 Peer Exchange entitled “Biologic Treatment Considerations for Asthma During the COVID-19 Pandemic and the Upcoming Flu Season.” I’m Dr. Stanley Goldstein of Allergy & Asthma Care of Long Island. Joining me today in this discussion are my colleagues, Dr. Giselle Mosnaim, attending physician, Division of Pulmonary, Allergy, Clinical Care Medicine, Northshore University Health System, Clinical Assistant Professor, University of Chicago, Pritzker School of Medicine; and Dr. Shahzad Mustafa of Rochester Regional Health, Clinical Associate Professor of Medicine, University of Rochester School of Medicine and Dentistry.

Our discussion today will focus on available biologic therapies for the treatment of asthma, and we’ll also review best practices to manage asthma in the current COVID-19 pandemic and the fast-approaching flu season. Let’s get started in this discussion. Since this discussion is going to revolve around severe, uncontrolled asthma, it will be helpful to discuss some of the basic pathophysiologic changes that occur during an asthma episode

The two basic tenets of asthma are bronchoconstriction and inflammation. When someone is having an asthma attack, they feel that their airways are narrowing and there’s also an influx of inflammatory cells which cause secretions and other issues that can block the airways., which This can lead to symptoms such as wheezing, and shortness of breath, coughing, and chest tightness.

 When you think about uncontrolled asthma and the symptoms you were discussing and the pathophysiology, what are some of the causes of having an asthma episode?

Typically triggers for an asthma episode, for some people it’s when they get an upper respiratory infection. They have the flu or a cold, particularly in the winter months, that can trigger an asthma episode. Other people it’s exercise. So, when you exercise, rather than breathing through your nose, you start to breathe through your mouth, and breathing in that dry, cold air through your mouth can cause fluid shifts, which can cause an asthma attack. Then, of course, allergens. Seasonal allergens such as outdoor pollens, and also indoor allergens such as furry pets, dust mite and mold, are typical triggers.

When we’re thinking about patients who are having asthma symptoms and we begin to think about patients who have uncontrolled asthma, could you give us some idea of how common is uncontrolled asthma is, and also, at the same time, why do people have uncontrolled asthma?

: If we look at the population of patients with asthma overall, the statistics show that about 40% to 60% have uncontrolled asthma. TSo that is very concerning. If we look at that population of all asthmatics, about 5% to 10% have severe asthma. In terms of causes of uncontrolled asthma in particular, you can have issues such as triggers. If you’re exposed to things that you’re allergic to, if there is high pollution, if there are’s things in the environment, that can cause asthma symptoms. Also, poor adherence to medications. A lot of patients and clinicians are concerned about the use of inhaled steroids. Inhaled steroids are the gold standard treatment for persistent asthma, and they work very well for persistent asthma, but adherence to inhaled steroids is low.

There are’s also technique issues. So even Even if patients are taking their medications, using proper technique can be an issue. There are ’s also issues of health literacy. When you give someone an asthma action plan for their asthma, it’s very important that the clinician go over the asthma action planit and make sure that the patient understands the instructions and feels comfortable with the instructionsthem. Many people are going to useing picture-based asthma action plans, so that the explanation is very clear and understandable.

 I’m going to dovetail off of two things that Dr. Mosnaim said, Giselle said. Unfortunately, many asthmatics are poorly controlled, that’s 40% to 60%. I think that’s really important as to why we’d want to use objective measures to gauge control for asthma. Often if you ask a patient “Hhow’s your asthma?”T and they tell you “Ookay.”, Bbut then if you dive into the details, they’re using their inhaler more often, they’re not doing things they want to be doing because their asthma is poorly controlled. So, using objective measures, whether it’s asthma questionnaires like the Asthma Control Test, it’s certainly in the office maybe breathing tests, even peak flow may help identify these individuals who have poorly controlled asthma.

Why does it matter? If people have poorly-controlledpoorly controlled asthma, they have a higher risk of exacerbation in the future. Additionally, one important point I think is, again, all the reasons that Giselle said for reasons for poor control are true, and I think we’re really starting to appreciate that asthma is a syndrome and not a disease, and everyone’s asthma is different, and exercise-induced asthma is very different than severe asthma. As clinicians, we need to get a better understanding of understanding everyone’s individual asthma, so we can tailor care to them. I know we’re going to talk about picking the right therapies for asthmatics in this session, but understanding asthma, not treating everyone the same, not having an algorithmic approach, will hopefully help improve our outcomes as we pick therapies.

 We’ve been discussing some reasons why patients are out of control— adherence, allergen exposure, respiratory infections, but we do know that also patients may be doing everything right. They may be taking all their medications appropriately, using inhalers appropriately, being strictly adheradherentence, and yet they still can be out of control. I think, Shahzad, that’s what you’re referring to as far as the different types of asthma.

Overview of Uncontrolled Asthmatic Episode

, MD:What are the issues with respect to quality of life in patients who have uncontrolled asthma? What does it mean for the patient? What does it mean for the health care system? What does it mean for the population at large?

 When people are poorly controlled, there are two things that we really want to talk about. One is their impact on quality of life, and then two, is their functional risk of future exacerbation. So, quality of life. Asthma obviously can affect people, what they can do, exercise Giselle mentioned is a big part of it. TSo things they can do, you know, illnesses, school days missed of work. Asthma obviously can affect all ages. ,Iso if your child has poorly controlled asthma and they’re staying home from school, that affects your job. We’re in a very, very unique time right now with this global pandemic.I So it has huge impact on what you can dodo, and it has huge effects on the ability to, you know, school absenteeism and attending work for missed days.

Then if you’re having symptoms, you end up in places like your primary care doctor, your allergist, your pulmonologist, urgent care, and the ED. There’s a huge amountnumber of asthmatics that are receiving care in the urgent care and ED because they’re having symptoms, they’re having exacerbation, and they’re getting courses of steroids;, oral steroids, which, in the moment, is obviously necessarily, but we all know has its downsides. We don’t want to be complacent about to being okay with treating our asthmatics with multiple courses of systemic steroids in a year. Anywhere beyond one course a year represents poor control, and that gives us an opportunity to help these individuals, to help their quality of life and to decrease their reliance on steroids and future exacerbation.

 We’ve been talking about exacerbations. and Wwhat are the downsides?, Oobviously, the treatment with oral corticosteroids and the downside and the long-term effects of that. But, how would a health care provider recognize a person that is at risk of having these exacerbations or at risk of being poorly controlled? What are some of the signs that they could see within a history or an objective measurement that can pick out that patient and say, “I need to step up therapy in that patient.”?

 If you look at the number of courses of oral steroids in a year, Dr. Mustafa was talking about how if you have to go on two or more courses of oral steroids in a year, that is a concern for poorly controlled and high risk asthma. If a patient has to go to the emergency department, if the patient is hospitalized for asthma, those are all high risk and we have to pay special attention to our patients in this situation. Then there’s also the impairment of quality of life. If someone is missing a significant amount of school, that affects academic performance, and if someone is missing a lot of work, that can also put their job at risk. TSo there’s educational and economic concerns. It also can lead to comorbidities. If someone isn’t able to be physically active because of their asthma, it can lead to weight gain, it can lead to other issues. W So we really want to make sure that we talk with our patients and counsel them about these different risks and these different situations.

 One more thing, we hear it right now. , Wwe hear a lot about health care costs, and at the end of the day, well controlled asthma is actually less expensive to manage for the health care system than poorly controlled asthma. . So that’sThat’s just one more thing, t. The bill, you rack it up when you end up in the emergency room and, unfortunately, hospitalized for asthmatics which continues to happen. That’s just one more factor, one more reason to really strive for getting our asthmatics under the best control possible.

