Profile: Chris Grainge
Royal Navy doctor and University of Southampton researcher Chris Grainge talks to Sarah Harrop about how his work on chronic asthma could lead to new ways of treating the disease, in the second of a series of profiles taken from our Annual Review 2011/12.
Not many MRC scientists have parachuted into icy cold oceans or researched the best way to escape from a wrecked submarine. But as a Royal Navy doctor, Chris Grainge has done both. When he’s not jumping out of planes, Chris is a respiratory medicine consultant at Southampton Hospital. Last year his MRC-funded research led to a new way of thinking about asthma which could help us use asthma drugs more effectively.
Although Chris’s medical and naval training saw him work as medical officer onboard a warship in the Caribbean and an icebreaker in Antarctica, his first love is working on the respiratory medicine wards. That’s because he gets to work with people of all ages with very different diseases. On a typical day he might see a young person with cystic fibrosis, an adult who has occupational lung disease or an older person with lung cancer or emphysema.
“I’m very fortunate in that I get to do research and clinical work,” he says. “Research is fantastically stimulating, but it can also be very frustrating. The highs are higher and the lows are lower. On the clinical side, I can work with patients from when they come in casualty, very sick with respiratory failure, right through to seeing them again in outpatients when they’re better – that’s very satisfying.”
One of the most common respiratory diseases seen by specialists like Chris is asthma. Nearly five and a half million people in the UK are currently being treated for the disease. In asthma patients, muscle tissue around the airways contracts and makes the airways narrower, causing wheezing, shortness of breath and coughing. For most people, these symptoms are easily kept in check with inhalers. But people with chronic asthma are harder to treat.
Over time the walls of the airways get thicker and produce more mucus; a process called airway remodelling. This can progress to a more serious and difficult to treat disease where there’s destruction of the lung. It’s long been thought that this long-term decline in lung function is down to airway inflammation caused by allergies or infection. But Chris and his research team suspected that this was only half of the picture.
“What we thought was, well maybe it’s actually the airway narrowing, the fluctuation in the size of the airway that’s important. We know that lots of tissues in the body are mechanically sensitive – so for example if you lift weights your arm gets bigger, and if you jump up and down a lot your bones get stronger. So we thought if these tissues are mechanically responsive, why not the airway?” he explains.
With MRC funding, the researchers designed a study to find out. Asthma patients volunteered to be exposed to various substances to make their asthma slightly worse. Some were treated with a substance which narrows the airways but doesn’t cause inflammation. Others breathed in house dust mite allergen to cause inflammation in their lungs, and the control group breathed in harmless saline solution.
When the team studied lung tissue samples from the patients they saw no difference between the group in which the airways had been narrowed and the group in whom the airways had been inflamed.
“That was a big moment,” Chris explains. “The airway wall had thickened and the airway was producing more mucus and was showing early signs of remodelling in both groups. So from that we concluded that airway inflammation wasn’t necessary for the remodelling we see in asthma patients, and that airway narrowing on its own can cause it.”
The impact of these findings is significant because it changes the established theory that airway remodelling over time is caused by repeated episodes of inflammation. It could explain why giving asthma sufferers high doses of anti-inflammatory drugs hasn’t been able to stop airway remodelling in the long term.
Chris says: “We know that inflammation is very important in asthma. But what people haven’t considered so much in the past is that the act of wheezing, the way that the airway narrows, can led to long-term changes. So now we need to think about both controlling the airway narrowing and inflammation.”
Comparatively few asthma patients have chronic disease, but the cost of treating these patients is vast. So a better understanding of how to treat them could have an economic impact as well as improving their quality of life.
“Chronic asthma is a very disabling condition; sufferers find it hard to hold down a job or pick the kids up from school. So we want to try and make their lives better, but if we can find better treatments it will also help to reduce the healthcare burden on society,” says Chris. The researchers’ next challenge will be to understand how airway narrowing leads to long-term lung damage, and then to carry out clinical trials to see if existing drugs to block airway narrowing will prevent it.
There’s unlikely to be a one-size-fits-all solution, explains Chris: “Although we lump all difficult-to-treat asthmatics together, they have maybe five or six very different diseases and a treatment that works in one group won’t work in another. It may be that specific drugs will one day come out of the work that we’re doing, but it also means that we’ll be able to use the drugs we already have more effectively.”
Download the MRC Annual Review 2011/12: Advancing medicine, changing lives, available in pdf or ebook formats.