Integrating Molecular, Genomic, Morphology and Environmental Features to Improve Precision Diagnosis and Treatment in Interstitial Lung Diseases (PRECISION-ILD)

Study Purpose

Integrating Molecular, Genomic, Morphology and Environmental Features to Improve Precision Diagnosis and Treatment in Interstitial Lung Diseases (PRECISION-ILD) Background: Interstitial Lung Diseases (ILDs) are a heterogeneous group of >100 different, rare diseases, which share the fate of progressive scarring and, ultimately, death. Two anti-fibrotic drugs have demonstrated to slow-down fibrotic progression and steroids/immunosuppressants are commonly used for inflammatory-driven ILDs. However, patient's response to therapeutic options is variable and unpredictable. Similarly, setting a correct diagnosis is difficult in most cases, especially when patients are too sick for invasive procedures. Objectives:

• (1) To investigate the differences and commonalities in genetic, genomic and environmental exposures/lifestyle in fibrotic ILDs depending on the entity, disease behavior (progressive fibrosis) and treatment response; (2) To integrate the biomarkers that most impact on prognosis and treatment response in diagnostic algorithms; and (3) To explore the feasibility and cost of implementing a P4 strategy in clinical practice for fibrotic ILDs.

Methods: The investigators will extend, update and unify existing ILD cohorts (Spanish SEPAR ILD Reg, Observatory IPF.cat, CIBERES IPF and Familial ILD cohorts) in whom the researchers will:

• (1) record demographic, epidemiological, clinical, physiological and lung morphology (radiological +/- histological) information; (2) obtain genetic variation, telomere length, and serum protein markers; (3) investigate environmental exposures (including air-pollution), (4) apply to integrative analytical methods to identify endotypes, predictive biomarkers of disease trajectories, theragnostic biomarkers and new therapeutic targets.

Results

• (5) will be validated in other fibrotic ILD cohorts (e.g.EuILDRegistry, Mexican fibrotic ILD Registry).

Besides, the investigators will explore how to translate this P4 medicine approach in clinical practice;

• (6) implementing a predictive score for prognosis and improving the diagnostic approach through biological data to reduce invasive procedures, and (7) estimate educational requirement and potential health cost implications.

Viability:This project is viable because:

• (1) cohorts already exist and can be expanded and updated; (2) investigators have ample expertise in translational research and actively participate in ILD consortia; (3) required knowledge and methodology is already in being used by the consortium.

Clinical relevance: Due to the lethality, high social and economic burden of fibrotic ILDs, identifying the best diagnostic and therapeutic approach through preventive, personalized and precise measures is a unique opportunity to improve survival in these patients and efficiency of health-care resources.