COPD: the disease that too often goes undetected

Team Finds What's Driving Long COVID Inflammation In Lung Cells

Existing prescription medications  may be able to stop the chronic inflammation found in people with long COVID, a new study suggests. While researchers didn't test the drug in people, they uncovered more details about how cells produce inflammation after COVID-19 infection clears up — and suggest the drugs may be able to help.

One such medication is baricitinib (Olumiant), currently used to treat rheumatoid arthritis.

Jie Sun, PhD, a professor at University of Virginia School of Medicine, found that COVID-19 caused changes in immune cells inside lung tissue. The changes led to scarring and inflammation, which makes it hard for people to breathe after the initial infection has passed.

The investigators looked at cell samples from the lower airways of lab mice and humans. In both sets of samples, they found that immune cells known as macrophages and T cells were acting abnormally and interacting harmfully. These cells, which normally help the body fight off the disease, were still fighting. Instead, the macrophages overwhelmed the lungs in abnormal numbers, and promoted tissue scarring. The T cells were producing interferon, a substance that causes inflammation, according to the report published July 17 in Science Translational Medicine.

"Our study identified a root cause of the respiratory complication of long COVID by performing comparative analysis of both clinical samples and a relevant animal model," Sun said in a statement. "We hope that the identification of the 'driving' mechanisms will help to rationally design clinical studies repurposing those Food and Drug Administration-approved drugs for respiratory long COVID soon."

Chest pain, shortness of breath and chronic lung scarring known as interstitial lung disease are common long COVID symptoms. 

The drugs could break the cycle of inflammation and alleviate symptoms, Sun said, adding that more research is needed. He hopes their study leads to new treatments for long COVID.

"We hope our clinical colleagues around the globe could perform clinical trials soon to test the efficacy of baricitinib or other similar drugs targeting the same inflammatory pathway in long COVID," Sun said. "Our new study has established a foundation for identification of new therapeutic interventions for long COVID by combining rigorous clinical testing and basic scientific research."

Radiation A Curative-Intent Option In NSCLC And Interstitial Lung Disease

For some patients with early non-small cell lung cancer and lung scarring, stereotactic ablative radiotherapy may be a viable option, research has shown.

Stereotactic ablative radiotherapy (SABR) has been found to be a viable curative-intent treatment option among some patients with early-stage non-small cell lung cancer (NSCLC) and lung scarring known as interstitial lung disease, according to research.

"Our radiation has improved, just like the phones that we use have improved since the '80s, the technology changes have been on that massive scale," Dr. David Palma, a clinician scientist at the Ontario Institute for Cancer Research in Canada, explained in an interview with CURE®. "In the old days, [when] we used to deliver radiation to lung cancer, we would zap [patients] with a beam straight through from the front and a beam straight through from the back. So two beams just blasting right through, we couldn't see the tumor very well because the imaging wasn't very good and we'd have to treat a big area of the lung because you didn't know exactly where the tumor was.

"Now, when we deliver radiation, we can see a tumor as a patient is breathing, if it's moving up and down, and we can target it when it's right in the right spot within a design, very complicated radiation plans where the radiation is coming in from all these different angles. And what happens is you get the tumor very tightly enveloped in the high dose of radiation, so the side effects are a lot lower."

Palma was among the researchers on a trial, the findings of which were published in JAMA Oncology, studying the use of SABR in 39 patients with interstitial lung disease and early-stage NSCLC.

Researchers found overall survival (the time a patient lives, regardless of disease status) to be 79% at one year, with a median overall survival of 25 months. The median progression-free survival (the time a patient lives without their disease spreading or worsening) was 19 months and the two-year local control (no progression of the primary cancer) rate was 92%.

Regarding side effects, 30.8% of patients (12 patients) experienced grade 1 to 2 (mild or moderate) side effects, 10.3% (four patients) experienced grade 3 (severe) side effects and three patients, or 7.7%, experienced fatal, or grade 5 side effects, due to respiratory deterioration.

These findings, researchers wrote, support "the use of SABR for curative-intent treatment after a careful discussion of risks and benefits. Further studies exploring pharmacologic options to reduce radiotherapy-induced toxic effects may be beneficial in this population."

Palma spoke with CURE® about the study and its findings.

