Remission of Asthma: Review of Consensus Statement (Recording)

,

This webinar was recorded on November 12, 2024

With the introduction of new therapies for asthma like biologics, achieving disease remission has become a new goal of treatment and classifying asthma control is in transition. In December 2023, the Annals of Allergy, Asthma & Immunology published a consensus statement between the American College of Allergy, Asthma, and Immunology, American Academy of Allergy, Asthma, and Immunology, and American Thoracic Society to update the definition of clinical remission in asthma. In this webinar, learn more about the consensus statement and the outcomes of the working group.

Speaker:

  • Michael S. Blaiss, MD
    Clinical Professor of Pediatrics
    Medical College of Georgia at Augusta University
    Augusta, Georgia

Michael S. Blaiss, MD, is a clinical professor of pediatrics at Medical College of Georgia in Augusta, Georgia, and allergist at Good Samaritan Health Center of Gwinnett in Norcross, Georgia.  He received his medical degree from the University of Tennessee Center for Health Sciences and did pediatrics at University of Tennessee/Le Bonheur Children’s Medical Center in Memphis and completed a fellowship in allergy/immunology at Ochsner Medical Foundation in New Orleans, Louisiana.

He is past president of the American College of Allergy, Asthma and Immunology. He served as treasurer of the American Board of Allergy and Clinical Immunology, a past member of the Board of Directors of the World Allergy Organization and past president of the Tennessee and Louisiana Societies of Allergy, Asthma and Immunology. He was Executive Medical Director of the American College of Allergy, Asthma, and Immunology. Dr. Blaiss has published about 200 scientific peer-reviewed articles and presented at more than 500 meetings and seminars throughout the world.

This Advances webinar is 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 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

Logo for the American College of Allergy, Asthma & Immunology next to the word "allergist," both with stylized circular designs.

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.

Lynda: Hi, everyone. We will get started in a minute. Just waiting for more folks to log in. I appreciate all of you who joined us here today. If you want to tell us where you are from, that would be really great. If you don’t, that is OK, too. All right. We will go ahead and get started. Hello, everyone. Thank you for joining us today. I am Lynda Mitchell. Welcome to this afternoon’s webinar. We are going to hear a really interesting discussion on asthma with Dr. Michael Blaiss as today’s presenter. We have a few housekeeping items to go over before today’s webinar begins. All participants will be on mute for the webinar. We will be recording the webinar and posting it on our website within a few days after today’s session. You will be able to find the webinar on our website on the homepage if you just scroll down to where we keep all of our recorded webinars following their completion. You will also see upcoming webinars as well. This webinar will be one hour in length, and that will include time for questions at the end. But you can put your questions into the Q&A pane at any time and we will go through and keep track of them so we can ask them later on. The Q&A pane is at the bottom of your menu. There is a similar chat box to put your questions in the Q&A. We will get to as many questions as we can before we conclude today’s webinar. This is a webinar in partnership with the American College of Allergy, Asthma, and Immunology. ACAAI offers CME’s for physicians in attendance. You can create a free account and receive a certificate through the portal or the webinars. All attendees can have a certificate of attendance. If you would like that, we will drop a link in the chat and follow-up with an email and give you a link to it as well there. A few days after the webinar, you will receive an email of supplemental information to download the certificate of attendance. And we will try to also like I said add the certificate of attendance link in the chat. So let’s get started. Today’s topic is remission of asthma. What is it? With the introduction of new therapies, achieving disease remission has become a new goal for treatment and classifying asthma control in its transition. In December of 2023, the Annals of Allergy, Asthma, and Immunology published a consensus statement between the American College of Allergy, Asthma, and Immunology, the American Academy of Allergy, Asthma, and Immunology, and the American Thoracic Society to update the definition of clinical remission of asthma. It is my pleasure to introduce our speaker, Dr. Michael Blaiss. Dr. Blaiss is a clinical professor of pediatrics at the medical College of Georgia and of the stock, Georgia — in Augusta, Georgia. He received his medical degree from the University of Tennessee Center for health sciences and it pediatrics at the University of Tennessee while there. children’s Medical Center in Memphis and completed a fellowship at a medical foundation in New Orleans. He is president of the American College of Allergy, Asthma, and Immunology and also served as treasurer of the American Board of allergy and clinical immunology, and member of the board of directors of the world allergy organization, and past president of the Tennessee and the Louisiana societies of Allergy, Asthma, and Immunology. He was the executive director of the American College of Allergy, Asthma, and Immunology until recently. Dr. Blaiss has published over 200 peer-reviewed articles and presented with 500 meetings and seminars throughout the world so we are in for a real treat today. Thank you for being here, Dr. Blaiss. I will turn it over to you.

