A functional mathematical model to simulate the single-breath nitrogen washout

Area of Science:

• Pulmonary physiology
• Respiratory mechanics
• Mathematical modeling

Background:

• Pulmonary inhomogeneities significantly impact respiratory system function.
• The single-breath nitrogen washout (SBNW) test is sensitive to lung heterogeneity.
• Interpreting SBNW curves, particularly phase III and IV, requires understanding underlying physiological mechanisms.

Purpose of the Study:

• To develop and validate a nonlinear dynamic model of pulmonary inhomogeneities.
• To interpret the influence of lung inhomogeneities on the single-breath nitrogen washout (SBNW) curve.
• To elucidate the relationship between airway mechanical properties and SBNW phase III slope.

Main Methods:

• A two-parallel-zone nonlinear dynamic model was developed.
• Airways were modeled with pressure-dependent resistance and collapsible segments.
• Simulations were performed for reference (normal) and two pathological lung conditions.
• The model's output was analyzed for SBNW curve characteristics, including phase III slope and phase IV onset.

Main Results:

• The model accurately reproduced SBNW curves in normal and diseased states.
• In normal lungs, phase III was linear, with phase IV clearly demarcated.
• Pathological states showed an increased phase III slope (1.1% to 7.7% N2/1000ml) and blurred phase IV.
• The phase III slope was primarily driven by nitrogen concentration differences due to varying airway mechanical properties.

Conclusions:

• The proposed nonlinear dynamic model effectively captures the impact of pulmonary inhomogeneities on SBNW.
• Differences in respiratory airway mechanical properties are key determinants of the SBNW phase III slope.
• The model provides insights into physiological mechanisms underlying SBNW changes in health and disease.