The specific therapy for the treatment of Alpha-1-related lung disease is augmentation therapy – also called replacement therapy. Augmentation therapy is the use of alpha-1 antitrypsin protein (AAT) from the blood plasma of healthy human donors to augment (increase) the alpha-1 levels circulating in the blood and lungs of Alphas diagnosed with emphysema. The therapy is administered by a weekly intravenous infusion and, until other therapies become available, is considered ongoing and lifelong.
While augmentation therapy is considered the only specific therapy for Alpha-1 lung disease, the treatment plan for lung-affected individuals with Alpha-1 should also include the appropriate use of antibiotics, an immunization program including viral hepatitis and influenza strains, reduction or elimination of environmental risk factors, appropriate inhaled medications, an exercise program, and oxygen, if needed.
What are the goals of therapy?
The basic goal of augmentation therapy is to increase the level of alpha-1 protein in the lungs. Alpha-1 antitrypsin protects the lungs from the destructive effects of neutrophil elastase, an enzyme released by our body’s white blood cells as they respond to inflammation or infection.
The ultimate goal is to slow or stop the progression of lung destruction by replacing the deficient protein. The therapy cannot restore lost lung function — nor is it considered a cure. There is also some evidence that augmentation therapy can reduce the frequency and severity of pulmonary exacerbations (flare-ups of lung disease) and it appears to be an effective treatment for the Alpha-1 related skin disease, Necrotizing Panniculitis.
Currently available therapy
There are four augmentation therapy products approved by the U.S. Food and Drug Administration (FDA) and available in the United States, and more potential therapies are on the horizon. The five approved products are Prolastin-C® and Prolastin-C Liquid® from Grifols, Aralast NP™ from Shire, Zemaira® from CSL Behring and Glassia® from Kamada Ltd. A product named Trypsone® from Grifols is available in Spain. Prolastin has been marketed since 1988 and has an excellent safety record. Aralast NP and Zemaira were introduced to the marketplace in 2003 and Glassia was introduced in 2010. Each was approved by demonstrating that they were comparable to Prolastin in their safety and in augmenting blood and lung alpha-1 levels.
Augmentation infusions are typically given by healthcare professionals in the home, at a physician’s office, outpatient infusion center or other medical facility.
Sometimes Alphas choose to self-infuse after receiving appropriate instruction from a healthcare professional and with the approval of their physician. In 2016, Glassia received FDA approval for self-infusion. Health insurance payment rules often dictate the place of infusion. A quick reference chart describing the available products is at the end of this article.
Who should receive augmentation therapy and when should they start?
Augmentation therapy should be given to individuals with documented emphysema and severe Alpha-1 (defined as individuals with two abnormal alpha-1 genes). There has been some controversy, however, about giving augmentation therapy to anyone whose lung disease is very mild or very severe.
In some research studies conducted since the introduction of augmentation therapy, the benefits identified were primarily seen in certain groups of people. In these studies, the most dramatic effects were seen in those people whose lung function fell in the mid-range of severity.
Some members of the healthcare community have used these results incorrectly, to suggest that only those with moderate lung disease should receive augmentation therapy. However, because augmentation therapy is considered preventive rather than curative – it puts the brakes on lung destruction rather than reversing it – it seems logical to begin therapy as soon as possible after Alpha-1 lung disease has been detected, especially if the lung disease is progressing in spite of eliminating risk factors such as smoking.
In 2016, the Medical and Scientific Advisory Committee of the Alpha-1 Foundation released clinical recommendations designed to guide doctors on how to properly diagnose and treat Alpha-1 Antitrypsin Deficiency (Alpha-1) in adults. They are based on the latest evidence and recommend best practices on testing for Alpha-1, Alpha-1 lung and liver disease, and when augmentation therapy should be prescribed. The guidelines are intended to update a 2003 document from the American Thoracic Society and the European Respiratory Society on the diagnosis and management of Alpha-1.
The Clinical Practice Guidelines recommend augmentation therapy for all Alphas who have Alpha-1-related lung disease, although they point out that the evidence for treating those with an FEV1 less than or equal to 65 percent predicted is stronger than for those with better lung function. The guidelines also recommend augmentation therapy for anyone with necrotizing panniculitis.
See the Clinical Practice Guidelines - The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult as published in the Journal of the COPD Foundation.
Things to consider before beginning augmentation therapy
Before beginning augmentation therapy, a patient should be tested for IgA deficiency, a hereditary condition that makes potentially severe allergic reactions to plasma products more likely.
AlphaNet recommends that immunization against both Hepatitis A and B be considered for all Alphas to reduce the risk of liver injury. Vaccination entails a series of three injections, generally administered over six months. Augmentation therapy can be started independent of whether or when hepatitis vaccine will be given.
Are there any side effects from augmentation therapy?plus
Alphas receiving any of the available augmentation therapies have reported a variety of side effects, although the vast majority never have any significant problems. The most common side effect is a sense of feeling drained or having flu-like symptoms that typically last for up to 24 hours after an infusion. These symptoms can often be reduced or eliminated by slowing the rate of infusion.
Some Alphas have symptoms that seem like mild allergic reactions: rash or hives, itching, tightness in the chest, dyspnea, and/or wheezing. Many of them can continue receiving augmentation therapy if they take an antihistamine, such as Benadryl, before their infusions. Rarely, side effects are severe enough to cause an Alpha to stop augmentation therapy entirely.
The FDA has approved a dose of 60 mg/kg of body weight administered once a week for each of the currently available augmentation products. Therefore, the recommended dose for someone weighing 165 lbs (or 75 kg) would be 4,500 mg per week.
IV access for augmentation therapyplus
The overwhelming majority of Alphas receiving augmentation therapy choose to have a simple IV catheter or needle placed in the hand or arm at the time of each infusion. These catheters are well tolerated; remain in place for only a short time; and the complications are minimal. There are a variety of devices available, all designed to provide for ease of placement and patient comfort.
