Title: Investigating the role of specialist pro-resolving mediators in viral exacerbations of chronic obstructive pulmonary disease
Funder: The Academy of Medical Sciences

Abstract: Chronic obstructive lung disease (COPD) is characterised by airway inflammation. COPD exacerbations are commonly triggered by respiratory viral infections. Promoting resolution of during COPD exacerbations is a novel therapeutic strategy for reducing exacerbation severity and preventing disease progression. The aim of this study will be to define the expression of specialist pro-resolving mediators in viral induced COPD exacerbations and to investigate the relationship between specialist pro-resolving mediators and with inflammatory and symptomatic parameters. The objectives are; 1.To define how specialist pro-resolving mediators change during COPD exacerbations and the association between exacerbation triggers and their relationship to clinical features. 2.To investigate how viral infection leads to aberrant resolution of inflammation in bronchial epithelial cells (BECS) and alveolar macrophages (AMs) from COPD patients compared to healthy subjects which could lead to persistent airway inflammation. 3.To assess whether exogenous specialist resolving mediators e.g. Resolvin D1 or Protectin D1 can be used to manipulate the inflammatory response to viral infection in BECs and alveolar macrophages from COPD patients and healthy subjects forming the basis of a potential new therapeutic strategy for COPD exacerbations Longitudinal analysis of specialist resolving mediators during exacerbations will be performed utilising the London COPD cohort who are trained in exacerbation reporting. Alveolar macrophages and bronchial epithelial cells will be infected with rhinovirus ex-vivo to investigate SPM response to rhinovirus infection in COPD and healthy subjects. Defining the role of specialist pro-resolving mediators in COPD exacerbations will identify therapeutic targets to improve exacerbation recovery and prevent disease progression

Lay abstract: Chronic obstructive pulmonary disease (COPD) is a lung condition which causes the airways to become narrow and inflamed making it difficult to breathe. People who have COPD often have flare-ups called ‘exacerbations’ where their symptoms become a lot worse. About half of these events are caused by viruses such as the common cold virus which cause more inflammation in the lungs and further airway narrowing. Sometimes people take a long time to recover from exacerbations which causes their disease to deteriorate more rapidly. It is becoming increasingly apparent that the way that the body heals following a viral infection is an active process. This study will investigate whether there is a problem with the healing process within the airways following a viral infection in COPD. This study will focus on some signalling molecules called specialist pro-resolving mediators (SPMs) that reduce inflammation and help the body to heal following an infection. First, I will examine how SPMs are produced by the body during a COPD flare-up by taking blood samples and phlegm from COPD patients during these flare-ups. Then I will infect airway cells from COPD patients and healthy subjects with the common cold virus to examine whether there is a difference in the way that COPD airway cells produce these SPMs. Finally, I will assess whether adding SPMs to airway cells reduces inflammation in airway cells. This could lead to new treatments to reduce inflammation in the airways, improve recovery from exacerbations in COPD and prevent disease progression.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RESPIRATORY