Alpha-1 antitrypsin deficiency is a genetic disorder passed on from parents to children that may result in serious lung disease in adults and/or liver disease in infants, children, and adults. In this disorder, there is a severe lack (or deficiency) of a protein in the blood called alpha-1 antitrypsin (AAT). AAT is produced in the liver and protects the lungs from inflammation caused by infection and inhaled toxins such as tobacco smoke. The low level of AAT in the blood occurs because the AAT is abnormal and cannot be released from the liver. This also leads to a build up of AAT in the liver which can cause liver disease.

 

Alpha-1 can lead to lung disease such as chronic obstructive pulmonary disease (COPD), even if you are not a smoker. Alpha-1 also increases the risk of liver cirrhosis and a skin condition called panniculitis.

Chronic obstructive Pulmonary Disease (COPD) is a disorder characterized by airflow obstruction due to chronic bronchitis or emphysema. Symptoms include shortness of breath, difficulty breathing, coughing, and wheezing. COPD develops as a result of exposure to inhaled toxins, most commonly tobacco smoke, but can also develop due to having alpha-1. The diagnosis of COPD is made by taking a detailed medical history and confirmed by special breathing tests (spirometry) to document airflow obstruction and to determine the severity of the condition.

 

Chronic bronchitis is persistent inflammation of the airways. Symptoms include cough, phlegm production, and shortness of breath. When airways become inflamed, mucus glands multiply and mucus production increases, leading to coughing and shortness of breath. The lining of the airway also loses hair like projections (called cilia), making it more difficult to expel mucus. This creates more coughing, irritation and mucus production.

 

Emphysema is an irreversible condition characterized by destruction of the air sacs in the lungs. These air sacs, known as alveoli, allow for the absorption of oxygen into the bloodstream and for the elimination of carbon dioxide waste. Destruction of the alveoli results in larger air sacs that are less functional for oxygen exchange with the blood, and difficulty exhaling air out of the lungs. Symptoms include shortness of breath and chronic cough

Cirrhosis of the liver is a slowly progressing disease where normal liver tissue is replaced with scar tissue. Eventually this prevents the liver from functioning properly, as blood flow is diminished, causing slower processing of nutrients, hormones, drugs, etc. Symptoms of cirrhosis include nausea, weakness, abdominal pain, weight loss and flatulence. Alpha-1 severe liver cirrhosis and liver failure is rare, and scientists believe this may be due to the presence of other genetic and/or environmental factors. Alpha-1 liver disease is usually detected by simple blood tests. If more advanced liver problems appear, your doctor may recommend an ultrasound, abdominal CT scan, or liver biopsy.

Panniculitis is the inflammation of the fat beneath the skin, causing the skin to harden and form lumps, patches or lesions. Alpha-1 panniculitis is rare. 

Severe Alpha-1 Antitrypsin Deficiency occurs in 1 in 5,000 to 1 in 6,000of the North American population. Unfortunately, only about one in twenty patients with alpha-1 are correctly diagnosed by their doctors; most are mistakenly thought to have more commonplace lung conditions such as asthma.

Lung Symptoms

  • shortness of breath
  • wheezing
  • persistent or recurrent cough and phlegm production
  • recurring chest colds or bronchitis

 

Liver Symptoms

  • skin and eyes turning yellow (jaundice)
  • swelling of the abdomen
  • vomiting blood or passing blood in the stool

Half of your genes are passed on from each parent. Different versions of the genes results in different Alpha-1 Antitrypsin (AAT) production, including:

 

Version of Gene

AAT Production

M

Normal

S

 Low

Z

 Low

Rare

Very Low

Null

None

 

 

Different versions of the genes inherited from each parent combine to result in individuals that have these common genotypes:

 

Genotype

Disease

AAT Blood Levels

Risk for Symptoms

MM

Normal

Normal

None

MS

Carrier

80% of normal

Low

MZ

Carrier

60% of normal

Low

SS

Alpha-1

50% of normal

Low

SZ

Alpha-1

40% of normal

Moderate

ZZ

Alpha-1

10% of normal

Severe

Null Null

Alpha-1

None

Severe

 

 

Example: If one of your parents had normal levels of AAT (i.e. genotype MM) and the other had very low levels (i.e. genotype ZZ) then your genotype would be MZ (one gene from each parent) and you would be at low risk for symptoms as a carrier of Alpha-1.

Diagnosis involves two tests, a blood test to determine levels of Alpha-1 Antitrypsin (AAT), and genotyping:

1. A simple blood test detects the level of AATcirculating in your blood. If blood levels are lower than 150 mg/dL (1.5 g/L), your doctor will arrange for genetic testing to confirm the diagnosis of Alpha-1. Blood levels lower than 50 mg/dL (0.5 g/L or 11uM) are most strongly linked with emphysema and COPD.


2. Genotyping is carried out after an individual has low AAT levels in their blood. It is a genetic test that determines which two versions of the gene for AAT a person has (ie. M, S, Z, Rare, Null).Currently there is no cost, and there are two options for testing.

