Hallowell, Robert WIMAI, RYOSUKE2025-09-1820252025-05-022025Imai, Ryosuke. 2025. Understanding Disease Progression in Pulmonary Fibrosis: the Role of Autoantibodies and Functional Impairment. Masters Thesis, Harvard Medical School.32001698https://dash.harvard.edu/handle/1/42719835Overview of the thesis papers Interstitial lung disease (ILD) is characterized by progressive fibrosis of the lung parenchyma, ultimately leading to significant morbidity and mortality. The advent of antifibrotic therapies has made it increasingly important to identify and monitor disease progression, as timely intervention may improve patient outcomes. In this context, I conducted two studies to better understand disease progression in ILD. One focused on anti-Ro52 autoantibodies as a prognostic marker; the other on pulmonary functional impairment, focusing on FVC % predicted in patients without evident progression. The first paper addressed the clinical question: Does anti-Ro52 positivity predict poorer outcomes in ILD? In a retrospective cohort study, I identified patients tested for anti-Ro52 antibodies and compared those who were anti-Ro52 positive with those who were negative. The primary outcome was ILD progression or death, and results revealed that the anti-Ro52-positive group exhibited significantly higher rates of disease progression, lung transplantation, and all-cause mortality. These findings suggest that anti-Ro52 seropositivity is an important biomarker for prognostication and underscores the need for vigilant monitoring in affected patients. The second paper addressed another critical clinical question: Among patients with non-idiopathic pulmonary fibrosis ILD who do not meet the commonly used ≥5% absolute FVC decline criterion, is a lower FVC % predicted at one year nonetheless associated with a worse prognosis? A retrospective cohort study demonstrated that patients maintaining “stable” disease yet exhibiting a lower one-year FVC % predicted had significantly worse transplant-free survival. This indicates that even without measurable pulmonary function decline, functional impairment can still have prognostic significance, highlighting the need for close clinical monitoring in these patients.application/pdfenAnti-Ro52AutoantibodyILDInterstitial lung diseaseprogressive pulmonary fibrosisHealth sciencesThesis or Dissertation2025-09-180000-0002-3129-916X