Rhinosinusitis, Nasal Polyps and Asthma – What to do? (Recording)

This webinar was recoded on December 4, 2025

Research indicates that rhinosinusitis affects 5-12% of the global population, and among those with chronic rhinosinusitis, 25-30% also have nasal polyps. Often, rhinosinusitis is accompanied by nasal polyps—benign growths that can obstruct airflow—and asthma often worsens in patients with rhinosinusitis and nasal polyps due to shared inflammatory pathways. Join us as we delve into the pathophysiology of these conditions and how they exacerbate each other. Attendees are invited to join the discussion on advanced diagnostic techniques, contemporary pharmacological treatments, surgical interventions, and the role of biologics in managing refractory cases. Gain actionable strategies to enhance patient outcomes and optimize clinical management.

Speaker:
Andrew White, MD, FAAAAI, FACAAI

As an allergist and immunologist, Dr. Andrew White treats all types of allergic conditions, as well as those arising from immune system deficiencies. He frequently sees patients with asthma, hay fever, eczema, food allergies, skin allergies, and hives. Additionally, he diagnoses and treats immune deficiencies such as common variable immunodeficiency (CVID) and various other conditions that may increase the risk of infection. He also treats patients with chronic sinusitis and nasal polyposis. Aspirin-exacerbated respiratory disease (AERD), also known as Samter’s Syndrome, is another key area of focus. He is particularly interested in vocal cord dysfunction, mastocytosis, and mast cell activation syndromes. Dr. White believes in fostering a partnership with his patients. He emphasizes the importance of listening closely to his patients’ concerns to guide them to the best treatment options available. Alongside his clinical practice, he researches aspirin-exacerbated respiratory disease, a subject on which he has authored multiple publications and ongoing research protocols. Outside of work, he enjoys adventures with his wife and children, mountain biking, reading, and making music.

This Advances webinar is sponsored in partnership with the American College of Allergy, Asthma & Immunology. ACAAI offers CMEs for physicians for this webinar. If you are a member of ACAAI, you can obtain CME through the member portal for the Advances webinars.

All attendees will be offered a certificate of attendance. No other continuing education credit is provided.

CME is available through ACAAI for this webinar.

Sponsored by the American College of Allergy, Asthma and Immunology

Transcript: While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.

Ruthie: Good afternoon, thank you for joining us. My name is Ruthie Marker. I am delighted to welcome you to this webinar. We have a program focused on nasal polyps and asthma. I would like to go over a few housekeeping details. Everyone will remain muted. We will record today’s webinar and uploaded to our website at a week. You can watch her other recorded webinars at Allergy & Asthma Network.org. Feel free to submit your questions through the Q&A box at the bottom of the screen throughout the presentation. A team member will be monitoring the chat. We will do our best to answer as many questions as possible before we finish up today. This webinar is brought to you in collaboration with the American College of allergy, asthma and immunology. The college offers credits for physicians and attendance credits for all others. You can create a free account to earn credits for this webinar. All attendees will receive a certificate of attendance. Please note that no other continuing education credits will be provided. A few days after the webinar you should receive an email from Zoom with supplemental resources and a link to the recording and a link to download your certificate of attendance. Today’s webinar is titled “Rhinosinusitis, Nasal Polyps and Asthma–What to do?” Research indicates rhinosinusitis rhinosinusitis that affects 5%-12% of the global population among those with chronic rhinosinusitis, 25%-30% also have nasal polyps. Often rhinosinusitis is accompanied by nasal polyps, which are benign growths that obstruct our airflow. Asthma often worsens. Inpatients with rhinosinusitis due to the shared inflammatory pathways. It is my pleasure to introduce our presenter, Dr. Andrew White. Dr. White will discuss advanced techniques, pharmaceutical treatments, surgical interventions and the role of Biologics in managing refractory cases. Dr. Andrew White is a board-certified allergist who provides comprehensive care for patients with allergy and immune related conditions. He treats a wide range of concerns including asthma and food and skin allergies. Dr. White also specializes in diagnosing and managing immune deficiencies such as common variable immunodeficiency and other disorders. His clinical expertise extends to chronic sinusitis. He has additional interests in vocal cord dysfunction and mass cell activation syndrome with a focus on improving patients’ quality of life. With that, thank you, Dr. White, for being here. I will turn it over to you.