What are some of the objective measurements that a health care provider can do in order to help determine whether that person is at risk of having an exacerbation?

WSo we can start very crudely. We can ask people how often they use their rescue inhaler, albuterol. Typically, we say using it less than twice a week represents good control. Most albuterol inhalers, canisters, have about 200 doses in them. If you’re really well controlled, you shouldn’t be going through more than one in a year. So that’s a very crude measure of how often you’reare you reaching for your rescue inhaler. Then beyond that, we can certainly use peak flow. This is an interesting time with this global pandemic because it is more difficult to get objective measures of lung function like breathing tests, spirometry, pulmonary function tests, so if sometimes we’re using peak flow. But under normal circumstances, doing lung function testing I think is very important- spirometry, full PFTs, [Ppulmonary Ffunction Ttesting]. Then we also measure inflammation in the airway with a validated biomarker for asthma, which is exhaled nitric oxide. These are all opportunities to get objective measures of someone’s asthma, and for them to be in good control of asthma, you really want to hit all those criteria. If you’re missing any of those, that may be an opportunity to improve asthma care and improve outcomes.

 One of the things I would add to that is patients can do the Asthma Control Test, the ACT test. That’s a simple measurement that we all have available, health care providers, whether a primary care, internal medicine, allergist, pulmonologist, can have available for their patients. It’s a measurement of control. Just very simply put, if their total score, it’s five questions, if the total score is less than 20, it means they’re at risk of having exacerbation and they’re poorly controlled. We talk about, we all have electronic medical records, at least most of us at this point in time, there’s also a measurement called the ACQ, [Asthma Control Questionnaire]. It is an objective measurement that can be done. A lot of us don’t use it on a daily basis, it’s obviously spoken about in the medical literature, but it’s something else that can be used in order to help look at control.

Then I know we’re talking objective measurements, and I think, Giselle, you pointed out, or Shahzad, you also pointed out, lung function. Lung function is a fantastic tool for objective measurement of what’s going on. I know Shahzad, you just mentioned in this pandemic, a lot of us are not doing a lung function test because of the concerns of obviously exposure to the people and the other health care providers in that area. But peak flow is another objective measurement.

Quality of Life and Increased Risk of Asthma Exacerbations

I think we’ve been talking about uncontrolled asthma. I think there are two important issues when you think about uncontrolled asthma.. You may talk about the difficult-to-control asthmatic, and then you may talk about the uncontrolled asthmatic. As we here hear today, Shahzad, Giselle, and myself, see patients that are referred to us for asthma, how often do you see patients that are either underdiagnosed because of their asthma, or may be overdiagnosedover diagnosed? Maybe they don’t have asthma, but someone thinkgs that they do, and they keep getting medications pushed upon them, and even up theto dosages of oral corticosteroids. What are some of those types of patients that you would see in your practice?

In terms of the overdiagnosis, I do see some patients that have vocal cord dysfunction. These are patients that don’t have asthma, but their vocal cords close when you want them to be opening. These patients exhibit symptoms of shortness of breath, and for these patients, they often get prescribed repeat courses of oral steroids, which are not indicated for the treatment of vocal cord dysfunction. There are other patients that have vocal cord dysfunction and asthma, so that also, there’s some gray lines there because are you treating the vocal cord dysfunction? A, are you treating the asthma? A, are you treating both?. Also, patients with gastroesophageal reflux disease. We have patients that have cough due to gastroesophageal reflux disease, and that is being treated as asthma when that is not the case.

Then there’s also the comorbidities of allergic rhinitis and sinus disease. Many of our patients that have sinus disease also have asthma, and you’re trying to sort out are these difficulties breathing from the upper airway or the lower airway?. Many times when you treat the upper airway, when you treat their allergic rhinitis with intranasal steroids, or you treat their sinus disease, their asthma does improve. SoSo, you’re really trying to sort out these different symptoms.

: We also speak about the mimickers of asthma. You spoke about vocal cord dysfunction. Are there any other types of patients that you would say have a certain type of other disease process going on that may mimic asthma?

: Yes, it was touched upon very nicely. One of the most prominent symptoms of asthma is cough, and cough can be caused by a myriad of other things. But allergists always focused on the one airway hypothesis, the upper airway and the lower airway. So allergic rhinitis, sinusitis, can lead to cough. Reflux, gastroesophageal reflux, vocal cord dysfunction has been touched upon. Depending on the setting you’re in, if you’re taking care of adults and there’s multiple comorbidities, you always have to think about cardiac disease also, and you don’t want to miss that as an allergist. WSo we have to work through this.

Asthma can certainly be overdiagnosedover diagnosed due to mimickers, and I think it can also be underappreciated at times, where individuals are under-reporting symptoms, but they’re actually having more significant asthma than they appreciate. I think this goes back to, again, the importance of getting objective measures, trying to measure lung function. The guidelines would say whether it’s somewhere with asthma or it’s COPD [Chronic Obstructive Pulmonary Disease] emphysema. You would like to have at least one recorded lung function testing on record at some point. Again, the importance of objectifying people’s asthma to try to understand how they’re doing and then to move forward with the right therapiesy.

: While you’re talking about mimickers of asthma, and you were talking about the adults, Shahzad. , I just want to talk on the pediatric side because that’s where I came from. You definitely should think about a foreign body in very young children, you may think of other diseases such as cystic fibrosis in young children, even aspiration in young children. So, yes, that’s why objective measurement is important. In young children, you don’t have that tool of objective measurement as well, and that’s why it’s important taking that good history, putting it together as a puzzle and piecing together obviously response or no response, courses of steroids. It’s important to be aware of that in the health care provider.

When you think about health care providers overall, and we know that we are referred difficult patients, one of the areas, Shahzad, you pointed out is those patients who are undertreated. Often, I remember patients coming in saying, “Ooh, I’m using my albuterol often.”, and from their history, it sounds like they may have severe uncontrolled asthma. If you take the history appropriately, do your objective assessments appropriately, see what they’re taking or see what they’re not taking, find out pharmacy records; in this day and age with electronic medical records, it’s very easy to see if patients are filling their prescriptions and looking at all these surrounding parameters because they may have uncontrolled asthma, but there are specific reasons that you could improve their asthma control by putting them on more appropriate medications, dual controller, even now we’re talking about triple controller in certain asthma patients, and making sure they’re being adherent and using their inhalers correctly.

But at what point, I think as a group we should counsel or help our primary care physicians in deciding what are those types of patients that should be referred to the specialist, allergist or pulmonologist? What are your thoughts about that?

: I can chime in, and Dr. Mustafa, if you also have additional thoughts. If a person has multiple ED visits, so two or more ED visits a year, or if a person has a hospitalization for asthma, then that’s a good time to refer to a specialist. If you think that the person needs counseling on environmental triggers, so you’re thinking that it would be good to do allergy skin testing for environment allergens and counseling on those triggers, that’s a great time to refer to the allergist. There’s also the option of allergy immunotherapy for those patients. If you have patients that you think may not be taking their medicines correctly, so either they’re not taking them because they don’t think that they need them or they forget or other reasons, or they’re not taking them properly and you need some extra counseling on management for these patients, whether it be how to take your medication, when to take your medication, whether it be self-management on other issues, whether it be developing an asthma action plan together, that we go over together, these can all be reasons to refer. And also, if you’re concerned about comorbidities, t. Thehe allergist can be very helpful in examining whether it’s asthma, whether it’s asthma plus allergic rhinitis, GERD [Gastroesophageal Reflux Disease], other issues. TSo that’s a number of reasons.

And also if you’re considering a biologic, it varies across the United States. At our particular health system, the only specialty that administers biologics is the allergist immunologist. We’re very comfortable with administering injectable therapies, we’re comfortable monitoring anaphylaxis. This is something that we do. SoSo, we get referrals from all different specialties for this service.

