How chemicals mothers breathe affect their children

Christina Sumners:  Welcome to Science Sound Off. I’m Christina Sumners.

Tim Schnettler: And I’m her cohost Tim Schnettler.

Christina Sumners: And we are here today with Dr. Natalie Johnson from the Texas A&M School of Public Health. Welcome to the show.

Natalie Johnson: Howdy. Thanks for having me.

Christina Sumners: We’re thrilled you’re here. We’re excited to talk about your research, you’re doing some really interesting stuff. Yeah, it’ll be fun to talk about. So could you just start by telling people a little bit about an overview of what you do?

Natalie Johnson: Sure. So I joined the Texas A&M School of Public Health in 2013. It’s hard to believe that I’ve been building my research program for over six years now. And my main focus is on children’s health, and that can span a lot of different diseases and a lot of different exposures. Since I am trained as an environment toxicologist, I’m very interested in how exposures from the environment influence child development from the beginning when the fetus is forming, throughout gestation, early life, and into infancy and childhood. So really, what I’m interested in is how environmental exposures can impact health and development in children. As we talk, we can get into some of the more specific studies that we’ve been focused on recently, mainly dealing with how exposure to air pollution during the pregnancy, during that gestational period of fetal development, influences the development of the infant lung, and may render infant’s more susceptible to respiratory infections.

Christina Sumners: When you say environmental toxicologists, you’re talking about the toxins, essentially, in the environment, so you focus mostly on air pollution. So, how do you study what is actually in the air?

Natalie Johnson: So one of the first studies I did when I joined A&M was to look at, ‘What are some of the exposures women are experiencing during pregnancy?’ So to do that, we deployed small backpack samplers that had pumps on them that were intaking air at about the same rate as the human lung would. We sent them down with participants as part of an environmental health study in McAllen. These participants were in their third trimester of pregnancy. They carried the backpacks with them for 24 hours, and through that pump, we were able to collect information on what’s known as the particulate air pollution. The particulate matter is what you might think about as the solid matter that you would see when you’re looking into a smoky room, so wood smoke. You’re going to see a lot of that visible cloudiness or smokiness that is actually caused by particles. These particles can range in size, so they can be larger and filtered out in the nose, or they can be very, very small, less than 2.5 microns in diameter. This is known as the fine particulate matter. It can get deep into the lungs, cause a lot of inflammation, cause a lot of oxidative stress. That’s well-known that people that are exposed to smoke may have exacerbations in their asthma, may cause exacerbations in other existing diseases, like COPD. What we’re really interested in is even tinier particles; nano-sized particles that are less than 100 nanometers in diameter, that can actually traverse the alveolar regions, get into systemic circulation, and reach many parts of the body, including the brain. So a lot of people studying air pollution now are interested in how cognitive health may be affected. And, in terms of our studies, how that may actually traverse the placenta, directly impact the fetus, or that stress placed on the mom may impact outcomes later in childhood. So the particulate matter is one of the main things that we measure. Now, absorbed to those particles can be other toxic compounds. One classic compound’s known as polycyclic aromatic hydrocarbons: PAHs. They’re carcinogenic, they are immunotoxic, and they’ve been associated with increased risk of children developing asthma. So as part of that first study, we measured the PM2.5, the fine particles, and we measured the PAHs; those polycyclic aromatic hydrocarbons. Those are two areas we’ve been studying. In addition to the particulate matter, there’s also a lot of volatile organic compounds present in smoke, or in air pollution. And so some of our studies we’re getting into now are moving more into capturing, not only the particulate matter, but some of those other air toxics that are more volatile. Things you might think of, benzene, nitrous oxide, ozone, those types of things.

Christina Sumners: Interesting, those are all kind of wrapped up together, so I imagine it’s hard to tease out what’s doing what and how it all interacts to cause health effects.

