Victoria Maizes: Hi Andy.

Andrew Weil: Hi Victoria!

Victoria Maizes: Today we have one of our own, Dr. Randy Horowitz.

Andrew Weil: Who has been with our center forever, it seems. You know, as medical director, a very key faculty member.

Victoria Maizes: Yes, and he also is an expert on asthma, and that is what we will be talking about.

Andrew Weil: Great.

Victoria Maizes: let's get him on.

Dr. Victoria Maizes: Dr. Randy Horowitz is the medical director of the Andrew Weil Center for Integrative Medicine, and a professor at the University of Arizona. He obtained a PHD. In Immunology and molecular biology from the University of Florida, and his medical degree from the University of Illinois.

Victoria Maizes: Randy is triple board, certified in Internal medicine, allergy and Clinical Immunology and integrative Medicine. He's the editor of the Oxford University Press textbook, Integrative Rheumatology, and the founding chair of the American Board of Integrative Medicine, Welcome, Randy.

Dr. Randy Horwitz, MD, PhD: Thank you. Happy to be here.

Victoria Maizes: It's wonderful to have you on the podcast.

Andrew Weil: Yes.

Victoria Maizes: I think we should start with basics. What is asthma and what causes it?

Randy Horwitz, MD, PhD: Wow, there's a podcast right there.

Randy Horwitz, MD, PhD: So asthma, or, as I say in the UK asthma, goes back a ways. I think, Imhotep. In some of the papyri there are notations of symptoms that are congruent with what we call asthma. So asthma, as everyone knows, is a breathing disorder causes wheezing.

Randy Horwitz, MD, PhD: But there's 3 components to asthma that we analyze.

Randy Horwitz, MD, PhD: The 1st is bronchoconstriction. So if you think of your lungs for for nonclinical people think of your lungs as a sponge, and the air goes in those big openings in the sponge.

Randy Horwitz, MD, PhD: Well, around each opening is a layer of muscle tissue that can contract in response to triggers. That's bronchoconstriction.

Randy Horwitz, MD, PhD: And obviously it's like drinking through a straw. Less air is getting in. The second, component is hyper responsiveness. People that have asthma. They have twitchy airways. Their airways in response to a slight provocation, can clamp down quickly. An asthma attack or flare can start pretty rapidly.

Randy Horwitz, MD, PhD: And the 3rd component, which is interesting because it was noted by Osler, the father of internal medicine. Back in the the 1800’s, is inflammation.

Randy Horwitz, MD, PhD: We kind of forgot about it for a time. And now it came. The pendulum came back. And now it's a central component. So those 3 work together. Inflammation in the airway causes mucus production. So imagine that your airways clamp down because of bronchoconstriction, and you're getting mucus in there plugging things up.

Randy Horwitz, MD, PhD: It makes for very difficult breathing. So that's what asthma is. The causes. That's a trickier one. Certainly. There's a genetic predisposition but I think it

Randy Horwitz, MD, PhD: it actually relies on the question, how many types of asthma there are? In medicine this is a separate digression, but in medicine we often take symptoms, and lump people together, and see what works on the symptoms.

Randy Horwitz, MD, PhD: But truthfully, there are as many different endotypes, phenotypes, or subtypes, if you will, of asthma out there. And so it's really hard to say what causes it. We believe there's a genetic predisposition. There's an epigenetic or things that happen after you're born that can impact and cause asthma. And and then there's exogenous factors like viruses in a susceptible person, a virus early in life can really cause a problem.

Andrew Weil: What about the exercise induced asthma, allergic asthma. Stress induced asthma.

Randy Horwitz, MD, PhD: Okay. So when we trained Andy, and when I was in my allergy fellowship, there were 2 types of asthma, extrinsic and intrinsic, extrinsic asthma was allergic. Asthma. Intrinsic is what old people got. For whatever reason, we didn't know why the development of these subtypes or endotypes or phenotypes if you will, of asthma. There's dozens now, and they each reflect different pathophysiology. There may be different diseases. But again, we're lumpers, and we tend to put things under an umbrella.

What they have in common often are the physical symptoms that are the results. So exercise induced. You'll get the airway bronchoconstriction, which is prominent. There's there's certain kinetics about after you exercise. This occurs. That may be a whole separate disease. And so so yeah, you're right. There are dozens of types of asthma.

