Alpha-1 Information Thread

Discussion in 'Subcool's Old School Organics' started by subcool, Jul 12, 2013.


    subcool Well-Known Member

    Before the 1960s, the existence of Alpha-1 Antitrypsin Deficiency (Alpha-1) was not known to the medical profession or the public. In the early 1960s, investigators at Malmö General Hospital in the south of Sweden were using a laboratory technique known as serum protein electrophoresis (SPE), to look at a variety of disease conditions. SPE separates the proteins in serum into groups according to their movement in an electric field. Initially, it was noted that there were three major groups of serum proteins when blood was evaluated by this method. These three groups were named alpha (a), beta (b) and gamma (g), the first three letters of the Greek alphabet. The gamma group contains most of the antibody molecules of the blood, thus the term "gamma globulin." As the investigators in Malm refined their techniques, it became apparent that the alpha group of the SPE was actually made of two distinct groups, so these were named alpha1 and alpha2.

    Drs. Sten Eriksson and Carl-Bertil Laurell were using the SPE technique and noted that a group of patients with a strong family history of emphysema at a young age all lacked the alpha1 band of their serum proteins. They found that the alpha1 band was almost entirely made of a single protein that had been previously named "antitrypsin" because of its ability to block the action of one of the main enzymes in the digestive system, trypsin. In 1963, they published the first scientific article describing the association between familial emphysema and the deficiency of "alpha-1 antitrypsin."

    At approximately this same time, investigators in the United States were also evaluating emphysema in animals in a laboratory setting. In 1965, Dr. Paul Gross found that rats developed emphysema when a drop of a substance called papain was placed into their lungs. Papain, an enzyme preparation made from the sap of the papaya tree, is the active ingredient in commercial meat tenderizer powders. In Dr. Gross' studies, it only took a month for rats to develop the lung destruction characteristic of emphysema. Other investigators went on to show that the reason papain was able to cause emphysema was that it was able to destroy one particular protein in the lung, the protein elastin. Elastin gives tissues their elastic properties. In the lungs, elastin allows the air sacs to expand when breathing in, and return to their normal size when breathing out. Elastin also gives the skin and blood vessels their elastic properties.

    Enzymes that can destroy elastin are called, by scientific convention, elastase. It turned out that many kinds of elastase had been identified before the mid-1960s, so scientists tested each of these elastases in animals, and each was able to cause emphysema. Other types of enzymes that destroyed different kinds of tissues in the lungs were also tested, but only enzymes that could destroy elastin could cause emphysema. The problem with these studies was that human lungs are not normally exposed to these forms of elastase. So scientists were concerned the elastase in these studies might have nothing to do with the emphysema that humans develop.

    Then, in 1968, Dr. Aaron Janoff described a new elastase he had found within a particular kind of human white blood cell. This white blood cell was called a neutrophil, and the elastase was named human neutrophil elastase (HNE). Here was an elastase that was relevant to human beings, since neutrophils are continually carried through the lungs by the blood, and because neutrophils are the body's primary defense against acute lung infections. Dr. Janoff and his colleagues showed that HNE was very potent at causing emphysema in laboratory animals. They also showed that HNE's activity against elastin could be totally blocked by mixing in human alpha-1 antitrypsin (AAT).

    Dr. Janoff and his colleagues proposed that the lungs are constantly exposed to HNE by white blood cell activity in the lungs. They suggested that, in normal individuals, AAT is the primary defense against this destructive enzyme, but in individuals with a genetic deficiency of the AAT protein, the HNE can attack normal lung tissue, leading to emphysema. This group of scientists then went on to show that certain chemicals in tobacco smoke, called oxidants, could inactivate the protective function of AAT. (In fact, a single cigarette is capable of inactivating all the AAT in a normal lung.)

    This finding led to the suggestion that all emphysema is due to AAT deficiency in one way or another. In individuals who smoke regularly, the AAT deficiency is a functional deficiency, due to the action of tobacco smoke oxidants on AAT. In individuals with Alpha-1, the deficiency is genetic. Since individuals with Alpha-1, in general, have some circulating AAT (people with a severe deficiency usually have about 10 to 20 percent of the normal level), the combination of Alpha-1 and smoking can cause greatly increased risk of lung destruction.

    Approximately six years after the description of Alpha-1 as a condition that predisposes to hereditary emphysema, Dr. Harvey Sharp published the first description of liver disease of the newborn in association with Alpha-1. This so-called neonatal cirrhosis led to liver failure in several infants he described. We now know that liver disease in children can range from very mild to life-threatening, and that liver disease in adults with Alpha-1 is not uncommon.
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    subcool Well-Known Member

    During the 1970s, a large number of different genetic patterns were identified for Alpha-1. These are called alleles of the AAT gene. First 10, then 50, and now over 100 different alleles for AAT have been discovered. About 34 of these alleles are associated with a deficiency of AAT. The rest are slight variations from the normal AAT gene that seem to cause no problems.
    In the 1980s, investigators started to test whether it would be possible to replace or augment the deficient AAT protein in individuals with Alpha-1. This work was carried out primarily at the National Institutes of Health (NIH) facilities in Bethesda, Md. Investigators there isolated and purified AAT from normal volunteers, then administered it intravenously to patients with Alpha-1. They identified a dose that, when administered every week, could maintain AAT blood and lung levels at or above the level thought to protect against lung injury. This therapy became Prolastin[SUP]®[/SUP].

