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寻找蒸汽导致疾病的原因可以发现多种损害机制

Hunt for Cause of Vaping Illness Suggests Multiple Mechanisms of Damage
寻找蒸汽导致疾病的原因可以发现多种损害机制
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2019-09-26 22:37
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寻找蒸汽导致疾病的原因可以发现多种损害机制

Experts remain perplexed about what is causing the nationwide outbreak of mysterious vaping-related lung disease that has affected hundreds and killed at least six people. And even the nature of the disease itself is confounding clinicians and public health officials. The only certainty, they say, is that people should not be vaping anything until they figure it out.

全国范围内爆发的与蒸汽有关的肺部疾病已经造成数百人感染,至少6人死亡。甚至这种疾病本身的性质也让临床医生和公共卫生官员感到困惑。他们说,唯一可以肯定的是,人们在搞清楚之前不应该吸任何东西。

The sigh of relief was almost audible after news emerged in early September of a named culprit: vitamin E acetate. But the U.S. Food and Drug Administration soon dampened that enthusiasm, noting that not all tested samples even contain the oily substance. In fact, no candidate substances have consistently turned up across samples so far.

9月初,有消息称罪魁祸首是维生素E醋酸盐,这几乎让人松了一口气。但美国食品和药物管理局(U.S. Food and Drug Administration,简称fda)很快就打消了这种热情,指出并非所有被检测的样品都含有这种油性物质。事实上,到目前为止,还没有任何候选物质在样本中被发现。

And then there is the question of what people are actually vaping: although most cases involve pods containing THC (the active ingredient in can/nabis), not all of them do. Vaping-product manufacturers have sought to distinguish their goods from counterfeits acquired on the street and to blame the latter, but investigators have not yet confirmed the provenance of many of the products involved in the disease. In a good chunk of cases, patients say the one they vaped contained only nicotine. Although it is possible patients do not want to admit to THC use in states where it is not decriminalized, there is no evidence they are lying.

接下来的问题是,人们究竟在吸什么:尽管大多数情况下,含有四氢酚(can/nabis中的活性成分)的豆荚都含有四氢酚,但并非所有豆荚都含有四氢酚。蒸汽产品制造商一直试图将他们的产品与街头购买的假冒产品区分开来,并指责后者,但调查人员尚未证实许多与该疾病有关的产品的来源。在很多情况下,病人说他们吸的电子烟只含有尼古丁。虽然有可能病人不愿意承认THC的使用,但没有证据表明他们在说谎。

Mired in all of this mystery are the hundreds of occurrences of a puzzling and sometimes lethal respiratory illness whose only commonalities are that stricken patients recently vaped and they are all in the U.S. or its territories. Even the name of the condition remains a matter of debate. All of this confusion “is the strangest part,” says Sean J. Callahan, a pulmonologist at the University of Utah. Callahan, who has treated several patients with the mystery illness, says, “The heterogeneity just makes it really tough” to find a common cause.

接下来的问题是,人们究竟在吸什么:尽管大多数情况下,含有四氢酚(can/nabis中的活性成分)的豆荚都含有四氢大酚,但并非所有豆荚都含有四氢酚。蒸汽产品制造商一直试图将他们的产品与街头购买的假冒产品区分开来,并指责后者,但调查人员尚未证实许多与该疾病有关的产品的来源。在很多情况下,病人说他们吸的电子烟只含有尼古丁。虽然有可能病人不愿意承认THC的使用,但没有证据表明他们在说谎。

When the initial patients in this outbreak turned up in U.S. emergency rooms in April, they did not trigger a blip in public-health radars. Wisconsin and Illinois and their shared border region look like hotspots for cases and could provide clues to what is causing them. As patient numbers grew, the geography of the outbreak expanded, first largely affecting states that are contiguous with Wisconsin and Illinois and then other states bordering those. As of September 12, the U.S. Centers for Disease Control and Prevention had reported at least 380 confirmed and probable cases in 36 states and the U.S. Virgin Islands. The agency announced on September 16 that it had activated an emergency operations center in reaction to the outbreak.

