Frank Sciurba, MD, Professor of Medicine at University of Pittsburgh, Department of Medicine Division of Pulmonary, Allergy and Critical Care Medicine; and Director of the Emphysema COPD Research Center and Pulmonary Physiology Laboratories, talks about a new treatment for COPD.
Can you tell me a little bit about COPD and the common ways it is treated?
SCIURBA: Prior to the tragedies of opiate addiction and COVID, COPD was the third leading cause of death in this country and largely tobacco related. But it can also be caused by other diseases. In the third world, exposure to indoor burning is common in women who get COPD. What COPD primarily causes is both emphysema, which is destruction of the lung tissue, and obstruction of the small airway tubes that allow you to exhale the air. So, what happens is patients can’t exhale and wind up getting trapped air and then their lungs get overinflated. Then ultimately shortness of breath, cough, sputum production and then flare ups which cause bad days, admissions to the hospital, requirement for steroids and antibiotics to clear up.
What is the standard of treatment at this point?
SCIURBA: The treatment of COPD, first of all, is to quit smoking. Vaccinations are critical. Exercise and pulmonary rehab are the non-invasive things before we start giving medicines and other things. But as far as treatments, bronchodilators help open as much as possible those airways to allow folks to clear secretions, and inhaled steroids in some patients, not all patients, to decrease the inflammation in the lungs. But even after we treat patients maximally, they still have these flare ups. They still have shortness of breath. The thing about COPD, unlike asthma, is we can almost never completely clear the symptoms. The goal is to allow people to function as well as possible to maximize their quality of life and to decrease the bad days, the hospitalizations, and the flare ups.
What is targeted lobe denervation (TLD) and what is it designed to do?
SCIURBA: One of the aspects of COPD is increase tone of the smooth muscles that surround the airways, causing narrowing and then excess secretion of mucus by what we call these little goblet cells, which are cells in the airway that’s purpose is to secrete mucus. What innervates both the smooth muscle, and these mucus glands, is the vagus nerve, which starts up in the brain and has little terminals in the neck, but then eventually goes down over the main windpipe and into the peripheral airways. This nerve innervates the smooth muscle to cause it to constrict and the mucus glands to secrete. In fact, the bronchodilators’ purpose is to block the effects of the vagus nerve coming down to maximally open those airways. What targeted lobe denervation (TLD) does is at a very proximal level in the branching tree of the airways, a heat signal is generated called radio frequency ablation (RFA) that results in damage of those vagus nerve trunks going down over the airways. That then prevents all the peripheral airways or causes all the peripheral airways to die and all the innervation of the smooth muscle and the mucus glands.
So, you’re not getting that extra mucus secretion if you don’t have the vagus nerve?
SCIURBA: Without that vagus nerve signal, the goal would be to decrease that mucus secretion and decrease that smooth muscle tone that narrows the airways and optimize lung function. But what we’ve learned in the clinical trials, more importantly, is that it decreases those bad days and those flare ups.
Is this a cure in your world?
SCIURBA: No. There’s no cure for COPD and emphysema. The goal is to optimize the good days to maximize the quality of life in our patients. When there’s nothing left to do, to have something available gives hope. And in fact, this is potentially realistic hope if we can show in the larger trial what we’ve shown in the smaller trials.
How effective is it? How many more good days do your patients have with this?
SCIURBA: What we found in the European trials is that there’s about a 50% reduction in bad respiratory events and greater than 50% reduction in hospitalizations. Now, this is the preliminary data which gives us a lot of hope and optimism. But we now need to confirm this in a much larger trial and an international trial that includes patients in the United States as well as other countries around the world.
Is that much of a decrease a win in your book for patients?
SCIURBA: Absolutely a win for both the patient to improve their quality of life and the health care system. One of the greatest burdens for patients in the health care system are admissions to the hospital of our patients with COPD and those bad days, flare ups, unexpected or unplanned office visits, emergency room visits. That’s our goal really with this therapy to decrease the number of those.
Can you walk me through again how you go about ablating that trunk to the vagus nerve?
