Blood Markers to Direct Lung Cancer Screening; Name Change for PCOS

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

This week’s topics include a name change for polycystic ovary syndrome (PCOS), whole blood for trauma, antibiotics for wheezing in kids, and blood markers to direct lung cancer screening.

Program notes:

0:37 Prehospital resuscitation with whole blood

1:37 Compared with blood components

2:35 Easier to store

3:19 Azithromycin in wheezing kids

4:19 Treated for 5 days

5:26 Name change from PCOS to polyendocrine metabolic ovarian syndrome (PMOS)

6:26 Consensus build

7:28 Improved accuracy of pathophysiology

8:30 Adjust policy, change international classification

9:15 Biomarkers to direct lung cancer screening

10:15 Participants from several countries

11:15 What are barriers to those with a smoking history

12:24 End

Transcript:

Elizabeth: Should we administer whole blood in the field for trauma victims?

Rick: Do preschoolers who come to the emergency department [ED] with wheezing benefit from antibiotics?

Elizabeth: A new name for polycystic ovary syndrome.

Rick: And using biomarkers to direct lung cancer screening.

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, 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 Health El Paso.

Elizabeth: Rick, I’d like to turn to the New England Journal of Medicine first and I would like to talk about this prehospital resuscitation with type O whole blood for people who’ve experienced trauma and hemorrhage.

And as many of our listeners know, I have a chaplain role at Johns Hopkins, and so I see plenty of people in the ICU [intensive care unit] who have had this unfortunate experience of trauma. So, I’m very interested in this notion of, gosh, are there things we can do to help these people arrive alive at the hospital? And we have talked about a number of times over the years all kinds of things that EMS [emergency medical services] is now empowered to do in the field to help improve people’s chances of survival. And this is a study that’s looking at whether transfusion with whole blood versus transfusion with blood components has an impact on that survival.

So, this is a phase III study. There were 44 air medical bases in a 2:1 ratio who were empowered to use up to two units of whole blood in the field or, as indicated, blood components for prehospital transfusion in trauma patients. Their primary outcome was death from any cause within 30 days after their randomization. They had 1,020 eligible patients who were transported to hospitals by the air bases, 715 of whom got the whole blood; 305 got the blood components.

Mortality at 30 days was just shy of 26% in the whole blood group and about 21% in the component group. What looks like a fairly significant difference actually was obviated when they took a look at other factors that were related to that analysis. So, it sure looks like when they look at this strategy of giving whole blood versus the components in the field, it’s probably not very beneficial and it sure does not result in a lower 30-day mortality than using the blood components.

There are upsides to using whole blood. It’s less troubling than it is — in terms of storage and availability to maintain that — than it is to keep the blood components on hand. Maybe because there’s really no difference between these two strategies, it might be better to transition to that.

Rick: Yeah. Whole blood has all the components in it and it also has volume, and in people in shock, both of those components are incredibly important. What they’re using is type O; it has very few antibodies in it, low anti-A and low anti-B antibodies titers. It’s easier to collect. It’s easier to store. Also, whole blood has a long shelf life. Although this study did not show that whole blood was better than the components, it looked like they were equivalent, and that’s still good news.

Elizabeth: Staying in the New England Journal of Medicine, let’s turn to the use of azithromycin in wheezing children.

Rick: Among preschool aged children, wheezing illnesses are a leading cause of hospitalization. They’re oftentimes treated with antibiotics, and that’s because observational studies have shown that, in kids that wheeze, they’re more likely to have three different types of pathogenic bacteria: strep pneumonia, Moraxella catarrhalis, and haemophilus influenzae. OK, well even though viral illnesses may be the cause of most wheezing episodes, that the bacteria contributes in some way and that treating the kids with an antibiotic — especially one that has anti-inflammatory characteristics, — may be beneficial. And that antibiotic, by the way, would be azithromycin or Zithromax.

So what these investigators did was a multicenter trial where they randomly assigned patients that were 18 to 59 months of age, presented to an emergency department with moderate to severe wheezing, and then received either azithromycin once daily for 5 days or placebo. And after doing the study in 840 kids, the antibiotics did not benefit the kids with regard to severity of asthma, duration of asthma, or any of the secondary components.

Let’s look at the kids that test positive for those bacteria that I mentioned and those that test negative to see, well, maybe the kids that have the bacteria may respond, but in fact, they didn’t either.

Elizabeth: I’m going to ask questions about other strategies like inhalers or anti-inflammatories in these kids.

Rick: Those would obviously be first-line therapy. The most common cause for wheezing in these kids is either allergies or a viral illness. And what the study shows is that routinely giving these kids antibiotics doesn’t help, but either treating the allergies or giving bronchodilators, as you mentioned, can be beneficial in terms of relieving symptoms and the secondary outcomes.

Elizabeth: I would note that this is extremely troubling to bear witness to when a kid presents with this in the ED.

Rick: Yeah. I mean, it’s scary. Fortunately for most kids, they do well. Know there are about 30,000 admissions each year in the United States for recurrent asthma or wheezing.

