Gerry Lee, MD (Host): [00:00:00] Asthma exacerbations continue to affect over 40% of asthma patients each year, which not only disrupts their quality of life, but can lead to permanent loss of lung function. The goal of this podcast series, Shifting the Asthma Rescue Paradigm, is to review why an anti-inflmmatory reliever has become the standard of care in asthma management and also provide tips on how to implement this therapy in your practice.

Hello, everyone. My name is Gerry Lee. I'm an Associate Professor at Emory University and the host of this first part in a three-part mini-series entitled Shifting the Asthma Paradigm: A Call to Action, from the American College of Allergy, Asthma, and Immunology. In this episode, we will discuss the limitations of bronchodilator-only rescue. And in the next two parts, we'll review the [00:01:00] implementation strategies in mild and moderate to severe asthma patients.

I'm excited today to be joined by two experts in the field. The first expert is Dr. William Anderson. He is an Associate Professor of Pediatrics at Children's Hospital Colorado, and and University of Colorado School of Medicine. He is the Medical Director for their Allergy and Immunology section. Dr. Anderson's clinical and scholarly interests include the management of difficult-to-treat and severe asthma, pediatric-to-adult care transition, and technology in medicine, including electronic medication monitoring. He directs the Multidisciplinary Asthma Clinic and their Asthma Biologics Program, and leads a hospital-wide pediatric-to-adult transition initiatives for Children's Hospital Colorado as the Co-director of the Improving Pediatric to Adult Care Transition or imPACT Program. Bill, welcome to the podcast today.

William C. Anderson III, MD: Thanks, Gerry. Happy to be here today.

Host: And our [00:02:00] second expert is Dr. Alan Baptist. He is a Professor and Division Head of Allergy and Clinical Immunology at Henry Ford Health in Detroit, Michigan, and holds a joint appointment at University of Michigan School of Public Health in Ann Arbor, Michigan. He previously served on NHLBI 2020 Asthma Guidelines Update Committee, and his research interests include asthma and older adults, asthma healthcare disparities, and the implementation of asthma guidelines. Dr. Baptist has authored or co-authored over 80 peer-reviewed articles that have been published in journals such as The Journal of Allergy and Clinical Immunology and the Annals of Allergy, Asthma and Immunology. Alan, thank you for joining the podcast as well.

Alan P. Baptist, MD: Thanks, Gerry. Happy to participate.

Host: All right. Well, let's get started, everyone. Bill, let's start with you. I got some statistics here from the CDC, I pulled it off the website, that from 2001 to 2020, asthma attack prevalence in the past [00:03:00] year had decreased from 55. 8% to 40.7% of patients with emergency department visits decreasing by 20%. But if you take a step back, in 2020, that still represented 1.5 million emergency department visits per year for asthma. So in this 20-year span, we still have 40% of patients going to see the doctor for an asthma exacerbation each year. What is the cause of these exacerbations? What do we know about the pathophysiology of exacerbations?

William C. Anderson III, MD: When I think about exacerbations of asthma, I think it's a story of inflammation and bronchoconstriction. So, we know that at baseline with our patients with asthma, they do have underlying airway inflammation. It's inherent to the disease itself. But whenever they get exposed to a trigger, whether that is environmental allergies, viral illnesses, smoke, exercise, this [00:04:00] will associatively increase the inflammation that they have in their airways.

With this increased inflammation, you get airway edema, you get mucus in the airway, both increased production as well as impaired clearance, and then you also have this airway hyperresponsiveness with associated bronchoconstriction. By having this constriction of our smooth airway, this in turn leads to air trapping and the symptoms our patients have.

So, ultimately, when we're thinking about an exacerbation of asthma, we want to be thinking about the inflammation that's causing it as well as the bronchoconstriction that is leading to the symptoms our patients are having. As you'll see, I think this also leads to some of the thoughts that we now have in terms of the reliever therapies that we should be using for patients with asthma.

Host: You know, we have such a litany of therapeutics that target airway inflammation. Over the past 20 years, there's been so many different ways we've addressed [00:05:00] airway inflammation, but this is still a problem with millions of people with uncontrolled asthma. So, we know the cause of these exacerbations. But Alan, why are we still having a problem with them?

Alan P. Baptist, MD: Yeah, thanks, Gerry. I mean, that's a really good question, and I think Bill was bringing up some good points about, look, there are a lot of good therapies out there. Part of the problem is that asthma attacks really can look different if you look at different individuals. So, I'll give you some examples.

Some have symptoms that, you know, they say, "My asthma comes on gradually when I'm going to have an attack. I can kind of tell. I know it's going to worsen over a little bit of time. I get some warning signs." Other patients I have, they have what we call a more brittle asthma, where they're like, "You know, I was doing great, was feeling fine, and then all of a sudden, I just decompensated. My asthma just was terrible and I had this bad attack."

Not only that, the triggers for patients, they really can vary greatly. So, some people, it will be cold air, some it'll be exercise, it might be air pollution, it could be stress, it could be infections, even hormonal [00:06:00] fluctuations. So, all of these triggers vary. And many times, providers may not know or they don't have time, perhaps, to teach patients about all these possible triggers. And then, even once the patient is taught, whether by a provider, by an asthma nurse educator, or someone else, then the patients, they actually have to put in the effort to determine what their triggers might be. They may have to do some homework, if you will, and keep a journal or keep a diary to try to figure that out.

