- 作者列表："Hiroyuki Kaneda","Takahito Nakano","Tomohiro Murakawa
Abstract Background The initial management of pneumothorax remains controversial, and we speculated that this might be because there is no method available for evaluation of air leak during initial management. We have developed a system for measurement of intrapleural pressure in pneumothorax to address air leak without the need for chest drainage. The aim of this clinical study was to confirm the ability of this measurement system and to determine the clinical impact of management of air leak. Methods Patients in whom need aspiration was indicated for spontaneous pneumothorax were enrolled in the study. The intrapleural pressure was measured during stable breathing and data recorded when patients were coughing were excluded. Results Eleven patients were enrolled in the study between December 2016 to July 2017. The patterns in change of intrapleural pressure varied widely depending on the state of the pneumothorax. The mean intrapleural pressure values on end-inspiration and end-expiration in patients with persistent air leak was significantly lower than those in patients without persistent air leak (p = 0.020). The number of negative mean pressure recordings in end-inspiration and end-expiration was significantly lower in patients with persistent air leak than in those without persistent air leak (p = 0.0060). Conclusions In this study, we demonstrated that intrapleural pressure could be successfully measured and visualized in patients with pneumothorax. Whether or not the pressure value is a predictor of persistent air leak needs to be confirmed in the future.
摘要背景气胸的初始管理仍存在争议，我们推测这可能是因为在初始管理期间没有可用于评估空气泄漏的方法。我们开发了一种测量气胸中胸腔内压的系统，以解决漏气而不需要胸腔引流。本临床研究的目的是证实该测量系统的能力，并确定空气泄漏管理的临床影响。方法自发性气胸需抽吸的患者纳入研究。稳定呼吸时测量胸膜内压，排除患者咳嗽时记录数据。结果 2016年12月至 2017年7月期间，11 例患者入选研究。胸膜腔内压的变化规律因气胸的状态而异。持续漏气患者吸气末和呼气末的平均胸膜内压值明显低于无持续漏气患者 (p = 0.020)。持续漏气患者吸气末和呼气末的负压记录数量显著低于无持续漏气患者 (p = 0.0060)。结论在这项研究中，我们证明了在气胸患者中可以成功地测量和显示胸腔内压。压力值是否是持续漏气的预测因子，需要在将来确认。
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.