Andrew Weil: Is asthma in general, increasing in frequency in our society.

Randy Horwitz, MD, PhD: Yeah, it certainly is. And please don't ask me to explain why, because there's there's a myriad of hypotheses up there. The hygiene hypothesis. We're getting too clean in our environment. You have pets in your environment. You don't have pets, is it antigen or allergen exposure that leads to it. We have individual facts, but

Randy Horwitz, MD, PhD: you know the issue is, there are so many again, to digress. There are so many different components that can cause a medical condition. And and to just say one thing is responsible when people's genetic makeup is so different is very difficult to ascertain.

Randy Horwitz, MD, PhD: But we know some things may predispose a little bit having an allergic phenotype or someone who's allergic or atopic. Someone who gets a little kiddie who gets viruses early in life. Those are things that can predispose.

Randy Horwitz, MD, PhD: There's 1 other thing that's kind of interesting.

Randy Horwitz, MD, PhD: They did a study. A group did a study on mice, and what they did was they gave these mice antibiotics early in life they put it in the water supply so they would drink it. So right after weaning, they gave these weanlings antibiotic for 4 weeks, and they looked at the Gi system and saw that yeah the microbiome was affected and everything. Then they co-housed these mice with control animals who didn't get the antibiotic. Over time their microbiome regulated, and they were identical to the control mice. However, they then took the mice and sensitized them to an allergen. That's where you give them increasing doses, and then you can make them allergic. And they used house dust mite.

Randy Horwitz, MD, PhD: So they took the mice, the antibiotic ones and the control ones that were now physiologically identical, and they sensitized them, and then they expose them to house dust mite well, the ones that had the antibiotics remarkably sensitive, allergic, developed asthma like symptoms. So this was. This was months and months later, even though the microbiome had corrected itself. So maybe exposure to antibiotics early in life may be linked to human asthma as well.

Randy Horwitz, MD, PhD: Let me add one other thing.

Randy Horwitz, MD, PhD: I don't want to belabor it, but I think it’s really cool. They looked at what was different about these animals. And it turns out there's 1 particular metabolite of

Randy Horwitz, MD, PhD: I want to say, of tryptophan. I could be wrong on the amino acid one metabolite that was deficient in these mice and these animals that were exposed early in life.

Randy Horwitz, MD, PhD: When they repeated the experiment and gave them back this metabolite.

Randy Horwitz, MD, PhD: Then the asthma normalized and and controlled. So they're looking at possible therapeutic implications in in humans.

Victoria Maizes: That sounds like an epigenetic, then alteration.

Randy Horwitz, MD, PhD: Absolutely, absolutely.

Victoria Maizes: So you mentioned something that is paradoxical, that asthma could be caused by too much or by too little pet at home. Can you explain that.

Randy Horwitz, MD, PhD: So when I was growing up I had allergies and asthma, and of course we had no pets. I had my goldfish, Gefilta, but that was it. Nothing that I could pet, even though I tried to pet the fish and were my parents doing me a service or not.

Randy Horwitz, MD, PhD: it's it's hard to say. It's hard to say, because kiddies raised on farms and exposed to many farm animals seem to have less incidence of asthma and allergies in general. So it's it's really tough to say again, the problem is, there's so many other factors, genetic factors. And my background in in basic science we did experiments on mice, and they had to be inbred mice. You couldn't publish anything with just random wild mice. Why is that? Because they're disparate. They're different. And yet we're doing that in humans all the time. We're trying to reach conclusions when you have a population that's so different. So eventually, N equals 1. Which is why I like integrative medicine because you look at your patient as an N equals one entity, which is probably true.

Andrew Weil: Can asthma disappear? Can it go into total remission? People.

Randy Horwitz, MD, PhD: Yeah. So typically childhood asthma, you'll have a remission period of some years. It could be 10 years could be 20 years. People think they're cured. But then, usually allergic asthma comes back with a vengeance later in life. We don't understand exactly why it's it's interesting. They're looking at possible mechanisms for how this can occur. Are there certain cytokines that change in adolescence and come back later in life? But it's a typical pattern where asthma will, except in severe cases, asthma will go through a remission period, and then it'll return.

