Researchers discover how a skin disease may trigger a lung complaint

研究人员发现皮肤病可能引发肺部不适。

Eczema's link to asthma
 
ONE of the prices humanity seems to pay for getting richer is the rise of asthma. This life-threatening, allergy-driven lung disease is common in wealthy countries, absent from poor ones and on the rise in those making the transition. But exactly what causes it is unknown.

A number of explanations have been proposed. These range from the idea that clean modern living makes the immune system over-reactive to random allergens to the thought that chemicals in swimming pools are responsible. What these ideas have in common is the suggestion that some environmental change which accompanies economic development is the cause. A group of researchers led by Shadmehr Demehri of Washington University, in St Louis, believe these explanations are looking in the wrong place. Asthma is not, they think, caused directly by environmental factors. Rather, the link is indirect. The direct cause is a chemical distress signal produced in skin that is damaged by another hazard of modern life: eczema.

Eczema is also on the rise in the industrialised world, in the same sorts of countries where asthma is a problem. Unlike asthma it is not dangerous, so people rarely worry about it. Nevertheless, 17% of children in America have it, and similarly high figures are found in Australia, Britain and New Zealand. What is particularly intriguing is that many people with eczema go on to develop asthma (in America the figure is 70%). That compares with an asthma prevalence of 4-8% in the general population. As they describe in Public Library of Science Biology, Dr Demehri and his colleagues now believe they know what causes this link.
The culprit is thymic stromal lymphopoietin (TSLP), a signalling molecule secreted by damaged skin cells which elicits a strong immune response from the body to fight off invaders. Dr Demehri and his team hypothesised that eczema-induced TSLP enters the bloodstream and, when it arrives at the lungs, sensitises them so that they react to allergens that would not previously have bothered them. In other words, they become asthmatic.

They tested their hypothesis in a series of experiments on mice. First, using genetic engineering, they created mice prone to the kind of skin defects found in eczema. These mice were, as they hoped, susceptible to asthma. Then they used additional engineering to delete the gene for the receptor molecule which picks up TSLP in the lungs. These mice no longer developed asthma. Thirdly, they engineered mice to produce high levels of TSLP in their skin in the absence of other skin problems. These mice also developed asthma.

Taken together these experiments indicate—at least in mice—that skin damage creates susceptibility to asthma by releasing TSLP. If that proves true in people, too, it suggests several ways asthma might be prevented. One is to take eczema seriously, and treat it early. The usual treatment is to apply steroids to the damaged skin, but there is evidence that some parents reject this treatment for their children. If a link between eczema and asthma were properly established, that reluctance would probably diminish. In the longer term, it might be possible to devise drugs that inhibit the production of TSLP or interfere with TSLP-receptor molecules in the lungs. Better still, though, would be to work out what aspect of modern life causes eczema.

One possible culprit related both to cleanliness and bathing is the widespread use of detergents. By degreasing the skin, modern detergents might lead to infection and inflammation. At the moment, that idea is just speculation. But the question is an itch that certainly needs a scratch.

哮喘与湿疹的关系

人类在变得越来越富有的过程中要付出的代价之一，似乎就是哮喘病的增多。这种由过敏反应引起、能危及生命的肺部疾病在发达国家中很普遍，但在贫穷国家中很少见，而且在那些逐渐变得富裕的国家中，哮喘病患者也在上升。不过，人们仍然不知道哮喘病的确切发病原因。

人们对哮喘病的起因提出了很多的解释。在这些解释中，有人认为，清洁卫生的现代生活使得免疫系统对一些偶然的过敏原做出过度反应，而有人则认为游泳池中的化学物质导致了哮喘病。这些观点的一个共同点就是：经济发展中伴随的环境变化是哮喘病的发病原因。来自圣路易斯华盛顿大学（Washington University）的Shadmehr Demehri领导的研究小组认为，这些解释的着眼点不对。他们认为，环境因素不是哮喘病的直接原因，而是间接原因。直接原因是受损皮肤中所产生的一种化学求救信号（chemical distress signal），而这归因于另外一种现代生活的危害：湿疹。

