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Management

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Management of AATD is mainly aimed at treating the COPD or liver disease similarly to how they would be treated in non-AATD patients. This includes environmental exposure avoidance, preventative care, medications and possible transplant if necessary. Infusions of alpha-1 antitrypsin are available, but lack a strong evidence base.

First Steps after Confirming Diagnosis

Establish extent of disease:

  • CT chest for lung density measurement
  • Lung function assessment (spirometry, lung volumes, and diffusing capacity)
  • Liver function tests
  • Liver ultrasound for cirrhosis
  • Liver biopsy in those with liver disease
  • Deep excisional biopsy if panniculitis is suspected based on tender erythematous nodules with ulceration

Initial management should treat COPD with the usual therapy

  • Preventative vaccination (Pneumococcal, Influenza)
  • Bronchodilators
  • Steroids if needed
  • Supplemental oxygen if needed

Diet, Exercise, and Lifestyle Interventions

  • Smoking cessation is the single most important intervention

Longitudinal care

Alpha-1 Antitrypsin augmentation therapy

  • Possible clinical efficacy for those with moderate lung damage.
  • Observational studies show mortality benefit, but randomized controlled trails show no difference from placebo
  • Referral to specialist appropriate

Follow up testing/screening/monitoring.

  • Periodic pulmonary function tests to monitor lung function
  • Annual influenza vaccination
  • Pneumococcal vaccination
  • Hepatitis A & B vaccine if not already immunized
  • Periodic liver function tests in those with PI*ZZ genotypes
  • If signs of liver disease or liver failure, biopsy may be useful to ascertain the extent of disease

Care team members

Required

  • Primary Care Physician
  • Pulmonology
  • Genetic counselor

As Indicated

  • Hepatology if liver disease
  • Dermatology if skin manifestations
  • Rheumatology if vasculitis

Physical/occupational/speech/developmental therapy

Pulmonary rehabilitation for COPD as exercise capacity has been shown to predict health status

Medications

  • Long and short acting bronchodilators
  • Corticosteroids for COPD and/or panniculitis

Surgery and/or procedures

  • Liver transplantation for cirrhosis/Hepatocellular carcinoma can be curative because the donor’s organ produces AAT
  • Lung reduction surgery for COPD not recommended
  • Lung transplantation can be done for advanced COPD especially in young patients (<60) but it does not increase survival

Reproductive implications

Effect of the condition on fertility

No evidence that fertility is affected

Effect of the condition on pregnancy, delivery and/or the post-partum period

No evidence that pregnancy, delivery and/or the postpartum period is affected

Effect of pregnancy on manifestations of the condition

  • Risk of decline in respiratory function
    • A small number of published case reports show variable risk with pregnancy
  • Successful pregnancies reported, even with severe maternal airflow obstruction.
  • Frequent monitoring of maternal respiratory function is recommended

Prognosis

Penetrance

PI*ZZ:

  • COPD: 90% of smokers, 65% of non smokers
  • Infantile liver disease: 10% of infants
  • Adult liver disease: approximately 12%

PI*SZ or MZ:

  • COPD: 19% of patients
  • Infantile liver disease: no increased risk
  • Adult liver disease: risk appears low

Factors affecting expression

  • Smoking- Dose related relationship
    • Elevated risk of COPD development
    • Accelerated decline in FEV1
  • Environmental exposure - Associated with increased symptoms and decreased lung function
    • Use of kerosene heaters
    • Agricultural employment for >10 yrs
    • Mineral dust exposure

Effect on longevity/lifespan

  • PI*ZZ smokers have increased mortality
    • Median survival age 51.8 years
  • Data for PI*ZZ never-smokers is less consistent with some studies showing normal mortality and others with mean survival age of 66.8 years
  • Underlying causes of death
    • 72% COPD
    • 10% cirrhosis (more common as cause of death among non-smokers)

Effect on function and quality of life

AATD related COPD associated with more frequent hospitalizations and more frequent and severe respiratory symptoms than non-AATD COPD patients

Expected response to therapy

Therapy is targeted primarily at symptomatic relief.

How do genetic test results alter prognosis?

Genetic testing does not alter the prognosis

Presymptomatic or Asymptomatic Patients

  • Smoking avoidance
  • Periodic monitoring of lung function

Consensus Statements and Guidelines