Caratteristiche cliniche, molecolari e radiologiche nella patogenesi e progressione delle interstiziopatie polmonari

Interstitial lung diseases (ILDs) represent a broad and heterogeneous group of respiratory disorders characterized by various degrees of inflammation and fibrosis. More than 200 entities have been described; some are rare and “orphans.” Moreover, the prevalence, incidence, and mortality rates are still unknown for specific entities. Some patients may remain stable or improve over time. Conversely, about one-third of all ILDs may display progressive scarring of the lung parenchyma, thus becoming debilitating, showing poor response to conventional treatment, and leading to early mortality (these forms are called progressive ILD [PF-ILD]). An update of the guideline document on ‘’Idiopathic Pulmonary Fibrosis and Progressive Pulmonary Fibrosis in Adults” was published in May 2022. This guideline provides clinicians with evidence-based recommendations on diagnosing and managing IPF and PF-ILD. The new guideline highlights the importance of identifying factors that may predict the evolution toward a “progressive” phenotype. So far, several potential predictive biomarkers for PF-ILD have been studied. Nintedanib, an intracellular tyrosine kinase inhibitor (TKI) with antifibrotic properties, was one of the first drugs approved for the treatment of idiopathic pulmonary fibrosis (IPF) and more recently has also been approved for use in PF-ILD and in ILD secondary to systemic scleroderma (SSc). The availability of efficacious therapy has exponentially increased the interest of the respiratory community in these forms of ILD. It has made more urgent the need for reliable predictors of disease outcomes. My Ph.D. project focused on three lines of research: firstly, I investigated the role of monocytes in predicting disease course in patients with fibrotic ILD. I have shown that serum levels of monocytes may identify a subset of patients more likely to progress. As part of this project, I also focused on the histology of fibrotic ILD and suggested a possible predictive role of micro honeycombing in predicting patient survival. Secondly, I looked at the role of the diaphragm and spinal muscle mass in disease progression and survival in ILD. I found that the prevalence of loss of muscle mass was around 40% at diagnosis in patients with IPF and about 30% in those with ILD secondary to connective tissue disease. The last part of my project focused on basic science. I focused on the role of Hyaluronic Acid (HA) in reducing the production of galectin-3 (Gal-3), transforming growth factor (TGF-b), and collagen (Col-I) in a cellular in vitro model of pulmonary fibrosis. HA, a component of the extracellular matrix with water-retaining properties, acts as a regulator of fluid balance in the lung and has been widely used to treat eye, joint, and skin disorders. We have shown that HA might prevent and treat lung fibrosis by reducing Gal-3 production by stimulated fibroblasts. Finally, I performed one study, with others still ongoing, on Covid-19 pneumonia. Specifically, I looked at serum eosinophil levels as a marker of pulmonary sequelae following SARS CoV2 infection and their rise during hospitalization seems to be correlated with abnormal wound healing of the lung. Notably, we found persistent lung abnormalities in only a small minority of patients with COVID-19 pneumonia at the 6- and 12-month follow-up. These patients are more frequently older males and active smokers at the time of hospitalization. The role of eosinophils as predictors of persistent disease following COVID-19 pneumonia needs to be further investigated.