Unravelling the Role of Aspergillus in Chronic Airway Disease Exacerbations and Disease Progression

Website The University of Manchester

Details

Background: Exacerbations are a major health burden of chronic airway disease such as COPD or bronchiectasis. While bacterial and viral infections are known to play a part, the role of fungal organisms such as Aspergillus is not understood, despite their frequent isolation from sputum during exacerbations and steady state. A subset of COPD patients develops invasive or chronic pulmonary aspergillosis, but the risk factors and strategies for early detection are not defined. In addition, patients with evidence of Aspergillus colonisation have more severe disease, but is not known whether this is a contributor to the decline or a bystander.

Objectives: The project aims to explore the role of Aspergillus in steady state and exacerbations of chronic lung disease. Objectives are:

– to determine prevalence and risk factors for development of invasive or chronic aspergillosis by retrospective review of patient cohorts

– to evaluate the role of biomarkers in sputum and serum for early detection of aspergillosis in a prospective study of COPD admissions.

Methods:

Workstream 1: Retrospective review of medical notes of patients admitted with an exacerbation or followed in secondary care. Clinical, laboratory and demographic information will be extracted, along with outcome data including aspergillosis diagnoses. Multivariable and survival analyses will be performed.

Workstream 2: Prospective recruitment of patients presenting with an exacerbation or in steady state. Relevant fungal biomarkers and immunophenotyping will be performed and outcomes recorded.

Expected Outcomes:

This project is expected to define the prevalence, risk factors and outcomes of aspergillosis in chronic airways disease, and clarify whether Aspergillus represents clinically significant disease, a marker of severity or a contributor to exacerbations and decline. It will assess sputum and serum biomarkers for earlier detection, identify patients who may benefit from targeted surveillance, and provide evidence to inform future diagnostic pathways, interventional studies and personalised management strategies.

Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in Medicine, Biology or a related area / subject. Candidates with a clinical background and an interest in respiratory medicine, infection, mycology or microbiology are encouraged to apply.  

Eligibility  

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.  

 

Before you Apply  

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.   

How to Apply  

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Medical Mycology Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester  

If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk   

Equality, Diversity and Inclusion   

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester 

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/ 

References

Kosmidis C, Hashad R, Mathioudakis AG, McCahery T, Richardson MD, Vestbo J. Impact of self-reported environmental mould exposure on COPD outcomes. Pulmonology. 2023 Sep-Oct;29(5):375-384.
Mathioudakis AG, Janssens W, Sivapalan P, Singanayagam A, Dransfield MT, Jensen JU, Vestbo J. Acute exacerbations of chronic obstructive pulmonary disease: In search of diagnostic biomarkers and treatable traits. Thorax 2020; 75(6):520-527.
Bertuzzi, M., Howell, G., Thomson, D., Fortune-Grant, R., Möslinger, A., Dancer, P., Van Rhijn, N., Motsi, N., Codling, A., & Bignell, E. (2024). Epithelial uptake leads to fungal killing in vivo and is aberrant in COPD-derived epithelial cells. iScience, 27(6), Article 109939.

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