    Cutter Laboratories was the company that owned the product being tested at the NIH. Working with the NIH, they showed the product was safe and could augment the levels of AAT in the blood and lungs. The next step in drug development would be to do a study to prove the drug protected against the progression of emphysema. Experts in the field were brought together to discuss the design of such a study. They concluded, however, that such a study would take many years to complete, and it would be virtually impossible to study the number of Alpha-1 patients needed, since so few had been identified at that time. It was expected that Prolastin would never be approved without such a study.

    However, because there was no other available treatment for Alpha-1, and Prolastin could safely increase the amount of AAT levels in the lungs, the U.S. Food and Drug Administration (FDA) decided to approve Prolastin for prescription in the United States. Several countries in Europe also approved the drug. Prolastin became readily available in the United States in the beginning of 1988. Over the next several years, the companies marketing Prolastin changed from Cutter to Cutter/Miles, and then from Miles to Bayer. As of early 2003, two additional intravenous drugs have been approved for the treatment of Alpha-1: Aralast, marketed by Baxter Healthcare, and Zemaira, made by Aventis-Behring/ZLB Behring. Prolastin is now marketed by Talecris Biotherapeutics. Other medications may be approved in the future.
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    subcool Well-Known Member

    The 1990s saw the emergence of our understanding of Alpha-1 as a liver condition. Studies looking at the production of AAT determined that most of the AAT protein is made in liver cells. It was initially assumed that the reason AAT was found in low levels in individuals with Alpha-1 was because the liver cells must manufacture reduced amounts of this protein. This is not the case for the most common gene that causes Alpha-1. The liver cells make normal amounts of AAT; the problem is that the liver cells have problems transporting this protein out into the blood. The abnormal AAT gets hung up in the transport mechanism of the liver cells, and only a small fraction of the AAT protein made in the liver gets released into the blood. It is assumed that this clogging of the transport mechanism may explain how the liver injury develops in some Alpha-1 patients. Research is still progressing in this area.

    Currently, Alpha-1 is known to be a condition affecting the release of alpha-1 antitrpsin into the blood, causing low levels of this important protein in many tissues of the body. In the lungs, these low levels make them more likely to be injured by the body's own defense mechanisms. There is much yet to be written in the history book of Alpha-1.

    In the 1960s, the diagnosis of Alpha-1 was considered only in individuals who were diagnosed with emphysema at a young age. In the 1970s, newborns with unexplained severe liver problems were added to the list of potential Alpha-1 patients. Standardized laboratory criteria for the diagnosis were not well established, and individual labs set up their own testing methodology. Several labs around the United States, such as the Mayo Clinic and National Jewish Hospital, became magnets for the testing for Alpha-1. Each laboratory set its own "normal range" for alpha-1 antitrypsin (AAT) level testing, a practice that persists to this day. Laboratory standards, such as a reference solution of known concentration of AAT, were not available. Most phenotyping (see below) was done by starch gel electrophoresis, a technique that was more art than science.

    Today, thanks to improved methodology and national reference laboratories, the technical issues related to making the diagnosis of Alpha-1 are fairly well resolved. The problems today include physician awareness (so the testing can be ordered appropriately) and genetic discrimination, which raises issues related to whether a patient should agree to be tested.
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    subcool Well-Known Member

    Until it is appropriate to begin screening the general population for Alpha-1, there are some guidelines as to who should be tested for this condition. These include individuals with:

    • Family history of Alpha-1
    • Family history of emphysema, bronchiectasis, liver disease, or panniculitis
    • Early onset emphysema (age < 45 years)
    • Emphysema in the absence of, or out of proportion to a recognized risk factor, such as smoking, occupational exposure, etc.
    • Emphysema with a prominent basilar hyperlucency (worse disease at the bases of the lungs)
    • All individuals with a diagnosis of chronic obstructive pulmonary disease (COPD)
    • Bronchiectasis
    • Chronic asthma in adolescents and adults
    • Recurrent pneumonia or bronchitis
    • Unexplained liver disease
    • Wegener's granulomatosis (C-ANCA positive vasculitis)
    • Necrotizing panniculitis
    [FONT=verdana, arial, helvetica, sans-serif]Alpha-1 can be detected by a simple blood test. Your physician can order this test for you. Some companies providing augmentation therapy for Alphas have free testing programs. I suggest you do this anonymously to keep from being turned down for insurance!

    [/FONT]Alpha-1 coded testing trial
    Individuals may also choose to be tested on a confidential basis through the Alpha-1 Foundation's Alpha-1 Coded Testing (ACT) Trial.

    This trial offers free and confidential fingerstick testing for Alpha-1. The test is administered through a research study that evaluates the risks and benefits associated with receiving genetic information test results. Anyone can request to be tested. Participants or the participant's guardian will be asked to complete a short questionnaire before and after testing. This program, established by the Alpha-1 Foundation, is headquartered at the Research Registry Coordinating Center at the Medical University of South Carolina in Charleston.

    There are two types of tests for Alpha-1. These are the blood level testing and Pi-typing. Pi-typing can be done by looking at the AAT protein in the blood, called phenotyping, or by looking at the AAT gene, called genotyping.

