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Michael Wechsler, MD: Hello. I'm Dr Mike Wechsler and welcome to Medscape's InDiscussion series on moderate to severe asthma. Today we'll be discussing allergic asthma with Dr Mario Castro. Dr Castro is the L.E. Phillips and Lenora Carr Phillips professor and division chief of pulmonary critical care and sleep medicine at the University of Missouri-Kansas City School of Medicine. Welcome to InDiscussion, Mario, to this exciting topic of allergic asthma.
Mario Castro, MD, MPH: Thanks for having me.
Wechsler: It's great to have you back. You're a return guest. You were on one of our season one episodes last year, and we had a great discussion about severe asthma. We've had a lot of great feedback about severe asthma and all sorts of questions about different types of asthma since we last spoke. One of the topics that's come up is that of allergic asthma. What are your thoughts about all the different types of asthma, and is allergic asthma the same as asthma?
Castro: I consider allergic asthma as a phenotype, which is a cluster of characteristics that describe what our patients have. As we've talked about before, asthma is really a common chronic disease, but it represents many different types of diseases. It's quite heterogeneous in its manifestation. It's helpful for us as clinicians to think about who is that allergic asthma patient, and what are their characteristics? How do we diagnose them, and then how do we treat them differently?
Wechsler: Tell us what differentiates allergic asthma from other types of asthma.
Castro: Allergic asthma typically has an early onset. For example, I asked my patients in clinic this morning, "When did your asthma start?" If it started when they were a child, like one of my patients who started when she was 2 years old, that person has early-onset asthma. The typical cutoff we use is age 12 — before that being early childhood-onset asthma, and then that late-onset asthma being later on in life. That early-onset asthma tends to be more allergic, tends to have evidence of hypersensitivity to the allergens either by skin prick testing or by allergen-specific immunoglobulin E (IgE) testing, and has a higher incidence of allergic rhinitis and atopic dermatitis associated with that. When I see those features in a patient often, I find that they have early-onset asthma and have this allergic phenotype.
Wechsler: When you say that they're allergic, you're referring to specific triggers. What are some of the triggers that can cause asthma and allergic asthma, specifically?
Castro When we think about allergic asthma, this is certainly a group of patients who will give you that historical feature: "When the pollen count really went up, that's when my asthma started to flare up," or "I was out there cutting grass, and my asthma flared up," or "My girlfriend brought over the cat, and all of a sudden I started to wheeze when the cat jumped up, and I was petting the cat." They have these classic triggers that they're sensitized to, and it triggers their subsequent asthma symptoms. That's the history that we tried to attain is when you're exposed to things, what triggers you? Is it that classic allergic trigger, or is it like in a patient I saw this morning, where she described, "Well, it's more with cleaning products and perfumes." Those aren't classic allergic triggers. What we're talking about are those things that have a typically seasonal nature or they're year round, they're perennials that are classically indoor allergens, such as dust mites, and those things that are in the indoor setting, which can also be molds, cockroaches, and other things.
Wechsler: When you're talking about seasonal things, you're oftentimes talking about pollen from grass, trees, and weeds. It's so important to really talk about not only how the patient is doing right at the moment but also what happened during other times of the year. What are the typical times of the year in North America that we see some of these features?
Castro: In pediatrics, they will typically see these allergic triggers in the spring and fall months. Sometimes in those fall months, it's more often due to viral infections. Those are classic seasonal events that we see in pediatrics. It's also similar in adults. I think the one thing that's different in adults is they are often much more mobile and can be exposed to things almost year round.
Wechsler: It's always important to take a good history. You mentioned the workup of patients with allergic asthma and how you make a diagnosis of allergic asthma. So far, what you've gone through is a history. You take a good history, and even in 2023, it's important to take a good history. Beyond that, what's the rest of your workup? First, are you still doing physical exams on your patients? Second, what features of allergic asthma can you identify in patients with allergic asthma?
Castro: When we talk about the physical exam, I think after we've taken that history, if they have a component of allergic rhinitis or sinusitis, we're going to want to do a good nasal examination to see if they have evidence of boggy turbinates. Do they have evidence of secretions coming from their sinus or do they have polyps? That's an important part of our exam. Often, we as pulmonologists and our colleagues aren't doing that, even though the allergists are often doing that. I think it's important for us as asthma specialists to take that upper airway examination and look at that posterior pharynx to see if there's any evidence of cobblestoning, or you evidence that there's postnasal drainage. The next thing in terms of a focused exam is certainly listening to the lungs and seeing if there's evidence of any wheezing, expiratory slowing, or evidence of something else going on (such as rales). Lastly, in terms of the allergic phenomenon, you really want a careful look at the skin. Do they have evidence of eczema or other type of dermatitis that might be related to allergic exposures that would be consistent with that? As we mentioned earlier, that atopic dermatitis patient typically fits right into the allergic asthma patient.
