This project was designed to investigate lung growth and development using new techniques some of which were only available through our collaborators in Nottingham. As many participants from the cohorts will know, we can measure the volume of your lungs if you come to our laboratory and take the simple test that involves sitting in our special cabin. We can also measure how much any individual can blow out, which is a good guide to lung size, and this can be done on portable equipment such as that recently taken into schools. What is much more difficult to learn about is exactly how the tiny air sacs (alveoli) grow as a child or young person gets bigger. We know that the lungs are made of hundreds of millions of alveoli, and it has been widely believed that we get our final number of alveoli by the age of about 3 years, so that after that the individual alveoli get bigger but we can’t develop any new ones. We wanted to see if this was really the case.
Imagine a child who is 115 cm tall. His lungs will contain approximately 1 Litre of air. By the time he has grown to 155cm his lung volume will have doubled to contain 2 Litres of air. If it is true that he cannot develop new alveoli, then if follows that all his alveoli MUST increase in size as he grows. If only we could measure the size of the individual alveoli…
The new technique available to us in Nottingham is called Hyperpolarised helium-3 Magnetic Resonance (3-He MR). It doesn’t actually measure the size of the alveoli, but it gives a measurement – the ADC - that depends on alveolar size. If the alveoli get bigger with growth, then the ADC should also increase, by an amount which we can calculate.
We have been testing this by working with volunteer children and young people. We have measured their lung volume in Leicester, and then taken them to Nottingham for the 3-He MR. Some of the volunteers have been more than once, which helps us to look at changes in individuals as they grow (called a longitudinal study). We have also studied whether the size of the breath of helium or the final concentration of the helium within the lungs affected the measurement.
Two hundred and five children and young people have participated in the study, which is a really fantastic result. Most of them were from the Leicestershire cohorts, but we also invited some younger children to make sure we had a wide age range. What we found was that the ADC was bigger in the older, taller people, but it did not increase by as much as we would expect if the alveoli just got bigger when the lungs grew. Something else had to be going on, and we think that the lungs are able to grow more alveoli throughout childhood. This is very important because it shows that lungs that might be damaged in some way in childhood have the potential to recover. This has now been published in scientific literature (see Am J Respir Crit Care Med 2011; doi:10.1164/rccm.201107-1348OC).
One important part of the study was to look at people who had been born prematurely. We know that the last three months of pregnancy is a critical time for lung development. If someone is born early, their lungs need to take on the task of breathing air at a time when they would otherwise be filled with liquid. This is known to affect lung structure for some time afterwards, but detailed studies have not been possible because we have not had the techniques to look in detail. For this particular part of our work, we studied young people aged 11-13 who had been born extremely early. Half of them had suffered from chronic lung disease – in other words, they needed a lot of help with breathing for some considerable time. The others were less severely affected. We compared the measurements from these with other young people of the same age who had been born just a few weeks early, and another group of young people who had been born on time. Our preliminary data suggest that the number of alveoli is not very different between the groups. This suggests that the children who had been born prematurely had managed to catch up with the others.
We still have more work to do to analyse all the information we have gathered, including looking at the possible effect og growing up in a home where there is someone who smokes, or whether having allergies or wheezing makes a difference. As many of you will know, we performed additional tests, some of which tell us about how efficiently the lungs work, so there is a lot more information to come out! It comes as a surprise to many people that it can take considerable time to analyse all the measurements and work out their meaning once the measurements are complete, but it is important that we do all parts of the research project very carefully.
The purpose of this study is to learn how lungs grow in healthy & ill children and which genes are important in lung growth. We hope to learn how the lungs grow during early life and whether simple and common problems such as asthma or premature birth can affect the way in which the lungs grow. This will not provide any advantage to children who take part, but to future generations.
We have selected three kinds of participants:
Have a look for yourself! One of the children who has come to the lab allowed us to take pictures of the measurements he did, and explains what it all means in a short story. We are very grateful for his help!