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

Alpha-1-Antitrypsin Deficiency: its time for a cure!!!

Respiratory Decade is inviting you to important Respiratory events:

To celebrate the 50th Anniversary since the Discovery of Alpha-1-Antitrypsin (AAT) LOVEXAIR organized two key events: The International Scientific Conference related to AAT Deficiency and the 4th International Patient Congress, which will be celebrated from 11-13 April, in the Hotel Hilton Diagonal Mar, Barcelona, 2013. This year being the Year for Rare Disease in Spain. 

Barcelona will be the world capital in liver and lung disease research and specialized healthcare for this momentous occasion to create awareness about Alpha-1-Antitrypsin, in both research and  patient community empowerment. Sten Eriksson, one of the discoverers of AAT Deficiency, will also be attending this important event. 

For this special occasion we will welcome more than 200 delegates from around the world, with representatives from patient and scientific communities, particularly America and Europe, as well as leading scientific experts in this chronic rare disease.

The 4th International Patient Congress, 12-13 April will bring together patients and their family members and in parallel, an International Scientific Conference on Alpha-1 Research, 11-12 April, simultaneously attended by healthcare professionals and leading scientists in Alpha-1 research and industry with expertise in advanced therapies.

The main focus of this event is to create heightened awareness about Alpha-1-Antitrypsin deficiency; bring together representatives from Alpha-1 organizations from around the world and to promote debate and dialogue about the impact and the situation in each country; identify unmet needs; learn the latest developments in research in advanced and innovative therapies, and bring together both researchers and patients to improve and support building a cure for Alpha-1 in the future: "It's time for a cure".

The goal is also to empower patients and their organization leaders, build on sharing best- practices and skill-sets and form an international working group to move forward in key areas which are considered important, across the community as a result of participating in this event.

Phenotypes of Alpha 1 Antitrypsin Deficiency in Brazil

Today we are publishing abstract which was presented by doctor Maria Vera Cruz de Oliveira from Hospital do Servidor Público Estadual and ABRADAT (Associação Brasileira de Deficiência de Alfa 1 Antitripsina/Brazilian Association of Alpha 1 Antitrypsin Deficiency) on last American Thoracic Society (ATS) meeting.

We are grateful for this post to our most active member from Brazil: Marilia Varella!

Introduction

Alpha 1 Antitrypsin Deficiency (A1ATD) is a hereditary disease often under-diagnosed. The estimated prevalence of A1ATD is known in many countries, but in Brazil until 2005 only isolated cases were published or reported.

Brazilian Association of Alpha 1 Antitrypsin Deficiency (ABRADAT) was founded in 2005. ABRADAT has an education program for physicians and for general population and offer free phenotype tests for COPD patients with possible A1ATD.

The aim of the present study is to describe phenotypes in Brazilian COPD patients with A1ATD.

Methods

This is a descriptive transverse study of the phenotypes of COPD patients with A1ATD, characterized by serum concentration < 80 mg/dL. A paper filter for the blood sample collection was delivered by mail upon request of physicians from several parts of the country. All patients agreed with the test and signed an informed consent.

 

Results

Between February, 2005 and May, 2010, 106 phenotypes tests were performed in patients with COPD and alpha 1 antitrypsin concentration < 80 mg/dL. The tested samples came from 16 different States (Brazil has 27 States). Eighty eight cases with phenotypes not PiMM were found: 47 PiZZ (53, 4%), 27 PiMZ (30,7%), 10 PiSZ (11, 4%) and 4 PiMS (4, 5%) 

Discussion

In this survey phenotypes PI were identified in selected patients with COPD and A1AT serum levels below normal values. Brazil was discovered by Portugal, and was a Portuguese colony for 300 years. Genetic epidemiological studies show that Portugal has the predominant allele PiS, and de Serres estimated the prevalence of PI*S around 46.3 and PI*Z around 5.7 in Brazil (Figure 2). In Brazilian ethnic composition there is 53,4% of Caucasians, and although most of the immigrants are from Portugal, there are also from Germany, Italy and others European countries, so maybe the prevalence of PI phenotypes is different from de Serres study.

