This episode is sponsored by Grifols.

In this special sponsored episode, Dr. Thomas Ardiles, a pulmonary and critical care physician and medical director with Grifols, breaks down everything you need to know about alpha-1 antitrypsin deficiency. Discover why this genetic disorder often goes undiagnosed, its impact on lung and liver health, and the importance of early screening and diagnosis. Explore the benefits of comprehensive testing, the latest treatment options, and why raising awareness of alpha-1 is essential, despite its rarity.

VISIT SPONSOR → https://KevinMD.com/alpha

SUBSCRIBE TO THE PODCAST → https://kevinmd.com/podcast

Transcript

Kevin Pho: Hi and welcome to the show where we share the stories of the many who intersect with our health care system but are rarely heard from. Subscribe at KevinMD.com/podcast. Today we have a special sponsored episode from Grifols. Our guest is Thomas Ardiles. He’s a pulmonary critical care physician, and he’s the pulmonary medical director at Grifols.

Today’s topic is Understanding alpha-1 antitrypsin deficiency: What you need to know. Find out more at KevinMD.com/alpha. Thomas, welcome to the show.

Thomas Ardiles: Thank you, Kevin. Pleasure to be here.

Kevin Pho: So, let’s start by briefly sharing your story and journey that led you to where you are today.

Thomas Ardiles: Right. As a pulmonologist, you know, we all start to gravitate to an area of injuries, right? And in my case, I always gravitated to the early disease patients, right? Asthma and COPD are very interesting diseases that we have made quite a bit of progress over time. And, you know, taking care of very advanced disease and patients with COPD naturally led me to start finding patients with alpha-1.

And that’s how I started learning and realizing that there is quite a bit of potential of that we can do for the patients with alpha-1 and COPD.

Kevin Pho: And for our listeners who might not be familiar, what exactly is alpha-1 antitrypsin deficiency?

Thomas Ardiles: So, alpha-1 antitrypsin deficiency is a genetic disease, right? You are born with this. There’s nothing you’ve done wrong or you chose by yourself. And the way it makes you sick is that if you have the deficiency, your body does not have the genes to make a particular protein called alpha-1. So, when your body cannot make enough alpha-1, it is susceptible to certain inflammatory insults, right?

I always say, for example, if you hit your ankle against a curb, it will naturally swell up, but at some point, inflammation does stop, right? So our body has a way to regulate inflammation. And alpha-1 is our body’s natural anti-inflammatory. So if you put that into the lungs, for instance, right? If you get a cold and you don’t have a way to stop the damage from a cold, it could be much, much more exaggerated damage if you don’t have a way to stop that.

Kevin Pho: And why is it important for people to be aware of and think about alpha-1 antitrypsin deficiency?

Thomas Ardiles: So, when we look at a disease, as you know, it’s usually a combination of both your genetic predisposition and your environmental factors, right? So, if you don’t know that you are at risk or you have alpha-1 deficiency, you really don’t have the complete picture, right?

So, if you’re a pulmonary patient and you just don’t respond to treatment or you realize that, you know, everybody in your family is sick. So, what are we missing here? Right? So it would give you the complete picture of your disease.

Kevin Pho: What are the common characteristics or signs that an alpha-1 patient might exhibit?

Thomas Ardiles: This is a very good question and what leads to the need to have this conversation, right? I think one of the myths of alpha-1 is, you know, what little we had taught in medical school, right? Oh, I can spot an alpha-1 patient if I see one. Well, that really isn’t true, right? We know that alpha-1 patients present like any other patient with COPD or asthma, right?

A lot of them are told they had asthma as a child, and because they start having respiratory symptoms, you know, cough, flare-ups, they don’t get well after a cold, and they start developing lung disease. So, the symptoms really overlap very much with what we know of other lung diseases like asthma and COPD.

So, it’s really hard to distinguish it unless you test for it.

Kevin Pho: And how is alpha-1 antitrypsin deficiency tested or screened for?

Thomas Ardiles: So, as we mentioned earlier, it is a genetic disease. So, we have to find either the defective gene or the consequences of a defective gene, right? So, there are three main ways to test for it.

Finding the protein that the gene codes for, or the gene makes, it would be checking for an alpha-1 level, right? So, that’s one way to test for it. Another way to test for it is to actually test for the protein itself to look in for what we call the phenotype. And that is a technique that’s a little more complicated to do, but it can be done.

And this, there’s another way which we advocate for because it’s a little more accurate, is to look for the genotype, is to actually look for the specific defective genes for the disease.

Kevin Pho: And who should consider getting screened for alpha-1?

Thomas Ardiles: So, as I was saying before, most important is to recognize that patients with COPD or refractory asthma, you know, the asthmatic that’s just not doing well, can have alpha-1 deficiency, right?

So, most professional organizations like the American Thoracic Society, the COPD Foundation, they recommend that all patients with COPD should be screened for alpha-1 and all the patients with refractory asthma, right, your asthmatic that just doesn’t do well, doesn’t respond well to treatment, or patients that have persistent obstruction on the pulmonary function tests.

Or family members with alpha-1, all those patients should be screened.

Kevin Pho: And what are the typical costs associated with testing for alpha-1?

Thomas Ardiles: So, typically, if there is a patient with symptoms and there is the indication to screen, most insurances will cover the cost of screening through commercial tests.

So, there’s, you know, it might be, you know, the complexity of our care, they may be billed to the patient or whatnot, but some insurances will cover the testing for it. But there’s one alternative that we can offer, which is a screening test in which we can test for your genotype through our alpha ID program.

