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Transcriptomic profile of airway-centered myofibroblast areas as a potential biomarker of bronchiolocentric interstitial pneumonias: transitional approach to molecular diagnosis

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Sabrina Setembre Batah
Total Authors: 1
Document type: Master's Dissertation
Press: Ribeirão Preto.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
Defense date:
Examining board members:
Alexandre Todorovic Fabro; Lina Carvalho; Claudia dos Santos
Advisor: Alexandre Todorovic Fabro

Interstitial lung diseases are a large heterogeneous group of disorders that cause interstitial lung remodeling with different injury patterns. Among these patterns, bronchiolocentric interstitial pneumonitis is defined by a predominantly bronchiolocentric fibrotic remodeling, related to different etiologies, such as chronic microaspiration (ASP) of food/gastric content and hypersensitivity pneumonitis (HP) by inhaled antigens. Although the initial cause of the lesion differs between these etiologies, clinical, radiological, and histopathological findings often do not allow a precise etiological diagnosis, drastically affecting the management and prognosis of these patients. Thus, this project studied the molecular profile of the lesion areas, where the initial specific mechanism is present, in order to validate biomarkers for translational diagnosis. Thus, a detailed analysis of clinical, radiological, and histopathological data was performed, in addition to the transcriptome of lung tissue from patients with ASP and HP. The data integration with the transcriptomic profile of patients evidenced some gene clusters related to specific pathophysiological processes of each etiology, highlighting an up-expression of genes related to collagen and protection of bronchiolar epithelial cells in the ASP group. Furthermore, the data presented demonstrated, for these patients, a greater fibrosing lesion with extensive parenchymal remodeling, with restrictive pulmonary characteristics and worse prognosis. Thus, chronic microaspiration of oral/gastric content can modify the transcriptomic profile, which is responsible for the worst fibrous condition. These findings enable a better diagnostic accuracy for the specific treatment of ASP and PH, improving the clinical management. (AU)

FAPESP's process: 19/19591-5 - Transcriptomic profile of airway-centered myofibroblastic areas as potential biomarkers of bronchiocentric interstitial pneumonia
Grantee:Sabrina Setembre Batah
Support Opportunities: Scholarships in Brazil - Master