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American Journal of Respiratory Cell... Apr 2021is the leading cause of hospital community-acquired pneumonia. Patients with pneumococcal pneumonia may develop complicated parapneumonic effusions or empyema that can...
is the leading cause of hospital community-acquired pneumonia. Patients with pneumococcal pneumonia may develop complicated parapneumonic effusions or empyema that can lead to pleural organization and subsequent fibrosis. The pathogenesis of pleural organization and scarification involves complex interactions between the components of the immune system, coagulation, and fibrinolysis. EPCR (endothelial protein C receptor) is a critical component of the protein C anticoagulant pathway. The present study was performed to evaluate the role of EPCR in the pathogenesis of infection-induced pleural thickening and fibrosis. Our studies show that the pleural mesothelium expresses EPCR. Intrapleural instillation of impairs lung compliance and lung volume in wild-type and EPCR-overexpressing mice but not in EPCR-deficient mice. Intrapleural infection induces pleural thickening in wild-type mice. Pleural thickening is more pronounced in EPCR-overexpressing mice, whereas it is reduced in EPCR-deficient mice. Markers of mesomesenchymal transition are increased in the visceral pleura of infected wild-type and EPCR-overexpressing mice but not in EPCR-deficient mice. The lungs of wild-type and EPCR-overexpressing mice administered intrapleural showed increased infiltration of macrophages and neutrophils, which was significantly reduced in EPCR-deficient mice. An analysis of bacterial burden in the pleural lavage, the lungs, and blood revealed a significantly lower bacterial burden in EPCR-deficient mice compared with wild-type and EPCR-overexpressing mice. Overall, our data provide strong evidence that EPCR deficiency protects against infection-induced impairment of lung function and pleural remodeling.
Topics: Animals; Bacterial Load; Cells, Cultured; Disease Models, Animal; Endothelial Protein C Receptor; Female; Fibrosis; Host-Pathogen Interactions; Humans; Lung; Macrophages; Male; Mice, Inbred C57BL; Mice, Knockout; Neutrophil Infiltration; Neutrophils; Pleura; Pleural Effusion; Pleurisy; Pneumonia, Pneumococcal; Streptococcus pneumoniae; Mice
PubMed: 33600743
DOI: 10.1165/rcmb.2020-0328OC -
Toxicology and Applied Pharmacology Jul 2018This study provides an understanding of the biokinetics and potential toxicology in the lung and pleura following inhalation of brake-dust (brakes manufactured with... (Comparative Study)
Comparative Study
Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to chrysotile or crocidolite asbestos in a 28-day quantitative inhalation toxicology study.
This study provides an understanding of the biokinetics and potential toxicology in the lung and pleura following inhalation of brake-dust (brakes manufactured with chrysotile). The design included a 28-day repeated multi-dose inhalation exposure (6 h/d, 5 d/wk, 4 wks) followed by 28-days without exposure. Fiber control groups included a similar grade chrysotile as used in the brakes and a commercial crocidolite asbestos. Aerosol fiber distributions of the chrysotile and crocidolite were similar (fiber-length > 20 μm/cm: Chrysotile-low/high 42/62; Crocidolite-low/high 36/55; WHO-fibers/cm: Chrysotile-low/high 192/219; Crocidolite-low/high 211/255). The total number of aerosol particles/cm in the brake-dust was similar to that in the chrysotile (Brake-dust 710-1065; Chrysotile 532-1442). Brake-dust at particle exposure levels equal to or greater than chrysotile or crocidolite caused no indication of microgranulomas, epithelial hyperplasia, or fibrosis (Wagner score < 1.7) or changes in bronchoalveolar lavage (BAL) indices from the air control. Chrysotile BAL indices did not differ from the air control. Pathologically, there was low level of inflammation and epithelial hyperplasia, but no fibrosis (Wagner score ≤ 3). Crocidolite induced elevated neutrophils and cell damage (BAL), persistent inflammation, microgranulomas, and fibrosis (Wagner scores 4) which persisted through the post exposure period. Confocal microscopy of snap-frozen chestwalls showed no difference between control, brake-dust and chrysotile-HD groups or in thickness of visceral or parietal pleural. The crocidolite exposure resulted in extensive inflammatory response, collagen development and adhesions between the visceral and parietal surfaces with double the surface thickness. These results provide essential information for the design of a subsequent subchronic study.
