Read about the involvement of the professional experts below to find out how they are working together to improve our understanding of severe asthma.
Experts leading U-BIOPRED's research centres
Research centre Expert leading the research Adult or children's research AMST: Academic Medical Centre, University of Amsterdam Peter Sterk Adult University of Bergen Per Bakke Adult University Hospital Bern Geiser, Thomas Adult Department of Pulmonology, Semmelweis University Ildiko Horvath Adult U.O.C. Medicina Interna - Centro di Riferimento Regionale per l'Asma Grave Riccardo Polosa Adult Fraunhofer Institute, Hannover Norbert Krug Adult Karolinska Institutet Sven-Erik Dahlen Adult Jagiellonian University Medical College Jacek Musial Adult Imperial College, London Fan Chung Adult University of Manchester Stephen Fowler Adult University of the Mediterranean Pascal CHANEZ Adult University of Nottingham Dominic Shaw Adult University of Southampton Professor Djukanovic Adult University Hospital, Umea Thomas Sandstrom Adult Università Cattolica del Sacro Cuore Paolo Montuschi Adult AMST: Academic Medical Centre, University of Amsterdam Simone Hashimoto Children Bern Kinderklinik Singer, Florian Children Copenhagen (COPSAC) Klaus Bønnelykke Children Astrid Lindgren children's hospital Björn Nordlund Children Imperial College, London Louise Flemming Children University of Manchester Clare Murray Children University of Southampton Graham Roberts Children
Xian Yang: Bioinformatic data researcher
At the 2013 Annual General Meeting Peter Sterk, project lead, awarded Xian Yang the U-BIOPRED Trophy for outstanding work on the project.
We asked Xian Yang a few questions about herself and her role in the project.
Could you tell us a bit about yourself?
I grew up in China. After I get my first degree in Electronic Engineering I came to the United Kingdom for further study, and got an MSc degree in Digital Communication from the University of Bath. Then I came to Imperial College to do by PHD.
I work in the Department of Computing at Imperial College London, with Professor Yike Guo. We are currently working on data analysis for U-BIOPRED and hope to hire a Biostatistician soon, who will analyse data using statistics and apply it to areas of healthcare.
What is your professional background?
I am a 3rd year, part time, PhD student and a research assistant working on Bioinformatics, pathway modelling and Systems biology. This involves using techniques from computer science, mathematics and engineering to analyse biological data, and to build mathematical models of pathways in the body. These are pathways on the smallest scales, such as molecules and cells.
What is your role in U-BIOPRED?
I am part of Work Package 8 on data analysis. I analyse clinical data as well as omics, which in biology is the study of the fields ending in ‘omics’, such as genomics, proteomics and lipidomics.
Have you been involved from the beginning of U-BIOPRED?
I started to work on this project in May 2012 but was only officially employed to work on the project from September 2012.
What do you enjoy most about being involved in the project?
I am so happy to work with people from lots of different areas of health science, such as biologists and clinicians. The most exciting part of this project is that I get plenty of real human data to play with, and I feel that I am making a contribution to improving asthma treatment through my work.
What are your hopes for the project and the asthma treatment?
I hope that we can find the handprints of severe asthma which can link the biological and clinical information. If we can do this we can give real insight into asthma treatment therapy by finding the right drugs to treat each individual person with asthma.
What have you learnt from being involved in U-BIOPRED?
I’ve learned how to work together with people from different scientific backgrounds to achieve the same goal: to try and discover the handprint of severe asthma.
Peter Sterk: Project coordinator
Role: U-BIOPRED Project Coordinator, Professor of Medicine at the University of Amsterdam, The Netherlands
What is U-BIOPRED and where did the research idea come from?
It was two issues that came together to form the idea that asthma treatment could be revolutionised by using a systems approach:
1) Severe asthma is a serious condition which greatly affects the lives of those who have it. Oftentimes, current drugs do not work well enough or the procedures that usually help patients are not very effective in severe asthmatic patients.
2) Scientists, independent of asthma, were exploring new methods of describing patients, not only by asking questions and doing lung function measurements but also by measuring the biology of our bodies in a more extensive way, using an approach known as systems biology. We felt that this new way of looking at disease could also be applied to help develop new interventions and therapies for patients with severe asthma.
How did the project come together?