Dr. White: Great. Thank you so much, Ruthie, and thank you to the Allergy & Asthma Network for the invitation. I am at Scripps Clinic in Southern California. I have some disclosures that are listed for myself and our moderator. The learning objectives, we will talk a little bit about some of the basic inflammatory pathways relevant to nasal polyps. We will talk about some of the features that tie these diseases together. We will talk about some treatment strategies at the end. This is a challenging talk for me to put together because, including a talk that touches on both polyps and asthma, there are so many things to talk about. I am teasing out some of the more important aspects. There are probably a lot more I am not able to cover. I want to start by focusing on the idea of the unified airway. This is an old study from 2000 that I think does a great job of illustrating this idea of how the nose in the lungs are tied together. The investigators took patients that were grass allergic. They did a bronchoscopy. They sampled different areas of the respiratory tree following that. They looked in the lung, they looked at the upper lobe and they looked at the nose. That is what I want to highlight today. You put allergen in the right-middle lobe and if you go back in the next day you will see it is inflamed. In addition to the right-middle lobe that was instilled, you can see the next day — that is what we see with B, bottom right — there is an increase in the nasal passage. The localized exposure could trigger distant inflammation in the respiratory tract.

You can reverse this experiment and show the same thing. You can put allergen in the nose and demonstrate the lower airway is inflamed. This is where the concept of the unified airway comes from. It refers to the concept that the entire respiratory tract from the tip of the nose to the end of the terminal Gronk you will can be a continuous organ. The middle ear is considered in that. There is a study I just put the figure on the right of asthmatic patients. In that group of patients, they had only the intervention of increasing their inhaled steroid to better control the airways. They show just by doing that patients would have improvement. A fascinating way to connect this. In ARD patients, they suffer with in ear inflammation because it is part of this unified airway. This is an interesting way to think about it. Everything we talk about today will refer back to this idea. Obviously there are differences. This hypothesis can only take a so far. We do not form polyps in the lower airway. That is a disease isolated to the upper airway. In the lower airway we think about basement membrane thickening. The nose has vascular structures not replicated in the lower airway. We have smooth muscle bundles around the tubes that are not relevant to the upper airway. From its limitary standpoint, these things go together. There are a lot of studies looking at gene expression. This is one example of asthmatic children. Children with healthy controls, they sampled gene expression in the nose and trachea. 91% of the gene expression was the same in the upper and lower airway. Genes like the keratin genes that will be involved in us thinking about barrier function are not expressed. Another example. If we think about the inflammatory phenotypes, we know both asthma and sinus disease dominated by type-2 inflammation — it ties the diseases together. This is a study that is extremely highly cited from a group at Northwestern looking at inflammation from a t-1, t-w, or t-3 standpoint. Red is t-2. They did not find it type-1 or type-3.

There are phenotypes where there are mixed patterns. If you scroll down to the very bottom. 87% of these patients have some form of type-2 inflammation. That is what we think about in our patients with severe asthma. 85% have evidence of type-2 inflammation. A shared inflammatory pathway from the upper and lower airway. Just to remind you in this study, because it will continue to come up as we try to tease out these phenotypes, type-1 was defined by a gamma signal, type-3 by more of a neutrophil lick inflammatory signal. Type-2, crystals and protein. I wanted to shift down to talk about some of the basic concepts of how we think about polyp formation in general. Some of this is relevant to the lower airways and some of it is different in the upper airway. It is important as we think through where we are going next in a research and thinking about treating these disorders. The first concept is this idea of endogenous proteases. We are all confronted by things that can damage the epithelial barrier. Items like test mites have content and that can cleave these barriers. It will lead you to epidural water loss and the — as humans, we have endogenous anti-prote ases to balance that out. They irritate the airway. In patients that are prone to problems, they have a lower anti-proteases.

Another concept is cells that while trying to heal damage, the basal cell converts to a different type. These cells are less functional. They form a temporary bandage. Because of these cells, it contributes to some dysfunction of the airway because it is not repopulating in a way that is healthy. Polyps are full of fibrin. It is coming from serum leaking into the tissues because of inflammation. Inpatients that are prone to this you will cross fibrin. It turns out if you take a polyp out into the lab and you put a strong fiber molybdic on it, you can shrink and dissolve the polyp. We do not think about this as much in the other allergic diseases we treat. Some of those are key concepts of why we are forming polyps in the first place. Now we will talk more clinically. These patients that have polyp disease, we know that polyp recurrence is not unusual. Part of our disease control is designed to keep inflammation under control so patients do not re-polyps after surgery. Patients can prevent in a variety of different ways with comorbidities. As we move across to the right of this arrow, you add things like comorbid asthma or patients with AERD or fungal disease. Those patients will be more difficult to treat. We are starting to get the sense of how important comorbid asthma and the unified airway is when we think about treating polyps. It comes up in a Japanese study. They stratified patients into four categories based on the degree of involvement. It was determined by comorbid asthma, intolerance and how inflamed the sinuses were on imaging.

