Question 1 of 10

    Alpha-1 Antitrypsin Deficiency (Alpha-1-Antitrypsin Deficiency)

    Alpha–1 antitrypsin deficiency (AATD) is a common genetic inherited autosomal-codominant disorder.

    This disorder is triggered by the following process: hereditary.

    Presentation

    In many cases, signs and symptoms of AAT deficiency do not show up before the individual is above the age of 30 years. However, some individuals who smoke tend to develop symptoms in their early 20s. AAT deficiency gravely affects the functioning of the lungs and the liver. The signs and symptoms include the following:

    Liver, Gall & Pancreas
    Jaundice
    • Infants who develop jaundice secondary to alpha-1 antitrypsin deficiency usually have resolution of the jaundice within the first year of life.[rileychildrens.org]
    • : Jaundice Ascites (accumulation of fluid in the abdomen) Portal hypertension (increased blood vessel pressure in the portal vein) Although there is no cure for this condition, treatments can help to reduce symptoms associated with alpha-1 antitrypsin[columbiasurgery.org]
    • The signs and symptoms most people experience with this deficiency are: Chronic cough Emphysema COPD Liver failure Hepatitis Hepatomegaly ( enlarged liver ) Jaundice Cirrhosis Mutations in the gene termed SERPNA1 cause alpha –1 antitrypsin deficiency.[rxlist.com]
    • Symptoms in infancy include prolonged yellow appearance of the skin (jaundice), mildly elevated liver enzymes, and symptoms of cholestasis (e.g., jaundice, dark urine, pale stools and itching).[rarediseases.org]
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  • Entire body system
    Fatigue
    • In adults, symptoms may include shortness of breath; reduced ability to exercise; wheezing; respiratory infections; fatigue; vision problems; and weight loss.[rarediseases.info.nih.gov]
    • Individuals with alpha-1 antitrypsin deficiency usually experience respiratory symptoms, including shortness of breath following mild activity, reduced ability to exercise, wheezing, coughing, recurring respiratory infections, fatigue, and rapid heartbeat[chop.edu]
    • Other common symptoms include: Unintentional weight loss Vision changes Fatigue Repeated respiratory infections Rapid heartbeat when standing Barrel-shaped chest A1AD also can cause other conditions and patients may experience symptoms associated with[cedars-sinai.edu]
    • In adults, symptoms may include shortness of breath; reduced ability to exercise ; wheezing; respiratory infections; fatigue ; vision problems; and weight loss .[rxlist.com]
    • They may also become easily fatigued, or experience decreased appetite, swelling of the legs or abdomen, and/or enlargement of the liver (hepatomegaly).[rarediseases.org]
    Weakness
    • Each recommendation is rated by the strength of the opinion (strong, medium, weak) and the quality of evidence (high, moderate, low).[journal.copdfoundation.org]
    Weight Loss
    • Symptoms of AAT deficiency include Shortness of breath and wheezing Repeated lung infections Tiredness Rapid heartbeat upon standing Vision problems Weight loss Some people have no symptoms and do not develop complications.[medlineplus.gov]
    • In adults, symptoms may include shortness of breath; reduced ability to exercise; wheezing; respiratory infections; fatigue; vision problems; and weight loss.[rarediseases.info.nih.gov]
    • Unexplained weight loss and chronic respiratory infections associated with fever and rapid heart rate are additional findings that may be reported.[texasliver.com]
    • Other common symptoms include: Unintentional weight loss Vision changes Fatigue Repeated respiratory infections Rapid heartbeat when standing Barrel-shaped chest A1AD also can cause other conditions and patients may experience symptoms associated with[cedars-sinai.edu]
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  • respiratoric
    Cough
    • Patients with emphysema experience difficulty breathing, a hacking cough, and a barrel shaped chest.[chop.edu]
    • Those with recurrent coughs are often treated with courses of antibiotics and evaluated for postnasal drip, gastroesophageal reflux, or sinusitis.[1stclassmed.com]
    • COPD can make you cough up mucus , make you wheeze or have trouble breathing, and make your chest feel tight.[webmd.com]
