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Lung cancer is a leading cause of death worldwide. Radiation therapy (RT) is one method to treat this disease. A common side effect of RT for lung cancer is radiation-induced lung damage (RILD) which leads to loss of lung function. RILD often compounds pre-existing smoking-related regional lung function impairment. It is difficult to predict patient outcomes due to large variability in individual response to RT. In this study, the capability of image-based modelling of regional ventilation in lung cancer patients to predict lung function post-RT was investigated. Twenty-five patient-based models were created using CT images to define the airway geometry, size and location of tumour, and distribution of emphysema. Simulated ventilation within the 20 Gy isodose volume showed a statistically significant negative correlation with the change in forced expiratory volume in 1 s 12-months post-RT (p = 0.001, R = − 0.61). Patients with higher simulated ventilation within the 20 Gy isodose volume had a greater loss in lung function post-RT and vice versa. This relationship was only evident with the combined impact of tumour and emphysema, with the location of the emphysema relative to the dose-volume being important. Our results suggest that model-based ventilation measures can be used in the prediction of patient lung function post-RT. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) comprises a large proportion of the lung parenchymal tissue and is an important contributor to the mechanical properties of the lung. The lung tissue is a biologically active scaffold with a complex ECM matrix structure and composition that provides physical support to the surrounding cells. Nearly all respiratory pathologies result in changes in the structure and composition of the ECM; however, the impact of these alterations on the mechanical properties of the tissue is not well understood. In this study, a novel network model was developed to incorporate the combinatorial effect of lung tissue ECM constituents such as collagen, elastin and proteoglycans (PGs) and used to mimic the experimentally derived length–tension response of the tissue to uniaxial loading. By modelling the effect of collagen elasticity as an exponential function with strain, and in concert with the linear elastic response of elastin, the network model's mechanical response matched experimental stress–strain curves from the literature. In addition, by incorporating spring–dashpot viscoelastic elements, to represent the PGs, the hysteresis response was also simulated. Finally, by selectively reducing volume fractions of the different ECM constituents, we were able to gain insight into their relative mechanical contribution to the larger scale tissue mechanical response. [ABSTRACT FROM AUTHOR]

Hypoxic pulmonary vasoconstriction (HPV) is an adaptive response unique to the lung whereby blood flow is diverted away from areas of low alveolar oxygen to improve ventilation-perfusion matching and resultant gas exchange. Some previous experimental studies have suggested that the HPV response to hypoxia is blunted in acute pulmonary embolism (APE), while others have concluded that HPV contributes to elevated pulmonary blood pressures in APE. To understand these contradictory observations, we have used a structure-based computational model of integrated lung function in 10 subjects to study the impact of HPV on pulmonary hemodynamics and gas exchange in the presence of regional arterial occlusion. The integrated model includes an experimentally-derived model for HPV. Its function is validated against measurements of pulmonary vascular resistance in normal subjects at four levels of inspired oxygen. Our results show that the apparently disparate observations of previous studies can be explained within a single model: the model predicts that HPV increases mean pulmonary artery pressure in APE (by 8.2 ± 7.0% in these subjects), and concurrently shows a reduction in response to hypoxia in the subjects who have high levels of occlusion and therefore maximal HPV in normoxia. [ABSTRACT FROM AUTHOR]