🎙 Two Docs Talk Allergies and Asthma Part 3 The Evil Eosinophils Ep 108

Welcome to MedEvidence: Two Docs Talk Allergies and Asthma Part 3 The Evil Eosinophils.  In this episode, Dr. Michael Koren and Dr. Sunil Joshi explore allergy shots vs. allergy drops for managing allergic rhinitis. For people with allergic rhinitis, allergy shots and allergy drops are two options for managing symptoms. The doctors explain the difference between the two treatments and their effectiveness in reducing allergic rhinitis symptoms. They also discuss the pros and cons of each option and how to decide which one is best for you.

This series is the perfect resource for learning about allergies and asthma. Tune in to gain a deeper understanding of these important healthcare topics.

Listen to the whole series:
Two Docs Talk: Allergies and Asthma Pt 1 - Pollen Season & Symptoms Associated with Pollen Allergies
Two Docs Talk: Allergies and Asthma Pt 2 - Prevention, Testing & Treatment
Two Docs Talk: Allergies and Asthma Pt 3 - The Evil Eosinophils
Two Docs Talk: Allergies and Asthma Pt 4 - Eosinophil Asthma Research & Treatment

Common medications:

• The anti-IL5 products that affect eosinophil survival are mepolizumab (Nucala), benralizumab (Fasenra), reslizumab (Cinqair). 
• The anti-IL4/IL13 product is dupilumab (Dupixent)
• The anti-IgE agent is omalizumab (Xolair)
• The anti-TSLP agent is Tezepelumab. (Teszpire) 

Sunil Joshi, MD, is the President and Managing Partner of Family Allergy Asthma Consultants in Jacksonville, Florida. The Past-President of the Duval County Medical Society (the largest and oldest Medical Society in Florida) and a graduate for the University of Florida College of Medicine. Dr. Joshi received his Allergy/Immunology fellowship training at the University of Rochester in New York.  He truly enjoys treating patients with allergic disorders and believes that education about these disease processes can bring better care to the public.

Michael J. Koren, MD, is a practicing cardiologist and Chief Executive Officer at Jacksonville Center for Clinical Research, which conducts clinical trials at 7 locations in Florida. He received his medical degree cum laude at Harvard Medic

Be a part of advancing science by participating in clinical research.

Have a question for Dr. Koren? Email him at askDrKoren@MedEvidence.com

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Transcript

Transcript

Two Docs Talk Allergies and Asthma Part 3 Prevention, Testing and Treatment

Recorded Date: April 14, 2023

[Narrator] Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts. Powered by ENCORE Research Group and hosted by cardiologist and top medical researcher Dr. Michael Koren.

[Dr. Koren] I'm Dr. Michael Koren here to host another episode of MedEvidence! I have a tremendous guest today; Dr. Sunil Joshi is joining me. He's an allergist, an immunologist, and somebody involved in organized medicine as a past president of the Duval County Medical Society and Foundation. We also have a shared passion in clinical research and have had some great discussions already about some really interesting things including the hygiene hypothesis of allergies. We're going to jump into that. We left it off in the last session talking about eosinophils.

[Dr. Joshi]  Yes.

[Dr. Koren] We were talking about the fact that they're an immune cell. They can do good or bad things and are perhaps a mediator of different allergic issues that can affect multiple different tissues. These include the GI tract - we're doing studies as we speak in eosinophilic esophagitis. It can affect the heart; it's going to feel like myocarditis. It can certainly cause asthma. Since asthma is your bailiwick let's talk a little bit about that.  Let's talk about the role of eosinophils and asthma and then some of the interesting hypotheses about who's at risk for these things.

[Dr. Joshi] So definitely eosinophils play a role in asthma. The higher the eosinophil count is in the bloodstream - if somebody gets a blood test where they just get their screening blood work done - if their eosinophils are above 300, those patients who have asthma typically have more severe asthma. Our entire population of severe asthmatics makes up about five to ten percent of all of the asthma patients that are out there. Allergists of course see a skewed population and see a lot more of all the severe asthmatics. Between 70% and 90% of them have high eosinophils in their bloodstream, so we feel that the eosinophils drive their asthma to the point where they have to be on very high doses of inhaled steroids or other combination medicines just to control their asthma, or they need to be an oral steroids / systemic steroids to manage their asthma. The eosinophils are a marker of severe asthmatics.

[Dr. Koren] Interesting. You mentioned steroids and we are running clinical trials as we speak in eosinophilic asthma. So talk just a little bit about steroids versus some of the newer ideas for treating this. Then we'll get into that a little bit more down the road, but I want you to set that up for a reason I'll get to in a second.

