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General Information

Alpha-1 Week

What is COPD?

COPD is a chronic breathing condition wherein there is persistent, chronic obstruction to the flow of air through the lungs that makes it harder to breathe. The term "COPD" includes the disorders called chronic bronchitis and emphysema. It also includes some cases of refractory asthma where the airflow obstruction is not fully reversible despite medical treatment, and some cases of "bronchiectasis". 

The obstruction to the flow of air can result from narrowing of the airways (the "bronchial tubes" or "bronchi") in the lung due inflammation in the walls of the airways, constriction of the muscle in the airway walls, and/or excess production of mucus into the airways. The term "emphysema" means there is destruction of some of the air sacs in the lung. 

Inhalation of tobacco smoke is the biggest risk factor for developing COPD. Other risks include environmental exposures such as smoke from wood-burning stoves, organic cooking fuels, prolonged exposures to other chemicals, fumes or dusts, and frequent respiratory infections in early childhood.  Genetic factors also influence the risk of developing COPD.  The condition of alpha-1-antitrypsin deficiency is, to date, the best characterized genetically-inherited disorder associated with COPD.

What is Alpha-1-Antitrypsin Deficiency?

Alpha-1-antitrypsin deficiency is an inherited (genetic) disorder in which abnormal, insufficient amounts of a protein called alpha-1-antitrypsin (AAT) circulate in the blood. Under healthy conditions, the AAT protein helps protect tissues in the body, especially the lungs, from being degraded (destroyed) by other proteins in the body called "enzymes".  Deficiency of the AAT protein places the lungs at increased risk of gradual tissue destruction over time, with resultant impairment in lung function.   AAT Deficiency occurs because inheritance of abnormal genes leads to production of abnormal AAT by the liver. The liver can't secrete this abnormal protein, so circulating blood levels of AAT are low, yet abnormal amounts of the AAT protein can build up in the liver, also leading to risk of liver disease.  Skin problems can also occur in some people.

Alpha-1-antitrypsin deficiency can be identified in young adults as early as the third decade but can be diagnosed at any age. Both women and men can be affected. Each individual inherits one copy of each AAT gene from each of their parents. The normal AAT gene (allele) is called the "M" variant, so healthy individuals would have two "M" alleles and be referred to as "MM genotype". These individuals make a normal AAT protein and have normal AAT levels in the blood. Many abnormal genetic variations of the AAT gene have been identified.  The two variations most commonly associated with development of COPD and liver disease are the "Z" allele and the "S" allele.   Inheritance of the "S" variant is typically associated with milder deficiency of AAT and affected persons are at less risk of developing lung or liver disease.   In contrast, inheritance of two copies of the "Z" variant (one from each parent) typically leads to very low blood levels of AAT and carries increased risk of developing both lung disease (COPD) and liver disease.  People who have inherited one "M" and one "Z", or one "S" and one "Z" carry a slightly increased risk of developing lung or liver disease, but less so than those who have inherited two "Z" variants.

What are the major symptoms of COPD, including for those with AAT deficiency?

The major symptoms of COPD include shortness of breath, coughing (either with or without mucus production, and wheezing.  The shortness of breath tends to worsen during physical activities such as walking, running, carrying heavy items, ascending stairs or other forms of physical exertion. For those with more severe impairment of their lung function, even daily activities such as dressing, bathing, and eating can become difficult.   The amount of coughing, wheezing, and mucus production varies among individuals. While cough and/or mucus production are common and may occur on a daily basis for some, others have very little or none of these symptoms. Other common symptoms of COPD can include general fatigue, a sense of tiredness of the legs during activity, and sleep disruption.  Most people with COPD experience "good days and bad days" with regard to their symptoms. This variation can relate to changes in activity level, temperature and humidity of the air, pollen and/or air pollution levels, use of inhaled medications and other factors.

What are exacerbations of COPD?

Many people with COPD (including those with AAT deficiency) experience intermittent "acute exacerbations" of their disease. Acute exacerbations of COPD are present when there is a worsening of symptoms beyond the normal day-to-day variation that require a change in (intensification of) medical therapy. The worsening symptoms may include shortness of breath, coughing, wheezing, mucus production or a combination of these.  Some individuals experience more frequent exacerbations than others. Acute exacerbations of COPD vary in severity from mild to very severe.  While many can be managed at home (as an outpatient), some are severe enough that they require people to be hospitalized, and some can even lead to respiratory (breathing) failure requiring temporary breathing assistance from a mechanical ventilator (respirator).

How is COPD Diagnosed?

COPD is usually detected by a non-invasive lung function testing called "spirometry". This test involves taking deep breaths and exhaling air rapidly and forcefully through a mouthpiece into a machine that detects the flow of air.   Other tests such as imaging (especially CT scans) and blood tests can also be helpful in diagnosing and assessing COPD.

How is Alpha-1-Antitrypsin Deficiency Diagnosed?

