Diagnosis, Categorization, and Management of Patients With Asthma
In this episode, Dr Rizzo interviews Michael S. Blaiss, MD, to discuss allergic asthma and its comorbidities, including the definition, diagnosis, and management of patients with allergic asthma. They discussed the role of immunotherapy, inhaled steroids, biologics, and bronchial thermoplasty.
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Michael S. Blaiss, MD, is the Executive Medical Director of The American College of Allergy, Asthma, and Immunology (Arlington Heights, IL).
Albert A. Rizzo, MD, is the Chief Medical Officer of the American Lung Association and Pulmonary Staff Physician for the Center for Virtual Health at ChristianaCare (Newark, DE).
TRANSCRIPTION:
Speaker 1: Hello, and welcome to Critical Observations in Pulmonary Medicine led by Chief Medical Officer of the American Lung Association, Dr. Albert Rizzo. The views of the speakers are their own and do not reflect the views of their respective institutions.
Dr Albert Rizzo: Hello, and thank you for joining today. I'm Dr. Albert Rizzo, a pulmonologist and Chief Medical Officer of the American Lung Association. Welcome to Critical Observations in Pulmonary Medicine.
Today, I'm speaking with Dr Michael Blaiss. Dr Blaiss is a clinical professor of pediatrics at Medical College of Georgia in Augusta, Georgia, and Executive Medical Director of the American College of Allergy, Asthma, and Immunology. He has also served as President of the American College of Allergy, Asthma, and Immunology, and is a past member of the board of directors of the World Allergy Organization. Dr Blaiss has published more than 120 scientific peer-reviewed articles, and presented at more than 500 meetings and seminars throughout the world. He is eminently qualified to discuss our topic today, allergic asthma. I hope you enjoy.
Over the years, a number of terms have been used to describe or categorize asthma patients. These have included intrinsic, extrinsic, allergic, childhood, eosinophilic, high T2, low T2, severe, and on and on. When the term allergic asthma is used today, what should a clinician be thinking?
Dr Michael Blaiss: First, I have to say all these terms just fake drive us all pretty crazy. I always look at asthma as a syndrome, and there is no one particular category for a group of patients. I think everybody's asthma, is in fact, unique. And we're now using these type two high, and type two low, and now we know they're not. It gets very confusing. So I'll tell you how I look at allergic asthma as an allergist. And first, it's important and, what's the history of the patient? Do they also have other atopic conditions? So especially, do they have allergic rhinitis, or atopic dermatitis, or food allergy? But very importantly, is the history, is there any relationship between any particular exposure, any particular time of year? And in fact, increase flare-ups of the patient's asthma. And that doesn't always occur, because we have many allergens that are perennial, or year-round, like cat, and dust mite, and mold in certain areas of the country.
So I think. It's the history along with then, doing proper testing, and then, trying to put it all together to see if in fact, a component of the patient's asthma may be related to allergies. As you know, the only way we could really prove it, is in fact, to do a provocation test. So let's say the patient, we think, has a cat allergy, then to do an inhalation challenge with a cat, and see, if, in fact, you provoke the asthma. That's the only way 100% to say it. So what we're trying to do is our best guess, that there is in fact, an allergic component, and then treatment may, in fact, improve the patient's asthma.
Dr Albert Rizzo: And I guess that feeds into my next question, as far as, how do you support this diagnosis with the role of the allergy testing? Whether it's skin-prick testing or specific IgE testing, what's the utility of those at this point in time?
Dr Michael Blaiss: It gets back to, and one of the things I emphasize, whether it's allergic rhinitis, or asthma, or food allergy, testing alone, doesn't give you the answer. So really have to, again, try to relate the history, and then use appropriate testing that may, in fact, go along with the history. An example would be, a patient's asthma only flares up say, in the fall. So that could be viruses, but that could be ragweed. It could be mold in certain areas, but it sure wouldn't be tree pollen. It wouldn't be grass pollen.