Investigators, such as myself, worked collaboratively to develop the initial idea and then, working within a larger group, we put the idea forward of how to explore this idea within individuals with severe asthma. We worked for a year to put together this proposal for IMI in Brussels. IMI were interested in the idea and invited a number of pharmaceutical companies to see if they were interested in the idea and in co-sponsoring the work of IMI to raise the budget for such a large-scale extensive study. There was a lot of industry interest and the project is sponsored by the European Union and 10 pharmaceutical companies in Europe.
How did you identify which centres would be involved in the project and in the active recruitment of patients?
There are a number of hospitals and clinics in Europe who are focussing on severe asthma and so we asked those facilities to join us. And we selected those centres based on their expertise, their experience of patients with severe asthma or COPD patients so they really know what they are talking about when it comes to respiratory disease, and they have shown in the past to be able to do proper clinical trials so they have high quality, at least in our view. I think more centres would have been willing to join us and so at this stage we may expand our group of institutes to boost numbers and make recruitment faster.
How are you going to manage all the information that you will gather through the analysis stage, and maintain communication between all the research members?
This requires a so-called knowledge management system. It is how we get all the data together from all the laboratories into a proper safe and secure data system. And this is a group within the project who are working with the most modern knowledge management systems to ensure that all the information is secure, reliable and can be assessed and used for getting the right answers. The knowledge management system in U-BIOPRED is one of the leading systems within the EU and IMI projects within Europe.
Do you feel that the project is communicating effectively with the general public and people with asthma?
As well as being involved at the recruitment stage, patients and organisations representing patients have been involved throughout to influence the direction and design of the project: in the Patient Involvement Platform (PIP), annual project AGM, work package 9 (dissemination) and 10 (ethics and safety monitoring). In fact this is one of the first times that patients and researchers are working together on the same questions on such a large scale European project, and the patients have been instrumental in determining the project design, helping us to determine what is realistic to expect from patient participation e.g. can we ask patients to come for testing 3 times for tests that may take a couple of hours, and what is appropriate testing for children.
How is patient involvement influencing the project?
Also one of the primary achievements of having patients involved throughout the project has been to harmonise the definitions of what is a patient with severe asthma. Although you may think that disease definitions are already in the medicine textbooks, this study has shown that there is not consistency of definition between medical professionals, and between countries, so as a result of this study we have been able to create a harmonised definition to improve the communication and discussion of diseases across Europe, with everyone speaking the same language to categorise patients.
The website is also a valuable tool in enabling everyone involved to communicate and for the public to access the project and find out what we are doing. Also to improve communication with the public outside of the project we held an art competition to get people engaged with the study and to raise awareness of asthma. It is important to go out into the wider community and ask for involvement, to go to environments such as schools and workplaces to make as many people as possible aware of the impact of asthma on people’s lives, and how the project is addressing these issues.
How could the results of the project make a difference to the lives of people with asthma?
The ultimate aim is to improve the treatment of people with severe asthma, but this will take years because we first need to understand the disease properly. So the EU asked us to put together a better ‘map’ of all the people in Europe with asthma. There are many different class or groups of people with asthma, they are not all the same, and having this asthma ‘map’ will help us to provide the most appropriate treatment for each patient’s individual asthma type. So as a result of the project many new treatments can be created and existing treatments improved. For example, if we find that a particular group of people with asthma have abnormalities in their immune systems then interventions that target the immune system can begin to be provided. Also, by working the pharmaceutical companies and teaching them these new scientific methodologies and approaches to the treatment of asthma, they will and already are applying them to increase the range and effectiveness of their products. They will be better equipped to engineer specific treatments for specific groups of severe asthma, so this project will provide the instruments for improved medical practice, getting the right treatments to the right patients.
Julie Corfield: Biobanking
Role: Biobanking specialist for U-BIOPRED and Director of Areteva
What is a bio bank?
A biobank is the place where a collection of samples are kept together with data describing them. Biobanking is the means by which this is achieved in an organised way from the point of obtaining the sample, during its transport, storage, use and disposal.
For U-BIOPRED biobanking covers samples such as blood, lung tissues and urine that are collected from each participant in UBIOPRED. These samples are kept safely in a bio bank as part of the UBIOPRED collection, until there are enough samples for the UBIOPRED research to be carried out. The bio bank keeps records of the samples and arranges for their transport to centres for testing.