Kevin Pho: So, I’m a primary care physician, as you know. So, give us a picture of a typical patient in my exam room that may trigger me to think of alpha-1. What would a typical patient look like?

Thomas Ardiles: Right. So, we are trained to think of, you know, your typical patient would be the patient who is younger with advanced lung disease, right? And the problem is that, when I could show you a picture of how scattered they are in the disease spectrum and pulmonary function tests. So, that’s why one of the myths that we say is that you can’t really spot an alpha-1 when you see one. That’s why we’d really recommend screen all patients that have COPD.

Because you really can’t spot one when you see one. And it becomes a part of your routine, you know, it’s a box to check, you know.

Kevin Pho: Now, once tested, who has access to the results of an alpha-1 antitrypsin deficiency test?

Thomas Ardiles: So, if you go through our program for our alpha ID kit, the results are strictly confidential and they’re only available to you and your physician.

Kevin Pho: And how many alleles are typically screened for in alpha-1 testing?

Thomas Ardiles: So, this is a very interesting question because, you know, when I trained and I only learned about the classic ones, right? The S and the Zs. And so most commercial places that are not specialized in this will test for the most common alleles, which would be the normal M, the S variant, and the Z variant.

Right. And we’ve learned now that there are a lot more alleles. So, we can really have a more comprehensive evaluation when we test for more alleles.

Kevin Pho: And what are the benefits of screening for all 14 alleles related to alpha-1?

Thomas Ardiles: So, as I was saying, the more we look, the more we find. So, we have been screening for a long time. Our screening program in the U.S. has over a million patients that have been screened, and we’re seeing that about 15 percent of people have an abnormal allele, and obviously not all of them have severe disease. But another interesting thing that we’re seeing is that since we have identified what we call rare alleles, which are the 14, we’re finding more and more patients, right?

So, the accuracy of diagnosis increases significantly by checking for all the potential variants.

Kevin Pho: And why is it important to look at genotype versus serum levels when assessing for alpha-1?

Thomas Ardiles: Right. So, the serum levels of alpha-1 tend to go up and down. So, if you get sick, your levels naturally go up because it’s what we call an acute phase reactant.

Right? So, if you are not feeling well or you have a cold, you may have a slightly increased level and you may think that somebody doesn’t have a real deficiency and you may miss somebody that has deficiency just because you caught them in when they were sick. And also, if you have a level that doesn’t appear to be significantly abnormally low, right, you may miss the opportunity to identify that person and also that, and find one person also helps you follow up with their families as well, right?

So, there might be implications for the family by missing a diagnosis.

Kevin Pho: And what is the significance of knowing that someone has alpha-1 antitrypsin deficiency?

Thomas Ardiles: I personally think that it completes the picture, right? You know, you now know that you have a genetic predisposition to get sick, right? That your lungs are the organ that gets primarily affected, right?

So, let’s say we screen somebody and we find that they have, they are a carrier or they have the disease. And then they realize, you know what, all my children smoke, right? And then that person convinces them to get tested and they all get tested and they also realize, oh, I carry the gene too. The chances of all those three quitting smoking just went up through the roof because we know from studies and also psychologically, those people know, you know, I am predisposed to have lung problems, right?

So, the motivation to have lifestyle changes increases.

Kevin Pho: And given how rare alpha-1 is, why is widespread screening still so recommended?

Thomas Ardiles: Maybe a better way to ask the question would be to say widespread screening of all our patients with COPD, right? Because it’s one of the things that when you screen somebody, let’s say for colon cancer, right? You send them for a colonoscopy, really hoping they don’t have colon cancer, right? But, you know, it was the right thing to do, right? Check the box. You’re good. Let’s see what happens in 10 years or whatever period is appropriate.

So, I think it’s important to know that the person, your patient with COPD or with refractory asthma does not have a genetic predisposition, right? It’s following guidelines and recommendations, right?

Kevin Pho: So, once a patient is diagnosed with alpha-1, just in general, talk to us about the treatment options that are available. And if patients who have died, do all of those patients require treatment?

Thomas Ardiles: So, I think once a patient has alpha-1 and they need to be obviously seen by somebody with expertise, and then they need to see if they qualify for treatment, right? And the treatment is complementary to the treatment of their underlying COPD, right? So, you have somebody with COPD, they need to continue the treatment with COPD, for COPD, I’m sorry. But if they also have a severe deficiency and you see that they have, you know, emphysema, they would qualify for what we call augmentation therapy.

Kevin Pho: And in terms of these types of treatments, are you looking for an academic medical center? Do most community pulmonologists offer treatment for alpha-1?

Thomas Ardiles: So, a great resource to get connected to an alpha-1 specialist is through the Alpha One Foundation. They sponsored what we call CRCs, which are centers of excellence. So, if you go to their website, you can find the CRC that’s closest to your region, where you can find a specialist that treats with alpha-1.

Kevin Pho: And let’s end with some of your take-home messages that you’d like to leave with the audience.

Thomas Ardiles: Yes, thank you again. I would like to say that alpha-1 is not as rare as we think it is, right? We like to say that it’s rarely diagnosed. And I would plead with the audience that if you have patients with COPD or refractory asthma, just test for them, right? Testing is easy. It’s very available.

And just check that box, right? Every guideline tells you to do it. Your patient will appreciate to know that you are essentially, you know, turning every stone to understand their disease, right? So, that’s for them to know if they have that genetic disposition or not. And then, you know, I think everybody will feel better caring for the patient in a better way.

Kevin Pho: Thomas, thank you so much for coming on the show.

Thomas Ardiles: Thanks for having me.