Dr. Blaiss: Thank you, Lynda. Thanks for that kind introduction. Welcome, everyone. Thanks for joining me on a subject I am very passionate about, and that in fact is remission and asthma. So these are my disclosures for this particular lecture. And I have three learning objectives that I want to try to cover today with you. In one, very importantly, understanding the differences between the term asthma control, which is what we have been using for numerous years, and now we are starting to see in the literature the term for asthma remission, and with that I think it is very important for all of us to understand there are in fact different definitions of remission in asthma and one of the key points I will be covering is there is no complete consensus at this time worldwide exactly what we mean by remission in asthma. And because of that, we have developed, at I was on the workgroup, joint consensus statement as you heard Lynda mention through the American College and the American Academy of Allergy, Asthma, and Immunology and the American Thoracic Society on what we felt should be included if in fact we talk about remission on treatment and asthma. I will cover that in detail for you. So let’s first start talking about asthma control. Because that is what we have been talking about with our patients basically since the 1970’s. And with that, the reason we start to understand about asthma control is understanding that asthma is a chronic inflammatory condition of the airways. And if in fact we can control the underlying inflammation, we can decrease symptoms, exacerbations, and improve patients’s lung function. We started understanding this with the use of inherited corticosteroids — inhaled corticosteroids, and that is when we see the term asthma control. You may be familiar with the right on this slide, rules of two. I still in fact use this in my clinic situation. So they ask these three questions. Do you take a rescue inhaler for asthma symptoms more than two times per week? Do you wake up at night with your asthma symptoms more than two times per month? Do you refill your rescue inhaler more than two times per year? 

Again, if you answer yes to any of these, in fact your asthma is not under control. Now, we also have the GINA guidelines. GINA is the global initiative in asthma. This is a group of clinicians, others that are involved in asthma management throughout the world who put together a monogram on a yearly basis, including the most updated guidelines in the management of patients with asthma. For a long time, they in fact have talked about asthma control. And as you can see here, they mention that the level of asthma control, the extent to which the manifestations of asthma can be observed in the patient or have been reduced or removed by treatment. They talk about asthma control in fact in two major domains. One is what is going on presently, and that is symptom control. But very importantly, future risk of adverse outcomes. So if in fact we look at the GINA monograph, this comes from them. This is there — their assessment of asthma control. First we look at symptom control. It asks, what has happened over the past four weeks? There are four questions here. Do you have daytime symptoms more than twice a week? Nighttime awakenings due to asthma? Have you been using a reliever for symptoms more than twice a week? Any activity limitations due to asthma? If you answer no to all of these, you are well-controlled. If you answer yes to one or two of these my are partly controlled. If you answer yes to three or four of these, you are not controlled. For most of us, this is the definition we have been using. They also talk about risk factors for poor asthma control. In other words, future risk. One of the things they stress here is monitoring pulmonary functions after patients are placed on controller therapy, looking at the FEV1. And the reason they stress this is we know the lower the patient’s FEV1, the lower the risk for asthma exacerbation. With that, let’s move on and talk about the subject for today. That in fact is remission. So I am sure you are familiar that the term remission has been used in many different disease states that are commonly seen in our patient population. So probably the most common way we hear remission used in a diseased that is cancer. You see the finish and from the National Cancer Institute where remission is a decrease or disappearance of signs and symptoms of cancer. They talk about partial remission. They talk about complete remission. And in complete remission, all the signs and symptoms have disappeared but cancer may still be in the body. Also, we have edition of remission from the American diabetes Association related to type 2 diabetes. So they talk about remission as being defined as a return to the hemoglobin A1D to less than 6.5% following intervention or six months in the absence of usual glucose lowering therapy. The one I want to talk about today is related to rheumatoid arthritis because it relates more to asthma. So this definition as you can see talks about one or fewer swelling joints or tender joints. Also, look and see if it is in the body. And disease modifying drugs and Biologics have led to a great increase in remission in this particular condition. So if we — the model and how to achieve remission asthma, let’s compare the two. Rheumatoid arthritis is an incurable inflammatory condition. We can say the same thing for severe asthma. We talk about rheumatoid arthritis. We have disease progression that occurs in the patients. There reversible joint damage and visible disability. And again, we know in severe asthma we get a disease progression that can lead to fixed obstructive lung disease, irreversible decline. This can lead to significant disability in our patient population. In rheumatoid arthritis, we mentioned they have multiple targeted therapies. They can lead to a realistic goal of clinical remission. We now have in asthma several targeted therapies out there. The question is, do these possibly lead to remission in our patient population suffering with asthma. Now, when one goes through the literature and sees different types of remission in asthma and the one we are going to ke ony — key today because it is the one most commonly seen in studies out there is clinical remission. This could be on or off therapy but it is in most cases on therapy. Generally, this definition talks about no symptoms, no exacerbations, normal lung function. Also, you may see — including normalization. Normalization of the different biomarkers in asthma, such as inhaled nitric oxide. Now, this is an important slide because this — .