Teaching avoidance measures, self-monitoring, that all takes time in clinic. And many primary care providers and even asthma specialists, they may not really have the time, nor the resources, or the training to do so. So, I think all of those kind of contribute to the exacerbations and make it hard to really treat them.

Host: When you describe it that way, it sounds like there's so many challenges in the care of asthma and we have a lot of providers who are having challenge meeting those triggers or different aspects in the very bit of patients. You might almost say that a lot of asthmatic patients [00:07:00] just normalize exacerbations. This is just part of the illness. "I'm just going to accept that as part of my long-term disease." What are the consequences of asthma exacerbations? When we take that attitude that exacerbations are just going to happen, how does that affect the patient?

William C. Anderson III, MD: Gerry, you bring up a great point whenever you're saying that patients sometimes believe this is just an inherent part of the disease and something they have to cope with and deal with, but that approach leads to both short and long-term consequences for patients. Obviously, if you're having an asthma exacerbation on the short-term, you're going to be missing school if you're a pediatric patient. You're going to be missing work if you're an adult patient. And this is going to be associated with increased burden to families, as well as increased costs to the healthcare system by coming in with these recurrent exacerbations or unscheduled healthcare visits.

In the long run, though, you're also going to lead to some increased damage for our patients and their underlying airways. So, each time you have one of [00:08:00] these exacerbations, we believe that there is some lung remodeling that's occurring there. And progressively over time, this can lead to a reduction in lung function. So, I think that we need to be serious whenever we think about these exacerbations, not only in doing all the strategies we can to prevent them, but then once they finally do come on, treating them and preventing future ones beyond it.

Host: So, that permanent loss of lung function and including the decrease in quality of life are all things we all could do a better job at doing. And I know it's been an intense level of interest on the best ways to address this. And I think this is where we're going to focus on how the anti-inflammatory reliever has been proposed as a solution. So, this has been a newer concept that's been in guidelines, but Alan, it sounds like it's been there for a while. When did this concept actually start?

Alan P. Baptist, MD: You're absolutely right, Gerry. This concept has been around [00:09:00] for some time now. You know, we've known that asthma really at its heart and soul, what is asthma? It's airway inflammation. The treatment that we've used for acute attacks for a long time has been a short-acting bronchodilator, something like albuterol. And albuterol works great to bronchodilate, but it doesn't treat the airway inflammation. Inhaled corticosteroids, of course, have been around a long time, and we know they do have multiple mechanisms that actually can really suppress airway inflammation. So for example, they activate anti-inflammatory genes, they can switch off inflammatory genes, and they can actually inhibit inflammatory cells.

 There's been a lot of talk recently about SMART or MART therapy and anti-inflammatory reliever therapy with these new combination medications. And people think, "Boy, is this a brand new thought that just came around?" And that's actually not true. If you look back, there have been trials at least for 20 years that have been looking to say maybe bronchodilation isn't [00:10:00] enough. The early SMART therapy trials were actually done back in 2005. The first trials were published, you know, in the American Journal of Respiratory and Critical Care Medicine back then. And anti-inflmmatory reliever therapy is actually even older, even before 2005, it was published in the New England Journal. There's something called the imPACT trial and they looked at 200 subjects that either use an inhaled corticosteroid combined with the albuterol on an as-needed basis, they used both of those two on an as-needed basis, or they looked at maybe should you use an inhaled corticosteroid every day? And what they found is that both therapies were equally effective. And so, this idea has actually been around for over 20 years now.

Host: That's remarkable because 20 years later, we have great evidence that it does move the needle on exacerbations, but we're having decreased implementation. So, I think this is where we're going to set the stage on what are the available treatments [00:11:00] to address exacerbations through this method? And in the next two episodes, we're definitely going to address that. But I think the first point is the actual confusion about the terminology of different treatments, because, Alan, you actually mentioned two different approaches, which is anti-inflmmatory reliever or AIR, and a lot of people have heard a little bit about MART or maintenance reliever therapy, some people say SMART. So Bill, could you clarify the terminology and at least the thinking behind those two acronyms?

William C. Anderson III, MD: Yeah, certainly. So, AIR or anti-inflmmatory reliever therapy, I think of as a exclusively on-demand therapy, versus MART or SMART, single maintenance and reliever therapy, as the name implies, has that maintenance aspect in it. So in this sense that you're using this medicine both as a daily controller for your asthma, but also using it on-demand whenever you develop symptoms. And specifically with MART, we're talking about a [00:12:00] combination inhaled steroid and long-acting beta agonists, specifically formoterol, because of the quick onset of action that formoterol has. So, we would not want to be using this with other long-acting beta agonists, for example, salmeterol, because you're not going to be having that beneficial quick-onset effect.

Host: Of course, you have that maintenance approach, and so, you know, we do daily maintenance for more moderate, severe, and of course intermittent is just as needed. So, there's this nice distinguishing between the mild patient and the moderate to severe patient. So going forward, I think that's how we've structured this series.

Episode two, we're going to talk about the AIR therapy with just intermittent therapy, but then take a deep dive in the more moderate to severe patient for MART. And so, I invite you to join us for those next two episodes. This is the conclusion of our first part, of a three-part series, Shifting the Rescue Paradigm from the ACAAI. For more interesting [00:13:00] episodes from Allergy Talk, please go to our main website, that's college.acaai.org/allergytalk. My name is Gerry Lee. I'm from the American College of Allergy, Asthma, and Immunology. Have a wonderful day, everybody.