# Vascular Leak and Outcomes in IPF

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $177,348

## Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. Within IPF, however, there
exists marked disease heterogeneity as some patients experience a rapidly progressive course while others
experience prolonged periods of stability or stepwise declines triggered by disease exacerbations.
Unfortunately, there are no accepted means by which patients can be clinically “phenotyped” into these
different disease courses at the time of diagnosis. The ability to predict an individual patient’s pace of
progression would greatly impact patient care by enabling better prognostication, individualization of treatment
plans, and early evaluation for lung transplantation for those at highest risk of rapidly progressive disease.
Such knowledge could also be utilized as a cohort enrichment strategy allowing new IPF therapies to be
evaluated in patients at greatest risk of progression thus improving clinical trial feasibility. We hypothesize that
disease activity in IPF is driven by ongoing lung injury and that measurements of ongoing lung injury could be
utilized to predict prognosis and treatment response. Vascular leak, a cardinal response to tissue injury, has
been implicated in the development of IPF. Alveolar-capillary permeability is increased in the lungs of IPF
patients, and the extent of this increase has been shown to correlate with disease progression and mortality.
We will use the advanced magnetic resonance imaging (MRI) technique of dynamic contrast-enhanced (DCE)
MRI to assess vascular permeability in the lungs of IPF patients and healthy volunteers and prospectively
evaluate if these MRI-derived measures of lung vascular permeability predict subsequent IPF disease
progression. We will also evaluate whether increased plasma levels of soluble Ephrin-B2 (sEphrin-B2), a novel
molecular biomarker of lung injury in fibrosis, can identify IPF patients most likely to experience disease
progression. Lastly, we will perform lung DCE-MRI prior to and after initiation of anti-fibrotic therapy with
nintedanib, which we hypothesize will decrease lung vascular permeability by inhibiting vascular endothelial
growth factor (VEGF), to assess whether our MRI-derived lung vascular permeability measures are decreased
with treatment. This research will be performed by Dr. Sydney Montesi, a pulmonary and critical care physician
at Massachusetts General Hospital, an Instructor of Medicine at Harvard Medical School, and a specialist in
the care of patients with pulmonary fibrosis. She will receive first-rate training in advanced lung imaging and
biomarker development. She will be exceptionally mentored by Dr. Peter Caravan, a pioneer in molecular
imaging of fibrosis, and co-mentored by Dr. David Christiani, an expert in biomarker development for lung
injury. She will perform her research in a world-renowned academic center with all required resources available
to her. Dr. Montesi’s goal is to become a physician-scientist in patient-oriented resea...

## Key facts

- **NIH application ID:** 9871125
- **Project number:** 1K23HL150331-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Sydney Montesi
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $177,348
- **Award type:** 1
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9871125

## Citation

> US National Institutes of Health, RePORTER application 9871125, Vascular Leak and Outcomes in IPF (1K23HL150331-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9871125. Licensed CC0.

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