Update: Characteristics of a Nationwide Outbreak of E-cigarette, or Vaping, Product Use-Associated Lung Injury - United States, August 2019-January 2020.
更新: 全国范围内电子烟爆发的特点，或 Vaping，产品使用相关肺损伤-美国，2019年8月 17 年 2020年1月。
- 作者列表："Krishnasamy VP","Hallowell BD","Ko JY","Board A","Hartnett KP","Salvatore PP","Danielson M","Kite-Powell A","Twentyman E","Kim L","Cyrus A","Wallace M","Melstrom P","Haag B","King BA","Briss P","Jones CM","Pollack LA","Ellington S","Lung Injury Response Epidemiology\/Surveillance Task Force.
:Since August 2019, CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical stakeholders have been investigating a nationwide outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) (1). This report updates patient demographic characteristics, self-reported substance use, and hospitalization dates for EVALI patients reported to CDC by states, as well as the distribution of emergency department (ED) visits related to e-cigarette, or vaping, products analyzed through the National Syndromic Surveillance Program (NSSP). As of January 14, 2020, a total of 2,668 hospitalized EVALI cases had been reported to CDC. Median patient age was 24 years, and 66% were male. Overall, 82% of EVALI patients reported using any tetrahydrocannabinol (THC)-containing e-cigarette, or vaping, product (including 33% with exclusive THC-containing product use), and 57% of EVALI patients reported using any nicotine-containing product (including 14% with exclusive nicotine-containing product use). Syndromic surveillance indicates that ED visits related to e-cigarette, or vaping, products continue to decline after sharply increasing in August 2019 and peaking in September 2019. Clinicians and public health practitioners should remain vigilant for new EVALI cases. CDC recommends that persons not use THC-containing e-cigarette, or vaping, products, especially those acquired from informal sources such as friends, family members, or from in-person or online dealers. Vitamin E acetate is strongly linked to the EVALI outbreak and should not be added to any e-cigarette, or vaping, products (2). However, evidence is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC- or non-THC-containing products, in some reported EVALI cases.
: 自 2019年8月以来，CDC 、食品和药物管理局 (FDA) 、州和地方卫生部门以及公共卫生和临床利益相关者一直在调查全国范围内的电子烟爆发, 或 vaping，产品使用相关肺损伤 (EVALI) (1)。本报告更新了各州向 CDC 报告的 EVALI 患者的患者人口统计学特征、自我报告的物质使用和住院日期，以及急诊科 (ED) 的分布通过国家综合征监测计划 (NSSP) 分析与电子烟或 vaping 相关的产品的访视。截至 2020年1月14日，共向 CDC 报告了 2,668 例住院 EVALI 病例。患者的中位年龄为 24 岁，66% 为男性。总体而言，82% 的 EVALI 患者报告使用任何含四氢大麻酚 (THC) 的电子烟或 vaping 产品 (包括独家含 THC 产品使用的 33%), 57% 的 EVALI 患者报告使用任何含尼古丁的产品 (包括独家使用含尼古丁产品的 14%)。综合征监测表明，与电子烟或 vaping 相关的 ED 访视在 2019年8月急剧增加并于 2019年9月达到高峰后继续下降。临床医生和公共卫生从业人员应对新的 EVALI 病例保持警惕。CDC 建议人们不要使用含 THC 的电子烟或 vaping 产品，特别是那些从朋友、家人或当面或在线经销商等非正式来源获得的产品。维生素e 醋酸酯与 EVALI 爆发密切相关，不应添加到任何电子烟或 vaping 产品中 (2)。然而，在一些报告的 EVALI 案例中，证据不足以排除其他关注化学品的贡献，包括含 THC 或不含 THC 的产品中的化学品。
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.