Understanding the host-environmental interactions across the lifespan determining lung function trajectories and COPD

Introduction

Chronic Obstructive Pulmonary Disease (COPD) has been traditionally understood as a self-inflicted disease caused by tobacco smoking occurring in old individuals. Over the past few years, however, our group and others have proposed that the pathogenesis of COPD goes beyond smoking, and that there is a range of lung function trajectories through life (trajectome).

Lung Function Trajectories

Some of these trajectories have roots in early life and can lead to COPD, cardiovascular and metabolic morbidity, as well as premature death, while others are associated with healthy ageing. Here I propose that detrimental gene (G) and environment (E) interactions occurring early in life (T) constitute a ‘first injury hit’ that alters the normal lung developmental program and modifies the pace of normal lung aging by reducing the resilience of the lungs to future GxExT interactions.

Lifelong Interactions

Accordingly, lifelong GxExT interactions determine the individual trajectome and, eventually, the occurrence of COPD and associated multimorbidity. PredictCOPD aims to identify the interactions and mechanisms that determine which individuals will develop COPD and multimorbidity at some point in their life.

Specific Aims

The specific aims are:

1. To identify the lifelong environmental and host risk factors associated with the trajectome, COPD, and multimorbidity.
2. To use a novel liquid biopsy method to identify biological factors driving the trajectome, COPD, and multimorbidity.
3. To identify clinically relevant preventive and/or early therapeutic targets integrating the results from aims 1 and 2 with novel analytical approaches.
4. To validate findings both in vitro and in other available cohorts.

Project Resources

The project will leverage several available population and COPD patient studies with available clinical data and biological samples.

Potential Impact

The results of PredictCOPD have the potential to:

1. Promote healthy ageing by preventing and eventually eradicating COPD and associated multimorbidity.
2. Change COPD treatment from palliative to causal.