Clinical Practice Guidelines 2016: The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult (free full text)

Dear Respiratory friends we are happy to present you Clinical Practice Guidelines 2016: The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult published today in Journal of the COPD Foundation!

Summary of Recommendations

Testing for Alpha-1 Antitrypsin Deficiency (AATD):

· All individuals with COPD regardless of age or ethnicity should be tested for AATD.

· All individuals with unexplained chronic liver disease should be tested for AATD.

· All individuals with necrotizing panniculitis, granulomatosis with polyangiitis, or unexplained bronchiectasis should be tested for AATD.

· Parents, siblings, and children, as well as extended family of individuals identified with an abnormal gene for AAT, should be provided genetic counseling and offered testing for AATD (see guideline document for special considerations about testing minors).

· For family testing after a proband is identified, AAT level testing alone is not recommended because it does not fully characterize disease risk from AATD.

· For diagnostic testing of symptomatic individuals, we recommend genotyping for at least the S and Z alleles. Advanced or confirmatory testing should include Pi-typing, AAT level testing, and/or expanded genotyping.

Pulmonary function testing in those with AATD:

· Initial evaluation with complete lung function testing is recommended.

· Annual follow-up of adults with at least a spirometry test is recommended.

Computed Tomography (CT) scan of the chest in the evaluation in those with AATD:

· In newly diagnosed patients who are symptomatic and/or have abnormal pulmonary function testing, a baseline CT scan of the chest is recommended.

· Serial chest CT scanning to monitor progression of disease is not recommended.

Monitoring for liver disease in those with AATD:

· Monitoring for liver disease at annual intervals (or more frequently as indicated by clinical circumstances), with physical examination including focused exam for signs of liver disease, liver ultrasound, and laboratory monitoring of AST, ALT, GGT, albumin, bilirubin, INR, and platelets is recommended.

Management of lung disease in those with AATD:

· Every effort should be made to prevent exposure to tobacco smoke and facilitate cessation in those who are smoking.

· Lung volume reduction surgery is not recommended for individuals with COPD related to AATD.

Intravenous augmentation therapy in those with AATD is recommended for:

· Individuals with an FEV₁ less than or equal to 65% predicted.

o    For those with lung disease related to AATD and an FEV₁ greater than 65%, we recommend discussion with each individual regarding the potential benefits of reducing lung function decline with consideration of the cost of therapy and lack of evidence for such benefit.

·         Individuals with necrotizing panniculitis.

Intravenous augmentation therapy is not recommended for:

· Individuals with the MZ genotype of AATD.

· Individuals with lung disease due to AATD who continue to smoke.

· Individuals with AATD and emphysema or bronchiectasis who do not have airflow obstruction.

· The treatment of liver disease due to AATD.

· Individuals who have undergone liver transplantation.

Additional recommendations regarding dosing of intravenous augmentation therapy:

· Weekly doses higher than the current FDA-approved dose are not recommended.

· Monitoring of trough AAT blood levels to evaluate the adequacy of AAT augmentation dosing is not recommended.

- See more at: http://journal.copdfoundation.org/jcopdf/id/1115/The-Diagnosis-and-Management-of-Alpha-1-Antitrypsin-Deficiency-in-the-Adult#sthash.kM5BYEOk.dpuf

Alpha 1 Anti-trypsin week

Respiratory decade is pleased to recognize Alpha 1 Anti-trypsin week from September 13-19, 2015. 

Indeed a chance discovery by Dr. Carl Beril Laurell in 1962 revealed the absence of the Alpha-1 band in serum electrophoresis gels. Aided by further investigations by Dr. Eriksson the lack of the critical Alpha-1 anti-trypsin protein was noted in patients with emphysema.

Alpha-1 -anti-trypsin is the most prevalent potentially fatal genetic disorder of adult Caucasians in the United States, although all races can be affected. An estimated 25 million individuals carry deficient genes and over 100,000 Americans have severe Alpha-1 deficiency, but still sorry to say, less than 10% have been diagnosed. In contrast, other important respiratory diseases like cystic fibrosis affect 30,000 and idiopathic pulmonary fibrosis 128,000 patients. While effective treatment is available, much more research is needed to help patients with this condition and to cure it.

Patients and physicians should be aware of the clinical pulmonary presentations of A1A deficiency.

From two patient registries, 54% had emphysema, 72% had respiratory symptoms, 45% had chronic bronchitis and 35% have a diagnosis of asthma. Also, another important respiratory disease chronic bronchiectasis can occur in this population. It is extremely important to do testing for A1A deficiency because the clinical presentation does not distinguish A1A deficiency from typical non genetic types of COPD.

Alpha-1 anti-trypsin deficiency is an imbalance of neutrophil elastase, an important enzyme released in the lung and the protein A1A which provides protection from the elastase and prevents it from injuring the lung.  Prescreening for A1A deficiency is available from a number of providers. The A1A Foundation provides free kits for testing which can be sent to either the A1A testing center at the University of Florida or the Alpha-1 Registry at Medical University of South Carolina. Please remember that the disease, A1A deficiency can affect all ages ranging from severe biliary disease in children to emphysema, bronchiectasis, and chronic liver disease in adults. It is an extremely important disease that has the potential for treatment with replacement therapy for lung disease and exciting new therapies are being tested for liver involvement. Hence, it is imperative to know your diagnosis and be informed as much as possible about your condition.

Standards for Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency

In 2003, the American Journal of Respiratory and Critical Care Medicine published the ATS/ERS: Standards for Diagnosis and Management of Individuals with Alpha-1. The Standards recommend testing for Alpha-1 in all of your adult patients suffering from COPD, emphysema, incompletely reversible asthma, unexplained liver disease, and siblings of an individual with Alpha-1. 

Full text:

http://www.atsjournals.org/doi/abs/10.1164/rccm.168.7.818#.VdCbNpcXyUk