Difference between SF and N multiple breath washout kinetics is due to N back diffusion and error in N offset.

Measurement of lung clearance index (LCI) by multiple breath washout (MBW) is a sensitive method for monitoring lung disease in patients with cystic fibrosis (CF). To compare nitrogen MBW (N-MBW) and sulfur hexafluoride MBW (SF-MBW), we connected these two gas analysis systems in series to obtain truly simultaneous measurements, with no differences other than the gas used. Nonsmoking healthy controls (HC) and subjects with CF were recruited at two institutions. The Exhalyzer-D (for N-MBW measurement) was connected in series with the Innocor (for SF-MBW measurement). Subjects washed in SF from a Douglas bag with tidal breathing and washed out SF 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. N-MBW resulted in higher cumulative exhaled volume, functional residual capacity (FRC), and LCI when compared with SF-derived parameters in HC subjects ( < 0.0001 for all comparisons). All N-MBW parameters were also significantly higher than SF-MBW parameters in subjects with CF ( < 0.01 for all comparisons). After recalculation with a common FRC, N-MBW LCI was higher than SF-MBW LCI in subjects with CF (19.73 vs. 11.39; < 0.0001) and in HC (8.12 vs. 6.78; < 0.0001). Adjusting for N 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. This study provides important insights into the differences between the two techniques used for measuring lung clearance index (LCI): N and SF multiple breath washout. Differences between measurements made by these two methods in subjects with cystic fibrosis and healthy controls could be explained by nitrogen back diffusion and N offset error. This is important for use and interpretation of LCI data as an outcome measure for clinical trials and in routine clinical care.