Andrew Weil: How good are our treatments.

Randy Horwitz, MD, PhD: When I was in training, we used corticosteroids, and we use prednisone. We use steroids like water, because our severe our patients with severe asthma that kept them out of the hospital kept them out of the emergency room and we realized we were doing harm to them, but it was that balance that fine balance. So the steroids are the atom bomb.

Now we have biologic agents and biologic agents seek to get at the the root of the problem if you will and works well for certain patients. But out of the maybe half dozen biologics available They hit certain cytokines. There's no biologic agent that works for everyone. So what we've done is gone from the atom bomb to the sniper in terms of targeting pathophysiology.

Randy Horwitz, MD, PhD: Those are the the agents, the corticosteroids, and basically the the biologics that are trying to get at the root of the disease, our symptomatic therapies. We have bronchodilators which could be. There's a short acting sabas, long acting labas that last between 4 h and 12 h depending on the formulation. There's some dangers with using a long acting beta agonist, or a lava without any corticosteroid or anti-inflammatory with it.

So we have a whole gradation of of severity of asthma mild. Someone with mild asthma may use a beta agonist, maybe once or twice a week we'll add on to that an anti-inflammatory, usually inhaled, inhaled corticosteroid, and they'll be on that. Beyond that there's leukatrine inhibitors. But now people are going 1st line to these biologic agents which are tricky. I mean they they work great. I'm afraid the pharmaceutical companies are aiming to get them into 1st line therapy. I think that's their goal. That may be the case, but you know long term implications of using targeting these cytokines is a bit naive, and we don't know if someone's on these agents for 30 years what the effects may be.

Victoria Maizes: I know you're a big fan of tracking the results of your treatment and your disease with peak flow meters. Can you talk about? Why you think they're so important, and maybe how they're well used.

Randy Horwitz, MD, PhD: Yeah. So a peak flow meter is nothing more than a is it called an anemometer that measures wind? Yeah. So it's basically that you blow into it as hard and as fast as you can, it'll establish your well levels. There's a certain percentage of patients, maybe 30%. I haven't seen more than that

Randy Horwitz, MD, PhD: that. A day or 2 ahead of an asthma flare you'll start to see declines in the peak flows. So peak flow is the poor man's spirometry, which is the machine in in the doc's office.

For patients that respond. It's great. They do it once a day at a certain time of the day, and we can give them a treatment protocol usually traffic lights are what they use with little kids, red, yellow and green, depending on where their peak flow lies. They can intervene and try to stave off a flare. Our goal in all our patients with asthma is to keep them from having an exacerbation or a flare. So if we know in advance, we can intervene early, and what that might mean is cranking up the dose of inhaled corticosteroid, putting a patient on an oral corticosteroid. Or if you're an integrative practitioner, using the whole slew of modalities that have been shown to be effective.

So the peak flow meter is, it's good in some people. I like it because it gives the patient a sense of control, which is something you lose in asthma.

Andrew Weil: Have you found dietary modification to be useful in some patients? No, I often tell people to experiment with cutting out cow's milk in all of its forms, maybe wheat, maybe other forms of protein. See what happens.

Randy Horwitz, MD, PhD: Yes, it's interesting. The the problem I see is, I take patients off milk and wheat products and a whole bunch of them respond. Well, my problem is trying to find a mechanism to explain it. I've stopped trying to do it. It's it's a trial that's very simple and benefits a large proportion of people. Milk is supposed to be linked to mucus production. There is some evidence for that. But, but yeah, food sensitivity as a cause of asthma is often ignored. We view it as, oh, if you have allergies, you'll anaphylaxis to food. We don't think of asthma in the same terms, and maybe we should as a chronic condition. So I think dietary interventions are important. I think, Omega 3s have been shown to help most of my patients. I put them on a supplement rather than just increasing dietary, Omega 3s, and it seems to help quite a bit. There have been studies with Omega 3 s. That were very useful. The magic number is about 50%. About half the patients will respond, but when they do respond it's usually remarkable. And and again, the Omega threes. In this case, if you think of the arachidonic acid pathway which is the inflammatory pathway in the body, it leads to the production of compounds called Leukotrienes. It also produces prostaglandins, cyclooxygenase in the other arm, which is involved in maybe rheumatologic conditions. But the leukatrines leukotrine there's B,C,D,E. There's at least 4 of them, and they're the most potent broncho constrictors that we know of. If you instill leukatrines into the into the trachea lungs of animals, you'll really get a vicious response. So by circumventing that normal pathway, by adding and goosing up the amount of omega3, preventing the formation of leukotrines. It seems to help.