[Dr. Joshi] Okay! One of the things with asthma, since the more severe it is the more likely it is to be an eosinophilic disease, is we've learned through the years that steroids - whether they're topical steroids or oral steroids - do have a tendency to decrease the eosinophils. If you put eosinophils in a vat and put a drop of steroids in there they would die. So the treatment of choice to manage yeast milk asthma is topical inhaled steroids. These are steroids that go directly into the lungs, get into the tissue, and then then kind of suppress the eosinophils that are in there so that you have less disease. You have less scar tissue being laid down, less remodeling. Those tend to work. When they're not working then we have to go to oral steroids / systemic steroids. We know that if patients who have severe eosinophilic asthma go on oral steroids their eosinophils in the bloodstream drop at the same time that their symptoms improve. The steroids decrease the eosinophils in their bloodstream as well. The problem of course is that steroids are not safe. If you're on oral steroids at least two times a year or more you have a three times increased risk of having a bone fracture or a blood clot or even having sepsis - bloodstream infections. Let’s also mention the long-term consequences of diabetes, osteoporosis, glaucoma, and cataracts that can be associated with steroids. The topical steroids are much less likely to do that. In fact, when using the recommended doses correctly, it would take somebody five years of using an inhaled steroid to equal one five-day course of an oral steroid. But if the inhaled steroids aren't working that's where we're left with “what do we do now?” and we typically have had to do oral steroids.

[Dr. Koren] Explain a little bit more the difference between eosinophilic asthma and other forms of asthma and the use of steroids or other medications.

[Dr. Joshi] Eosinophilic asthma makes up the majority of severe asthmatics, almost up to 90 percent of them. The steroids (inhaled steroids and topical steroids) do have a tendency to work a lot better in these folks. In folks in which their asthma is not driven by eosinophils, they're typically then driven by what we call neutrophils which are other forms of white blood cells. In these patients, the inhaled steroids and oral steroids don't work nearly as well. They almost have more of a picture of a COPD patient or maybe a smoker - but in this case, they don't smoke and they happen to have asthma. We're still using topical steroids but in their cases, we're going to use more bronchodilators and more of what we call muscarinic antagonists. These actually prevent the bronchial areas from producing phlegm and mucus which also complicates these patients' symptoms. We call this triple therapy for these folks. These are going to be more likely to be effective than higher doses of inhaled steroids. Those are even more difficult to treat because we don't necessarily have great treatment for the neutrophilic asthmatics.

[Dr. Koren] Do we have ways of going at the eosinophils more directly than steroids?

[Dr. Joshi] Absolutely we do! That's one of the great things you know with the advances in medicine and in particular in immunology. We understand what the mediators are that drive eosinophils to come out of the bone marrow, survive when they're out of the bone marrow, and then go from the blood into the tissue. We could target a bunch of different areas to prevent that. There are specific targets to specific receptors that can help kill eosinophils, stop their survival and production in the bone marrow, and also some that prevent them from getting from the bloodstream into the tissue as well.

[Dr. Koren] Are any of these on the market?

[Dr. Joshi] Yeah, they are out there on the market and we use them routinely in our patients who qualify for them. There are some that block a certain inflammatory mediator that brings eosinophils out of the bone marrow, called IL-5. It blocks it directly and it also can block that receptor on the cell. Then there are some that actually block the ability of the eosinophils to get into the tissue by decreasing certain proteins that come onto the cell that drive it into the tissue. There's some out there that decrease the eosinophils without us having to use oral steroids.

[Dr. Koren] Interesting, interesting. Are these types of drugs equally good at treating eosinophilic asthma and other eosinophilic diseases? Do we know that yet?

[Dr. Joshi] Well and that's where the clinical trials come into play! 

[Dr. Koren] I knew they would come into play at some point.

[Dr. Joshi] Yeah! They come into play. Obviously, the ones that are on the market for asthma do help to decrease exacerbation rates and some of them help to decrease the need for oral steroids as well in these patients. There are some that also work for chronic sinusitis that have eosinophils disease which is called nasal polyps. There are a few that are approved for that as well. But there are other disease processes we have to look at. You were mentioning the eosinophils in the esophagus, but even just high levels of eosinophils in the bloodstream are not good for the body because they can start to attack these other organs such as the heart, the skin, the lungs, and the kidney. There's some agents that just can reduce the eosinophils in the bloodstream as well.

[Dr. Koren] Interesting. In your opinion, is the future of dealing with these issues going directly at the bone marrow, or more tissue basis, or somewhere in between?

[Dr. Joshi] Well, where do the eosinophils cause the problem? They cause the problem in the tissue. So ultimately the goal for the patient is to be better no matter what the case is. But the goal is for us to try to diminish the adverse effects of the eosinophils. Where do they have their adverse effects? In the tissue. Whether that's in the sinus cavity, in the lungs, in the heart, or on the skin, that's where they do their damage. If we were able to develop treatment options that could prevent the eosinophils from getting into the tissue or them while they're in the tissue, then we're winning the game.