Alpha-1-AT deficiency may cause emphysema, chronic bronchitis, "bronchiectasis" or may present as chronic asthma. Individuals with any of these conditions (particularly those who develop them at a young age), or who have a family history of AAT deficiency or a history of chronic liver disease should be tested for AAT deficiency. Testing involves obtaining a sample of blood from the vein. The levels of the AAT protein, and the genetic variants "alleles" you inherited can be tested in this manner.

What are the available treatments for COPD?

COPD is not "curable", in that it is still present despite maximal treatment. As such, the available treatments often do not make symptoms resolve altogether. However, symptoms can usually be greatly improved by treating COPD! Key goals of treatment are to reduce symptoms and improve activity/exercise tolerance as much as possible, improve quality of life, prevent acute exacerbations of COPD, avoid hospitalizations, and stabilize lung function over time. 

There are several components of treatment for COPD and AAT Deficiency. 

Smoking Cessation:
Avoidance of tobacco use (or passive exposure to it) is an essential component of treatment for all people with COPD.  Notably, cigarette smoking and exposure to second hand smoke markedly increases the risk of developing emphysema or other aspects of COPD for people with AAT deficiency. People with AAT who never smoke and who avoid contact with environmental pollutants may not develop lung disease.  However, those who are current smokers are advised to quit immediately if diagnosed with AAT deficiency, to decrease the chances of developing or worsening lung destruction.

Alpha-1-Antitrypsin Replacement Therapy:
Individuals with very low blood levels of the AAT protein who have evidence of emphysema may be candidates to receive replacement, "augmentation" therapy with AAT Protein that has been purified from healthy human blood donors. The AAT protein is administered into a vein by intravenous ("IV") infusion once weekly. This can be done at home or at an outpatient hospital-based infusion center. This treatment can increase the levels of AAT in the blood, and may decrease the chance of worsening of lung disease over time. AAT augmentation therapy does not reverse existing lung disease, and is not helpful to prevent or treat liver disease associated with AAT deficiency.   Your healthcare provider can advise you as to whether you may be a candidate to receive AAT augmentation therapy.

Non-pharmacologic Treatments:
Some people with COPD, typically those with more severe disease, require treatment with supplemental oxygen therapy. This is usually required when the lungs become unable to extract sufficient amounts of oxygen from the air to achieve adequate amounts in the bloodstream.   Oxygen therapy is typically prescribed when blood oxygen saturation levels are less than 88 to 90%, either at rest, during exertion and/or during sleep.  There are many different types of oxygen systems now available for use in the home as well as for portable use outside the home.  Some people also can benefit from use of non-invasive machines to assist breathing (commonly referred to as CPAP or BiPAP machines), particularly when breathing becomes inefficient during sleep despite use of supplemental oxygen or when a condition called "obstructive sleep apnea" is also present.

Pulmonary rehabilitation (PR) is an essential component of the treatment of COPD for individuals who remain symptomatic despite regular use of inhaled medications. Pulmonary rehabilitation involves gradual exercise reconditioning to improve strength and endurance for daily activities and education designed to help patients manage and cope with their COPD as best as possible. Expected benefits of PR include a reduction in breathlessness, improvements in activity and exercise tolerance and quality of life. Participation in PR can also reduce the risk of future exacerbations and hospitalizations.

Surgical treatments such as lung volume reduction surgery and lung transplantation are considered for some patients with advanced disease that cannot be managed adequately with alternative treatment options.  Individuals can consult with their healthcare providers to see if they may be suitable candidates for these treatments.

What is the expected course of COPD?

While in general COPD tends to be a progressive disease wherein lung function gets worse over time, the rate at which lung function worsens varies a lot among individuals. Some people are more prone to having more rapid decline in lung function than others. A key goal of COPD treatment is to maintain lung function as stable as possible for as long as possible.  When COPD (including AAT deficiency) is present, smoking cessation and abstinence from tobacco inhalation is essential to help stabilize and prevent further loss of lung function.  Regular use of inhaled medications, avoidance of triggers for exacerbations of symptoms, maintenance of a regular daily physical activity routine, participation in pulmonary rehabilitation and use of supplemental oxygen as needed, and close partnering with healthcare professionals can all help to maintain stability of COPD over time.

Where can I go for additional information?

There are many excellent sources of additional information available on COPD and AAT deficiency.  Some of these include:

The COPD Foundationwww.copdfoundation.org or COPD Information Line: 1-866-316-COPD

The Patient Information page of the Global Initiative for Obstructive Lung Diseaseswww.goldcopd.org

Living Well with COPD:  www.livingwellwithcopd.com

Alpha-1-Foundation: www.alphaone.org or 1-877-2cure-A1 (1-877-228-7321)

AlphaNET: www.alphanet.org, or 1-800-577-2638


Four Facts About Alpha-1

  1. Alpha-1 Antitrypsin Deficiency (Alpha-1) is a genetic (inherited) condition – it is passed from parents to their children through their genes.

  2. Alpha-1 may result in serious lung disease in adults and/or liver disease at any age.

  3. Alpha-1 has been identified in nearly all populations and ethnic groups. It is estimated that about 1 in every 2,500 Americans have Alpha-1.

  4. Alpha-1 is the most common known genetic risk factor for emphysema.