Randy Horwitz, MD, PhD: I found that it helps. I don't know whether that's the exact mechanism, but at least when they did studies in animals and actually in people. When you, supplement a crappy American diet with just a couple of pills of of EPA, you change the composition of the cell membrane within 6 weeks, 3 weeks.

81

00:16:46.340 --> 00:17:03.526

Randy Horwitz, MD, PhD: So I I think that's a very plausible explanation for how they work. So omega 3s. Vitamin D another supplement. I know it's not really nutritional, but supplementing vitamin D. There's a fellow named Rand Sutherland used to be at Mayo.

He did experiments and showed that increasing vitamin D levels are associated with fewer asthma exacerbations. If you look at people with poorly controlled asthma. If they have a low vitamin D level their airway hyper responsiveness or twitchiness tends to be higher. Their fev one or their lung function tends to be lower. So again, I found in some patients, and I can't predict which ones when you pull up their vitamin D level to say 50 you can get dramatic responses.

Victoria Maizes: What About some of the other supplements that people take like Quercetin or Butterbur?

Randy Horwitz, MD, PhD: So, quercetin, and Its pharmaceutical brother, chromalin, are really important. And chromalin is something we use in integrative medicine. A lot if I can digress for just a sec. Chromalin was developed by a doctor named Roger Altunian and when he was young. He had terrible asthma. He did did as an adult as well. His grandma would give him tea from Ami. Visnaga was the name of the plant or the Kella plant would give tea, and that would help him help him greatly. So he promised his grandmother that he would find out and make her tea famous.

He went to work for a company called Feizens in Great Britain, back in the sixties, and he had a shoestring budget. So he experimented on himself. He was allergic to guinea pigs, so they had a room down the hall with guinea pigs. He would test compounds out of the tea and then he would go and rub guinea pigs and see protected him.

And, actually in. I think it's in the NIH. They have his. They have his his pulmonary testing. When he found cromolyn he found a compound that prevented mast cell degranulation, and it prevented allergies and asthma. They had to find a way to get this dry, desiccated powder into lungs. It just so happened that Altunian was an RAF Pilot, so he said, I'm going to make something like the propeller on my plane. So he made something called a spinhaler, which was an airplane propeller in a little tube, and then a needle that punctured the capsule of Cromolyn as you inhale through the tube, it spins, the propeller dispersing the powder throughout the lungs. That was the original cromolyn. So, anyway, getting back to your point, cromolyn is a great compound. Before we had inhaled corticosteroids or nebulized, we would give it to pregnant women. We would give it to babies, nebulize it. It was. It's a great compound, very very safe. And it inhibits mast, cell degranulation. Quercetin is a similar compound, and and cromolyn, by the way, is now only available in the US by nebulized doses, but it works great.

Quercetin has the same activity, so quercetin will also inhibit mast cell debrina. In fact, on a mole per mole basis. It's far more potent, maybe twice as potent as cromolyn. The problem is with any of the bioflavonoids like like quercetin, they're great compounds. How do you get them into the body. How do you get good absorption so often? They'll combine them with other compounds. vitamin C, bromelain, something like that. But that's the challenge. So these 2 compounds work really well at inhibiting allergic asthma in in a large proportion of people.

So I think those are great. I think, when it comes to allergic asthma. If you could stave off the allergic inflammation, using either an antihistamine which we don't favor, or a natural antihistamine, as you mentioned. That's another alternative doesn't affect the breathing quite as much. I think people have to realize when we're talking about either supplements or even botanicals, especially there are botanical analogs for just about every medication that we use for asthma, whether it's Ma wang tea as a beta agonist, which which works well, or if it's anticholinergics that we use sometimes, ifatropium versus, what would be the natural? Well, thattura? But you don't want to use.

Andrew Weil: The door, cigarettes.

Randy Horwitz, MD, PhD: Yeah, that's tough.

