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How eczema might lead to asthma

‘Scientists believe they have found what triggers many children with eczema to go on to develop asthma,’ BBC news reported.
Brought to you by NHS Choices

It said that allergies and asthma often develop in the same people, and that 50-70% of children with atopic dermatitis (severe allergic skin problems) subsequently develop asthma. It said a recent study has shown that, in mice, a protein called thymic stromal lymphopoietin (TSLP), which is made in damaged skin, “triggered asthma symptoms”. The researchers reportedly hope that treating the skin rash early and blocking production of the protein might stop young people with eczema from developing asthma.

This study in genetically engineered mice identified a protein that could be part of the link between atopic dermatitis and asthma. However, this link is likely to be complex and involve various other proteins. Further research needs to determine whether TSLP is also elevated in humans with atopic dermatitis and plays a similar role in asthma risk, and to identify other proteins involved in this process. This type of research may eventually lead to the development of drugs to block the development of asthma in people with atopic dermatitis, but such a development will take time.

Where did the story come from?

The research was carried out by Dr Shadmehr Demehri and colleagues from Washington University School of Medicine. The authors received grants and support from the National Institute of General Medical Sciences (one of the US National Institutes of Health), Washington University, the Toyobo Biotechnology Foundation and the Japanese Society for the Promotion of Science. The study was published in the open access, peer-reviewed scientific journal PLoS Biology.

What kind of scientific study was this?

This animal study looked at the relationship between atopic dermatitis (also known as allergic eczema) and asthma. In allergic asthma, exposure of the surface of the lungs to a foreign substance (an allergen) provokes an immune response, resulting in inflammation of the airways, which makes it difficult to breathe. Atopic dermatitis is also the result of inflammation in response to exposure of the skin to allergens. Asthma is much more common in people who have had severe atopic dermatitis than in the general population. This is called atopic march. Researchers think that if they can understand the relationship between the two conditions, they may be able to stop asthma developing in this susceptible population, that is, to stop the atopic march.

There are several theories about this link. One theory is that if the skin’s protective external barrier against the environment has defects, this could lead to the immune system producing an allergic inflammatory response to any allergens present on the surface of the body, including the surface of the airways in the lungs. The researchers in the current study investigated this possibility using mice.

The researchers used genetically engineered mice that lack the gene with the instructions for making a protein called RBP-j in their skin, and so do not develop a normal skin barrier. The researchers observed the mice to see whether they developed skin symptoms.

They also exposed these mice and a group of normal mice to an allergen called ovalbumin (initially by injection and then through their noses) to see if they would develop allergic asthma-like symptoms. They then investigated whether a protein called thymic stromal lymphopoietin (TSLP) played a role in this process. TSLP is an immune-system-activating protein that is produced in greater amounts by skin with barrier defects (including in mice lacking RBP-j), and which has been suggested to play a role in both atopic dermatitis and eczema. They investigated TSLP’s role by further genetically engineering the mice lacking the RBP-j protein to block the effects of TSLP. As TSLP is present in the blood stream and moves around the body, the researchers thought that it might be sensitising the lungs to the development of asthma.

Finally, the researchers wanted to investigate whether high levels of TSLP alone were able to make mice sensitive to developing asthma-like symptoms in response to allergens. To do this they genetically engineered mice to produce high levels of TSLP in its skin (without lacking RBP-j). They exposed these mice and normal mice to allergens and looked at whether they developed asthma-like symptoms. They then repeated these experiments, but blocked the action of TSLP, to see if this had an effect. They also repeated these experiments in mice that were genetically engineered to have high levels of TSLP, but did not show any skin symptoms.

What were the results of the study?

The researchers found that genetically engineered mice that did not form a skin barrier because they lacked the RBP-j protein in their skin developed atopic dermatitis-like skin inflammation. If these mice were exposed to an allergen through their noses after an injection sensitising them to the allergen, they developed more severe allergic asthma-like symptoms than normal mice treated in the same way.

The RBP-j-lacking mice produced high levels of the immune-system-activating protein thymic stromal lymphopoietin (TSLP) in their skin. Mice that were genetically engineered so that the effects of TSLP were blocked developed less severe asthma-like symptoms in response to allergen exposure. However, their immune systems still had signs of activation, they had some skin-barrier problems, and their skin still became inflamed when it was exposed to allergens. This suggested that other proteins similar to TSLP might play a role in these skin symptoms.

Mice that had been genetically engineered to have high levels of TSLP but no skin symptoms also developed severe asthma-like symptoms when exposed to the allergen, but normal mice did not.

What interpretations did the researchers draw from these results?

The researchers conclude that blocking the action of TSLP might be important in treating skin-barrier defects, and “may be the key to blocking the development of asthma in [atopic dermatitis] patients”.

What does the NHS Knowledge Service make of this study?

This animal study has identified a protein (TSLP) that may play an important role in the link between atopic dermatitis and asthma. The link between atopic dermatitis and asthma is likely to be complex and involve various other proteins. Further research will now be needed to determine whether TSLP levels are increased in humans with atopic dermatitis, whether it plays a similar role in asthma risk and to identify other proteins involved in this process. This type of research may eventually lead to the development of drugs to block the development of asthma in people with atopic dermatitis, but such a development will take time.

Links to the headlines

Eczema’s link to asthma uncovered. BBC News, May 26 2009

Links to the science

Demehri S, Morimoto M, Holtzman MJ, Kopan R. Skin-Derived TSLP Triggers Progression from Epidermal-Barrier Defects to Asthma. PLOS Biology 2009; May: Open Access

Further reading

Abramson MJ, Puy RM, Weiner JM. Allergen immunotherapy for asthma. Cochrane Database Syst Rev 2003, Issue 4