Over and Under Diagnosis of Asthma

: When you’re thinking about getting into a biologic, I think it would be helpful to define whowhat are those type of patients, who just by definition of a patient that would potentially need a biologic. We have in the literature, just to point that out, is the ERS, [European Respiratory Society], and ATS definition of what a severe asthma patient is. Severe asthma patient is a patient that would require high-dose inhaled corticosteroids, plus another controller medicine, or may require oral corticosteroids for 50% of the year or greater and still be in control. So, that may define a severe asthma patient. Then you have those patients who are taking all those controller medicines or oral corticosteroids and continue to be poorly uncontrolled. TI think these are the patients that we’re referring to when you think about the need for a biologic either because they continue to be uncontrolled on their inhaled medications or even controlled on oral corticosteroids.

Since we now begin to now talk about biologic and they are referred to allergists and pulmonologists, let’s think about the pathology of asthma. I think Shahzad, you pointed this out before as you were talking about asthma as a syndrome and all the other types of asthma underneath that. If you could just address some of the pathology of asthma, when you think about the different inflammatory processes.

: Sure. Dr. Mosnaim mentioned earlier, we have bronchoconstriction and inflammation. On, and overly simplistically in asthma, we’re really thinking about eosinophilic inflammation or Th2 [T helper Type 2] inflammation, which kind of varies and compares to COPD emphysema, which we think of as a predominately is neutrophilic inflammation. But nothing is binary, so there are shades of gray here. But we’re classically thinking of eosinophilic inflammation, and many, in fact, I think all of the biologics currently that are FDA approved for asthma are all really addressing that type of inflammation. WSo wanting to know what type of inflammation an individual has, whether it’s eosinophilic or neutrophilic, is important, and how are ways you can do that?

In the office, looking at the background, the patient’s background, are they allergic? If they have a lot of allergic conditions, then they’re more likely to be eosinophilic versus not. We can check for exhaled nitric oxide, which is a validated biomarker for eosinophilic airway inflammation. And although many of us are not doing lung function testing and spirometry because of the risk for aerosolization and risk of potential spreading of infection for people with COVID right now, checking exhaled nitric oxide is a non-aerosolized procedure. So, that’s a tool we can use even amongst this global pandemic.

Then when we’re thinking about these biologics, we can also check for eosinophils with a simple blood count, a CBC [complete blood count] with differential. There we’re using the eosinophils in the blood, peripheral eosinophilia as a surrogate for airway eosinophilia. T So trying to understand what type of inflammation an individual has is very, very important because the biologics we have are really directed at eosinophilic inflammation.

In the literature, we all talk about phenotype and endotype. I think it’s would be important to discuss what is meant by a phenotype, because when you look at a group of researchers called the SARP, [Severe Asthma Research Program], they look at patients, they first try to put patients in buckets, and those buckets are based upon the patient’s phenotype. When we talk about phenotype, it means the observable characteristics of that person. What do you see in that person as far as what’s similar? SoSo, you put them in buckets. But we know when we think about phenotype, it doesn’t help define what type of biologics you would use, it may put them in buckets. Then it’s important to think about the endotype, which is . What is the endotype? It’s the inflammatory process that we’ve all been referring to, that occurs in that specific patient. Let’s discuss about, I know you brought it up already, Shahzad, but the different endotypes that may be related to some of these phenotypes, or maybe discuss the different phenotypes of asthma patients.

: I like starting with phenotypes, and Dr. Mosnaim can chime in as well., too. TI think the first important thing is we can even start(?) the phenotype for asthmatics without ever talking to them, by just looking at them from across the room. Age is important. Younger asthmatics tend to be more Th2 or eosinophilic versus a later onset asthmatics, who may be more neutrophilic. Race is very important. We talk about health care disparities in America. But even outcomes and responses to medications. , we know thereThere are racial differences in responses to asthma medications. So thinking about that. Body habitus, body mass index, obesity is important. Obesity in addition to this potential physical restriction also affects your response to medications for asthma. Obesity impacts your response to inhaled corticosteroids. So, just looking at an individual starts to teaches you about their phenotype.

And then in the office, in our specialist office, at an allergist’s office, there’s a lot of testing we can do. Giselle, Dr. Mosnaim mentioned skin testing for allergic rhinitis and comorbidities. Skin testing tells us a lot about lung health and has a lot to do with asthma outcomes., we know that. Lung function testing, are they reversible with a bronchodilator, are they not reversible? Do they have high exhaled nitric oxide for eosinophilic disease versus non-eosinophilic disease? SoSo, there’s those phenotypes, and then we can order tests. For blood work,, many of us are ordering blood work— pulmonologists, allergists, and other specialists. We can check for eosinophils with a CBC, [a complete blood count] with differential. We can check for total IgE [Immunoglobulin E] levels, which again these are going to help us understand the patient’s particular asthma. There may be a role for imaging. So we have all these tools to better understand someone’s asthma, which can then hopefully better help us personalize their medical regimen that suits them most.

Targeted Pathology for the Treatment of Asthma

Maybe now we could address the specific endotypes that may be a function of what these patients’ phenotypes are. We want to be thinking about those potential biologics and grouping these patients based upon what we would think would be best to help them in their uncontrolled asthma.

If you look at endotypes, this is the way I look at it. There are different focuses, but one would be to focus on the pathways that the different biologics focus on. For example, the first biologic, omalizumab, focuses on binding free IgE.

Another thing to focus on is eosinophil levels. We have reslizumab, we have mepolizumab, that focus on reducing eosinophil levels. And then we also have benralizumab that binds to the IL-5 receptor, and IL-5 promotes eosinophil maturation development. Then we have dupilumab, which binds to the IL-4 receptor alpha, and it inhibits IL-4 and IL-13 pathways in asthma. Depending on the different mechanisms, there are different biologics for those mechanisms. As Dr. Mustafa alluded to, while we don’t have them currently available, we are looking at biologics that would treat also Th2-low asthma. These are not approved yet, but it’s something that we’re looking at because the current biologics are focusing on Th2-high asthma, and we have many patients that are Th2-low asthma and we want to make sure to be able to offer therapies for them as well.

: Before we start getting into the specifics about the biologics, we know you’ve both been talking about T2-high and T2-low. What percentage of patients in the United States with uncontrolled asthma are T2-high versus T2-low, and what does that specific patient need? We know there’s a lot of variability in looking at the endotypes, about the biomarkers, and patients may have multiple biomarkers. How do you make that decision, to leap to decide which type of biologic they would benefit from? First, let’s address the T2-high and T2-low as far as how common they are among our patients.

: The majority of asthmatics fall into a T2-high, an allergic or eosinophilic inflammation kind of picture. With that being said, when we’re getting into poorly controlled asthmatics, the ratio starts to skew a little bit over to T2-low. As Dr. Mosnaim said, we have less therapeutic options in that space, so they are a little bit more difficult to control for us. As an overall picture, it’s much more of an allergic asthmatic or eosinophilic asthmatic, but as we get into the poorly controlled ones, we see a skew going up towards a more T2-low picture.

: But we know that there are overlaps in the T2-high asthma patient population. There may be an overlap. We know that in the United States, 60% of patients, and as far as adults who have asthma have an underlying allergic cause or association. In children, that’s 80%. Four out of every five children who have asthma have an allergic cause for it. We have to try to piece together what is the driving force for that person’s asthma, and therefore try to decide what’s the appropriate biologic. At the same time, can we use any biomarkers that help us determine outcomes for asthma? If we’re going to put them on a biologic, are there any biomarkers that we could say, “Well, if this goes down or this goes up, this patient definitely is a sign that they’re going to be better”? Anything in that regard that can help us? Shahzad, you were smiling at that question. I’m sure you have some answers that you could …..