Andrew Weil: That was, that was a that that was tratoro. That was a, you know, a Jimson weed cigarette.

Randy Horwitz, MD, PhD: Now the problem is, you have high school kids one a year, maybe will overdose on that. And and what about methyl xanthines? Theophylline 1st discovered it in Camellia sinensis. So all of these things they have a basis of biologically plausible basis for their activity.

Andrew Weil: Any role for mind- body interventions.

Randy Horwitz, MD, PhD: Huge, huge role. And I I love min- body and patients that often it's difficult with patients because you have to convince them of the the power of the mind, body, connection, and there was a 1 of my mentors was Regis Mcfadden. He was at the Brigham way back when he did an experiment with suggestion, where he advertised and took 40 patients from the Boston area with with allergic asthma, and they wrote down what they were allergic to and his whole experiment used saline. And so patient A would come in and say, diesel fumes. So they'd say, Okay, this tube has diesel fumes. You're gonna nebulize it. And what he saw remarkable about half the people had severe asthma attacks the thing that was interesting. They used a beta agonist to rescue them, which was also just saline, and the patients responded, well, that article is a classic in suggestion.

So we use hypnotherapy quite a bit meditation therapy, regular run of the mill psychotherapy.

Randy Horwitz, MD, PhD: if we think about national Jewish Hospital, which is the foremost respiratory hospital in the in the world. Perhaps their 1st director was a doc named Murray Peshkin. And what he found was this, he was admitting little kids to the wards with asthma. They'd be in the holding area. Parents would be in the waiting room. The kids would start getting better before any treatment was administered. He saw it so many times he wrote an article, and he said, what we need is the parentectomy removal of the parents.

Victoria Maizes: I don't think the attachment theory. People probably like that very much.

Randy Horwitz, MD, PhD: It didn't have universal appeal. There's still a there's still a plaque up about that. The parentectomy, mind, body is huge journaling. They did a study in JAMA where they had journaling people with asthma journaled 3 days, 20 min a day. That was it, I mean, can you imagine the grant? Just a pad of paper and a pencil, and then at 2, 4, and 16 weeks later, that was all the journaling they did, those 3 sessions 2, 4, and 16 weeks later they measured Feb ones or basically airflow from these individuals, and the improvement was remarkable, and it persisted even from those 3 days they were journaling the most the most impactful and most emotionally upheaval events in their life. The control group was doing diary entries. They didn't see any change whatsoever in the FEV1. And I actually called the authors because I said, 
wouldn't that emotional upheaval of writing about stressful events make your asthma worse? And they said, Yeah, we thought so too. It wasn't the case. So my body is huge, and it's it's not used much.

Andrew Weil: Yeah, my experience is that one of the most distressing symptoms that people can experience is air hunger, you know, that can occur in other respiratory diseases as well, the feeling of not being able to get enough air in. And I think if anything you can teach people to do to help them relax and and not be as distressed by that. I I use the 4 7, 8 breath. But I think there's other techniques that can be helpful.

Randy Horwitz, MD, PhD: Also you know, and the and breathing exercises were shown to help asthma in general. They didn't assign it to a mind body practice instead, saying, maybe it's a pulmonary effect. But articles have been published showing that breathing exercises are really valuable in folks with asthma.

Victoria Maizes: I'd like to hear from you what you think the effect of air pollution, and you know, potentially other environmental toxins.

Randy Horwitz, MD, PhD: Wow, yeah. You know, there's a famous case in Great Britain, and I don't have it at the top of my head of a a young girl who died, and the cause of death was listed as air pollution. Someone with asthma.

Victoria Maizes: She had 9 million other people a year.

\Randy Horwitz, MD, PhD: Yeah, what was remarkable here was. It was the 1st time pollution was listed as a cause of death.

Andrew Weil: You know, one type of pollution that has become much more common is forest fires. Smoke, breathing, smoke, I think, is one of the most harmful things to the respiratory system, and an awful lot of people in the West are being exposed to the smoke.

Victoria Maizes: And it's now not just the trees that are burning, but the products of combustion from people's homes that bear a lot of additional chemicals beyond the wood.

