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Steroids and Asthma; One-Time PSA: It's PodMed Double T!

— This week's topics include the dangers of e-cigarettes, steroids and asthma, five types of diabetes, and a single PSA measurement and outcomes.

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PodMed Double T 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. A transcript of the podcast is below the summary.

This week's topics include the dangers of e-cigarettes, steroids and asthma, five types of diabetes, and a single PSA measurement and outcomes.

Program notes:

0:41 Looking at metabolites of e-cigarettes

1:41 Increased organic compounds in blood

2:43 Targeting to this population

3:00 One time screening for prostate cancer

4:00 Did not decrease prostate cancer mortality at all

5:00 New tests will become available

5:17 Five subtypes of diabetes

6:17 Severe insulin deficient

7:16 Previously only classified by HbA1c

8:19 Metabolic measures

8:39 300 million people worldwide with asthma

9:45 Make sure they are optimally managed

10:33 End

Transcript:

Elizabeth Tracey: What do we know about the dangers of e-cigarettes for kids?

Rick Lange, MD: Can a single PSA screening decrease prostate cancer and mortality?

Elizabeth: Should classification of diabetes be divided into five subgroups?

Rick: Does increasing inhaled steroids prevent asthma exacerbations?

Elizabeth: That's what we're talking about this week on PodMed TT, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I'm Elizabeth Tracey, a medical journalist at Johns Hopkins, and we're posting this on March 9th, 2018.

Rick: I'm Rick Lange, President of Texas Tech University Health Sciences Center in El Paso and Dean of the Paul L. Foster School of Medicine.

Elizabeth: I would like to start first with Pediatrics. I've been looking for this for a long time. This is admittedly not a huge study, but in this one, they took a look at the metabolites of e-cigarettes in a small group of kids average age of 16.4 years. They had 67 participants who used only e-cigarettes, 16 who used both, and 20 who acted as controls who didn't use either one of these two things. They took a look at metabolites of smoking: cotinine -- we're familiar with that -- something abbreviated NNAL, and then eight other volatile, organic compounds in the blood.

What they found, it's kind of not surprising in some ways. The highest levels of these things were in those who used the dual forms of nicotine delivery, shall I call it. But concerningly and revelatorily -- which is not a word, but I'll use it anyway -- they found out that those who used only the e-cigarettes also had increased amounts of these volatile organic compounds in their blood. For me, this is really a smoking gun that says, "Hello, e-cigarettes are not safe either."

Rick: Let's take a step back and inform our listeners that now, among teenagers, e-cigarette use is twice as common as tobacco use. Now these volatile organic chemicals that you're talking about are actually carcinogens. It was presumed that using e-cigarettes or vaping would expose you to nicotine so you get that effect, but it probably didn't expose you to potentially carcinogenic chemicals. But what this study shows is in fact, it does, and then when they looked at these compounds compared to controls, they were five times higher. This is the first evidence I'm aware of that has looked at these compounds after e-cigarettes.

Elizabeth: I would love to see it be evidence that would cause us, at least, to restrict the use of e-cigarettes to those age 21 and older, as so many states have already done, and of course, around the world with traditional combustible cigarettes.

Rick: Because studies have clearly shown that if you introduce e-cigarettes to adolescents, it increases their use of tobacco as well. So many of these companies are targeting e-cigarettes to this particular population. Elizabeth, I agree. Restricting them to prevent future tobacco use and to prevent the harms, increased nicotine and also this carcinogen exposure, I think is really important.

Elizabeth: Let's turn to one of yours. A perennial favorite, this idea of who ought to be screened for prostate cancer, how often should we do that, is it really predictive? That's in the Journal of the American Medical Association.

Rick: One of the issues with repeated prostate cancer screening is the overdetection and overtreatment of prostate cancer that otherwise wouldn't result in a mortal event. One of the ways to prevent that overdetection is to do just a single PSA [prostate-specific antigen] screening between the ages of 50 to 70. If the PSA is elevated, then to refer them for additional studies, and then if they're positive, then to treat it.

This study examined that assessment and treatment strategy, and they had over 400,000 men in this study. Half of them were unscreened. The other half were recommended to undergo a single PSA screening, and if it was elevated, then to do the further assessment and treatment. Then they looked over 10 years to see whether that single PSA measurement would decrease prostate cancer mortality. What they discovered was that the individuals who had the single screening were more likely to be diagnosed with prostate cancer. Over the course of 10 years, this strategy did not decrease prostate cancer mortality at all.

Elizabeth: As you're well aware, so many of my colleagues here at Hopkins are specialists in this area of prostate cancer, and I guess my concern is does this mean we're just going to throw out screening entirely and then return to an era where men who presented with prostate cancer presented with really advanced disease?

