Turning lung clearance index on its head. Reference data for SF₆ multiple-breath washout derived ventilation...

Area of Science:

• Pulmonary Physiology
• Respiratory Medicine
• Medical Device Technology

Background:

• Cystic fibrosis (CF) lung disease involves increased ventilation inhomogeneity (VI), commonly measured by lung clearance index (LCI) from multiple-breath washout (MBW).
• Existing reference equations for SF6 MBW are often unsuitable for updated equipment, and LCI's non-linear relationship with dead space ventilation complicates interpretation.

Purpose of the Study:

• To evaluate historical SF6 MBW reference equations against updated equipment data.
• To develop device-specific equations and explore improved VI outcome measures.
• To introduce ventilation distribution efficiency (VDE) as a potentially superior index for VI.

Main Methods:

• Performed SF6 MBW in 327 healthy children to generate reference equations.
• Calculated z-scores using published and newly derived equations.
• Investigated the relationship between VI and dead space ventilation (VD/VT) in healthy children, CF patients, and adults with lung disease.

Main Results:

• Historical SF6 MBW reference equations were unsuitable for the EXHALYZER D device.
• Ventilation distribution efficiency (1/LCI) demonstrated a linear relationship with VD/VT, unlike LCI.
• New reference equations for VDE and log10(FRC) were established, with age, sex, height, and posture as significant predictors.

Conclusions:

• Ventilation distribution efficiency (VDE) offers a more interpretable measure of VI than LCI, especially for advanced CF lung disease and longitudinal monitoring.
• The developed VDE reference equations provide a valuable tool for clinical assessment.
• Further clinical validation, including longitudinal imaging studies, is recommended.