Natalie Johnson: Definitely, and that has been one of the major obstacles in using traditional epidemiologic approaches, where you have observational studies that you would look, kind of what we did. In a population, you’d have to look at multiple constituents in the air, and those are often varied from day-to-day. So if you’re looking at long-term health effects, even just nine months of exposure during pregnancy, there’s going to be a lot of variability. One way that we’re able to overcome these limitations is by fine tuning exposure models using animals in the laboratory to look at that dose response relationship.

Christina Sumners: So you can really see how different chemicals are affecting individuals.

Natalie Johnson: Exactly. So right now, the way that the EPA regulates air pollution exposure, it’s all based on size. So as I was mentioning, the larger particle sizes are the PM2.5.The nano-sized particles are currently not regulated. So it makes you wonder, is that truly protective of health outcomes in children? And, in addition to not regulating those nano-sized particles, the different constituents are not regulated either. So you may have different sources in different cities, urban or rural, different parts of the country that may have different characteristics associated with that particulate matter, that could elicit very different toxicological responses. So one of the main goals of our research is to tease apart how the different PM, the particulate matter constituents may impact the toxicity and resulting children’s health consequences.

Tim Schnettler: Now, we know how pollutants and toxins affect adults and us as individuals, how does it impact a fetus? You mentioned the absorption and stuff like that. So what are the consequences for something like that?

Natalie Johnson: So great question. There’s a lot of different things that can happen. One of the first things that’s been shown, is that there’s an increased risk of low birth weight. And low birth weight is predictive of many adverse health outcomes later in life. It’s also been linked with reduced gestational time, or pre-term birth, which is also going to have consequences for children later in life. So those are some of the first two immediate impacts on children. Other impacts have been shown to cause an increased likelihood of children developing asthma. So in addition to just exacerbating existing asthma cases in children, it may actually cause different ways of the pulmonary immune system developing that may predispose children to having asthma later in life. A large area of interest now is also revolving around impact on cognition and brain development. So as I mentioned earlier, these particles can reach throughout the body, and not only impact the lung, but also perhaps, impact the brain. So those are a couple areas of developing interest, is how these particles may actually impact learning and development of children.

Christina Sumners: So these nano particles, they can reach, like you were saying, the brain, all these places that we hadn’t normally thought of air pollution as affecting. So how do you know which even diseases or conditions to start with when you’re looking at something like this?

Natalie Johnson: What our approach has been, to really look at what are the major areas of need in children’s health. One thing that kept coming up in our research, in our background review, was the high prevalence of childhood respiratory disease. One of the main reasons infants are going into hospitals is because they’re developing respiratory infections. One of the most common causes of respiratory infection is due to a virus known as respiratory syncytial virus, or RSV. I’m a parent of two children, so I’m well acquainted with RSV as a mom talking with pediatricians. Pediatricians will often mention how they have very limited treatment options for kids once they develop severe respiratory infections that progress to these bronchiolitis-type conditions, where there’s a lot of inflammation in the very, very tiny airways of young children. So since this was causing such a large percentage of morbidity, and even mortality in extreme cases, that was where we chose to tackle first. There have been a couple studies done in observational human epidemiologic studies looking at moms that are exposed to high levels of the particulate matter 2.5, the fine PM, living in urban environments. They’re more likely to have kids that go into the hospital for severe lower respiratory tract infections in those first couple years of life. What’s unknown from those studies is what the mechanism is, so what’s really happening. And so that’s one of our major goals is to study what’s going on. An interesting part of that study, that researchers pointed out, was that there were certain women that had genetic predispositions, or what’s known as polymorphisms. So they have different genetic sequences in certain enzymes and transcription factors, that may actually cause an increased likelihood of their child being hospitalized. One of those transcription factors that was shown to put children at risk for having a respiratory infection associated with high PM2.5 exposure, was a transcription factor known as Nrf2. Often, people say Nerf 2. During my time as a postdoctoral fellow, I actually studied this transcription factor, because it’s at the heart of an antioxidant response pathway. So we all know when we have a little bit of environmental stress, our body can handle it. We have this amazing system, this Nrf2 keep one antioxidant response pathway that’s going to cause a lot of genes to become turned on, that say turn on enzymes that can now start breaking down toxins. So if individuals cannot mount that antioxidant response as easy

Christina Sumners: Because of the genetics.