SCIURBA: Sure. What we have is a catheter that has ice water that runs through it to cool the main airway. Then a heat signal is generated. Because of that ice water, there is no damage to what we call the epithelium, the lining of the airway and the cartilage. But then that heat signal occurs right on the surface of the bronchial tube where the vagus nerve runs. And just a 60-degree temperature is enough to damage and destroy that vagus nerve and all the peripheral roots that go down into the airway. We do up to eight activations in 90-degree segments. We do the right lung in four 90-degree segments and then the left lung. With the exception that we’ve learned we can’t get too close to the esophagus where the vagus nerve supplies the stomach and gut because we can get some issues with nausea and gastrointestinal issues. That’s why these preliminary trials were so important is that we learn to avoid that esophageal vagus nerve and have much less gastrointestinal side effects now. We may do even only six activations if we find that the vagus nerve is too close to the airway.
What is the risk to having this signal interrupted?
SCIURBA: The risk that we found early on is damaging vagus branches that don’t go to the lung and that esophageal branch that supplies the stomach. But the company has really developed techniques to be very careful to avoid this. In the latest trial, there was much greater success at eliminating that side effect. In the international trials, there’s never been a death from the procedure. Overall, it’s very well tolerated. The clinical trial that is moving forward does not even require admission to the hospital afterwards. As we convince ourselves of the safety which has been shown in the previous trials, we may discharge patients the same day, which is acceptable within the trial.
Is this a phase three clinical trial? How many do you plan to enroll here in Pittsburgh?
SCIURBA: This is an FDA-approved clinical trial. It is what would be considered a pivotal trial. If it has good results, we’re hopeful that it would lead the FDA to approve this device in the United States. It would involve 400 patients with the bronchoscopist doing the intervention blind to the procedure. But that individual, the bronchoscopist who does the procedure and everybody in the treatment room, will never see that patient again so that we can’t influence the results. Both the patients in the control group and the intervention group will go into the bronchoscopy lab. They’ll either get the procedure or they’ll get the denervation procedure, or a sham procedure that they won’t know whether they actually had the nerves burned or not. If everything goes well, at 12 months, we will allow those patients to cross over and get the procedure so that they are still able to have that option. The primary outcome will be evaluated at 12 months in those patients where both the evaluating physicians and staff are blind to whether they really got it. Then we’ll determine whether those that got the procedure do better than those that didn’t or whether there’s any difference in adverse effects with the procedure versus those that didn’t.
Can you tell me a little bit about your patient Jim? Was he in one arm of the trial?
SCIURBA: I can tell you that in this trial we have two, what we call, roll-ins. They won’t be included in the final analysis and you can call it practice because in any procedure, there’s theoretically some startup. We thought we did a very good job. But I think it’s appropriate that we do two procedures where the organization is making sure we have everything down right. So, moving forward, we get a true assessment of the effects of the procedure and that there’s not a learning effect that’s interfering with that.
What made Jim a good candidate?
SCIURBA: To be included in the clinical trial, Jim had to meet the inclusion criteria, which included at least two flare ups in the prior year as an outpatient or one admission to the hospital. Jim did have two flare ups that resulted in those symptoms. He was also on maximal medical treatment and everything that we could possibly do up to this point and was still having flare ups. At that point, he was frustrated with his quality of life, frustrated with these flare ups and how COPD interfered with his life. We informed him of the potential benefits and that this was a clinical trial. And he wanted to proceed.
What are the implications of this procedure in being available to patients?
SCIURBA: The very frustrating thing with COPD is that, despite everything we do for them, there remains this unmet need. These folks have a poor quality of life in many cases and have this recurrent contact with the health care system. If they had a choice, they wouldn’t want to see me no matter how nice I try to be with them. They’d rather be living their lives, playing with their children, their grandchildren, their pets and spouses. So, to have another option where we can give them more good days to avoid the health care system is potentially huge and what we’re looking for in developing new medications and other interventions with COPD. The interesting thing is as we’ve gotten better in understanding this disease and understanding the different variants of that disease, we can do more personalized treatment to those individuals who have those qualities that would qualify them for this trial specifically. And, hopefully other therapies for other individuals might be coming down the pike as well.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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