Fibrosis Pernia Marin, Monica; Salvatore, Mary
Journal of translational medicine,
01/2023, Letnik:
21, Številka:
1
Journal Article
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Myofibroblasts are mesenchymal cells with several origins; several experimental studies have described the co-expression of endothelial and mesenchymal cell markers in fibroblasts isolated from ...animal models of fibrosis suggesting that endothelial cells can differentiate into myofibroblasts during a process called endothelial to mesenchymal transition which is particularly relevant in the pathophysiology of cardiac, renal, and pulmonary fibrosis 3,4,5,6. There are several cell types and signaling pathways responsible for the development of lung fibrosis following repetitive exposure of the alveolar epithelial cells to a variety of injurious stimuli in combination with individual genetic, epigenetic, and immunological characteristics or predisposition 7. The advanced stages of organ-specific fibrosis are usually associated with great deterioration of the overall functional capacity and quality of life with deeply negative implications for the psychosocial health and well-being of patients and caregivers.
To address the frequency of identifying nonsolid nodules, diagnosing lung cancer manifesting as such nodules, and the long-term outcome after treatment in a prospective cohort, the International ...Early Lung Cancer Action Program.
A total of 57,496 participants underwent baseline and subsequent annual repeat computed tomographic (CT) screenings according to an institutional review board, HIPAA-compliant protocol. Informed consent was obtained. The frequency of participants with nonsolid nodules, the course of the nodule at follow-up, and the resulting diagnoses of lung cancer, treatment, and outcome are given separately for baseline and annual repeat rounds of screening. The χ(2) statistic was used to compare percentages.
A nonsolid nodule was identified in 2392 (4.2%) of 57,496 baseline screenings, and pathologic pursuit led to the diagnosis of 73 cases of adenocarcinoma. A new nonsolid nodule was identified in 485 (0.7%) of 64,677 annual repeat screenings, and 11 had a diagnosis of stage I adenocarcinoma; none were in nodules 15 mm or larger in diameter. Nonsolid nodules resolved or decreased more frequently in annual repeat than in baseline rounds (322 66% of 485 vs 628 26% of 2392, P < .0001). Treatment of the cases of lung cancer was with lobectomy in 55, bilobectomy in two, sublobar resection in 26, and radiation therapy in one. Median time to treatment was 19 months (interquartile range IQR, 6-41 months). A solid component had developed in 22 cases prior to treatment (median transition time from nonsolid to part-solid, 25 months). The lung cancer-survival rate was 100% with median follow-up since diagnosis of 78 months (IQR, 45-122 months).
Nonsolid nodules of any size can be safely followed with CT at 12-month intervals to assess transition to part-solid. Surgery was 100% curative in all cases, regardless of the time to treatment.
•COVID-19 patients have more CT evidence of lung ischemia than non-COVID-19 patients with pulmonary emboli.•The bronchial circulation is available to compensate for pulmonary emboli but in COVID-19, ...the bronchial endothelial cells are vulnerable to infection and may be compromised.•The micro-thrombotic disease of COVID-19 effects vessels smaller than 3 mm, which are more often associated with infarction.
The risk factors for development of fibrotic-like radiographic abnormalities after severe COVID-19 are incompletely described and the extent to which CT findings correlate with symptoms and physical ...function after hospitalisation remains unclear. At 4 months after hospitalisation, fibrotic-like patterns were more common in those who underwent mechanical ventilation (72%) than in those who did not (20%). We demonstrate that severity of initial illness, duration of mechanical ventilation, lactate dehydrogenase on admission and leucocyte telomere length are independent risk factors for fibrotic-like radiographic abnormalities. These fibrotic-like changes correlate with lung function, cough and measures of frailty, but not with dyspnoea.
The periphery of malignant tumors and the leading edge of fibrotic tissue have analogous metabolic pathways. Both use glycolysis as the primary source of energy to produce biomass with consequential ...acidification of the microenvironment. A low PH has been shown to increase the ability of cancer cells to invade the surrounding tissue in both in vitro and in vivo studies. The pH-dependent activation of TGF-B leading to myofibroblast activation is an important step in the initiation and progression of fibrosis. Markers of accelerated cell proliferation have also been reported in the periphery of malignant tumors and the leading edge of fibrosis. Understanding the shared molecular and metabolic characteristics of these conditions may explain the increased prevalence of cancer among patients with fibrosis.
Abstract The transforming growth factor-beta (TGF-β) signaling pathway is a vital regulator of cell proliferation, differentiation, apoptosis, and extracellular matrix production. It functions ...through canonical SMAD-mediated processes and noncanonical pathways involving MAPK cascades, PI3K/AKT, Rho-like GTPases, and NF-κB signaling. This intricate signaling system is finely tuned by interactions between canonical and noncanonical pathways and plays key roles in both physiologic and pathologic conditions including tissue homeostasis, fibrosis, and cancer progression. TGF-β signaling is known to have paradoxical actions. Under normal physiologic conditions, TGF-β signaling promotes cell quiescence and apoptosis, acting as a tumor suppressor. In contrast, in pathological states such as inflammation and cancer, it triggers processes that facilitate cancer progression and tissue remodeling, thus promoting tumor development and fibrosis. Here, we detail the role that TGF-β plays in cancer and fibrosis and highlight the potential for future theranostics targeting this pathway.
Chest Computed tomography (CT) scans detect lung nodules and assess pulmonary fibrosis. While pulmonary fibrosis indicates increased lung cancer risk, current clinical practice characterizes nodule ...risk of malignancy based on nodule size and smoking history; little consideration is given to the fibrotic microenvironment.