Lynda: We lost you for just a minute. I don’t know if your Internet connectivity is a little off. And you are on mute. While Dr. Blaiss is working on his connectivity, just wanted to let you know there was a question about the slides. We don’t provide slides but will provide a recording and will be following up with that in a few days. Also, the consensus statement that Dr. Blaiss will be referring to, we will provide you with a link to that in the Journal so that you can take a look at the whole thing. With that, I will hand it back to Dr. Blaiss. Dr. Blaiss: OK. Sorry about that. Not sure what happened there. Going back to the slide, how do we assess remission in asthma? Because now we are talking about, what things do we do to define it? One is clinical symptoms. So how long do you have sustained absence of symptoms? So some of the definitions we see are six months, some are one year, some are longer, so you have to know that. One is the use of validated instruments in asthma control. Are they using the asthma control questionnaire? And what score are they using? Are they using less than 1.25 or 0.75? Less than 0.75 is a higher standard so this patients would fall under the definition of having remission. And does it measure use of bronchodilators or not? Do these definitions of remission monitor bronchodilators? What about no exacerbations? Does that mean no burst of oral corticosteroids, no hospitalizations? No one scheduled doctors visits due to asthma. No one missed school or work due to asthma. What about lung function? Is instable lung function? Is it normal lung function? Do you have to show improvement in lung function? Such as the greater than equal to 100 milliliters Such as the greater than equal to 100 milliliters? What about medication requirements? Are there none or do you have to show a decrease in need for medication like inhaled steroids? Do you have to show a decrease in rescue inhaler use? And if we are talking about complete remission, what about normalization of asthma pathophysiology? Do you measure biomarkers or have to have a negative test or show normal histology? The point being here, depending on which of these things you use is going to in fact define again what percent of patients may in fact fall under remission. If we only use two or three of these, a higher percentage may be in remission versus using several of these, so I think we always have to look at that when looking at papers that now are defining remission since there is no true standard. So is remission possible? The answer is absolutely yes. We know spontaneous remission of occurs in our patients with asthma. In fact, it is not uncommon in the pediatric population. It is part of the natural history of the disease. So this is a study that was in the Journal of allergy — in the Journal of Allergy, Asthma, and Immunology. 

They look at childhood asthma at the age of eight. It can predict remission of disease by early adulthood. If we look here, if in fact at the age of eight it is less than 80%, the rate of going into spontaneous remission by young adulthood was between 9.5% up to 27.6%. But if it was greater than 80% at the age of eight, it ranged anywhere from 53.8% up to 82.6%. So remission we know can occur. Now, this is a study out of Finland, and they looked at asthma remission by age, a diagnosis, and gender in a population study. These were physician diagnosed asthma patients, and they were characterized whether they had early onset asthma between the ages of zero and 11 years of age, intermediate 12 to 39 years , and late diagnosis, 40 to 69 years. So if you look over on the left and you look at the portion of remission related to age and diagnosis, you will see here that for the zero to 11 group, about 30% went into remission. The 12 to 39 age group, about 17%. In the late diagnosed, 40 to 69 years, about 5%. If you look at the right, here we are looking at gender, so males and females. You will notice for the zero to 11 group that much higher statistically higher rate of going into remission for male children with asthma versus female. OK. Now this paper that was published back in 2020 really started people to look at the Biologics as far as a clinical remission in the patient population. So here was their definition of clinical remission on treatment. That is what we will key on here. They talk about for 12 months or greater so you have to see this for at least 12 months. Sustained absence of significant asthma symptoms based on a validated instrument. Optimized and stabilized lung function. They did not get exactly what they meant there. 

