New Fissure-Attached Nodules in Lung Cancer Screening: A Brief Report From The NELSON Study.
肺癌筛查中的新裂隙附着结节: NELSON 研究的简要报告。
- 作者列表："Han D","Heuvelmans MA","van der Aalst CM","van Smoorenburg LH","Dorrius MD","Rook M","Nackaerts K","Walter JE","Groen HJM","Vliegenthart R","de Koning HJ","Oudkerk M
INTRODUCTION:In incidence lung cancer screening rounds, new pulmonary nodules are regular findings. They have a higher lung cancer probability than baseline nodules. Previous studies have shown that baseline perifissural nodules (PFNs) represent benign lesions. Whether this is also the case for incident PFNs is unknown. This study evaluated newly detected nodules in the Dutch-Belgian randomized-controlled NELSON study with respect to incidence of fissure-attached nodules, their classification, and lung cancer probability. METHODS:Within the NELSON trial, 7557 participants underwent baseline screening between April 2004 and December 2006. Participants with new nodules detected after baseline were included. Nodules were classified based on location and attachment. Fissure-attached nodules were re-evaluated to be classified as typical, atypical, or non-PFN by two radiologists without knowledge of participant lung cancer status. RESULTS:One thousand four hundred eighty-four new nodules were detected in 949 participants (77.4% male, median age 59 years [interquartile range: 55-63 years]) in the second, third, and final NELSON screening round. Based on 2-year follow-up or pathology, 1393 nodules (93.8%) were benign. In total, 97 (6.5%) were fissure-attached, including 10 malignant nodules. None of the new fissure-attached malignant nodules was classified as typical or atypical PFN. CONCLUSIONS:In the NELSON study, 6.5% of incident lung nodules were fissure-attached. None of the lung cancers that originated from a new fissure-attached nodule in the incidence lung cancer screening rounds was classified as a typical or atypical PFN. Our results suggest that also in the case of a new PFN, it is highly unlikely that these PFNs will be diagnosed as lung cancer.
导读: 在发病率肺癌筛查查房中，新发肺结节是规律性的发现。它们比基线结节有更高的肺癌概率。既往研究表明，基线腓骨周围结节 (PFNs) 代表良性病变。事件 PFNs 是否也是这种情况尚不清楚。本研究评价了荷兰-比利时随机对照 NELSON 研究中新发现的结节，包括裂隙附着结节的发生率、分类和肺癌概率。 方法: 在 NELSON 试验中，7557 名参与者在 2004年4月至 2006年12月期间接受了基线筛查。纳入基线后检测到新结节的参与者。根据位置和附件对结节进行分类。由两名不了解参与者肺癌状态的放射科医生重新评估裂隙附着结节，将其归类为典型、非典型或非 PFN。 结果: 在 400 名参与者 (949 名男性，中位年龄 59 岁 [四分位距: 55-63 岁]) 中检测到 77.4% 个新结节，在第二，第三, 最后的尼尔森筛选回合。根据 2 年的随访或病理，1393 个结节 (93.8%) 为良性。共有 97 个 (6.5%) 为裂隙附着，包括 10 个恶性结节。新发裂隙附着的恶性结节均未归类为典型或非典型 PFN。 结论: 在 NELSON 研究中，6.5% 的肺结节是裂隙附着的。在发病率肺癌筛查中，起源于新的裂隙附着结节的肺癌均未被归类为典型或非典型 PFN。我们的结果表明，同样在一种新的 PFN 的情况下，这些 PFN 被诊断为肺癌的可能性很小。
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.