I am an Alpha. I was diagnosed in 1996, and I am a ZZ. I have two questions for you. The most common complaint that we Alphas have is “inflammation.” So why aren’t the Alpha-1 docs and/or scientist/researchers doing something to try to find some kind of medicine besides steroids, antibiotics, NSAIDs and anti-inflammatory meds that some of us who are on blood thinners cannot take, and we have to turn to pain medicine for help. Why hasn’t anyone tried to get us help in that area?
The next is: stem cells. This could be our one and only shot for help. At least it will give us a chance to live a normal life for a little while. I haven’t had a normal life in almost 20 years, and I am sick and tired of taking steroids, antibiotics, inhalers, getting infusions, etc. Has anyone thought of using people with Alpha-1 for clinical trials for Darrell Kotton, MD, and his stem cell research? I would like to be one. I know you have said that it may be 10 years for stem cells to be out there, but Dr. Sandhaus, excuse me, stem cells are here. They are being used for all kinds of medical diseases, and they are working. The FDA [U.S. Food and Drug Administration] does see this. We just need someone to keep on it. There are a few institutes that are doing lung stem-cell therapy. Why aren’t the Alpha docs and scientists getting together to do the same?
Please help us.
A. I’m pleased to try and respond to your questions about Alpha-1. I suspect that my answers will be both informative and frustrating. The primary frustration is likely to be the apparent glacially slow rate at which medical research progresses, especially when viewed by someone suffering from the problem being studied.
With respect to inflammation, I’m not sure if you and I are talking about the same thing. All scientists working in Alpha-1 appreciate that the lung disease of Alpha-1 has an inflammatory component. In fact, the protein alpha-1 antitrypsin is one of the most potent natural anti-inflammatory agents known. Patients requiring augmentation therapy have been shown to have a dramatic drop in inflammation after starting augmentation.
But it sounds like you are speaking about some kind of pain you are experiencing. Pain is not a common condition associated with Alpha-1, so I’m not exactly sure what issue you are referring to that requires you to take pain medications.
With respect to stem cells, you must make a distinction between the charlatan “institutes” that claim to treat all sorts of disease by giving “stem cell injections.” None of these has been shown to be successful. They have many miraculous cures presented as patient testimonials but there is no evidence, especially in chronic lung diseases, that these do anything but empty patients’ wallets.
Real stem cell research, such as that done by Dr. Kotton, may well provide exciting new therapies for conditions like Alpha-1. It is not that we are holding these therapies back, but that there is still great concern that these stem cells will become cancer cells when injected into humans. As soon as the safety of stem cells can be assured, human trials will begin. I realize that some people with advanced disease may wish to risk taking a drug or treatment even if the safety has not been assured and I encourage you to contact Dr. Kotton and let him know of your willingness to participate in trials once they begin. But please be sure to evaluate both the likely risks and potential benefits before jumping into any study of a new approach.
I’m writing this note while sitting in a meeting of scientists, Alpha-1 docs, and the FDA to try and move therapies for Alpha-1 forward more quickly. Like you, I hope this meeting will lead to quicker approval of more therapies for Alpha-1.
Get full workup to evaluate multiple issues in MZplus
Q: I have an 18-year-old daughter who has had a complicated medical history. Upon looking into her medical records, I found she was tested for Alpha-1 and was MZ. She has had a chronic cough and gets upper respiratory infections often. I always thought her cough was unusual, but no doctor listens. I took her to a pulmonologist and he said it was a habit cough — I think that’s ridiculous! I asked for more labs and a level was done and it was 84. More recently another level was done, and its now 60. I’m not sure what that means. She also has unexplained elevated lipase and trypsin levels with no evidence of pancreatitis. She has a low albumin level. For a year-and-a-half I have been trying to piece this bizarre medical puzzle together. Could you please give me your thoughts and recommendations? I am desperate for her to be accurately diagnosed and tested.
A: You should be somewhat reassured that your daughter has the MZ genotype and a relatively normal level. Variations in blood levels of alpha-1 antitrypsin are not unusual. The vast majority of those with an MZ genotype never suffer any medical issues due to carrying a single abnormal gene.