Patient and health care provider agreement regarding disease remission. That to me is kind of a soft measure because I am not sure any of us know exactly how to define remission as yet. And no use of systemic corticosteroid therapy for exacerbation treatment or long-term disease control, which I think is something we could all agree on. Now, what we have seen over the last few years is numerous countries, different societies in these countries, pulmonology, allergy, that in fact have developed definitions for clinical remission. This is not the whole list, but I put it on here. There are five of these here. Germany, Spain, Italy, Japan. And that U.S. guidelines we will talk about in a minute. So you can see here symptom assessment. And again, you can see differences here. Germany and Spain, it says absence of symptoms. If you go over to Italy, you see the ACT and ACQ. Japan uses a very high standard in the control test. Greater than or equal to 23. As I will talk about for the U.S. guidelines that was published, you can use these three validated instruments the ACT, ARQ, or the ACQ with a higher standard of less than 0.75. Lung function, some of these have to be stable. Others say they have to be optimized. All agreed on no exacerbations, no oral corticosteroid use. As you can see for the U.S. one, we added several other things like no missed school or work, no hire than the Ora Media inhaled dose — no higher than Ora Media inhaled dose of steroid. These are looking at different Biologics and multiple Biologics. These are all post hoc analysis from the Phase 3 or open label extension studies out there. And what we see here if you look at absence of symptoms, you see different standards being used as far as validated instruments. If we look at optimized stabilized lung function, some are using FEV greater than 80%. 

Some have to show a 100 milliliter increase. Some are not using any lung function data. All have no exacerbations, no oral corticosteroid use. When you look at the prevalence of clinical remission, you can see it can range anywhere from 14% to 43%. Again, most of this variation is because people are using different definitions. In just a second, I will show you the 2022 Danish registry where the prevalence of clinical remission was in fact 19%. I think it is one of the best studies that has been done so far. Now, one of the things I did was look at all of these studies and in fact look at post hoc analysis. These were all Phase 3 studies. Three different Biologics. They had to do this for at least 12 months. So if we look here for our first asthma control, you will see the one on the left and the one on the right used a higher standard for asthma control, so that will have a difference. Then if we look at lung function, we can see the one on the left showed greater than 100 milliliters improvement. With the middle, you just had to show the FEV1 was greater than 80%. And on the right, two definitions could be given including greater than 20% from baseline. When we get to the no oral corticosteroid use, none of these were on maintenance. They did not use any steroids. No severe exacerbations. If you look at the clinical remission rate here, it falls under 14.5% , 20%, 12.7%. Now you will say the one on the right is not as good, but they added another measure. They added the health care professional and patient assessment of severity. So that is probably why their numbers are in fact lower. Again, depending on how you define remission, you will get different clinical remission rates, so do not be fooled. Now, this is the study published this year in chest that looked at clinical response and remission. , it was part of the Danish — it was part of the Danish severe asthma registry. They are placed on a biologic in Denmark and go on this registry. They defined clinical response after 12 months was either a 50% reduction in exacerbation or greater than 50% reduction, maintenance, or corticosteroid does. We want to keep on their definition for clinical remission. It is not super rigorous. Sensation of exacerbations and maintenance of oral corticosteroids, normalization of lung function FEV

[LAUGHTER]

