Dr. Cori Cross: Welcome to Ped's Cast, a podcast brought to you by Children's of Alabama. I'm your host, Dr. Cori Cross. Today we are joined by Dr. Ahmed Asfari, who is an Assistant Professor in the Department of Pediatrics and the Division of Cardiology at the University of Alabama at Birmingham. He is also a Cardiac Intensivist at the Congenital Heart Center at Children's of Alabama.

Dr. Asfari, thank you for being here with us today.

Ahmed Asfari, MD: Thank you for having me.

Host: Lung injury is a common complication in children following cardiac surgery and mechanical ventilation is often required to support these patients for hours to days in the ICU afterwards. But the severity of the lung injury can vary greatly by patient and being able to predict which patients are at a higher risk and may require respiratory support is really crucial, but we can't really do that very well, until now. So my understanding is your heart center has made a huge breakthrough towards making this possible. Can you tell us a little bit about the novel blood biomarker that your center recently discovered and how it correlates with lung injury?

Ahmed Asfari, MD: Absolutely. I mean, you said exactly what's going on or as part of the care that we provide for babies, infants, neonates, children with congenital heart surgery. Part of the care is supporting them with mechanical ventilation or different type of oxygen supply.

And, almost all of them they're exposed to this kind of acute lung injury after being on the heart and lung bypass machine now. Before, we used to, it depends on our clinical assessment, exam, and then also the numbers that we have on the ventilator whenever the patient is on ventilator to say, the patient has maybe moderate or severe amount of lung injury. But as our field advanced and as all other aspects of care, either like heart failure or infection or inflammation, we depend on lab tests and biomarkers.

So there has been nothing like this in regards to acute lung injury, especially, for our patient population with congenital heart surgery. In general, nothing like this for acute lung injury for other reason like pneumonia or sepsis or ARDS. So what we found that there is a specific biomarker, that when we tested in the blood of patients with very long mechanical ventilation duration and compare them to patients with short duration of mechanical ventilation; we found that the level of this marker goes down, especially within two days after surgery. So, this is the first time that it's reported and we started about this, we went initially with no known biomarkers.

So, we started with very general testing. We used Serum Empire's proteomic analysis where we tested samples for patients in each group, the group for patients with long mechanical ventilation versus the one with short mechanical ventilation, and we analyzed their serum plasma for around 2,000 protein, and the top head or the top protein that was variable or was significantly different, between the two group was the proteoglycan 4, or as commonly known as lubricin. So this is the first time that this finding is reported in the nation or even for adult with acute lung injury.

Host: That's amazing. And so I think you touched on this, but could you explain to us how your biorepository really aided you in being able to do this? Because from what I understand, you had to look at quite a few patients to be able to see where the similarity was or where the difference was between those who had been on prolonged mechanical ventilation versus those who had not.

Ahmed Asfari, MD: Yes, so for our patients, all patients that we admit to our heart center for heart surgery, we consent them for a blood sample to be stored. And all patients less than eight years, we collect their blood sample. And it's not just at one time point. We do it before by being on bypass and after being bypass at several time point.

Host: And this is what you call your biorepository, right? It's basically all of the storage of this blood and this information.

Ahmed Asfari, MD: Exactly. And we have samples goes to back to 2012. So we have stored their samples and these samples, we consented the parents for it. And we can run tests either serum or gene testing also. So we have this very, very important ability that we can go back and test all our patients that we have.

We started initially with just testing these samples at five time points before bypass, after bypass, at zero hour, four hour, at 12 hour, 24 and 48 hour. And we saw that trend, for initially limited number of patients, only for an ensemble. But that was, we used the experience that we have at the UAB with Dr. Mobiley, James Mobiley Lab, where he's world expert in the serum N piaspotumic analysis. And we were able to identify this biomarker. Then we did even further validation where we did ELISA testing for this biomarker and we've on large number of patients 20 patients in each group at two time point before bypass and 48 hour after bypass and we found that patients with longer duration of mechanical ventilation that they have lower level of this serum biomarker. So this results were published in the Critical Care Exploration Journal, and after we published this, the result of our study, Dr. Tannin Schmidt from the University of Connecticut, which he's also Associate Professor at the University of Connecticut School of Bioengineering, he reached out and he's a world expert in this specific protein.

