Mapping lungs and attacking Asthma

Asthma is becoming more common. The chest disease can lead to life-threatening breathing difficulties when the airways constrict and the lung tissue overproduces mucus; this is often caused by an allergic reaction that can be worsened by air pollution. But our understanding of what’s going on in an asthmatic lung to cause the condition is still quite limited. But now for the first time scientists at the Sanger Institute near Cambridge have used a new technique to document and examine every cell in lung samples from both healthy and asthmatic patients to discover what’s changing when a person develops asthma. Chris Smith was joined by Charlotte Summers who is an intensive care medicine doctor and lung specialist from the University of Cambridge. She took a look at the study for us, published in Science by Felipe Vieira Braga.

Charlotte - For the first time these researchers took tissue from the nose, from the airway walls, and from out in the peripheries of the lung and looked at every single cell type that they could find at those particular sites, and tried to find out how many types of cells and what kind of cells where there at those sites. And they did this in people who were healthy and people who had had asthma since they were a child.

Chris -  And what did that reveal?

Charlotte - It revealed that there was more than 20 different types of cells in the healthy lung and that depending on the site that you sampled the types of cells that you found were different. But in people who have asthma, they found some pathological cells, so some cells that were contributing to the disease that they didn't find in the healthy people.

Chris - And are there any clues as to where they came from? Are they cells that were born in the lung and they’re there normally at such low levels we can't see them or did they come in from outside?

Charlotte - A bit of both actually. They found what are probably some cells that came originally from the blood that they found, so one of the immune cells that are resident in the lungs with people who have asthma. But that those cells also cause changes in cells that were resident such as the epithelial cells that are in the lung.

Chris - So why did those blood cells come in in the first place?

Charlotte - Well, that's a question that we may not necessarily have really strong answers to, but I think it's to do with the changes in the inflammatory mediators that were present in the lung.

Chris - Would you suggest then that something winds up the lung tissue? I mentioned the beginning often we regard asthma as an allergic reaction, so could it be that that inflammation recruits these cells in and they then start to distort what should be going on?

Charlotte - Yes. So I think, particularly in these patients, they were people who had childhood asthma which we know is much more likely to be of an allergic problem, and the information they found would be supportive of that, but actually that's exactly what was happening.

Chris - And so those cells, these abnormal immune cells come in, how did they in turn then change what the lung is doing? How do they change the behaviour of the lung and make the mucus different?

Charlotte - The immune cells that come into the lung secrete inflammatory mediators, which they think from this study induced a change in one of the epithelial cells from being what's called "ciliated" to being a type of cell that produce mucus too, as well as causing what we knew already to have more mucus-producing cells in the lungs of asthmatics.

Chris - That's quite interesting then isn't it? Because you basically can persuade a cell to almost have a facelift: stop being a cell that would clean the lungs, and become one that makes goo-ey mucus?

Charlotte - Exactly. And gooey mucus is a problem in people who've got asthma.

Chris - Now, given that we have this insight, and that they've got this baseline - because they looked at lots of healthy people, and they also looked at lots of people with asthma - but given that we've now got this baseline of what normal should be, I presume that's going to be really useful because we now understand what we should be like and we can then begin to compare that to all kinds of different lung conditions using the same sort of technique?

Charlotte - Absolutely. So I think one of the most exciting things about this paper is, for the first time, we have a proper map of what normal should look like for all the different cell types in the airway: everything from the nose right the way down to the alveolus of the lung. And from there you can say "well, how is it changing in a whole host of diseases?" - in fibrosis, in asthma, in cancer, a whole host of respiratory diseases, a lot of which don't have any active therapies or things that work..

Chris - And talking of therapies, will this inform how we make drugs?

Charlotte - I think it probably will. I think part of the reason the researchers did this work - as part of a collaboration called "Open Targets" - is to try and look at what's actually going wrong in respiratory disease so that we can have better, more efficacious therapies that actually target the mechanisms.

Chris - So understanding what causes the disease in the first place you can then work out better ways to treat it?

Charlotte - Exactly.

Chris - And you can work out if your drug actually works because you know where you're trying to get to?

Charlotte - Yeah. You've got to have a target to aim your therapy at. If you don't understand what's going wrong, you don't have a target...