The role of environmental factors in cystic fibrosis disease progression

PROJECT SUMMARY The projects will focus on analyses of the CF Registry data in relation to environmental factors, including air pollution, to rigorously quantify possible causative interactions, with a particular focus on respiratory disease. As for many projects conducted within SAHSU, this will require the use of detailed geographical information to enable accurate exposure assignment for all individuals with CF in order to conduct detailed analyses & estimate each individual's exposure to a range of environmental factors known or suspected to influence disease progression.
Data protection and information governance are key priorities for SAHSU & we have experience in assigning environmental exposures to address or postcode level working with a number of UK cohorts including ALSPAC, UK Biobank and the 1946 birth cohort. A careful assessment of the most appropriate datasets for individual exposure to a range of environmental factors will be conducted.
The projects will involve conducting a systematic review and meta-analysis as well as using specific epidemiological tools for small-area studies and environmental exposure analyses, such as time-series analyses, geographical information systems (GIS) and statistical methods. The projects will be conducted in close collaboration with the UK CF Trust and the successful candidates will be encouraged to build on preliminary collaborations established in the UK and internationally.
EXPECTED OUTCOMES - Successful candidates will be expected to produce excellent academic research to be presented at national and international conferences, and published in peer-reviewed journals. They will actively engage with the community of scientists and clinicians involved but also, importantly, with the CF Trust and the community of patients and their relatives, including through active participation at the Annual Meeting of the CF Trust. Translating research results into useful advice for individuals with CF will be the ultimate outcome of these projects.
BACKGROUND - CF is a life-limiting inherited condition caused by a faulty gene that controls the movement of salt and water in and out of cells. It causes mucus to gather in the lungs and digestive system and creates a range of challenging problems with lung function and the digestive system, and chronic bacterial infections. Estimates of disease incidence are around 1 in 3,000 live births in northern Europeans, with Ireland having the highest incidence at 1 in 1,400 live births. Incidence is estimated to 1 in 4,000 to 10,000 in Latin Americans and 1 in 15,000 to 20,000 in African Americans, with even lower incidence rates in people of Asian background. In addition, millions of asymptomatic people carry the faulty gene (2.5 million in the UK, corresponding to 1 in 25 individuals). Each week five babies are born with CF, and two CF patients die. More than half of the CF population in the UK will now live past. Improved care & treatments continue to improve the survival and quality of life of individuals with CF. There is currently no cure for CF but many treatments are available to manage it, including physiotherapy, exercise, medication and nutrition. Marked variations still exist in CF health outcomes. The clinical course of CF for any individual with CF is determined by the interaction of genetic factors (including CFTR and modifier genes) and non-genetic factors. The latter include the physical environment (e.g. environmental tobacco smoke, outdoor pollution, and pathogenic microorganisms), the sociodemographic, cultural, and family context (which mediates stress, social support, and disease self-management skills), & variations in delivery & acceptance of healthcare treatments. Ongoing efforts are currently focusing on genetic factors influencing disease progression. Although a better understanding of non-genetic factors could provide a more immediate way of improving disease outcomes, this area of research is currently neglected