PhD project title

Use of sputum rheology to predict disease progression and efficacy of treatment in people with cystic fibrosis (PWCF)

Outline description, including interdisciplinary, intersectoral and international dimensions 

Outline: In PWCF, sputum bacterial load is associated with increased airway inflammation and poor clinical outcomes, especially in those patients with high bacterial load. Moreover, patients frequently have flare-ups of their condition (pulmonary exacerbations) which result in a permanent loss of lung function and are a significant cause of morbidity and mortality. Sputum rheological properties may predict disease progression and assess the efficacy of treatment. The aim of this project will be to determine how rheological profile in sputum changes with age/disease severity and between clinically stable disease and pulmonary exacerbation.

A longitudinal, observation study will be performed which will recruit PWCF across a range of ages and disease severity. Sputum samples will be collected when patients are clinically stable as well as at the start, during and end of intravenous antibiotic treatment for pulmonary exacerbations. Bacterial abundance will be measured by quantitative real time PCR with inflammatory biomarkers such as neutrophil elastase measured using immunoassays. This approach will be complemented by next generation sequencing (Illumina) to analyse overall microbiota community richness and diversity. Dynamic rheology parameters including sputum linear (elastic and viscous moduli, G’ and G”, respectively) and non-linear (critical stress s_c) properties and sputum tack (ratio of G’’/G’²) will be measured. Demographic data (age, sex), clinical measures (lung function [FEV₁] and serum inflammatory markers), and details of therapy will be recorded from patient notes. Disease severity will be assessed by nutritional status, pancreatic status and lung function. A range of statistical analysis methodologies including principal components analysis will be used to determine the relationship between rheological profile, clinical status and microbial load/community composition.

This interdisciplinary project, which will utilise expertise across a range of disciplines including pharmacy, microbiology, clinical medicine and physical science, will provide extensive training in molecular biology, sputum rheology and bioinformatic data analysis as part of an internationally renowned research team.

Key words/descriptors

Cystic fibrosis, infection, sputum rheology, microbiota, inflammation

Fit to CITI-GENS theme(s)

Life Sciences: Advanced clinical healthcare i-REACH

Supervisor Information

First Supervisor: Professor Michael Tunney                                                      School: Pharmacy

Second Supervisor: Professor Stuart Elborn/Dr Damian Downey                 School: MDBS

Third Supervisor: Dr Jeremy Patarin                                                                   Company: Rheonova

Name of non-HEI partner(s)

Contribution of non-HEI partner(s) to the project:

Costs associated with rheological assessment of samples will be funded by Rheonova. Jeremy Patarin, CEO/PhD, and Matthieu Robert de Saint Vincent, PhD, Principal Scientist, will be in charge of the project supervision. One PhD student is already supervised in the company.

Partner Profile   

Rheonova is based in Grenoble, the Medtech city in France. Expertise in our team bridges fluid mechanics, engineering and biomedical science. Our five-patent-protected technique is designed to assess treatment efficacy and disease progression and is currently commercialised for clinical trials and academic projects. Phase 1 and Phase 2a clinical trials demonstrate the reproducibility and the robustness of our biomarkers based on mucus rheological properties, and also their relationship with biomarkers of inflammation in sputum. The CE label was granted in March 2019 for medical use to assess the rheological properties of sputum. The device Rheomuco provides a unique monitoring test based on the rheology of lung secretions. Rheonova takes part in research collaborations in France, Belgium, UK, Switzerland, Japan, China and USA.

The academic team at Queen’s and Rheonova have undertaken several pilot studies with results presented at the European Cystic Fibrosis Conference in 2019.

Rheonova are willing to host a placement of a minimum of 1-3 weeks but the placement is likely to be much longer than this to enable training of the student in use of the rheological analysis system and processing samples.