Acute effects of e-cigarette vaping on pulmonary function and airway inflammation in healthy individuals and in patients with asthma.
- 作者列表："Kotoulas SC","Pataka A","Domvri K","Spyratos D","Katsaounou P","Porpodis K","Fouka E","Markopoulou A","Passa-Fekete K","Grigoriou I","Kontakiotis T","Argyropoulou P","Papakosta D
BACKGROUND AND OBJECTIVE:The acute effects of e-cigarettes have not been scientifically demonstrated yet. The aim of this study was to assess the acute changes in pulmonary function and airway inflammation in patients with asthma after vaping one e-cigarette. METHODS:Twenty-five smokers suffering from stable moderate asthma according to GINA guidelines with no other comorbidities and 25 healthy smokers matched with the baseline characteristics of the asthmatic patients were recruited. PFT, IOS, FeNO and EBC were performed before and after vaping one e-cigarette with nicotine. pH and concentrations of IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17A, TNF-α, ISO8 and LTB4 were measured in EBC. RESULTS:FFEV1/FVC ratio and PEF were reduced in asthmatic patients after e-cigarette. Z5Hz and R5Hz, R10Hz and R20Hz increased in both groups. FeNO and EBC pH increased by 3.60 ppb (P = 0.001) and 0.15 (P = 0.014) in asthmatic patients after e-cigarette, whereas they decreased in control group by 3.28 ppb (P < 0.001) and 0.12 (P = 0.064), respectively. The concentrations of IL-10, TNF-α and ISO8 in EBC increased in asthmatic patients after e-cigarette and the changes in concentrations of IL-1β and IL-4 differed significantly between the two groups. CONCLUSION:E-cigarette vaping resulted in acute alteration of both pulmonary function and airway inflammation in stable moderate asthmatic patients.
背景和目的: 电子烟的急性效应尚未得到科学证明。本研究的目的是评估哮喘患者在吸一根电子烟后肺功能和气道炎症的急性变化。 方法: 根据 GINA 指南，25 例患有稳定中度哮喘且无其他合并症的吸烟者和 25 例符合哮喘患者基线特征的健康吸烟者。PFT 、 IOS 、 FeNO 和 EBC 在用尼古丁汽化一根电子烟之前和之后进行。测定 EBC 中 il-1 β 、 IL-4 、 IL-5 、 IL-6 、 IL-8 、 IL-10 、 IL-13 、 IL-17A 、、 TNF-α 、 ISO8 和 LTB4 的浓度。 结果: 电子烟后哮喘患者 FFEV1/FVC 比值和 PEF 降低。Z5Hz 和 R5Hz，R10Hz 和 R20Hz 两组均有所增加。电子烟后哮喘患者 FeNO 和 EBC pH 分别增加 3.60 ppppb (P = 0.001) 和 0.15 (P = 0.014),而对照组分别降低 3.28 ppb (P <0.001) 和 0.12 (P = 0.064)。电子烟后哮喘患者 EBC 中 IL-10 、 TNF-α 和 ISO8 浓度升高，两组间 il-1 β 和 IL-4 浓度变化差异有统计学意义。 结论: 电子烟雾化吸入可导致稳定中度哮喘患者肺功能和气道炎症的急性改变。
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.