Pulmonary Fibrosis

Background:

Interstitial Lung Diseases (ILDs) are a heterogeneous group of >200 different, rare diseases, which share the fate of progressive scarring and, ultimately, death. Two anti-fibrotic drugs have demonstrated to slow-down disease 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 behaviour (progressive fibrosis, appearance of comorbidities, etc.) and treatment response; (2) To integrate the biomarkers that most impact on prognosis and treatment response in diagnostic algorithms; and (3) To develop experimental models to study both the progression of pulmonary fibrosis and new potential treatments.

Methods:

We will extend, update and unify existing ILD cohorts (Spanish SEPAR ILD Reg, Observatory IPF.cat, CIBERES IPF and Familial ILD cohorts), including those with ILD as a sequel to COVID, in whom we 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); (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 are already 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 approaches are a unique opportunity to improve survival in these patients and efficiency of health-care resources.