This transcript has been edited for clarity.
Michael Wechsler, MD: Hello and welcome to Medscape's InDiscussion series on moderate to severe asthma. I'm Dr Mike Wechsler from National Jewish in Denver, Colorado, and this is episode five of the first season. Today we'll be discussing the social and environmental determinants of asthma. First, let me introduce my guests, Drs Monica Kraft and Juan Carlos Cardet. Monica Kraft is the Murray Rosenberg Professor of Medicine and System Chair of the Department of Medicine at Mount Sinai Health System and the Icahn School of Medicine at Mount Sinai in New York. Juan Carlos Cardet is an assistant professor in the Department of Internal Medicine in the Division of Allergy and Immunology at the University of South Florida Morsani College of Medicine. Welcome, everybody, to InDiscussion. Monica and JC, great to have you both.
Juan Carlos Cardet, MD: Great to be here. Thank you for having me.
Monica Kraft, MD: Thanks for having us.
Wechsler: I'd like to warm people up a little bit…get people going. Why don't you share with our listeners something that people don't know about you?
Kraft: Well, you know that I recently moved from the University of Arizona to Mount Sinai but you may not know that I'm a black belt in karate.
Wechsler: Whoa…all right! I'm glad that we're doing this over Zoom because I'm sure I'll say something that will make you want to hit me. JC, what about you?
Cardet: But Monica, we sort of knew that — we worked together for the past ten years and, when the rumors spread, we all know. I live in Tampa and I enjoy going to the beach with my children. All of us can skateboard, which is something we enjoy doing.
Wechsler: That's cool…nice. All right, great…we've got an athletic group today! This is the fifth episode of the Medscape InDiscussion series on moderate to severe asthma. We've had a great session so far, with episodes featuring Geoff Chupp discussing precision medicine and asthma, and Mario Castro talking about clinical trials and the PrecISE Network. We've also reviewed some advances in severe asthma with Praveen Akuthota, and we're going to be discussing multidisciplinary approaches to treatment of asthma with David Jackson. Today, we're going to talk about environmental and social determinants of asthma. I think, over the last several years, we've come to recognize that asthma is so heterogeneous and so complex that it isn't just the underlying environment that people live in, it isn't just the social determinants…there are also genetic factors. Maybe both of you can talk a little bit about the heterogeneity of asthma, and then we can talk about some of the features that contribute to uncontrolled asthma in our patients. Monica, tell me a little bit about your thoughts on the keys to appreciating the heterogeneity of asthma?
Kraft: Sure. Thanks, Mike, again for having me. It's great to be here. You know, I think we've come to realize that we don't have a one-size-fits-all approach to asthma, in that there are different kinds of asthma. As clinicians who take care of these patients, really the onus is on us to appreciate that and then to figure out what kind of asthma a particular patient has in the clinical arena because now we have some interesting precision-based therapies to offer. We're here talking about the environment and social determinants of health, which I think further add to the heterogeneity, because this lung is exposed to the environment all the time. There are lots of different ways that the lung can be interrogated, if you will. And then, of course, the other part of the environment is the social environment — the other side of the coin — that can also alter the way asthma presents itself and whether it's controlled.
Wechsler: It certainly is complex. The heterogeneity manifests itself in many ways. It manifests itself in the way patients present in terms of their symptoms. It also manifests itself in terms of a patient's response to different therapies or their lack of response. And I agree with you: I think that there's heterogeneity inherently in everyone due to the complexity and different genes that we all have, the different gene expression profiles that we all have, the different cytokines that we all produce, and the different anatomy that we have. JC, maybe you can share with us some of your thoughts about how environmental factors could be contributing and how some of the social determinants in asthma could be contributing to this heterogeneity.
Cardet: Well, first, that requires a definition. Social determinants of health…what are those? I think a simple definition would be the conditions where people are born. Then, [where] they grow up, they work, they get educated, they live. It's about how those components can affect the quality of life and the health that a person achieves during life. I think there are multiple social determinants of health. Each one of those pieces is associated with differences in asthma morbidity. For example, income: if someone is [living] under poverty conditions, that is, as we know from multiple lines of research, associated with asthma morbidity. Access to healthcare, insurance, the environment in which people live…maybe that's pollution or violence or discrimination where they live, transportation, each one of those conditions, if you look at the research, each one of those has been associated with asthma morbidity.
Wechsler: What about educational components and appreciation and understanding of disease? Monica, what are your thoughts about how there might be differences in understanding of disease and what role the clinician can play in terms of educating patients to appreciate their underlying disease?