Natalie Johnson: Because of the genetics then they may not be able to handle that environmental stress. And so getting into those mechanisms now, what we’re able to do is actually see what happens in the laboratory if you knock out the Nrf2 pathway, do you now see an increased susceptibility to respiratory disease. And then coming from a public health side; prevention. How can you turn that pathway on to actually get enhanced protection? And there’s been many, many phytochemicals , extracts from fruits and vegetables that have been shown they can actually, protect against cancer development. What the heart of that is, some of these compounds can activate Nrf2 and cause an increased expression of those good enzymes to break down toxins, and that’s exactly what our lab is trying to do. Specifically we are going to be working with a broccoli sprout extract. So as you remember as a kid your parents always tell you to

Christina Sumners: Eat your broccoli

Natalie Johnson: Eat your broccoli. There’s some science behind that and it has to do with an active compound within broccoli known as sulfurophane. There is another precursor known as glucoraphanin. Glucoraphanin, when you chew can release sulfurophane and sulfurophane is the active component that can activate the Nrf2 pathway and cause the positive downstream effects of increasing antioxidant enzymes. So people have done this before, my post doc mentors actually have done clinical trials in China, in areas of very high pollution, where they gave broccoli sprout beverages and looked at different ways of giving the intervention and saw that it did elicit an increased ability of individuals to rapidly metabolize air pollutants such as benzene and acrolein some of those air toxins. Now what we wanna do is transfer that model to a transplacental chemo protection, or transplacental asthma prevention. What can you do if you’re pregnant and you live close to a highway or you live in an urban environment and you’re worried about your children’s respiratory health or even cognitive health? And so what we hope to do is design these preventive interventions in a food based form, something that would be safe to take during pregnancy and help elicit an antioxidant response pathway in the mom and hopefully protect fetal development.

Christina Sumners: That’s incredible that something as simple as food could have this sort of effect.

Natalie Johnson: Right, and so that’s at the heart of public health, we know that exercising is good for us, we know that eating healthy is good for us, so we really do hope to partner with other people doing health promotion to help get that word out about how you can make sure that your child has the best start in life.

Tim Schnettler: I’m going to say though that I bet my parents didn’t know that eating my broccoli would do that for me. You know they always told me that but I’m guessing they didn’t know that.

Christina Sumners: They didn’t know the science behind it.

Tim Schnettler: Right exactly.

Natalie Johnson: I’m sure my kids will glaze over if I give them that explanation.

Christina Sumners: So are there any other tips that you can give pregnant women from your research? I mean I know this all still in its early stages but are there other things that people could be eating, I mean are air masks helpful, or are these particles so small that doesn’t even probably filter them out?

Natalie Johnson: Unfortunately many of these particles are going to be small enough to get through some of the common air masks. You would need a full-blown respirator which wouldn’t be useful to wear in an everyday environment. What you can do is make sure you have good filters in your car that you’re driving. You can even smell it sometimes when you’re driving and you get behind a dirty truck and if you’re not using the recirculate button in your vehicle and your pulling in fresh air from outside you can smell those fumes from the diesel exhaust. So having good in cabin filtration in your vehicle and using that recirculate button is one common thing that I always do when I’m driving. Same thing goes for in your house making sure you have good filtration systems. And then when you’re outside you can monitor what the air quality is like by going online and seeing what the air quality is in your region. And you can just do things such as making sure you’re getting great prenatal care, so working with your OB/GYN, with your you know clinician to ensure that you are taking care of yourself, making those appointments, but also doing things such as eating healthy and trying to breathe the best quality air that you can. Sometimes that’s outside of your hands, so that’s why we continue to push for better policies to ensure that we have clean air in our communities, is one of the major focuses.

Christina Sumners: So how did you become interested in this field to begin with?

