Alpha-1 Lung Disease

Alpha-1 antitrypsin protein acts to protect the lungs’ air sacs, or alveoli, from damage when the immune system is doing work to protect the lungs. One type of the body’s own white blood cells, the neutrophil, releases a chemical called neutrophil elastase when it encounters inflammation or infection. Although neutrophil elastase can be helpful in protecting the lungs from attach, it can also damage the lungs and cause emphysema if not held in check.

Alpha-1 antitrypsin protein holds blocks elastase and protects normal tissue in the lungs. If there is not enough alpha-1 antitrypsin produced in and released by the liver, there will not be enough to protect the lungs’ alveoli, and emphysema or COPD develops. This is Alpha-1 lung disease.

About 1 in every 3,500 people has severe Alpha-1. The majority of people who have Alpha-1 are of Northern European decent, especially Scandinavians, but it has been found in all ethnic groups.

Symptoms of Alpha-1 Lung Disease

People who develop Alpha-1 lung disease can develop shortness of breath by the time they are 40 or 50 years old, frequently earlier in those who smoke cigarettes. Some with Alpha-1 lung disease will develop bronchitis and eventual disruption of the normal architecture of the bronchial tubes and air sacs, such as bronchiectasis and emphysema. This can lead to recurrent episodes of cough, sputum production and even pneumonia. But shortness of breath is the most common symptom with developing Alpha-1 lung disease.

Associated Conditions with Alpha-1 Lung Disease

Liver Disease

In addition to causing lung disease, 25 percent of people with Alpha-1 deficiency due to the PiZZ genes will develop liver disease.  Liver disease from Alpha-1 can also affect newborns and children.

Skin Disease

Panniculitis is a disorder of skin tissue, including fat that lies underneath the skin. It usually involves inflamed, red lumps, often found on the legs. This condition is very rare. Alpha-1 antitrypsin replacement therapy is effective for the treatment of skin lesions.

Pulmonary Hypertension

This is a disorder of large and small blood vessels in the lung that leads to increased pressure, or hypertension, in the large vessels leading to the lungs from the right side of the heart. In very severe cases, the increasing pressure inside the right side of the heart can lead to right heart failure. This can be evaluated by cardiac ultrasound (cardiac echo) or heart catheterization.

Hypoxemia

Low oxygen levels in the bloodstream (hypoxemia) can be measured using a finger pulse oximeter. Severe emphysema and living at high altitude can be associated with hypoxemia and will require you to wear oxygen when walking, with sleep, or even 24 hours a day. Prolonged hypoxemia can cause pulmonary hypertension.

Cachexia

Significant weight loss, poor appetite, muscle atrophy and fatigue in someone who is not trying to lose weight is called cachexia. In people with Alpha-1, this condition is caused by the spillover of the inflammatory chemicals from the affected lung or liver into the main bloodstream and by the increasing amount of the body’s energy that is devoted to the respiratory muscles.

Deconditioning

This is decreased ability to sustain a physical effort, from walking to carrying grocery bags. The diagnosis of deconditioning is based on your symptoms and completion of a cardiopulmonary exercise test ordered by your doctor.

Cardiovascular Disease

Overlap with coronary artery disease and hypertension is common in people with Alpha-1. The shortness of breath, hypoxemia and deconditioning may be worse. All people with Alpha-1 may be screened for cardiac disease. Attention should be paid to medications prescribed for the treatment of both conditions, as several lung medications can worsen a heart condition, and some medications used to treat hypertension and angina can negatively affect the lung.

Thromboembolic Disease

People with Alpha-1 can develop blood clots, especially in the veins of the calves and thighs, which later can migrate into the lung circulation and cause pulmonary embolism. Engorged and painful veins or acute severe shortness of breath are symptoms associated with this disease. Testing in a hospital setting is necessary to perform a leg ultrasound and chest computed tomography. Treatment with blood thinners is the usual treatment.

Infections

Nontuberculous mycobacteria lung infection, also called NTM, MAC or MAI, may occur more often in people with Alpha-1, even in heterozygous people, such as PiMZ. Nontuberculous mycobacteria are organisms commonly found in water and soil that can cause a lung disease resembling tuberculosis, although not contagious. Nontuberculous mycobacteria are difficult to treat, and consultation with an infectious disease specialist is often helpful.

