The biggest project on severe asthma to date
About 300 million people worldwide suffer from asthma, with 250 000 annual deaths attributed to the disease and it is estimated that the number of people with asthma will grow by more than 100 million by 2025. Despite these statistics, not many new drugs have been developed to treat this disease since the invention of corticosteroids in mid 1940s. That’s partly because corticosteroids work well for 92-97% of asthma patients and there was no strong commercial incentive to look for new drugs. However, 3-8% of patients—those with severe asthma—do not respond to corticosteroids or other existing treatments. What’s more, those patients require frequent hospital admissions and account for half of all the asthma healthcare costs.
The U-BIOPRED project was the biggest and most complex research project undertaken to understand severe asthma to date. It aimed to speed up the development of better treatments for patients with severe asthma by understanding the disease in more depth. More specifically, its main goal was to identify different subtypes or ‘handprints’ of severe asthma by adding complex biological markers to clinical characteristics, so that new treatments can better target the disease in different patients.
Groundbreaking discovery of asthma subtypes
This was done in several stages: first the researchers recruited 1 025 patients with severe asthma – both adults and children. Secondly, researchers took blood, airway, breath and urine samples of those patients and analysed tens of thousands of proteins and molecules looking for common patterns. They wanted to know if patients could be divided into subtypes based on a combination of those biomolecules as well as a number of other clinical indicators.
Analysing all this information in 1 025 patients and looking for patterns was no small feat but thanks to bioinformatics specialists in the project, it was a success. By the end of the project, the analysis revealed that there are four to five subtypes of severe asthma among adult patients (depending on the clinical and biological markers used), a discovery which is already paving the way for the development of more effective treatments. Initial results also show that there might be several, slightly different subtypes of asthma in children, but that analysis is still on-going.
Unprecedented cooperation and other achievements
In addition to discovering a number of subtypes of severe asthma in adult patients, the project recorded a number of other achievements, including:
- Reaching a consensus between industry and the academic partners on what constitutes severe asthma and how it differs from ‘difficult’ asthma. The consensus was published and is being taken up by others, such as the International Primary Care Respiratory Group. It will be updated in the near future to include final project results.
- Building a registry with data from 1 025 patients belonging to eight different groups (so-called ‘cohorts’), some of which have never been studied before. For example, the project included four different groups of children, from preschool wheezers to asthmatic school-age children. This is significant because no study has ever studied children of various ages in combination with adults before – until now they were considered young adults. The registry will be an asset in future research.
- Establishing exemplary cooperation between all project partners, including 12 pharmaceutical companies, academia and patient groups. According to project participants, the results achieved in this project could not have been achieved by one company or academic institution alone. It was a truly collaborative effort.
- Building a biobank with more than 50 000 severe asthma patient samples (e.g. blood, sputum, lung tissue, urine), available for future research.
- Creating a certified rhinovirus challenge model which can mimic asthma attacks or exacerbations. Exacerbations are a key unresolved problem in severe asthma and it is difficult to recruit patients when they suffer from them. Therefore this virus could be an important asset in future research.
- Nourishing exemplary patient involvement. Patients played a big role in the project, including participation in the scientific and the ethics boards. They helped in many aspects of the project, including fine-tuning research protocols and providing encouragement during difficult times. A handbook on how to successfully ensure patient participation in research was also produced.
- Producing almost 70 scientific papers which are now in various stages of preparation.
The data from U-BIOPRED to benefit companies, patients and academia
The knowledge and data from U-BIOPRED is already being used extensively by the pharmaceutical companies to address a number of key bottlenecks in drug discovery which will bring immense benefits to patients:
- Identifying and validating drug targets. As U-BIOPRED has mapped the biological processes of severe asthma in patients, companies now have a clearer view on which biological processes should be targeted with future drugs.
- Decisions on which drugs to invest in. Thanks to the U-BIOPRED data, companies can now predict whether some of the drugs which they have in the pipeline will be effective for severe asthma patients.