: We have biomarkers that help us predict what we think a patient’s response will be. As eosinophil levels increase, we think their response to the anti-IL-5, the anti-eosinophil agents such as a reslizumab, mepolizumab, benralizumab, should get better. But, we are still not good in medicine about predicting the future and predicting outcomes. For omalizumab, we’re thinking about this in individuals with allergic asthma, with elevated IgE levels, but it is hard to predict their response. So I think that is an important part of us putting patients on these medications with our best guess, but our ability to predict a response remains suboptimal. But we do want to try to think through it like we have with phenotypes and endotypes to give us the best chance of success. And not only can we not potentially predict their response, we don’t necessarily change the course of their asthma. I think that’s an important point. We try to help symptoms, we try to decrease exacerbations, and these are very effective, well-tolerated mediations that we’re going to get into, but we don’t actually change the course of their asthma. That’s an important point that we all have to appreciate.

Giselle, anything to add to that discussion?

What I would like to add is a little bit different. You had mentioned earlier the difference between difficult-to-control asthma and severe asthma. Ycan have someone with severe asthma that is well controlled, so they have severe disease, but they take their medications, they avoid triggers, all of these things so they can be well controlled. And you can have someone that doesn’t have as severe disease, but they can be quite uncontrolled and require repeat courses of oral steroids, emergency department visits, and hospitalizations. It’s very difficult to really disentangle all of this.

Common Biomarkers of Asthma to Determine Treatment Efficacy

When you think about biologics and the percentage of patients in the United States who have moderate to severe uncontrolled asthma. About 5% to 10% of the patient population in the United States has moderate to severe uncontrolled asthma. If you put that in numbers, it’s about one million to two million patients. There are 25 million people in the United States who have asthma, so that amounts to about one to two million patients who you would think may deserve a biologic. When we think about the uptake of biologics, how many patients would you say are being treated with biologics at this point in the United States? And the question really points to our specialists, including ourselves as allergists and pulmonologists, are they using the biologics, or maybe they are still missing those patients who deserve biologics? So let’s think about that in numbers. At this point in time, maybe 100,000-plus patients in the United States are receiving biologics for the treatment of uncontrolled asthma, and you put that into the numbers, that means there are probably at least another 900,000 patients or 800,000 patients continue to not be treated with biologics when you would think they would deserve a biologic. Would you agree to say that even though allergists, pulmonologists, respiratory specialists if you want to call them, are still missing a lot of patients when you think about those patients who would deserve to be treated with a biologic?

I would agree that there are many patients that would require a biologic. Patients that are using their medications, are using them properly, and despite high-dose inhaled steroid plus another controller are still struggling and having to go on oral steroids. I think on a regular basis, I am seeing these patients referred to me in my practice, and I put them on a biologic and that can be life-changing for these patients. That’s an amazing thing as a physician, to be able to make a dramatic improvement in an individual’s quality of life.

: .. there’s a lot that varies regionally in access to specialists, also. It depends on where you live and the patterns there. As you said, respiratory specialists, allergists, pulmonologists are comfortable with biologics, but we have to see the individual. It’s really important to raise awareness with the primary care community, about that these drugs are available, they are efficacious, they are safe, and with each passing day the FDA approval of the age on these biologics is getting lower and lower. We’re down to age six now, which gives us an opportunity to help these individuals who may not have had options before. Raising awareness is always a good thing, educating our referral base, working with them, so we can have a team approach. We have tools now that we didn’t have years ago, and it’s a privilege to offer them to patients and see their excellent response.

One of the things that I’m also excited about and that is currently available, and I’m hoping that we will start to use this more, is remote monitoring. If a patient can have an inhaler that has a Bluetooth monitor on it, so that every time the patient takes a dose of their inhaled steroid or takes a dose of their quick reliever medication, this information gets sent to their personal app, so they can monitor their asthma. They can monitor their adherence to the inhaled steroid, they can self-monitor overuse of bronchodilators, and this information can also go to a clinician’s dashboard. So physicians and other health care providers can see remotely if a person is overusing their albuterol, if a person has not taken their inhaled steroid in a number of days, and there can be automatic alerts set up for patients and for clinicians so we can start to see really what’s going on. Is the patient uncontrolled because they’re either not taking their inhaled steroid, or they’re taking it, but they’re not taking it properly? Are they overusing their rescue medications in certain situations; for example, are they using a lot of albuterol for nighttime symptoms? So really trying to get a better understanding.

These apps can also look at location though GPS, so you can look at air pollution levels, air quality levels. So, we’re really going to be able to get a better idea of what’s going on in the asthma patient’s day-to-day life. The patient will get that feedback to themselves on the app, they can self-monitor better, and clinicians can assist a patient better. If we see that they’re taking their inhaled steroid regularly, they have good technique so we can measure peak inspiratory flow, the app can tell the patient “You had good flow, you had inadequate flow” the physician can know if the person had good peak inspiratory flow, if the medicine was delivered to the lungs. Ifsomeone is taking their medications, it’s getting delivered to the lungs, they’re doing all these things and they’re still having to go on oral steroids or have emergency room visits or hospitalizations, then that’s a time that we would think that this is a severe asthmatic.

Raising Awareness Among Physicians Regarding Biologics

: Let’s now get into the discussion about the specific biologics. We’ve heard terms that we’ve been throwing out already; omalizumab, mepolizumab, benralizumab, reslizumab, dupilumab. What are some of these differences? Let me first address, I think, Giselle, you already started to address omalizumab, the treatment of omalizumab. What does that do? We know omalizumab is the only biologic that targets and blocks IgE, as you already mentioned, Giselle. By blocking IgE, what happens physiologically, is that you have a downregulation of the high-affinity IgE receptors. They that are sitting on inflammatory cells such as mast cells, basophils, including dendritic cells, and that will result in thea prevention of cross leaking of IgE antibodies, therefore limiting degranulation and limiting the media(?) as it’s being released. It’s actually been addressed in the literature as far as omalizumab does havehaving anti-inflammatory effects in asthma.

As a matter of fact, there was an article in early 2000s by Ducanovic(?). He wrote an article on what is actually going on by looking at patients, and doing biopsy, y and looking at sputum eosinophils, andeosinophils. showed that omalizumab also will result in; Tthey had the patients whothat were in the study on uncontrolled asthma, had 2% of sputum eosinophils or greater. After treating them with omalizumab, he did showed that there was a statistical reduction in eosinophils in the sputum, and also eosinophils in the tissue. So, there’s an overlap between allergic and eosinophilic asthma.

When you think about eosinophils in allergic asthma, eosinophils still play a major role in allergic asthma. If you look at the demographic data of patients in the two pivotal trials in omalizumab, you find that the mean value of eosinophils in these patients were on the order of in the low 300s, and you find that also in post-hoc analyses, you can look at; to understand the pivotal trials in omalizumab, you can think about that those patients were not enriched patients in any way. They weren’t enriched upon their eosinophils,eosinophils; they weren’t enriched as far as their pheno.

I don’t think we even knew what pheno was then, like 20 years ago. So theyThey weren’t an enriched patient population. But if you doubt, what they’ve done is they’ve taken those studies and looked at a post-hoc analysis and what happens if you enrich that patient population based upon their eosinophils. Ananear(?) showed that if you look at those patients in the omalizumab trials, looking at exacerbations, you find that those patients who had an eosinophil count of greater than 300 versus lower than 300, had a better response as far as decrease in exacerbations. Those patients who had eosinophils below 300 also had a good response, but it was better with higher eosinophil counts.