    • Cough - this is another common symptom.[patient.info]
    Decreased Breath Sounds
    • A physical examination may reveal a barrel-shaped chest, wheezing, or decreased breath sounds.[medlineplus.gov]
    • For example, AATD may be suspected when a physical examination reveals a barrel-shaped chest, or, when listening to the chest with a stethoscope, wheezing, crackles or decreased breath sounds are heard.[genome.gov]
    Dyspnea
    • When dyspnea occurs, you can be well into the course of the disease.[1stclassmed.com]
    • (M1.GI.22) A 36-year-old male with no prior history of smoking presents to his primary care physician with a complaint of recurrent dyspnea on exertion and shortness of breath.[medbullets.com]
    • (signs of a liver problem) Frequent (present in 30%-79% of cases) Cirrhosis (a complication of liver disease) Occasional (present in 5%-29% of cases) Autosomal recessive inheritance COPD ( chronic obstructive pulmonary disease ) Shortness of breath (Dyspnea[rxlist.com]
    • […] obstructive pulmonary disease (COPD) are estimated to have alpha1-antitrypsin deficiency. [4] Although extremely rare, emphysema in children with AATD has been reported. [ 3 ] The incidence of liver disease increases with age. [3] Slowly progressive dyspnea[emedicine.medscape.com]
    Labored Breathing
    • COPD is characterized by coughing, shortness of breath, sputum production, rapid breathing, wheezing, and weight loss due to the energy required for labored breathing.[en.wikibooks.org]
    Pneumonia
    • In addition, annual flu and pneumonia shots are especially important for patients with the disease, as respiratory infections can cause lung damage.[cedars-sinai.edu]
    • The treatment of emphysema related to alpha-1 includes all the usual medications: medicines to open up the airways, broncodilators; preventive strategies like influenza vaccine, pneumonia vaccine; occasionally oxygen when the individual's oxygen level[scientificamerican.com]
    • You shouldn’t smoke, and you need to get a pneumonia vaccine and your annual flu shot .[webmd.com]
    • Avoid lung irritants such as dust and fumes, get regular vaccinations to protect against pneumococcal pneumonia and Haemophilus influenzae type b infections, for example, and an annual influenza shot, get prompt medical attention for lung infections,[labcorp.com]
    • Reasons for being tested [ edit ] There are ways to help prevent further tissue damage in the lung such as: receive immunizations for flu and pneumonia receive early treatment for lung infections by seeing your doctor at the first sign of a cold or other[en.wikibooks.org]
    Rales
    • It usually produces some degree of disability and reduces life expectancy. [1] Signs and symptoms [ edit ] Symptoms of alpha-1 antitrypsin deficiency include shortness of breath , wheezing , rhonchi , and rales .[en.wikipedia.org]
    Sputum Production
    • Symptoms The initial symptoms of Alpha 1 antitrypsin deficiency include: Chronic cough Sputum production Wheezing If patients present with wheezing, they're often told that they have asthma.[1stclassmed.com]
    • COPD is characterized by coughing, shortness of breath, sputum production, rapid breathing, wheezing, and weight loss due to the energy required for labored breathing.[en.wikibooks.org]
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  • cardiovascular
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  • Eyes
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  • Workup

    The condition of AATD is usually diagnosed when an individual complains of shortness of breath or is suffering from lung or liver disorders. Lung and liver disease are the preliminary features of AATD.

    Blood test to determine the levels of AAT is carried out. In addition, a phenotype blood test is also done to assess the presence of the causing gene. Several other diagnostic tests such as lung functioning tests known as spirometry are done to evaluate the functioning ability of the lungs.

    Imaging studies that include an X-ray and CT scan of the chest is also done to further understand the capacity of the lungs. CT scan of the chest would reveal whether the patient has emphysema and its degree of severity. Liver function tests may also be done in order to assess the functioning of the organ.

