Wildfires and COVID; Healthcare Inequities; A New Migraine Treatment

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week’s topics include wildfire smoke and COVID, metabolic rate throughout the lifespan, a new agent for migraines, and minority disparities in healthcare.

Program notes:

0:32 Wildfires and COVID

1:35 Increase of almost half a million exposures per year

2:32 Strong evidence of strong association with death

3:30 Wildfires increase inflammation

4:12 Heatlhcare inequities

5:15 2.4 trillion dollars spent

6:15 Outpatient versus inpatient

7:00 Daily energy expenditure through the life course

8:02 Four distinct phases of life

9:01 90 years and older

10:01 Many implications for recommendations

10:18 New treatment for migraines

11:10 Oral agent for prevention

12:11 What percentage of migraine sufferers?

13:03 End

Transcript:

Elizabeth Tracey: How are wildfires impacting on COVID infection?

Rick Lange, MD: Preventing migraine headaches.

Elizabeth: What do we really know about metabolism through the lifetime?

Rick: And healthcare inequities in the United States.

Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist,

Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso where I’m also dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, let’s talk first about wildfires and COVID. This is an article that’s published in Science Advances, the first time we’ve ever discussed anything in this particular journal. What these investigators did is they looked at short-term exposure to a part of wildfire smoke that’s called PM 2.5 — that’s particulate matter 2.5 — and we’ve talked about this a number of times with regard to other health conditions and things like heart attacks. They also looked at that in association with the increased risk of COVID-19 cases and deaths.

They looked at publicly available data, 92 western U.S. counties that were affected by 2020 wildfires. And as we know, in our era of climate change, these wildfires are taking place more often and right now we have some really big wildfires that are going on.

They cite some statistics relative to history and say in the last 4 years the United States has experienced record-breaking wildfires with an increase of almost half a million daily exposures per year. Wildfires contribute up to 25% of the PM 2.5 concentrations in the atmosphere in the United States. And I would also note that when we take a look at that wildfire smoke and we see how it makes its way across the country, it could be impacting a whole lot more than just these counties they examine.

These 92 counties were in California, Washington, and Oregon where most of those wildfires in 2020 occurred. They also took a look at what they called the lag effect: how much did this wildfire exposure affect COVID-19 cases 14 and 21 days post exposure? The upshot of the whole thing is that, sure enough, when they pooled all of this data, they found daily increases of 10 μg/m3 in PM 2.5 per 28 subsequent days found an almost 12% increase in COVID-19 cases.

With regard to deaths, they found that 17 of 92 counties had strong evidence of a positive association between exposure to these particles and increased risk of death 4 weeks later. That varied quite a bit among the different counties that they looked at, but it was a persistent association — clearly something that’s very concerning, because what are we going to do about this?

Rick: Here, the association is between wildfires — which by the way have consumed 10 million acres in the western U.S. this past year — and increased COVID infections and deaths. You ask yourself, is there a biologic plausibility? Because you can make an association just about with anything statistically.

There seems to be consistency across most of these counties. Although a lot of heterogeneity, the average increase of death is about 8% and the increase in cases is about 12% for every 10 μg/m3 increase. But in some counties it was as high as 60% or 70% in terms of deaths and rates.

The plausibility is that wildfires increase inflammation in the lung, they may suppress the immune system, and therefore make it more likely for people to get COVID several weeks after the wildfire was reported.

The other possibility is perhaps the particulate matter helps the virus to transport further distances. It looks like this association does have some biologic plausibility.

Elizabeth: Sure, and we’ve talked about this before. As I said, though, it’s unclear to me exactly how we are going to impact on this association.

Rick: We talk about high-risk people, those with the comorbidities; there are also high-risk situations. We need to be more vigilant about exercising preventive measures we know are effective in terms of social isolation, wearing masks, and particularly vaccination.

Elizabeth: Okay. Now which of your two would you like to turn to?

Rick: Let’s talk about health care inequities. The COVID-19 pandemic is not only associated with wildfires, but also highlights the persistent inequities among several communities in terms of their infection rate, or their morbidity, or mortality associated with — particularly American Indians, Blacks, Latinos, and even Native Hawaiians and Pacific Islanders.

We have three articles and one editorial to kind of report on in JAMA that all focus on health inequities. One did a 20-year analysis looking at the National Health Interview Survey data of almost 600,000 individuals to examine self-reported health status and access to and use of healthcare.

Health status was reportedly worse in minority populations, especially in low-income minority populations. For example, almost a third of low-income Blacks reported they had poor health and not much access to healthcare; 6% of whites that are in the middle to high income reported that.

Another study examined 7.3 million visits, admissions, and prescriptions over about a 15-year period. We spent $2.4 trillion in 2016 across healthcare; 72% of that was accounted by White patients, although we just make up 61% of the population. Latinos and African Americans, which make up a lower percent of the population, had a much lower health care expenditure, especially with regard to outpatient. Now, interestingly enough, they had an increased inpatient and ICU expenditure.

Then the last study looked at Medicare and Medicare Advantage populations. Even though enrollment in Medicare Advantage and traditional Medicare was associated with better outcomes for access and quality care among minorities, still the minority beneficiaries were significantly more likely to experience worse outcomes for access and quality measures than Whites. I’m going to call it structural racism. There are structural things in the system that somehow disadvantage non-White patients.