What you see on the left is the curve for occurrence, patients that had been categorized as severe in their component were the most likely to recur. The patients that had — or the least likely to recur. This is something we have been aware of for quite some time, thinking about this in greater detail. One of the greatest things on this list is comorbid asthma. Let’s talk about this. Chronic rhinosinusitis and asthma frequently coexist. This is something allergists are comfortable thinking about. It is different for our ENT colleagues because they are not always thinking about the asthma component. Pulmonary colleagues may not be focused on comorbid sinus disease. How often is asthma a component of CRS? 5%, 10%, 40% or 90%? The answer here — the best answer out of this group would be 40%. Somewhere between 20% and 60%. We can look at this from the CRS perspective and that asthma perspective. Here, the blue slice of the pie are patients with asthma. Someone comes into your clinic with chronic sinus disease. About a 40% chance you find they have comorbid asthma. The other way is less of a strong signal. All asthmatics, 20% have comorbid sinus disease. This is borne out in terms of looking at some of the registry studies for patients with asthma. You can find a significant amount of the patients in the trials have comorbid polyp disease and vice versa. This is a study we did many years ago looking at BERD. As you add more components to their airway disease, the more likely they will have underlying sensitivity. Severe asthma, 15%. A group of patients have comorbid asthma, close to 1/3 will have asked for respiratory disease. Pulling the sinuses and asthma together and thinking about how they influence each other. That brings us to our next slide. How did these actually influence each other? They have been together, but does it matter? Does the upper airway influence the lower airway? I am sure you can see where I am going with this. Here are some bullet points for the effect of sinus surgery on asthma.

This is a great way to tease out the components. Sinus surgery will have an effect in terms of its target on the sinuses. It is not like a biologic where you think you will have effects on the upper and lower. With endoscopic sinus surgery, there are studies that can show improvements on FEV1. Asthma related quality of life, decreased asthma exacerbation rates, decreased hospitalization rates and decreased systemic steroid use. We have seen these patients in her career where there asthma has continued to worsen, we find they have significant sinus disease and we send the presurgery and they come back and there asthma is a lot better, as well. We have considered that is part of the treatment for their asthma. Proper sinus surgery and sinus evaluation. I love this study. This is a group that looked at patients who had the onset of sinus disease and ultimately win for sinus surgery. The very beginning of the study was the moment that first sinus disease diagnosis was entered in the chart. They were followed up until they had sinus surgery. None of the patients could have a diagnosis of asthma at the beginning. What they were looking for was how far along the way and how likely it was for patients to develop an asthma diagnosis from the beginning there sinus disease diagnosis and up until surgery. With it is really important observation in blue that the patients had sinus surgery halted the development of their asthma diagnoses. It seems to have a disease modifying effect. If you look at the rate of asthma diagnosis, if the patients had not had surgery, there is a 4.5 percent rate of asthma diagnosis in that group in red. Once you had the sinus surgery it drops to .4%. A tensile difference. Remember, none of these patients had asthma as they are waiting for surgery. That is what we are looking for. To me, this is a huge effect telling us sinus surgery can have a disease modifying effect purely on the lower airway. This is another study I love to cite. These patients all by definition have reactivity.

