Asthma is one of the most common conditions in childhood, affecting nearly 10% of children in the United States. Experts from the Mount Sinai Institute for Exposomic Research explain how studying the environment can help prevent and better treat asthma, especially in children.
Discussion
We spoke with Rosalind Wright, MD, MPH, Alison Lee, MD, and Kecia Carroll, MD, MPH of the Institute for Exposomic Research at Mount Sinai about how they’re applying exposomics approaches and methodologies to study asthma risk and prevention. Read the full interview transcript below.
How is exposomics integrated into asthma research?
Dr. Lee: What we’re interested in trying to understand is, what are the environmental exposures and mechanisms that really increase risk for the development of asthma. Within that, we’re trying to characterize all of the different exposures that are occurring over pregnancy and early childhood. Some of those exposures are related to air pollution, and air pollution is a very complex mixture. Initially we started studying fine particulate matter but now we’re expanding that to look at multiple pollutants. There are other chemical exposures as well that you can think about impacting asthma, like pesticides. And then there are also non-chemical exposures, such as stress and trauma, whether those are in the mother or in early childhood. Exposomics is really trying to characterize all those potential exposures and then relate them to health.
Asthma is a lung disease where you have reactive airways. So what’s interesting about asthma as compared to something like COPD is that you may have a child who’s completely asymptomatic at one time point and then they have an exposure or something triggering and all of a sudden they develop symptoms, such as wheezing. Over time, if you have more poorly controlled asthma that can actually lead to changes in your airways. Narrowing of the airways, for example, is going to cause more persistent symptoms. So we can try to understand not only the different exposures that may increase risk for the development of asthma but also think about different exposures that are increasing risk for exacerbations and more poorly controlled asthma.
There is a genetic component to asthma but environment plays a huge role, both in the development of asthma and also in asthma control. As clinicians, when we see a patient in the office who has asthma, typically we’ll ask them, “Is there mold in your household? Do you have any pets? Do you have rugs?” There’s a list of different exposures to help them try to control their asthma through their environment. We need to expand those to think of other exposures that, at least in our research, may be major contributors to asthma.
Dr. Wright: Childhood asthma is a good example of how important it is to study exposomics, or comprehensively study environmental influences on the onset of certain diseases. I’m a pulmonologist, so asthma is near and dear to me because it’s a respiratory disease. Asthma itself is a disease of disrupted immunity. Anything that can change your immune system can make you more vulnerable to developing asthma.
There are many things that can affect the immune system. An array of different environmental influences: psychosocial stress, for example. If you’re in a stressful situation, say you’re a student in school and you’ve got exams coming. You’re not sleeping as well, not resting. Those things get in and change your immune system. And you may be more likely to get sick in a period like that. That is one factor we know can affect the onset of asthma. But there are also external exposures. We know that dust mite and pollen can affect the onset of asthma, but what about breathing in air pollutants that come from either being exposed to somebody who’s smoking or being a smoker yourself? Or what about being exposed to ambient air pollution from traffic or industrial sources, wild fires and more? These can also affect your immune system and other systems that relate to that. When you start to think like that, what we have to account for gets bigger and bigger pretty fast–like how many factors can potentially affect asthma, how many environmental factors, well how do we measure that? The idea of exposomics in that context is, how can we challenge ourselves? How can we leverage existing technologies, existing instrumentation, existing computational science, the mathematicians, and the biostatisticians that need to help us model all those things together and get answers.
Dr. Carroll: Asthma is one of the most common conditions in childhood. It can affect up to almost 10% of children in the United States, and most children who develop asthma will have symptoms before the age of five or six. So if we want to prevent asthma, we really need to start prenatally or early in life, in terms of understanding the risk factors and the protective factors in terms of preventing disease. We know that environmental exposures influence health, and oftentimes, we may look at a single exposure, whether it’s stress or whether it’s air pollution or whether it’s nutrition, in relationship to the development of asthma. But we know that people experience multiple exposures, and that multiple exposures will influence a child’s risk of developing asthma, and so what I’m really excited about doing is moving from looking at single exposures, to looking at mixtures of exposures like what we experience in the real world.
Describe the importance of prenatal exposures when looking at the risk of developing asthma.