And then Tom Casale, good old friend Tom, did a post-hoc analysis on looking at the patients in those two pivotal trials that were done for the registration of omalizumab. He spread out and looked at the eosinophil counts from below 200 up into the order of greater than 400, and there was a gradual increase in the reduction of exacerbations; where overall, if you look at the reductions of exacerbations with omalizumab, it’s in the order around 53%. But, when you enrich that patient population by looking at the eosinophils, in those patients who have eosinophil counts of greater than 400, you can enrich that by a reduction in exacerbation rates by 73%. 

Now, something important that gets misconstrued in with the physicians that who treat biologics, when you look at total, and when you’re thinking about allergic asthma, we can talk about total IgE and we can think about specific IgE. Total IgE doesn’t tell us anything about that patient, whether they are highly allergic or not allergic. It’s just a way of dosing omalizumab because you’re dosing it based upon the total amount of IgE. When you give a first dose of omalizumab, within 24 hours you’re reducing that specific IgE by 96%. That’s a significant number because that’s what results in the decrease in the high-affinity IgE receptors.

When you’re thinking about allergic asthma, andasthma and defining what do you mean by ‘allergic asthma’ and who’s what’s right for that patient with omalizumab, you want to know that these patients have perennial allergens that are associated with the worsening of their disease, their exposure. That’s why when you’re looking at to define whether they need it, you’re looking at specific IgE. So it’s specific IgE to determine whether a person needs omalizumab, and it’s total IgE and the weight as far as dosing of omalizumab.

FDA Approved Agent Omalizumab for Asthma

Shahzad, you mentioned that we have biologics approved down to the age of six, and in allergic asthma, we have omalizumab approved down to the age of six. It’s indicated for those patients who have a perennial allergen, continue to be uncontrolled on inhaled corticosteroids and may be taking another controller, and obviously they’re showing a decrease in exacerbations.

The question always comes up, we see patients who have allergic asthma and non-allergic asthma. Omalizumab has been present for the last 18 years. It was approved in the early 2000s, and it was the only standalone biologic for many years up until maybe five or six years ago, when the eosinophilic phenotypic asthma biologics became available. We know that there were both allergic and non-allergic asthma patients being treated with a biologic indicated for, so to speak, allergic asthma.

What’s the data on that? It’s interesting. There was a recent study, probably not so recent anymore, maybe two to three years ago, called the PROSPERO study, which was a prospective look in a real-world situation, looking at patients who were treated with omalizumab. In order to be in that study, patients had to be approved for omalizumab, and they looked at 48 weeks of patients who had a response. Response could have been improvement in lung function, decrease in exacerbations, or a decrease in their Asthma Control Test scores. Actually, 80% of patients had a response to omalizumab.

The interesting thing about that is that within those patient populations, they found patients who were used out of the specific total IgE that omalizumab is approved for. Right now, it’s approved in the United States for 12 and above, for those patients who have a total IgE of 30 up until 700, and there’s a grid which helps you decide what dosage to use of omalizumab. But we know in the prospective study, PROSPERO, they had patients who fell out of those total IgE, with either low IgE, under 30, or high IgE, above 700, and these patients also showed a response.

There’s this question, can you have a non-allergic asthmatic respond to omalizumab? There was a Spanish study called FENOMA which did look at specific patient population, allergic and non-allergic, and they also found there was a significant number of patients in that study which did not have allergic asthma. Obviously, we have choices now, and that’s why we have allergic asthma being treated with omalizumab, and then we have non-allergic asthma being treated with the other patient populations.

: for the omalizumab, if a patient also has chronic idiopathic urticaria, omalizumab is a very nice choice because then you can treat both the asthma and the chronic idiopathic urticaria. More recently, the omalizumab, after the first four doses in the office, the patient can now self-administer it at home. With COVID, it’s nice that we can have patients self-administer these medications at home. All of the biologics that we are discussing today that are in subcutaneous form, can now be delivered at home. Xolair still needs to be delivered in the office for the first four doses, and if that goes well, then it can be transitioned to home. The reslizumab is intravenous, so that cannot be delivered at home. But the home delivery has been a huge help with COVID, so that’s a big advantage in terms of options. So that’s a big factor that I talk about with patients, is dosing, their comfort level with the dosing. We do a visit in the office with the patient and a nurse to make sure that they are comfortable with self-administration. For the omalizumab or for some of the others, we’re going to get into it with dupilumab, some of the things that you need to do in terms of storing the medication, if you need to allow it to come to a certain temperature before administration. Some of these issues are important in shared decision-making.

Patient Factors That Determine the Use of Omalizumab in Asthma 

: Let’s discuss the other biologics now. We’ve discussed omalizumab. What about the anti-IL-5, anti-eosinophilic? Can you pick up and discuss mepolizumab and benralizumab?

: Yes, I can take that. There are 3 FDA-approved biologics that are anti-IL-5 or what you would say anti-eosinophilic, mepolizumab, reslizumab, and benralizumab. They have similarities, but benralizumab’s mechanism of action being a little different than reslizumab and mepolizumab. But, at the end of the day, these are anti-IL-5 agents that are aimed at decreasing eosinophils and eosinophilic inflammation. There are subtleties in delivery, whereas reslizumab is an IV infusion, the others are subcutaneous injection, whether it’s at 4 weeks or 8 weights. There are subtleties, but that’s the general principal for all 3 of these as allergists and pulmonologists use them regularly. 

When you’re considering them, and Stan touched upon this very nicely, these patients are not binary. There’s tremendous overlap in these individuals. You may have individuals with elevated IgE and elevated eosinophils, which is not uncommon, and I’m sure we all see that in our clinical practice. With individuals with elevated eosinophils, which depending on the specific drug, the studies looked at 150 eosinophils in the blood count, peripherally up to 300, 400, but the bottom line is individuals with elevated eosinophils may benefit from these agents. Here, the best predictor of response is the eosinophil count. The higher the eosinophil level, the more likely the individual is to respond to the medication. By response, I mean most of these studies which now date back several years and there’s been multiple landmark studies on all of these agents, is that primary outcome is generally decreasing steroid-requiring exacerbations. In all-comers, if you look at a big Cochrane review, the general rule of thumb is that you’re going to hopefully decrease steroid-requiring exacerbations by about 50% with these patients, and if that happens, it’s considered a success.

Of course, we would like to improve symptoms, we’ve talked about quality of life, we’d like to improve lung function, and those are secondary outcomes that we hope to see with these agents as well. But the primary goal remains decreasing steroid-requiring exacerbations, keeping these guys out of the urgent care, EDs, certainly the hospital. That’s the biomarker that we’re using for these anti-IL-5 agents, is eosinophils. But, again, Stan touched upon it very nicely, and I think it’s very important that we are working in a Th2-high space, and all of these biologics fall in that space. These are not individual options. There’s a lot of overlap, and I think that’s where the clinician comes in in trying to make a good judgment. Even though we’re not great at predicting the future, making a good judgment of which one of these biologics would be best for this patient. This is an important decision, as Dr. Mosnaim said, it could have huge impact and huge improvement if we get it right.

: Thanks for that discussion. Let’s say we have a patient who has high eosinophils, and we’re thinking about an anti-IL-5 agent, is there any specific way that you could determine which one you would use? How do you think about that and how do you have the patient involved in that conversation, and how do you have the referring physician involved in that conversation?

: This is the buzzword into what we should all be doing right now, is shared decision-making. As physicians, we know the science, we know studies, and we present that information to our patients and their families and then we come to a decision together that may be best for them. Every individual brings different perspectives, different backgrounds to the discussion, so it’s hard for us to just deliver information. These agents should be similarly efficacious, so it comes down to dosing— an IV infusion versus a self-injectable, whether you can do it at a doctor’s office, or at home, whether mepolizumab is dosed every 4 weeks versus benralizumab which can be eventually dosed every 8 weeks.

