Germany
  2. 2 Department of Pneumology and Critical Care Medicine, Thoraxklinik at University Hospital Heidelberg, Translational Lung Research Centre Heidelberg (TLRC), Member of German Centre for Lung Research (DZL), Heidelberg, Baden-Württemberg, Germany
  3. 3 Department of Biomedical Informatics, Centre for Preventive Medicine & Digital Health Baden-Württemberg, University Medical Centre Mannheim, Mannheim, Germany
  4. 4 Department of Neuroradiology, University Medical Centre Mannheim, Mannheim, Germany
  5. 5 Institute for Clinical Radiology and Nuclear Medicine, University Medical Centre Mannheim, Mannheim, Germany
  6. 6 DZHK (German Centre for Cardiovascular Research), Mannheim, Germany
  1. Correspondence to Dr Frederik Trinkmann, 1st Department of Medicine, University Medical Centre Mannheim, Mannheim, Baden-Württemberg, Germany; frederik.trinkmann{at}


Background Multiple breath washout (MBW) using sulfur hexafluoride (SF6) has the potential to reveal ventilation heterogeneity which is frequent in patients with obstructive lung disease and associated small airway dysfunction. However, reference data are scarce for this technique and mostly restricted to younger cohorts. We therefore set out to evaluate the influence of anthropometric parameters on SF6-MBW reference values in pulmonary healthy adults.

Methods We evaluated cross-sectional data from 100 pulmonary healthy never-smokers and smokers (mean 51 (SD 20), range 20–88 years). Lung clearance index (LCI), acinar (Sacin) and conductive (Scond) ventilation heterogeneity were derived from triplicate SF6-MBW measurements. Global ventilation heterogeneity was calculated for the 2.5% (LCI2.5) and 5% (LCI5) stopping points. Upper limit of normal (ULN) was defined as the 95th percentile.

Results Age was the only meaningful parameter influencing SF6-MBW parameters, explaining 47% (CI 33% to 59%) of the variance in LCI, 32% (CI 18% to 47%) in Sacin and 10% (CI 2% to 22%) in Scond. Mean LCI increases from 6.3 (ULN 7.4) to 8.8 (ULN 9.9) in subjects between 20 and 90 years. Smoking accounted for 2% (CI 0% to 8%) of the variability in LCI, 4% (CI 0% to 13%) in Sacin and 3% (CI 0% to 13%) in Scond.

Conclusion SF6-MBW outcome parameters showed an age-dependent increase from early adulthood to old age. The effect was most pronounced for global and acinar ventilation heterogeneity and smaller for conductive ventilation heterogeneity. No influence of height, weight and sex was seen. Reference values can now be provided for all important SF6-MBW outcome parameters over the whole age range.

Trial registration number NCT04099225.

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  • Presented at An abstract containing preliminary analysis of the underlying data was presented at the online 2020 annual congress of the American Thoracic Society.

  • Contributors All authors read and approved the final version of the manuscript. FT: writing the first draft of the manuscript, study design, data management, data analysis. MM: data analysis, statistical advice. KR: data collection, data management. AH: data management, data collection. JuS: data management, data analysis. JG: data analysis, study design, data management. JoS: study design, data analysis. IA: study design, revision of the first draft of the manuscript. MB: study design, revision of the manuscript. FJFH: study design, data analysis, revision of the manuscript. TG: data analysis, data management, revision of the first draft of the manuscript.

  • Funding Parts of our work received external funding from Ms Ester Knorr (Germany, private donation) and Markedsmodningsfonden (Denmark, public grant). Internal financial support was given by Heidelberg University (MEAMEDMA, internal grant).

  • Competing interests The following financial activities outside the submitted work exist: FT received travel support from Actelion, Berlin Chemie, Boehringer Ingelheim, Chiesi, Novartis, Mundipharma and TEVA, as well as speaker or consultation fees from AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, GlaxoSmithKline, Roche, Novartis and Sanofi-Aventis. JoS received travel support and speaker fees from Boehringer Ingelheim, GlaxoSmithKline, Novartis and Roche. MB received speaker or consultation fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo, Impulse Dynamics and Zoll Medical. IA received travel support as well as speaker or consultation fees from Abiomed, Bayer, Boehringer Ingelheim and St Jude Medical.

  • Patient consent for publication Not required.

  • Ethics approval The study protocol was approved by the Medical Ethics Committee II of the Medical Faculty Mannheim (Heidelberg University), compliant with the Declaration of Helsinki.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. The models generated and analysed during the current study are available for download from an online repository (

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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