They challenged all of these patients like we normally do to prove they have reactivity — this is before surgery. They had a full head of polyps. And then they went to sinus surgery and three or four weeks later they repeated the challenge posed surgery. Only 12 out of 18 patients reacted, meaning six of these patients or 1/3 of the group temporary luster reactivity by simply removing polyps. They had a significant reduction in the mediator with the challenge. Another huge effect — excuse me. A huge effect of the surgery alone just having an effect on Aspen reactivity. The next question, is this just one disease? Are these two different diseases? This is a question for our patients. One of the hypotheses for how this can be if this is one disease? If we make a differential diagnosis. Maybe there is something like IgE. If you are cat allergic, it would make sense that could affect the airway. That falls very short because most of our patients do not have the kind of sensitization and could not explain it. That falls apart. Is this a systemic inflammation but only occurring in the airway? There are a lot of problems with thinking about it from that standpoint. Is this some sort of a trafficking issue? Like we talked about with the asthma challenge study I mentioned at the very beginning — they are trying to get to the lung but maybe there are also being drawn into the upper airway. I think there are some problems with that, for sure. I will share with you a slide about bitter taste receptors that are throughout her respiratory tract and are an interesting way to connect the upper and the lower. I think the best explanation is these patients are prone to problems with barrier and barrier repair and that will occur in the upper and lower airway. There could be other components of their genetics that may predispose them for more of an asthma phenotype. We will see. It will be interesting as we learn more about how to think about the patients that have asthma alone, the patients that have sinus disease alone in the patients that have both of those diseases together. Another study I wanted to highlight connecting both the upper and the lower airway is looking at asthma or COPD related readmission rates. In looking at features that increase the risk for these readmissions.

For asthma, I do not think it would be a surprise for us to stay if you have comorbid allergic rhinosinusitis, maybe that would be a factor. Tobacco use. Some of these things we already know. To me what is very fascinating, and asthmatic patients, even having nonallergic rhinitis is a hazard. You could say maybe this is a feature of asthma. That is true in COPD. COPD patients with nonallergic rhinitis. This is a striking way to say this is not just a problem with allergic sensitization, not just allergic to asthma. There is something about having the upper airway inflamed and dysfunctional along with having a lower airway disease that these things really influence each other. This is a fascinating study. I think it raises a lot more questions about what is happening there with nonallergic rhinitis that is influencing the lower airway. I said I would mention the neurological contribution. These are cell types, sensory cells, modified receptors. They are wired into some of the neurologic responses. You can have increased mucus production, changes in frequency, etc.. These modified taste receptors are able to sense changes from a chemo sensory standpoint. They might sense a drop in glucose because there is a letter bacteria chewing up the glucose. These are known by different names. It is something we will continue to hear more about. A lot of great work in helping us think through these contributions to her respiratory health. This is showing how these are wired in. You can see the cell on the right. The bacteria around it is triggering some sensing from that. It will get wired down into a sensory neuron and he will have the potential for some cholinergic af effects. Now we will switch and talk about treatment. It is something I am pretty passionate about. I will get to some areas I think we need to try to continue to push the needle from a research standpoint. I am coming at this again from the polyp standpoint. That is the easiest way because comorbid asthma is so common and clearly influential. We have advanced therapies in this space. This is coming from euphoria and sharing high level about how we think about using biologics in patients with nasal polyps. History of surgery, if you have recurrence you will have a lower bar to the biologic.

One of the things on the list is diagnosis of comorbid asthma. It is considered one of the features you could use to justify starting a biologic therapy. We look through, how do we decide Biologics and how do we monitor? One of the most important things off the top is thinking about comorbid asthma, N-ERD is the same as AERD. It is clear to all of us if you have CRSwNP, you need to have an asthma specialist involved because she will think a lot more about Biologics and how you will deploy them in that particular type of patient. If we talk about treatment, do we have any evidence that topical treatment for the nose or sinuses could influence asthma? Unfortunately we do not have much evidence at all. There is this one study I put at the top of almost 400 adults and children. They were treated with corticosteroids. They had uncontrolled asthma and they had CRS. This was a double-blind placebo-controlled trial. Treating the upper airway alone did lead to improvements in asthma symptoms but not a major change in FEV1 or asthma quality of life. There is some data that we have. Not aware of any good data for looking at sinus rinses using the delivery system in treating this sinuses to look for improvement in asthma. Similarly, with the steroid eluting stents, we do not have data on that. From a topical standpoint, we do not have much evidence to help us in terms of connecting both the upper and lower airway together. We talked about topical steroids. I have one more slide I will share on that. I will briefly touch on aspirin therapy. That is for patients with comorbid sinus disease. I will talk about Biologics. I talked about surgery in terms of what we know in terms of influence of the lower airway. From a nasal steroid standpoint, we have guidelines I want to share. This is looking at patients with nasal polyps. IFAR states these are better than placebo. Twice-daily might have more of an effect than once daily.