    Tests for Alpha-1

    • Blood level testing
    • Pi-typing
    Other tests can suggest the diagnosis of Alpha-1. For instance, a test called a "serum protein electrophoresis" may show a reduced or absent Alpha-1 peak in patients with severe deficiency. A liver biopsy may show granules inside liver cells that may suggest that a diagnosis of Alpha-1 should be considered. A chest X-ray may have a pattern of lung destruction at the bases, which is sometimes characteristic of Alpha-1. These tests must still be confirmed by the specific tests mentioned above.Tests suggesting the diagnosis of Alpha-1

    • Serum protein electrophoresis
    • Liver biopsy
    • Chest X-ray
    Blood level testing
    The amount of total AAT can be measured in the blood. In general, this test is performed on serum. Serum is the liquid component of blood that is left after blood is allowed to coagulate (form a blood clot) in a test tube. In normal individuals, there is a large amount of AAT circulating in the blood. The normal range can be as high as 400 mg/dL or 4 grams in each quart of blood. The level can be measured using one of a variety of techniques but, most commonly, antibodies against AAT are used to quantify the amount of AAT in the serum. The results are expressed either in mg/dL (milligrams per 100 cc of blood) or in µM (micromoles). Local labs tend to use the mg/dL units and the normal range, as mentioned above, tends to vary from lab to lab, with the low end of the normal range varying from 70 to 200 mg/dL. In general, individuals with severe deficiencies tend to have an AAT level of less than 40 mg/dL. The national testing laboratories use theµM system, and the low end of the normal range is approximately 28 µM in this system. Individuals with a level less than 11 µM are considered to have severe deficiency of AAT.

    Most low levels need to be confirmed by genotyping or phenotyping. In order to understand these tests, one needs to understand how a protein like AAT is made in the body. Each protein in the body starts out as a code in the structure of DNA (a gene). This code is translated into a protein by the protein-synthesizing apparatus of the cell. Individuals with Alpha-1 have at least one abnormal gene and make an abnormal AAT protein.

    Phenotyping looks at the type of AAT protein floating in the blood and evaluates whether it is normal or abnormal. Currently, this is usually done by a technique known as "isoelectric focusing." The abnormal AAT protein of Alpha-1 individuals has a different balance of plus and minus charges than the normal protein. Isoelectric focusing takes advantage of this difference by looking at how the AAT moves in a gel when an electric field is applied to it. Experienced laboratory personnel can look at the gels of different individuals and evaluate whether the AAT protein is migrating normally or abnormally. If the migration is abnormal, there are specific patterns that indicate the type of abnormal AAT protein present.
    Every individual has the same genes in each cell of their body and, in fact, have two genes for each protein being made: one that was inherited from the father and one from the mother. In the case of Alpha-1, the important cell is the liver cell, which makes almost all the AAT circulating in our blood.

    Genotyping looks at the DNA code for AAT in our cells to see whether that code would produce a normal AAT protein or an abnormal one. Sometimes the AAT gene inherited from each parent is different. One could be normal and the other abnormal. Genotyping can detect both genes (just as phenotyping can detect both types of protein being made).
    Genotyping lends itself to automation much more easily than phenotyping, which is very labor-intensive and requires expertise in interpreting the results.
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    subcool Well-Known Member

    Phenotypes and genotypes of Alpha-1 are reported as letters of the alphabet. These letter assignments were first made when starch gel electrophoresis was the common technique used for testing phenotypes. In this system, the phenotype was determined by how fast the AAT protein moved in a gel. The system was designed so the normal protein moved about halfway up the gel and, therefore, the normal protein was assigned a letter from the middle of the alphabet: M. The most common deficient AAT protein moved hardly at all and was assigned the letter Z.

    This scheme was called the "Protease Inhibitor naming system," or "Pi-typing," for short. Normal individuals inherit a normal gene from each parent and are therefore labeled Pi MM (or simply Pi M). Individuals who inherit an AAT deficiency gene from each parent have Pi-typing based on the abnormal genes inherited, such as Pi ZZ (or Pi Z). If the status of an individual was determined by genotyping (asopposed to phenotyping), an asterisk is placed between the Pi and the type of gene (for example, Pi*M and Pi*Z). Individuals can inherit a normal gene from one parent and an abnormal gene from the other. For instance, an individual could be reported as Pi MZ or Pi*MZ.

    As more and more individuals have been tested, more and more types of AAT have been found. Each of these types is called an allele. With more than 100 different alleles identified, scientists long ago ran out of letters of the alphabet and resorted to naming them based on the city in which the discovery was made. Thus, for example, one rare deficient gene has been labeled MPITTSBURGH. There are also at least four variations of the normal AAT gene labeled M1, M2, M3, and M4. Not all alleles result in disease or in deficiency. In fact, most non-M alleles cause no problems whatsoever. Many, however, do cause lower than normal levels of AAT in the blood and put people at increased risk of Alpha-1 related disease.

    One unusual result that can be seen is the so-called "Null allele." The Null allele results in no AAT protein made, and thus, an AAT level of zero in the blood. There are actually many different gene abnormalities that can lead to the Null phenotype. Any gene that codes for a protein that is so abnormal that it cannot be made, or that codes for only a small piece of the AAT protein, can lead to the inability of the liver cell to make any AAT at all. Pi Null/Null individuals have the lowest levels of AAT in blood (zero). Individuals with one normal gene and one Null gene (Pi*M/Null) can be very difficult to identify since their phenotype looks like M. That is because all the AAT protein circulating in the blood is of the normal type, since no Null protein is made. The only clue that someone might bePI*M/Null is that their phenotype is normal, but their blood level is only half-normal.

    Another unusual Pi-type is the F allele. The F protein is made in normal amounts, but it is dysfunctional. Thus, an individual who is Pi F would have normalAAT levels in the blood but would be unable to block the activity of neutrophil elastase.

