COPD-PARASOL-ILD

Chronic obstructive pulmonary disease (COPD) and fibrotic interstitial lung disease (ILD) are two chronic lung conditions that despite having common risk factors (smoking and age), and overlapping mechanisms, have starkly different clinical presentations. COPD is characterised by slow progressive loss of lung function while fibrotic ILD patients tend to experience more rapid decline in lung function. Moreover, a hallmark of COPD is loss of lung tissue due to destruction of the alveolar wall (emphysema), whereas in fibrotic ILD increased tissue mass by excessive production of extracellular matrix causes alveolar destruction. Both COPD and fibrotic ILD are associated with a high burden of disease and a high mortality and there are currently no curative treatments for either.

Diagnosis and treatment of these lung diseases currently is too late and too generic. A more personalized approach could optimize treatment. For COPD and ILD the pathobiology underlying the diseases differs amongst individuals and depends on the phase (early/late) of disease. A better understanding of processes leading from health to disease and to progression of disease would enable a more targeted approach for treatment.

For prevention of lung disease, there is mainly attention for prevention/quitting smoking. However, the effect of the exposome on lung health (all non-genetic factors that influence health) is becoming more clear and could potentially be intervened on as well.

The P4O2 consortium focuses on prevention and early treatment of lung disease, in a personalized manner. In this specific proposal we will arrange a follow-up visit in the SHERLOCK cohort. Furthermore, we will sample very small fluid particles from deep in the lungs. This will make it possible to perform proteomics analyses in lung fluid in ILD in a non-invasive way. We will also gather exposome data in the ILD cohort. These steps will add important data that will lead to new biomarkers that can be used to develop diagnostic tests and treatments. 

 Objectives:

We aim to:

1.     Deepen mechanistic understanding of molecular pathways in (progression of) COPD/ILD.

2.     Compare omics analyses between people without lung disease, those at high risk, and those with a diagnosis of ILD/COPD to discover biomarkers that can identify disease earlier.

3.     Deepen our understanding of the role of exposome in the development of ILD.

4.     Structure the new knowledge into conceptual models (adverse outcome pathways (AOPs)).

Hypotheses:

1. Use of omics analyses in ILD/COPD will deepen mechanistic understanding of molecular pathways and will lead to new diagnostic/therapeutic targets.
2. Comparison of omics analyses between people without, at high risk, and those with a diagnosis of ILD/COPD will lead to discovery of biomarkers that can identify people with the disease earlier. Those biomarkers can be used to find targets for prevention and treatment.
3. Exposome plays a role in the early development of COPD and ILD. This knowledge will lead to interventions on a personal level.
4. AOPs will help to accelerate transfer of knowledge and accelerate translation of that knowledge into clinical impact.