Detection and diagnosis of lung phenotypes in severe pneumonia
Summary
Pneumonia is the leading infectious disease killer worldwide, responsible for an estimated 2.5 million deaths a year. It is one of the major drivers of antimicrobial use in hospitals, raising the risk of antimicrobial resistance.
One of the major diagnostic challenges is distinguishing pneumonia from sterile lung inflammation, and determining which patients would benefit from antimicrobials.
Distinguishing sterile inflammation from infection is challenging because the clinical picture does not map neatly onto the biological findings in the lungs. My group has recently identified distinct endotypes in severe pneumonia (termed ‘pneumotypes (Pn)’). These ‘pneumotypes’ are underpinned by changes in gene expression profile, frequency of immune cell types and levels of inflammatory proteins in the lungs, that are not represented in the peripheral blood.
Despite similar severity of illness at onset, each pneumotype is associated with distinct outcomes and different patterns of microorganisms. Being able to identify the pneumotype and microorganisms present would allow for trials of stratified immunomodulatory therapy and targeted antimicrobials.
Project aims
The aim of this project is to validate the findings from my original derivation cohort. Using lung samples from patients with clinically suspected pneumonia, RNA sequencing, multi-dimensional flow cytometry and cytokine assays will be used to identify the pneumotypes.
The second step will be to develop a diagnostic test based on host transcriptional responses and integrate this with our existing pathogen-focussed molecular diagnostic.
Finally, we will develop a diagnostic-informed clinical decision tree for testing in subsequent stratified randomised controlled trials in partnership with the industrial partner EDX Medical.
Contact details
Dr Andrew Conway Morris - ac926@cam.ac.uk
Opportunities
This project is open to applicants who want to do a:
- PhD