There are a number of laws and procedures called ‘safeguards’ which regulate bio banking to protect the rights of the person who provided the samples and to ensure the safekeeping of the samples for future research.
These safeguards ensure that:
- the people who take and process the samples are properly trained
- samples are kept safe with only certain people having access to them
- samples are only used for what the people who gave the samples agreed to
- samples are kept in the right conditions to ensure they are of good enough quality to be used
- the identities of the people who provided the samples are not known to the people in the biobank or to those who use them for research
- that any sample can be located and destroyed, if someone no longer wants their sample to be used
Why is biobanking important?
Biobanking is essential to make sure that human biological samples are kept in a good condition and that the legal and ethical requirements that protect research with human samples are met. It gives both patients and researchers the confidence that the samples that patients have contributed to the project are being handled and used in the right way.
Without experts in biobanking it is likely that samples would not be kept correctly and may be used for the wrong tests. If samples are looked after correctly the greatest use can be made of them. For example, once the U-BIOPRED is complete, there might still be samples available in the biobank that have not used up during the project. There will be a process to enable access to those samples so that they can continue to be used for medical research and not wasted. Of course this system would only be acceptable if rigorous checking and were in place to ensure that the samples were still suitable for use and only used for the right tests by the right researchers.
In this way it is really important to think about what happens after U-BIOPRED to ensure that all those samples collected really are put to good use. The vision of many in research is for there to be open-access to samples to researchers, with an overseeing governing body that evaluates requests for use to allow access. However, this is not a reality yet.
How is biobanking used in U-BIOPRED?
When a patient takes part in the U-BIOPRED project a number of tests are done that provide the samples for the researchers to do analysis on. By collecting and studying these samples with data that have been collected in the clinic for the individual patients they can build up a greater understanding of asthma.
Samples collected from patients by one centre will be analysed with samples from another. For the different centres and people involved in the project to share and analyse these samples the U-BIOPRED project is using a biobank facility to log and store the samples for them.
The biobank used by U-BIOPRED was chosen because it can perform all the sample operations required by the project, which is a huge task. This includes providing kits with all the sample tubes for every patient to each centre, organising the couriers to and from the centres, receiving the samples, storing the samples at a high enough standard to ensure their quality over time and picking relevant samples from their store to be sent to centres for analysis. The centralised biobank for U-BIOPRED is situated in Manchester in the UK it is licensed under the Human Tissue Authority which means that they meet the high standards set within the UK.
What samples are being collected and how are they processed?
The samples taken can be described as biofluids such as blood and urine, volatile substances such as gases from the breath, and solid samples such as pieces of lung. These samples are taken at different points of the study depending upon the project design agreed by all the researchers. This means that all the centres are collecting, processing, analysing, storing and transporting their samples in exactly the same way, to the same high standards. This is done by following what are called standard operating procedures (SOPs). It also means that the samples are likely to be of a high quality for analysis and that reliable results should be produced.
Blood and urine samples are collected from every participant but bronchoscopy samples (taken from the lungs) are only collected from some, and it is optional. A complicated procedure is also used to produce sputum by coughing it up. This type of sample contains saliva and substances such as mucus or phlegm from the respiratory tract.
The samples are collected and processed according to the type of analysis that needs to be performed on them. For example there are three different types of analyses that need to be performed on the blood. Each processed blood sample results in there being many sub samples. This means that only the minimum amount, say 1 out of 20 subsamples, is used in one analysis.
Another example is the bronchoscopies which are subdivided into samples to be processed and stored at room temperature or processed in a particular chemical or frozen. All the biofluids, such as blood and urine, are also frozen and sent to the bio bank.
What policy governs bio banking?