Randy Horwitz, MD, PhD: Right. Right. And there are so many compounds in wildfire smoke that trigger asthma, I mean, it's a huge list. And my patients who often vacation there in the in both in Canada and in the Northwest, have to leave especially, and in California everything blows. And it's it's ridiculous that we have so many so many air alerts, even in areas without wildfires. I mean in Arizona. Now, we're getting days that are that are high on air quality and or low on air quality. And yeah, it's just scary. But that has to contribute to asthma exacerbation. So there's no doubt in my mind.

Victoria Maizes: So how well does a HEPA filter in the bedroom, or the home or the office work in that situation?

Randy Horwitz, MD, PhD: It works well. The problem is, if you're in a in a tough area with a lot of wildfire smoke you'll have to change filter frequently. The only thing HEPA filters don't work well for

A lot of allergens when people put them in their home. For some allergens, cat allergen, for example, is very sticky and floats, and often it will stick to the wall, stick to the floor. So some allergens are really difficult to get out of the air with HEPA. But if you're talking about environmental, if you're talking about pollens, things like that, absolutely HEPA Filter is, is worth an investment especially if you, if you can't afford one for the whole house, put it in your bedroom and seal it off somewhat.

Victoria Maizes: So where are we now with the hygiene hypothesis? There it was, so interesting, as you know, that became more widely known that maybe we're just too clean. Maybe we're not getting exposed to parasites enough you know, it's wonderful. We're preventing all these viral illnesses with vaccines. But maybe there's a consequence in how our immune system develops. What's the thinking currently.

Randy Horwitz, MD, PhD: I think the current thinking is again rather mixed. We come into situations. The hygiene hypothesis. The pendulum swings. We expose our kids to everything. I don't know if they still have chicken pox parties and things like that. They expose kids to everything. And then there's a pandemic. Everything swings the other way. So for years kids are being isolated again. So I think it's up in the air. I don't think there's consensus at this point. But it's a rich area for study I wish I could give advice and say, expose your kids to everything at one time. But, we just don't know.

Victoria Maizes: Randy, I feel like you've given us so much wonderful information are there other things, you want people who either themselves have asthma or have children or grandchildren with asthma? What else should people know.

Randy Horwitz, MD, PhD: Well, since we are all involved in integrative medicine, I have to say that there are other modalities. And and we're gradually changing conventional thinking. For example, there's a famous Doc named Zumin Lee, who was at Mount Sinai now is somewhere else. And she came to Mount Sinai and Hugh Sampson was in charge of allergy there, and he's he was the president of the Allergy Academy, and he's pretty rigid, and she said, I have formulas that I use in acupuncture and when I was young that work for asthma. And he said, Okay, you can take a little time and look at it. She found from ancient ancient text formulations, and she want us to try them 1st on animal models. And he said, Okay, but you've got to take every one of those and purify it. I want to see the mass spectroscopy on every one of those 13 different components. She went through the arduous work of doing that went through it took several years, came up with a compound that she named Ashmi A. SH. Mi. It had 3 things in it. It had licorice root. It had reishi, and it had safara. Those were the 3 she pinned down from the 13. She used it on animal models, and it worked as well as corticosteroids, but it did not immune, suppress against what they call th one or normal infections. So it was a non-immunosuppressive targeted therapy. She tried it in people, and again it worked in a large proportion of people as well. I don't know the status of it right now I know that they submitted to, perhaps patented, and everything. But I think the key with asthma is keep looking for things that might work for you, and obviously don't do anything without the advice of a trained clinician. And hopefully, someone trained in integrative medicine. They can guide you through these. You're not going to start new therapies and drop your old therapies without adequate supervision, because asthma is still a serious condition, still kills people. So you have to treat it with respect. But having said that, you have to have an open mind, as well to other modalities.

Victoria Maizes: Well, Randy, this has been such a rich conversation. And I just really want our listeners to appreciate your expertise and you are, of course, a core faculty member at the Andrew Weil Center for Integrative Medicine, and have been so for 2 decades, and people who come and study with us get to study with Randy. Not just Andy, Randy.

Randy Horwitz, MD, PhD: Thank you, thank you. And I kept beard before I came here. So.

Victoria Maizes: Gotta grow it longer.

Randy Horwitz, MD, PhD: It's turning white. It's turning white.

Thank you.