Our GRADE guidelines that are relatively recent recommend corticosteroids for patients with nasal polyps. Sadly, we do not have as strong of evidence as we would like. This is a low certainty and conditional recommendation. What you see here are the various ways you can use to treat so you can have the steroid stent, steroid spray, steroid rents or drops. The stronger the green color, the stronger the clinical benefit. There is no red, not much harm on the list. We are comfortable with the fact it should be a first-line therapy for any of our patients that have CRS with nasal polyps. Aspirin desensitization, we call this aspirin therapy to distinguish the ongoing treatment is different than the desensitization that takes place in the office. We have a lot of studies, about 1000 patients. Five studies is probably not a lot but five double-blind placebo-controlled analysis. This is looking at a variety of therapies including the Biologics. Their summary is that there is a strong effect on polyp growth rate. Secondarily on sinus symptoms. It does not have a regressing effect on polyp’s. Patients that are full of polyps, this will not be a good treatment for them. This should get surgery first. In terms of the unified airway, the lower airway, the effect on asthma is secondary. This is not aspirin therapy, it does not seem to be a treatment that will have a huge effect if the patient is having unstable and difficult to control asthma. It will have a much better effect on the upper airway. There are side effects, especially GI toxicity. 15% of patients will not be able to tolerate being on aspirin. Then we think about the Biologics. That is where we focus a lot of our attention.

We have a lot of options and a lot of ways to think about this. We first have these four agents that have FDA approvals for both asthma and CRS with nasal polyps. We think about these two diseases together we will probably more focused on the top four. Benralizumab did not get FDA approval for CRSwNP. They are not pursuing that anymore. For patients with comorbid disease and were thinking about the unified airway, it might be less of a choice. Everything we have been talking about is for CRS with nasal polyps. We have this big uncertainty. What about the patients that have CRS without nasal polyps? We have no Biologics that are approved for this. The only treatment that has any FDA approval is a delivery. This presents a challenge for us and is the next chapter in therapies for airway disease. How do we think about patients that have non-type-2 signals but still have that same unified airway pathology? I will touch briefly on the different Biologics. I will call out both the upper and the lower airway diseases. Remember, these are all FDA approved for both asthma and nasal polyps, so we know they work. If we look at the Dupilu mab studies, sinus 24 and 52, about 50% of patients had either AERD or asthma or both. This is the unified airway population we want to be talking about. People who have both. You can look at the comorbidities, 63% had surgery, 28% total had AERD. The drug worked and there was improvement in the SNOT 22 score. In the polyp population, you can look at patients who had comorbid asthma and see there is a small improvement in FEV1 and asthma symptoms. This is what we want to see.

We want to see we are treating the upper airway but even in the patients that have asthma, we are simultaneously improving some of their outcomes. In the polyp 1 and polyp 2 studies, these lead to the FDA approval. About a quarter of this group had AERD. Even though you are treating polyps, these patients also have asthma. In these studies we can look at the subgroups and think about it from that standpoint. Are you more likely to get improvement in your polyps if you had comorbid asthma? You can see there is a bit of a stratification there. Patients with AERD might have done better than asthmatic patients in general compared to no asthma. Mepolizumab. Similar analysis. You can see patients that had comorbid asthma did have improvement in their polyp score compared to patients who did not have asthma. This is not necessarily looking at asthma control in the polyp population but looking at asthma is a way to predict response to it therapy. Patients with comorbid asthma may do better. The newest kid on the block is Tezepelumab. We have had approval for asthma in a while but now we have approval for CRSwNP. 17% of the study had AERD. 60% had asthma. It met the primary endpoints are polyp score and symptom improvement. Significant improvement in SNOT 22 score, as well. If you look at some of the tables that are buried deep, you can see the effects of underlying AERD or asthma on response rates. We do not see it as much of the difference here as we did. It does not seem like that has as much of an influence. The final one which is not yet on the market, Depemokimab. They have showed positive studies in both asthma and — 18% in their polyp cohort had AERD. 55% with asthma. Maybe similar to what we saw in a study it supports the patients will have a better response compared to the patients that do not have asthma and do not have AERD. We have started to use the term remission in asthma.