We didn’t have data about the real prevalence of A1ATD in Brazil until now, but this program to identify individuals with A1ATD is important for the appropriate management of these patients.

Conclusion

The most common phenotype associated with A1ATD in Brazil is PiZZ, followed by PiMZ.

Alpha-1 antitrypsin deficiency: a clinically under-recognized inherited disorder

Dear Respiratory Friends, we are happy to present new post from Doctor Marilia Varella (Brazil) abot Alpha-1 antitrypsin deficiency!

What is Alpha-1 antitrypsin deficiency?

It is a clinically under-recognized inherited disorder affecting the lung (emphysema), liver (neonatal hepatitis, chronic liver disease), and rarely, skin (panniculitis). Emphysema is thought to result from an imbalance between neutrophil elastase in the lung and the elastase inhibitor AAT, which protects against proteolytic degradation of elastin.

The prevalence of AAT varies considerably from one country to another; however, it is estimated that more than 3 million people worldwide have allele combinations associated with severe AAT deficiency.

Recent surveys demonstrated that there is an average delay of 7.2 years between the first onset of symptoms and the diagnosis even in individuals with severe deficiency; those individuals also reported seeing at least three (up to ten) clinicians before the diagnosis of AAT deficiency was first made.

It`s also important to notice that under-recognition persists despite extensive educational efforts and the publication of evidence-based guidelines for diagnosis and management of AAT deficiency.

Risk factors:

AAT (encoded by the gene PI, MIM +107400) is a member of the serpin family of protease inhibitors. The normal alpha-1 antitrypsin allele is the M allele. Over 100 allelic variants have been described, of which the most common severely deficient variant is the Z allele.

The normal plasma concentration of AAT ranges from 20 to 48 µmol /L. Population studies suggest a protective threshold of 11 µmol per L, below which there is insufficient AAT to protect the lung.

Severe deficiency of AAT poses a strong risk factor for early-onset emphysema, but not every severely deficient individual is destined to develop emphysema. Smoking is the major factor influencing the course of COPD.

Symptoms:

The clinical manifestations of AAT deficiency during the first two to three decades of life is that of liver disease, specifically chronic elevation of liver enzymes or cirrhosis.

Beyond the first two to three decades of life, patients with severe deficiency of AAT have an accelerated rate of lung function decline.

The clinical presentation of emphysema due to AAT deficiency has many features in common with usual COPD. However, the onset of emphysema in AAT-deficient individuals may be earlier than that in non-AAT-deficient individuals, who usually present in the sixth and seventh decades of life.

Emphysema associated with AAT deficiency often shows a characteristic chest radiographic pattern, in which bullous changes are more prominent at the lung bases than at the apices.

Diagnosis:

Patients with persistent airflow obstruction on spirometry should be tested. Additional features that should lead clinicians to test for severe AAT deficiency include:

·        Emphysema in a young individual (≤45 years)

·        Emphysema in a nonsmoker or minimal smoker

·        Emphysema characterized by predominant basilar changes on the X-Ray

·        A family history of emphysema and/or liver disease

·        Clinical findings or history of panniculitis

·        Clinical findings or history of unexplained chronic liver disease

The diagnosis of severe AAT deficiency is confirmed by demonstrating a serum level below 11 micromol/L in combination with confirmation of a severe deficient genotype (generally determined by isoelectric focusing or polymerase chain reaction testing).

Browse through the links listed below to learn more about AAT deficiency:

http://patients.thoracic.org/information-series/en/resources/what-is-alpha-1-antitrypsin-deficiency.pdf

http://www.ers-education.org/media/2007/pdf/40253.pdf

http://alpha-1foundation.org/

http://www.lunguk.org/you-and-your-lungs/conditions-and-diseases/alpha-1-antitrypsin-deficiency

http://www.nationaljewish.org/healthinfo/conditions/alpha-1/