David J. Nagel, MD, PhD

David J. Nagel, MD, PhD

David J. Nagel, MD, PhD

“Idiopathic pulmonary fibrosis is this type of disease that gets worse no matter what, even with medication,” said David Nagel, MD, PhD.

That’s why it’s meaningful that his recent research—funded by a CHEST Clinical Research Grant in Pulmonary Fibrosis—identified a novel biomarker for idiopathic pulmonary fibrosis (IPF). While it’s early days for Dr. Nagel’s research, this is a big moment: The existence of this biomarker and observations on its effect on the lungs mean a potentially swifter path to diagnosis of IPF, as well as new treatment pathways to explore.

About 100,000 people in the United States have IPF. The disease causes fibrosis (scar tissue) on the lungs, making the lungs less effective at delivering oxygen throughout the body. IPF is tricky to diagnose, yet catching it early is important for treatment. Currently, available medications only slow down scarring and don’t reverse fibrosis or cure the disease.

Here is a look at how the CHEST grant helped fuel Dr. Nagel’s research into biomarkers for IPF and what to expect next.

From in vitro to in vivo

When Dr. Nagel received his CHEST grant in 2013, he already had preliminary cell culture data.

“We were looking at the by-product of what happens when people have scarring of their lungs,” said Dr. Nagel, an assistant professor of the Division of Pulmonary and Critical Care Medicine at the University of Rochester Medical Center.

As the composition of the lungs changes, a set of proteins known as elastin degradation products (EDPs) is released. “What we found, at the in vitro level, is that this by-product actually promoted fibrotic signal changes,” Dr. Nagel said. That is, EDPs cause more scarring and also serve as a signal that scarring has occurred.

With the grant from CHEST, Dr. Nagel wanted to know: Does the same process of releasing a by-product occur in people?

To find out, Dr. Nagel and his team examined both healthy volunteers and people with IPF. They split the latter “into groups of three based on the degree of elevation of this [EDP] protein,” Dr. Nagel said.

People with higher levels of the protein by-product had worse outcomes as measured by FVC (a lung function parameter) and three-year transplant-free survival. The funds received from CHEST allowed Dr. Nagel to develop and purchase reagents to perform this analysis.

A discovery with big potential

From this research, possibilities—not certainties—unfold.

Consider this: Patients with IPF may have fairly normal lung function without many symptoms, noted Dr. Nagel. “IPF is probably subclinical, meaning it’s under the surface for decades before we actually make a diagnosis,” Dr. Nagel said. People may think symptoms are a natural part of getting older or seek a cardiological workup first since shortness of breath is a common symptom, he added. Plus, not all pulmonologists are familiar with IPF, which is classified as a rare disease. Testing for EDPs could potentially reveal a diagnosis earlier.

That’s not the only hopeful outcome. Currently, there are two antifibrotic medications available, with a third currently under US Food and Drug Administration review. If a medication is effective, levels of the by-product would stay the same or go down, Dr. Nagel said. So, if the levels instead went up, it could be a cue to switch to the alternate medication for potentially more efficacious results, he said.

Of course, a cure for IPF is the biggest goal. “It'd be great if we could find medications that actually reverse the scarring, rather than just make it less worse,” Dr. Nagel said.

Personal and professional growth

Making it possible to enact this research—with all its potential for people diagnosed with pulmonary fibrosis—is the most important aspect of receiving the CHEST grant, but it’s also had personal and professional benefits for Dr. Nagel.

First off: the personal. The National Institutes of Health offers Loan Repayment Programs with the goal of furthering biomedical research. Dr. Nagel first applied as a fellow. “On my last renewal, I used the preliminary data that were at least partly used for the CHEST grant as well, and so at the end of my tenure with that grant, all of my medical school debt will be paid for,” he said.

The grant has opened career doors as well. “This, in part, has gotten me to be used more as a reviewer for articles that are published in prestigious journals,” Dr. Nagel said. Receiving the CHEST grant has led to additional funding opportunities. Plus, it’s helped him become a presence in the research community.

What’s next?

There’s much promise in his research, but Dr. Nagel is keen to note it is still at an early phase. Other small IPF studies have previously revealed promising biomarkers that aren’t ultimately the answer to the puzzle of treating this disease, Dr. Nagel said.

This research, which began in vitro and grew to in vivo, will grow further. “Part of what the [CHEST] grant led to is applying for additional funds to get larger sample sizes to see whether the same thing holds up when we have more people in a more geographically diverse bioregistry—because we're going to use a national registry next instead of a single-institution registry,” Dr. Nagel said.

This will allow Dr. Nagel to expand to more samples—and also open a door to potential future research grasping the difference between the by-product’s presence for people with IPF as opposed to other forms of interstitial lung disease.