WP1

COPD Phenotyping

Broad activities

  • Establishment of a WP management committee, an ethico-legal & safety board.
  • Development of a data sharing and knowledge management platform
  • Follow-up assessments to validate and assess the reproducibility of candidate biomarkers of exacerbation sub-phenotypes, muscle dysfunction and sub-phenotypes of disease progression such as ‘emphysema’ versus ‘small airway disease’.
  • Bio-statistical analysis to determine the replication of candidates from aim (iii) and modelling of patient sub-phenotypes.
  • Bio-resource: collection of patient samples to support phenotyping effort of WP1 and mechanistic studies in the other WPs.

WP2

Mechanisms, impact and therapeutic targeting of microbial and viral colonisation in COPD

Broad activities

Workstream A: How does bacterial and viral colonisation relate to abnormal innate and adaptive immunity and to clinical outcomes?
  • Phenotyping of innate and adaptive immune profile in BAL
  • Relationship of immune profile to bacterial and viral colonisation
  • Relationship of immune profile to clinical phenotype
  • Measurement of bacterial and viral clearance by inflammatory cells
Workstream B: Elucidation of the mechanisms of defective innate immune responses and identification of novel therapeutic targets.
  • Elucidation of mechanisms of defective macrophage phagocytosis of bacteria and apoptotic cells in COPD
  • Elucidation of mechanisms of defective neutrophil phagocytosis function in COPD
  • Normalisation of defective innate responses in both macrophages and neutrophils

WP3

Tissue repair and injury

Broad activities

  • Management
  • Identification of patients and validation/optimisation of methodology.
  • Workstream A: Oxidative stress as a driver of airway remodelling
  • Workstream B: Innate immune dysfunction of airway epithelial cells

WP4

Reducing the burden of COPD by targeting skeletal muscle mass and function. Targets and endpoints for drug development

Broad activities

  • Regulatory track
  • Pathway identification and validation track
  • Biomarker track