今年4月,当此次疫情的首批患者出现在美国的急诊室时,他们并没有引发公共卫生雷达的信号。威斯康辛州和伊利诺斯州以及它们共同的边境地区看起来像是病例的热点地区,并可能提供导致这些病例的线索。随着患者人数的增加,疫情的地理范围也在扩大,首先主要影响到与威斯康辛州和伊利诺伊州相邻的州,然后是与这些州接壤的其他州。截至9月12日,美国疾病控制和预防中心(U.S. Centers for Disease Control and Prevention,简称cdc)报告了36个州和美属维尔京群岛至少380例确诊病例和疑似病例。该机构于9月16日宣布,已经启动了一个应急行动中心,以应对疫情。

But oddly enough, the disease seems to have stopped cold at the Canadian border, despite its proximity to Wisconsin.* In response to a query about this apparent dividing line, a spokesperson for Health Canada, the country’s national health agency, pointed to its tough laws around vaping, which prohibit all sales of such products, with or without nicotine, to people under the age of 18 and strictly control their promotion at point of sale and even on social media. Canada is also stepping up enforcement and compliance programs.

但奇怪的是,尽管离威斯康辛州很近,这种疾病似乎在加拿大边境就已经停止了传播。*在回答查询关于这个明显的分界线,加拿大卫生部的发言人,国家健康机构指出vap严厉的法律,禁止所有此类产品的销售,有或没有尼古丁,18岁以下的人,严格控制在销售点促销甚至在社交媒体上。加拿大也在加强执法和合规项目。

A recent development could be related to the concentration of early cases in Wisconsin: On September 11, local authorities announced several arrests of residents of the state for manufacturing and selling their own THC-laced vape products. The arrests stem from an incident in early July, said Dan Baumann, a police captain at Wisconsin’s Waukesha Police Department, in a news conference. Two parents turned up at the police station, seeking consequences for their teenage son, who they discovered?had been peddling THC vaping products to his high-school peers. The family’s cooperation led law enforcement from Waukesha County to the state’s Kenosha and Racine counties—regions where the earliest cases cropped up. The busts netted THC product worth $1.5 million in street value, along with 31,200 filled vape cartridges and 98,000 unfilled cartridges, officials said.

最近的事态发展可能与威斯康辛州早期病例的集中有关:9月11日,当地政府宣布,该州几名居民因制造和销售含有四氢酚的vape产品而被捕。威斯康辛州沃基夏警察局(Waukesha police Department)警官丹鲍曼(Dan Baumann)在新闻发布会上说,逮捕行动源于7月初的一起事件。两名家长出现在警察局,要求对他们十几岁的儿子承担后果。他们发现,儿子一直在向高中同学兜售THC蒸汽产品。在他们的合作下,执法部门从华克沙县(Waukesha County)一直到该州的基诺沙县(Kenosha)和拉辛县(Racine County)——这两个县是最早发现此类案件的地区。官员们说,THC公司的这款产品,连同31,200个填充的vape墨盒和98,000个未填充的vape墨盒,在此次破产中净赚了150万美元。

In its first burst, the outbreak seemed to fit with a pattern of distribution among a group of high schoolers: most of those affected were in their late teens and male. As case numbers mounted, however, the age range has expanded. And despite a battery of tests performed in both patients and product samples, the disease remains a deep mystery. Because some tissue samples from patients have turned up immune cells full of fats, or lipids, a diagnosis of lipoid pneumonia has gained favor among physicians, especially because vitamin E acetate, the only candidate put forward, is a lipid. But Callahan thinks that conclusion is questionable.

第一次爆发时,疫情似乎符合一群高中生的分布模式:大多数受影响的人都是十几岁的晚期青少年和男性。然而,随着病例数量的增加,年龄范围扩大了。尽管对患者和产品样本都进行了一系列测试,但这种疾病仍然是一个谜。由于从病人身上提取的一些组织样本中发现了富含脂肪或脂质的免疫细胞,因此医生们对诊断类脂性肺炎颇有好感,尤其是因为提出的唯一候选药物维生素E醋酸盐是一种脂质。但是卡拉汉认为这个结论值得怀疑。

Patients with lipoid pneumonia, he says, usually present at an outpatient clinic visit, not at the hospital. They tend to be older and to have accidentally inhaled something oily, such as a mineral oil. On clinical images, the substance in their lungs “looks like fat,” Callahan says, but “that’s not the case with our patients. They’re coming in super-duper sick, acting like they almost have infectious pneumonia, with high inflammatory markers in their blood. They’re just really sick.” If he had to give it a name in the absence of a vaping link, he says he would call it a pneumonitis, or inflammatory lung condition. But Callahan favors a designation he says the CDC has floated: vaping-associated lung injury, or VALI. What he does know, he adds, is that “this is not reminiscent of classic lipoid pneumonia.”