Topics: Animals; Asbestos, Crocidolite; Asbestos, Serpentine; Dose-Response Relationship, Drug; Dust; Inhalation Exposure; Lung; Particle Size; Pleura; Rats; Time Factors
PubMed: 29705295
DOI: 10.1016/j.taap.2018.04.033 -
Clinics (Sao Paulo, Brazil) 2024Lung lymphatic drainage occurs mainly through a peribronchial path, but it is hypothesized that visceral pleural invasion could alter this path. This study aims to...
BACKGROUND
Lung lymphatic drainage occurs mainly through a peribronchial path, but it is hypothesized that visceral pleural invasion could alter this path. This study aims to investigate the association between visceral pleural invasion, node upstaging, and N2 skip metastasis and the impact on survival in a population of patients with non-small cell lung cancer of 3 cm or smaller.
METHODS
We retrospectively queried our institutional database of lung cancer resection for all patients with clinical stage IA NSCLC between June 2009 and June 2022. We collected baseline characteristics and clinical and pathological staging data. Patients were classified into two groups: The non-VPI group with negative visceral pleural invasion and the VPI group with positive. The primary results analyzed were the occurrence of nodal upstaging, skip N2 metastasis and recurrence.
RESULTS
There were 320 patients analyzed. 61.3 % were women; the median age was 65.4 years. The pleural invasion occurred in 44 patients (13.7 %). VPI group had larger nodules (2.3 vs. 1.7 cm; p < 0.0001), higher 18F-FDG uptake (7.4 vs. 3.4; p < 0.0001), and lymph-vascular invasion (35.7 % vs. 13.5 %, p = 0.001). Also, the VPI group had more nodal disease (25.6 % vs. 8.7 %; p = 0.001) and skip N2 metastasis (9.3 % vs. 1.8 %; p = 0.006). VPI was a statistically independent factor for skip N2 metastasis. Recurrence occurred in 17.2 % of the population. 5-year disease-free and overall survival were worse in the VPI group.
CONCLUSIONS
The visceral pleural invasion was an independent factor associated with N2 skip metastasis and had worse disease-free and overall survival.
Topics: Humans; Female; Aged; Male; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Retrospective Studies; Neoplasm Staging; Pleura; Neoplasm Invasiveness; Prognosis
PubMed: 38484584
DOI: 10.1016/j.clinsp.2024.100334 -
American Journal of Respiratory and... Dec 2013
Topics: Animals; Humans; Lung; Male; Pleura; Positive-Pressure Respiration; Pressure; Respiration; Respiratory Distress Syndrome
PubMed: 24328769
DOI: 10.1164/rccm.201311-1993ED -
PloS One 2013Mesothelia, which cover all coelomic organs and body cavities in vertebrates, perform diverse functions in embryonic and adult life. Yet, mesothelia are traditionally...
Mesothelia, which cover all coelomic organs and body cavities in vertebrates, perform diverse functions in embryonic and adult life. Yet, mesothelia are traditionally viewed as simple, uniform epithelia. Here we demonstrate distinct differences between visceral and parietal mesothelia, the most basic subdivision of this tissue type, in terms of gene expression, adhesion, migration, and invasion. Gene profiling determined that autotaxin, a secreted lysophospholipase D originally discovered as a tumor cell-motility-stimulating factor, was expressed exclusively in the more motile and invasive visceral mesothelia and at abnormally high levels in mesotheliomas. Gain and loss of function studies demonstrate that autotaxin signaling is indeed a critical factor responsible for phenotypic differences within mesothelia. Furthermore, we demonstrate that known and novel small molecule inhibitors of the autotaxin signaling pathway dramatically blunt migratory and invasive behaviors of aggressive mesotheliomas. Taken together, this study reveals distinct phenotypes within the mesothelial cell lineage, demonstrates that differential autotaxin expression is the molecular underpinning for these differences, and provides a novel target and lead compounds to intervene in invasive mesotheliomas.
