Chronic Obstructive Pulmonary Disease

Coordinator: Dr. Francisco de Borja García-Cosío Piqueras

From disease activity to lung function trajectories. 

From disease activity to lung function trajectories.

COPD is a highly prevalent disease affecting about 44 million people in Europe. In contrast to other major causes of death, its prevalence has been increasing in the past three decades. However, the natural history of COPD is still poorly understood, which limits the targets for intervention.

We have previously proposed that different levels of disease activity can lead to different natural histories of COPD, ranging from the asymptomatic patient with preserved lung function over time with little or no exacerbations, to the fragile symptomatic patient with accelerated loss of lung function and frequent exacerbations. Recently, investigators from COPD line at CIBERES have shown that there can be different lung function trajectories to develop COPD, this is in line with that hypothesis. The COPD line at CIBERES has previously set the conditions and started the study of patients at early stages of disease (Early COPD cohort), the most fragile stage (BIOMEPOC cohort), and mimicked in animal models both conditions, with the aim to study the different biomarkers (from the clinical, biological, microbiological or imaging domains) that could help to define disease activity. In parallel, we have demonstrated that changes in bronchial microbioma could be linked to disease activity and severity. These biomarkers could be used as treatable traits. COPD patients (mainly those with emphysema) have a higher risk of lung cancer than smokers without COPD, which can be due to different levels/types of biological activity, including abnormalities of lung mesenchymal cell (LMSC) function and immune response.

Objectives

The strategic objectives of the present project are:

1. To investigate the molecular basis and phenotypic expression (including non-pulmonary manifestations) of the different vital lung function trajectories described recently using both CIBERES cohorts and other international cohorts;
2. To identify and validate circulating biomarkers of these different trajectories;
3. To use these validated biomarkers to explore its clinical relevance, both in young subjects at risk of developing COPD and in patients with full-blown severe COPD
4. To understand whether specific aspects of the lung microbiome relate to disease manifestations and progression of the disease, and to define how changes in the bacterial community structure might predict exacerbation and lung function impairment, and
5. To use network medicine methods to study the relation between COPD, emphysema and lung cancer.