[Dr. Koren] Gotcha. For these types of eosinophilic therapies are they pills or injections and how frequently do you get them?

[Dr. Joshi] Typically the ones that are on the market right now are injection therapies. There are some that target the eosinophils directly and are taken every month and there's one of the agents that's done every other month. We typically ask these people to come to our office to receive these injections, but they can do them at home as well; the FDA has approved that. There's also an agent that actually blocks the eosinophils directly from coming into the tissue that's done every two weeks. These are subcutaneous injections so they're not IV and they're not going into the muscle. They're just going into the subcutaneous fat; almost like a diabetic needle.

[Dr. Koren] You mentioned interleukins and things that block interleukins. I'm not an allergy or immunologist but I can explain that those are our protein signals that amplify the immune system, such as eosinophils in this case. Can you comment a little bit more on how that works in terms of therapies? Are we doing direct poisons to the eosinophils or are we blocking the mechanisms to amplify their numbers or their effects?

[Dr. Joshi] We're doing both! One of the interleukins is IL-5 and this molecule is important for the eosinophils to develop in the bone marrow, come out of the bone marrow, and come into tissue. There's an agent that blocks IL-5 directly. As it blocks IL-5 directly it can reduce eosinophils in the peripheral bloodstream by 75% within two days. 

[Dr. Koren] Wow!

[Dr. Joshi] A significant decrease! There's another agent that actually blocks the receptor for IL-5 which is found on the eosinophil itself. As it blocks that receptor IL-5 the body recognizes it and kills the eosinophils.

[Dr. Koren] Oh wow!

[Dr. Joshi] So these eosinophils come out of the bone marrow but then are killed because of this particular agent. You target the IL-5 directly, which is important for eosinophil survival, or you target the receptor for IL-5 so the IL-5 can't do anything for the eosinophils and the body recognizes to kill it. Two different ways to reduce eosinophil count.

[Dr. Koren] Fascinating! How long does that treatment last? Is it recurrent? Give us a little insight into that.

[Dr. Joshi] You do need to do the treatment once a month if you're blocking IL-5 directly. If you're actually killing the eosinophils that particular agent is used every two months.

[Dr. Koren] Is this something that people are committed to for life? How long is a typical course?

[Dr. Joshi] That's a good question. We don't modify the progression of the disease with these agents. When you stop it, theoretically, the symptoms should come back. We hate to tell people that they're going to be on something lifelong. Each doctor is different and, anecdotally speaking, my patients want to come off of drugs once they're better. We come to an agreement that will do this for a year or maybe two to get you really well controlled. Then we can try to slowly back off of the agent, understanding that each patient is different. Not every patient fits what we see in the studies and there may be some patients who, instead of needing it once a month, might be able to get away with it once every three months. Maybe some could even stop it completely. Their eosinophils count may come back up, but if we're able to manage their disease (remember we're treating the patient) and they're better, then maybe they don't need the agent anymore!

[Dr. Koren] Interesting, interesting. We are, as you mentioned, doing clinical trials in this area and using these types of products. Are there any snippets that you can share? For example, people who were being treated for the eosinophilic disease in one realm seem to get benefits in another realm? Give us a little sense about this crossover phenomenon.

[Dr. Joshi] That's a great question. Obviously, we medical professionals are to use drugs for what they're intended to be used for. But sometimes we have hopes that it'll help with something else, right?

[Dr. Koren] Exactly!

[Dr. Joshi]  So we see that! Absolutely, I've seen that in my patients. The very first patient that I put on an anti-IL-5 drug was a lady who had severe eosinophilic asthma, but also had chronic sinus disease and had eosinophilic esophagitis. 

[Dr. Koren] Interesting.

[Dr. Joshi] We really needed to help her asthma out. She was requiring oral steroids very frequently, she was interested in something that was not steroid-based and we got the drug approved for her. We reduced her eosinophil count very quickly. Her asthma got better, but suddenly she was swallowing better too! She was having much less acid reflux and much less heartburn. Then about a year into treatment she went to go see her GI for her regular upper endoscopy and the eosinophils were gone!

[Dr. Koren] Wow!

[Dr. Joshi] Now her asthma is really well controlled and I haven't had her on steroids in about three years. I'm thinking about backing off on the agent but she doesn't want to stop it because it's helped her heartburn. Her eosinophilic esophagitis has gotten better and she's like “no I don't want to stop it!” That's just an anecdotal example but there are other people with similar things with their sinuses and their skin as well.

[Dr. Koren] That's fabulous! I love that anecdote and we're gonna go into this concept of cross fertilization of different disease processes in our next segment.

[Narrator] Thanks for joining the MedEvidence podcast. To learn more head over to medevidence.com or subscribe to our podcast on your favorite podcast platform.