    While most individuals with Alpha-1 are familiar with the normal alpha-1 antitrypsin gene and its resultant "M" protein and the severe alpha-1 antitrypsin "Z" deficient gene, the most common deficient gene for Alpha-1 is the "S" gene. Even though it is more common than the Z gene, it is less studied and less understood, primarily because it causes a less severe deficiency than the Z gene and appears to impart little or no risk of liver disease.

    Individuals with the MS Pi-type or even the SS Pi-type are felt by most to be at little or no risk of lung disease compared with normal individuals. Those with the SZ Pi-type demonstrate great variability in their baseline serum alpha-1 antitrypsin levels. The risk of developing lung disease in an SZ individual seems to be entirely related to their baseline serum and lung alpha-1 antitrypsin levels. Infact, the target dosage of augmentation therapy, such as Prolastin, was calculated based on the evaluation of a group of SZ individuals. In that group, it was found that emphysema was extremely unlikely in those with serum levels of alpha-1 antitrypsin greater than 80 mg/dL. Thus, this became the target level sought with augmentation therapy.

    The S protein is manufactured in the liver at a somewhat slower rate than the M protein and may be cleared from the circulation at a faster rate than the M protein. This causes the lower blood levels seen in those with the S gene. This mechanism is different than the build-up of defective protein seen in those with the Z gene and may account for the lack of liver injury associated with the S gene.
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    subcool Well-Known Member

    In this Reference Guide, we will talk about a number of the benefits associated with being tested for Alpha-1. For instance, knowing you have Alpha-1 can provide you with the motivation to minimize or eliminate your exposure to environmental risk factors. Knowing your diagnosis also allows you and your health care provider to utilize effective, appropriate treatments for Alpha-1 related diseases, should they develop.

    Should every adult get tested? Why not test every newborn for Alpha-1? These questions deserve serious consideration because, while there are benefits to testing, there are also risks. For example, there are currently no available treatments for healthy children diagnosed with Alpha-1, and some feel that labeling such a young person with a genetic condition can unnecessarily worry parents and relatives. Some studies have shown that many parents of healthy children diagnosed with Alpha-1 actually wish the testing had never been done.

    Other people may feel that being tested for Alpha-1 could put them at risk for genetic discrimination. Although the Americans with Disabilities Act (ADA) may provide some protection against this form of discrimination, there are still many genuine concerns associated with genetic testing. This can take the form of denial of health insurance, denial of life insurance, or employment discrimination. Some individuals with Alpha-1 have lost their jobs after their diagnosis was disclosed. Sometimes, healthy children with Alpha-1 have not been able to get health insurance or have been denied life insurance after they reached adulthood. In addition to the ADA, some individual states have created laws addressing the issue of genetic discrimination.

    Individuals with Alpha-1 may donate blood as long as they do not have emphysema or liver disease and are not receiving augmentation therapy. Plasma donation may be made by Alphas; however, that decision will be made by the physician at the particular plasma site where you wish to make your donation. Your plasma may be used for other plasma products not related to making Alpha-1 augmentation therapies. Carriers of Alpha-1 may donate both blood and plasma. Your local blood donation center may provide more information.
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    subcool Well-Known Member

    So you're an Alpha. Now what? There are two important initial steps to take once you've been told you're an Alpha. First, make sure the diagnosis of Alpha-1 is correct and second, find an Alpha-1 Aware health care provider.
    One of the first concerns any new Alpha should have is whether their diagnosis is correct. A final diagnosis of Alpha-1 should not be made without confirmation. In addition, it should not be made on the basis of a single blood level test, or on a single phenotype or genotype test. If the diagnosis was initially based on a single blood level or single phenotype test result, it is reasonable to obtain both a level and phenotype or genotype for confirmation. Even the most reputable Alpha-1 laboratories recommend confirmatory testing. Having confirmed the diagnosis, it is not necessary to test again in the future, since as a genetic condition, your Alpha-1 status will not change unless some extraordinary measures are taken, such as a liver transplant or gene therapy.
    Finding an Alpha-1 Aware physician may be the most difficult part of getting the most appropriate treatment plan for you. In many cases, the individual with Alpha-1 must "create" an Alpha-1 Aware physician or Alpha-1 Aware health care professional themselves. You can do this by educating yourself about your condition and finding a receptive physician, physician's assistant, or nurse, and getting them the information they need to make them Alpha-1 Aware.

    I was lucky enough to be contacted my Centrex who I gave permission to give my Info to Alphanet this phone called Saved my Life!!

    One of the best ways of ensuring that your physician or other health care provider is Alpha-1 Aware is to provide them with a copy of this Reference Guide. Sample physician treatment plans can be found at the back of this Guide. They provide an excellent tool for your physician.

    Even for Alphas that are able to find an Alpha-1 "expert" in their local community, consulting with an Alpha-1 Clinical Resource Center (CRC) is recommended. Over 50 Clinical Resource Centers have been established throughout North America with a focus on Alpha-1 patient care, including pulmonary and liver centers. CRCs are at the heart of the Alpha-1 Foundation's research network. The leading experts in clinical practice and/or research relating to Alpha-1 are available at the centers for consultation. Individuals and their physicians are encouraged to call their regional CRC for information and guidance.

    Being an Alpha means living with a life-long condition. This means that at some level you'll be involved with the health care system for the rest of your life. The health care system is a complex and often frightening world with unique systems and language. To make it work for you, understanding some of its basic concepts will help.

