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Melanie Cole (Host): Welcome. Here to tell us about the Alpha-1 Clinic at UAB Medicine today is my guest, Dr. Mike Wells. He’s an associate professor in pulmonary and critical care medicine at UAB medicine. Dr. Wells explain a little bit about Alpha-1 and the people that are at risk. Is this disease underrecognized?

Mike Wells, MD (Host): Thank you for having me. So, yeah, so the – your first question about what exactly is Alpha-1 antitrypsin deficiency. So, it is a genetic disorder. It’s one of the most common genetic causes for chronic obstructive pulmonary disease or emphysema and it’s characterized by an abnormal production of this alpha-1 antitrypsin protein by the liver. And so, under normal circumstances, the liver makes the protein and then it goes to the lung and kind of helps sort of clean up the lung from lung damage that may occur in response to the environment or infections or other things. And so for patients who have alpha-1 antitrypsin deficiency, this protein is not secreted normally and it is misfolded in the liver which can accumulate in the liver and can lead to some liver damage and liver destruction, but also reduces the overall amount of alph-1 antitrypsin that circulates in the blood. And ultimately this can lead to – if there is a low amount of this in the lungs it leads to kind of an unchecked amount of inflammation that goes on in the lungs and puts people at risk for emphysema or other lung conditions that are not necessarily in response to cigarette smoking. And it is something that because of it, it’s a genetically inherited condition, it tends to affect either – it can affect – it can present in childhood, typically with liver disease or in patients that are as young as 30-years-old tend to start manifesting signs and symptoms of chronic lung disease. The estimates right now are that between one and 2500 and one and 3000 Caucasians in the US or at least – may have alpha-1 antitrypsin deficiency, which is kind of comparable to the rates that are seen with other genetic lung diseases like cystic fibrosis.

And I guess your third question was is it an underrecognized condition well I guess of course the answer is yes it is. We know that COPD and emphysema are highly prevalent in the United States and affect up to 24 million people and alpha-1 accounts for between one and three percent of those patients. And even within those people, most of the one to three percent we believe is probably underrecognized and the actual number of alpha-1 patients with alpha-1 may actually be higher than that.

Melanie: So interesting and Dr. Wells you answered my first four questions as well. So, that was an excellent description. Thank you so much. Now speak about who should get tested. What does testing look like and tell us about the issue that could rise and what some of the results of this testing could have an effect for the patients’ lives.

Dr. Wells: Okay, yeah. So, testing is absolutely essential and critical to the diagnosis and especially because it’s so underrepresented; the current recommendations by the American Thoracic Society and the other COPD groups and the Alpha-1 Foundation is that any patient that’s ever been diagnosed with COPD or emphysema should be checked for alpha-1 antitrypsin deficiency at least once. Other recommendations are that patients that have chronic asthma, that have a family member that has been diagnosed with alpha-1 antitrypsin deficiency or people that have chronic liver disease; should all be checked. There are some other kind of rarer conditions that if a patient were to have these; they should get tested as well and those would include other lung conditions like bronchiectasis which is an enlarging of the airways or a skin condition called panniculitis which is pretty rare or other rare conditions like vasculitis or problems with I guess vasculopathies and things as well as liver cancers.

So, again those are less common causes but it certainly can associate with alpha-1 antitrypsin and so in order to get tested; well I guess kind of taking one step back and just talking about the genetics of the condition. So, I mentioned earlier that under normal circumstances, this alph-1 antitrypsin protein is made in the liver. For patients who are normal, who don’t have alpha-1 deficiency; they have two copies of the genetic allele called MM and so that means that these patients don’t have any – they don’t have an alpha-1 disorder and do not carry any altered alpha-1 genetics. This is sort of coinherited from patients and so you get one M copy from your mother and one copy from your father. The other condition that’s most commonly associated with this misfolded protein is something called a Z-protein and so if you have one copy of a Z and the other copy is an M, you are considered a carrier and these patients tend to have kind of a mild to moderate increased risk for symptom development and may lead to emphysema and then probably the most severe and the most well-characterized is something called ZZ, so meaning that you got one copy of a Z from your mother and one copy of the Z from your father. So, all of the alpha-1 protein would get sort of misfolded in the liver and lead to some liver damage, but then would have very low circulating blood levels of alpha-1 antitrypsin.

And these patients are at pretty severe – pretty high risk for developing emphysema and then you can also imagine they are also at increased risk for chronic liver injury and cirrhosis based on I guess where it’s being retained. There are some other genetic things that can happen as well, something called an S which is kind of an intermediate form or I guess intermediate severity between being normal and having a Z. So, we do see – so I guess in the spectrum of things, and kind of summarizing so if you are normal and you have two copies of the normal; you are considered an MM and that means you are in no increased risk for lung or liver damage. If you are an MZ meaning you have one normal allele and one abnormally folded allele you do kind of have a mild to moderate increased risk for symptoms, and that’s considered a carrier. There is also a carrier that’s an MS meaning you have one normal copy and one S copy and so this is maybe a little bit milder presentation than the MZ patients and then the true alpha-1 antitrypsin deficient patients are either a ZZ meaning they have two copies of the Z, one from the mother and one from the father or an SZ and so these are the patients that are at highest risk for lung and liver injury.