Kraft: I think that's a huge component. We don't have enough time in our healthcare system to allow for that as much as, personally, I would like to see. We do have asthma educators but not every clinic has them. So, there's a lot of burden on clinicians to provide that information. I think the biggest one is controller medications, like inhaled steroids, to make sure patients have the right expectations about what they're going to experience when they start controller meds — that it's not going to be a quick fix. It can take [from] 6 weeks to 3 months to really see the maximum benefit of inhaled corticosteroids, and understanding that is key because it also takes a while for the effects to wear off. And so, if patients start to feel better, often what you'll see is that they'll say, "Well, you know, I'm feeling so much better, I don't really need these inhalers." And they'll stop them, and it won't be for a few weeks until they start to experience the ramifications of that. Explaining that in the clinic is key to making sure patients understand why they're taking the medicines, how they should work, and what they can expect. And of course, this extends to bronchodilators as well as the biologics, which we can get into as well.
Wechsler: Yeah, and I think one of the key components of all that is educating patients about how to use their inhalers as well. If a patient isn't using his or her inhaler properly, then they're not going to achieve the maximal benefits of the therapies that we're offering them. We think that every inhaler should work but if the patient is not using them properly, then obviously there's a good chance that it may not work in a given individual.
Kraft: There are so many different devices now. And I have a lot of million-dollar workups that have been avoided, just through educating [patients] on these different devices. But that means training your staff, too, on how to use them and making sure you know how to use all of them because there are plenty out there these days.
Wechsler: Exactly. One of the other components, JC, that I was going to ask you about is the environment, and you have a background in allergies. Tell us about the role that allergies and the environment play in terms of precipitating asthma and worsening asthma exacerbations, and what role you play as an allergist in terms of educating your patients about avoidance and things like that.
Cardet: There's a strong association between allergen exposure and the development of an asthma attack, which is, I think, one of the outcomes or one of the conditions within asthma that patients and their caregivers fear or dread the most. The relationship is there. And then the other question is what to do about it. The results have been inconsistent when it comes to public health initiatives and doing interventions in schools. But, for example, the results of the SICAS [School Inner-City Asthma] Study that was led by Wanda Phipatanakul, those students and their schools in which there was a multi-pronged intervention to reduce different kinds of allergens (and that means rodents, for example, or cockroaches), those students saw decreases in asthma symptoms compared to the control group, especially in fall and winter. So that tells you two things: allergens are important in triggering worse asthma, and doing something about it, as a public health initiative, is effective. As physicians and stewards of the healthcare system, this is something we can do to try to minimize asthma attacks. As allergists, the [approach] endorsed by NAEPP [National Asthma Education and Prevention Program] — the American Guidelines for Asthma Management — is allergen desensitization, and allergen desensitization for many asthmatics can be very helpful, very powerful in reducing the burden of disease from asthma.
Wechsler: I think it's so important to address a lot of the environmental components of asthma. Monica, can you talk about all the different types of stimuli that can impact patients with asthma and maybe talk very briefly about how they can impact different endotypes of asthma?
Kraft: Absolutely. So, like I mentioned, the lung is exposed to the environment all the time. Allergens are a key type of agent that can get into the lungs. But there are also infectious agents, viruses, bacteria, fungi, as well as pollutants. And we used to think of this airway epithelium, the cells that line the airway, as a sort of innocent bystander, a sort of barrier. Yes, they're a barrier, but they're anything but innocent. They are very much engaged in the inflammatory process. And they interact with all of these entities and elicit a host of inflammatory responses. There are a lot of different mediators that are produced. And I'll use an example like TSLP (thymic stromal lymphopoietin) or IL-33 [interleukin-33]. Those are two big ones that can come as a result. And IL-25 is part of this initial response by the epithelium. That brings in other cells that lead to edema, inflammation, and then bronchoconstriction, and, at the end of the day, it leads to the symptoms that bring our patients to see us. These types of responses, depending on which one is really the major driver, can lead to type 2 inflammation, which we commonly see with certain types of asthma, IL-4, -5, and -13, but can also lead to a non–type 2 type of inflammation not associated with those cytokines, where we might see IL-6, we might see TNF [tumor necrosis factor], or we might see IL-17…other types of cytokines that lead to a different sort of inflammation. But still, the result of this airway constriction — wheezing cough, shortness of breath — is what brings our patients to us for care.
Wechsler: It's so important to appreciate all these nuances and how heterogeneous all of these different components [are] because everyone's exposed to different environments, and they get exposed at different times of their lives to different environmental stimuli. It can vary from season to season or from day to day. Today you might be exposed to your kid who comes home from daycare and brings a virus. You might then go to a party where people are smoking and that might bring out some other kind of stimulus, and you might go outdoors during allergy season that might bring out a different stimulus. I think it's important to appreciate all the different types of environmental stimuli and how they can really impact patients with asthma.