    In Section B you will learn how to:

    • Collaborate with your health care providers in creating your treatment plan.
    • Identify and minimize the risk factors associated with Alpha-1 related diseases.
    • Develop good nutritional habits to attain an ideal weight and help prevent disease.
    • Develop stress management skills.
    • Create a fitness plan to reduce fatigue and improve your overall health.
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    subcool Well-Known Member

    Throughout this Reference Guide, the person you see at your physician's office or clinic is referred to as a physician, doctor, health care provider, or a physician extender. These terms have been used interchangeably in many parts of this Guide. It's important to know, however, that only a licensed physician or specific health care extender can prescribe therapies. Health care providers that are licensed to prescribe are, in general, defined by state laws and regulations. In addition to your doctor, the term health care provider encompasses the professions of the physician assistant, nurse, and nurse practitioner, as well as a variety of other professionals such as physical therapists, occupational therapists, respiratory therapists, psychologists, social workers, and others. The health care environment has been changing rapidly, with work that used to be the specific responsibility of the physician being shared by a variety of highly trained professionals. What is important is finding an Alpha-1 Aware health care provider, regardless of their title. Depending on how your care is delivered, please feel free to substitute the appropriate professional for the words used in this Guide.

    There are several good reasons for learning something about the system physicians use for evaluating your health problems. If you understand what information is needed, you will be able to provide that information more efficiently, and avoid forgetting or missing any important points. Learning this step-by-step process can also help you develop a good relationship with your health care provider, one based on good communication and an honest exchange of ideas. In addition, the more you learn about how health care providers organize and analyze the information they gather, the more you will understand about the types of tests and evaluations your health care providers might be recommending for you.

    Many people like to invite family members to accompany them to their health care visits. Someone who is close to you can often help you remember all the things you intend to talk about, and can also be there to support you if you are confronted with difficult health care decisions. Being prepared for your health care visits is one more positive step you can take to help create a treatment plan you can live with.

    When you visit your physician or health care provider, they will generally use a standard problem-solving method for collecting information that will allow them to make an assessment and treatment recommendations. Many different methods and formats are used; however, all of them have key elements in common. In general, the problem-solving system your health care provider will use can be categorized into four parts: subjective data, objective data, assessment, and treatment planning.
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    subcool Well-Known Member

    The objective category includes items that the health care provider observes or evaluates through examination or testing. During an initial visit, or follow-up visit after a prolonged interval, a complete physical exam may be performed. This usually involves a head-to-toe examination, often including parts of the body that seem to have no relationship to the current problem. It is often important to examine the body as a whole, because sometimes the chief problem can be related to another issue about which you may be unaware. In addition, it is often a good idea to review the entire body to identify potential problems before they occur. Once again, at follow-up visits, when there is a specific acute problem being addressed, or when you are visiting a specialist, a more limited exam may be performed.

    Also included in the objective category are any laboratory tests, X-rays, pulmonary function tests, arterial blood gases, exercise testing, evaluations by consultants, etc., that may have been ordered.
    After all the information is gathered, the health care provider will make an assessment. The assessment includes the identification of specific problems leading to a diagnosis. It may include more general comments about what might be the cause of the problem, and what additional actions or testing may be anticipated.
    Once the data is gathered and the assessment is made, you and your physician will develop a plan for dealing with any problems. Some plans are referred to as "short-term treatment plans." These are intended to deal only with the specific problems identified during that specific visit with your health care provider.

    For Alphas, however, a treatment plan that is comprehensive enough to encompass longer term health care issues, arising from your diagnosis of Alpha-1 Antitrypsin Deficiency, should be developed. These plans may be referred to as a "long-term treatment plan." The use of this Reference Guide will help you facilitate the evolution of a simple visit plan into a more comprehensive treatment plan, tailored to meet your specific needs.
    Any treatment plan, but particularly a long-term plan for Alpha-1, is not something that your health care provider can simply give to you. Instead, the treatment plan most likely to be successful will require the collaborative efforts of both you and your health care provider.

    While there are elements of every treatment plan that may be common for Alphas, there is no "one-size-fits-all" Alpha-1 treatment plan. Alpha-1 Antitrypsin Deficiency is not a simple disorder. In some Alphas, disease never develops and they live a normal and healthy life. In others, diseases of the lung, liver, and other body systems develop and vary significantly in how they affect the individual. Some Alphas develop severe debilitating diseases, while others develop only mild symptoms of those same diseases.

    Regardless of where you are on the health spectrum, from healthy to severely ill, the importance of treatment planning in Alpha-1 remains unchanged.

    If you're a healthy Alpha, treatment plans may be as simple as avoiding risk factors, obtaining genetic counseling, and scheduling routine follow-up visits with your health care provider. Alphas with severe symptoms of disease may have complex and frequently changing treatment plans. In any case, treatment planning is a central tenant of all health care and provides the tools for you and your health care provider to manage this complex life-long disorder.

    Your health care provider's first responsibility is to diagnose your condition, and then to ensure that a recommended treatment is consistent with the established "standards of care" for Alpha-1. Typically, the "standards of care" for a particular medical condition are based on results of clinical studies conducted in patients who have that specific condition. The treatment of Alpha-1 poses a problem for many health care providers, however, because few clinical studies have been conducted exclusively in Alphas.

    One of the goals of this Guide is to offer you and your health care providers medical practice guidelines that can be used to develop a treatment plan. The guidelines presented in this document are consistent with the current understanding of Alpha-1 Antitrypsin Deficiency, as described in the American Thoracic Society's "Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin (AAT) Deficiency," and other existing standards for diseases that are frequently seen in Alpha-1.