Natalie Johnson: I think three separate things initially got me interested in air pollution and children’s health. They all kinda happened throughout my career. Early on when I was doing my doctoral work with Dr. Tim Phillips, here at Texas A&M, I was really focused on exposure to food toxins. And we were working in a rural population in Ghana, a west African country, where there had been a lot of exposure to foodborne toxins and we were working with communities to reduce that exposure. So on a visit to our study site, it was incredibly common to see people cooking over open fires, and the issue of biomass burning for cooking and heating is probably the most important environmental health issue globally. Many low and middle income countries, that’s all that people have to rely on to cook and heat their homes, and so in the process of cooking with wood or cooking with straw or even coal in some cases, moms and children are exposed to extremely high levels of smoke.

Christina Sumners: They’re just breathing it in while they’re cooking…

Natalie Johnson: Exactly so it’s mostly moms that are responsible for cooking and tending those fires throughout the day. And so they have exposure during pregnancy, often will be caring young children with them, shortly after delivery. And so that was my first kinda preview into one of the major environmental health issues associated with maternal and child health. And sadly a lot of the children that are exposed early in life will succumb to pneumonia because they’ll have suppressed immune systems and they won’t be able to fend off infections. So that was sort of my first preview. I was there studying food, we did measure some of the polycyclic aromatic hydrocarbons in samples from our study participants and we were able to see that there was a high level exposure what you may see akin to a smoker here in the U.S. I continue research, I graduate, I go to Johns Hopkins to do my post doc fellowship and that’s when I was pregnant with my first child who is now six. I would sit and I would wait on the bus because the parking was pretty expensive and so you had to park off-site and ride a bus to the school of public health. So you can kinda imagine this urban environment; tall buildings a lot of buses sitting there and running off diesel and breathing in these fumes…

Christina Sumners: While you’re pregnant…

Natalie Johnson: Exactly, while I’m pregnant, across the street you have a lot of people that are smoking, so you have second hand smoke exposure so that was when I really firsthand experienced ‘What can I do to protect my developing child?’ in this type of unavoidable exposure environment. And then fast forward to 2013, I joined A&M and I found out about the center that we have in McAllen in the valley. This is an area with some of the highest prevalence of childhood asthma. And so I began working with Dr. Genny Carrillo who does a lot on asthma education, how children can manage their asthma, reduce triggers, prevent repeat hospitalization. And I told her as a toxicologist I’m really interested in what the etiology, what’s the root cause of why kids are having high asthma? And, so that’s when all those different backgrounds came together and I thought I would really dedicate my research program to looking at early life effects of air pollution on childhood health.

Christina Sumners: So it’s really interesting how all of that came together to build your research program. So what’s next what is your next line of research going to be?

Natalie Johnson: So we’re deep in the midst of our current project and that’s really driving where we’ll go in the future. So right now we’re studying how the immune system is suppressed following exposure to this ultra-fine and fine particulate matter. We’re then moving on to the broccoli sprout intervention which we’ll do in a preclinical model first to look at, can we actually reduce maternal oxidative stress by activating Nerf 2, and prevent these RSV infections in the neonate and then work on how we can actually work with clinical partners to see the best way to design interventions for pregnant women. In addition to the particulate matter project we are really interested in moving into reducing benzene exposure. I got interested in benzene shortly after Hurricane Harvey. There were reports of increased emissions from chemical leakages and then just recently in the news we all have heard about the fires in Houston and Deer Park where colleagues in the School of Public Health have actually measured on the ground high levels of benzene exposure. So benzene is a well-known human leukemogen so in associated with childhood leukemia. And in addition to respiratory disease now we really wanna see if our same approach will fit the mold for prevention of childhood cancers.

Christina Sumners: With like leukemia?

Natalie Johnson: Exactly.

Christina Sumners: That’s wonderful and it’s such interesting and needed work that you’re doing. Thank you so much for taking the time to come chat with us today.

Natalie Johnson: Thank you so much for having me, my pleasure.

Christina Sumners: And thank you all so much for listening, and we’ll see you next time.


Source: TAMU Health Science Center

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