    Pathology

    Biopsy
    Hepatocellular Carcinoma
    • Answer 4: Figure D demonstrates hepatocellular carcinoma.[medbullets.com]
    • With cirrhosis there is a risk of hepatocellular carcinoma.[patient.info]
    • In adults with AAT deficiency, the risk of developing chronic liver disease, cirrhosis , and liver cancer (hepatocellular carcinoma) is increased.[labtestsonline.org]
    • carcinoma, not always associated with cirrhosis PiMZ: intermediate plasma levels of AAT (expression of alleles is autosomal codominant) Pi null: rare variant with no detectable serum AAT PiS: low serum AAT but no disease AAT deficiency variants: secretory[pathologyoutlines.com]
    • Associations asthma pancreatitis aneurysms, including intracranial aneurysms 18 Complications cirrhosis with increased risk of hepatocellular carcinoma 19 AAT deficiency carriers are at 70-100% increased risk of lung cancer 20 Thoracic manifestations[radiopaedia.org]
    Liver Biopsy
    • The physician, concerned about the etiology of this patient's condition orders a liver biopsy.[medbullets.com]
    • biopsy to determine extent of histologic damage Microscopic (histologic) description Round to oval cytoplasmic eosinophilic globular inclusions in periportal hepatocytes Rare Mallory bodies and fatty change Also hepatocellular degeneration, giant cell[pathologyoutlines.com]
    • Liver functioning tests, pulmonary tests, or a liver biopsy may also be performed to diagnose any conditions that may have resulted from A1AD.[cedars-sinai.edu]
    • Tests can include: Blood tests to examine if AAT levels in your blood are low Chest x-ray to take radiographic pictures of your lungs Lung function testing CT scanning Genetic testing to locate the inherited gene that caused the AATD Liver biopsy where[1stclassmed.com]
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  • Test Results

    Pulmonary Function Test
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  • Laboratory

    Serum
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  • Imaging

    X-ray
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  • Treatment

    So far there is no known treatment plan to cure this genetic disorder. Treatment methods are designed to effectively manage the disease condition and slow down the progression of the disease. Medications form the primary basis of the treatment program. The individual is put on drugs such as a steroids and bronchodilators to help manage the inflammation and flare-ups of emphysema. Antibiotics may also have to be prescribed if the individual is also suffering from infection of the chest. Theophylline that works as a bronchodilator is also prescribed to patients. Augmentation therapy with intravenous alpha-1 antitrypsin protein may afford some benefits for patients with low levels of AAT below 11 µM [8].

    Surgery is often the last resort when the patients with COPD develop bullae characterized by large air–filled sacs. Liver transplantation may be required among patients with cirrhosis due to AAT deficiency [9].

    Immunizations shots are also given to individuals with emphysema. Some individuals may also be advised to undergo home oxygen therapy. Individuals with recurrent bouts of emphysema may benefit from this. Portable oxygen cylinders are available and oxygen is supplied either through tubes or masks.

    Prognosis

    The prognosis of the disease condition varies with the degree of symptoms and the pace at which the disease progresses. However, with prompt diagnosis and effective treatment regime, individuals are thought to recover well. The progression of the disease can be arrested and the symptoms put to rest. Since this is an inherited disease condition, it cannot be cured but managed well with appropriate treatment.