So in other words, that type of history, I would do appropriate testing for the things that could occur during that time, to in fact, see if the patient does have a sensitivity, and then try to correlate it. So one of the things that is bothering me, and allergists around the country, is a lot more of the direct-to-consumer allergy test. Whether it's inhaler testing, or whether it's food testing, and it just sends back all these positives, that doesn't mean it's clinically relevant. Again, you have to have a history that goes along within doing the appropriate testing. So whether it's allergy skin testing by the prick method, or the blood studies, and in fact, the blood studies now, and most of the labs are very good and very accurate.
Dr Albert Rizzo: When do you then decide about desensitization or immunotherapy in some of these patients? Where in the treatment algorithm do you put that?
Dr Michael Blaiss: It really depends upon, again, the history, the severity of the problem, what already has been tried in the patient itself. So, I go through a threefold approach in that patient with allergic asthma.
One is, what have I done? And we can talk about this later. What have I done in the environment to see if that would, in fact, help the patient. Number two, have I done appropriate therapy? And then with that, in many cases, then I will, many times, try allergen immunotherapy. But the patient has to understand the possible benefits, the possible risk, associated with it. The good news is, we know that allergen immunotherapy, or desensitization, is the only disease-modifying treatment we have for allergic conditions. Which, in fact, does have an effect on the immune system, switching it from that Th2 high to more of a Th2 low or a non-Th2, whatever term you want to use now.
And there is data in the literature, that shows that it does, in fact, improve asthma. Probably the best studies, in fact, have come out of Europe, with the dust mite sublingual tablet. Where in fact, they have an indication in Europe, to use this tablet, in the treatment of patients with dust mite-induced asthma, where they've shown that they're able to decrease the exacerbation rate in the patient population. We believe the same thing happens, whether we're giving subcutaneous immunotherapy, which is what's typically done in the United States, so we don't have as rigorous studies as we do for the sublingual tablets. So I think it is an adjuvant for many patients that are suffering with allergies, including allergic asthma, but it doesn't mean every patient with allergic asthma should be placed on immunotherapy
Dr Albert Rizzo: And sublingual therapy is only available for certain specific allergens. Is that correct?
Dr Michael Blaiss: Yeah. So in the United States, the only FDA-approved sublingual immunotherapy is for the Northern grasses, for dust mite, but just in the adult population at this time, though, that's going to be changing, I think, by the FDA, hopefully, in the very near future, the Phase III studies look very good. And ragweed, in fact, is available in Canada. They also have birch, which also cross-reacts with oak in the United States, but that's not approved in the United States.
All the other sublingual preparations, the drops that are done in the United States, are all off-label. None of them have been approved by the FDA, and that's why insurance doesn't cover them. That's why patients have to pay out of pocket. And at least, my review of the literature, and I've written on this several times, we don't have studies, that definitely say that the way it's being done in the United States with sublingual drops is efficacious.
It's done differently in Europe, where sublingual drops are approved. The sublingual drops in Europe, you get each allergen separately. So let's say, you are allergic to dust mites and grass. You get a vial of dust mite, you get a vial of grass, and then, you would do drops of each one. In the United States, what's done is all of these are mixed together. And we don't have studies that have been done, that show mixing the allergens, as such, shows efficacy. So I think, patients should understand that. And physicians that don't prescribe immunotherapy, should understand that also.
Dr Albert Rizzo: I suspect, patients like it, because they don't have to get shots. I guess that's one attractive reason for the sublingual if it's an offering for them.
Dr Michael Blaiss: No. It obviously is. There are a lot of attractions for sublingual. One is obviously, the injection. Two is that you don't have to come to the physician's office on a regular basis to get injections, it's just done at home. And the side effect profile is much, much less, when you look at anaphylaxis. Basically, anaphylaxis is unbelievably rare with sublingual compared to, it's still rare with injection, but if you look at one versus the other, it's much, much rarer with sublingual. So there definitely are advantages.
You look at the clinical data. If both are done correctly, subcutaneous, sublingual, they both are about equal efficacy.
Dr Albert Rizzo: I've heard that it may take anywhere from 6 to 12 months to start seeing benefits from desensitization therapy. Is that correct?
Dr Michael Blaiss: Yeah, that's correct. And we tell patients that, I always tell them, it can be up to a year, if in fact, they're adherent, and then, we start weaning them down.