- Getting the right drugs to the right patients. There are already some new drugs for asthma and severe asthma which work in some patients and not in others. By using the handprints as part of clinical trials, companies and caretakers can now start predicting whether or not a certain drug will be effective in individual patients. In the long run, this will be very beneficial for patients because they won’t be unnecessarily treated by drugs which don’t work for their asthma subtype.
The project will also benefit the academic community as the knowledge, networks and experience gained will inform many future studies and collaborations.
What happens next?
Even though the official funding for the project ended, the analysis and validation of the data will continue through on-going contributions from various consortium members and other organisations such as the European Respiratory Society. In the long-term, the researchers will try to answer some of the following questions:
- How well do different subtypes of asthma identified in this project persist over time?
- Do individual patients move between different subtypes of severe asthma?
- Are the same subtypes of severe asthma present in other populations?
- What are the similarities and discrepancies of handprints between severe asthma and the chronic obstructive pulmonary disease?
Some of these research questions might be addressed in future H2020-funded studies and IMI projects.
Achievements & News
IMI severe asthma project U-BIOPRED has produced a short, practical guide on how to involve patients across all stages of healthcare research. Aimed at people planning on applying for, or developing EU healthcare research projects, the booklet sets out top tips for successful patient involvement based on the experiences of the project’s Patient Input Platform (PIP).### The project’s advice can be summarised as follows:
- Before the project starts, get patients involved as soon as possible, budget for their involvement, and set up a patient input platform.
- During the project, provide coordination and support for patients and communicate with them regularly and clearly. Patients can provide input on all aspects of projects, especially issues such as patient ecruitment in clinical studies, and communication with wider (non-scientific) audiences.
- As projects draw to a close, patients can play a key role in gaining visibility for projects in public, patient and policy settings, and encouraging other patients to get involved in research.
U-BIOPRED proved successful at integrating patients’ input into its work. ‘U-BIOPRED PIP members hope that by sharing their experiences of involvement, they can provide practical guidance to achieve successful and meaningful patient involvement to optimise your research outcomes,’ the authors write.
‘This ideological project has seemingly succeeded where so many others have failed, challenging the culture of how science is done by systematically collecting and analysing data in a successful pan-European collaboration involving academia, industry, and patients.’### This is how IMI’s severe asthma project U-BIOPRED is summed up in an editorial in the renowned medical journal Lancet Respiratory Diseases. The paper notes that the vast amounts of data gathered by the project, coupled with its use of knowledge management platforms like TRANSMART, will allow experts to distinguish different types of asthma that could lead to new or more effective treatment approaches. U-BIOPRED is also praised for its ‘liberal approach to data sharing’; the project has pledged to make much of its data publicly available.
IMI’s severe asthma project U-BIOPRED has unveiled its first classification of severe asthma types at the European Respiratory Society’s recent international congress in Amsterdam, the Netherlands. The findings will help scientists identify and, if necessary, develop treatments best suited for each category. Severe asthma affects around half a million people in Europe. ###Despite taking many medicines, severe asthma patients often struggle to keep their condition in check and find it hard to go to work or school and lead normal lives. U-BIOPRED has gathered vast amounts of samples and data from severe asthma patients as well as healthy people from across Europe, in a bid to identify distinct types of the disease. In this study, scientists analysed gene activity and levels of certain proteins and lipids in sputum samples from severe asthma patients. They were able to identify three distinct patient clusters. ‘We believe that our work, dividing severe asthmatics into meaningful categories, is the first step towards being able to provide each sufferer with optimal individualised treatment, the ultimate goal of personalised medicine,’ commented Diane Lefaudeux of the European Institute of Systems Biology and Medicine, who presented the findings.
- Read the press release
- Download the ERS conference abstract via the ERS website (search for ‘Lefaudeux’ under Speaker)
IMI’s severe asthma project U-BIOPRED has pioneered a patient-centric approach to research since before the start of the project. Now the project’s Patient Input Platform has drawn on its experience to produce five recommendations for meaningful patient engagement in research.### The group’s findings are published in the journal Research Involvement and Engagement and combine concrete advice as well as case studies from the U-BIOPRED project and can be summarised as follows:
- Involve early (i.e. during project formation);
- Involve deeply (i.e. in all day-to-day activities of the project);
- Gain patient feedback on the project’s progress;
- Include patients in dissemination;
- Encourage patients to tell their own story.