Obviously, I can’t render an opinion on the care or the diagnosis of your daughter based on a simple email. The issues your daughter is experiencing require a more serious evaluation than she has apparently received. I’d suggest you consider making an appointment at an institution that specializes in working up multiple medical issues like this. My own institution, National Jewish Hospital, specializes in such work-ups. There are many patients with unexplained cough who have found an explanation and treatment by going to a center like mine. Often in a young adult, the cough can represent occult asthma or unappreciated gastroesophageal reflux. The other problems you’ve mentioned can be evaluated at the same time.
I hope this is of some help to you.
Cautions for child with FZ diagnosisplus
Q: My daughter, 18 months old, was just tested for Alpha-1 because my father has Alpha-1. My father had to get a liver transplant a few years back and his lungs are also very poor.We found out my daughter has a phenotype of FZ. I was wondering if you had any information related to this phenotype because it is not very common. Her levels are currently at a 92 and just wondering how serious is this going to be for her.
A: I’m happy to provide some preliminary answers. Your daughter will have many years to learn more about this condition. I have both good and not as good news for you about the FZ genotype of Alpha-1. First, I hope that your doctor or you have done additional testing to confirm her genotype. it would be a shame to raise concerns and then find out there was a lab error of some sort.
The FZ genotype is considered to be a severely deficient genotype, comparable to ZZ in terms of the risk of lung disease. The good news is that your daughter’s risk for liver disease is considerably lower than that for a ZZ individual. You might wonder how the FZ genotype results in a high risk of lung disease when the alpha-1 protein levels found are in the normal range. Unfortunately, although the F genotype yields normal levels of alpha-1 antitrypsin protein, the resulting F protein is dysfunctional and provides decreased protection against lung destruction.
The best news is that, with education and lifestyle choices, the risks of lung injury can be dramatically reduced. Just as in ZZ Alpha-1, many individuals with the FZ genotype can lead normal lives, with normal life spans, and no health problems from their Alpha-1 Antitrypsin Deficiency. Obviously, the most important thing is for your daughter to avoid cigarette smoke at all costs. That includes preventing her from starting smoking and also preventing exposure to second-hand smoke, especially at home. She needs to have any lung infections treated immediately and aggressively. And, when she grows up, she needs to avoid occupations that involve exposures to smoke, fumes, and/or dust.
I encourage you to learn more about Alpha-1. The Foundation can supply educational materials at your request and the Big Fat Reference Guide to Alpha-1 (the BFRG) is available online at alpha1.org/Alphas-Friends-Family/Publications/Big-Fat-Reference-Guide. Most of the sections referring to severe deficiency as it relates to lung disease will apply to your daughter. The sections about liver disease would not.
I hope this is helpful. The Foundation will be here to help educate your family. I hope that other family members have been tested for Alpha-1, so that they can have the head start at good health that your daughter now has.
Is lung volume reduction (LVRS) appropriate for Alphas?plus
Q: I am a British man, 38, a carrier of Alpha-1 (MS phenotype) with emphysema in upper lobes of both lungs and severe bullae [bullae are air-filled bulges or blebs in the lungs, sometimes found in emphysema – Editor] on upper lobes of both lungs. I have good lung function at present, 70% FEV1 scores and only get out of breath with heavy exercise. I quit smoking after 22 years on finding out four months ago I was an Alpha-1 carrier.
My specialist has recently sent me to see a surgeon to speak about lung volume reduction surgery (LVRS).
1. Is LVRS advisable for Alphas?
2. After LVRS, it seems that your situation improves for about five years, then goes back to how it was and continues to get worse. Is this the reason people don’t usually have it done until their lung function is lower than 50%?
3. Do the bullae grow back after LVRS?
4. Is it possible that the operation might not work and my situation can be made worse?
The surgeon said I do not need to have the operation yet. He said that if I have another collapsed lung (happened once in 1999 and possibly one four months ago, but nobody was certain) or if the bullae start growing or restricting my breathing more, then the surgeon would like to do it because if bullae grow too big it makes the operation more risky.
5. If I need the operation soon because the bullae grow or pop, then what happens in five years if I start to deteriorate? Will I then have to apply for a transplant because this will be the only option left? Can I have a transplant after a lung volume reduction?