他说,患有类脂性肺炎的患者通常在门诊就诊,而不是在医院。他们往往年龄更大,偶尔会吸入一些含油的东西,比如矿物油。卡拉汉说,从临床图像上看,他们肺部的物质“看起来像脂肪”,但“我们的病人却不是这样。”他们病得很重,就像得了传染性肺炎一样,血液中有很高的炎症指标。他们只是病得很重。他说,如果必须在没有蒸汽链接的情况下给它起个名字,他会把它叫做肺炎,或者炎症性肺病。但是卡拉汉倾向于一个他说疾控中心已经提出的名称:蒸汽相关肺损伤(VALI)。他补充说,他所知道的是,“这不会让人想起经典的类脂性肺炎。

In a case series published on September 6 in the New England Journal of Medicine, which described 53 patients in Illinois and Wisconsin, 100 percent of patients had abnormal lung imaging, one in two showed signs of liver problems, and almost a third had a fever. More baffling, the majority of patients had gastrointestinal symptoms, including nausea, vomiting and diarrhea. Callahan says no one knows why. “Someone brought up the idea that this is something like cyclic vomiting syndrome you see in people who smoke a lot of marijuana,” he says. “But this isn’t really the same.”

在9月6日发表在《新英格兰医学杂志》(New England Journal of Medicine)上的一系列病例中,有53名伊利诺斯州和威斯康辛州的患者,100%的患者出现了肺部成像异常,二分之一的患者出现了肝脏问题的迹象,近三分之一的患者出现了发烧。更令人困惑的是,大多数患者都有胃肠道症状,包括恶心、呕吐和腹泻。卡拉汉说,没有人知道为什么。他说:“有人提出,这是一种循环呕吐综合症,你可以在大量吸食的人身上看到。”“但这真的不一样。”

Travis Henry, a radiologist who specializes in heart and lung imaging at the University of California, San Francisco, agrees that lipoid pneumonia is not an apt term for the vaping-related disease, given that the former usually develops incrementally, over a longer period of time. He prefers calling this condition acute lung injury because of the rapid deterioration associated with it.

加州大学旧金山分校(University of California, San Francisco)专攻心肺成像的放射科医生特拉维斯·亨利(Travis Henry)也认为,鉴于类脂性肺炎通常是在较长一段时间内逐渐发展起来的,用这个词来形容这种与蒸汽有关的疾病并不合适。他更愿意称这种情况为急性肺损伤,因为它会迅速恶化。

Henry and his colleaguespublished a separate analysis in the NEJM of lung imaging of 34 patients with vaping-associated lung injury. The researchers concluded that the variety of patterns on the imaging suggests a similar variety of pathways to lung injury. They also wrote that the imaging lacks evidence of fat buildup in the lungs, which is a “hallmark of lipoid pneumonia.” How fat ended up inside immune cells in fluid washed through the lungs remains “total speculation,” Callahan says, but one possibility involves the slippery substance, called surfactant, that coats the lungs where they swap out oxygen for carbon dioxide from the blood. If something badly inflames the lungs, he adds, the lipids in the surfactant might break down and overwhelm the immune cells, filling them with fat.