To evaluate the effect of incorporating fibrotic microenvironment into classifying malignancy of lung nodules in chest CT images using deep learning techniques.
We developed a visualizable 3D classification model trained with in-house CT dataset for the nodule malignancy classification task. Three slightly-modified datasets were created: (1) nodule alone (microenvironment removed); (2) nodule with surrounding lung microenvironment; and (3) nodule in microenvironment with semantic fibrosis metadata. For each of the models, tenfold cross-validation was performed. Results were evaluated using quantitative measures, such as accuracy, sensitivity, specificity, and area-under-curve (AUC), as well as qualitative assessments, such as attention maps and class activation maps (CAM).
The classification model trained with nodule alone achieved 75.61% accuracy, 50.00% sensitivity, 88.46% specificity, and 0.78 AUC; the model trained with nodule and microenvironment achieved 79.03% accuracy, 65.46% sensitivity, 85.86% specificity, and 0.84 AUC. The model trained with additional semantic fibrosis metadata achieved 80.84% accuracy, 74.67% sensitivity, 84.95% specificity, and 0.89 AUC. Our visual evaluation of attention maps and CAM suggested that both the nodules and the microenvironment contributed to the task.
The nodule malignancy classification performance was found to be improving with microenvironment data. Further improvement was found when incorporating semantic fibrosis information.
•Use Hounsfield unit (HU) techniques to diagnose more with less imaging•After standardization, open-access HU databases could facilitate diagnosis.•HU thresholds have proven use for diagnosis and ...treatment decisions.•Imaging features in radiomics provide more ways to interpret HUs.•Artificial intelligence models can identify useful radiomics features.
Some interstitial lung diseases are associated with lung cancer. However, it is unclear whether asymptomatic interstitial lung abnormalities convey an independent risk.
The goal of this study was to ...assess whether interstitial lung abnormalities are associated with an increased risk of lung cancer.
Data from all participants in the National Lung Cancer Trial were analyzed, except for subjects with preexisting interstitial lung disease or prevalent lung cancers. The primary analysis included those who underwent low-dose CT imaging; those undergoing chest radiography were included in a confirmatory analysis. Participants with evidence of reticular/reticulonodular opacities, honeycombing, fibrosis, or scarring were classified as having interstitial lung abnormalities. Lung cancer incidence and mortality in participants with and without interstitial lung abnormalities were compared by using Poisson and Cox regression, respectively.
Of the 25,041 participants undergoing low-dose CT imaging included in the primary analysis, 20.2% had interstitial lung abnormalities. Participants with interstitial lung abnormalities had a higher incidence of lung cancer (incidence rate ratio, 1.61; 95% CI, 1.30-1.99). Interstitial lung abnormalities were associated with higher lung cancer incidence on adjusted analyses (incidence rate ratio, 1.33; 95% CI, 1.07-1.65). Lung cancer-specific mortality was also greater in participants with interstitial lung abnormalities. Similar findings were obtained in the analysis of participants undergoing chest radiography.
Asymptomatic interstitial lung abnormalities are an independent risk factor for lung cancer that can be incorporated into risk score models.
•Diaphragmatic excursion (DE) correlates with change in lung volume on expiratory imaging.•Patients may not demonstrate a change in tracheal morphology between inspiratory and expiratory phase ...imaging.•DE is an easily derived metric that can be used to determine if there has been a satisfactory end-expiratory effort.
To evaluate diaphragmatic excursion as a quantitative metric for change in lung volume between inspiratory and expiratory chest computed tomography (CT) images.
A 12-month retrospective review identified 226 chest CT exams with inspiratory and expiratory phase imaging, 63 in individuals referred with diagnosis of asthma by ICD9/10 code. Exams acquired in the supine position at 1.25 mm slice thickness in each phase were included (n = 30, mean age = 62, M = 15, F = 15). Diaphragmatic excursion was calculated as the difference between axial slices through the lungs on inspiration and expiration, using the lung apex as the cranial bound, and the hemidiaphragm caudally. Inspiratory and expiratory lung and tracheal volumes were calculated through volumetric segmentation. Tracheal morphology was assessed at 1 cm above the level of the aortic arch, and 1 cm above the carina.
Inspiratory and expiratory lung volumes were higher in men (mean I = 5 + 1.6 L, E = 3.1 + 1.2 L) than women (mean I = 3.6 + 0.8 L, E = 2.4 + 0.7 L), p = .005 and p = .047, respectively. Average inspiratory and expiratory tracheal volumes were higher in men (I = 61 + 17 mL, E = 43 + 14) than women (I = 44 + 14, E = 30 + 8), p = .006 and p = .005. Average change in lung and tracheal volume between inspiratory and expiratory scans did not significantly differ between men and women. Average diaphragmatic excursion was 2.5 cm between inspiratory and expiratory scans (2.7 cm in men, 2.3 cm in women; p = .5). There was a strong positive correlation between diaphragmatic excursion and change in lung (r = .84) and tracheal volume (r = .79). A moderate correlation was also found between change in tracheal volume and change in lung volume (r = 0.67). Change in tracheal morphology between inspiratory and expiratory imaging was associated with change in tracheal volume at both 1 cm above the aortic arch (p = .04) and 1 cm above the carina (p = .008); there was no association with diaphragmatic excursion or lung volume.
Diaphragmatic excursion is a quantitative measure of expiratory effort as validated by both lung and tracheal volumes in asthma patients, and may be more accurate than qualitative assessment based on tracheal morphology.
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