Elizabeth: One of the things that’s noteworthy here is this disparity between hospitalization and outpatient utilization, and suggests to me that people sometimes avoid the healthcare system until they’re at a place where they have to be hospitalized because their illness is so advanced.

Rick: That speaks to several things: one is, do they have access to outpatient care? If they do, do they use it? Third, is it delivered in a culturally competent way? Most of us would like to see a doctor that looks like us, understands us, and understands our culture as well.

Elizabeth: Many fronts on which this needs to be addressed.

Rick: Yes, it shines a light on it. These particular studies don’t shed any insight into why it is, so we need a lot of work. There is a long way to go.

Elizabeth: Let’s turn now to Science. This is a study that got a lot of attention. This is taking a look at daily energy expenditure through the human life course. You ought to see the number of authors who are a part of this study.

What is so curious to me is that previously, most large studies that have looked at human energy expenditure have been limited to just our basal expenditure or metabolic rate at rest. They take a look in this study at doubly labeled water studies that measure the total expenditure in free-living subjects. These were males and females aged 8 days to 95 years, fat-free, mass-adjusted expenditure. They had 6,421 subjects, 64% of whom were female. They had 29 countries represented. They also had basal expenditure measured with indirect calorimetry for 2,008 subjects. Both basal and total expenditure increased with fat-free mass, so that’s not surprising.

They were able to discern four distinct areas of life in which this metabolism changes. They have their first phase that’s neonates and that’s up to 1 year of age. Interestingly, when these babies are born, they have a metabolic rate that’s very similar to their moms, but then it increases a lot.

The second phase is that of juveniles, 1 to 20 years of age. During this period, total and basal expenditure increased with age throughout childhood and adolescence along with their fat-free mass, but their size-adjusted expenditures steadily declined. Then when they get to be 20.5 years, they plateau at these adult levels, and that’s our third phase, adulthood from 20 to 60 years of age.

Then finally, it’s older adults, a little disconcertingly at age 60, total and basal expenditure begin to decline along with fat-free mass and fat mass. Until finally, if you’re 90 years old or older, you’ve got about 26% less basal metabolic rate than that of a middle-aged adult.

Previously, we’ve made all these noises about different states like pregnancy that we thought were associated with this accelerated energy expenditure and it turns out that that’s just really not the case. Now we need to recalculate a lot of recommendations.

Rick: I realized that expenditure increased in youngsters under 1 year of age. I didn’t realize how much higher it was — adjusted for mass — compared to adults. It’s over 50% higher than it is adults. It goes up dramatically.

It kind of dwindles between ages one and 20, which I was surprised at. It stays very stable for ages 20 to 60 and then declines after that. I was surprised it doesn’t go up in the pregnancy period or afterwards. You say, well, obviously expenditure goes up. But when they adjust for the mother and the neonate together, it stays relatively constant.

The other thing that is interesting is that the sex had no effect on the total expenditure compared to fat-free mass as well, which I was a little bit surprised at.

Elizabeth: I think this paper has a lot of implications for recommendations that are made for folks when they come and present to their primary care doc, for example.

Rick: I think it even occurs way earlier than that. I mean, if total expenditures increased very early on in early development, that’s a critical period.

Elizabeth: Let’s turn to the New England Journal of Medicine,:a very common problem, migraines, and maybe we have something that’s going to help.

Rick: Migraines are caused when there is vasospasm, the blood vessels in the brain contract and relax that causes some physical discomfort, but also inflammation as well that’s perpetuated. We talked about a year or a year and a half ago about a new pathway that was discovered. It’s called the calcitonin gene-related peptide (CGRP).

During migraine attacks, levels of this went up in the bloodstream. If you actually administer this peptide, you could actually precipitate migraines and there is an antibody that can be given — injected — that can help treat this. Unfortunately, that involves monthly injections, hence the desire to have an oral agent. That’s exactly what we’re reporting on today, an oral agent named atogepant, which is a small-molecule calcitonin gene-related peptide receptor antagonist.

In this particular study, they use it not to treat migraines, but actually to prevent migraines. They had 873 people they analyzed that received either placebo or one of three doses of this. These are people that had long-standing four to 14 migraine days per month.

Those that received just the placebo, it decreased their migraine days per month by two and a half days per month. The use of the atogepant reduced it about four days per month. Side effects were relatively minor, but they consisted primarily of constipation; 4.5% to 6% experienced nausea as well.

Elizabeth: Did you tell me, is this phase III?

Rick: This is a phase III trial. It’s a little unusual because usually in phase III trials you’re not doing dose escalation.

Elizabeth: We’ve talked before about how this thing that is called migraine could result from a multitude of conditions. I’m wondering what percentage of people who suffer from migraines might benefit from this particular drug in this pathway.

Rick: I wish I had an answer to that. This is a very specific group, moderate migraines. I wish I knew the percentage. I just don’t know.

Elizabeth: At least hope for some, and maybe more specific and precision medicine kind of endeavor if we can identify, “Hey, this pathway is active in you.”

Rick: Yeah. To give a medication that’s oral rather than an injectable and then hopefully this will bring the cost of prevention down as well, because the injectable antibody is just expensive. I wish I could tell you what this would cost per patient; I tried to find it online. I was unable to do so, but hopefully it will drive the cost down.

Elizabeth: On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.