Companies have policies for biobanking. For UBIOPRED some of the policy requirements are specified in the protocol and in the consent that the patient signs when agreeing to participate in the study. The purpose of policies in biobanking is to set rules to ensure high standards of ethical and research practice.These include:
- consent (ensuring that all people who have provided samples have given their written permission for their samples to be used in the study)
- withdrawal of consent (that this can be done by the patient at any time, without question and without affecting their access to medical care)
- scope of acquisition (making sure that samples are only taken from appropriate sources by qualified people and handled correctly)
- confidentiality (protecting the identities of the people who provided the samples)
- data privacy (making sure that no one can access the samples or information about them without being checked and given permission)
Another important aspect of policy is to ensure there are processes in place to track samples from the point they are collected to when they are disposed, with the location of the samples being recorded. Within U-BIOPRED an electronic record system has been developed so that each sample has its own unique barcode and can be scanned into the system at the clinic like scanning items of shopping at the supermarket. When samples are received at the biobank and when they are sent to a centre for analysis they are logged into other systems to make sure they are always tracked.
This also means that if a participant decides not to be involved in the study anymore, their samples can be found from checking the systems and destroyed. It is the legal right of any participant to withdraw from the study at any time and their samples must destroy immediately, however it is very rare for people to decide to withdraw.
What are the patients told about biobanking when they get involved in the project?
The patient information and consent provided to patients getting involved in the project has a lot about bio banking in it, and every patient must read and sign it before samples can be taken or tests done. In this document it says that their samples can be kept for up to twenty years. This is the policy for samples required by the study, but the patient also has the option of donating additional samples, for example bronchoscopy and genetic samples such as blood samples for extracting DNA for genetic analysis. Genetic testing is a debated area of research and therefore patients are given the option of donating genetic samples, rather than it being required for the study, in case they are uncomfortable with the idea.
Has the process of taking and dispatching samples to the bio bank begun yet?
Many samples have been taken. At the end of June the biobank had 10,737 samples/subsamples.
Analyses have already been performed on blood, urine and sputum samples from 60 participants. Samples continue to be dispatched from the clinical centres to the biobank on a regular basis.
What, if anything, have you been doing for the U-BIOPRED project for the last year?
During the last year, I have been developing the biobanking systems required by the U-BIOPRED project. This has meant working across all aspects of sample operations and with the clinical leads for the project. I have also been working with the academic lead to manage ‘omic technologies’ area of UBIOPRED, which involves using specialised technologies to analyse samples.
Has any governing legislation or policy changed within the last year or since the project commenced?
There have not been any significant changes in the law that would effect on the project, but it is essential to be aware of what discussions are on-going to be able to be part of any decisions or changes made in the future.
Charles Auffray: Systems biology
Role: Centre National Recherche Scientifique (CNRS) and co-leader of WP8 on bioinformatics and systems biology
What is the systems approach in the context of the U-BIOPRED project?
The systems approach is a research strategy to analyse patient samples and their features globally. The basic principle is to take samples from individuals and look at them using the most advanced experimental and computational tools, but without applying any preconceptions or assumptions. Clinicians and scientists in the project will take these samples, analyse them and organise them into groups based on their similarities, thus building models of disease states. A number of such models will be produced and through developing, testing and refining these models we will construct a model of severe asthma from which we can better understand individual disease history, develop novel diagnostic biomarkers and drug targets, and ultimately predict reactions to disease treatment.
What stages are involved in the systems approach?
Stage 1: The first stage of the systems approach is to collect diverse types of information about every part of the lungs and the body, in a very systematic and unbiased way. Each type of data collected is analysed with statistical tools to obtain a mathematical model known as a fingerprint. We expect that each fingerprint will help us distinguish subgroups of patients with similar disease characteristics. Eventually we hope to use these fingerprints to make initial predictions about the development of the disease and to help predict the reactions of people to disease treatment.
Stage 2: After we have identified these diverse fingerprints we will enter the second stage, where we use the fingerprints as the starting point and build another type of model that combines all the fingerprint data types, this time taking into account how they interact within pathways and networks at the molecular and cellular levels. We called this a handprint as it is based on a combination of all the fingerprint data and provides scientists with more complete and computable models to work from. We expect therefore that the handprints will increase our ability to identify possible targets for therapy and to develop tools for the diagnosis of the disease.
Stage 3: The final stage involves testing the potential diagnostic biomarkers and drug targets identified from the fingerprints and handprints obtained in stages 1 and 2. This will be performed by designing and performing additional cycles of experimental data collection and analysis in human and animal models of the disease.
This overall repetitive and integrative process is the systems approach we are implementing in U-BIOPRED toward better understanding and treatment of severe asthma.
How will the success of the approach be measured?