Wechsler: That's really important. You take a history, you do a physical exam, and then what other things are important in the workup of allergic asthma? You mentioned a few things already. Let's review for the practicing clinician, either for the pulmonologist or allergist, what should a primary care doctor order in advance of referring to a specialist?
Castro: We typically want to measure the biomarkers in all of our patients who have persistent disease. If I'm seeing a patient for the first time, I'll typically get a complete blood count (CBC) with differential, and I'll look on that differential to see what their absolute eosinophil count is and, as Global Initiative for Asthma (GINA) guidelines suggest, anything above 150 cells/μL could be considered elevated for that individual. Other than that, I typically will get my patients a total IgE, and this helps me define whether they're atopic. It doesn't have any predictive value, but it does have value in terms of identifying whether they're atopic. If they do have that allergic history, I want to get specific antigens appropriate for their region. I have a panel here that I use for the Midwest. You probably might have one for the Colorado region. That panel helps me identify the top allergens in this environment that I should be testing for in terms of sensitization.
Sometimes, though, that patient tells me, "I have a chicken coop in the backyard that I go through. " Then, you want to add some specific things that are specific to their history that you might want to delve into a little bit further. So, CBC with differential, IgE (total IgE, specific IgE), and I like to have some imaging. Ideally, I would love to have a chest CT in everybody, but not all insurance companies would like that. I just start off with a plain chest radiograph, proximal and lateral. and as we know, the chest x-ray proximal and lateral is not a very sensitive instrument, but it's helpful for us to exclude other disorders that may be contributing to that. If you have evidence of heart failure, for example, or if you have evidence that they have some changes — cardiomegaly that may be suggestive or enlargement in the pulmonary arteries, these are all things that may be triggered by your initial imaging. I just had a patient this week who presented to me after she had been on five different biologics, and she did not respond to any of those biologics, so they were sending it to me to help them out. Looking at her imaging, I said, "Wow, she has very generous pulmonary heart rates, and she saw the cardiologist 5 years ago, and her pulmonary artery pressures were mildly elevated then. I'm wondering now why she has lower extremity edema and dyspnea that's not responding to her asthma treatment."
Lo and behold, she does have significant pulmonary hypertension now that she's developed. I do think that those are my key things that I like to obtain for pretty much all these patients who have persistent asthma, in addition to pulmonary function testing, which should be available for all patients with asthma. Then we delve more into the detailed testing dependent upon their history, their physical exam, and their response or lack of response to therapy.
Wechsler: You mentioned spirometry, eosinophils, [total] IgE, and specific IgE. More quick questions: When do you refer for allergy skin testing as opposed radioallergosorbent (RAST) testing? And second, what about exhaled nitric oxide — how does that fit into the whole picture? I know that isn't available in a lot of places.
Castro: I tend to get my allergist involved when I have a patient who has multiple allergens that are triggers for them or has coexistent allergic disease, such as atopic dermatitis, eosinophilic esophagitis (EOE), or something else that is not just straightforward asthma that's also contributing to their disease.
Say [you're treating] somebody with pretty significant allergic rhinosinusitis or chronic rhinosinusitis. You've tried the antihistamine approach. You've tried using nasal steroids, nasal antihistamines, and they're just not getting controlled, and it keeps triggering their asthma. I think at that point that getting the allergist involved is very important in terms of addressing that as their allergic trigger for the particular individual. Your second question is a great one — exhaled nitric oxide — I think, in general, we tend to underutilize that for testing purposes. The recent National Asthma Education and Prevention Program (NAEPP) guidelines have now incorporated that into part of the testing algorithm in terms of looking at diagnostic utility of exhaled nitric oxide or fractional exhaled nitric oxide (FeNO), and also have used it for looking at prediction of response to biologic therapy. I find it helpful, because it's helps me identify sometimes that patient that has type 2 interleukin (IL)-13-driven disease that is really something that I may need to address in terms of a biologic therapy that I wouldn't have had that information without doing an exhaled nitric oxide level. As you mentioned, the caveat is that sometimes the payers won't cover it, so we have got to be careful about whether we're going to bill for it. What if the payers don't cover it? How are you going to cover that cost?