A: Your lung disease probably has little or nothing to do with your Alpha-1 (MS) status. Lung volume reduction surgery (LVRS) does not appear appropriate for you (but other surgery might be indicated).
You have classic smoking-related emphysema. Perhaps your MS phenotype made the effects of cigarette smoke a bit worse. Another possibility is that you were born with blebs in your upper lobes that have been worsened by years of cigarette smoking.
While you would not usually be considered for LVRS, if recurrent pneumothorax (collapsed lung) is a problem, there are several surgical approaches that can prevent their recurrence. The options include “roughing up” the pleura using a scope inserted between the lungs and the chest wall, and bullectomy (removal of the bullae). Bullectomy in this situation could be considered a type of LVRS in that the bullae are removed surgically, usually using a scope (called VATS or video assisted thoracoscopic surgery).
Taking your questions in order:
1. Lung volume reduction surgery is often not the best approach for an Alpha with typical Alpha-1 related lung disease. This is because the type of lung disease that most ZZ Alphas get is basilar diffuse disease with a low diffusing capacity. Both of these (basilar diffuse disease and low diffusing capacity) make it likely that the outcome of LVRS will be worse than doing nothing. While there are a number of Alphas who do well after LVRS, they are far fewer than those who are turned away, have no improvement after LVRS, or die soon after LVRS.
2. There have been several long-term follow-up studies on LVRS, which have shown that the improvements can last for a short or long period but that in Alpha-1 patients, the improvements tend to be shorter. The improvements noted are much more dramatic in people with more severe lung disease, since the improvements tend to be modest. In other words, an improvement of 0.5 liters in someone with end stage lung disease (say an FEV1 of 0.5 liters to start) tends to improve someone’s life much more than an equal improvement in someone whose initial FEV1 is 4.0 liters (about 70% predicted in an average young man). LVRS tends to be a one-shot deal. It is extremely rare for a second LVRS to be done (I’ve never heard of one).
3. It is possible for new bullae to appear after LVRS. If the emphysema is due to smoking and the person has stopped smoking and most of the emphysema is removed during LVRS, it is not likely for the “emphysema to come back”. Usually, however, there is more emphysema in the lung than can be seen on an x-ray or CT, so there is usually some diseased lung left behind.
4. Yes. There is always a possibility that the surgery could make the situation worse.
5. LVRS does not prevent someone from having a lung transplant at a later date, although there is little indication that you will ever need a lung transplant. I know of no center in the United States that would ever consider an individual for LVRS or transplant who had a lung function that was 70% of predicted.
In family testing, genotype or phenotype better than just testing levelsplus
Q: My father recently was diagnosed as a carrier of Alpha-1 and his doctor recommended that my sister and I be tested. We had the test and my level was 104 and hers was 107. The normal range provided on the test was 90-200.
Should we consider having any additional testing done? Or are the levels considered normal and no further testing needed?
A: For family testing, where the goal is to discover whether siblings or offspring might be carrying one or two genes for Alpha-1 Antitrypsin Deficiency, we usually recommend checking a genotype or phenotype, rather than just a level.
The alpha-1 antitrypsin levels that you and your sister were given could mean that you have either two normal genes for Alpha-1 or one abnormal gene and one normal one.
Why would you want to know if you have a single abnormal gene?plus
Because there is a slightly increased risk of developing lung or liver disease, even with just one abnormal gene. Perhaps of greater importance, if you have children or are planning on having children, you may want to know so you will be able to determine the probability of passing an abnormal gene on to them.
For more information, see our web page on testing, or call the Alpha-1 Research Registry Program at the Medical University of South Carolina toll-free at 1-877-886-2383.
Alpha-1 “carrier” has early-onset emphysemaplus
Q: I am a 40-year-old female smoker, just diagnosed with mild emphysema. I am quitting smoking, of course! I asked my docs to test for Alpha-1. They reluctantly agreed.