The authors acknowledge the barriers that may hinder greater patient engagement in research and propose solutions to get round these. ‘The journey for patients working in EU projects has only just started, and the future is exciting,’ the authors conclude. ‘The more patients get involved, the more opportunities for impact can be realised.’
The U-BIOPRED project is now drawing to a close; in June, the project presented its latest results at a symposium; the key achievements are summarised in a report on the project website.
Severe asthma is often difficult to manage and many patients are unresponsive to treatment. IMI’s U-BIOPRED project aims to make severe asthma diagnosis and treatment more personalised by creating ‘handprints’ that identify sub-phenotypes of asthma.### The eTRIKS project has been working with U-BIOPRED by deploying analytical techniques to help them in their research, in order to create an environment where the diverse ‘big data’ sets can be compared and analysed. “eTRIKS provides gel without which we could be floating in pools of excess data with no direction,” said Professor Ian Adcock at Imperial College. “U-BIOPRED is using these data to produce at least 60 publications to advance the understanding of the complex causes and subtypes of severe asthma. The eTRIKS/tranSMART platform is a key ingredient to making this happen.”
- Read the press release
Save the date! U-BIOPRED results symposium
Save the date! IMI’s project U-BIOPRED is holding a results symposium on Wednesday 24 June in Leuven, Belgium. Project partners will showcase major achievements and findings from the project and outline future steps for the consortium, building upon the results of this multi-centre project.### The event will also present the U-BIOPRED experience of patient-research collaboration to support the clinical trials and ensure relevance of the project to the lives of people living with asthma.
U-BIOPRED is one of IMI’s first projects and is due to finish in September 2015. The project has been working over the last 5 years to speed up the development of personalised and targeted treatment of patients with severe asthma by creating a novel way to identify different types of chronic asthma using a ‘handprint’ – a combination of biological characteristics (biomarkers) that indicates what type of asthma a patient is suffering from.
IMI project U-BIOPRED is making great strides towards its goal of identifying distinct subtypes of severe asthma, something that will ultimately help to pave the way for personalised treatments for this serious health problem.### The project presented a number of its findings at the recent European Respiratory Society Congress in Munich, Germany. U-BIOPRED highlights from the event include:
- initial evidence of distinct groups of patients in the U-BIOPRED study;
- an association between certain genetic variants and clinical traits;
- using an electronic nose to analyse the exhaled breath of children with asthma could identify different subtypes of asthma in children;
- the flu virus appears to exacerbate asthma more than the cold virus.
Links to these abstracts and more can be found on U-BIOPRED’s Twitter feed. Patients have been key in driving U-BIOPRED’s successes, and U-BIOPRED patient experts were also in attendance at the ERS Congress. One patient, Martine Puhl, recorded her experiences in two reports on the opening ceremony and the U-BIOPRED symposium.
IMI’s severe asthma project U-BIOPRED has won a best practice award in the research and drug discovery category at the Bio-IT World Conference and Expo in the US.### The award highlights how U-BIOPRED has successfully used the tranSMART platform to integrate and analyse different types of data from diverse sources, and enable the secure sharing of data among over 30 project partners. U-BIOPRED is working to identify different types of severe asthma to ensure patients receive the right treatments. The project is using the tranSMART platform for its knowledge management needs; tranSMART is in turn being further developed by the IMI project eTRIKS for use by IMI and other projects.
Set up in 2003, the Bio-IT World awards recognise cutting-edge approaches to the use of information technology to advance basic biomedical research, drug discovery, and clinical trials.
- Watch a video of U-BIOPRED scientist Yannis Pandis explaining knowledge management in the project.
