Approved Research

Determinants of lung fibrosis development and progression in the UK Biobank cohort

Lay summary

Idiopathic pulmonary fibrosis (IPF) is a lung disease where the ability of the lungs to allow entry of oxygen into the blood is impaired.  No cure is available, and the disease proves fatal, on average 2-4 years after diagnosis.  Research has suggested that one trigger for these structural changes may be repeated stress to the lung lining, a source of which could be air pollution.  A small number of studies have shown that increased levels of air pollution exposure are associated with a greater risk of developing IPF, and worsening of existing IPF, but findings are inconsistent because of the relatively rare incidence of IPF and difficulties in determining pollution exposure.  Based on understanding of how air pollution affects our lungs the cells of our lungs, it is indeed feasible that air pollution exposure may cause IPF, but we do not understand why some individuals may be more at risk than others.

One possible underlying factor may involve telomeres - structures which protect our DNA, but with age become shorter and less effective.  Telomeres have been suggested to be shorter in IPF, and may also be shortened by stress to cells.  In the whole UK Biobank cohort, there has, perhaps surprisingly, been found to be no association between air pollution exposure and telomere length, but we hypothesise the air pollution exposure may shorten telomeres in a section of the population whose genes render them susceptible, and this may increase the risk of developing IPF.

In this 3-year project, we aim to:

1. Determine whether exposure to air pollution is associated with altered telomere length in a way which is different between individuals with IPF and those who do not have IPF;
2. Determine whether genetic factors associated with maintenance of telomere length or response to air pollution may underlie these differences;
3. Investigate how the observed associations with air pollution might be further influenced by factors relating to lifestyle;
4. Study whether other sources of exposure, such as workplace of domestic, may also be important

The results of this study will help us to understand more about how air pollution exposure might be involved in the development of IPF, as well as improving our knowledge about the processes involved.  By studying the role of genetic factors alongside exposures, it may help us identify those most at risk, and thus who would most benefit from interventions to reduce their risk of disease.