    Complications

    If timely diagnosis and treatment is not initiated, then AAT deficiency can bring along life threatening complications. These include:

    Complications

    Bronchiectasis
    • Alpha-1 antitrypsin is a protein that protects us from enzymes that destroy the lungs (causing emphysema or bronchiectasis).[health.ucsd.edu]
    • Read more about COPD and bronchiectasis .[blf.org.uk]
    • Prominent features of AATD COPD include basilar predominant panacinar emphysema, frequent radiographic bronchiectasis, and a prominent interaction with environmental factors that influence clinical disease phenotypes.[clinicaltrials.gov]
    • 2003 guidelines, the American Thoracic Society recommends AAT testing when individuals are diagnosed with certain conditions such as: Emphysema at a young age (younger than 45 years old) and/or no obvious risk factors for the disease, such as smoking Bronchiectasis[labtestsonline.org]
    • Asthma, bronchiectasis and chronic obstructive pulmonary disease are also more prevalent.[dermnetnz.org]
    Chronic Active Hepatitis
    • A1AD-associated liver disease findings in adults are any or all of the following: chronic active hepatitis, cirrhosis, portal hypertension, and hepatocellular carcinoma.[rarediseases.org]
    Chronic Liver Disease
    • In adults, AATD leads to chronic liver disease in the fifth decade of life.[emedicine.medscape.com]
    • In adults with AAT deficiency, the risk of developing chronic liver disease, cirrhosis , and liver cancer (hepatocellular carcinoma) is increased.[labtestsonline.org]
    • Accumulation of altered alpha-1 antitrypsin in hepatocytes incites inflammatory response and chronic liver disease.[radiopaedia.org]
    • Studies have shown that A1AT heterozygosity can be an important co-factor in the aetiology of chronic liver disease and a modifier for hepatitis C virus, end-stage liver disease, cirrhosis and hepatocellular carcinoma. [ 4 ] Epidemiology A1AT deficiency[patient.info]
    Liver Disease
    • The liver disease requires standard therapy for cirrhosis and liver failure as in many liver diseases.[netdoctor.co.uk]
    • In Rosen HR, Martin P (eds): Metabolic Liver Disease: Clinics in Liver Disease, vol 2.[clevelandclinicmeded.com]
    • Disease We presented new pre-clinical data on ALN-AAT, an RNAi therapeutic targeting alpha-1 antitrypsin (AAT) in development for the treatment of liver disease associated with AAT deficiency.[alnylam.com]
    • Treatment Liver disease Mild liver disease may need no specific treatment.[liver.ca]
    • The Children’s Liver Disease Foundation website has more information on liver disease caused by alpha-1-antitrypsin deficiency.[blf.org.uk]
    Neonatal Hepatitis
    • PiZZ: 1 per 7,000; have 10 - 15% of normal AAT levels, are at high risk for clinical disease; accumulate AAT variant Z in endoplasmic reticulum and have slowdown in degradation pathway but only 10% get clinical disease PiZZ hepatic syndromes range from neonatal[pathologyoutlines.com]
    • The most severe forms are characterized by neonatal hepatitis, chronic hepatitis, cirrhosis, hepatocellular cancer, and early-onset emphysema.[clevelandclinicmeded.com]
    • Diagnosis 1 -Antitrypsin deficiency is usually suspected in infants with neonatal hepatitis, cholestatic jaundice or cirrhosis, or adults with cirrhosis and/or hepatocellular carcinoma.[nature.com]
    Panniculitis
    • PANNICULITIS The dermatologic manifestation of A1AD is a rare form of skin disease called panniculitis.[rarediseases.org]
    • In their 2016 guidelines, intended to update the American Thoracic Society's guidelines, the Alpha-1 Foundation recommends AAT testing for all individuals with: COPD Liver disease with no known cause Necrotizing panniculitis Granulomatosis with polyangiitis[labtestsonline.org]
    • Rarely, AATD can cause a skin condition called panniculitis . [1] AATD is caused by mutations in the SERPINA1 gene and is inherited in a codominant manner. [2] Treatment is based on each person's symptoms and may include bronchodilators ; antibiotics[rarediseases.info.nih.gov]
    • Panniculitis varies in severity and can occur at any age.[genome.gov]
    Pneumothorax
    • Antitrypsin Deficiency, occurring due to paucity of AAT in circulation allowing uninhibited inflammation in lungs, and accumulation of mutated AAT in the liver α 1 -antitrypsin deficiency has been associated with a number of diseases: Cirrhosis COPD Pneumothorax[en.wikipedia.org]
    Pulmonary Emphysema
    • Alpha-1 Antitrypsin Deficiency (AATD, Alpha-1) is a genetic condition that predisposes to early onset pulmonary emphysema and airways obstruction, often indistinguishable from usual smoker's chronic obstructive pulmonary disease (COPD).[clinicaltrials.gov]
    • Definition (MSH) Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS.[fpnotebook.com]
    • Deficiency of the protease inhibitor alpha 1-antitrypsin that manifests primarily as pulmonary emphysema and liver cirrhosis.[icd10data.com]
    • AAT AATD alpha-1 protease inhibitor deficiency alpha-1 related emphysema genetic emphysema hereditary pulmonary emphysema inherited emphysema Carrell RW, Lomas DA.[ghr.nlm.nih.gov]
    Sinusitis
    • Those with recurrent coughs are often treated with courses of antibiotics and evaluated for postnasal drip, gastroesophageal reflux, or sinusitis.[1stclassmed.com]
    • In clinical studies, the following adverse reactions were reported in at least 5% of subjects receiving Zemaira: headache, sinusitis, upper respiratory infection, bronchitis, fatigue, increased cough, fever, injection-site bleeding, nasal symptoms, sore[zemaira.com]
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  • Etiology