IMI’s U-BIOPRED project has used an electronic nose platform to identify four clusters of severe asthma patients based on the pattern of molecules in their breath.### The findings, presented at the European Respiratory Society’s Annual Congress in Barcelona, represent a first step towards the project’s goal of identifying distinct subtypes of severe asthma based on the extensive biological characterisation of patients. Elsewhere at the congress, the project released results demonstrating that people with severe asthma are less controlled by treatment than those with mild asthma. According to the team, 55% of adults with severe asthma regularly took corticosteroids yet showed greater airway obstruction and continued to suffer from exacerbations and other severe symptoms.
Commenting on the findings, project coordinator Peter Sterk of the University of Amsterdam said: ‘The findings of both these studies take us one step closer to understanding more about severe asthma. In order for us to help improve the lives of patients, we need to make a full biological and clinical “fingerprint” of each patient, by embarking on a huge analysis of data including a wide-range of samples from CT scans, to sputum samples, analysis of a person’s genetics and results from bronchoscopies. The U-BIOPRED project is doing that and we are confident that it will take us one step closer to developing personalised treatment for this condition.’
IMI's U-BIOPRED project has achieved its goal of recruiting 1025 people (including almost 300 children) into its pan-European study on severe asthma. Severe asthma is notoriously difficult to treat, and the aim of U-BIOPRED is to find out why.### For their study, the researchers recruited different kinds of asthma patients, include non-smoking adults and children with severe and mild asthma and smokers with severe asthma, as well as small children with wheezing, and healthy adults. The study participants have provided blood and tissue samples, exhaled air samples, and reports of their symptoms. They have also undergone lung function tests and examinations of their airways. The researchers are now drawing on this data to build up a detailed picture (or ‘handprint’) of each individual’s condition. By comparing data from so many different people, the team hopes to identify groups of patients with similar handprints. These groups will allow researchers to define different kinds of severe asthma, paving the way towards personalised treatments for patients. 'We are now starting to perform analyses on the data,' explained project coordinator Peter Sterk of the University of Amsterdam. 'This is being done by a strong, collaborative effort – the most modern analytical and statistical technology is available and is being worked with during the interim analyses of the data'. Patients are heavily involved in the project; as well as taking part in the clinical study, they have provided advice on ethical, scientific, and communication issues, giving the patient's perspective throughout.
On 28 September IMI projects U-BIOPRED and PROactive and the European Lung Foundation will hold a special event for patients and the public.### IMI Executive Director Michel Goldman will open the event with a presentation on how Europe is responding to the needs of respiratory patients. Other talks will explain how patients and scientists are working together in the U-BIOPRED and PROactive projects and Marc Decramer, President of the European Respiratory Society, will discuss the roadmap for respiratory research in the years ahead. There will also be time for attendees to ask questions of some of Europe’s leading respiratory researchers. The event is part of the 2011 European Respiratory Society (ERS) Annual Congress in Amsterdam.
- For more information and to register, visit the event web page
Knowledge management is key to the success of many IMI projects, and the tranSMART system is proving a popular tool for this. TranSMART is a translational medicine platform based on open source software and data that was originally developed by Johnson & Johnson for its own projects.### However, it quickly became clear that the system could be extremely useful for other groups. Today, tranSMART is used by research consortia on both sides of the Atlantic. The first IMI project to use tranSMART was U-BIOPRED, which is using it to collate data on asthma and chronic obstructive pulmonary disease (COPD) from four different companies, for example. Eventually, U-BIOPRED partners will be able to access the data and use it to test new hypotheses. Other ongoing projects that are implementing or about to implement tranSMART are OncoTrack, SAFE-T and BT Cure; some of the 3rd Call projects are also planning to use the system. Looking to the future, the 4th Call topic eTRIKS (European Translational Information & Knowledge Management Services) will support efforts to take tranSMART to the next level.