There are two metrics of success:
- Whether we are able to identify a new mechanism underlying the development of severe asthma compared to prior knowledge.
- Whether the fingerprints and handprints generated have a predictive capability with regard to the onset of disease, disease history and severity, and people’s reaction to treatment. In short, the approach will be proved to be a success if we discover and validate new disease mechanisms and obtain biomarkers with predictive power for severe asthma conditions.
How will you collect data from patients?
The clinical centres are collecting samples of blood, exhaled air, sputum, and in some cases bronchoscopies, from the patients enrolled in the study after compliance with ethical and safety regulations. The clinicians are assessing biological and clinical parameters using a range of different tests according to international guidelines and standards for best practices as described in the U-BIOPRED protocol developed with input of the patient representatives.
The samples are collected and stored in a central biobank (a storage space for human biological samples for use in research) and the associated information is registered in a secure database. A variety of data types will then be collected from the biobanked samples in a standardized way using advanced high-throughput functional genomics platforms of the project partners according to the U-BIOPRED study reference manual and data analysis plan. In order to ensure the integration of these different components, we have developed within U-BIOPRED a knowledge management platform that provides a framework for their efficient and collaborative use by clinicians, scientists and patients. It is essential for the success of such a complex project.
How will constructing this model help to personalise treatment in the future for asthma patients?
For decades scientists and clinicians in academy and industry have been focusing on trying to understand specific and simple mechanisms of asthma to help develop more targeted medications. But we know that this has met with limited success when it comes to understanding and managing severe asthma conditions. The working idea underlying the systems approach to disease is that the reason for these difficulties is that the classical analytical approaches are too limited in scope, as they do not reflect properly the molecular, cellular and organ-level complexities underlying the disease, nor their interplay with environmental influences. We know now that in order to take them into account, we need to build fingerprints that are complex in nature and handprints that are even more complex. This means that instead of focusing on a very restricted set of elements as in classical biomarkers, fingerprints and handprints will have to combine sets of multiple interacting elements that, when combined together, can explain the underlying mechanisms and be able to help us predict disease progression. We hope through implementation of the systems approach to better understand what happens during exacerbations, thus helping each patient to manage their asthma and reach a more controlled state, whether they have mild, moderate or severe asthma.
What underlies the systems approach is a shift from analysing samples separately with preconceived ideas about the data to a more global assessment of the data for all samples in an integrated and standardized way. Using the knowledge management platform in support of the generation of fingerprints and handprints as described above will provide us with the ability to repeat the process to ensure that the U-BIOPRED model of severe asthma is thorough and usable by the clinical and industrial partners of U-BIOPRED to improve the conditions of the individual patients.
Is there anything new about the way that U-BIOPRED is using this systems biology approach?
For the first time, the U-BIOPRED project is joining together the most advanced and state-of-the-art expertise from academic, clinical, and industrial partners, with input from the patients, to deploy a systems biology approach to improve understanding, diagnosis and treatment of a complex human respiratory disease.
We are also involved in harmonising our efforts with projects having complementary goals and expertise to develop jointly the best practices for deploying a systems biology approach to pulmonary diseases and allergy. This includes AirPROM and Synergy-COPD, two projects supported by the Information and Communication Technology Directorate of the European Commission, which will enrich the data from U-BIOPRED with genetics and lung imaging, and provide additional capabilities for data analysis and handprint modelling integrating from the molecular and cellular to the organ and patient levels. We are also deploying the systems biology approach in MeDALL, a project supported by the Health Directorate of the EC to tackle the mechanisms of the development of allergy, which will provide a broader epidemiological base for interpretation of U-BIOPRED findings. Finally, our approach is now being adopted by a number of other projects, particularly those based on public-private partnerships supported by the IMI, which could use the U-BIOPRED knowledge management platform in support of other research efforts.
Publication produced by Dr Auffray and U-BIOPRED founders describing the systems biology approach of U-BIOPRED
Charles Auffray, Ian M. Adcock, Kian Fan Chung, Ratko Djukanovic, Christophe Pison and Peter J. Sterk (2010), ‘An Integrative Systems Biology Approach to Understanding Pulmonary Diseases’. Chest, 137, 1410-1416.
