Corresponding author:
Prof. Dr. med. Philipp Latzin, PhD
Inselspital, University Children’s Hospital of Bern
Freiburgstrasse 15, 3010 Bern, Switzerland
E-mail: philipp.latzin@insel.ch
Phone: +41 31 632 9353
Keywords: Multiple-breath washout; Cystic fibrosis, pulmonary function testing
Running title: LCI properties hold after correction of sensor error
Word count: 2942/3500
Figures and tables: 5/6 (1 Table, 4 Figures)
References: 24/40
Online Supplement: This manuscript has supplemental material.
Abstract (221/250)
Background: The recently described sensor-crosstalk error in the multiple-breath washout (MBW) device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) could highly influence clinimetric properties and the current interpretation of MBW results. This study reanalyzes MBW data from clinical routine in the corrected software version Spiroware® 3.3.1 and evaluates the effect on outcomes.
Methods: We included nitrogen-MBW data from healthy children and children with CF from previously published trials and ongoing cohort studies. We specifically compared LCI analyzed in Spiroware 3.2.1 and 3.3.1 with regards to i) feasibility, ii) repeatability and iii) validity as outcome parameters in children with CF.
Results: (i) All previously collected measurements could be reanalyzed and resulted in unchanged feasibility in Spiroware 3.3.1. (ii) Short- and midterm repeatability of LCI was similar in both software versions. (iii) Clinical validity of LCI remained similar in Spiroware 3.3.1, however, resulted in lower values. Discrimination between health and disease was comparable between both software versions. The increase in LCI over time was less pronounced with 0.16 LCI units/year (95% CI 0.08; 0.24) vs. 0.30 LCI units/year (95% CI 0.21; 0.38) in 3.2.1. Response to intervention in children receiving CFTR-modulator therapy resulted in a comparable improvement in LCI in both Spiroware versions.
Conclusion: Our study confirms that clinimetric properties of LCI remain unaffected after correction for the cross-sensitivity error in Spiroware software.
Introduction
We recently described and characterized a substantial sensor-crosstalk error in a commercially available and widely used multiple-breath washout (MBW) device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) and suggested a possible correction which is now available in an updated version of Spiroware analysis software (Spiroware 3.3.1, Eco Medics AG, Duernten, Switzerland) 1. There is an obvious sense of concern in the MBW community as the potential impact of these findings on existing and ongoing studies could highly influence clinimetric properties of MBW results and their current clinical interpretation2.
MBW has become an important diagnostic tool in cystic fibrosis (CF) for both, clinical follow-up of the patients and as an endpoint for clinical trials of new therapies 3-8. The lung clearance index (LCI) is a feasible, repeatable, and sensitive marker of ventilation inhomogeneity that correlates well with structural lung disease and tracks disease progression in children with CF5,6,9,10. LCI is calculated as the ratio of the cumulative expired volume divided by the functional residual capacity (FRC), based on indirect calculation of nitrogen (N2) from oxygen (O2) and carbon dioxide (CO2) signals. This results in inherent sensitivity to measurement errors in these signals, and the error described above previously resulted in a prolongation of the washout with falsely elevated LCI values 1.
To evaluate the potential clinical impact of these findings, this study aims to reanalyze published and collected MBW data from clinical routine by applying the corrected signal processing algorithm and evaluating the effect on outcomes. We assessed if previously described clinimetric properties of LCI hold for corrected results. We specifically examined corrected LCI with regards to i) feasibility, ii) repeatability, and iii) validity as outcome parameters in children with CF.
Methods