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There is growing evidence that microvascular dysfunction also plays a role in disease progression, but large human translational studies are lacking. In this research, we aim to identify a proteomic signature of microvascular instability and assess the impact of current therapeutics on the microvasculature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Olink proteomic data from patients with IPF were obtained from the Pulmonary Fibrosis Foundation Patient Registry (PFF-PR) (n=914) and an independent validation cohort (n=366). Among the PFF-PR, 640 patients also have whole-blood RNA sequencing data available. A subset of 79 microvascular-associated proteins was curated, and their associations with disease severity and transplant-free survival were examined. An adaptive least absolute shrinkage and selection operator was used to generate a novel microvascular risk score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Higher plasma levels of five microvascular-associated proteins (SDC1, MMP10, THBS2, HGF and SERPINA5) were associated with lung function and survival in both cohorts. Whole-blood RNA sequencing of patients with microvascular risk revealed enrichment of immune-mediated processes. Patients with higher microvascular risk who were subsequently put on nintedanib in the following year had significantly better 3-year transplant-free survival compared with patients who did not receive antifibrotic intervention (HR 0.56, 95%\u2009CI 0.35 to 0.89, p=0.0142).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Integrative multi-omics analyses suggest that perturbations to microvascular remodelling contribute to disease severity and progression in IPF. This analysis offers a framework for a precision medicine approach for IPF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/thorax-2026-225147","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:25:16Z","timestamp":1789061116000},"page":"thorax-2026-225147","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Markers of microvascular instability predict severity and survival in idiopathic pulmonary fibrosis"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-7811","authenticated-orcid":false,"given":"David J","family":"Csordas","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of Virginia School of Engineering and Applied Science, Charlottesville, Virginia, USA"},{"name":"Robert M. 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