Cardet: We can talk about what we saw in the PREPARE (The PeRson EmPowered Asthma Relief) study…you were a scientific advisor on it, so you know exactly what I'm talking about. It's Justin Salciccioli's work. This work is about after COVID relative to before COVID, with the introduction of masks and staying mostly indoors and social isolation. There was a decrease in the number of asthma attacks in the population that we were studying, which was 1201 Black and Latinx adults with moderate to severe asthma. The thought there was, after accounting for changes in pollution exposure and adjustments, the decrease was about just wearing masks indoors. Now, wearing a mask indoors is not a long-term solution. That's not what we want to peddle to our patients, right? But it does say something about the impact that exposure to viruses and allergens and other particulate matter might have on people who have asthma.
Kraft: I've had patients tell me that now that we have a culture where we wear masks if we want to, when spring comes, they will wear a mask because it made such a difference in their lives around allergen exposure. Not all my patients are saying it but they came up with this spontaneously. I think they have noticed that by reducing an environmental exposure, their asthma control was much improved, especially in those where the environment was a big driver. They have another intervention they can employ.
Wechsler: I think it's important to appreciate all those different features and appreciate the role that the environment plays. We also need to educate patients about smoking itself; you know, about 15% of Americans are still smoking and 15% of patients with asthma still smoke; it is shocking to me that the numbers are so high. I think that's another important contributor in terms of being an environmental factor.
Kraft: And one thing I wanted to mention about smoking, before we move on, is that it can actually lead to a steroid-resistant state. And I think most of us know this but I don't know if everyone knows this, that all clinicians know this. It can make it harder to treat somebody with asthma if they're smoking, simply [because] they don't respond as well in general to inhaled steroids. And we did that study back with ACRN as well and looked at that and showed that there was reduced response.
Wechsler: I'd like to move on and talk a little bit about some of the social determinants in asthma. One of the things that you mentioned, JC, is the importance of education and the environment that people are living in. Maybe we can talk a bit about where people live and how that can impact their asthma. We've discussed a bit about health literacy as well, but maybe we can briefly discuss the effect of income and home environments on asthma outcomes.
Cardet: Well, I was checking that out and there's a study by Nardone and others that looked at redlining, which describes policies instituted more than 50 years ago about race and ethnicity [and] who gets loans for purchasing houses. And this was an ecological study done in L.A. but within those housing zones that were defined many, many, many years ago, decades ago. There are correlations with the amount of pollution that people get exposed to [which is] ultimately associated with the degree of asthma morbidity. Pollution matters. The neighborhood where somebody lives matters. And if you look at the different exposures that you can get from a specific neighborhood, each one of those components has — not all of them, but many — been associated with worse asthma, morbidity, for example. And this is work from, I think, Esteban Burchard's group. And it has to do with violence. This is a SAGE (Study of African Americans, Asthma, Genes, and Environments) cohort. The greater the likelihood of listening to gunshots, the greater the current asthma symptoms were, or were in this study — this is maybe five years old or something like that.
Wechsler: Yeah, there's been a lot of work in that regard. I think Rosalind Wright published about home violence, and even kids who watch violence on TV are more likely to have an asthma exacerbation than kids who aren't exposed to violence on TV. It's been a fascinating appreciation of the interaction between the environment and one's asthma. Can we discuss briefly some of the efforts and research that have looked at race and ethnicity as pertaining to how people respond to different therapies? Both of you have been involved in different studies. Monica, you and I were part of the AsthmaNet or the Asthma Clinical Research Network, and we found that there were differential responses to different asthma therapies between Caucasians and African Americans. And we did a prospective study called the BARD study in both adults and kids, where we found that there were differences between adults and kids in the Black population, evaluating differential responses to different therapies. Maybe you could comment a little bit about some of that and then we can talk about the PREPARE study in greater detail.
Kraft: I think your points, JC, are well taken around the exposure, the stress levels, and how that can affect asthma control as well. But with regard to BARD, there have been a lot of questions about whether in these dose-escalation studies that have been done as asthma control worsens, often participants of color were not included. BARD really asked the question, is there a differential response to inhaled corticosteroids and long-acting beta agonists (LABAs) in a dose-escalation setting between Black people and White people and [between] children and adults? What was interesting was that in contrast to Black adults and White persons of all ages, almost half the children who had at least one grandparent identified as Black and who had poorly controlled asthma had a superior response to an increased dose of an inhaled steroid over the addition of a long-acting beta agonist. So, a differential response to steroids vs LABAs in Black children but not necessarily in Black adults or White persons of all ages. It suggests that there may be some ancestry drivers, if you will, of response to medications. This is important to realize when you take care of a diverse group of patients. Anything you want to add anything to that, Mike?