亨利和他的同事在《新英格兰医学杂志》(NEJM)上发表了一篇独立的分析文章,分析了34名与蒸汽有关的肺损伤患者的肺成像。研究人员得出的结论是,图像上的各种模式表明,导致肺损伤的途径也有类似的变化。他们还写道,成像缺乏证据表明肺部脂肪堆积,这是“类脂性肺炎的一个标志”。卡拉汉说,脂肪最终是如何进入免疫细胞的仍是“完全的猜测”,但其中一种可能性与一种叫做表面活性剂的滑润物质有关。他补充说,如果有什么东西使肺部严重发炎,表面活性剂中的脂质可能会分解,淹没免疫细胞,让它们充满脂肪。

Callahan thinks that whatever VALI is, it is a novel condition, and others agree. Jennifer Layden, chief medical officer at the Illinois Department of Public Health, asserted in a CDC briefing on September 6 that authorities cannot say for certain that this is a new disease entity. But, she added, emergency room visits for severe respiratory illnesses among young people spiked in mid-2019 over 2018 levels for the same period. That kind of upward shift “would suggest that it’s a new phenomenon,” she said.

卡拉汉认为无论VALI是什么,它都是一种新情况,其他人也同意这一观点。伊利诺斯州公共卫生部的首席医疗官Jennifer Layden在9月6日疾控中心的简报中声称,当局不能确定这是一个新的疾病实体。但她补充说,2019年年中,年轻人因严重呼吸系统疾病就诊使急诊室数量较2018年同期大幅增加。她说,这种上升趋势“表明这是一种新现象”。

Getting final answers to such questions will be a fine-grain process, says Philip Huang, director of the Dallas County Health and Human Services Department, which is following some cases in Texas. “This is what public health does,” he says, comparing the response to tracking down the source of a foodborne outbreak. “You get specimens, you see if there’s contamination, you look through medical charts, you get consistent definitions for clinical symptoms.” In that sense, he says, it is not unlike any other public health outbreak investigation. Yet, he adds, “it’s just crazy to me. These are previously normal healthy teenagers getting intubated and [put] on ventilators.”

达拉斯县卫生与公众服务部主任Philip Huang说,要想得到这些问题的最终答案将要经历一个精细的过程。他说,“这就是公共卫生所做的事情,并将应对措施比作追踪食源性疾病爆发的源头。“你得到样本,看看是否有污染,你查看医疗图表,你得到对临床症状的一致定义。他说,从这个意义上讲,这与其他任何公共卫生疫情调查都没有什么不同。然而,他补充道,“这对我来说太疯狂了。这些之前正常健康的青少年现在却需要插管并使用呼吸机。”

The Trump administration has weighed in as the process unfolds, announcing a plan to ban flavoring in e-cigarettes, with the exception of tobacco flavoring, although finalizing that ban will take weeks. States such as Michigan and New York have moved on their own to enact similar bans. In the meantime, Huang says, the only way to prevent the disease is not to vape.

随着这一进程的展开,特朗普政府也加入了进来,宣布了一项禁止在电子烟中添加香精的计划,但烟草香精除外,不过最终实施这一禁令将需要数周时间。密歇根和纽约等州已自行采取行动,颁布了类似的禁令。与此同时,黄说,预防这种疾病的唯一方法就是不要吸烟。

Callahan agrees. “What’s discouraging to me is that the vaping industry has been trying to push forward this idea that this comes from black-market vaping material,” he says. “My patients are flatly denying that to me, and I think that’s important to point out. The safest thing is to not do this stuff until we figure this out.”

卡拉汉表示同意。他说:“让我感到沮丧的是,蒸汽工业一直在努力推进这一观点,即蒸汽来自黑市。”“我的病人断然否认这一点,我认为有必要指出这一点。最安全的做法是在我们搞清楚之前不要做这件事。”

*Editor's Note (9/19/19):?After this story was published, Canada reported its first case of a vaping illness: a high schooler who vaped daily was admitted to a hospital earlier earlier this summer, but has since recovered.

*编者(9/19/19):这篇报道发表后,加拿大报道了首例吸电子烟的病例:今年夏初,一名每天吸电子烟的高中生入院治疗,但现已康复。

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Emily Willingham

艾米丽·威林汉

Emily Willingham is a science writer and co-author, with Tara Haelle, of?The Informed Parent: A Science-Based Resource for Your Child's First Four Years?(TarcherPerigee, 2016). She writes at the intersection of brain research and society.

艾米丽·威林汉是科学作家,与塔拉·海勒合着了《知情的父母:为孩子头四年提供基于科学的资源》(The Informed Parent: a science - based Resource for Your Child’s First Four Years, TarcherPerigee, 2016)一书。她在大脑研究和社会的交叉点上撰文。

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