Greater than 80% — lung function, FEV1 greater than 80%, and a CQ of — ACQ less than 1.5. We have 500 patients placed on Biologics in this registry. What you will notice in the red part of the pie chart over on the left, that is no response. The kind of dark blue is the clinical response. And then the gray is in fact remission. So you will notice all the Biologics. There was about 21% that had no response to the biologically replaced on. 79% had a clinical response. If we look over at the right of the pie chart, now we are looking at what percent of patients that got a clinical response met their definition of remission. Of that, it was 24%. Out of the total patients that were placed on a Biologic, 19% went into remission. And then it lists some things here I will not go over in detail of things that say distinguished likelihood of clinical response versus clinical remission. In other words, if we look here, females were less likely to go into clinical remission. Patients with a higher BMI were less likely to go into remission. If we look at nasal polyps, they were more likely to go into remission. Now, what I showing you here is the criteria that they use in Denmark as far as determining when to put a patient on a biologic and then which biologic. It pretty much falls in line with what we doing the United States. Maybe a little stricter. 

These are patients on a high dose of steroid and at least another controller. They could have been on maintenance oral corticosteroids. They had at least two exacerbations in the last 12 months or steroids 50% of the time. Used pretty much the same definitions that we use for these Biologics decide which one to put the patient on. Allergy symptoms after exposure to allergen , the drugs related to blood, and for the offer products, exhaled nitric oxide. Now we will look at the results of which biologic the patient was placed on. So if we look at the top of the pie chart, we are looking at ANTI-IGE. 28% had no response. Out of the total group, 6% went into remission. If we look at the IL5 drugs, 22% had no response. Of the total, 19% went into remission. If we look at the offer drugs, 8% had no response. 30% of the total went into remission. If you look at the right, we are looking at characteristics that may help tell us which patients. If you look at the top, you will notice not surprising that the higher they were, the more likely the offer drugs would show clinical remission. If we look at total IGE, kind of interesting. Anti-IGE, there was not any relationship, but there was with the anti-IL5 products. And then for inhaled nitric oxide, not surprising again the offer drugs more likely go in remission. If you look at anti-IGE, they are less likely to infect fact go into remission. I think this is some interesting data. Everyone using the same measure, it gives you an idea of what one may see using the modified criteria for clinical response. 

This is an interesting study out of Israel that was also published this year in respiratory medicine. It is looking at a comparison of clinical remission for severe asthma patients receiving biologic therapy. So these were adults. They had to have been on the Biologics for at least six months. And then they used lots of different definitions. The reason I am trimming this is to show you that depending on what definitions are used will determine what percent of patients are “in remission.” They look at things like no steroid use for six months or 12 months. No exacerbations for six months or 12 months. They used four different criteria for lung function. So things like a FEV1 or improvement of 100 milliliters or 10%. For asthma symptom control, they used ACQ — ACT and they used the different ACQ scores, less than 1.5 and less than 0.75. Now, these were the treatments that were used. What they saw here was 31 of these patients, 12 or 31% received at least one biologic before the current and three had two different Biologics previously. The most common reason again, and we see this in the clinic, is in response to treatment. That was 83.3%. So again, kind of like we saw from the Danish study. This is looking at these different criteria. What percent of the patients met that criteria for remission. If you look at no corticosteroid use, the top one, number one, if it was six months, 71 .5% made that as far as remission. If you go to 12 months, it drops to 74.4%. You see the same type of thing for exacerbations if you look at six months versus 12 months. Again, less at 12 months. If you look at lung function, you will see a big difference here. If you measure the FEV1 greater than or equal to 0.75, it was only 48.7%. If it was approved by greater than 100 milliliters, it was 76.3%. And then if you look at symptom control, you can see here. Look at 4B and 4C. 4B was the lower standard. But if you use a higher standard, it drops down to 38.5%. So when you kind of put all of this together, if you look over at the right, the combined criteria with no systemic steroids or exacerbations for 12 months, the total rate of remission depending on how you define it goes anywhere from as high as 41% to an fact as low as 20.5%. So again, depending on what is used in the definition of remission, it is going to make a major difference in patients that in fact have remission. That is what you look at that when you look at studies purporting this particular drug had a high level of remission. They may not have used a very strong criteria. OK. So the remainder of the time I want to spend on the college and Academy and ATS framework for on treatment clinical remission. So in this definition, in fact, it includes things you have already heard a lot. No exacerbations requiring oral steroids. Stabilized, optimized FEV1. And using symptom controlled validated measures. ACQ with the higher standard. But also, we felt information has to be a higher standard than control, so we added several other things we think should be added. 