Rick: Well, I think this study shows that a single PSA screening isn't helpful. Now there have been other studies that looked at repetitive screening every 2 to 4 years. What they show is there is a very small decrease in cancer-related mortality at the expense of overdetection and overtreatment. I think it's important for men to know that if you're going to do repeated screening, for every avoided prostate cancer death, there are 27 additional men diagnosed with prostate cancer over the course of about 13 years. Armed with this information, I think it's important for the man to decide are they going to have repetitive screening or not?

The other thing that will happen over the course of the next several decades is we'll have different screening. What I would tell our listeners is stay tuned, and as these new tests become available and tested, we'll inform them of their best use.

Elizabeth: Exactly. Of course, one day we're all going to be genotyped and there's going to be a lot more prediction of what we're susceptible to, to begin with.

Rick: Speaking of that, in terms of doing more precision medicine, Liz, why don't you talk about the diabetes study?

Elizabeth: Indeed. In The Lancet Diabetes & Endocrinology, this was a sweeter study taking a look at just shy of 9,000 subjects as part of what they call their "All New Diabetes in Scania Cohort." Boy, those people are so amazing. I find them that way, anyway, because they gather so much data about all their citizens. It might make me a little nervous, maybe, but in any case, what they did was they did a blood draw. They looked at fasting plasma glucose. They also did genotyping, and they did a lot of other assessments as well.

They divided, then, all of these subjects into five -- no longer just two types of diabetes, folks, five. I'm going to bore you with some of the details. About 6.4% of these folks they now call early onset severe autoimmune disease diabetes, and that, I guess, would be more or less synonymous with type 1 diabetes or juvenile diabetes. In their second division that was about 17.5% of the folks, these were characterized as severe insulin deficient. The third one, 15.3%, severe insulin resistant with increased body mass index. The fourth, 21.6%, a high BMI, but not insulin resistant. Finally, the largest cohort, almost 40%, they called mild-obesity-related diabetes.

My view of this is that it's really great from a scientific standpoint and for the nerds among us, and I think it has clinical implications for the management of these folks, but I struggle. I think right now people who have diabetes are often not really sure who they have [sic] and what they have. All they want to know is, "Hey, how do I stay healthy?" and some of them don't even do that. I think this might be useful for clinicians, but not terribly useful for people with diabetes.

Rick: As you said, these were all type 2 diabetics. Previously, we only classified them based upon what their hemoglobin A1c was. But we know that treatment of some individuals really didn't decrease the incidents of kidney disease. In other individuals, it did help prevent retinopathy, but how do you distinguish who these individuals are? What they did by clustering these using these six different tests is to categorize these individuals to find out what's the outcome of these individuals and to find out whether treatments have been effective for these particular clusters. This is novel. It's interesting. I think it has implications for the clinicians and for treatment in the future.

Elizabeth: I think there's no question about that. Actually, I applaud it, because as we see with so many entities, what we call something clinically is just the tip of the iceberg. What causes it is everything that's below the surface of the water, and that's highly individual. I would also add that you and I are both familiar with research that's showing that there's also a subtype of diabetes that might be involved with the ultimate development of dementia. There are some other ways that we could slice this pie that might be also clinically important.

Rick: Right. What they measured were metabolic measures, glucose, insulin resistance, insulin production. Will we develop other things as well that help us hone down a little bit more?

Elizabeth: Let's turn to your last one, then. That's this look at asthma exacerbations. Gosh, is there anything we can do about those? Is it really helpful to use corticosteroids? That's from the New England Journal of Medicine.

Rick: Elizabeth, 300 million people worldwide have asthma. We know there are a number of effective treatments in treating acute asthma, but more importantly in trying to prevent exacerbations. One of those happens to be inhaled steroids, and a lot of individuals are on those, and despite that, they may have an exacerbation.

Before they develop a full exacerbation, these individuals oftentimes know that their breathing is becoming more difficult. This is called the "yellow zone." When individuals are in that yellow zone, oftentimes their physicians will say, "Well, increase your dose of inhaled steroids to try to prevent it." The real question is, is that beneficial?

Individuals in the yellow zone were instructed to either quadruple or quintuple their dose of inhaled steroids. In the kids between the ages of 5 and 11, increasing it dramatically didn't really help. In the adolescents and adults, it decreased the development of acute exacerbation by only about 19%.

Elizabeth: But as we talked about before, acute asthma exacerbations can be life-threatening. Seems to me that with the plethora of pharmaceuticals we have out there for trying to manage this condition, what do you think?

Rick: First of all, we need to make sure people are being optimally managed. We need to make sure they're compliant with their medications, because one of the reasons people have asthma exacerbations is they're not really compliant. They're feeling well so they stop their medications. We should focus on prevention as well. People exposed to allergens, stress, or anxiety, or exposed to air pollutants can also exacerbate these as well. When people are in that yellow zone, people were put on oral steroids or they need to see a healthcare provider to receive parenteral therapy.

Elizabeth: On that note, I'm going to, of course, talk about the Pediatrics study on the dangers of e-cigarettes on the blog this week. That's a look at this week's medical headlines from Texas Tech. I'm Elizabeth Tracey.

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