Chris Harris, one of our neonatal research colleagues, has recently started measuring patients for his major study comparing the effects of two types of ventilation for babies born prematurely. The United Kingdom Oscillation Study started in 1998 and recruited over 300 babies who were born 12-17 weeks early and needed help with their breathing from a ventilator. All of the babies were given one of two types of breathing support – normal ventilation, where air is pushed into the lungs at a rate and depth about the same as they would do on their own, or ‘high-frequency oscillation ventilation’ or HFOV, where the lungs are inflated and then small amounts of air vibrated, or oscillated, in and out of the lungs at a very fast rate. The idea of the HFOV is that it doesn’t involve the same amount of stretch to the lungs as normal ventilation, possibly preventing some of the damage that can occur to premature babies’ delicate lungs during the crucial weeks after birth while so much lung growth and development is taking place. Chris is also doing some cellular biology as part of his PhD, stretching lung cells in the lab and seeing what inflammatory chemicals are released. This will help give a more complete picture of why HFOV may (or may not) be beneficial.
The UKOS participants were last studied at 11-14 years of age; the results then showed that HFOV seemed to have protected the lungs somewhat, particularly the smaller airways further down in the lungs. These airways are particularly prone to damage as they are still forming during the stage at which these babies were born, and the HFOV perhaps allowed those parts of the lung to continue developing more normally, as they would have done were the babies still in the womb.
The current stage of the research will make detailed lung function measurements again in as many of the participants who are able to come back for more testing, and again compare the children who received HFOV to those who received normal ventilator support. The UKOS “babies” are now young adults, aged 16-18, and so have probably grown a huge amount since their last tests; this growth will have affected their lung function so that’s why it’s important to see how they’re getting on now. Chris has had four patients participate so far and all has gone well thanks to their brilliant efforts, so we’re looking forward to seeing the data come in!
We have a not-so-new researcher in the lab – just a bit late introducing him to the readership… Manuel is an engineer from Barcelona, who has joined us for a year with the support of a fellowship grant from the European Respiratory Society. Manuel and his colleagues in Barcelona have a huge amount of expertise in analysing biological signals, and so Manuel is going to be working on new ways that we can process and analyse the data that we obtain in our studies. Ultimately, this could mean that we will be able to extract much more information from every study we do, and extract it more quickly – what’s not to like about that? Manuel arrived in December and has already done some very impressive work, not least sorting out the crazy number of wires he needs to connect up all of the many, many pieces of equipment he uses. There’s some pretty serious maths and physics in what he does, so there may be an explanatory blog post to come…
Maryam Waseem-Sayeed and Asha Omar are Year 12 students at Burntwood School and are members of our Student Advisory Panel. Over the summer, they spent a day in the lab watching one of our studies, and have produced this video showing many of the techniques we use. Thanks Asha and Maryam for your hard work and we look forward to more cinematic genius to come!
This summer we have had Dan, a King’s medical student, working in the lab on a study examining how blood flow to the brain changes during periods of intense breathing effort. His cousin, Tom, came into the lab on Friday to participate in Dan’s research. Tom is an English teacher in north-west London, so we are hoping soon to welcome some students from his school to the blog (hello, if you’re reading this!). Tom kindly allowed us to take a few photos and a video of him during the study. Maryam and Asha from our student panel filmed another subject doing the same study recently, so we will have a video with a full explanation coming soon, but here you can still see some of the techniques. On the left, Dan is inserting the tubes via Tom’s nostril into his stomach. The tubes allow us to measure the pressure and electrical activity generated by the diaphragm when it contracts. On the right, Tom is just starting the study – he is breathing from a chamber that is connected to a vacuum, meaning that his breathing muscles have to work harder to move air into his lungs. The video shows Dan stimulating Tom’s phrenic nerves (the nerves that supply the diaphragm) with a pair of magnets – this allows us to measure how strong the diaphragm is, and how fatigued it has become after breathing against the vacuum. You can see that his arms move with the stimulation too – this is because the nerves supplying the arm muscles are located in the same area as the phrenic nerves. I don’t think any of us stop finding the ‘arm flailing’ funny…
Dr Howard, a junior doctor at King’s College Hospital, is currently performing research into a possible link between Sudden Infant Death Syndrome (the sudden and unexplained death of an infant younger than one year old) and carbon dioxide (CO2). The exact causes of Cot Death (Sudden Infant Death Syndrome) are still unknown but it is thought that certain environmental factors, such as the mother smoking whilst the foetus is in the womb and the baby being in a smoking household once born, increase the risk of dying prematurely.
Increased CO2 levels make the blood more acidic and normally specialised cells in the brain detect the CO2 molecules, tailoring the breathing rate accordingly, which in this case means speeding it up so that more carbon dioxide is expelled from the lungs and more oxygen is taken in. However, babies that suddenly die may have a problem with the parts of the brain that detect CO2, meaning that the CO2 level goes up but the brain cells don’t respond to it, so the baby dies when the acidity causes injury to body cells, or when the respiratory rate does not change accordingly.