My dad has pulmonary fibrosis. I also have a new intolerance to alcohol. It seems to make me quite sick now. Although I am not a drinker, I would like the occasional drink! I already have multiple health issues, autonomic dysfunction and coagulation abnormalities, and I am currently being tested for autoimmune illnesses. So, it will take a while before this gets sorted out.
The Alpha1 test results just came and I am a carrier — which I thought meant I was healthy. The Alpha-1 level is 26.8mm, phenotype is PiMZ, and genotype was not performed. So, if I am just a carrier, why do I already have emphysema and could this be related to the alcohol intolerance?
What exactly does it mean to be a carrier? My doctor wrote that I am a carrier but my blood level is normal. Then why do I have these problems? And do I need treatment? And should I have my liver investigated further?
A: It sounds like you’ve had an extensive workup at an academic center. Unfortunately, it also sounds like you are suffering from the conditions you’ve been diagnosed with. You were certainly correct to request the Alpha-1 testing.
The results present three possibilities.
The first, and the one that needs to be evaluated first, is that the results are incorrect. With coagulation abnormalities and the MZ results, it is important to be sure the result is correct. There is a rare Alpha-1 abnormality, the Mpittsburgh phenotype, which leads to a normal level with coagulation problems. It can sometimes be confused with the M phenotype. If you were PiMpittsburghZ, this is a severely deficient phenotype and should be treated.
It might be wise to send a blood sample to a national reference laboratory such as the Alpha-1 Detection Lab at the University of Florida with a note about the possible results.
The second possibility is that the results are correct (PiMZ) and that the combination of this mild deficiency and your smoking has led to your early-onset emphysema. People with an MZ phenotype have been shown to have about a 2.3 times increased risk of getting emphysema if they smoke, compared with the general population of smokers. In this case, smoking cessation and avoiding environmental risk factors is the treatment of choice.
The third possibility is that the PiMZ phenotype is correct and it has absolutely nothing to do with your early-onset emphysema. There are some people with entirely normal Alpha-1 genes who get early-onset emphysema. We assume that there are other genes involved that have yet to be identified in these people.
Some ZZ Alphas can keep normal lung function, stay disease-freeplus
Q: Does Alpha-1 (PIZZ type) always hurt the lungs?
If you’re healthy, exercise, don’t smoke, etc., are the lungs still being damaged regardless? In other words, is there any way to NOT lose lung function?
A: Under most circumstances, people with PIZZ Alpha-1 have plenty of circulating alpha-1 antitrypsin to protect the lungs and they are not being damaged.
Lung damage seems to occur only during times when the alpha-1 antitrypsin protein is harmed (as from smoking or other environmental exposures) or when the alpha-1 antitrypsin protein protection of the lungs is overwhelmed by a large number of white blood cells coming into the lungs (such as during pneumonia and other lung infections).
Therefore it is certainly possible for the lung to remain healthy and not lose lung function, even in PIZZ individuals. And we see this every day, because there are many adults with PIZZ who have no lung disease late into their lives.
Singulair, Tylenol are OK for Alpha-1 kidsplus
Q: My daughter has Alpha-1 and was diagnosed with asthma when she was three. Her pediatrician put her on Singulair as a preventive. Is Singulair safe for children that have Alpha-1? I am worried about its long-term effects. Also, I have always heard that Tylenol is unsafe for Alpha-1 children. Is this true?
A: There are no known problems with Singulair in Alpha-1 kids. Tylenol is OK when taken as directed. Make sure that the recommended dose is not exceeded. There are much worse risks in children from using aspirin than Tylenol, even in Alpha-1 kids.
Lung, liver symptoms call for Alpha-1 testingplus
Q: I am 51 years old, a female diagnosed with COPD about five years ago. I found this to be extremely odd as I have NEVER smoked in my life. However, I was raised in a home where both parents were chain smokers.
For the past two years I have had elevated liver enzymes, with no explanation. I felt intuitively that the two were somehow connected.
I do not drink alcohol and have never used illegal drugs. Except for the asthma/COPD and some osteoporosis, I am currently OK. My question is, how do I bring this up to my doctor, and am I better off seeing an allergy/asthma specialist that I met a while ago? Any guidance would be greatly appreciated.
A: All diagnosed Alphas should consider seeing a pulmonary specialist with experience in Alpha-1.