We think patients should not have to have high dust inhaled steroid which can have side effects, slow to medium dose inhaled steroid — so low to medium dose inhaled steroid. They should not be missing days of school or work and they should rarely need to use upper reliever treatment. So why did we develop this consensus statement? And the reason was that we felt it had to be on the professional mama — the professional medical societies that do this. GINA hopefully will do something in the future. Maybe we can all come together, but we really felt that it needed to be the organizations. As I probably already told you, there is a left confusion out there — a lot of confusions out there with definitions. We really need over time to come to some kind of consensus. The real reason we put this together again as we felt this definition had to be higher than asthma control. Otherwise, all we are talking about his glorified control. So we felt this consensus statement was a framework. It is not what has to be, but it is a framework. It is a first step as far as a unified definition. Hopefully again the different groups can come together and again get a unified definition like we have for asthma control. So the above organizations and the American Academy of pediatrics had members on this consensus report. It was also endorsed by a European group, the European forum for research and education in allergy and airway diseases. So how did the work group come up with the six criteria? So we used the modified Delphi approach. We all worked together and went back and forth developing definitions and then getting at least a consensus of the members to agree to it. So there were two things that was unanimous. That was no exacerbations requiring physician visit, emergency care, hospitalization, steroid use for asthma. The other thing that is not in the other remission definitions you have seen again is this no missed school or work over a 12 month period due to asthma related symptoms. We thought that was important because we want a higher standard than just control. Then we said stable and optimized lung functions over the 12 month period with a minimum of two measurements during the year. All of these other definitions can use only one. But does not really tell you what is going on over a 12 month period? So we felt it had to be a minimum of two. One of the things we did not say is FEV1 greater than 80% or a particular improvement in lung function. The reason we did not do that is because we know that some of these patients are going to already have remodeling. They are going to have a degree of fixed obstructive lung disease, especially if you have severe asthma. We did not want any absolute numbers. So to give you an example here, if you have a patient with FEV1 65% over 12 months and they improved to 70% but they still meet all the other criteria we have for remission, we would say that patient is in remission because we have optimized their lung function. They just have an element of fixed lung disease. And number four here we felt also very strongly about. 

That is, what medications can the patient still be on? To say in fact they are in remission. Our thought here was, again, that if the patient is on Biologics and still needs high dose inhaled corticosteroid, window that can lead to systemic side effects. So again, if we wanted a higher standard than just control, we felt that the inhaled corticosteroids needed to be tapered down to a low to medium dose. We know there are no long-term studies validating this, but they need to be done. But to us, we felt that again if we are going to call it remission, it needs to be a higher standard.And then the symptoms as far as being measured with validated instruments, ACT, ARQ, ACQ, we thought that there has to be a minimum of two measurements over a year period of time. Remember, these questionnaires ask the patient how they have been over the last four weeks so even if you only do two, that is eight weeks or to month out of the 12. This is a higher standard than other people have set. And then very importantly we felt that you needed to measure reliever use. Reliever use is measured in control. We mentioned that previously. We thought it had to be a higher standard than what asthma control is. We came up and this took a lot of discussion back and forth and a lot of debate between the different members. We came up with a consensus that it should be no more than one time that they need to use reliever therapy over a one-month period. We know this is just a starting point. And again, I think all of us around the world interested in asthma and remission would eventually need to come together and make some decision here, but we felt that it had to be a higher standard than what was seen with asthma control. So we felt or needed some way to evaluate symptoms. The good news is exacerbations in oral steroid bursts are not regular events in the vast majority of our asthma patients. So rescue use, missing days of school and work really give us more information on how the patient is doing daily. And again, this is a step up from asthma control. So what we are dealing with here is in most cases we could get control of the patients now. There may be a small percentage of patients that can in fact reach clinical remission depending on what definition is used. Hopefully in the future we can get to complete remission where we see histologic changes back to normal. And then obviously what we want for all of our patients and hopefully one day we will have that is a true cure for this condition. So what I want to leave you with is in fact remission is an evolving process here. So be careful when you hear somebody say that this patient’s asthma is in remission, because we don’t really have a definitive definition yet. We need to take all of this. It needs to be validated, refined, and to come to a consensus worldwide exactly what we mean by remission and asthma. The good news is GINA this year did a talk about remission in their paper. And hopefully we will see may be the future they will develop a criteria. They talked about validating proposed criteria for remission on treatment will depend on intended purposes. They are kind of looking at it right now, looking at different things. Whether you have remission as an assessment tool for clinical practice, and I don’t think we are anywhere near there and will never tell a patient at this point they are in remission. Prognosis for continued long-term stability and for identifying new targets of therapy. So in conclusion, remission in asthma is a concept in motion. 

