Abstract
The multiple-breath washout (MBW) is a lung function test that measures the degree of ventilation inhomogeneity (VI). The test is used to identify small airway impairment in patients with lung diseases like cystic fibrosis. However, the physical and physiological factors that influence the test outcomes and differentiate health from disease are not well understood. Computational models have been used to better understand the interaction between anatomical structure and physiological properties of the lung, but none of them has dealt in depth with the tracer gas washout test in a whole. Thus, our aim was to create a lung model that simulates the entire MBW and investigate the role of lung morphology and tissue mechanics on the tracer gas washout procedure. To this end, we developed a multi-scale lung model to simulate the inert gas transport in airways of all size. We then applied systematically different modifications to geometrical and mechanical properties of the lung model (compliance, residual airway volume and flow resistance) which have been associated with VI. The modifications were applied to distinct parts of the model, and their effects on the gas distribution within the lung and on the gas concentration profile were assessed. We found that variability in compliance and residual volume of the airways, as well as the spatial distribution of this variability in the lung had a direct influence on gas distribution among airways and on the MBW pattern (washout duration, characteristic concentration profile during each expiration), while the effects of variable flow resistance were negligible. Based on these findings, it is possible to classify different types of inhomogeneities in the lung and relate them to specific features of the MBW pattern, which builds the basis for a more detailed association of lung function and structure.
Highlights
The multiple-breath washout (MBW) is a lung function test that measures the degree of ventilation inhomogeneity [1] and is increasingly used for both research and clinical purposes in patients with obstructive lung disease, such as cystic fibrosis, primary ciliary dyskinesia, etc. [2,3,4]
We presented a multi-scale model of the whole lung that simulates the gas transport and washout in conducting and acinar airways, including non-linear tissue mechanics
In order to mimic a physiological degree of ventilation inhomogeneity as described in healthy lungs, we introduced modifications in mechanical and geometrical properties on a lobular level
Summary
The multiple-breath washout (MBW) is a lung function test that measures the degree of ventilation inhomogeneity [1] and is increasingly used for both research and clinical purposes in patients with obstructive lung disease, such as cystic fibrosis, primary ciliary dyskinesia, etc. [2,3,4]. The test is based on the clearance of a tracer gas during multiple tidal breaths. Each MBW test comprises a washin and a washout phase. The tracer gas (normally an inert extrinsic gas) is delivered in a known concentration. When the tracer gas concentration reaches an equilibrium in the lung, the washout phase starts. In the case of inert intrinsic gases (N2), the test is simplified, as no washin phase is needed. The progressive decrease in tracer gas concentration during the washout (washout envelope) as well as the breath-bybreath analysis provide useful information about the distribution of ventilation within the lung [1], and for this reason the test is of increasing importance for the medical community. The biomechanical phenomena that influence the specific washout profile of a tracer gas are not well understood
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