But first, you should be tested for Alpha-1. You can ask your current doctor to order an Alpha-1 blood test, based on your symptoms, all of them good reasons to be tested. If for any reason your doctor is reluctant to do the testing, you can see the asthma/allergy specialist you mentioned.
You can also get free and confidential testing by a finger stick done in your home through the Foundation’s Coded Testing Study. For information, see our web page on testing, or call the Alpha-1 Research Registry Program at the Medical University of South Carolina toll-free at 1-877-886-2383.
What’s the best way to rinse after using an inhaler?plus
Q: Should I rinse my mouth after using an inhaler? What’s better, plain water or gargling with a mouthwash?
A: Many side effects caused by using an inhaler or nebulizer can be greatly reduced by rinsing your mouth after using them. This is especially true for inhaled or nebulized steroids (Advair is one common example).
The goal of rinsing your mouth is to get rid of any medication that didn’t make it into your lungs and is still sitting in your mouth and throat. Swishing and spitting, or gargling and spitting, are the recommended methods. It’s okay to use water, but some have suggested that an alcohol-containing mouthwash is more effective. You can also brush your teeth and rinse, immediately after using an inhaler or nebulizer.
A spacer is another way to reduce the amount of medication landing in your mouth, though spacers are not needed with dry powder inhalers such as Spiriva and Advair.
Finally, if you are using a steroid inhaler and develop pain with swallowing, accompanied by white and red patches in your throat, this could be a sign of a fungal infection called thrush. If this doesn’t go away with more vigorous rinsing, it’s best to consult your doctor because more specific therapy might be needed.
The purpose of augmentation therapyplus
Q: What is the primary purpose of augmentation therapy? What results can people expect if they are taking augmentation therapy? Do these expectations change depending on the severity of the underlying lung disease?
A: Augmentation therapy (also called replacement therapy) infusions are intended to augment (add to) the amount of alpha-1 antitrypsin protein (AAT) floating in the blood and bathing the tissues of the body in people with lung disease related to Alpha-1 Antitrypsin Deficiency. Although some people report that they notice improvements in their health when on augmentation therapy, and there is some evidence for a decrease in the number of lung infections in individuals receiving augmentation therapy, the primary aim of this therapy is to reduce the rate of decline of lung function towards normal and, therefore, improve the long-term quality of life and even the lifespan of those with lung disease due to Alpha-1.
Everyone loses lung function during their adult life, whether they have Alpha-1 or not. Alphas with lung disease lose their lung function at a more rapid rate than normal. If augmentation therapy is effective, it will be expected to slow this increased rate of decline, regardless of the severity of the underlying lung disease.
How often should AAT blood levels be checked?plus
Q: How often should AAT levels in the blood be checked?
A: It usually is not necessary to have more than one AAT level checked during an Alpha’s lifetime, just as it usually is not necessary to have an Alpha’s phenotype or genotype checked more than once in a lifetime. However, there are some exceptions. When the initial diagnosis is made, it is reasonable to recheck and confirm it, preferably at a reference laboratory with experience in testing for Alpha-1.
Some people with unusual phenotypes and evidence of lung disease may have their levels rechecked to evaluate whether their baseline level is low enough to cause concern. It is not recommended that levels be checked following institution of augmentation therapy. It is also important to know that phenotype tests will be inaccurate in those receiving augmentation therapy. Physicians should not make changes from the recommended dosing of augmentation therapy based on blood levels of AAT.
Why Alpha docs test for IgA deficiencyplus
Q: What is the deal about augmentation therapy and IgA deficiency?
A: IgA is one of the most common hereditary immune deficiencies. IgA deficiency, like Alpha-1, can be associated with lung and allergic-type symptoms. People with either of these conditions (IgA deficiency or Alpha-1) can lead normal, healthy lives without ever knowing they have one of these conditions.
Those with Alpha-1 who are about to start augmentation therapy should be tested for IgA deficiency, because giving repeated infusions of a plasma-derived product can lead to severe allergic reactions in IgA deficient individuals. This is due to the small amount of IgA protein contained in each vial of augmentation therapy. Anyone with hereditary IgA deficiency has circulating antibodies to the IgA molecule and these antibodies can cause an allergic reaction when even small amounts of IgA protein are delivered intravenously.