He has been doing multiple tests about this protein and has been doing animal study about it, and he has developed a specific ELISA testing to do it at commercial basis. So we validated our results further at his lab. We used his lab, and his lab was blinded to our patients like if they are from the study versus the control group and we did the testing on 40 further patients.

So we had for each patient, two samples before and after bypass and our results still, were the same. And we recently published that results in the Translational Pediatric Journal. And, we're going now through the third stage of our research.

Host: That's amazing. So you already knew that the proteoglycan 4 biomarker existed, but prior to your study, you hadn't realized the importance it had in predicting acute lung injury after bypass. Is that right?

Ahmed Asfari, MD: That's exactly right. You know, when I started, I did not know the end result of our test. We weren't really exploring, and it was completely organic research study that step by step, experience and experts from the nation, you know, gathered to do this testing.

Host: So how does your discovery change the landscape for care? And I'll extrapolate a little bit in what I'm trying to say. When you see the biomarker go down in these patients, you can then predict that they're going to have lung injury or they're already starting to have lung injury and that's why the biomarker goes down?

Ahmed Asfari, MD: So, at this stage is only association, but the care for pediatric patients with heart surgery can be really complicated and extra information can help. So, when we have a patient with acute lung injury, most often it's the acute lung injury is as a combined of respiratory failure and heart failure, but how much is respiratory failure compared to lung failure compared to heart failure is really unknown and having the ability in the future, having the ability to have serum biomarker that we can use to grade the level of acute lung injury will be extremely helpful, especially for our patient population.

Host: And that's not just true for the immediate future after their surgeries, but also for their lifetime. This is probably something that you can follow to see and sort of get a look at what's going on inside, correct?

Ahmed Asfari, MD: Yes, absolutely. At this time, we're limited in our testing with the sample that we have, which is, it goes in only to two days after surgery, but currently we expand our testing to include larger number of patients and patients with different age group and cardiac physiology and cardiac anatomy on different type of surgery and on bypass and off bypass.

So we have total of 200 samples for 100 patients. And once we finish this analysis that we're doing now, and the next step of our research will be to doing it prospectively, really, looking at the patients, healthy children, and then also patients with acute lung injury with different physiology, not just heart disease, and over a longer period of time to investigate and verify again our results.

Host: That's very exciting for the future. Do you foresee that this biomarker will be available in all hospitals and will become almost like a gold standard?

Ahmed Asfari, MD: We have very good potential to do that. At this point, through, like, two stages of validation, we found this association to be strong. Further testing, doing it at a different age as what we're doing now, doing it over a longer period of time, in the next stage and then also, doing it in different bodily fluids, like pleural fluids, tracheal aspirate fluids, urine sample, even can shine the light on that biomarker.

And then we can say, you know, what it can be like available, to be done at commercial bases. And then can be validated further with really large number of cohort. And then I think, you know, it has very good potential to be used at bedside.

Host: Yeah, the potential is extremely interesting. In summary, is there anything else you would like to share with our listeners today?

Ahmed Asfari, MD: I think just shine the light on the role of customized medicine for the future, like in 20 years or 25 years from now, we may have based on the several other biomarkers that we have, or we're going to discover, or the field, our field will discover; we can adjust our care that we provide for patients, based on these biomarkers and, it seems very hard reach, but it's doable in the future, in the near future. We are working now on another biomarker that can predict low cardiac output status after a heart surgery. So as we're talking now, there are other centers that they are thinking on the same wavelength and they're doing similar study about other physiology. So I think this, this kind of study and research is very important in the future to adjust the care that we'll provide for each individual patient.

Host: I couldn't agree with you more, Dr. Asfari. It's just so interesting where we are in science and really medicine right now that we're right on the verge of being able to provide personalized care based on what your body specifically needs or how it reacts to certain things. This has been such an interesting discussion. Thank you so much for sharing your expertise with us today.

Ahmed Asfari, MD: Thank you so much for having me.

Host: If you would like more information or to refer patients to Children's of Alabama, visit www.childrensal.org. That concludes this episode of Children's of Alabama Peds Cast. If you found this podcast helpful, please share it on your social channels and be sure to check out the entire podcast library for other topics that might be of interest to you.

Please remember to subscribe, rate, and review this podcast. Thanks for listening to this episode of Children's of Alabama Peds Cast. I'm your host, Dr. Cori Cross.