在工业化国家中，湿疹也呈上升之势，而就在这些同样的工业化国家中，哮喘病是个大问题。湿疹和哮喘病不一样，它不危及生命，因此人们很少担心这种病。不过，在美国17%的儿童患有湿疹，而在澳大利亚、英国以及新西兰，患湿疹儿童的比例也差不多有这样高。尤其引人注意的是，许多湿疹患者又接着患上了哮喘病（在美国，这个比例是70%）。而在普通人群中，哮喘病患者的比例是4-8%。Demehri博士和同事在《科学公共图书馆：生物》（Public Library of Science Biology）杂志上发表了研究结果，他们相信他们找到了哮喘病和湿疹之间的联系。

罪魁祸首就是胸腺基质淋巴生成素（简称TSLP），这是一种由受损的皮肤分泌的信号分子，受损的皮肤引起身体强烈的免疫反应以便对抗入侵细胞。Demehri博士和同事假设，湿疹引发的TSLP进入到血液，当TSLP达到肺部后，肺部对TSLP产生感应，这样一来肺部对原本不产生反应的过敏原就产生反应了。换言之，肺部成哮喘肺了。
 
研究者们在对老鼠的一些列实验中检验了他们的假说。首先，他们利用基因工程技术制造出易于患上湿疹皮肤病的老鼠。正如他们希望的一样，这些老鼠容易患上哮喘。然后研究人员再使用基因工程技术去除受体分子基因，这些受体分子在肺部中结合TSLP。经历过这些处理后，这些老鼠不再患上哮喘病。再接下来，在没有其它皮肤病的情况下，他们利用基因工程技术让老鼠在皮肤中产生大量的TSLP，这些老鼠也患上了哮喘病。

所有的这些实验综合起来表明---至少在老鼠身上如此---受损皮肤通过释放TSLP从而导致易患哮喘病。如果该结论也适合人的话，这表明通过几种方式可以预防哮喘。方法之一就是认真对待湿疹，尽早治疗。常规的治疗方法是对受损皮肤使用类固醇药，但是有证据表明，有些父母亲拒绝对他们的孩子实施这种疗法。如果湿疹和哮喘之间有联系的话，那么父母亲可能也会同意类固醇的治疗方法了。从长期来看，人们有可能设计出抑制TSLP生成的药物，或者这些药物能干涉肺部中的TSLP受体分子。当然，更好的方案就是找出现代生活的哪个方面导致了湿疹。

其中一个与清洁和洗浴都可能相关的罪魁祸首就是洗涤剂的使用。在洗掉皮肤的油脂时候，现代洗涤剂可能也导致了皮肤的感染和发炎。目前，这个想法仅仅只是猜测，但是这个让人“发痒”的问题肯定需要“抓挠”一番了。

Vocabulary:

Trigger：（动词）引发，触发；（名词）扳机
Complaint：抱怨
Eczema：湿疹
Asthma：哮喘
Allergy：过敏反应
Absent：缺席；不存在
Immune system：免疫系统
Allergen：过敏原
Distress：痛苦
Hazard：危害
Intriguing：引人入胜的；神秘的
Prevalence：盛行
Culprit：罪犯；肇事者
Secrete：分泌
Elicit：引出；诱出
Invader：入侵者
Hypothesize：提出假设
Prone: 易于遭受
Defect: 缺陷；缺点
Susceptible: 易受影响（或伤害等）； 过敏
Delete: 删除
Steroid: 类固醇
Reject: 拒绝
Diminish: 减少
Inhibit: 抑制
Interfere: 干涉
Detergent: 洗涤剂
Degrease:去除油垢
Inflammation：炎症
Speculation：推测；猜测
Itch：痒
Scratch：抓；挠