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Nitrogen-based lung clearance index: a valid physiological biomarker for the clinic
Chantal Darquenne1, Rebecca J Theilmann2, Janelle M Fine1
1Department of Medicine, University of California, San Diego, California.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|April 21, 2022
Summary
Multiple breath washout (MBW) testing using indirect nitrogen (N2) measurement is a valid physiological tool. Direct measurements confirmed that indirect N2 measurement and gas solubility do not significantly impact functional residual capacity or lung clearance index results.
Area of Science:
- Pulmonary Physiology
- Respiratory Medicine
- Medical Devices
Background:
- Multiple breath washout (MBW) testing is increasingly utilized in clinical settings.
- Commercial devices often use indirect nitrogen (N2) measurement, raising concerns about accuracy.
- Potential pitfalls include indirect N2 measurement and N2 blood solubility.
Purpose of the Study:
- To evaluate the physiological validity of indirect N2 measurement in MBW testing.
- To quantify the impact of indirect N2 measurement and N2 blood solubility on MBW indices.
- To compare direct and indirect N2 measurements during MBW.
Main Methods:
- Performed MBW in 12 healthy adults using a commercial indirect N2 device.
- Simultaneously conducted direct N2 measurements via mass spectrometry.
- Measured argon washout to assess the effect of gas solubility.
Main Results:
- N2 concentration traces were highly similar between direct and indirect methods.
- No significant differences were found in functional residual capacity (FRC) or lung clearance index (LCI) between methods.
- Argon washouts were slightly slower than N2, with blood-tissue impact on LCI < 0.5 units.
Conclusions:
- Indirect N2 measurement in MBW testing provides meaningful physiological data.
- The effects of indirect measurement and N2 blood solubility are minimal in healthy subjects.
- Commercial MBW devices using indirect N2 measurement are reliable for clinical use.