 

a) Through your Doctor: Your family doctor may refer you to a specialist for lung symptoms. Your specialist may complete a requisition form for Alpha-1 genetic testing, and a detailed response is provided within 30 days that outlines the results of the test. If you have low blood AAT levels and your family doctor or specialist is not familiar with Alpha-1, please see option b) and direct your doctor to this web site (under For Physicians).

 

b) AlphaKit Blood Drop Cards: Grifols, the makers of Prolastin®-C, have developed and received government approval for an Alpha-1 test kit. Once your doctor has determined your AAT level is low, you or your doctor can call the Alpha-1 Canadian Registry at 1- 800-352-8186 to order a test kit. The Registry will mail you the test kit, and you will provide three dry blood drop samplesthat you mailto a testing facility at the University of Florida (postage paid envelope pre-addressed to the testing facility is provided). Within four to six weeks the registry will receive the results and contact you immediately. There is no charge for the test kit or results. Note: this program is being managed and operated for Grifols by third parties; Grifols will not have access to anyone’s test results.

 

Early detection of Alpha-1 is critically important, and the only way to detect Alpha-1 is through testing. Once you know you have Alpha-1, you can make important lifestyle changes and receive treatment to slow the progression of the disease (see 'What is the treatment plan for Alpha 1?'). 

  • Everyone with emphysema, chronic obstructive pulmonary disease (COPD), chronic bronchitis or asthma that is incompletely reversible after aggressive treatment 
  • Blood relatives, especially siblings and children, of those diagnosed with Alpha-1
  • Individuals with a family history of early emphysema, with or without smoking.
  • Individuals with family history of liver disease
  • Newborns, children, adults with unexplained liver disease
  • Individuals with a skin condition known as panniculitis
  • Individuals with a lung condition known as bronchiectasis

 

Siblings of those diagnosed with severe Alpha-1 Antitrypsin Deficiency have a 25% risk of having the same severe deficiency (children have a 2% risk).

Please download the following letters to give to your blood relatives outlining why testing for Alpha-1 is important for them.

They can take this letter to their own doctors to pursue appropriate testing or they can contact the Alpha-1 Canadian Registry at 1-800-352-8186 for further information.

Download Sibling letter

Download Children letter

There are three main options of treatment for patients diagnosed with Alpha-1, including targeted treatmentsfor lung disease, targeted treatment for Alpha-1, and lifestyle changes that may reduce symptoms.

 

1. Targeted Treatments for Lung Disease

 

a) Bronchodilators
Bronchodilators are prescription medicines taken by inhaler.They are used to relax tight airway muscles, relieving  the symptoms of wheezing and shortness of breath. Short acting preparations are available for quick relief, while long acting preparations help prevent the symptoms of shortness of breath.

Medication

Use/Action

Common side effects

Short Acting Beta-2 Agonists

ventolinbricanyl  Airomir

Ventolin®(Salbutamol)
Bricanyl® (Terbutaline)
Airomir® (Salbutamol)

For acute attacks, provides quick relief

Relaxes tightened airway muscles within 5 minutes

Effects lasting 4 hours

May experience shakiness, nervousness, fast heart rate when first taken

Headache if taken frequently

Short Acting Anticholinergics

http://www.alpha1canadianregistry.com/content/drugimages/Atrovent.jpg

Atrovent® (Ipratropium bromide)

Slow action, 30-60 minutes before relief is felt

Relaxes tightened airway muscles

Usually prescribed for regular use

May cause dry mouth, metallic taste

Long Acting Beta-2 Agonists

http://www.alpha1canadianregistry.com/content/drugimages/Serevent.jpghttp://www.alpha1canadianregistry.com/content/drugimages/Oxeze.jpg

Serevent® (Salmeterol)
Oxeze® (Formoterol)

Onbrez (indacaterol)

Salmeterol relaxes the airway muscles within 20-30 minutes and last up to 12 hours

Formoterol relaxes airway muscles within 3 minutes and last 12 hours

Indacaterol relaxes airway muscles within 5 minutes and lasts for 24 hours.

Tremors, headache, fast 
heart rate, muscle cramps.

If sensitive to the drug, may develop rash, feel itchy or have breathing problems

Long Acting Anticholinergics

http://www.alpha1canadianregistry.com/content/drugimages/Spiriva.jpg

Spiriva® (Tiotropium bromide)

Spiriva and Seebri are taken once daily.  Tudorza is taken twice daily.

Relaxes airway muscles and lasts 24 hours (12 hours for Tudorza).

Wash hands after use to 
prevent medication getting into eyes

Headache, dry mouth, skin rash, constipation

Use with caution in bladder or prostate problems

 

b) Anti-inflammatory drugs

Anti-inflammatory medications provide long-term control for COPD by reducing inflammation within and around the airways.