Comorbidity is an important one, too. Some of these medications are now, we’re certainly looking at all of them in other conditions that are not all FDA approved yet, but there is some data for a different one of these agents in different conditions; for example, mepolizumab has good data in Churg-Strauss or EGPA. You want to be thinking about what other conditions can be improved while we take care of the patient’s asthma, because as we talked about earlier, so many of these patients have comorbidities. 

I present the data to the patient, to their family, and we discuss through it with the type of dosing, where they want dosing, what their comfort level is. The safety profile, which we’ll talk about, these are generally very well tolerated medications. They do have subtle differences, so we work through that as well, but it really should be a collaborative effort between the clinician and the patient because very rarely is one obviously better than the other, at least in my opinion. I’d love to hear you guys weigh in, too. But there are options and how you wade through that I think is important with shared decision-making.

IL-5 Inhibitors for Treatment of Asthma

You mentioned dupilumab. Let’s hear some more information regarding dupilumab, because that may be in its own class by itself and how . How do you decide?. Let’s talk about the mechanism of action of dupilumab and also, again, where you would place it in the algorithm.

Dupilumab blocks the IL-4 receptor alpha, and it is important for the IL-4 and IL-13 pathways in asthma. Dupilumab is a self-injection at home every two 2 weeks. It’s also approved for atopic dermatitis. So, in this situation, if I have a patient with asthma and comorbidities of atopic dermatitis, dupilumab has a nice fit there. In terms of the safety profile with Ddupilumab, it has a very good safety profile. I do caution patients about potential eye symptoms, but that has not seemed to be too much of an issue. Again, we have the patients get the first injection in our office with nurse teaching, and then after that they continue treatment at home.

Do you have any other thoughts about as far as the mechanism of action and when you would use an anti-IL-5 or dupilumab? I know you’ve mentioned the comorbid conditions, obviously chronic rhinosinusitis and nasal polyps. Giselle, yYou also mentioned, Giselle, about the differentiation with that, is it’s home therapy. It’s always been home therapy. I should say, Aas opposed to the other ones which were initially administered in the office, but now mepolizumab and benralizumab also have home therapies as well. Any other way of deciding when to when am I going to use a dupilumab? Bbesides we discussed the comorbid conditions.? We know if you look at the data as far as the patients as, the demographics of the patients in the phase 3 dupilumab studies included patients with atopic disease. They have the approval to specific indication, dupilumab is approved for those patients who have the eosinophilic phenotype, but we know that in the clinical studies, you had those patients who, yes, had the eosinophilic phenotype, they also had patients with an atopic phenotype, and they speak about also the mixed phenotype. So howHow do you fit that into the whole decision-making of when you’re going to use it? , Bbesides obviously shared decision with what’s easier for that patient. ? How about just the physiologic mechanism? Thoughts about that?

I think this is the big, big question right now. I think that inIn this field, I think we’re all discussing and trying to figure out which biologic to start with, how long to stay on a particular biologic before you assess efficacy, do you switch to another biologic and under what circumstances do you switch?. These are the big questions that we’re having asking right now. I tend to choose biologics very much in terms of what the patient, when I explain the different dosing plans, that’s a huge thing for the patient. When I look at the comorbidities, that’s also something very big that I look at. I tend to keep the patient on the medication for at least three 3 months before assessing maximal efficacy. So I let the patients know “We need to stay on this for three 3 months to really see how well it’s working for you.” I have seen dramatic improvements, patients that have been on daily oral steroids, patients that have had huge impact on their quality of life, and then we go on to a biologic and after three 3 months they’re off of their oral steroids, they’re blood pressure is better, their blood sugars are better, their quality of life is tremendously improved.

Dupilumab for Moderate to Severe Asthma

: As I think Shahzad mentioned, that the primary outcome of all the biologics studies, are looking at reduction in exacerbation. Giselle, you also just mentioned how biologics help reduce oral corticosteroids in our patients, and there are specific biologics that have been investigated in that. What do you think about lung function? Does that play a role in biologics and looking at that as far as improvement in lung function?

Yes. The dupilumab has some very nice data on improving lung function, and as Dr. Mustafa was saying before, being able to have objective measures; if you’re able to show this is lung function before starting the medication, and then the start of the medication and then do lung function (test) and show an improvement, that’s very impactful for the patient to see those numbers, so when they’re feeling better and they also see those objective numbers. I think for clinicians as well, when we see those objective numbers, that is very reinforcing. Unfortunately, right now, we’re not able to do the spirometry because of coronavirus, and that’s very challenging. But that is a very important outcome to measure.

: One of the reasons I think that many physicians, including specialists, I’m talking about pulmonologists and allergists, sometimes may not treat with a biologic or will not have a conversation with a patient regarding a biologic, is because they are concerned about adverse effects, they’re concerned about the safety profile of the biologics. What could we tell our colleagues or our patients about safety of these products?

I can talk a little bit about that. With the omalizumab, at the beginning there was some concern about increased risk of malignancies. Larger studies have shown that there is no increased rate of malignancy with omalizumab. That was an original concern and it is no longer a concern. With omalizumab, there is a very small, but real risk of anaphylaxis. That is why we give the first 4 injections either in the allergist immunologist office or the infusion center, and we have patients wait for 2 hours after the first several doses, and then we decrease it down to 30 minutes and then the patients can self-administer at home. Most of the anaphylaxis, most of the adverse reactions happen in the first few doses, so that’s how we do that with the omalizumab.

In terms of the anti-IL-5s, we have not had significant issues at least in our practice in terms of anaphylaxis, so those are self-administered at home. We teach them how to do the first dose and then they can be administered at home. Then in terms of the dupilumab, there have been some concerns over ocular symptoms, and if that is the case, then we would stop the medication. In general, that has not been a major safety concern for our patients. If they have a little bit of ocular symptoms, they are overall, in general, very pleased with the improvement in their asthma, improvement in their atopic dermatitis, and they want to continue on the therapy. That’s been the experience that we’ve had.

: I think a small point, Stan, with dupilumab and the ocular side effects, and I think the literature would say we see that more in the atopic dermatitis space than in the asthma indication. I think that’s interesting, where the side effect is almost dependent on the condition that you’re treating, we see that a little bit. One small point that I think specialists appreciate, but I still get this question from primary care referral base, is any 5 of the biologics that are FDA approved for asthma, they are not considered to be immunosuppressive. I think that’s an important point. I think we sometimes think of injectables and monoclonal antibodies and biologics as immunosuppressive because we’ve used so many anti-TNF agents and things like that. These 5 medications are really not felt to be immunosuppressive, and I think that’s an important point that still comes up a lot, that the literature certainly supports, but there still remains this misconception. I think that’s an important point.

At the end of the day, so many asthmatics are getting so many courses of systemic steroids, so they’re on them all the time. The risk-benefit profile, the safety of these biologics compared to frequent courses of oral steroids. It’s a very beneficial safety profile. Certainly they’re not benign, there are important considerations, but these are safe and effective medications when used in the right way.

: Thank you, Shahzad, for those important points, and thank you, Giselle, for adding in. 

Safety Profile of Biologics When Treating Asthma

 let’s get into the pandemic and coronavirus. With respect to asthma, obviously that’s what we’re discussing today, are asthma patients at higher risk for contracting COVID-19?

: The literature shows that eosinophilic asthma and that phenotype may actually be, in a way, protective. On the other hand, if you have uncontrolled asthma, that can put you at increased risk of having worse outcomes if you get coronavirus. I try to counsel all of my patients with asthma, now, more than ever, it’s important to take your inhaled steroids, take your other controller medications, make sure to have your albuterol inhalers on hand at home. I can’t stress enough that the symptoms of allergic rhinitis and the symptoms of asthma have a lot of overlap also with symptoms of the flu and symptoms of coronavirus. With coronavrius, you can have nasal congestion, runny nose, cough, shortness of breath, and these are symptoms that we see with asthma and allergic rhinitis. These are also symptoms that we see with the flu. For the asthma and allergic rhinitis patients, please get your flu shots, please make sure to take all of your asthma medications, and if you do have a coromavirus exposure or any signs of coronavirus disease, make sure to get treatment early, before you’re in trouble.

