Work

Patient-specific tracheal deformation, predicted toxicant uptake and histopathology in lung fibrosis

Year: 2024

Type: article

Abstract: • This is a novel investigation of the common clinical observation of a deformed trachea among persons with pulmonary fibrosis and connects state-of-the-art patient-specific environmental toxicology modelling with, in a small sample, their matched distal pathologic observations. • We have used an interdisciplinary approach, linking patient-specific radiographic information and histopathological observations of tissue samples. • Our computational methods provide a powerful tool to predict focal sites of epithelial injury and to interrogate crosstalk between airway exposure and the incidence, exacerbation risk and progression of fibrotic lung disease. Our simulations previously predicted focal areas of gaseous pollutant dose delivered to the airway mucosa of a patient with idiopathic pulmonary fibrosis (IPF). We hypothesize a relation between these dose predictions and clinically meaningful endpoints in IPF which link toxicant-driven epithelial injury and disrepair to IPF etiology and pathogenesis. To determine associations between patient-specific modeling of tracheal geometry, computer simulations of toxicant dose, and lung histopathology in patients with IPF. The first three conducting airway generations of ten patients diagnosed with IPF were reconstructed from their high-resolution CT chest scans. We quantified geometric abnormalities of the reconstructed tracheas based on their curvature and eccentricity (cross-sectional flattening), and performed three-dimensional computer simulations to predict the average and upper values ( i.e. hotspots) of reactive toxicant dose to the underlying mucosa. Distal biopsy tissue samples were characterized by epithelial cell phenotype, extent of fibrosis, and histopathologic severity scores. Non-parametric correlation analysis examined associations between these descriptors. Computed values for curvature and eccentricity of IPF-deformed trachea varied widely among patients and correlated with more subjective rankings of tracheal deformation, and with predicted toxicant dose. Overall histopathologic severity was positively correlated with tracheal deformation and upper decile toxicant uptake. Tracheal curvature was significantly correlated with fibroblastic foci. These results demonstrate an association of tracheal curvature with predicted toxicant dose and with histopathologic indicators in distal tissue. This suggests that these measures may be predictors of risk for acute IPF exacerbations, subsequent clinical deterioration, and disease progression. Toxicant wall uptake in large airways can be modelled to relate to patient specific histopathological changes.

Source: Hygiene and Environmental Health Advances

DOI: 10.1016/j.heha.2024.100117