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J Appl Physiol (1985). 2018 Jul 26. doi: 10.1152/japplphysiol.00326.2018. [Epub ahead of print]

Difference between SF6 and N2 Multiple Breath Washout kinetics is due to N2 back diffusion and error in N2 offset.

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Pediatrics, Emory University School of Medicine, United States.
Center for Cystic Fibrosis and Airways Disease Research, Emory University.
Pulmo Trace, Inc.
PulmoTrace, Inc., United States.
Department of Pediatrics, University of Pittsburgh.



Measurement of Lung Clearance Index (LCI) by Multiple Breath Washout (MBW) is a sensitive method for monitoring of lung disease in Cystic Fibrosis (CF). To compare N2MBW and SF6MBW, we connected these two gas analysis systems in series to obtain truly simultaneous measurements, with no differences other than the gas used.


Non-smoking healthy controls (HC) and subjects with CF were recruited at two institutions. The Exhalyzer-D (for N2MBW measurement) was connected in series with the Innocor (for SF6MBW measurement). Subjects washed in SF6 from a Douglas bag with tidal breathing, and washed out SF6 and nitrogen with 100% oxygen provided as bias flow. Washout of both gases was continued past the LCI point (1/40th of equilibration concentration) in triplicate.


N2MBW resulted in higher Cumulative Exhaled Volume (CEV), Functional Residual Capacity (FRC), and LCI when compared to SF6 derived parameters in HC subjects (p<0.0001 for all comparisons). All N2MBW parameters were also significantly higher than SF6MBW parameters in CF subjects (p<0.01 for all comparisons). After recalculation with a common FRC, N2MBW-LCI was higher than SF6MBW-LCI in CF subjects (19.73 vs. 11.39; p<0.0001) and in HC (8.12 vs. 6.78; p<0.0001). Adjusting for N2 back diffusion and an offset error in the nitrogen measurement resulted in near complete agreement between the two methodologies.


We found significant differences in LCI and FRC measurements using two different gases for MBW. This may have significant implications for the future use and interpretation of LCI data in clinical trials and routine clinical care.


Cystic Fibrosis; Lung Clearance Index; Lung Function; Pulmonary Function Testing; Ventilation inhomogeneity

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