Some people have veins that are hard to see and hard to access. Devices implanted under the skin – most often a port – can make regular infusions more convenient. See “Veins or a Port” below.
This information is based on AlphaNet’s booklet, Augmentation Therapy, The Specific Therapy for Alpha-1 Lung Disease. The booklet is part of the Skinny Little Reference Guide series, extracted from AlphaNet’s Big Fat Reference Guide to Alpha-1. These resources are available on AlphaNet’s website, www.alphanet.org. The Alpha-1 Foundation is grateful to AlphaNet for its generous help.
Your Veins or a Port?plus
What an Alpha Needs to Know
Some Alphas, often directed by their healthcare providers, choose a device placed under the skin for their infusions. These devices include the Implanted Vascular Access Device (IVAD), usually called a port, and various types of tunneled central catheters or Peripherally Inserted Central Catheters (PICC)
The decision to choose one method of IV access over another should be a well-researched and informed decision. Having such a device in place may make the infusion process easier, but it may pose some additional risk to you.
Be sure that you clearly understand the procedures involved in the insertion of each of these devices when making your decision. It is important to discuss the risks and benefits of any type of IV access thoroughly with your healthcare provider and then choose the IV device that makes the most sense for your particular situation.
The major points to consider
What to consider when choosing an implanted vascular access device (a port) or a central catheter:
- What is the general condition of your veins? Are they visible on the back of the hands and forearms?
- Are they accessible?
- What is your infusion schedule?
- Have you had difficulty with peripheral IV insertion?
- Have you had good experience with IVs given by certain healthcare providers and bad experiences with others?
- Have you been informed of the risks and benefits of the particular device and do the benefits outweigh the risks?
- Do you understand the procedures for insertion?
- Have you talked with others who have had an implanted device?
- Do you plan to do your own infusions, or have a spouse or significant other do them for you?
- Do you understand the special care and maintenance required of the device?
Port and central catheter infections
Infection of the port or central catheter can pose an important challenge for healthcare providers and Alphas receiving augmentation therapy — because the signs and symptoms of a port infection often mimic the signs and symptoms of a reaction to augmentation therapy.
An infection can be external, located at the site where the port or central catheter is implanted, under the skin in the “pouch,” or along the tunneled area of the catheter. An infection also can occur within the reservoir of a port, or along the walls of the central catheter in the vein. Bacteria can be inadvertently introduced into the device through lapses in sterile technique; inadequate skin preparation; or contaminated equipment. The device may attract bacteria from other infections in the body, which can flourish in the port or central catheter. If an infection is present, when the device is accessed and flushed, a shower of bacteria can be sent into the bloodstream.
Important signs of infection include:
- Localized site redness, swelling, tenderness, drainage
- Body aches
- Shaking, chills, and/or fever over 101° F
- Abdominal pain
- Nausea and vomiting
- Increased difficulty breathing
Many people mistakenly assume these symptoms are caused by a reaction to their medication. Both situations have similar symptoms, and one can mimic the other. Though some patients do have side effects from their therapy, a patient with an indwelling port or a central catheter must first consider an infection, and this should be ruled out before assuming that a medication reaction has occurred.
What to do if you have symptoms after an infusion and you have a port or central catheterplus
If you have a port or other implanted device and you experience problems during or shortly after your infusion, report this immediately to your nurse and physician. Check your temperature, especially if you experience shaking or chills. Call your doctor promptly if you have a fever over 101°. If symptoms are severe, seek immediate medical attention.
Your physician will want you to have laboratory tests to check for the presence of an infection. The diagnosis of an infection is based on results from blood cultures, often drawn from a vein in your arm as well as from the port or other device.
If you are due for an infusion while undergoing a work-up for infection, you still may receive your infusion if approved by your physician. It is recommended, however, you DO NOT USE the port for the infusion. The infusion should be administered through an IV catheter placed in your hand or arm.
Watching for symptoms during this peripheral infusion will help to determine if a medication side effect is the source of the problems, or if the symptoms are related to the port or central catheter.
If an infection has been confirmed, depending on the severity or the bacteria involved, IV antibiotics may be required to treat the infection. In some instances, the device will need to be removed. If all blood cultures are negative, further monitoring is required, and investigation into a reaction to the medication should be pursued.
Prevention is the best intervention
The best intervention for a port or other central catheter infection is prevention. Preventing infection should be the priority of everyone who has a port or other central device, as well as a top priority for those healthcare providers who access these devices. Because these devices provide a direct connection from the outside environment into the large blood vessels of the body, excellent hand washing and the maintenance of sterile technique while performing all procedures is essential in the prevention of infection.
It’s a good idea to limit the number of people who handle the port or central line — and never allow anyone who is ill to handle the device. It is generally recommended that anyone caring for these devices wear a mask. A mask is provided in most central device access kits for just this purpose.
Augmentation Questions and Answers
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 is 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. 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 alpha-1 blood levels be checked?plus
Q: How often should the levels of alpha-1 protein in the blood be checked?
A: It usually is not necessary to have more than one alpha-1 protein 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 after augmentation therapy begins. 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 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.
Alphas 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 people who are IgA-deficient. 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.
The American Thoracic Society and European Respiratory Society have established standards for testing and management of Alpha-1 Antitrypsin Deficiency. The American Journal of Respiratory and Critical Care Medicine published the standards in 2003. Learn more about the ATS/ERS Standards document.
The Alpha-1 Foundation has a web page on Access and Reimbursement for augmentation therapy.
The Alpha-1 Foundation has published a press release in response to a review published by the Cochrane Library recommending against the use of Alpha-1 augmentation therapy. Read the response