4.4 Clinical relevance and outlook
Although there is a significant change with the corrected algorithm, we
show that the clinimetric properties of LCI still hold. This means that
clinical utility and our understanding of LCI and its changes remain
valid. This also suggests that previously published papers do not need
to be withdrawn. However, this implies also that for absolute correct
estimation of effect sizes, previously published datasets need to be
reanalyzed to enable comparison with results from Spiroware 3.3.1.
Besides, we will need to closely evaluate changes within individuals
applying the new software, to adjust individual therapeutic goals but
also to capture individual disease progression at this new level. The
option of retrospective correction has the great advantage that all
previously collected data in Spiroware can be reanalyzed and corrected.
Conclusion
Our study confirms that clinimetric
properties of LCI remain unaffected after correction for the recently
detected measurement error in the widely used Spiroware software.
However, the correction results in lower LCI values, with the concurrent
need to redefine existing thresholds and adjust clinical understanding
of LCI and its changes on this new level.
Acknowledgements
We thank all our patients and study participants as well as their
families for allowing their MBW data to be used for research. In
addition, we thank the lab technicians and study nurses for their
contribution by performing MBW measurements. Furthermore, we thank the
physicians from our department, especially Insa Korten and Elisabeth
Kieninger.
Funding
This project was funded by the Swiss National Science Foundation, Grant
Nos. 182719 (to P. Latzin) and 179905 (to S. Yammine).
Author contributions
Bettina Sarah Frauchiger: Conceptualization, Methodology, Formal
analysis, Investigation, Resources, Writing - Original Draft, Review &
Editing, Visualization.
Marc-Alexander Oestreich: Conceptualization, Data Curation, Methodology,
Formal analysis, Investigation, Resources, Writing - Original Draft,
Review & Editing, Visualization.
Florian Wyler: Software.
Nathalie Monney: Resources.
Corin Willers: Resources.
Sophie Yammine: Writing - Original Draft, Review & Editing.
Philipp Latzin: Conceptualization, Supervision, Project administration,
Funding acquisition.
- Wyler F, Oestreich MA, Frauchiger BS, Ramsey KA, Latzin P. 2021.
Correction of sensor crosstalk error in exhalyzer d multiple-breath
washout device significantly impacts outcomes in children with cystic
fibrosis. Journal of applied physiology (Bethesda, Md : 1985).
131(3):1148-1156.
- Robinson PD, Jensen R, Seeto RA, Stanojevic S, Saunders C, Short C,
Davies JC, Ratjen F. 2021. Impact of cross-sensitivity error
correction on representative nitrogen-based multiple breath washout
data from clinical trials. Journal of Cystic Fibrosis.
- Amin R, Stanojevic S, Kane M, Webster H, Ratjen F. 2016. A randomized
controlled trial to evaluate the lung clearance index as an outcome
measure for early phase studies in patients with cystic fibrosis.
Respiratory medicine. 112:59-64.
- Davies G, Stanojevic S, Raywood E, Duncan JA, Stocks J, Lum S, Bush A,
Viviani L, Wade A, Calder A et al. 2020. An observational study of the
lung clearance index throughout childhood in cystic fibrosis: Early
years matter. The European respiratory journal.2000006.
- Frauchiger BS, Binggeli S, Yammine S, Spycher B, Kruger L, Ramsey KA,
Latzin P. 2021. Longitudinal course of clinical lung clearance index
in children with cystic fibrosis. The European respiratory journal.
58(1):2002686.
- Perrem L, Stanojevic S, Shaw M, Jensen R, McDonald N, Isaac SM, Davis
M, Clem C, Guido J, Jara S et al. 2020. Lung clearance index to track
acute respiratory events in school-age children with cystic fibrosis.
Am J Respir Crit Care Med.
- Rayment JH, Stanojevic S, Davis SD, Retsch-Bogart G, Ratjen F. 2018.
Lung clearance index to monitor treatment response in pulmonary
exacerbations in preschool children with cystic fibrosis. Thorax.
73(5):451-458.
- Voldby C, Green K, Kongstad T, Ring AM, Sandvik RM, Skov M, Buchvald
F, Pressler T, Nielsen KG. 2020. Lung clearance index-triggered
intervention in children with cystic fibrosis - a randomised pilot
study. Journal of cystic fibrosis : official journal of the European
Cystic Fibrosis Society. 19(6):934-941.