    Alpha–1 antitrypsin deficiency is a genetic disorder. If a child inherits two AAT genes from both the parents, then he is said to have developed the AAT deficiency.

    The faulty AAT gene that is known to cause the genetic disorder is known as PiZ. Now, if the child inherits one normal AAT gene and one faulty AAT gene (Piz) then he would not suffer from AAT deficiency. However, in such cases, there is a possibility that the child transfers the faulty PiZ gene to the next generation.

    Epidemiology

    About 1.1 million individuals across the globe fall prey to this genetic disease. Earlier it was thought that AAT deficiency is only the disease of Caucasians. However, with in depth research it was revealed that this inherited genetic disorder exists amongst all racial groups. It has also been estimated, that about 3.1 million Americans suffer from COPD.

    Of these about 1.9% individuals suffer from COPD as a result of AAT deficiency. Statistics have also revealed that about 1 in every 3000 to 5000 individuals of UK suffer from AAT deficiency. Of the 100,000 person with AAT deficiency in the world only less than 10% are identified clinically [5].

    The median time from the instance the symptoms were observed to the time of clinical diagnosis is 8 years making mortality rate for symptomatic patients very high [6].

    Sex distribution
    Age distribution

    Pathophysiology

    AAT deficiency is an inherited autosomal disorder that occurs due to mutations in a specific gene that is known to alter the configuration of the alpha–1 antitrypsin molecule. This specific gene is named as SERPINA1 and is located in the long arm of chromosome 14. Alteration of the configuration of AAT prevents its release from the hepatocytes causing a significant decrease in its serum levels. This sequence of events gives rise to the condition related to AAT deficiency.

    Prevention

    AAT being an inherited disorder has no prevention. However, early detection of this disease can help in better management of the disease condition. If parents suffer from the same, then diagnosis of their children at an early age can help early initiation of treatment. Making small changes in lifestyle can go a long way in better management of the disease condition. The following practices can be adopted:

    • The practice of smoking cigarettes should be discontinued. It not only aggravates the existing condition but also speeds up the development of signs and symptoms of the disease.
    • Alcohol should be avoided as it would further aggravate the condition in individuals suffering from liver disease as a secondary complication of AAT.
    • The administration of pneumococcal and influenza vaccination have significantly lowered the incidence of emergency room visits of AAT deficient patients with clinical emphysema [10].

    Summary

    Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that occurs due to absence of alpha–1 antitrypsin (AAT) enzyme. This heritable disorder predisposes an individual to fall prey to an array of clinical diseases especially early onset emphysema [1]. However, the lungs and the liver are the two main organs that are severely affected. The effects of AATD are not evident until one is of 30 years of age [2].