I am sure everyone is familiar with this. That is being extended for sinus disease as well. I would advocate a lot of patients who have comorbid disease, we want their entire respiratory tract to be in remission. Both asthma remission and polyp remission — full remission. Cure means you have had sustained remission for five years. Off of treatment, you are no longer on treatment. Most of the time we are aiming for remission as the best we can get right now. I want to start thinking about this because many of the patients who are coming to us in our allergy practices have both sinus disease and asthma. We know we are trying to treat both of these at the same time. Thinking through that and juggling through that, understanding with the patient wants is important. We need to start finding studies that will help with that, as well. This is a small study from Europe. They looked at 20 patients who had severe asthma and comorbid nasal polyps. There asthma was under reasonably good control of the biologic. Their polyp disease was not well-controlled. These patients were then switched to dupilumab. These patients were not having good sinus disease control. This led to improvement in sinus outcomes in all of the patients. We have moved from having good asthma control to now having good control of the entire airway, except for one patient whether asthma worsened. We improve their sinus disease but that particular patient now had asthma problems. This really illustrates the problem we are being faced with. We know these drugs work for the diseases they are FDA approved for, but many of our patients have upper and lower disease simultaneously. The patients will want one treatment that does it all. That is the goal. I think this is where we need to have a lot more studies like this and really thinking through reasonable goals for our therapy. We do not have a lot of studies. These are just a few I will highlight. This is looking at Tezepulumab for severe asthma. Many of these patients had sinus disease and an elevated SNOT 22 score, meaning to had a lot of sinus symptoms. If you take asthma patients and put them on Tezepulumab, not only does their asthma improved but there is an improvement in SNOT-22 . Score’s importantly, it was improving the outcome for them. They were treating both upper and lower airway simultaneously. This is another paper I would like to see replicated in a lot of different ways and in bigger numbers. This is a European group that looked at what they called super responders. That took patients with comorbid asthma and CRS with nasal polyps and they wanted to see in their group — they wanted to identify patients on Mepolizumab that essentially had complete control. No exacerbations of Astra, they did not need any oral corticosteroids. Simultaneously, their sinus disease was completely controlled and they used a SNOT-22 control score of less than eight, meaning no real symptoms at all. Upper and lower airways completely controlled and they call that super responders. They were able to identify of these 19 subjects that 12 of them at that definition. They were able to do some gene expression and identify some gene signals that could be unique to this cohort and would be great for us as clinicians if we could identify early on some ways to predict which biologic may lead to this super responders status. I think it is important to define this and have this be a goal of therapy.

If you were this patient being on Mepolizumab, I am sure their goal would be into this super responder category where they have virtually no symptoms. This is another study that gets at that. It is looking at patients that have severe asthma that had comorbid disease and looking at improvement in sense of smell. In this study they did not have access — we are looking at Omalizumab, Mepolizumab. There is a small percentage of patients that had a 20% improvement in their sense of smell. Another 15% had personal improvement. A big part of the group did not have improvement in their sense of smell. That is something we see clinically. . We have asthma patients with comorbid disease but they are bothered by other things. That is the end of the talk. I am going to give you my thoughts on some ideas for going forward. And then I am happy if we have some questions or time for discussion. When we see these patients that have both upper and lower airway disease together, especially with nasal polyposis, part of our job is to identify if there is part of the disease that is most important? Often there is. The patients probably have both but they may say my sinuses are going crazy, the surgeons are sending them back because their polyps are regrowing. Despite their asthma, we are focused more on upper airway disease. The opposite is also true. We get referrals from the patient being hospitalized twice for asthma in the last year. We see they have polyps. We do a Ct, we find they have a problem but that is not what is bothering the patient the most are contributing the most to their morbidity. And some of those patients we are focused more on the lower airway. For many patients it is both. You look at how many times they use prednisone in a year. Was that for your sinuses or your asthma? They stare blankly at me — it is for both. It happens every time I flare up, the whole thing flairs up. It is a really important thing. I would encourage if you do not do this to use some sort of symptom or control testing in the clinic. We do SNOT-22 scores, ACT scores on all of our patients at every visit.

I am surprised at how often I will be talking mostly about the asthma, the patient does not bring up their airway and I look at their SNOT-22 score ended is 40. You are symptomatic. Talk about your sinuses. We need more evidence and more discussion about the role of sinus surgery in a patient that has comorbid asthma. I think there is a lot of potential for great collaboration here. As we think through our workflow for surgery and Biologics and patients that have polyp disease, this will be an important ongoing area of discussion. The opposite would be the patients we identify in their disease course maybe earlier on that have some really significant risk factors for early recurrence of their sinus disease. Or of their asthma. Maybe we do not necessarily wait for them to fail their first surgery, or have their third asthma exacerbation, starting to get remodeling. If we can identify some of these features early on, try to get things under control and aim toward remission of the upper airway and lower airway disease together, I think that will be a great target. We need more studies and evidence to help us as we are figuring this out. It is really exciting because we have all of these agents that have shared benefits in the upper and lower airway together. I think with that — yep, I am finished and we have time for questions. I am happy to field any of them, or comments, if there are any comments, as well.

