Personalised approach to antifungal treatment in chronic fungal lung disease

About the Project

Chronic and allergic pulmonary aspergillosis syndromes complicate asthma, COPD and bronchiectasis, leading to symptoms, admissions and mortality. Antifungal treatment with azoles is the mainstay of treatment, however response rates are suboptimal, eg 60% in CPA suggesting that concomitant patient of microbial factors may have an impact. Several phenotypes of allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA) exist, yet treatment recommendations are not individualised. Atopy, bronchiectasis, COPD, or concomitant infection may affect antifungal treatment response resulting in deterioration, hospital admissions and mortality. In addition, patients with chronic lung disease may not have the full criteria for diagnosis of ABPA or CPA, but may have evidence of Aspergillus lung colonisation; some evidence indicates that these patients have worse outcomes, however no treatment recommendation exists.

This project will explore the potential for a personalised approach to management of aspergillosis in chronic lung disease via 2 distinct workstreams.

Workstream 1: Real-world large scale data analysis: By accessing data from a large primary care database, this workstream will explore the effect of antifungal treatment on the outcomes of patients with chronic lung disease, when prescribed for indications outside well defined aspergillosis infection syndromes. The student will use advanced statistical methods and will be supported by supervisors experienced in such analyses.

Workstream 2: Prospective precision medicine trial: This workstream will explore the role of patient factors and biomarkers in the response to antifungal treatment in ABPA and CPA. Antifungals have a role in ABPA and CPA, although several phenotypes of these diseases exist, justifying the need for personalised treatment in these patients. A prospective trial of assessment of antifungal treatment response in patients with ABPA and CPA will be undertaken. The use of biomarkers such as aspergillus serology, FeNO, peripheral eosinophil count, volatile organic compounds will be explored as potential predictors of treatment response.

Eligibility

Candidates are expected to hold (or be about to obtain) a minimum upper second-class honours degree (or equivalent) in Medicine, Biology or a related area / subject. Candidates with a clinical background, such as in respiratory medicine or infectious disease, a laboratory background in microbiology or chemistry and/or with experience in mathematics or statistics are encouraged to apply.

How to Apply

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/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Infectious Diseases.

Equality, Diversity & 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 Website

Funding Notes

Applications are invited from self-funded students. This project has a Band 2 fee. Details of our different fee bands can be found on our website: View Website

References

Kosmidis C, Smith H, Mollett G, Harris C, Akili S, Bazaz R. Predictive factors for treatment response and mortality in chronic pulmonary aspergillosis. Mycoses. 2023 Nov;66(11):960-968. doi: 10.1111/myc.13641. Epub 2023 Aug 8. PMID: 37553558.

Sengupta A, Ray A, Upadhyay AD, Izumikawa K, Tashiro M, Kimura Y, Bongomin F, Su X, Maitre T, Cadranel J, de Oliveira VF, Iqbal N, Irfan M, Uzunhan Y, Aguilar-Company J, Munteanu O, Beardsley J, Furuuchi K, Takazono T, Ito A, Kosmidis C, Denning DW. Mortality in chronic pulmonary aspergillosis: a systematic review and individual patient data meta-analysis. Lancet Infect Dis. 2025 Mar;25(3):312-324. doi: 10.1016/S1473-3099(24)00567-X. Epub 2024 Nov 29. Erratum in: Lancet Infect Dis. 2025 Mar;25(3):e137. doi: 10.1016/S1473-3099(25)00098-2. PMID: 39617023.