Wechsler: That's a really important factor as well. I think we always have to think about patients and not overcharging them but trying to get as much information as possible because I think it does add a lot of value. How does allergic asthma differ from type 2 asthma? Is it just a subset, or is it a different entity? When would you call someone type 2? And when would you call someone allergic, or would you say this person has type 2 allergic?
Castro: Great question. I think in terms of type 2 inflammation as being inclusive of allergic asthma. When we think about the type 2 cytokines, we're talking about IL-4, 5, and 13. Those are the classic type 2 cytokines that drive type 2 disease.
But we also know that there's other mechanisms to elicit type 2-type cytokines, including the two pathways. One can envision that somebody has classic antigen driven, driving through antigen-presenting cells, activation dendritic cells, and then downstream signaling through that allergic cascade to activate the IgE itself.
And then, activating mast cells and basophils — that's the classic allergic pathway. But we also know that you can have somebody with type 2 inflammation where it's not going necessarily through the allergic pathway but going more with eosinophilic asthma. That may be more IL-5, IL-13 driven or through the innate lymphoid cells (ILC)-2 cells. This is where I think understanding the pathophysiology helps understand why it is helpful to call somebody allergic or non-allergic, and how that helps you think about potential treatment for that patient.
Wechsler: That's a great segue. I think we talked about what allergic asthma is. We've talked about diagnosing allergic asthma, and how to differentiate from other types of asthma. Let's move on and talk about treatment. I think the topic of treatment of allergic asthma is a little bit controversial. There's a lot of areas where there's good evidence; there are other areas where the evidence is a little bit less robust. I think the general approach is to avoid allergens, if you can, but it can be hard if you've got a dog in the home. Getting rid of the dog, convincing your patient to get rid of the dog can be a bit of a challenge. But it is something that's feasible. It's hard, on the other hand, to avoid outdoor allergens: the pollen, the trees, and the grasses that are occurring. Let's talk a about some of the strategies about allergic asthma management.
Castro: The first thing I always think about is, what is the underlying severity and the control of that patient's asthma? That helps me guide how much I'm going into evaluating that patient further. And then, as we talked about the very beginning, thinking about that exposure history, that trigger history will help me also think about how much to dive into environmental modification for that patient. I think the testing that we just talked about is critical because when I talked about environmental modification for patients, I want to know specifically what they are sensitized to and what do we focus on because I think if you take a broad approach, "Oh well, you got to get rid of the cat. You have to do the dust mites, you got to do the dog, you got to do the pollen." Patients just get confused, right? If you have that allergy skin test, I show them results. I show them, "Hey, you're very allergic to dust mites. Let's work on that. You're very allergic to cockroaches. Let's work on that." Then, I specifically tailor that approach to that patient based on what they're sensitized to. Ideally it would be great if you have a single allergen you can tackle. As you know, in our patients, sometimes it's multiple allergens that are contributing to their disease, but I still take it a step at a time with my patients and focus on what's triggering their disease in terms of that treatment component.
Wechsler: Now, a lot of patients ask me about specific mitigation strategies: air purifiers, HEPA filters, mattress covers, impermeable pillows, and things like that. First, how good are the data for those strategies? What do you recommend? How do you respond to patients when they ask about those things?
Castro: The NAEPP guidelines were recently updated about this and really recommended that environmental modification and this treatment of their allergens be part of a multi-component mitigation strategy. If you just focus on one thing, and they're allergic to 10 things, you may not eventually get there. I do think it's important to start at a step at a time and not overwhelm the patients. So, if they're dust-mite allergic, I talk to them about getting mattress covers, getting them impermeable pillow covers, and the importance of humidity in terms of dust mites and how they propagate. I always talk about how the bedroom is where we want to focus first, because if you talk about the entire house, that's sometimes overwhelming to patients. Let's just focus on your bedroom first and get that to the best strategy possible. I will focus on getting those mattress covers so they're dust mite allergic. I will talk about the use of HEPA filters that are within that bedroom to try to purify the air within that environment. I also use ventilation covers or filters to at least try to make that bedroom as pure as possible. That's where we start. Down the road, maybe you start talking about removal of carpets and those kinds of things, but that's not usually where I start off first.