Ruthie: OK. I was getting scared. My microphone did not want to work. We do have some questions. You were ending on the topic of a couple of our questions, which were in regard to Biologics. In your experience — maybe it is more so specific to your patients but also in studies — how do Biologics compare with endoscopic sinus surgery and long-term outcomes and quality of life of your patients?

Dr. White: That is a great question. The question gets to the dilemma we are faced with here. When you have a patient that is full of polyps and they are miserable and they have not had surgery at that point, if you were to compare surgery to biologic therapy, how do we do that? We know there is a significant portion of patients they can have long-term control of their disease after surgery. Because of that, there is a cost-effectiveness argument to be made and not using a biologic that will be a long-term treatment for a patient if they may do well for five or 10 years after surgery. That is where the argument comes from. We have little evidence to look at these compare to each other. There are some studies that look at biologic therapy and then compare that. They will take patients that have surgery, they look at them at six months. They have patients who start a biologic and look at them at six months. It is not randomized but they can see the benefit. In general, it seems to have comparable outcomes in terms of what you get. I think the other question is the durability of the response and that is something we do not know. Share, at six months we may see they stack up the same but what about it two years and three years? Those are things we do not have evidence for but there are starting to be some studies looking at biologic plus surgery and then biologic against surgery to see how they stack up.

Ruthie: Thank you. Another question — are there emerging biomarkers that could allow early detection of type-2 diseases in these patients?

Dr. White: There are potentially going to be some gene expression. They will not be super accessible right off the bat but that could be helpful. There is a lot of work looking at nasal gene expression and how it might predict response to therapies. Also something like — there are some more localized biomarkers that may also start to come up as useful for us. I do not think we are there yet. I would encourage if you can to get your pathologists to count surgical tissue. We have started to do that. Although we do not have a hard and fast cut off in what constitutes disease, having that count will be helpful as we move forward. Even if it is 10 versus less than 10, something like that could be useful. There is work in that direction but we are not there yet.

Ruthie: There is a question, if you could, it might be from more of a caregiver/provider standpoint. Expanding a little bit more on the sinus surgery that is being done on patients that have recurrent nasal polyps.

Dr. White: Maybe the question is — there are a couple ways to think about sinus surgery — caveat, I am not a surgeon so I’m telling you from an allergist’s perspective. There is a standard first step sinus surgery focused in an area that will ventilate the sinuses and open up the air cells. That is a standard surgery that is commonly done as a first step. Patients can have recurrence from that surgery. Very early recurrence would be a red flag that may be the patient should be on a biologic. But what if it is 2, 3, four years down the line? There is a more extensive surgery that is called a frontal drill out or a draft 3. The surgery goes up into the frontal sinuses, over in the forehead, and makes the opening even wider and can get out more disease. There is a consideration a more extensive surgery could help certain patients. There is debate in the ENT literature on whether patients who present with more severe disease should have an extensive surgery. The final thing I will tell you, it is a new concept that has emerged from ENT. It is called COSI, the completeness of surgery index. It is a great way for the surgeons to be able to more objectively assess previous surgery. If you had sinus surgery and then you come in a year or two later with recurrent disease, the ENT doctors can have a scoring system and say, well, you have a complete surgery, there is not more surgery to do. We should think about a medical therapy. Versus your surgical index completeness of surgery is pretty low. There is a lot of benefit from finishing the job. Those are the ways I would about surgery. It is certainly worth getting a second opinion because there is a lot in the eye of the beholder from the surgeon in terms of what they think could benefit the patient. I hope that answer the question.

Ruthie: I think so. That is all the time we have for today. I appreciate your presentation and your thoughtful responses to the questions we had today, Dr. White. In a couple of days, Zoom will email you a link with a link with the recording and supplemental resources. You will also have an evaluation sent to you after today’s webinar, as well as a resource link that will be emailed to you. Be sure to check out and register for our upcoming webinar in January, on January 20. Dr. Mora will be presenting on RSV. As always, thank you for being here today and for participating in our advances webinar series. Thank you so much and I hope everyone has a great day. Thank you, Dr. White.