UNICORN (Unified Cohorts Research Network): Disaggregating asthma

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Asthma and allergies are the most common chronic diseases in childhood and adolescence. They usually start before school age and are responsible for a heavy burden of ill health, including premature death. It is increasingly recognised that asthma is an umbrella term covering several different diseases, which creates a barrier to delivering personalised treatments (i.e., treatments tailored to the individual patient). We propose an innovative scientific research program (UNICORN, Unified Cohorts Research Network), which embraces a team-science approach to understand heterogeneity of asthma and allergies. We have many ways of researching illnesses: (1) studies of children from their birth (birth cohorts); (2) studies of patients with severe disease; (3) randomised controlled trials (RCTs, where patients are allocated by chance to receive one of several treatments). We propose that we can begin to understand the variation seen in common diseases such as asthma and allergies if we look at all these together. This will help us to predict who will respond best to different treatments. Such a collaborative approach is currently prevented by the lack of a system to jointly manage and analyse the data from different studies. We will form an alliance between the STELAR consortium of 5 UK birth cohort studies aimed at studying asthma and allergic diseases (in total more than 15,000 participants who have been followed from before birth to adulthood) and clinical studies which recruited large numbers of patients with severe asthma (more than 1000). Our birth cohorts measured environmental exposures before the onset of the disease and contain detailed information on the development of asthma and allergies from early childhood to adulthood. In UNICORN, these will be supplemented by the information collected in studies of patients with severe asthma. These studies measure additional clinical markers (for example, more detailed lung function), and collect biological samples which are not available in birth cohorts (such as sputum, nasal secretions, and airway biopsies). These samples are needed to understand the mechanisms underlying different types of asthma. RCTs provide further important and accurate information about responses to treatment. Thus, birth cohorts, patient cohorts, and RCTs are complementary, and combining them by linking the data appropriately will provide invaluable insights into the mechanisms of different asthma subtypes, markers to predict future risk, and individual responses to treatment. UNICORN builds on substantial prior investments in the science and infrastructure underpinning asthma research. We will pull together and build upon several earlier investments in data management platforms and in tools that have been created to help data harmonisation and joint analysis. In Workstream 1, we will develop efficient software solutions to integrate, manage, harmonise and analyse different types of studies together. Combining detailed research observations in cohort studies, with less thorough, but more frequent, information from routine clinical records, holds huge potential. In Workstream 2, we will enrich detailed information collected from before birth to early adulthood in STELAR birth cohorts with data from primary care and hospital records. Our programme of work will create conditions that enable collaborative research. The shared digital environment will provide our team of scientists with tools to efficiently analyse existing and newly collected data and help interpretation of findings, and rapid implementation for patient benefit. In Workstream 3, we will use asthma as exemplar to develop and apply methods to jointly analyse data from different settings. Our findings will underpin new trials of asthma and allergy prevention and treatment, personalised for specific subtypes, and may help identify novel targets for the discovery of subtype-specific treatments required for personalised medicine.