Differences in lung clearance index and functional residual capacity between two commercial multiple-breath nitrogen washout devices in healthy children and adults

Abstract

Multiple-breath nitrogen washout (MBNW) and its clinical parameter lung clearance index (LCI) are gaining increasing attention for the assessment of small airway function. Measurement of LCI relies on accurate assessment of functional residual capacity (FRC). The EasyOne Pro LAB (ndd) and Exhalyzer D (EM) are two commercially available MBNW devices. The aim of the study was to compare these two devices in vitro and in vivo in healthy subjects with regard to FRC, LCI and secondary outcome parameters and to relate FRCMBNW to FRC measured by body plethysmography (pleth) and helium dilution technique. MBNW measurements were performed using a lung model (FRC between 500 and 4000 mL) in vitro and in 38 subjects aged 6–65 years followed by helium dilution and pleth in vivo using fixed and relaxed breathing techniques. In vitro accuracy within 5% of lung model FRC was 67.3% for ndd, FRC was >5% higher for EM in all tests. In vivo, FRCpleth ranged from 1.2 to 5.6 L. Mean differences (limits of agreement) between FRCpleth and FRCMBNW were −7.0%, (−23.2 to 9.2%) and 5.7% (−11.2 to 22.6%) using ndd and EM, respectively. FRCndd was consistently lower than FRCEM (−11.8% (−25.6 to 2%)). LCI was comparable between the two devices (−1.3% (−21.9 to 19.3%)). There was a difference of >10 % in LCI in 12 of 38 subjects. Using the most recent software updates, both devices show relevant deviations in FRC measurement both in vitro and in vivo and individual differences in LCI in a significant proportion of subjects. The devices are therefore not interchangeable.

Controlledversusfree breathing for multiple breath nitrogen washout in healthy adults

“…However the between-session coefficient of repeatability (equal to 1.96× sd of the mean differences) of LCI, S cond and S acin was greater in our study, which may reflect the different time between sessions (weeks/months versus days). There is a paucity of repeatability data in health, and previous reports may not be generalisable due to persistent between-device differences [ 17 , 18 , 26 ]. Nevertheless, the excellent between-session repeatability for FRC and LCI [ 25 , 27 – 29 ] but poor repeatability in S acin and S cond [ 25 , 28 ] has been noted with the free breathing protocol by other investigators, regardless of device, tracer gas or disease.…”

A non-systematic signal-correction error in a commercial multiple-breath washout device significantly impacts outcomes in children and adults

“…Previous studies reported significant differences in main MBW outcomes between the commercial EasyOne and Exhalyzer D MBW devices and FRC from other lung function tests (e.g. body plethysmography) 10,12 . Differences in the underlying algorithms for signal processing of raw data and the calculation of MBW outcomes, as well as potential effects of on-demand oxygen supply via variable bias flows on the breathing pattern have been the focus of attention.…”

“…We characterized the RQ-based signal correction and resulting non-systematic error in carbon dioxide and nitrogen concentration. Previous validation studies using in-vitro lung models did not specifically examine the influence of continuous and/or physiological CO 2 concentrations over the course of the washout 10,12 , mainly because of two reasons: i) additional CO 2 causes a volume drift when added to a Plexiglas model, and ii) a starting concentration of (e.g. 5%) CO 2 in the lung compartment of a lung model without continuously added CO 2 influx will washout over the first few breaths of the washout, thus missing the vulnerable period at the end of the washout where small errors may have a big impact on derived nitrogen concentrations.…”

“…Currently, two commercially available N 2 -MBW devices are mainly used in clinical trials, the EasyOne Pro LAB (EasyOne; ndd Medzintechnik AG; clinicaltrials.gov identifier: NCT04138589, NCT03691779) and the Exhalyzer D (Eco Medics AG; clinicaltrials.gov identifier: NCT04537793) 8,9 . Both devices derive the nitrogen concentration indirectly based on molar mass and gas measurements, but there is poor agreement in outcomes between setups and the devices can not be used interchangeably 10-12 . Previous studies have suggested several factors that might contribute to the disagreement between devices, including i) algorithms used to compute outcomes 10,11 , ii) dead space volumes 11,12 , iii) impact of on-demand oxygen supply on breathing pattern 10,12 , and iv) potential sensor errors 12 .…”

“…Both devices derive the nitrogen concentration indirectly based on molar mass and gas measurements, but there is poor agreement in outcomes between setups and the devices can not be used interchangeably 10-12 . Previous studies have suggested several factors that might contribute to the disagreement between devices, including i) algorithms used to compute outcomes 10,11 , ii) dead space volumes 11,12 , iii) impact of on-demand oxygen supply on breathing pattern 10,12 , and iv) potential sensor errors 12 .…”