Elizabeth: I would advocate for prophylaxis here if that’s possible. Let’s turn to The Lancet. It’s not a study. It is basically a report of a consensus, an international consensus that is going to change the name of polycystic ovary syndrome, or PCOS, to polyendocrine metabolic ovarian syndrome, or PMOS.

I thought it was uplifting for a number of reasons. What they were able to do was get together this international group of experts in this particular syndrome and survey them multiple times — not just the expert opinions, but also patients who have this — and say, “What are the primary deficits that give rise to this syndrome? Is there a more appropriate way to name this?” And that’s practical because it helps to improve the accuracy of the diagnosis as well as the management. Then they went out and got money in order to help propel this thing forward.

So, I thought this was just a powerful example of people coming together and saying, “Look, we’re not going to agree 100%,” because they did not get 100% agreement on this transition to PMOS. However, they got the vast majority of people to agree. They also got the World Health Organization to agree and they’re going to change the coding relative to this condition.

Interestingly, what was previously called polycystic ovary syndrome affects one in eight women. There’s significant delayed diagnosis, fragmentation of care, and stigma that’s been associated with it. They got 56 leading academic clinical and patient organizations involved in this process. They had 14,000-plus people who have the condition and multidisciplinary health professionals from all world regions who were involved.

They surveyed them on what are the terms that would reflect the condition’s multisystem pathophysiology. Polyendocrine metabolic ovarian syndrome was the consensus new name; they’ve improved accuracy by omitting cysts and by capturing the endocrine, metabolic, and ovarian dysfunction that are a part of this particular syndrome. So I, for one, applaud this effort.

Rick: Yeah, I know, it’s confusing when you tell the patient that they have polycystic ovarian syndrome and they don’t have cysts. Pathologic ovarian cysts really are not a feature of the condition, but it does have endocrine, metabolic, and reproductive disorders, psychologic disorders, and even dermatologic features. That name by itself — polycystic ovary syndrome — indicates it’s one organ. It’s just the ovary. So, the doctor thinks that that’s the major feature and doesn’t recognize these other things. It sometimes delays the diagnosis.

Elizabeth, I was kind of surprised you chose this because we almost always do studies, but this talks again about a global way of changing it in a very strategic way. And oh, by the way, they say it’s going to take about 3 years to do all this, disseminating it to the public and academics. How do you adjust policy and research alignment, change the international classification, then provide the guideline?

I think one of the reasons why Lancet published it is this could be a roadmap for how other things need to change in an international way as well.

Elizabeth: Exactly. And just such an amazing cooperation among all these groups with different vested interests in the outcome. I do have to note that they did ask all of their participants before they did their first workshop to complete a code of conduct that covered expected behaviors, confidentiality, and agreement to respect publication embargo and streamlined communication and messaging.

Rick: When you think there are about 14,000 people involved in this, that was pretty amazing.

Elizabeth: Kudos to these people. On to your next one.

Rick: This one’s in JAMA — using biomarkers to direct lung cancer screening. This was an unusual study, Elizabeth, in that they used biomarkers not to identify cancer, but actually to direct lung cancer screening.

Lung cancer screening has been effective in high-risk individuals in detecting early cancers that could be responsive to treatment. The USPSTF [U.S. Preventive Services Task Force] criteria require you be 50 to 80 years of age, at least 20 pack-years of smoking, and no more than 15 years since cessation of smoking. Those are individuals that undergo low-dose computed tomography scanning.

About a third of patients that develop lung cancer in the future don’t fall within those guidelines. We want to catch other individuals that may not otherwise have been identified. Can we use biomarkers, proteins in the blood, to identify which individuals are at high risk of developing cancer over the next year? Those are the individuals that we want to make sure we extend screening to.

They looked at cohorts in the Lung Cancer Cohort Consortium and they recruited research participants in the U.S., Europe, Asia, and Australia between 1985 and 2009, and they followed them through 2021. And then they used blood to assess 12 different proteins associated with lung cancer. They used this panel to train about 2,000 patients to estimate the absolute risk of being diagnosed with lung cancer based upon the age, smoking history, and the proteins. They used another cohort with about 1,700 individuals to test the validity.

When they use this risk model, they’re able to capture about 85% of lung cancer cases that would develop over the next year compared with about 63% just by the criteria I mentioned. And oh, by the way, there’s also another screening thing that just is a questionnaire. They only identified about 70%. Unfortunately, it was less predictive 2 or 3 years down the road.

Elizabeth: First of all, I would like to point out that, I think, didn’t we talk about the recommendations about those with a 10-year pack history? So, that has been reduced to try to capture more of that population.

I just can’t understand how somebody who has a history of cigarette smoking would not go in and have spiral CT to see whether or not they have any suspicious lesions. So, when I move that outward, I wonder if anybody’s going to be willing to have this kind of screening that you’re describing either. If the model is really the ostrich model — I don’t want to pay attention to this until it rears its ugly head and I have to — then I’m not sure either method is going to overcome the reluctance.

Rick: Yeah. The reason some individuals don’t have screening is because they don’t fall within those “guidelines.” If those criteria fail to identify approximately one-third of future lung cancer cases, you just miss them. And what this protein test was, it’ll widen it a bit. In fairness, this is an exploratory analysis, needs to be confirmed in larger studies.

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.