Researchers discover how a skin disease may trigger a lung complaint

研究人員發現皮膚病可能引發肺部不適。

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.

哮喘與濕疹的關系

人類在變得越來越富有的過程中要付出的代價之一，似乎就是哮喘病的增多。這種由過敏反應引起、能危及生命的肺部疾病在發達國家中很普遍，但在貧窮國家中很少見，而且在那些逐漸變得富裕的國家中，哮喘病患者也在上升。不過，人們仍然不知道哮喘病的確切發病原因。

人們對哮喘病的起因提出了很多的解釋。在這些解釋中，有人認為，清潔衛生的現代生活使得免疫系統對一些偶然的過敏原做出過度反應，而有人則認為游泳池中的化學物質導致了哮喘病。這些觀點的一個共同點就是：經濟發展中伴隨的環境變化是哮喘病的發病原因。來自圣路易斯華盛頓大學（Washington University）的Shadmehr Demehri領導的研究小組認為，這些解釋的著眼點不對。他們認為，環境因素不是哮喘病的直接原因，而是間接原因。直接原因是受損皮膚中所產生的一種化學求救信號（chemical distress signal），而這歸因于另外一種現代生活的危害：濕疹。

在工業化國家中，濕疹也呈上升之勢，而就在這些同樣的工業化國家中，哮喘病是個大問題。濕疹和哮喘病不一樣，它不危及生命，因此人們很少擔心這種病。不過，在美國17%的兒童患有濕疹，而在澳大利亞、英國以及新西蘭，患濕疹兒童的比例也差不多有這樣高。尤其引人注意的是，許多濕疹患者又接著患上了哮喘病（在美國，這個比例是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《科學公共圖書館：生物》（Public Library of Science Biology）雜志上發表了研究結果，他們相信他們找到了哮喘病和濕疹之間的聯系。

罪魁禍首就是胸腺基質淋巴生成素（簡稱TSLP），這是一種由受損的皮膚分泌的信號分子，受損的皮膚引起身體強烈的免疫反應以便對抗入侵細胞。Demehri博士和同事假設，濕疹引發的TSLP進入到血液，當TSLP達到肺部后，肺部對TSLP產生感應，這樣一來肺部對原本不產生反應的過敏原就產生反應了。換言之，肺部成哮喘肺了。
 
研究者們在對老鼠的一些列實驗中檢驗了他們的假說。首先，他們利用基因工程技術制造出易于患上濕疹皮膚病的老鼠。正如他們希望的一樣，這些老鼠容易患上哮喘。然后研究人員再使用基因工程技術去除受體分子基因，這些受體分子在肺部中結合TSLP。經歷過這些處理后，這些老鼠不再患上哮喘病。再接下來，在沒有其它皮膚病的情況下，他們利用基因工程技術讓老鼠在皮膚中產生大量的TSLP，這些老鼠也患上了哮喘病。

所有的這些實驗綜合起來表明---至少在老鼠身上如此---受損皮膚通過釋放TSLP從而導致易患哮喘病。如果該結論也適合人的話，這表明通過幾種方式可以預防哮喘。方法之一就是認真對待濕疹，盡早治療。常規的治療方法是對受損皮膚使用類固醇藥，但是有證據表明，有些父母親拒絕對他們的孩子實施這種療法。如果濕疹和哮喘之間有聯系的話，那么父母親可能也會同意類固醇的治療方法了。從長期來看，人們有可能設計出抑制TSLP生成的藥物，或者這些藥物能干涉肺部中的TSLP受體分子。當然，更好的方案就是找出現代生活的哪個方面導致了濕疹。

其中一個與清潔和洗浴都可能相關的罪魁禍首就是洗滌劑的使用。在洗掉皮膚的油脂時候，現代洗滌劑可能也導致了皮膚的感染和發炎。目前，這個想法僅僅只是猜測，但是這個讓人“發癢”的問題肯定需要“抓撓”一番了。

Vocabulary:

Trigger：（動詞）引發，觸發；（名詞）扳機
Complaint：抱怨
Eczema：濕疹
Asthma：哮喘
Allergy：過敏反應
Absent：缺席；不存在
Immune system：免疫系統
Allergen：過敏原
Distress：痛苦
Hazard：危害
Intriguing：引人入勝的；神秘的
Prevalence：盛行
Culprit：罪犯；肇事者
Secrete：分泌
Elicit：引出；誘出
Invader：入侵者
Hypothesize：提出假設
Prone: 易于遭受
Defect: 缺陷；缺點
Susceptible: 易受影響（或傷害等）； 過敏
Delete: 刪除
Steroid: 類固醇
Reject: 拒絕
Diminish: 減少
Inhibit: 抑制
Interfere: 干涉
Detergent: 洗滌劑
Degrease:去除油垢
Inflammation：炎癥
Speculation：推測；猜測
Itch：癢
Scratch：抓；撓