Reclassificação de doenças pulmonares intersticiais fibróticas através de estudos ambientais e genéticos

The problem we are tackling concerns the challenges of diagnosing and predicting the disease behaviour in fibrotic interstitial lung disease (ILD). Several key observations underscore the urgency of addressing this issue: - Almost half (45%) of the lung transplants in our hospital centre from 2005 to 2019 were attributed to hypersensitivity pneumonitis (HP); - In our clinical practice, HP constitutes approximately 46% of cases with pulmonary fibrosis which contrast with the European and North American epidemiological data; - Provisional diagnosis of HP is often of low confidence due to unidentified exposure or no lymphocytosis in the bronchoalveolar lavage (BAL) fluid; - There is a notable disagreement among multidisciplinary medical teams from different backgrounds regarding ILD diagnoses, often requiring invasive procedures such as lung biopsy; - Significant idiopathic pulmonary fibrosis (IPF) diagnoses have been reclassified as HP upon environmental exposure assessment; - Within the FIBRALUNG cohort, near 9% of fibrotic ILD cases received a final diagnosis of unclassifiable ILD (uILD); - Unrecognized and underestimated long-term exposure to indoor mould may account for a significant risk of pulmonary fibrosis development and progression, not only among patients with HP, but also in those diagnosed as IPF or unclassifiable ILD; - Currently, there is no established risk assessment tool that combines clinical factors, molecular profiling and potential environmental triggers to individualize management. The FIREGENS proposal envisions to contribute for the advance of precision medicine in ILD field, laying the foundations for individualized preventive and therapeutic approaches. Specifically, we aim to accomplish the following objectives: 1. Comprehensively characterize individuals beyond the scope of disease etiopathogenesis. Expand our understanding of endotypes and phenotypes to encompass genetic and environmental risk factors (addressed in Section 8 - Task 1); 2. Implement a non-invasive testing method to confirm antigen sensitization. To improve HP diagnosis and to investigate the impact of occult environmental factors in the pathophysiology of other fibrotic ILDs, we will develop an optimized test using as readout the activation of a fungal-specific T cell response (Task 2); 3. Develop a treatable traits approach in fibrotic ILDs. This strategy combines both modifiable factors, such as airborne exposure (Tasks 1-2), and measurable biomarkers (Task 3), that inform prognosis and treatment response, intended to enable adaptable therapeutic recommendations as the disease progresses; 4. Elaborate a predictive model to improve diagnosis and prognosis definition. Upon achieving the aforementioned objectives as demonstrated by the outcomes of Tasks 1-3, we aim to enhance the accuracy of ILD classification through nationwide validation. This effort particularly targets cases with overlapping features and unclassifiable ILDs, encompassing the risk of disease progression (Task 4). By unravelling genetic, phenotypic and environmental factors, the FIREGENS project paves the way for improved clinical outcomes through precision medicine, addressing the current challenges of diagnosing and predicting disease behaviour in fibrotic ILDs.