Dutch student Marije Kootstra has been named as the winner of the U-BIOPRED asthma art contest. The winning painting can be seen on the U-BIOPRED website.### ‘Asthma plays an important role in my life,’ explains Marije, who is 17. In order to control her condition, she takes 10 medicines, sees a specialist regularly and has undergone a nose operation as well as other treatments. Yet despite these efforts, Marije’s asthma is still not fully under control; in poor weather, she cannot cycle to school and so misses classes. She has even been hospitalised following severe asthma attacks. Nevertheless, Marije remains hopeful for the future. ‘I hope that with the right medicines I can again get my asthma back under control,’ she says. Marije wins a trip for two to Amsterdam, where she will pick up her prize at the opening ceremony of the European Respiratory Society meeting in September. U-BIOPRED is working to speed up the development of new, more effective treatments for severe asthma. Patients are strongly represented in the project through the participation of six patients’ organisations.
IMI project U-BIOPRED has recruited the first of over 1 000 people into a major new study of severe asthma. U-BIOPRED researchers will draw on data from blood and tissue samples###, lung function tests, exhaled air samples and examinations of the airways, plus reports of people’s own experiences, to build up a detailed picture (or ‘handprint’) of each individual’s condition. By comparing data from hundreds of people, the team hopes to identify groups of patients with similar handprints. These groups will allow researchers to define different kinds of severe asthma, paving the way towards personalised treatments for patients. U-BIOPRED project coordinator Peter Sterk of the University of Amsterdam said that running such a study would have been “unthinkable” without IMI.
Work in the U-BIOPRED project has proven the value of data sharing by generating an important result in asthma research. Both GSK and Pfizer were working on a similar animal model of severe asthma, but when data from both companies was combined, it quickly became clear that the model would not be as useful as was hoped.### If they had continued working on their own, it would have taken the companies months to realise this. Data sharing in U-BIOPRED has since been given a further boost by the presence in the consortium of a new partner in the form of pharmaceutical company Centocor B.V., a member of the J&J group of companies. In addition to expertise, Centocor brings to the consortium a knowledge management system called TransMART.
Elsewhere, U-BIOPRED has published research in the journal Thorax that will help to clarify the diagnosis of severe asthma, something that will help doctors to manage these patients more effectively. The paper provides information on what clinicians should check for when considering classifying a patient as having severe asthma. Developing more individualised characterisations of severe asthma contributes to U-BIOPRED’s goal of redefining severe asthma and lays the foundation for personalised treatments for severe asthma sufferers.
Finally, as part of its efforts to connect patients with researchers and clinicians, U-BIOPRED has launched an Asthma Art Contest. Anyone with severe asthma can enter the competition, and all art forms are welcome.
‘Without IMI this would have never happened’ – an interview with U-BIOPRED’s Peter Sterk
U-BIOPRED was one of the first IMI projects to launch back in 2009. Now the project, which focused on severe asthma, is drawing to a close. In an interview with the IMI Programme Office, the project’s scientific coordinator, Peter Sterk of the University of Amsterdam, explains how the project has increased our understanding of severe asthma ###and how researchers are already using this knowledge in the development of new treatments. He also talks about how the project benefited from the involvement of patients, and how they put the concept of ‘big data’ into practice to achieve their ground-breaking results. You can also read about the project’s achievements and impacts on the U-BIOPRED factsheet on the IMI website. (September 2016)
ParticipantsShow participants on map