Topics: Animals; Cell Line, Tumor; Epithelial Cells; Epithelium; Gene Expression; Genetic Heterogeneity; Humans; Intestine, Small; Lung Neoplasms; Mesothelioma; Mice; Mice, Transgenic; Omentum; Peritoneal Neoplasms; Phenotype; Phosphoric Diester Hydrolases; Pleura; Signal Transduction; Viscera
PubMed: 23936085
DOI: 10.1371/journal.pone.0069712 -
Occupational and Environmental Medicine Aug 2015To conduct a systematic review of changes in lung function in relation to presence of pleural plaques in asbestos-exposed populations. (Review)
Review
OBJECTIVES
To conduct a systematic review of changes in lung function in relation to presence of pleural plaques in asbestos-exposed populations.
METHODS
Database searches of PubMed and Web of Science were supplemented by review of papers' reference lists and journals' tables of contents. Methodological features (eg, consideration of potential confounding by smoking) of identified articles were reviewed by ≥ two reviewers. Meta-analyses of 20 studies estimated a summary effect of the decrements in per cent predicted (%pred) forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) associated with presence of pleural plaques.
RESULTS
Among asbestos-exposed workers, the presence of pleural plaques was associated with statistically significant decrements in FVC (4.09%pred, 95% CI 2.31 to 5.86) and FEV1 (1.99%pred, 95% CI 0.22 to 3.77). Effects of similar magnitude were seen when stratifying by imaging type (X-ray or high-resolution CT) and when excluding studies with potential methodological limitations. Undetected asbestosis was considered as an unlikely explanation of the observed decrements. Several studies provided evidence of an association between size of pleural plaques and degree of pulmonary decrease, and presence of pleural plaques and increased rate or degree of pulmonary impairment.
CONCLUSIONS
The presence of pleural plaques is associated with a small, but statistically significant mean difference in FVC and FEV1 in comparison to asbestos-exposed individuals without plaques or other abnormalities. From a public health perspective, small group mean decrements in lung function coupled with an increased rate of decline in lung function of the exposed population may be consequential.
Topics: Asbestos; Asbestosis; Forced Expiratory Volume; Humans; Lung; Lung Diseases; Occupational Diseases; Occupational Exposure; Pleura; Pleural Diseases; Smoking; Vital Capacity
PubMed: 25504898
DOI: 10.1136/oemed-2014-102468 -
Zhongguo Fei Ai Za Zhi = Chinese... Apr 2022Lung cancer is still the malignant tumor with the highest morbidity and mortality in China. Lung adenocarcinoma is the most common subtype, and the number of lung cancer...
BACKGROUND
Lung cancer is still the malignant tumor with the highest morbidity and mortality in China. Lung adenocarcinoma is the most common subtype, and the number of lung cancer presenting as mixed ground glass nodule (mGGN) in imaging is gradually increasing. Visceral pleural invasion (VPI) is an important factor affecting the prognosis of mGGN type lung adenocarcinoma. The aim of the study is to explore and analyze the risk factors for VPI in mGGN type lung adenocarcinoma.
METHODS
From November 2016 to November 2019, 128 patients with mGGN lung adenocarcinoma underwent radical surgical resection in the First Affiliated Hospital of Nanjing Medical University. Their clinical data, including imaging, pathological and biological features, were collected and analyzed retrospectively. There were 40 males and 88 females, aged 60.3±9.3 years ranging from 30 to 81 years. Single factor Chi-square test and multivariate Logistic regression were used to analyze the risk factors of VPI in mGGN type lung adenocarcinoma.