Wechsler: Great. So, allergen avoidance and trying to mitigate things as best as one can. What about treatment options? Let's presume that the patient is adherent to their inhaled corticosteroids and their bronchodilators. Let's presume that you have addressed all comorbidities that can complicate asthma: the sinusitis, the reflux, and all of the other things that can complicate it. Where do you go in the severe allergic asthma patient? First, in terms of choosing a biologic therapy, and then I'm going to ask you about subcutaneous immunotherapy, or allergy shots, and what the role is there.
Castro: Before we go to biologic therapy, I would say that we know that allergic rhinosinusitis or chronic rhinosinusitis is going to contribute to our lack of control in our patients. So, treating that allergic comorbidity first is the highest priority. I've had some patients come to me, and they're miserable. They're stuffy and just draining all the time, and they've taken intermittent antihistamines, and really haven't had a consistent treatment basis. We talk about consistent use of a nasal steroid, using an antihistamine, and then if they have rhinosinusitis components, significant chronic rhinosinusitis, then introducing sinus rinses. That's the first step in terms of treating allergic asthma. The second step is the considerations for biologic therapy for somebody who has a classic allergen-driven history — this is every time those pollen counts go up, their asthma goes out of control. They have preserved lung function, so they have relatively normal lung function. Then, I think anti-IgE therapy with omalizumab is often very helpful in that particular patient. The nice thing about omalizumab is we have 20 years of history of dealing with it, so it's something that we have been managing for a long time in our patient population and have a lot of great data in terms of how to use it well in our patient population.
Wechsler: When do you use omalizumab, and when do you choose some other biologics like dupilumab, tezepelumab, or any of the anti-IL-5s? Because there's data that those drugs are also effective in patients with allergic asthma.
Castro: You're spot on, Mike. When we looked at the data for the anti-IL-5s, we looked at IL-4 receptors, and for the latest one, anti-thymic stromal lymphopoietin (TSLP). In all three of these categories, they have broken down the patient population that participate in the pivotal studies into those who are allergic and those who are non-allergic. And it's clear that it works even in the allergic group just as well as the non-allergic groups. Those biologics, the six that we have available, all have evidence for working in allergic asthma. Now the question is, when do you use those other ones as opposed to, say, an anti-IgE approach? I alluded to that by thinking about their lung function coming in. If I have somebody who is highly allergic, uncontrolled, and I want to improve their lung function, I'm not necessarily going to omalizumab first. Typically, if they have a significant eosinophilic component as well, we'll use an anti-IL-5, or dupilumab, or an anti-TSLP. All three of those are shown to be effective in that allergic asthmatic population. And there's a little bit of what we call shared decision making and understanding: Well, is that patient okay with a subcutaneous injection they have to do every 2 weeks, or would they prefer something that we can get to every 2 months after the first 3 months? So, that helps me also guide which biologic to use.
Wechsler: Also, if they've got concomitant urticaria, for instance, that might point you to using anti-IgE because it has that indication. Before we wrap up, I just want to get your quick, 15-second thoughts on allergy immunotherapy. You're a pulmonologist. Tell me your thoughts about allergy shots.
Castro: Allergy immunotherapy has been around longer than you and I, Mike. It's been around for a long time. The GINA guidelines as well as the NAEPP guidelines have come to a consistent message that it's not indicated for severe asthma, uncontrolled asthma — that should not be the immunotherapy patient that you should be introducing. But in that patient who has non-severe disease — mild to moderate asthma that has a significant allergic component — if they're easily controlled with antihistamine or with nasal steroid, that necessarily is not going to be the appropriate patient to go with immunotherapy, subcutaneous or oral. If they aren't achieving control with that, then certainly involving the allergist at that point to implement immunotherapy would be my next step.
Wechsler: Great. This has been a great discussion, Mario. Thank you so much for joining us today. We've been talking about allergic asthma, the importance of doing an extensive workup, evaluating what type of asthma the patient has, evaluating all the different triggers that a patient has from the environment, doing a thorough physical exam, good history, and then working to try to mitigate allergens and also other novel biologic treatment approaches.
I want to thank you all for listening to our podcast. We've had Dr Mario Castro with us, and this is Mike Wechsler. We look forward to our next episode on this Medscape program.
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Cite this: Does Your Patient Have Allergic Asthma? - Medscape - Jul 13, 2023.