There is data with the tablets, to suggest that you may see efficacy sooner, especially if they're started before the season, is what's recommended for grass and ragweed. But in general, yes, you will see improvement usually, if done correctly within that year.
Dr Albert Rizzo: Good. And you touched on this a little bit earlier, but what's some great advice for these individuals, just in general, with regard to their environment, in order to avoid flares? Are there specific things that an allergic patient should pay attention to, on a regular basis?
Dr Michael Blaiss: Sure. And a lot of it depends on what they're allergic to. So one of the reasons I think allergy testing is helpful is, finding out what it is, or what may be causing it, and then trying to avoid that. So the patient that say, has a pet allergy, which is extremely common in the United States. Ideally, there shouldn't be any pets in the house if the person has an allergy. The problem is, and I deal with this on a regular basis, a lot of times let's say, a couple's getting married, and one has cats that they love, and the other one is allergic to cats. And most cases, the person who would rather keep their cats than have a new spouse. So there are things that we have to try to do. One is, keeping the pets out of the bedroom because that's where you spend a majority of your time in a 24-hour period. HEPA filters may help a little bit.
There is now, a new pet food, that decreases levels of Fel d 1, which is the major allergen in cats, binds it up. And there's data suggests that may be helpful too. Things like pollen, the spring and the fall, keeping the windows to the house and car closed, so the pollen doesn't come in. Don't dry clothing outside. Staying indoors in the early morning hours, late in the afternoon, when pollen levels seem to be the highest. If you had been working outside, when you come in, shower, make sure you get all the pollen off of you.
Other things are a little harder. Dust mites, which are little microscopic bugs that go on the carpet and the bedding. We try to get patients especially to work in the bedroom again. So removing carpet, removing dust collectors, washing all the bedding with hot water. Dust mites grow in hot humid temperatures. So keeping the humidity down, keeping the temperature down, will also help decrease dust mite levels.
And there are other things we do for other things. The main thing is, to try to give the patient information on, here's some things that can help maybe hopefully decrease. It's not going to cure your problem in most cases but definitely decrease your symptomatology.
Dr Albert Rizzo: And is there a role for some indoor air filters? You mentioned, I believe, HEPA filters might be helpful for some patients.
Dr Michael Blaiss: Yeah. This gets very controversial because there's not a lot of strong data out there. In general, they're not that efficacious. But of the ones that we do recommend, the HEPA filter seems to be the best. And what I tell patients is that, one, use one that's in that, so not a simple one for the house, but one in that particular bedroom, where that patient, in fact, is sleeping. And made sure that you get a size that does enough circulations of air per hour, to help, in fact, clean the air. But it doesn't get rid of things like dust mites that don't stay up in the air. It may help a little bit with pets. But in general, they're not that effective for general allergies. So I don't have patients.
There are studies going on, and there are some devices in Europe, where it's a special type of filter that goes over the bed, things like that, but we're still waiting for these clinical studies, but in general, the ones you have now. What I would definitely say, is you don't want an air purifier. Okay. An air purifier sometimes produces ozone and other things, that we know are very irritant to the lungs, and in fact, can make asthma worse. So the only thing I do recommend is a HEPA filter.
Dr Albert Rizzo: Very good. Thank you for that. Let switch gears a little bit. In general, inhaled steroids remain the foundation for asthma therapy, and then, the addition of bronchodilators. When patients are starting to need further therapy, what are some parameters you suggest help defining that patient that may need to go on to an asthma biologic? Which certainly, we're getting more and more of them available to us these days. And do the comorbidities you mentioned earlier, did that help you play a role in figuring out which may be the best biologic for certain patients?
Dr Michael Blaiss: So there are certain things, and I have a checklist that I go through before making a decision that a patient that has been on inhaled corticosteroids and long-acting beta-agonists, say on a moderate dose, is now a possible candidate for, even going first to a LABA, or again, a biologic, as you mentioned.
So one is, I want to make sure they're adherent to the medication I've already given them, because I find that becomes a major problem, and costs there becomes a problem for many of my patients.