Wechsler: I think what we appreciate is that first, there are differences between adults and kids in these patient populations, with differential responses to inhaled corticosteroids vs long-acting beta agonists. We're still trying to get a better understanding because we didn't identify any predictive biomarkers for response of those specific therapies. There are some genetic loci that we've published on that may predict responsiveness, either in terms of bronchodilator response or airway hyperresponsiveness and mutations to the beta receptor which may contribute. JC, tell us a little bit about the PREPARE study, what the design of that study was and what some of the key outcomes were.
Cardet: For the PREPARE study, the idea behind it goes back to what we were talking about before: education and patients wanting to use medicine for their asthma symptoms. The guidelines say unless you have the mildest of mild asthma, you're supposed to take this inhaled corticosteroid inhaler every single day, regardless of your level of symptoms. A lot of patients struggle with doing that. Why? If my knee doesn't hurt, why should I take ibuprofen? Why should I take a medicine for a symptom that I don't have? And we know that. So, adherence rates to controller therapy and asthma are as low as 25% based on refill data. There are other strategies that try to use controllers as rescue therapy but they have not been adopted in the healthcare system that we have. There are many reasons, and we can talk about those, too. There is now this inhaler that combines inhaled corticosteroids, which decreases the inflammation that goes in the lungs that drives the asthma, combined with the rescue inhaler. But it's new and it's driven by the pharmaceutical company. I don't know if it's going to be equally distributed across all racial/ethnic groups and other social groups, right? So, we wanted to create an intervention that's easily accessible by the entire public. And we focus specifically on Black and Latinx [patients] because Black people have a mortality rate from asthma that's twice as high as that of other races. And within Hispanic and Puerto Rican populations, that rate is four-fold higher for mortality from asthma. That's in terms of the study design. Those were the populations. It was a real-world pragmatic trial. Essentially, if patients had moderate to severe asthma, regardless of whatever controller or therapy regimen they were on, as long as they included a daily inhaled corticosteroid (the intervention arm), they were asked to "keep doing what your doctor tells you to do. But every time that you use the rescue inhaler, puff yourself with this inhaled corticosteroid that we provided for free for the 15 months of the study" vs the usual care group, [who were instructed] to "keep doing what your doctor tells you to do." It's an inhaled corticosteroid, anti-inflammatory supplementation strategy driven by symptoms. Using this strategy, we found a 15% reduction in the asthma attack rate that these patients experienced relative to the usual care [group] that's very comparable to the absolute reduction.
Wechsler: The key component there is that these susceptible populations, I think, need new interventions and new strategies. And maybe using inhaled corticosteroids as a needed strategy can benefit those patient populations in particular. We're coming toward the end of our time here, but I think we've had a great discussion so far. I think we realize that asthma is a very heterogeneous entity, and we talked about the complexities and how important the environmental and social determinants are in terms of addressing asthma. We need to look forward in terms of trying to address some of the inequities that are out there. Certainly, addressing psychosocial issues, lowering costs of medications, addressing poor health literacy, and making sure that our patients are educated about why they need to take their inhalers continually, even if they don't have symptoms, and also address, obviously, poor inhaler technique. We didn't really talk about this but we need to address other issues, including comorbidities and their importance in the management of asthma, as well as outdoor and indoor allergies, and more globally, we probably need to address pollution and other environmental factors as well. Monica, I wanted to give you the last word and get your closing thoughts on the importance of environmental and social determinants in asthma and how we can try to move forward in this space.
Kraft: Okay, sure, thank you. I'm talking for myself, but I think as clinicians, when we care for patients, we focus on the symptoms and the lung function. We have to remember to take the outward piece into consideration. When we have the patient with us, we can look at their data, the biomarkers, et cetera, but there's more to asthma than that. And what looks like a certain kind of asthma may be very much influenced by the environment a patient lives in, and not just the natural environment (the pollution, the environment) but also the social aspects. I think we must remember that when we're taking a really good history and getting to know our patients, and take that into consideration when designing the best treatments for them.
Wechsler: I couldn't have said it better myself. You did a great job summing things up, so I want to thank you both, and I also want to thank our listeners for participating today. We've had a great discussion today with national experts Drs Monica Kraft and Juan Carlos Cardet. We've hit on some of the important concepts of the social and environmental determinants of asthma. And I think it's going to perhaps lead to significant improvements in outcomes for many of our patients. Thank you both for joining us today, and I look forward to another great discussion in episode six. Thank you to our listeners. This is Dr Mike Wechsler again for InDiscussion. Thank you all for participating.
Cardet: Thank you.
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Cite this: Smoking, Rats, and Violence: What Are the Social and Environmental Determinants of Asthma? - Medscape - Nov 02, 2022.