B3947 - A deep clinical phenotyping study of a group of participants on a low lung function trajectory - 16/12/2021

B number: 
Principal applicant name: 
George Nava | University of Bristol; Academic Respiratory Unit, Southmead Hospital; NIHR-funded position (UK)
Dr James Dodd, Dr Raquel Granell, Professor Nicholas Timpson
Title of project: 
A deep clinical phenotyping study of a group of participants on a low lung function trajectory.
Proposal summary: 

Chronic lung diseases such as Chronic Obstructive Pulmonary Disease (COPD) are incurable but potentially preventable. Studies in cohorts such as ALSPAC have identified that everyone’s lung capacity increases in childhood, peaks in their early 20s and declines from the age of 30. Some groups never reach a normal peak, and some decline more quickly than others. Those on low lung function trajectories are at higher risk of developing lung diseases, diseases of other organs and dying younger. The reasons that these different trajectories exist are not fully understood. Without addressing this question, we cannot improve outcomes for patients with poor lung health and reduce the burden of chronic lung disease. This project aims to improve this understanding and identify potential targets for future interventions.

We will undertake a series of detailed assessments on a small group of ALSPAC Generation 1 participants to look for evidence of early lung disease. We will compare those on a low lung function trajectory with those on a normal one. The assessment will include an interview with a respiratory doctor, breathing tests and a state-of-the-art scan of the lungs at the University of Sheffield, which is a safe new technique of looking in detail at the structure and function of the lungs. This will complement the lung function tests that are aiming to collect data for >4000 participants in the Clinic at 30.

This study will have a range of applications and create future research opportunities to improve our understanding of normal and abnormal lung function development and finding ways of improving everyone’s lung health.

Impact of research: 
There are a range of potential impacts of this research. Firstly, this research aims to address the issue the need to prevent the development of significant respiratory disease. Trends in across all of healthcare are moving towards early recognition and prevention of medical conditions. Millions of people suffer and die from respiratory diseases each year. Many chronic diseases remain subclinical for years, however once the symptoms emerge, the pathology is irreversible and advanced. This research will contribute to our understanding of the pathogenesis of lung disease and contribute to the search for biomarkers of early disease that could form the focus of interventions to prevent or limit disease progression. This could have significant impacts to populations across the world. For the ALSPAC G1 participants specifically, it is possible that we will identify undiagnosed respiratory disease, such as uncontrolled asthma, that we will be able to recommend management in line with current NHS treatment pathways. Furthermore, if aligned research is able to identify new interventions or treatments, then these participants would represent an ideal group to offer these to. For our research team and Bristol University as a whole, it will provide a deeper understanding of the subjects of current and future lung function trajectory studies. This could both enhance the ability to interpret gained from these studies, but it will also provide a wealth of legacy data from which future studies can be design. It will also act as pilot data from which a larger study could be expanded. In addition, we are currently in discussions with the POLARIS (Pulmonary, Lung and Respiratory Imaging Sheffield) research team at the University of Sheffield about developing the capabilities to perform hyperpolarised xenon-129 imaging in Bristol. This will be the first time that a study from Bristol has employed this exciting technology and this experience will strengthen future applications to bring this technique to our university. For other researchers in the field, it will be the first time that a birth cohort has had deep clinical phenotyping or cross-sectional imaging of the lungs at the critical timepoint in lung development. It will contribute to international collaborations such as CADSET and may help to mould research across other cohorts.
Date proposal received: 
Tuesday, 7 December, 2021
Date proposal approved: 
Wednesday, 8 December, 2021
Epidemiology, Respiratory - asthma, Medical imaging, Clinical endotyping and phenotyping, Ageing, Equipment - MRI, Environment - enviromental exposure, pollution, Lung function