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(EPSRC DTP) Quantitative measurement and prediction of breath biomarkers using mathematical modelling.

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  • Full or part time
    Dr S Fowler
    Dr A Horsley
    Dr Maxim Wilkinson
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Sampling of volatile organic compounds (VOCs) in breath has the potential for real time detection and monitoring of a wide range of diseases. Over 1000 VOCs have been detected in breath to date and provide a rich dataset for a non-invasive source of biomarkers and information about the underlying metabolic state of the body.

Whilst increasingly large scale studies have been conducted in the last ten years, a clinically relevant breath VOC test has yet to be widely implemented. One reason for this is the number of confounding factors that must be accounted for during breath collection which makes reproducing published results difficult. Recent work on breath holding, oral versus nasal breathing (Sukul et al. 2014, 2017) and time of day (Wilkinson et al. 2019) has highlighted the need for standardised sampling protocols. Fractional exhaled nitric oxide levels, which are routinely used for asthma diagnosis, are highly effected by these physiological parameters and it is therefore likely that the level of breath VOCs is similarly impacted. These differences are of particular concern in respiratory diseases where the underlying lung physiology for an individual may change dramatically over time.

Further complicating the pursuit for biomarkers is the fact that field is predominantly moving away from the concept that there will be unique biomarkers for particular diseases. Instead, relative changes in the levels of common VOCs between groups are considered more likely for the majority of non-pathogenic diseases, highlighting the importance of profiling the variation in an individual’s breath profile. Whilst there has been previous interest in the variability of breath samples collected over a very short time frame (Phillips et al. 2014) further work is needed to investigate changes across hours and days. Additionally, seasonal changes in the levels of blood metabolites have been previously described (Gangwisch 2013) there is no current data on how breath volatiles are impacted potentially confounding long sampling campaigns.

This project aims to build on sampling expertise within the group to assess the impact of measure the impact of clinically relevant changes in lung physiology on exhaled VOCs and investigate the short and long term variation observed in an individual’s breath profile. These results will contribute to the optimisation of an existing lung function model which that uniquely incorporates realistic rendering of ventilation heterogeneity and gas washout in order to determine the factors governing exhaled VOC concentrations in health and in obstructive lung disease.


Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

On the online application form select PhD Medical/Clinical Science. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/)

Funding Notes

EPSRC DTP studentship with funding for a duration of 3.5 years to commence in September 2020. The studentship covers UK/EU tuition fees and an annual minimum stipend £15,285 per annum. Due to funding restrictions, the studentship is open to UK and EU nationals with 3 years residency in the UK.

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Gangwisch, J. E. (2013). Seasonal variation in metabolism: Evidence for the role of circannual rhythms in metabolism. Hypertension Research, 36, 392–393.

Phillips, C., Parthaláin, N. Mac, Syed, Y., Deganello, D., Claypole, T., & Lewis, K. (2014). Short-term intra-subject variation in exhaled volatile organic compounds (VOCs) in COPD patients and healthy controls and its effect on disease classification. Metabolites, 4, 300–318.

Sukul, P., Oertel, P., Kamysek, S., & Trefz, P. (2017). Oral or nasal breathing? Real-time effects of switching sampling route onto exhaled VOC concentrations. Journal of Breath Research, 11, 027101.

Sukul, P., Trefz, P., Schubert, J. K., & Miekisch, W. (2014). Immediate effects of breath holding maneuvers onto composition of exhaled breath. Journal of Breath Research, 8, 037102.

Wilkinson, M., Maidstone, R., Loudon, A., Blaikley, J., White, I. R., Singh, D., Ray, D., Goodacre, R., Fowler, S. J., & Durrington, H. J. (2019). Circadian rhythm of exhaled biomarkers in health and asthma. European Respiratory Journal, 15, 1901068.



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