Cohort of Spanish population in post-infectious bronchiolitis obliterans, role of epigenetic regulation by microRNAs

<bold>Objectives:</bold> To describe the clinical characteristics and outcomes of Post-Infectious Bronquiolitis Obliterans (PIBO) in a Spanish cohort, as a basis to carry out future studies of biomarkers related to the natural history. <bold>Material and methods:</bold> Retrospective observational study of cases diagnosed with PiBO at Vall d'Hebron University Hospital between 2010-2022. Clinical characteristics, lung function and outcome are reviewed. Blood samples from 20 patients and healthy controls were analysed for microRNA expression by next-generation sequencing (NGS). <bold>Results:</bold> 80 cases were reviewed during 11 years. 59% male, with a mean age at diagnosis of 21 months. 69% required hospital admission, of which 60% required oxygen therapy and 26% mechanical ventilation. The etiology of the initial infection was unknown in 56.3% of them, and Adenovirus was the most frequently agent in the rest. Spirometry showed a fixed non-reversible obstructive pattern, plethysmography hyperinflation with air trapping, pulmonary clearance index revealed inhomogeneity in tracer elimination, and an increase in resistance was detected with oscillometry. During follow-up, only 10% presented chronic respiratory failure and 7 patients required a lung transplant of which one died after. NGS analysis showed an aberrant miRNA expression profile in PiBO patients, with statistical significance for miR-30d-5p, miR-361-5p, and mir 140-3p compared to controls. Conclusions: Our series includes a high number of patients who initially present severe bronchial obstruction with long-term stabilization, with low morbidity and mortality during the subsequent clinical course and demonstrate an aberrant miRNA expression profile in PiBO, affecting pathways responsible for the regulation of inflammation and fibrosis.