Interrogation of the inflammasome to identify biomarkers of progressive interstitial lung disease

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Project Summary Interstitial lung disease (ILD) comprises a diverse group of diffuse parenchymal disorders with variable degrees of inflammation and fibrosis. Among the most common fibrosing ILDs with preceding inflammation are chronic hypersensitivity pneumonitis (CHP) and connective tissue disease-associated ILD (CTD-ILD). Substantial proportions of patients with CHP and CTD-ILD develop a progressive phenotype, which negative impacts survival and quality of life. Both conditions are generally treated with immunosuppressive therapy and may now also benefit from anti-fibrotic therapy. Because some patients will remain stable without therapy, there exists a critical need to more reliably identify CHP and CTD-ILD patients that will develop progressive ILD and define an optimal treatment strategy for such patients. This proposal seeks to address this gap in knowledge by employing a proteomic approach to identify inflammatory proteins predictive of progressive ILD and differential immunosuppressant response in patients with CHP and CTD-ILD. This proposal will lay the foundation for subsequent targeted protein investigation that will facilitate the development of biomarkers to guide clinical decision making in this patient population.