One of the things, just to bounce off what you said, Giselle, as far as those eosinophilic asthmatics, don’t seem to have a higher risk of getting coronavius. When we’re looking at all the data now, obviously there are so many cuts of data with respect to coronavirus and asthma. When you think about allergic asthma patients have a lowered amount of ACE2 receptor

ACE2 is the receptor that the coromavirus would bind to. There is theoretically a lower incidence of coronavirus in patients with allergic asthma because of the decrease in ACE2 receptor expression, which is an interesting thought. But when you think about all the studies that are ongoing, first of all, they’re retrospective and they’re observation studies, obviously there’s no controlled studies, but this is all we have to go off of now and bounce off of. As a matter of fact, there was a recent study in 

 called the Open Safety study. They looked at asthma patients during this coronavirus pandemic, and they felt that those patients who have severe asthma, and their characterization of their severe asthma patients were those patients who required oral corticosteroids or high-dose inhaled corticosteroids, did show that they had a higher risk factor of having more severe coronavirus disease when they did contract coronavirus.

There are other studies from Spain which showed that that was not so, that in the sense that if you needed a biologic, there was no problem, but the point is that patients with asthma generally, even severe asthma, did not have greater problems. Giselle, you pointed out the lung function, and I think we all agree that if you have a patient with decreasing lung function because of their asthma, those are patients who are probably at higher risk of having problems with the coronavirus.

: One point about the importance of controlling your asthma, and that’s something that we all think is more important than ever. It appears that patients are taking us up on that advice, and there are pharmacy records since March that show asthmatics filling their inhalers more regularly than before. That may also be playing a role, that improved adherence, people taking this seriously, and, of course, all the other precautions we’re taking. We talked about triggers of viral infection and allergens, many of us are being encouraged to social distance and wear a mask. So, all of those exposures may be decreased. People are using their medications more, which is encouraging because we haven’t seen our asthmatics really suffer from suboptimal outcomes compared to the general population.

Managing Asthma During COVID-19

In addressing some of those points about biologics, should you stop biologics? You mentioned, Shahzad, that they’re not immunosuppressive. Should you start a biologic during the COVID coronavirus period? In my own patient population, I say why not? If you want to get in better control, sure. As you mentioned, they’re not immunosuppressives, so there’s no reason to stop it. But during the COVID coronavirus period of time when I think our offices were closed, we weren’t seeing patients, we were only seeing them by telehealth, it was very important to educate these patients that they should continue their biologic, because what you don’t want to do is really result in an exacerbation and decrease in lung function, and then if they would get COVIDcoronavirus, I think they would be at higher risk of having problems.

But what are you seeing in your offices now, when you think about the workplace? Patients coming in saying my asthma is worse, I need a letter for my workplace to say that I have compromised lung function and a risk if I develop COVID coronavirus that I’ll have worse disease. What do you tell your patients? How do you decide what to do and whether you provide them a note or not a note? It’s a difficult situation, butsituation but tell me what your thoughts are about that.

Yeah, I can share my approach, and I do think there may be some various approaches depending on where you are in the country and what things look like locally for your COVID coronavirus rates. But generally, I do try to reassure my patients as the three of us have discussed….. the three of us, that asthma, especially well-controlled asthma, does not appear to be a risk for acquiring COVID coronavirus or COVIDcoronavirus-related complications. I think that’s important to tell people, to reassure people, because often people are nervous. From what you know, and again, Stan, you said the studies, that the science is changing quickly, but we know what we know. In asthmaAs of right now right now, I try to reassure them. With that being said, and as was touched by Dr. Mosnaim, a lot of the symptoms of allergies, upper airway symptoms, common colds overlap, but this is no time to be coughing in the workplace and sniffling. It raises eyebrows. So controlling Controlling the asthma is so important.

And thenThen for individuals who are concerned, we really do try to focus on even more adherence to wearing a masks and social distancing and hand hygiene. In my opinion, the vast majority of my asthmatics can go on with their regular occupations. A vast majority of my asthmatics can attend school, and that’s how I try to approach it, by maximizing in best controlling their asthma. I think it’s a very small percentage of individuals for outstanding circumstances or their specific occupation, that we may want to revisit that. But that’s been my general approach— reassurance, maximizing asthma care, excellent counseling because I do think from what we’re seeing in the community, at least here locally, again it may depend on your local COVID coronavirus rates, but it’s going fairly well.

I will say, I will chime in and say masks should not be exacerbating an individual’s asthma. Masks are safe to wear when you have chronic respiratory illness. They take getting used to, they’re uncomfortable. I don’t have asthma and they make me uncomfortable. Gyms in New York are requiring you to work out and exercise while wearing a mask. So thereThere is certainly getting used to it. But I do not think, and my opinion, again I’d love to hear you guys chime in, is I do not think having asthma or respiratory disease is a reason not to wear a mask. I actually can’t think of any real medical condition that should preclude you from wearing a mask. For many individuals with medical conditions, it’s even more important to wear a mask to protect yourself and the community around you. So that’sThat’s my approach with my patients.

Just want to chime in, I completely agree what you’re saying, Shahzad. But some other added points. First of all, in children, talk to pediatricians, they’ve seen less respiratory problems from children as far as viruses that turn on asthma, rhinovirus, for instance, so, therefore, less asthma. Why are they seeing less respiratory problems? Because the kids are not mixing with other kids, they’re not in school, they haven’t been in school. Now they are back in school, but up until this point in time, up until Labor Day this year, they weren’t in school. T So they had really very little respiratory infections. If they’re wearing masks in school, also a decrease in respiratory infections. That’s also helping keep patients who have asthma under better control. Besides taking their medications, they are also having less actual exposure to these viral infections.

Precautions Taken to Control Asthma During COVID-19

It just so happened in the New York City Department of Education, they have given notices to all the employees saying, “Well, if you have asthma and you bring us a letter from your physician we could give you the consent to work from home.” I have all my asthmatic patients coming in asking for a letter.

The other issue is the anxiety. Anxiety levels in our asthmatic patients have increased, just like in the rest of the population. All of a sudden, they think they’re having difficulty in breathing, they can’t sleep. Is it because of their asthma? Maybe. I have them come into the office. I’ll check their lung functions and try to determine is it really their asthma bothering them or it’s really anxiety. There’s a tremendous amount, as we already know, psychological and psychiatric issues coming out of this coronavirus pandemic, and it ties in with our asthma, it ties in with the symptoms that they think are asthma. If a patient has normal lung function, and I read the lung function test in the office now, even though they may be using albuterol a lot because they think they’re having trouble, and if we assess their asthma as well controlled, I tell them, “Look, I think it’s anxiety.” A lot of them appreciate the fact when I tell them this is anxiety, say, “Oh, thank God it’s not my asthma.” Then they will then continue to work where they’re supposed to, as opposed to asking for a letter so they should be working from home.

As a matter of fact, it says in the New York City Department of Education directions, that if it says if you have moderate or severe asthma, bring us a letter and then we would let you work from home, and I look at their lung function, I look at a more objective assessment of what’s going on. A lot of anxiety on top of it, and I want to be very appropriate both to the patient and to wherever they’re working, and say, look, I’m not concerned about them. If they get coronavirus, they would handle it the same way because their asthma is in control, or if they already have poor lung function and they got coronavirus, I’d be concerned, so therefore they should work from home. I wanted to know if you guys are experiencing these same types of patients in your offices.