It was previously thought that brain cells responded to the acid in the blood and that only the cells in the brain stem carried out this function. However, it is being discovered that not only are neurones (nerve cells) in parts of the brain other than the brainstem involved, but also that they are responding to the actual molecule of CO2, rather than pH (blood acidity). Therefore, Dr Howard is looking at where the areas of neurones are that contribute to the response to carbon dioxide as well as what they specifically respond to.
Dr Howard carries out searches of current published papers to obtain background knowledge on her research topic. She also compiles information from current medical journals and research in order to say what the latest thinking is. Her aim is to publish her completed paper on Sudden Infant Death Syndrome in a journal so that the public and other scientific professionals can access a up-to-date summary of the current research into Cot Death.
I was interested in writing about Dr Howard’s research because I wanted to find out more about the dangers of having an excess of carbon dioxide in your blood, despite it being a vital gas for our survival; it truly lives up to the saying that ‘too much of anything is bad’! What’s more, it was completely new to me that failure to respond to surplus CO2 could be one of the causes of Sudden Infant Death Syndrome, which therefore made it a fascinating possibility to delve into. Through producing this summary of Dr Howard’s research, I have gained a richer understanding of the condition, which I hope you will too by reading it.
Lottricia Millett, Student Advisory Panel member, Burntwood School
Vicky recently started working on a new study in the lab. She is working with Professor Anne Greenough to measure lung function in a group of children who were born prematurely (early). When babies are born early, their lungs have not had enough time to develop and often don’t work very well. The machines and oxygen we use to support their breathing while they are growing can also cause some lung damage, though we are now much better (thanks to research) at giving the right breathing support.
A group of about 150 babies took part in a study between 2008 and 2009 where they had lung function measurements made when they were just ready to go home from the hospital, and then again when they were a year old. Some also had measurements made at two years old. During these first one or two years, researchers recorded whether the babies got any chest infections, and if so then they took a sample of snot to look at what bugs were causing the infection. Using the lung function measurements, the researchers could see what bugs did more damage to babies’ lungs during that early part of their lives when they were growing and developing fast. They found that babies with worse lung function when they left hospital were more likely to get infections, and also that having particular genes put babies at higher risk of getting chest infections.
Vicky’s new study is to measure lung function and breathing muscle activity in these children (who are now 6 or 7 years old). We will then be able to look back and see what difference particular bugs, as well as the genes and the babies’ early lung function measurements, made to how well their lungs work now. Other recent research has shown that the lungs can grow a lot more after birth than we first thought they could, and so it might be that it’s not necessarily just as simple as having smaller lungs earlier on or getting one nasty bug being the thing that decides how well your lungs work once you get a bit older.
Vicky has measured four children already this week and they’ve all been really brilliant at trying hard at the tests. The study will be going until July next year – it will take a long time to measure 150 children!
I come here to help the researchers with their projects by letting them experiment with my breathing. This is my fourth time here. Sometimes I think I’m going to be bored, but when I get here there is always something to do! I’ve started to learn what traces (squiggly lines on the computer) mean.
The researchers test my breathing by using: sticky stickers, masks and cubicles (I’m sitting in one in the picture). Every year they change subjects but the thing that stays the same is breathing.
It’s all for a good cause because it helps people who have problems with their breathing.
My name is Louise Taylor and I’m 7 years old. I have been here 4 times in the last 4 years. We are here to help people with asthma. We put sticky plasters on our chest and once a breathing mask. A computer measures our breathing by showing lots of wiggly lines. It’s fun but sometimes a bit scary at the start, but it’s worth it because we help other children.
i did lots of breathing through a tube and sometimes it got harder. i had to say how i felt by pointing at pictures. i was nervous before i started but then i got used to it. lorna was very nice. if you are wondering whether to do the study, i would say “it’s ok”!
Kathryn, age 7.
(You can see from the picture that Kathryn was keen to get going!)
I came all the way from Bedford to London to help Lorna with her study. I had to breathe through a tube attached to a machine and have a nosepeg on my nose. The machine made it harder to breathe sometimes, and I had to point to some pictures to tell Lorna how hard or easy it felt. A computer measured my heartbeat and my breathing muscles, and how much air I breathed in and out. It took about two hours and I had to concentrate lots. After that, I went into a machine that was like a big see-through Tardis! When I was in that machine, I had to breathe in and out and do big breaths while a different computer measured how big my breaths were. At the end, I had to fill in a questionnaire about my asthma. I also helped Lorna and Vicky decide what pictures were better than others to use to describe how hard or easy it was to breathe.
I was a little bit worried before we started and I didn’t really understand what I was going to do, but once we started it was quite easy. If I was talking to another child who was thinking about doing the study, I would say not to be nervous because there will be one or two people with you all the time to explain what you need to do. My advice is to always keep relaxed!