Susan Wilson: Immunopathology coordinator
Doctor Susan Wilson is an Associate Professor and Head of the Histochemistry Research Unit at the University of Southampton. She has over 25 years of experience in histopathology and has dedicated her research to the pathobiology of asthma and severe asthma for a large number of years.
Within the framework of the U-BIOPRED Project
Doctor Wilson has been coordinating the immunopathology for the biopsies that was undertaken in her research unit. Her research unit ran several training workshops on the handling of the biopsies, to bring other centres up to speed with the protocols, and wrote the corresponding standard operating procedures for these protocols.
What will your work contribute?
At this very moment, they are describing the immunopathology that characterises the study participants. When novel biomarkers can be identified, based on ‘omics information, they will go back to the tissue samples to see which cells may be expressing these markers and how this contributes to the disease pathogenesis
What are main results and when will the main results be seen?
They described the basic immunopathology for the four groups of patients that have been identified. At this moment they are further exploring what this may mean and how the clusters can be connected to other ‘omics platforms in the study.
What is the expected impact and legacy of your work?
Overall the project will hopefully lead to a better understanding of clinical asthma and its pathology. It is key to know what exactly is happening in the actual lungs, to ensure we correctly interpret the ‘omics data. With the aim of researching whether the invasive procedures, such as bronchoscopies, for diagnosis can be prevented in the future by using biomarkers in blood, sputum or urine.
What will your work mean for the patients?
The goal of the overall study is to be able to have a point of contact method to determine the diagnosis and the fitting treatment and care plan for patients. In doing so, patients can have their therapies chosen and administered there and then, so that they no longer have to wait for a longer procedure.
Tony Postle: Lipidomics expert
Tell us a bit about yourself
I am a Professor of Biochemistry at the University of Southampton, specialising in the field of lipidomics in a wide range of conditions, including lung disease such as asthma. Lipidomics is the analysis and study by sophisticated and sensitive mass spectrometry techniques of the extensive range of individual lipid (fat) molecules in biological and clinical samples. In turn, lipidomics is a specialised form of metabolomics, the study of the chemical markers (fingerprints) which can tell us how specific cell types function and interact with their environment.
How have you been involved in the development of U-BIOPRED?
I have been involved since 2007, when the project was being set up. This involved the great, but time-consuming, achievement of agreeing the project’s protocols. These were the processes and standards that would be used by every testing centre so that they all collect and analyse the data from the study participants to the same high standards.
The aim of U-BIOPRED is to identify clusters of clinical and biochemical characteristics that indicate from what type of severe asthma a person suffers (their asthma phenotype). We wish to target specific treatments to these different asthma phenotypes. A successful therapy for one patient won’t necessarily work for a different person even if they present to the doctor with very similar asthma symptoms.
My work, along with all my colleagues, is to analyse samples from the patients without any knowledge of their clinical condition. Instead of looking at the characteristics with which a person comes into the doctor’s surgery, such as their spirometry test results or medical history, we look at the raw data from a person’s sputum and plasma samples to examine patterns in the ‘omics’ data (lipidomics, metabolomics, proteomics, transcriptomics).
Omics is the analysis of the different types of molecules that make up the cells of a person i.e. metabolomics is the study of metabolites; lipidomics is the study of fats and their function; proteomics is the study of proteins. Patterns (clusters) derived these ‘omics’ analyses will provide fingerprints of patient characteristics which will be combined to generate an overall pattern that we call a handprint. We will then compare these biochemical fingerprints and handprints with the extensive clinical information gathered on all the volunteers in U-BIOPRED. The goal is to see if a selective combination of these extensive analyses can provide readily measured biomarkers that will be predictive of type of asthma and outcome and that can eventually guide targeted therapy.
We are currently working hard to produce the biochemical results from U-BIOPRED. This involves collecting the samples from all the contributing sites, storing them safely in the U-BIOPRED Biobank and then conducting a rigorous quality control check on all samples before analysis.
What are the challenges to this way of looking at data?
Collecting samples is time consuming but relatively straightforward. Whereas analysing the data is complex and interpreting the data is mind-blowingly intricate!
There is a huge amount of data to play with, especially when you are trying to look at it in a new way. Technology has moved on a lot since the project was first designed, which means that the researchers are constantly having to try and respond to new advances and apply new techniques to the project.