RESULTS
Among 128 mGGN patients who met the inclusion criteria, 57 cases were pathologically confirmed with pleural invasion. Between the VPI (+) and VPI (-) group (P<0.05), there were significant differences in gender, maximum diameter of solid component, consolidation tumor ratio (CTR), spicule sign, history of lung disease, family history of hypertension, relation of lesion to pleura (RLP), coursing relationship between bronchi and nodules. In multivariate Logistic regression analysis, RLP (OR=3.529, 95%CI: 1.430-8.713, P=0.006) and coursing relationship between bronchi and nodules (OR=3.993, 95%CI: 1.517-10.51, P=0.005) were found to be independent risk factors for VPI (P<0.05).
CONCLUSIONS
The possibility of VPI in m GGN lung adenocarcinoma should be evaluated by combining these parameters in clinical diagnosis and treatment. As independent risk factors, RLP and coursing relationship between bronchi and nodules are instructive to identify VPI in mGGN type lung adenocarcinoma.
Topics: Adenocarcinoma of Lung; Female; Humans; Lung Neoplasms; Male; Neoplasm Invasiveness; Pleura; Retrospective Studies; Risk Factors
PubMed: 35477187
DOI: 10.3779/j.issn.1009-3419.2022.102.07 -
Contrast Media & Molecular Imaging 2022This study aims to investigate the diagnostic value of 18F-FDG PET/CT in tuberculous pleurisy (TBP) and the differential diagnostic value of 18F-FDG PET/CT between TBP...
The Value of 18F-FDG PET/CT in the Diagnosis of Tuberculous Pleurisy and in the Differential Diagnosis between Tuberculous Pleurisy and Pleural Metastasis from Lung Adenocarcinoma.
OBJECTIVES
This study aims to investigate the diagnostic value of 18F-FDG PET/CT in tuberculous pleurisy (TBP) and the differential diagnostic value of 18F-FDG PET/CT between TBP and pleural metastasis from lung adenocarcinoma (PMLAC).
MATERIALS AND METHODS
The features of pleura on PET and hybrid CT were retrospectively studied in 20 patients with TBP and 32 patients with PMLAC. The ROC curve was used to evaluate the diagnostic effectiveness of these indices for TBP and PMLAC, and binary logistic regression analysis was conducted to identify independent predictors of TBP and PMLAC.
RESULTS
There were significant differences in pleural 18F-FDG uptake pattern on PET (=0.001), pleural morphology pattern on CT (=0.002), the maximum diameter of the pleural nodule (=0.001), and interlobular fissure nodule (=0.001) between TBP and PMLAC groups. The diffused pleural FDG uptake type on PET (odds ratio (OR) = 6.0, 95% CI 2.216-16.248, =0.001) and the lamellar pleural thickening type on CT (OR = 4.4, 95% CI 2.536-7.635, =0.001) were independent predictors of TBP, with 60% and 55% sensitivity, 96.6% and 90.6% specificity, and 82.7% and 77.0% accuracy. The combined diagnostic sensitivity, specificity, and accuracy for TBP were 70%, 87.5%, and 80.8%. The mixed pleural FDG uptake type on PET (OR = 5.106, 95% CI 2.024-12.879, =0.001), the mixed pleural thickening type on CT (OR = 2.289, 95% CI 1.442-3.634, =0.001), and the maximum diameter of the pleural nodule (OR = 1.027, 95% CI 1.012-1.042, =0.001) were independent predictors of PMLAC, with 78.1%, 71.9%, and 87.5% sensitivity, 85%, 80%, and 85% specificity, and 80.8%, 75%, and 86.5% accuracy. The combined diagnostic sensitivity, specificity, and accuracy for PMLAC were 96.9%, 85%, and 90.4%.
CONCLUSIONS
18F-FDG PET/CT is of great clinical value in the diagnosis of TBP and in the differential diagnosis between TBP and PMLAC.
