Integrative Computational Models of Lung Structure-Function Interactions

Anatomically based integrative models of the lung and their interaction with other key components of the respiratory system provide unique capabilities for investigating both normal and abnormal lung function. There is substantial regional variability in both structure and function within the normal lung, yet it remains capable of relatively efficient gas exchange by providing close matching of air delivery (ventilation) and blood delivery (perfusion) to regions of gas exchange tissue from the scale of the whole organ to the smallest continuous gas exchange units. This is despite remarkably different mechanisms of air and blood delivery, different fluid properties, and unique scale-dependent anatomical structures through which the blood and air are transported. This inherent heterogeneity can be exacerbated in the presence of disease or when the body is under stress. Current computational power and data availability allow for the construction of sophisticated data-driven integrative models that can mimic respiratory system structure, function, and response to intervention. Computational models do not have the same technical and ethical issues that can limit experimental studies and biomedical imaging, and if they are solidly grounded in physiology and physics they facilitate investigation of the underlying interaction between mechanisms that determine respiratory function and dysfunction, and to estimate otherwise difficult-to-access measures. © 2021 American Physiological Society. Compr Physiol 11:1501-1530, 2021.