People with Alpha-1 who have a catheter like a port or PICC line for weekly Alpha-1 antitrypsin augmentation therapy administration can develop catheter-related bloodstream infections with bacteria found commonly on the skin. Testing in a hospital setting is necessary to collect blood cultures. It is recommended to remove the catheter while receiving antibiotic treatment and carefully reconsider placing a new catheter.

Lung Cancer

There is some evidence that people with Alpha-1 Z or S genes may be at increased risk of developing lung cancer, even in the absence of exposure to cigarette smoke or asbestos, the two most common risk factors for lung cancer. A CT of the chest is a useful screening method for lung cancer.

Diagnosis of Alpha-1 Lung Disease

There are a couple core screening tests that are used to diagnose alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin blood level, Pi-type or phenotype (structure of the protein made by the Alpha-1 gene), and genotype (testing the Alpha-1 DNA)

In people with Alpha-1 lung disease, the blood level of alpha-1 antitrypsin will often be very low, less than 20 percent of the normal level. The phenotype (Pi-type) of the alpha-1 antitrypsin protein in a person is determined by identifying how the protein moves on an electrified gel. A normal protein is referred to as an M protein. A person with normal alpha-1 antitrypsin proteins is referred to as Pi MM. The most common abnormal proteins are S, Z and F. Sometimes a gene will make no protein; this a “null” gene. When you have two Z genes, you are Pi ZZ, and a person that is most likely to get Alpha-1 lung and/or liver disease.

Chest radiograph or Chest CT scan

A chest x-ray may reveal that the lungs are hyperinflated due to emphysema. A chest CT will show a pattern of emphysema specific to Alpha-1. When the normal small air sacs (alveoli) of the lungs break down and consolidate, they look like large holes in the lung, like the holes in Swiss cheese. In those who smoke but don’t have Alpha-1, emphysema will occur more frequently in the upper part of the lung. In those with Alpha-1 emphysema, the lower parts of the lung are most commonly affected. Bronchiectasis can occur in those with Alpha-1 lung disease. This is the permanent dilation and thickening of the bronchial tubes from chronic inflammation.

Treatment of Alpha-1 Lung Disease

Treatment for Alpha-1 is important and includes:

Medications

People with Alpha-1 may live long, healthy lives without ever getting lung or liver problems from their Alpha-1.  For those who develop emphysema or COPD, treatment starts with the same medications and therapies used for those who get COPD without Alpha-1. The medications include:

• Inhaled bronchodilators
• Combination medication
• Inhaled corticosteroids
• Medication to prevent COPD flare-ups

In addition, specific therapy has been available for Alpha-1 lung disease since 1987, a class of medicine called augmentation therapy. This medication augments the alpha-1 antitrypsin protein in the blood with normal alpha-1 antitrypsin from healthy plasma donors and is infused into an arm vein. The dose is adjusted based on body weight, and this treatment is given once a week. This therapy does not help people with liver disease due to Alpha-1. There are currently four brands of augmentation therapy approved in the U.S. They include:

• Prolastin®
• AralastTM
• Zemaira®
• Glassia®

Other Treatment Options

• Avoiding infection
• Oxygen therapy for those with oxygen saturation levels below 89%
• Breathing Retraining
• Techniques to bring up mucus
• Pulmonary rehabilitation
• Surgery is a treatment option for Alpha-1, depending on the type and severity of disease. This could include:
  1. Lung transplant
  2. Lung volume reduction surgery (LVRS) although often people with Alpha-1 lung disease are not good candidates for surgical lung volume reduction surgery.
  3. Liver transplantation may be an option for people severely affected by Alpha-1 liver disease.

Healthy Lifestyle

A healthy lifestyle is important for everyone, including people with Alpha-1 and their caregivers: A healthy lifestyle includes:

• Regular exercise
• Giving up smoking and avoiding secondhand smoke. This is important in managing Alpha-1. Smoking can accelerate or speed the development of Alpha-1 related emphysema and shorten lifespan.
• Healthy eating

Remember, people with Alpha-1 can live a full life.

What Specialist should I see if I have Alpha-1 Lung Disease?

If you have any abnormal Alpha-1 genes (e.g., Z, S, F, null), discuss the risk of lung disease with your Alpha-1 doctor. Different Alpha-1 genes lead to different risk for disease. You may be referred to a pulmonologist who specializes in Alpha-1 lung disease.