There is an ongoing debate about the exact criteria for clinical remission in asthma. Everyone agrees on those systemic corticosteroids and no asthma exacerbations. Really, all the other aspects are still under discussion. Most workgroups have stated all criteria needs to be done for at least 12 months. All remission guidelines agree that excellent asthma control and improved or stabilized lung functions are essential, but the best way is not clear yet. Whereas biologic medications seem to increase remission rates based on some definitions, these rates are still low, 20% to 30%. Remember, the Danish study I said was 19%. No studies yet use the stricter criteria we developed in the U.S. consensus paper. At least in my opinion that would lead to a lower remission rate percentage related to the Biologics. So there is no doubt biologic medications have revolutionized asthma treatment, especially in our severe asthma patients. But I think it is important to realize they alone are not a guaranteed path to remission, let alone a complete remission. We need even better treatments for our patients with asthma and much more research is needed in remission for all of our patients suffering with this condition. So I am going to stop there. I apologize for the interruption we had. I am happy to answer any questions. Thank you.

Lynda: Thank you, Dr. Blaiss. That was really a wonderful presentation about some exciting opportunities to have asthma remission when it was not possible in the past. We do have some questions. I have a feeling once we get started some more on come in. The first one we had was “thank you for your insightful presentation. I know exacerbations informs a lot of the definitions. Are exacerbations consistently defined or assessed by different clinical societies, clinicians, and researchers?” Dr. Blaiss: That is a wonderful question. Generally, we are talking about most of these definitions are using severe exacerbation where in cases where patients are ending up requiring a burst of oral steroids or they end up in the emergency department and and up requiring corticosteroids or they are hospitalized. The U.S. consensus because we added rescue treatment would be even what you would consider a mild exacerbation. So again, all of this needs to eventually be worked out. If you look at the Biologics and studies, there have been the post hoc analysis. Those are all severe exacerbation. But we felt that any exacerbation requiring albuterol was significant. If it was more than once a month, it would lead to the patient not in fact having remission.

Lynda: Great. Thank you. Next question. This is possible for a patient with asthma who smokes or vapes to obtain clinical remission? Is there a definition statement on this? Would it be helpful or motivating for those with asthma to quit or increase the potential for experiencing remission?

Dr. Blaiss: So, one, there is no definition or anything like that in the consensus statement or from any of the other countries that I have seen. Obviously, patients that smoke and vape we no intent to have more severe disease and do not respond as well to the particular treatment. We could tell those particular patients that are much less likely to go on remission. But I also want to make some comment here. I would never use at this point in time remission in an asthma patient in the clinical situation. One is we do not have a true definition. Two, I get concerned that when patients hear they are doing so well and now you defined them as in remission that they are going to cut back treatments, whether it is there Biologics or other treatments, because if I am in remission, why in the world do I need to take medication? I think one has to be very careful in a clinical situation to tell a patient that in fact they meet someone’s criteria for remission.

Lynda: Great. Thank you. Next question. All the studies seem to focus on Th-2 asthma for those with Biologics. Can you comment on information as possible for non-TH-2 patients?

Dr. Blaiss: The answer is yes. If you look at the consensus statement, you can have it on inhaled corticosteroids. If you are on a low dose inhaled corticosteroid and you meet all of those other criteria and you are not using albuterol more than once a month and you have not missed any days of school or work, by definition you are in remission. The definition is not just the way we did this for severe asthma, but it has for any severity of asthma, whether you want to talk about mild, moderate, or severe. As long as you meet those criteria. So we felt that is extremely important, but it should not be restricted to only patients on Biologics. It should be any patient with asthma that meets that specific criteria.