Since augmentation therapy is only given to patients with lung disease due to Alpha-1, it is hard to know whether those with IgA deficiency have worse lung problems than those without. It is logical to assume they would. Both Alpha-1 and IgA deficiency, when they cause problems, can lead to recurrent lung infections and bronchiectasis and there may well be some additive effects of having both.
Asthma medicine can also help Alphasplus
Q: Why do Alphas with lung disease take asthma medicines?
A: Many people with emphysema, especially Alphas, have asthma as well. One study indicates that over 70 percent of Alphas with lung disease have asthma at some time during their lives.
Asthma is defined as obstruction to the outflow of air from the lungs (when you exhale) that can be reversed with medication. The obstruction caused by emphysema itself (thought to be due to loss of the connective tissue that holds the airways open during exhalation) is generally fixed and permanent. Obstruction that can be reversed by bronchodilators, steroids, theophylline, etc., is by definition, asthma. Asthma is generally thought to be due to spasm of the muscles of the bronchial tubes (bronchospasm), inflammation of the airways with swelling, and increased mucus production blocking the airways.
If you have lung disease from Alpha-1, you can think of emphysema as the component causing the slow, steady decline in lung function that can’t be reversed (with current technology) and asthma as the part that gives you the daily, weekly, or monthly ups and downs in your breathing.
Augmentation therapy is designed to slow down the emphysema-related decline. The inhalers and pills (and emergency room IVs) that people take are designed to reverse the asthmatic side. Of even greater importance, long-acting bronchodilators and inhaled steroids have been shown to reduce the number and severity of flare-ups of lung disease, also called exacerbations, in patients with emphysema.
Prevention is the best defense against infectionsplus
Q: What are the best methods for fighting viral infections? What about bacterial infections?
A: The best method for fighting viral and bacterial infections is prevention. Avoid crowds, young children, and people who are sick. Wash your hands often. Get flu shots and pneumonia shots. Consider immunization against Hemophilus influenzae, hepatitis B, and hepatitis A.
Once a viral infection sets in, there is often little that can be done, unless the virus-causing disease is one of the few that have a specific therapy. Most treatments for viral infections treat symptoms – to make you feel better while the body fights the virus on its own.
In Alphas who develop a viral respiratory tract infection, it is often recommended they start immediately on an antibiotic. Classic antibiotics do nothing to treat the virus, rather they are used to prevent or treat the possibility that a bacterial infection will develop in the airways already injured by the viral infection.
The best method for treating a known bacterial infection is to give an appropriate antibiotic at the earliest possible time. No one antibiotic is necessarily better or stronger than another; rather, a particular bacteria may be more sensitive and better killed by certain antibiotics than by others. The simplest antibiotic, for instance penicillin, can be just as effective as the newest and most expensive antibiotic if the organism causing the infection is sensitive to it.
The problem is, one often doesn’t know what bacteria is causing a particular infection and one often doesn’t know what antibiotic it might be sensitive to. Antibiotic resistance tends to be different in different geographic areas, so it’s important to let your physician recommend the antibiotic that seems to have the best effect at the current time in your area.
Exacerbations: Hit them hard and earlyplus
Q: What is the best philosophy for fighting exacerbations?
A: The best philosophy for fighting exacerbations is to hit them hard and early. Know your own disease; know how your lungs react during an exacerbation. Start early with increasing your usual medications, perhaps starting steroids and/or antibiotics, etc., in consultation with your own physician.
Why are stairs such a challenge for Alphas?plus
Q: Why are stairs so difficult for Alphas to walk up?
A: Stairs represent one of the hardest challenges for those with obstructive lung disease. They are everywhere; they require that the large muscles of the legs lift the entire body weight with each step; and they represent a measurable amount of activity. For example, you may recall that six months or a year ago you could reach the top of the stairs without stopping, then have to rest and catch your breath, while now you find that you have to stop and rest two steps from the top. It may not seem that walking up 12 steps represents much greater effort than walking 12 steps on an even surface.