Number two, are they using it correctly? Nine times out of 10, when I have the patients demonstrate their inhalers to me, they're not using them correctly. I used to teach at the University of Tennessee. I would always bet the medical students if any of them could use a meter-dosed inhaler correctly, I'd go and exempt them, and give them an, A, for the asthma part. I never had one in 10 years. Medical students don't know how to use them.
So those are the first two things. Then we look at comorbidities, like you said, and are they being treated? So is the patient's underlying allergic rhinitis being treated? Do they have sinus disease? As we know, many of the adult patients also have nasal polyps, which we know can aggravate their asthma. Do they have GERD that may, in fact, be aggravating their asthma? So I rule out all of those types of things also.
And then, if in fact, we've done all those things, and still feel like, now it's time maybe to up it. Then I do think it's worth looking at, I guess we now have, what six? I think I've got that correct. Six biologics that are approved by the FDA, and basically all of them, to a certain degree, well, they all tend to work better, the higher the blood eosinophils only one has a label that theoretically be used in patients with low eosinophils. And then, I would make a decision on what their blood studies show, but probably more important than that is, what the insurance will cover, as these are extremely expensive medications. They don't cure the condition, they control the condition. And therefore, obviously, we have to look at costs. So, in a lot of cases, I'm happy with any of the biologics. I think they all work, but a lot of it's, again, is related to cost. One of the issues I do have-
Dr Albert Rizzo: Is that something you see often and is that often hard to detect, or does it go back to the history once again? That's also important.
Dr Michael Blaiss: Yeah, it really does go back, when I start them on a biologic, it really is trial and error. We'll try it for four to six months, and if we don't see significant improvement, we may need to try another one. So I think, unfortunately, we can't tell the patient at this time, that if I put you on biologic A, I'm like 95% sure this is going to get your asthma under control. So that's one of the issues we do have with biologics right now.
Dr Albert Rizzo: And you mentioned the eosinophils. Do you still see a role for IgE levels and nitric oxide measurements in some of these patients?
Dr Michael Blaiss: I'll be honest with you, I don't find them that helpful. Because one of the things, and this goes with eosinophils too, and I know I'm talking against the labels and stuff. But eosinophils fluctuate so much, that levels change dramatically over time. There's a recent paper by CHIPS that was in ATS, a journal, that they followed eosinophil levels for one year, every month. And patients kept switching categories from high to low, even the month of the year that the eosinophils were drawn, they used July as the baseline, they were 25% higher in January and in December, than what they were in July. So I always tell docs when they ask me, I go, "Keep drawing them, and eventually, you'll get an eosinophil level that'll let you qualify for a biologic." So I do have a problem with all of these biomarkers, at this time, they're just not accurate.
Dr Albert Rizzo: Well, I appreciate your candor and real-world advice in that regard. I wanted to touch briefly on, when it comes along, as far as a patient, possibly having a work-related or occupational asthma, is that something you see often, and is that often hard to detect, or does it go back to the history once again, that's also important?
Dr Michael Blaiss: Yeah. It really does go back to the history. So obviously, we want to know, when we get ideally, a total environmental history on the patient, obviously, one of the questions I always ask is, "What do you do for a living?" And I do see, right now in the clinic I'm working at, is an underserved clinic, and I see lots of painters, and I see lots of housekeepers and hairdressers. And so, they're around a lot of irritants that could, in fact, be provoking their asthma. So I do think, you have to, in certain cases, it's their only livelihood. We try to work with different things, and so that we can hopefully, get them increased relief.
And many of them will come in and tell me, "It's only when I'm painting, or doing these types of things." But, it's their only livelihood. So it becomes a difficult situation. But it's extremely important, in every asthma patient, to get that work-related occupational history, because there may be, in fact, times where things can be done. I'll get the painters to get the different, in fact, respirator mask, and things like that, to help decrease exposure. Hopefully, allows them to paint without exacerbations
Dr Albert Rizzo: Often there's a relationship found between obesity and asthma. Does this apply to the type of patient we're talking about today, the allergic asthma as well, do you feel?