    Your health care provider has the responsibility to communicate clearly with you. They are expected, as thoroughly as possible, to inform you about your condition and be certain that you have understood the explanation. You should expect your health care provider to discuss the specifics of treatment with you. What are the available treatments? What are the expected outcomes of each treatment? What are the treatment options and alternatives? Are there any side effects from the treatments? Your health care provider recommends and prescribes treatments based on these discussions, knowledge of the relevant "standards," and their individual experience and skill in the practice of health care

    Additionally, your health care provider has the responsibility to assess any changes, both good and bad, in your health status. These changes may be due to disease progression, prescribed treatments, or responses to specific therapies.

    Your health care provider will recommend specific follow-up steps to ensure that appropriate reassessment occurs. These recommendations for follow-up may include routine office visits and repeat testing at specific intervals. You may also receive instructions about the types of concerns you might have, for which you can telephone your doctor, versus those conditions that require immediate medical attention.

    This reassessment of subjective and objective data will then be used to make adjustments to your treatment plan. Remember ... the treatment plan is a "living document." This means that it is not "carved in stone," and it will change as you do.

    The goal of good treatment planning is to optimize your health. The responsibilities of your health care provider in the process are fairly well defined. What part do you play in the development of your treatment plan? Let's discuss what you can do.


    subcool Well-Known Member

    You have an equally important role in the treatment planning process. First and foremost, you are responsible for carrying out many of the elements of your treatment plan. Many health care providers are faced with the dilemma of having to evaluate the success of a treatment plan when the recommendations have not been followed. Your plan may include taking medication, having tests done, or making changes in your lifestyle. You may find these things difficult to do if you do not understand their purpose. Many people report that they fail to comply with recommendations because they simply don't understand them.

    That's why it's essential that treatment planning be a collaborative effort between you and your health care provider, and not simply a set of instructions. Let's be clear ... communication is a two-way street! You have the same responsibility to communicate with your health care provider that they have with you. If there are things that you do not understand, if your health care provider is making recommendations that you do not agree with, or if you know that you will not be able to comply with specific recommendations, it is your responsibility to tell your health care provider! Speak up! Don't be afraid, ashamed or intimidated! Your health care provider will appreciate the information; after all, they want what you want — your health!

    Once you and your health care provider have agreed on a treatment plan, it is then your responsibility to comply with it. This responsibility also includes reporting changes in your health status, and/or your response to treatments, accurately and in a timely manner to your physician.

    This Reference Guide provides much of the information you will need to understand the elements of your treatment plan. With adequate information you can fully participate in the process and appreciate the importance of your role in carrying out that plan.

    Because this document cannot answer all of the questions you may have about Alpha-1, you will want to build a relationship with your health care provider that is based on good communication and trust.

    Getting good health care and maintaining your health is not a passive activity. You must actively participate in the system to make it work for you. Successfully managing the condition Alpha-1, involves a partnership between you and your health care provider. Participating in the development of your treatment plan and adhering to that treatment plan, are perhaps two of the most important ways in which Alphas can control the course of their health and well-being

    Many elements of a treatment plan are common to all Alphas. The following outline represents general categories or elements of a treatment plan and is intended as a sample framework. A comprehensive treatment plan form is provided in Appendix D-5. You and your physician will find that form a useful tool as you develop a treatment plan specific to your needs.

    Diagnostic testing
    • Alpha-1 specific laboratory diagnostic tests
      • Phenotype, genotype, serum

    • Other laboratory diagnostic tests — examples
      • Liver function tests (LFTs), Complete Blood Count (CBC), Pulmonary Function Tests (PFTs)

    Diagnostic imaging (radiology) — examples
    • Chest X-ray, CT Scan
    • Medication
    • Immunization
    • Detailed discussion of Alpha-1
    • Genetic counseling and consideration of family testing
    • Discussion of coping strategies in dealing with Alpha-1 diagnosis
    • Potential referral for supportive/family counseling
    • Detailed discussion of risk factors and avoidance strategies
    • Schedule routine office visits
    • Repeat diagnostic testing at specified intervals
    • Report changes in heath status to health care provider
    • Fitness activities and/or pulmonary rehabilitation
    • Diet and nutrition planning
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    subcool Well-Known Member

    Alpha-1 usually does not, in and of itself, cause disease of the lungs or other organs. Rather, Alpha-1 makes individuals more susceptible to the risk factors that have the potential of causing organ damage in anyone. Thus, while some individuals with Alpha-1 develop severe forms of liver and lung disease, others develop only mild symptoms. Indeed many individuals with Alpha-1 never develop any symptoms of these diseases. While some of this variability may be related to each individual's total genetic makeup, the major influences on the development of disease appear to be exposure to risk factors that are entirely or partially controllable.
    This chapter will help identify these risk factors and suggest ways that you can modify or reduce your exposure to them. Because this chapter deals with factors that you have direct control of, you have the opportunity to take steps to prevent disease or slow its progression. This may well be the most important chapter of this Reference Guide.

    For individuals who are "carriers" of a single abnormal Alpha-1 gene, reduction of risk factors deserves special attention as well. Although the risk of developing diseases may be lower for carriers when compared to Alphas with two abnormal genes, there is a growing appreciation that carriers are also at increased risk for disease development. Therefore, controlling your exposure to these same risk factors is just as important for you.