So, a lot of the genetics and the inheritance and things are very complex and complicated, but I guess fortunately, the testing is very easy. Like I mentioned earlier, the recommendations are that patients with any of those presenting signs or chronic illnesses be evaluated at least once and this is done through a blood test. There are several different assays that can be done. Some can be just a routine blood draw. There are others that can be done through just a finger prick dry bloodspot test and depending on how the tests are done and where they are done; the typical turnaround time can be just a couple of weeks before you get an answer for I guess the genotype.

Melanie: So, Dr. Wells based on the risk for lung and liver disease; what does this mean for the patient in terms of work, insurance and what do you want primary care providers to do? What role do they play in helping with lifestyle modification and behaviors, smoking cessation, secondhand smoke, alcohol consumption, all of these things that go along with recognizing that somebody has this gene?

Dr. Wells: Right. So, yes, I guess the recommendations are that once a patient has been diagnosed with alpha-1 antitrypsin deficiency or even being a carrier for alpha-1 antitrypsin; lifestyle modification, work modification if necessary, things like that are kind of the first major common recommendations. And so, smoking cessation is first and foremost the primary thing that we work on, not just for alpha-1, but for any patients, especially those with chronic lung disease. There are patients who are lifelong nonsmokers that can develop emphysema just based purely on having alpha-1 antitrypsin deficiency. But we do know cigarette smoke increases that risk tremendously. Secondhand smoke, other things can lead to this chronic inflammation that can also increase the risk for emphysema. I mentioned at work. I guess that is very dependent on I guess the type of work and career that the patient has. If their job requires a lot of exposure to dusts and coal or other things like that or work in a chemical plant or something; they may need to talk with their occupational health people at their company and make sure they wear protective clothing and things like that. Otherwise, we, ideally want to minimally impact work as much as possible. There are some studies out there that do show that other environmental pollutants, ozone and things like that can also lead to kind of worsening of the lung condition like an exacerbation – can precipitate exacerbations or things kind of periodically. But those are kind of the major things.

You mentioned alcohol and that’s something that can be a sensitive topic for some patients, but we do know that the damage from chronic alcohol use even at lower amounts than kind of what’s recommended by the NIH and other groups can still lead to some subtle liver impairment in patients that have alpha-1 antitrypsin deficiency, particularly those that are ZZ patients.

And then I guess the last thing would be just like we recommend for all patients just developing an exercise program and being active as much as possible. It’s not only good for lung health and liver health; but just health in general.

Melanie: Tell us about the Alpha-1 Clinic at UAB Medicine Dr. Wells and what type of providers are involved? Tell us about the multidisciplinary care you have got going there.

Dr. Wells: Yeah, absolutely. Absolutely, so, the Alpha-1 – we are an Alpha-1 Clinical Resource Center that’s recognized by the Alpha-1 Foundation. We provide screening tests for patients or for family members of patients who have been diagnosed with Alpha-1 antitrypsin deficiency and then we offer comprehensive evaluations including history physical, some of the medical testing and therapies that go along with having Alpha-1 antitrypsin deficiency. We collaborate closely with our hepatology group here so if there is any signs of liver injury, liver damage, like I said we work really closely with them and try to make sure that we are addressing any need whether we are aware of it or not. And then we also can offer genetic counseling and things for people who have questions and are considering things like insurance and family planning and other conditions.

Melanie: Such an interesting topic Dr. Wells. Thank you so much for joining us. So, do you have anything further? What would you like other physicians to know about alpha-1 and managing this or testing their patients, or counseling their patients about getting tested?

Dr. Wells: Yeah, so I think the main message is that it is an underdiagnosed condition and it’s probably more common than what we appreciate and that we should be actively screening for this in any of our patients with chronic lung disease and for patients who are family members of those that have a known diagnosis of alpha-1 antitrypsin deficiency. One of the things I didn’t mention before is there are treatments out there that can lead to some improvements in lung function and the testing and the screening tests are very easy and simple and minimally invasive and so, I would encourage everyone to think about alpha-1 and to check patients for alpha-1.

Melanie: Thank you so much Dr. Wells for coming on and explaining alpha-1 to us and sharing your expertise and telling us about the Alpha-1 Clinic at UAB Medicine. Thanks again. A community physician can refer a patient to UAB Medicine by calling the MIST line at 1-800-UAB-MIST. That’s 1-800-822-6478. You’re listening to UAB Med Cast. For more information on resources available at UAB Medicine you can go to www.uabmedicine.org/physician, that’s www.uabmedicine.org/physician. This is Melanie Cole. Thanks so much for listening.