- 作者列表："Fortin M","Cabon E","Berbis J","Laroumagne S","Guinde J","Elharrar X","Dutau H","Astoul P
BACKGROUND:Medical history, thoracentesis, and imaging features are usually the first steps in the investigation of a possible malignant pleural effusion (MPE). Unfortunately, the diagnostic yield of thoracentesis in this situation is suboptimal even if the procedure is repeated, especially in the context of malignant pleural mesothelioma (MPM). The next step for confirming the diagnosis, if clinically appropriate, is thoracoscopy, but not all patients are fit to undergo this procedure, so the diagnosis is then based on the medical history and imaging features only. OBJECTIVES:Our objective was to evaluate the diagnostic value of the medical history and imaging features in MPM. METHODS:We reviewed the imaging and medical charts of 92 patients with a final diagnosis of MPE included in our prospective medical thoracoscopy database. The clinical characteristics and imaging features of patients with primary MPE were compared with those of patients with secondary MPE. RESULTS:Male sex (82 vs. 59%, p = 0.02), asbestos exposure (58 vs. 10%, p < 0.001), and mediastinal (68 vs. 33%, p = 0.04), diaphragmatic (75 vs. 31%, p = 0.001) and circumferential pleural thickening (55 vs. 19% p = 0.001) were significantly more frequent in MPM patients. In a multivariate linear regression model, only asbestos exposure (OR 11.2; 95% CI 3.4-36.9) and circumferential pleural thickening (OR 4.7; 95% CI 1.6-13.9) were significantly associated with a diagnosis of MPM. CONCLUSION:In situations where it is impossible to obtain adequate pleural samples to differentiate MPM from a secondary pleural malignancy, the combination of circumferential pleural thickening and a history of asbestos exposure may be sufficient to make a clinical diagnosis.
背景: 病史、胸腔穿刺和影像学特征通常是可能的恶性胸腔积液 (MPE) 调查的第一步。不幸的是，即使重复操作，在这种情况下胸腔穿刺术的诊断率也不理想，特别是在恶性胸膜间皮瘤 (MPM) 的背景下。如果临床适当，确认诊断的下一步是胸腔镜检查，但并非所有患者都适合接受该手术,因此，诊断仅基于病史和影像学特征。 目的: 我们的目的是评估病史和影像学特征对 MPM 的诊断价值。 方法: 我们回顾了我们的前瞻性内科胸腔镜数据库中纳入的 92 例最终诊断为 MPE 的患者的影像学和医学图表。比较原发性 MPE 患者与继发性 MPE 患者的临床特征及影像学特征。 成果: 男性性别 (82 vs。59%，p = 0.02) 、石棉接触 (58。10%，p <0.001) 和纵隔 (68 vs. 33%，p = 0.04) 、膈肌 (75 vs. 31%，p = 0.001) 和环状胸膜增厚 (55 vs。19% p = 0.001)在 MPM 患者中明显更频繁。在多元线性回归模型中，仅石棉暴露 (OR 11.2; 95% CI 3.4-36.9) 和环状胸膜增厚 (OR 4.7; 95% CI 1.6-13.9) 与 MPM 的诊断显著相关。 结论: 在无法获得足够的胸膜样本来区分 MPM 和继发性胸膜恶性肿瘤的情况下,环状胸膜增厚和石棉接触史的组合可能足以做出临床诊断。
METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.
METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.
METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.