One novel and exciting approach to analysing the whole data set is called topographical data analysis, which visualises common biochemical features between individual patients and then correlates the patterns generated with all the clinical data. This approach has huge potential to identify the novel biomarkers that are the fundamental aim of U-BIOPRED.
Have there been any unexpected achievements of U-BIOPRED?
One of the great strengths of U-BIOPRED has been how it has involved and linked up junior researchers. Post-doctoral researchers have been employed in the different centres to work on U-BIOPRED, with the opportunity to come together at the annual meetings and scientific meetings to share their ideas and learn from each other. This has led to a real community atmosphere within U-BIOPRED.
What is your dream for the future of severe asthma?
The ultimate goal would be to develop a completely non-invasive way of collecting a sample, such as a tube that someone with asthma could breathe into, like a spirometer. Samples collected by such a device would then need to be analysed for identified biomarkers to identify the person’s asthma phenotype, so that the doctor would know what the best treatment was for that individual.
Currently, researchers like me have to take a sample of sputum from the person with asthma, but it is not possible to take sputum from every adult or child. Consequently, it will be important to use techniques to generate samples for biochemical analysis that don’t involve having to go inside a person’s body to take what is needed.
Exhaled breath is one way that this might be possible in future, and studies linked to U-BIOPRED are already experimenting, for example, ENOSE breath analysis. We will need to explore in the future which of the asthma phenotype biomarkers identified in U-BIOPRED can be measured in such samples, which is a very exciting possibility.
Graham Roberts: Paediatric pulmonologist and allergologist
Professor Graham Roberts is a paediatric pulmonologist and allergologist working at the University of Southampton. He is the lead for the paediatric cohort, the clinical representative on Work Package 10 and part of the management board.
What will your work contribute?
Together with my colleagues I have been responsible for the creation of the paediatric cohort that together with the adult cohort covers more than a thousand patients. The analysis of the collected data will help us better understand the mechanisms of severe asthma. It will help us to find out what the differences are between the patients with controlled asthma and others where their asthma is not controllable.
What are main results and when will the main results be seen?
At the moment we have managed to recruit a large cohort of children with severe asthma and pre-schoolers with severe wheeze. A comparative group of children was made, with mild-moderate asthma and pre-schoolers with mild-moderate wheeze. We then followed them up over the years, collecting a large amount of data and samples.
What is the expected impact and legacy of your work?
We aim to provide a better understanding of severe asthma and severe wheeze in childhood. From that understanding we can better target treatment to children with severe asthma and/or severe wheeze. Hopefully, we will then be able to understand patients with severe asthma and match them to the best treatment … maybe a new treatment.
What will your work mean for the patients?
Through this work, we aim to understand severe asthma and in the medium term (five to ten years) help to better manage patients that suffer from it. If we work out how to cluster the severe asthmatics, we can predict that one group might respond better to one treatment and one group better to another. We should then prove that this is correct and whether this can improve patient outcomes. If so, it can be used in the future to direct therapy and by the clinicians in a clinic. This will have an impact on care in five-ten years.
Bertrand de Meulder: Researcher at CNRS-EISBM Lyon
What will your work contribute?
We are at the end of the omics ‘chain’: we are currently analyzing, integrating and harmonizing all the data that will enable us to develop the handprint of severe asthma. We are now waiting for the final version of the clinical data from WP3 and omics data from WP7; according to our plans, if we have all data we could be able to produce the first version of the handprint by July 2015. Once developed, the handprint will go back to the rest of the consortium for interpretation.
What is the expected impact and legacy of your work?
Thanks to the handprint we will be able to better identify the characteristics of asthma patients. This will lead to more precision in analysis and in the creation of effective new treatment; in fact U-BIOPRED’s findings could be used to select patients for running more clinical trials that will lead to the development of personalized drugs by the pharmaceutical companies. This can represent a breakthrough in the treatment of severe asthma patients in particular, since these patients have unmet needs and therefore if we will be able to better identify them through the handprint, we will also be able to target the drug development towards their needs.
What will your work mean for the patients?
We are developing a methodology that can be applied to different diseases and in particular to complex diseases (eg. COPD). We already have applied the same methodology to study allergy and failed lung transplantation. At the end of the project patients will know more about their asthma and will be able to better manage their disease; at the same time, we are confident we made great contribution to the development of new drugs.