    There is no cure to this disease. The symptoms can however be managed with an effective treatment regime. An estimated 1-5% of adults with chronic obstructive pulmonary disease (COPD) may have AAT deficiency [3]. Although adults AATD cases are more predisposed to emphysema, cases of children with AAT deficiency presenting with emphysema symptoms may occur rarely [4].

    Patient Information

    Definition

    Alpha-1 antitrypsin (AATD) deficiency is an inherited genetic disorder caused due to deficiency of the alpha–1 antitrypsin. This disorder generally affects the lungs and liver of the individual. So far there is no cure to this disease, but with appropriate treatment regime, the symptoms can be managed and the progression of the condition slowed down.

    Cause

    Two faulty genes of AATD are responsible for the causation of the disease condition. These faulty genes are known as PiZ. If the individual inherits one faulty gene and one normal then he would not develop AATD; however he may pass on the faulty gene to his children.

    Symptoms

    AATD generally presents lung and liver disorders. Coughing, wheezing, shortness of breath, chest infection, fatigue and unexplained weight loss are some of the grave symptoms of this genetic disorder.

    Diagnosis

    The condition is usually diagnosed through blood tests that detect the level of alpha–1 antitrypsin. In addition spirometry is also done to assess the lung functioning. Imaging studies that include X-ray and CT scan of the chest are done to evaluate emphysema.

    Treatment

    Treatment of AATD includes medications that are given to control the wheezing and coughing problem. Antibiotics and steroids are administered to combat the infection and bring down the inflammation.

    Self-assessment

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    References

    1. Stoller JK, Aboussouan LS. A review of a1-antitrypsin deficiency. Am J Respir Crit Care Med. Feb 1 2012; 185(3):246-59.
    2. Kauppi P, Jokelainen K. Alpha-1 antitrypsin deficiency. Duodecim. 2011; 127(18):1911-8 (ISSN: 0012-7183)
    3. Marciniuk DD, Hernandez P, Balter M, Bourbeau J, Chapman KR, Ford GT, et al. Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society clinical practice guideline. Can Respir J. Mar-Apr 2012; 19(2):109-16.
    4. Stoller JK, Lacbawan FL, Aboussouan LS. Alpha-1 Antitrypsin Deficiency. 1993
    5. Greene DN, Elliott-Jelf MC, Straseski JA, Grenache DG. Facilitating the laboratory diagnosis of a1-antitrypsin deficiency. Am J Clin Pathol. Feb 2013; 139(2):184-91.
    6. Bornhorst JA, Greene DN, Ashwood ER, Grenache DG. A1-Antitrypsin phenotypes and associated serum protein concentrations in a large clinical population. Chest. Apr 2013; 143(4):1000-8.
    7. Serapinas D, Obrikyte V, Vaicius D, Balciuviene R, Valavicius A, Sakalauskas R. Alpha-1 antitrypsin deficiency and spontaneous pneumothorax: possible causal relationship. Pneumologia. 2014; 63(1):32-5 (ISSN: 2067-2993)
    8. Campos MA, Lascano J. a1 Antitrypsin deficiency: current best practice in testing and augmentation therapy.Ther Adv Respir Dis. Jul 9 2014
    9. Carey EJ, Iyer VN, Nelson DR, Nguyen JH, Krowka MJ. Outcomes for recipients of liver transplantation for alpha-1-antitrypsin deficiency–related cirrhosis. Liver Transpl. 2013; 19(12):1370-6 (ISSN: 1527-6473)
    10. Köhnlein T, Janciauskiene S, Welte T. Diagnostic delay and clinical modifiers in alpha-1 antitrypsin deficiency. Ther Adv Respir Dis. 2010; 4(5):279-87 (ISSN: 1753-4666)