Medication

Use/Action

Common side effects

Anti-Inflammatory Drugs

http://www.alpha1canadianregistry.com/content/drugimages/Qvar.jpghttp://www.alpha1canadianregistry.com/content/drugimages/Pulmicort.jpghttp://www.alpha1canadianregistry.com/content/drugimages/Flovent.jpghttp://www.alpha1canadianregistry.com/content/drugimages/Alvesco.gif

Qvar® (Beclomethasonedipropionate)
Pulmicort® (Budesonide)
Flovent® (Fluticasone propionate) 
Alvesco® (Ciclesonide)

These medicines are used commonly in asthma.  If used in COPD, they are usually combined with other inhalers. 

Slow action

Prevent swelling and reduces mucus secretions in the airways

Prevents twitchiness of the airways

Hoarseness or oral thrush

Rinsing mouth after use will reduce the risk of side effects

May use with an Aerochamber® with an aerosol inhaler to reduce possibility of side effects

 

c) Combination Medicines

Medication

Use/Action

Common side effects

Combination Medicines – LABA/LAMA’s

anoro_frontdevice_open_mr20final.jpg duaklir-Inhaler.jpguntitled.png

Anoro (umeclidinium/vilanterol)

Duaklir (aclidinium/formoterol)

Inspiolto (tiotropium/olodaterol)

Ultibro (glycopyrronium/indacaterol)

Relax airway muscles and open narrow breathing passages

Relax airway muscles for 12 hours (Duaklir) or 24 hours (Anoro, Inspiolto, Ultibro)

Dry mouth, constipation, tremor, urinary problems related to the prostate

 

Anti-inflammatory drugs and long acting bronchodilators can be combined into one inhaler to relieve symptoms.

Medication

Use/Action

Common side effects

Combination Medicines – ICS/LABA’s

http://www.alpha1canadianregistry.com/content/drugimages/Advair.jpghttp://www.alpha1canadianregistry.com/content/drugimages/Symbicort.jpg

Advair® (Fluticasone+Salmeterol)
Symbicort® (Budesonide/Formoterol Fumarate)

Breo

Reduce and prevent airway inflammation

Relax airway muscles for 12 hours (Advair, Symbicort) or 24 hours (Breo)

Relief from Advair within 10-15 minutes

Relief from Symbicort® within 3 minutes

Relief from Breo with 5 minutes

Anti-inflammatory and long acting bronchodilator in one inhaler

Rinse mouth after use to prevent oral thrush

 

d) Antibiotics

Antibiotic treatment is used at the first signs of a chest infection because individuals with Alpha-1 may suffer rapid loss of lung function during infections. Symptoms of chest infection include: fever (with or without chills), increased shortness of breath and coughing, changes in colour and thickness of phlegm.  Your doctor may consider giving you standby prescriptions for antibiotics to use at the first sign of such infection.  See the Canadian Thoracic Society's COPD Flare Up Action Plan here.

 

e) Prednisone

With bad chest infections, your doctor may add the oral medication prednisone, a strong steroid medication that can help speed recovery.

 

f) Vaccinations

Preventative vaccinations such as the annual flu shot are recommended. A pneumonia vaccination is also recommended every 5 to 10 years.

 

g) Supplemental Oxygen

Supplemental oxygen may be useful in some cases to assist with the activities of daily living and prolong life.

 

h) Surgical Options

There are 2 surgical options for severe Alpha-1: lung volume reduction (removal of damaged lung tissue), and lung transplantation (of one or both lungs).

 

Please consult your health care provider regarding the above options.

 

 2. Targeted Treatment for Alpha-1

The only existing medication for treating Alpha-1 Antitrypsin Deficiency is called Augmentation Therapy. Augmentation therapy is the weekly intravenous infusion of Alpha-1 Antitrypsin (AAT) protein that has been purified from the blood of human donors with normal levels of ATT. This therapy increases AAT protein levels in the blood and has been shown to slow the progression of emphysema in severe Alpha-1. Augmentation therapy is not a cure, and will not reverse lung damage that has already occurred, nor will it treat liver problems related to Alpha-1.

 

Prolastin-C (offered by Grifols Canada Ltd.) is the only currently approved Augmentation therapy in Canada. Augmentation therapy is  covered by some private insurance policies.  It is also covered by provincial healthcare in British Columbia, Alberta, Manitoba and Quebec. Clinical research may be another option to receive Augmentation therapy free of charge (click here for more information on current clinical trials).

 

3. Lifestyle Changes

There are several lifestyle changes that can be made by individuals diagnosed with Alpha-1 that may reduce disease progression, including:

  • Quitting smoking and keeping away from second hand smoke
  • Low, infrequent or no alcohol consumption (especially in those with the ZZ genotype), as it may cause additional damage to the liver
  • Avoiding exposure to dust or fumes
  • Exercising regularly
  • Eating a well balanced diet
  • Maintaining a desirable body weight
  • Increasing hand hygiene to reduce bacterial and viral infections