Transcript:

For patients who have lung cancer, some of these patients have an underlying lung condition that shows up as scarring of their lungs. This lung condition is called interstitial lung disease. So, it's a chronic scarring that some patients have, and these patients who have this lung scarring tend to be more likely to get cancer. And this lung scarring, this interstitial lung disease, can be caused by a lot of things. It can be associated with autoimmune things like rheumatoid arthritis, it can be associated with exposures, like asbestos, or even to pets or birds. And we know that people who have this lung scarring if they have lung cancer, their risks of side effects are a lot higher. So if you have this lung scarring and they need to remove part of the lungs, your risk of a bad outcome is higher, because your lungs don't work as well.

Same with radiation, and radiation is often used as a treatment for lung cancer to try to cure it. As a background, we have this very precise form of radiation that we use a lot for people with lung cancer to try to cure their lung cancer. And that radiation is called stereotactic radiation. And there's been a bit of concern in the past about giving stereotactic radiation to these patients with this lung scarring, this interstitial lung disease, because the risk of side effects, in some reports, has been really, really high. And that's because when you already have some lung scarring, and we give radiation on top of that, you can get more lung scarring and that can be a big problem. And that puts us into a bind.

Because ... What happens as the patient is that you have a new lung cancer, which if you don't treat is usually going to cause problems, it could be fatal. But if you treat it with radiation, then you have the potential of a very serious side effect. So, a few years ago, we designed this study. The idea was that if we give the radiation very carefully, with a lot of support from lung doctors [and] radiation doctors, to manage any side effects that come up, can we deliver this safely to try to give patients a chance to get their cancer treated? What we had said with this study is that we were hoping to show that by giving the radiation, the side effects would be lower than we had worried about and that patients on average would survive more than a year. Because the reason I put that year mark, is we know that if you don't treat lung cancer, usually within a year, it can be fatal. So, we enrolled over 39 patients, and we delivered this radiation carefully. We had careful assessments by lung doctors called pulmonologists. And we found that the outcomes for patients were way better than we expected. And the average survival wasn't a year — it was over two years. And although there were some patients with serious side effects, the rates of side effects were a lot lower than we expected.

Transcript has been edited for clarity and conciseness.

For more news on cancer updates, research and education, don't forget to subscribe to CURE®'s newsletters here.

Researchers Believe Anti-inflammatory Medicine Could Help Long COVID Patients

CHARLOTTESVILLE, Va. (CBS19 NEWS) -- Researchers at the University of Virginia School of Medicine think they have found a way to help people suffering from ongoing respiratory symptoms associated with long COVID.

According to a release, the researchers have identified certain arthritis medications that may be an effective treatment after finding an unknown cause of the condition inside the lungs.

They found that COVID-19 can cause major changes to the immune cells present in lung tissues, which promote scarring and ongoing inflammation even after the initial infection has passed.

The researchers believe this inflammation drives respiratory symptoms that continue for a long time, such as cough and difficulty breathing.

They say this research indicates that doctors may be able to stop this chronic inflammation by using drugs that are already used to treat rheumatoid arthritis, such as baricitinib.

Such anti-inflammatory medications have previously gotten emergency authorization to treat the uncontrolled inflammation that was seen in severe COVID-19 cases.

"Our study identified a root cause of the respiratory complication of long COVID by performing comparative analysis of both clinical samples and a relevant animal model," said Jie Sun, PhD, of UVA's Carter Center for Immunology Research and UVA's Division of Infectious Diseases and International Health. "We hope that the identification of the 'driving' mechanisms will help to rationally design clinical studies repurposing those FDA-approved drugs for respiratory long COVID soon."

Globally, long COVID is estimated to affect more than 60 million people, who experience symptoms lasting weeks, months or even years after a COVID-19 infection.

Symptoms of long COVID can include respiratory issues such as shortness of breath, chest pain and chronic lung scarring.

The release says these researchers specifically wanted to see what changes took place in lung tissues themselves instead of solely looking at the blood.

So they looked at cell samples taken from the lower airways of both lab mice and human patients, finding immune cells known as macrophages and T cells that were having harmful interactions.

In a normal situation, these types of cells help to fight off disease, but in these samples, the cells never stopped fighting even though the infection had passed.

Instead, these cells flooded the lungs in abnormal numbers, promoting scarring and inflammation.

The researchers believe doctors may be able to break this inflammation cycle by using rheumatoid arthritis medications.

However, more research is needed.

"We hope our clinical colleagues around the globe could perform clinical trials soon to test the efficacy of baricitinib or other similar drugs targeting the same inflammatory pathway in long COVID," Sun said. "Our new study has established a foundation for identification of new therapeutic interventions for long COVID by combining rigorous clinical testing and basic scientific research."

These findings have been published in the journal Science Translational Medicine.

---