Difference between SF₆ and N₂ multiple breath washout kinetics is due to N₂ back diffusion and error in N₂ offset

Area of Science:

• Pulmonary Physiology
• Respiratory Medicine
• Diagnostic Imaging

Background:

• Lung clearance index (LCI) via multiple breath washout (MBW) is a sensitive tool for monitoring lung disease in cystic fibrosis (CF).
• Simultaneous measurement of LCI using different gases (nitrogen and sulfur hexafluoride) is crucial for method validation.

Purpose of the Study:

• To directly compare nitrogen MBW (N₂-MBW) and sulfur hexafluoride MBW (SF₆-MBW) for LCI measurement.
• To identify and address discrepancies between N₂-MBW and SF₆-MBW in healthy controls and CF patients.

Main Methods:

• N₂-MBW and SF₆-MBW systems were connected in series for simultaneous measurements in healthy controls and CF subjects.
• Subjects performed tidal breathing wash-in of SF₆ and wash-out of SF₆ and nitrogen with 100% oxygen.
• Data analysis included recalculation with common functional residual capacity (FRC) and adjustments for nitrogen back diffusion and offset error.

Main Results:

• N₂-MBW yielded significantly higher cumulative exhaled volume, FRC, and LCI compared to SF₆-MBW in both healthy controls and CF subjects.
• After recalculation with a common FRC, N₂-MBW LCI remained higher than SF₆-MBW LCI in both groups.
• Adjusting for nitrogen back diffusion and offset error led to near-complete agreement between the two MBW methodologies.

Conclusions:

• Significant differences exist between N₂-MBW and SF₆-MBW measurements of LCI and FRC.
• Nitrogen back diffusion and measurement offset errors explain the observed discrepancies.
• Accurate interpretation of LCI data in clinical trials and routine care requires accounting for these methodological differences.