- Oude Engberink E, Stanojevic S, Ratjen F. 2016. Clinimetric properties
of the lung clearance index in adults and children with cystic
fibrosis. Chest. 150(6):1412-1413.
- Ramsey KA, Rosenow T, Turkovic L, Skoric B, Banton G, Adams A-M,
Simpson SJ, Murray C, Ranganathan SC, Stick SM et al. 2016. Lung
clearance index and structural lung disease on computed tomography in
early cystic fibrosis. Am J Respir Crit Care Med. 193(1):60–67.
- Fuchs O, Latzin P, Kuehni CE, Frey U. 2012. Cohort profile: The bern
infant lung development cohort. Int J Epidemiol. 41(2):366–376.
- Korten I, Kieninger E, Yammine S, Regamey N, Nyilas S, Ramsey K,
Casaulta C, Latzin P, For TSSG. 2018. The swiss cystic fibrosis infant
lung development (scild) cohort. Swiss Med Wkly. 148:w14618.
- Robinson PD, Latzin P, Ramsey KA, Stanojevic S, Aurora P, Davis SD,
Gappa M, Hall GL, Horsley A, Jensen R et al. 2018. Preschool
multiple-breath washout testing. An official american thoracic society
technical statement. Am J Respir Crit Care Med. 197(5):e1-e19.
- Robinson PD, Latzin P, Verbanck S, Hall GL, Horsley A, Gappa M,
Thamrin C, Arets HGM, Aurora P, Fuchs SI et al. 2013. Consensus
statement for inert gas washout measurement using multiple- and
single- breath tests. Eur Respir J. 41(3):507–522.
- Frauchiger BS, Carlens J, Herger A, Moeller A, Latzin P, Ramsey KA.
2021. Multiple breath washout quality control in the clinical setting.
Pediatr Pulmonol. 56(1):105-112.
- Jensen R, Stanojevic S, Klingel M, Pizarro ME, Hall GL, Ramsey K,
Foong R, Saunders C, Robinson PD, Webster H et al. 2016. A systematic
approach to multiple breath nitrogen washout test quality. PLoS One.
11(6):e0157523.
- Roethlisberger K, Nyilas S, Riedel T, Wolfensberger J, Singer F,
Latzin P. 2018. Short-term effects of elastic chest wall restriction
on pulmonary function in children with cystic fibrosis. Respiration.
96(6):535-542.
- Nyilas S, Bauman G, Pusterla O, Ramsey K, Singer F, Stranzinger E,
Yammine S, Casaulta C, Bieri O, Latzin P. 2019. Ventilation and
perfusion assessed by functional mri in children with cf:
Reproducibility in comparison to lung function. Journal of Cystic
Fibrosis. 18(4):543-550.
- Willers C, Bauman G, Andermatt S, Santini F, Sandkühler R, Ramsey KA,
Cattin PC, Bieri O, Pusterla O, Latzin P. 2021. The impact of
segmentation on whole-lung functional mri quantification:
Repeatability and reproducibility from multiple human observers and an
artificial neural network. Magn Reson Med. 85(2):1079-1092.
- Nyilas S, Bauman G, Sommer G, Stranzinger E, Pusterla O, Frey U,
Korten I, Singer F, Casaulta C, Bieri O et al. 2017. Novel magnetic
resonance technique for functional imaging of cystic fibrosis lung
disease. The European respiratory journal. 50(6):1701464.
- Grégoire TG, Schabenberger O, Barrett JP. 1995. Linear modelling of
irregularly spaced, unbalanced, longitudinal data from permanent-plot
measurements. Canadian Journal of Forest Research. 25(1):137-156.
- Yammine S, Summermatter S, Singer F, Lauener R, Latzin P. 2016.
Feasibility of nitrogen multiple-breath washout in inexperienced
children younger than 7 years. Pediatr Pulmonol. 51(11):1183-1190.
- Bayfield KJ, Shaar A, Robinson PD. 2021. Further considerations on
normative data for multiple breath washout outcomes. Eur Respir J.
57(4):2004536.