- Almirall SA, Barcelona, Spain
- Amgen, Brussels, Belgium
- Astrazeneca AB, Södertälje, Sweden
- Boehringer Ingelheim Internationalgmbh, Ingelheim, Germany
- Chiesi Farmaceutici S.A, Parma, Italy
- F. Hoffmann-La Roche AG, Basel, Switzerland
- Glaxosmithkline Research And Development LTD., Brentford, Middlesex, United Kingdom
- Janssen Biologics BV, Leiden, Netherlands
- Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, United States
- Novartis Pharma AG, Basel, Switzerland
- UCB Pharma SA, Brussels, Belgium
Universities, research organisations, public bodies, non-profit groups
- Academisch Medisch Centrum Bij De Universiteit Van Amsterdam, Amsterdam, Netherlands
- Centre National De La Recherche Scientifique Cnrs, Paris, France
- Fraunhofer Gesellschaft Zur Forderung Der Angewandten Forschung Ev, München, Germany
- Hvidovre Hospital, Hvidovre, Denmark
- Imperial College Of Science Technology And Medicine, London, United Kingdom
- International Primary Care Respiratory Group, Edinburgh, United Kingdom
- Karolinska Institutet, Stockholm, Sweden
- Kobenhavns Universitet, Copenhagen, Denmark
- Semmelweis Egyetem, Budapest, Hungary
- The University Of Manchester, Manchester, United Kingdom
- The University Of Nottingham, Nottingham, United Kingdom
- Umea Universitet, Umea, Sweden
- Universita Cattolica Del Sacro Cuore, Milan, Italy
- Universita Degli Studi Di Catania, Catania, Italy
- Universita Degli Studi Di Roma Tor Vergata, Rome, Italy
- Universitaet Bern, Bern, Switzerland
- Universite D'Aix Marseille, Marseille, France
- Universiteit Gent, Gent, Belgium
- Universitetet I Bergen, P.O. Box 7800, Bergen, Norway
- University Of Southampton, Southampton, United Kingdom
- Uniwersytet Jagiellonski, Krakow, Poland
Small and medium-sized enterprises (SMEs)
- Aerocrine AB, Solna, Sweden
- Biosci Consulting Bvba, Maasmechelen, Belgium
- Synairgen Research Ltd, Southampton, United Kingdom
- Asthma Uk Lbg, London, United Kingdom
- European Federation Of Asthma &Allergy Associations Ideell Forening, Brussels, Belgium
- European Lung Foundation, Sheffield, United Kingdom
- Lega ltaliana Anti Fumo, Catania, Italy
- Netherlands Asthma Foundation, Leusden, Netherlands
- Amc Medical Research BV, Amsterdam, Netherlands
- Centre Hospitalier Regional De Marseille Assistance Publique-Hopitaux Marseille, Marseille, France
- Nottingham University Hospitals Nhs Trust, Nottingham, United Kingdom
- University Hospital Of South Manchester Nhs Foundation Trust, Wythenshaw, United Kingdom
- University Hospitals Southampton Nhs Foundation Trust, Southampton, United Kingdom
Non EFPIA companies
- Philips Electronics Nederland BV, Eindhoven, Netherlands
|Name||IHI funding in €|
|Academisch Medisch Centrum Bij De Universiteit Van Amsterdam||1 708 837|
|Aerocrine AB||30 400|
|Asthma Uk Lbg||94 660|
|Biosci Consulting Bvba||605 700|
|Centre National De La Recherche Scientifique Cnrs||555 414|
|European Federation Of Asthma &Allergy Associations Ideell Forening||94 660|
|European Lung Foundation||118 660|
|Fraunhofer Gesellschaft Zur Forderung Der Angewandten Forschung Ev||587 555|
|Hvidovre Hospital||7 060|
|Imperial College Of Science Technology And Medicine||1 110 668|
|International Primary Care Respiratory Group||94 660|
|Karolinska Institutet||778 783|
|Kobenhavns Universitet||60 943|
|Lega ltaliana Anti Fumo||80 260|
|Netherlands Asthma Foundation||100 660|
|Semmelweis Egyetem||84 197|
|Synairgen Research Ltd||38 050|
|The University Of Manchester||515 433|
|The University Of Nottingham||41 012|
|Umea Universitet||75 002|
|Universita Cattolica Del Sacro Cuore||133 403|
|Universita Degli Studi Di Catania||216 780|
|Universita Degli Studi Di Roma Tor Vergata||96 226|
|Universitaet Bern||137 171|
|Universite D'Aix Marseille||99 960|
|Universiteit Gent||212 485|
|Universitetet I Bergen||63 767|
|University Of Southampton||966 335|
|Uniwersytet Jagiellonski||158 480|
|Name||Funding in €|
|Centre Hospitalier Regional De Marseille Assistance Publique-Hopitaux Marseille||89 314|
|Nottingham University Hospitals Nhs Trust||113 886|
|University Hospital Of South Manchester Nhs Foundation Trust||416 200|
|University Hospitals Southampton Nhs Foundation Trust||448 880|
|Total Cost||9 935 501|