integrating Metabolism ENvironment and Diet for sub-phenotyping of obstructive lung disease (iMEND)

Bakgrund:

Obstructive lung disease is an increasing global health problem of pandemic proportions, with COPD alone affecting >10% of the population. COPD and asthma are umbrella diagnoses that are caused by a multitude of etiologies, involving a complex interplay of metabolic, dietary and environmental factors. This project will identify molecular markers for disease sub-phenotyping in order to develop a standardized clinical assay for stratification of patients with obstructive lung disease.

Målsättning:

The primary study aim is to examine the molecular associations between metabolism, diet, and environmental exposure in relation to incidence of respiratory disease. This project will examine three primary hypotheses: 1) dietary fat speciation is associated with the onset and severity of obstructive lung disease, 2) the combination of metabolism, diet and environmental exposure discriminates the non-genetic component of obstructive lung disease, and 3) molecular markers of obstructive lung disease can be used in stratified medicine to identify disease sub-phenotypes.

Arbetsplan:

We will identify molecular markers of asthma and COPD using metabolomics-based approaches. The effects of dietary omega-6 and omega-3 fatty acids upon the onset and severity of lung disease will be determined using tissue culture systems and murine models. Focus will be placed upon determining the production and function of the lipid mediator products of both omega-6 and omega-3 fatty acids.

An exposome-based approach will be used to determine the relationship between environmental exposure and onset of respiratory disease. Finally, molecular markers will be combined from these 3 components to develop an Analysome for identifying disease sub-phenotypes. This molecular panel will be validated in an independent cohort of asthmatics and COPD.

Betydelse:

This project will determine the contribution of dietary fat and environmental exposure to the onset and severity of obstructive lung disease. This information will be combined with metabolic profiles to identify a discrete panel of molecular markers of disease – the Analysome. Results will assist in generating sub-phenotype specific diagnostic and prognostic tools to be applied in the clinic, as well as stratify patients for treatment strategies (e.g., biologics).

This will enable clinicians to intervene at earlier stages, improve treatment targeting with biologics, and reduce costs as well as improve patient quality of life.