    Readers of this chapter will learn:

    • The major known and suspected risk factors for lung disease in Alpha-1
    • Ways to minimize the effects of these risk factors
    • Cigarette smoke is the most important risk factor for lung disease in Alpha-1
    • How to identify reliable smoking cessation treatments and programs
    • Risk factors for lung disease include lung infections and prolonged exposure to dusts, organic fumes, and other inhaled toxins
    • The known or suspected risk factors for liver disease
    • To identify simple lifestyle changes to reduce risk exposure

    First among the controllable risk factors associated with development of lung disease in Alpha-1 is exposure to cigarette smoke. Whether from personal use or secondhand exposure, cigarette smoke has been undeniably shown to exert the greatest risk.

    For the smoker, inhaling cigarette smoke is known to accelerate the destructive processes at work in the lungs and puts the development of lung disease on the "fast-track." For Alphas who smoke, that fast-track becomes an "express train." But it is not only the risk to the smoker that is of concern. Secondhand smoke can also cause considerable damage to the lungs of Alphas who do not smoke themselves.

    In addition, children of smokers appear to have a much higher incidence of asthma than children of non-smokers. If your child is either an Alpha or an Alpha-1 carrier, the risk of developing lung disease in later life will be greatly increased by exposure to secondhand smoke (see "Disease Prevention in Alpha-1 Children" in Section C of this Guide). The risks associated with cigarette smoke, especially in the presence of Alpha-1, are clear and profound.

    Although cigarette smoking is recognized as a controllable risk factor, it is clear that, in many cases, it is not an easily avoidable one. Some Alphas live with smokers who are unwilling to quit. Although some Alphas never take another puff of a cigarette after they are diagnosed, this is certainly not always the case. It is important to understand that dealing with a cigarette addiction, as with any addiction, may be very difficult. Successful change takes knowledge, help from others, and a long-term commitment to health.
    The facts about smoking
    Nearly 500,000 people in the United States die each year from smoking cigarettes. Smoking is a well-known cause of cancer, stroke, heart disease, COPD and peripheral vascular disease, and exerts harmful effects on many other systems in the body as well. Recent long-term studies indicate that approximately one-half of all regular cigarette smokers will eventually die from their addiction.

    Since having Alpha-1 already puts you at an increased risk for developing lung disease, the damage inflicted by smoking will almost guarantee it. Therefore, your first priority for managing the risk factors associated with developing lung disease in Alpha-1 should be the elimination of exposure to all forms of tobacco smoke.

    The effects of smoking in Alpha-1 Antitrypsin Deficiency
    Smoking affects every part of the body. Cigarette smokers inhale over 400 toxins and 43 known carcinogens every time they puff. As smoke enters the respiratory tree and lungs, it causes irritation and triggers inflammation. This inflammation causes the body's defenses to send white blood cells to the area. While performing their normal function, the white blood cells release a powerful enzyme, known as neutrophil elastase. Neutrophil elastase is destructive to unprotected lung tissue. As you have already learned, alpha-1 antitrypsin (AAT) is the protein in our bodies that provides protection to the lungs by neutralizing this powerful enzyme.
    We know the chemicals created from burning tobacco destroy alpha-1 antitrypsin. In fact, a single cigarette destroys all the alpha-1 antitrypsin in the lungs. Because each cigarette smoked results in a repeated episode of irritation and inflammation, this process may therefore account for a significant portion of the lung disease seen even in non-Alphas. Among individuals with normal AAT levels, this damaging process generally occurs gradually. The symptoms of lung disease in these individuals, if they occur, tend to develop during their 50s or 60s.

    For Alphas, where protection against neutrophil elastase is already compromised by reduced AAT levels, the exposure to cigarette smoke increases the risk that lung damage will occur and will result in significant symptoms of lung disease. As opposed to "normal" individuals, this damaging process is accelerated in Alphas and their symptoms may develop as early as in their 30s.

    In view of the relationship between smoking and AAT levels, individuals preparing to receive augmentation therapy for Alpha-1 should be smoke-free and successful in maintaining smoking cessation before therapy is initiated. This makes sense if you remember that "augmentation" therapy is simply giving you a "boost" of AAT. If you smoke, the AAT boost will be destroyed just as your own AAT is destroyed by cigarette smoke.

    While almost everyone is aware of the links between smoking and heart and lung disease, few people think about the effects of smoking on other parts of the body. When the various toxins and products of cigarette smoke enter the lungs, they subsequently enter the bloodstream, where they circulate to the remainder of the body. One of the liver's primary functions is the processing of drugs, alcohol, chemicals, and other toxins to remove them from the body. Evidence suggests that smoking alters the ability of the liver to handle and "detoxify" such substances. Some research also suggests smoking can aggravate the course of the liver disease caused by excessive alcohol intake. Despite this damage, additional research has shown that the harmful effects of smoking on the liver are temporary and that most problems can be reversed when the individual stops smoking.
    Why quit?
    Despite knowing the harmful effects of smoking, smoking cessation can be a challenging and difficult undertaking because it involves overcoming physical dependency and nicotine addiction, as well as psychological factors. Nevertheless, the benefits of quitting are numerous, significant, and undeniable. Some of these benefits include:

    • Decreased airway inflammation
    • Prevention of the inactivation of alpha-1 antitrypsin
    • Decreased morbidity — you'll live longer
    • Decreased risk of heart disease, lung disease, and cancer
    • Decreased risk of other health effects
    • Improved lung function — less shortness of breath
    • Slowed rate of decline of lung function
    • Increased energy
    • Smoker's cough goes away
    • Digestion normalizes
    • The functioning of the liver normalizes
    • Create healthier environment for those who live with you, especially children
    • Release from the mess, smell, and burn holes in clothing and furniture
    • More money to spend on other things
    Developing a smoking cessation plan
    There are numerous resources available for individuals who want to quit smoking.