Dr Lee: We know that the fetus is developing sequentially across gestation with certain parts of lung development occurring at certain times. So there may be specific aspects of long development that are more susceptible to a particular exposure. If the mom has a heightened exposure during those time periods, termed windows of susceptibility, this may actually have an outsize effect on the fetus’s future health.
We have been able to show that higher air pollution exposure is related to risk of asthma in the first eight years of life. Children that have higher air pollution exposures in pregnancy have poorer lung function by age eight. It’s not, however, just about one exposure. We’ve also demonstrated that maternal stress in pregnancy, which can be considered a non-chemical exposure, is associated with the development of asthma in childhood, and with poor lung function. What’s interesting is we’ve been able to use statistical modeling to look at interactions between those exposures, and what those models tell us is that children who are born to mothers with higher exposures, higher air pollution exposure, and also higher stress, are most affected.
Dr Wright: All of our organ systems are developing very rapidly during pregnancy, as the fetus develops. And because things are happening so rapidly and they are not as capable as you and I of detoxifying things they might encounter in their environment through their mother they’re much more susceptible to environmental changes in their organ systems development and subsequently that’s going to manifest as disease.
We just published a paper, the first in the United States to look at ultra-fine particles from traffic. It shows that if moms are having higher level exposure during pregnancy, their kids are more likely to develop asthma by the time that they reach school age. But it also has implications for how the baby grows, how much weight mom gains over pregnancy and her own cardiovascular and cardiometabolic health after the pregnancy. Also, we know that if mom smokes during pregnancy that has implications to the baby’s health and risk for chronic disease. And if mom experienced a lot of stress during pregnancy, for example from negative life events or trauma, that has an effect independent of the chemical toxins. Having two or three of those exposures together is more than just simply summing up the health effects of the three, it’s multiplicative. So that kind of speaks to this notion of why we need to do exposomics research. Understanding these interactions allows us to come up with methods to counteract and mitigate those exposures.
How can the study of exposomics and asthma advance environmental justice and health equity?
Dr. Carroll: I believe exposomics is really important in advancing health equity for a number of reasons. When we look at differences that we see by factors such as race and ethnicity, we know that race is not a biologic construct, it’s a social construct and a power construct. We see increased increased disease risk in African Americans – for example, African American children have higher rates of asthma. It’s not likely genetic, but due to environmental factors that may be due to social factors, such as where you live. You can have different exposure to chemicals. You can have different exposure to air pollution. You can have different exposure to healthy spaces or different exposure to healthy food. And so exposomics, really looking at the larger context of the environment can help us understand what’s driving the inequities in health that we may see by race or that we may see by income.
Race is a social construct, closely linked with slavery in the justification of slavery. Structural racism is integrated throughout sort of all systems and in the United States. And it influenced where people were able to live, where people were able to work, where people were able to go to school or the level of education they have. These are all factors that are linked with health. And we know that health inequities related to race aren’t due to genetics, but to environmental factors that vary by race and that are linked to opportunities and privileges and all of the different social factors that influence health.
How can the study of exposomics advance asthma research in the future?
Dr. Wright: I actually think we’ll be able to prevent asthma in five to ten years, and I think that’s going to happen at the very roots of it. It’s going to be in utero. We are going to be able to biosample and analyze environmental samples as well as the individual’s biosamples, to be able to say, given this collection of signals, this profile that we’re getting from our data science, our artificial intelligence, this baby could be at increased risk of developing asthma. But we also know that we see these other signals that are protective. And so we’re going to optimize those signals. It’s really where we are now: understanding how do we elucidate those signals, those profiles, so that we can give them to our clinicians so that they can make decisions in the clinic on that particular patient. We’re really already there in our ability to do high dimensional data interrogation to be able to find those profiles in a group of people, maybe not the individual, but a narrower group of people to be able to guide them in that way.
Dr. Carroll: Exposomics can offer hope because it can really help us understand what components of a person’s environment, if reduced or if enhanced, can influence child health in a meaningful way and prevent disease – and that is the Holy Grail – prevention. I am a general pediatrician, and I want to be able to maximize child health. So when I think about asthma, for example, and the impacts that it has on child health, the family, school performance, it’s from a general pediatrician standpoint: understanding how we could prevent asthma in future generations.