Topics: Adenocarcinoma of Lung; Diagnosis, Differential; Fluorodeoxyglucose F18; Humans; Lung Neoplasms; Pleura; Positron Emission Tomography Computed Tomography; Retrospective Studies; Tuberculosis, Pleural
PubMed: 35965614
DOI: 10.1155/2022/4082291 -
BMC Cancer Sep 2022Pleural deformation is associated with the invasiveness of lung adenocarcinoma(LAC). Our study focused on the pathological components of the area adjacent pleura in...
BACKGROUND
Pleural deformation is associated with the invasiveness of lung adenocarcinoma(LAC). Our study focused on the pathological components of the area adjacent pleura in pulmonary pure ground-glass nodules(pGGNs) with pleural deformations(P-pGGNs) confirmed to be invasive LAC without visceral pleural invasion (VPI) pathologically.
METHODS
Computed tomography(CT) imaging features of nodules and pathological components of the area adjacent pleura were analyzed and recorded. Statistical analysis was performed for subgroups of P-pGGNs.
RESULTS
The 81 enrolled patients with 81 P-pGGNs were finally involved in the analysis. None of solid/micropapillary group and none of VPI was observed, 54 alveoli/lepidics and 27 acinar/papillarys were observed. In P-pGGN with acinar/papillary components of the area adjacent pleura, invasive adenocarcinoma (IAC) was more common compared to minimally invasive adenocarcinoma (MIA, 74.07% vs. 25.93%; p < 0.001). The distance in alveoli/lepidic group was significantly larger (1.50 mm vs. 0.00 mm; p < 0.001) and the depth was significantly smaller (2.00 mm vs. 6.00 mm; p < 0.001) than that in acinar/papillary group. The CT attenuation value, maximum diameter and maximum vertical diameter was valuable to distinguish acinar/papillary group form alveoli/lepidic group(p < 0.05). The type d pleural deformation was the common pleural deformation in IAC(p = 0.028).
CONCLUSIONS
The pathological components of the area adjacent pleura in P-pGGN without VPI confirmed to be invasive LAC could included alveoli/lepidics and acinar/papillarys. Some CT indicators that can identify the pathological invasive components of the area adjacent pleura in P-pGGNs.
Topics: Adenocarcinoma; Adenocarcinoma of Lung; Humans; Lung Neoplasms; Neoplasm Invasiveness; Pleura; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 36068487
DOI: 10.1186/s12885-022-10043-2 -
BMC Physiology Mar 2012Matrix metalloproteinases (MMPs) 2 and 9 are two gelatinase members which have been found elevated in exudative pleural effusions. In endothelial cells these MMPs...
BACKGROUND
Matrix metalloproteinases (MMPs) 2 and 9 are two gelatinase members which have been found elevated in exudative pleural effusions. In endothelial cells these MMPs increase paracellular permeability via the disruption of tight junction (TJ) proteins occludin and claudin. In the present study it was investigated if MMP2 and MMP9 alter permeability properties of the pleura tissue by degradation of TJ proteins in pleural mesothelium.
RESULTS
In the present study the transmesothelial resistance (RTM) of sheep pleura tissue was recorded in Ussing chambers after the addition of MMP2 or MMP9. Both enzymes reduced RTM of the pleura, implying an increase in pleural permeability. The localization and expression of TJ proteins, occludin and claudin-1, were assessed after incubation with MMPs by indirect immunofluorescence and western blot analysis. Our results revealed that incubation with MMPs did not alter neither proteins localization at cell periphery nor their expression.
CONCLUSIONS
MMP2 and MMP9 increase the permeability of sheep pleura and this finding suggests a role for MMPs in pleural fluid formation. Tight junction proteins remain intact after incubation with MMPs, contrary to previous studies which have shown TJ degradation by MMPs. Probably MMP2 and MMP9 augment pleural permeability via other mechanisms.
Topics: Animals; In Vitro Techniques; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Permeability; Pleura; Sheep
PubMed: 22424238
DOI: 10.1186/1472-6793-12-2