    • Alpha (1)-antitrypsin deficiency, liver disease and emphysema. - H Parfrey, R Mahadeva, DA Lomas - The international journal of , 2003 - ukpmc.ac.uk
    • Are there predictive factors of severe liver fibrosis in morbidly obese patients with non-alcoholic steatohepatitis? - J Crespo, P Fernández-Gil, M Hernández-Guerra - Obesity surgery, 2001 - Springer
    • A review of alpha-1 antitrypsin deficiency - J Ranes, JK Stoller - Seminars in respiratory and critical care , 2005 - thieme-connect.com
    • Alpha 1-antitrypsin deficiency alleles in cystic fibrosis lung disease. - DD Frangolias, J Ruan, PJ Wilcox - American journal of , 2003 - ukpmc.ac.uk
    • Causes of acute and recurrent pancreatitis: clinical considerations and clues to diagnosis - S Bank, A Indaram - Gastroenterology Clinics of North America, 1999 - Elsevier
    • Alpha~ 1-Antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy - DA Lomas, R Mahadeva - Journal of Clinical Investigation, 2002 - Am Soc Clin Investig
    • Alpha-1 antitrypsin deficiency - AG TO - 1995 - alpha1.org.au
    • Alpha-1-antitrypsin replacement therapy: current status - H Abusriwil, RA Stockley - Current opinion in pulmonary medicine, 2006 - journals.lww.com
    • 1-Antitrypsin deficiency: a variant with no detectable 1-antitrypsin. - RC Talamo, CE Langley, CE Reed, S Makino - Science (New York, NY , 1973 - ukpmc.ac.uk
    • Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy. - RG Crystal - Journal of Clinical Investigation, 1990 - ncbi.nlm.nih.gov
    • A role for intermediate, heterozygous alpha 1-antitrypsin deficiency in obstructive lung disease. - J Lieberman, C Colp - CHEST Journal, 1990 - journal.publications.chestnet.org
    • Alpha 1-antitrypsin administered by aerosol augments lower respiratory tract antineutrophil elastase defenses in individuals with alpha 1-antitrypsin deficiency. - RC Hubbard, NG McElvaney, SE Sellers - Journal of Clinical , 1989 - ncbi.nlm.nih.gov
    • A national program for detection of α1-antitrypsin deficiency in Italy - M Luisetti, G Massi, M Massobrio, P Guarraci - Respiratory , 1999 - Elsevier
    • A lag in intracellular degradation of mutant alpha 1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha 1-antitrypsin deficiency - Y Wu, I Whitman, E Molmenti, K Moore - Proceedings of the , 1994 - National Acad Sciences
    • Alpha-1-antitrypsin deficiency presenting as a bleeding diathesis in the newborn. - PL Hope, MA Hall, GH Millward-Sadler - Archives of disease in , 1982 - ncbi.nlm.nih.gov
    • Alpha 1-antitrypsin administered by aerosol augments lower respiratory tract antineutrophil elastase defenses in individuals with alpha 1-antitrypsin deficiency. - RC Hubbard, NG McElvaney, SE Sellers - Journal of Clinical , 1989 - ncbi.nlm.nih.gov
    • , management, and prevention of chronic obstructive pulmonary disease NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop - RA Pauwels, AS Buist, PMA Calverley - American journal of , 2001 - Am Thoracic Soc
    • Accumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice. - JA Carlson, BB Rogers, RN Sifers - Journal of Clinical , 1989 - ncbi.nlm.nih.gov
    • Disease in adults with severe alpha 1-antitrypsin deficiency (PiZZ): is chronic viral hepatitis B or C an additional risk factor for cirrhosis and hepatocellular carcinoma? - AN Elzouki, S Eriksson - European journal of gastroenterology & , 1996 - ukpmc.ac.uk
    • Accumulation of PiZ alpha 1-antitrypsin causes liver damage in transgenic mice. - JA Carlson, BB Rogers, RN Sifers - Journal of Clinical , 1989 - ncbi.nlm.nih.gov

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