Yes, we’re definitely having those questions come up. Something that we’re counseling many patients on is that you want to optimize your asthma control, and we want them to make sure and let their employer know that they have some of these symptoms at baseline. They may have some baseline symptoms of nasal congestion, some baseline symptoms of cough that go with the asthma or the allergies. But if there’s a change in baseline symptoms, that’s where the concern is. Again, if things are at baseline, it’s okay to go to work, but if there’s a change from baseline in symptoms, then that’s when they should be more concerned, when they should not go to work, when they should notify us so that we can evaluate do we need to better optimize their asthma and allergy care, is this the flu, is this coronavirus, what’s going on?

: Giselle, you mentioned allergies and talking about these different patient populations. I mentioned anxiety, but it’s very interesting to think about allergies. We have had many more patients coming in complaining of their nasal allergies, sneezing, stuffiness, congestion. Why? Because they’re spending time at home, 24/7. They’re exposed to the dust mite, they’re exposed to their animal dander, and they’re actually having increase in their allergic symptoms, and if they’re taking their asthma medication, they’re staying well controlled. I completely agree, just the exposures have changed.

Anxiety Among Patients With Asthma During COVID-19

We know that we’re talking about the coronavirus pandemic overlapping with the flu season. First of all, on a clinical presentation, do they differ in how they would present to help us differentiate them? We could do rapid testing now for coronavirus, you could do a test for the flu. That’s been available for years. But clinically, could you determind if there is a difference from person who has the flu or a person who has coronavirus when it comes to their symptoms?

cutely, up front, it would be very difficult to clinically differentiate between the two infections. These are respiratory viruses, very different families of respiratory viruses, but they’re going to present very similarly in my opinion with potentially fever, upper respiratory symptoms, myalgias, things like that. Over time certainly, coronavirus and influenza are not the same, we know that, they are very different. They have a different time course, whereas you might be thinking you’re going to be getting better with influenza after several days, and with coronavirus infection, there may be a second worsening right after several days. But initially it’s going to be difficult to determine the difference.

As was said, there is the ability to test. But if there’s any change in clinical status, coughing, fever, certainly increased nasal symptoms, upper respiratory symptoms, I think many symptoms have the option to test hopefully in America now for coronavirus, but also at the same time test for influenza as well, because you would like to know that because it would certainly change your management. We always say we’re the allergists, we’re immunologists, we believe in vaccination. But if ever before, vaccination with influenza vaccine this year is more important than ever. This global pandemic has got me down, too, but I like to be the eternal optimist. We just saw Australia go through their flu season, and for the first time in decades, they had the lowest rate of hospitalization for influenza in Australia. That gives me hope that there is a way to do this right, where if we do this with masking, social distancing, all the precautions we should be taking, we may actually see better outcomes with other infectious diseases like influenza that we typically do in the winter. It’s very important that there’s an opportunity here to do better.

: Very true. Talking about the flu vaccine, what are you seeing when it comes to patients coming in for the flu vaccine? I know in my own patient population; they are coming by the droves for their flu vaccine. It’s never been this high in my own patient population. I think they’re totally aware of the crossover between the flu symptoms and the coronavirus symptoms, and they are hearing the message. Shahzad, you mentioned hearing the message about wearing masks and social distancing. That would be nice, but that’s one of the problems that’s ongoing. Are you seeing the same thing with patients requesting flu vaccine?

:We always offer influenza vaccine to every patient that comes in that qualifies, which is nearly everyone. We haven’t given many. Because they’ve already all gotten it. It’s even one more step than you. It’s only middle of October and that’s great, but many of my patients have already received their influenza vaccine. Anecdotally, I think, more people are being vaccinated locally, at least that’s my opinion. Sorry, Giselle, to cut you off.

Not at all. I also am seeing that patients are being much more proactive about getting their flu shots this year. I’ve been doing a number of telemedicine visits as well; many colleges are requiring that students that are on campus get the flu shot. I am having my young asthmatics that are in college, they’re being very proactive about getting their flu shots as well. I think college campuses across the country are being proactive about the flu shot, locally the message to patients about getting their flu shots is definitely being heard.

I’ll just take this opportunity, I know this is an asthma talk, but I think it’s important as allergists, and there’s still this misconception in the community, we still hear it, that there are very few reasons not to get the flu shot. An egg allergy, which still comes up, especially in our pediatric population, is not a reason for the kid not to get the flu shot. Even if you have egg allergy, a severe egg allergy, a severe reaction, it is safe and recommended you get your flu shot. I just want to add that. There are very few reasons not to get your flu shot. If you think there is a good reason not to get your flu shot and you are interested in it, please reach out to an allergist, your primary care doctor, a provider who can counsel you and talk you through the risks, because again the importance has never been higher.

Thank you for that important health care informative message. Doctors, thank you both. I think the discussion has been great. It’s been an informative discussion both for myself, I’m sure for you guys, and for the audience that will be viewing it. Before we conclude, maybe you already gave me your final thoughts, but any other final thoughts that you would like to add? Now’s your chance. Giselle, anything?

The final thought is that we’re all in this together, this coronavirus pandemic. I think that we are all trying to get back to a functioning society. For our patients with asthma, again keep doing what you’re doing, getting your flu shot, optimizing your management of your asthma, taking your controller medications. If you are on a biologic, continue to take your biologic. We’re just trying to make sure that we take the best possible care of our patients.

I echo everything that was just said. We are really in this together. We will get through this together. But this is difficult, and I think it’s okay to say that this is really difficult for many people on many levels. But as health care providers, we have tools for our asthmatics to control outcomes, have good outcomes. We as a community have tools get through this with the appropriate precautions. If you have questions or concerns about how to best get through the global pandemic, how to take care of your asthma during this, please reach out to us. 

It is safe and appropriate to get health care, whether it’s in person, whether it’s with telemedicine. It sounds like all of us are doing a little bit of that and we will continue to. Your providers are here for you. We have some good information on how to get through this, whether it’s asthma or other chronic conditions or just the global pandemic itself. Thank you for the discussion today, I really enjoyed it and I learned a lot from both of you.

: Thanks. I’d like to sum it up in one phrase. It may be the worst of times in the sense that people are getting sick with flu and coronavirus, but, in a way, as has just been pointed out both by Shahzad and Giselle, it may be the best of times. People coming in for their flu immunization vaccines, people wearing masks, people social distancing, and they have the opportunity, as mentioned, to reach out to your physician in your environment, in your area, your specialist physicians, allergists or pulmonologists, and knowing what to do and how to move forward.

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Biologic Treatment Considerations for Asthma During the COVID-19 Pandemic and the Upcoming Flu Season

EP 1: Overview of Uncontrolled Asthmatic Episode

EP 2: Quality of Life and Increased Risk of Asthma Exacerbations

EP 3: Over and Under Diagnosis of Asthma

EP 4: Targeted Pathology for the Treatment of Asthma

EP 5: Common Biomarkers of Asthma to Determine Treatment Efficacy

EP 6: Raising Awareness Among Physicians Regarding Biologics

EP 7: FDA Approved Agent Omalizumab for Asthma

EP 8: Patient Factors That Determine the Use of Omalizumab in Asthma

EP 9: IL-5 Inhibitors for Treatment of Asthma

EP 10: Dupilumab for Moderate to Severe Asthma

EP 11: Safety Profile of Biologics When Treating Asthma

EP 12: Managing Asthma During COVID-19

EP 13: Precautions Taken to Control Asthma During COVID-19

EP 14: Anxiety Among Patients With Asthma During COVID-19

EP 15: Importance of Flu Shots for Patients With Asthma During COVID-19