Lynda: Thank you for that. So I was just talking with a colleague, and she was just talking about how even if somebody is on Biologics, you still need good environmental controls, indoor controls, or you will still have the symptoms even if you are on the best medication for you. I think that is what this next question is. Can you give us your thoughts on environmental controls and clinical remission like airflow attrition using cleaners or personal products, air quality in general? Can you comment on that?

Dr. Blaiss: I think air quality and allergy importance are important. — allergy avoidance are important. Anything to avoid the patient having an exacerbation. I think it is also important that we talk about not just medication, but in fact are we controlling underlying comorbidities that could be making the patients’s asthma worse. Are they having problems with GERT or sleep apnea? Do they have underlying allergic rhinitis that could be worsening their condition or chronic rhino sinusitis with nasal polyps? I think environmental treatment is extremely important. Allergy avoidance, clean air, all of that is very important. I think looking for comorbidities that can in fact make asthma worse, that can help increase the number of patients that in fact would get under better control and possibly remission. So I think it is not just treating patients with medicine. I think asthma is so much more than that is the person asked this question. The environment is extremely important. Controlling comorbidities. Adherence to treatment. The vast majority of patients that are referred to me for asthma in my clinic in fact have poor adherence or an fact are not using their inhalers correctly. So they are going to end up having more exacerbations and end up on stronger medications including Biologics where they may not even need them. I think we have to do, and the GINA guidelines have a nice thing on this, every time we see a patient, to assess everything going on and make sure in fact we are doing all of these other things that can improve their asthma. No smoking, no vaping as we heard from the other question. The environmental, the comorbidities. We know obesity can lead to worsening asthma. Now that there are treatment for obesity, we have to look at that in those patients that are having significant problems with their asthma. All of that along with treatment needs to be done to get optimal improvement in our patients.

Lynda: Great. I got time for one more question or so. Is there any biomarker yet available to predict the 19% to 30% remission rates after a biologic?

Dr. Blaiss: So we know from the Danish study and there is also a German study that generally the higher the ENO’s are, the higher the inhaled nitric oxide, those patients tend to have a much higher rate of going into remission with one of the type to Biologics because they are very type two types of patients but it is by no means 100%. And what you did see, and I wanted to make sure it is clear, there are a lot of patients that do not respond to the first or second biologic. The problem is the biomarkers we have right now, nitric oxide and others are not as accurate as we need. There is work going on trying to find more accurate biomarkers. At this point in time, generally the higher the ENO , more likely to see remission with one of the type two Biologics.

Lynda: Great. Thank you. I will ask one more question if you don’t mind. With regard to your slideshow and the summary of remission across different societies, I have to look for the question so bear with me for a second. The question is, given the variances — oops, it just moved on me. Bear with me. Given the variances across definitions and measurement tools, I am looking for a high-level summary of key improvement criteria. Are there any?

Dr. Blaiss: So as far as for all of those countries, they have all published exactly what all their criteria is. And so what I did on that chart was just a very quick summary. Some are not as detailed as others where they kind of do not give an exact objective definition. We see that with lung function at times. We also see that in certain cases with symptom control. So I think if you are reading a paper and they talk about remission, what you’ve got to do is go to the methods. You’ve got to see what criteria they are using for remission and what standards they are using for validated instruments and lung function. Because you cannot compare one paper’s definition of remission with another’s and say that this biologic gets a higher remission than Johnny’s biologic. I think that is leading to a lot of confusion out there. Until we really have a true standard that I think one has to look at all of this with a jaded eye until we have.

Lynda: Thank you so much. So I am just going to summarize by the last comment on chat. This was a fantastic and important presentation and discussion. There were similar comments that came in along the way. So just want to give you a big thanks for taking the time to share this important information with us. And with that, I will say we will move on to tell you about the next webinar. It will be vaccines, new developments, and how to address vaccine have visited — vaccine hesitancy. Join us on December 5 for that. For those of you who would like to learn more about COPD and the Hispanic, Latino community, we have a virtual conference on December 4. We will send you information about that as well. On behalf of allergy and asthma network, I want to say thank you for joining us today. We will see you next time. Thanks, Dr. Blaiss. Really appreciate it.

Dr. Blaiss: Thank you.