Dr Michael Blaiss: Yeah. There's no doubt that we do see obese allergic asthmatic patients.
Dr Albert Rizzo: Yeah.
Dr Michael Blaiss: And I don't think there's any doubt that the obesity, in fact, worsens the condition. I know there's a phenotype of primarily adult women obese, that tend to have asthma, and they don't tend to be allergic. But I see many pediatric patients with allergic asthma, they're obese in again, the adult population. And I think we're really starting to understand, more and more about the obesity. We know that it can increase certain inflammatory mediators, leptin and others, that may, in fact, be part of this. The diet, in and of themselves. Patients in general, especially, I'm seeing in inner city population, the obesity. A lot of this is related to processed foods, which, high in saturated fats, low antioxidant diet, and that may also contribute to problems.
And then, just the obesity itself, can lead to difficulty, as far as worsening their asthma and breathing problems. So one of the things, we try to work on, probably the hardest thing to work on in that asthma patient is, in fact, the obesity. And many of them are scared to exercise, because they're worried about their asthma. So again, trying to get their asthma under control, so that they can start slowly exercising, and then try to work slowly with them on their diet. So I do think, like almost any other chronic disease now, we have to look at obesity itself as a chronic disease, and work with our patients on that.
Dr Albert Rizzo: So based on your experience, and certainly, where you are in the field, what do you see are some likely advances, either in the diagnosis, or better characterization of this patient population, and hopefully, therapies? Where do you see things in the future?
Dr Michael Blaiss: I really think what we need, we keep talking about precision medicine. And everyone was saying, "Well the type two high type two, well that's precision." But we're really not there yet. And we really need better molecular genetic biomarkers that we can find at each patient, so we can really do targeted therapy. Which right now, we've got better therapies, but they're not really in what I would call, as we talk about in cancer, true targeted therapies. And so to me, there's some interesting work going on in the NIH, looking at more genetic or molecular type of biomarkers, and really trying to get a better understanding of truly being able to phenotype asthma patients, and then, get directed therapy for their conditions. So that's what we really need. We're far behind our oncologist friends, and we've got to do a better job there. I think, to me, that's the number one thing.
As far as new treatments, we still need treatments for patients with what we call, non-eosinophilic asthma. With the biologics we have now, we see about a 50% decrease in exacerbation. So we definitely, they're not perfect by any stretch of the imagination. It's better. So again, we need more targeted therapies that hopefully, will work at other locations. We're looking, obviously, we have one that's recently approved for one of the alarmins, TSLP, but maybe we need a cocktail of maybe the other alarmins also, 33 and 25, to really get to better. So there's a lot of research going on, on IL-33. There's work going on at, IL-25, at least mouse studies, and hopefully, human studies in the near future. So maybe blocking further upstream will work better for many of our patients.
There's a lot of work now on drugs that affect the mast cells, and we know their importance in asthma. So we'll have to wait and see what happens related to those particular treatments.
And to me, the most exciting thing is, can we prevent asthma? So we present atopic disease. So I'm really waiting for the results of the PARK study, which is a study that's been going on now, I guess, it's close to five years in the US. So it'll be wrapping up soon. Where they've used one of the biologics, in this case, omalizumab, in young children, two to three, with allergic rhinitis. And to see if, in fact, with several years of treatment of omalizumab, can you prevent them from developing asthma? So to me, one of the exciting things, are there treatments? And maybe some of these biologics, maybe if omalizumab does it, maybe some of the others will, that if we could start them early, we could block that atopic march, and therefore, prevent the development of asthma. So to me, I'm really hope that study is positive. Even if it's negative, we'll still learn a lot, but maybe there'll be other agents in the pipeline that we, in fact, will lead to a prevention of asthma in the population.
Dr Albert Rizzo: They've given us a pretty good horizon to look for, as far as some of the anticipations in what's going on in research. And I want to thank you for your time today. You did a comprehensive job with a lot of pearls in there, that hopefully our listeners are going to take to heart, and use in their patient population. So thank you again for the time today, Dr. Blaiss.
Dr Michael Blaiss: Yeah. And thank you for inviting me.
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