    • Organizations such as the American Lung Association and the American Cancer Society offer smoking cessation programs.
    • Your local hospital and your health care provider can provide you with treatment options and a list of smoking cessation programs in your area.
    • There are also countless resources on the Internet, for those who have access to this valuable tool.
    The first step is to have the desire and motivation to quit. For some, the diagnosis of Alpha-1 is the primary motivation. Once the decision is made, discuss developing a smoking cessation plan with your health care provider and your family and friends. Enlist their help and support. If other members of your family are smokers, encourage them to join you in quitting. The importance of maintaining a smoke-free environment within the home should be stressed and promoted. A few steps towards being smoke-free are:

    1. Set a date to quit: Some studies have shown that quitting altogether on one day is more successful than trying to gradually cut down on the number of cigarettes smoked.

    2. Change your immediate surroundings: Remove all cigarettes, lighters, matches, and ashtrays in the home, in your car, and at your work. DO NOT let people smoke in your home or vehicle.

    3. Get medicine to help you quit: Nicotine gum or patches are available at the local pharmacy. Your doctor can prescribe other medications that can help you, including nicotine nasal spray, nicotine inhaler, and oral medication, such as Bupropion, all of which can help reduce the urge and cravings for cigarettes.

    4. Substitute other activities: Change old patterns by substituting new and healthy activities in place of smoking, such as walking, biking, or gardening.

    5. Exercise and eat right: Some people gain a little weight when they stop smoking, but this is usually temporary and can be avoided with regular exercise and proper nutrition.

    6. Plan rewards: Plan a special reward for yourself and your family with the money you save.

    7. Maintain: Continue to work at your plan, instituting the successful changes and new behaviors to remain smoke free.

    Nicotine addiction and withdrawal
    Smoking cigarettes creates an addiction to nicotine, and individuals may experience withdrawal symptoms when they quit smoking. These symptoms can include irritability, restlessness, aggressiveness, depression, increased hunger, and cravings. Difficulty concentrating and decreased performance on mental and psychomotor tests have also been documented. These symptoms are transient and are most likely to occur within the first week of cessation. If they are particularly troublesome, the use of nicotine substitution products, such as chewing gum, patches, and nasal sprays, can help reduce the symptoms of nicotine withdrawal.

    Alternative smoking cessation methods
    Acupuncture is being more widely used but has yielded variable results, and it may be too soon to know whether or not this approach will ultimately prove to be of benefit. Behavioral techniques, such as hypnosis and counseling have been of benefit for some, as has participation in smoking cessation programs and support groups. In fact, combining more than one form of treatment may increase your chances of success.

    If at first you don't succeed ...

    Most smokers will have tried to stop on several occasions with varying degrees of success before they finally "kick the habit" for good. Smokers need to be constantly encouraged by their physician and family members. The physician's active participation in the process is invaluable. Ask your friends or family for their support. They may want to stay in touch with you to offer ongoing support. If you should suffer a lapse and return to smoking, then it's back to the starting point: set a date, make a plan, and put the plan back into action.

    Of the various smoking cessation strategies, none have been shown to be consistently more effective than another, but one may succeed where another has failed. So if you are not successful the first time, don't give up! Seek help and support. If you resume smoking after having stopped for a period of time, evaluate where your difficulty arose and consider utilizing nicotine replacement therapy, behavioral intervention, or individual or group counseling to help improve your chances of success.
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    jon daly

    jon daly Member

    fucking amazing report. thanks for all the info sub!

    hexthat Well-Known Member

    do you have some issue and that is why you say you have a "medical conditions" and you don't smoke BHO?

    subcool Well-Known Member

    I don't smoke BHO because I am informed.
    Yes I am an Alpha-1 ZZ

    TrichomeBob New Member

    Thanks sub, I'm gonna inquire more with my doc about this, good read too

    Shawns Active Member

    Hey Sub you should check this stuff out called Fossil Shell Flour for human consumption its FDA approved 100% safe for human and animal consumption it's all natural and does many good things for your body just trust me check it out

    subcool Well-Known Member

    Very kind but there is no medication that will allow the trapped Enzyme out of my liver I have to have the transfusions

    I do take a double hand full of respiratory lung supplements each day but it's most likely a waste of money.
    It's kind of like giving an asprin to someone with Malaria, but I do still try the alternate route.

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    hexthat Well-Known Member

    I like keif myself =] ill still take a rip of BHO despite the health concerns i may have but im still young and dont think much about my health... which is why i have no health insurance:D

    beuffer420 Well-Known Member

    still wouldn't hurt if can make your body healthier:)

    cripfingers New Member

    Hey Sub,

    I just got diagnosed A1AD a few months ago. I am ZZ type also. I have emphysema at 33 years old! We don't have infusions here in the UK so I dunno what my options are yet. I just wanted to say that before I got this diagnosis you were my weed hero, but now I know we're both Alphas you're my sick hero too!
    I recently started watching the weed nerd on youtube trying to raise my standards which is how I came to know about your diagnosis. Imagine my shock when you mentioned the A1AD.

    Anyway, I wanted to say hello and to say I have great respect for you and just also to let you know that there is another who knows how it feels :D

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