What are the guideline sources, guidelines and references for Alpha-1 antitrypsin deficiency ?
Guideline sources The following summarized guidelines for the evaluation and management of alpha-1 antitrypsin deficiency (AATD) are prepared by our editorial team based on guidelines from the National Comprehensive Cancer Network (NCCN 2022), the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2022), the European Respiratory Society (ERS 2017), the Alpha-1 Foundation (Alpha-1 2016), the American Association for the Study of Liver Diseases (AASLD 2014), and the Canadian Thoracic Society (CTS 2012). 1 2 3 4 5 6 7 Guidelines 1. Screening and diagnosis Clinical presentation: Recognize that lung disease in AAT deficiency generally presents at a younger age than usual COPD and may be misdiagnosed as asthma. E Recognize that patients with AAT deficiency are more likely to have basal emphysema than patients with usual COPD. E Screening of family relatives: https://web.pathway.md/diseases/recnIrSPaCPOnucJJ 1/5 6/23/23, 2:19 AM Alpha-1 antitrypsin deficiency Pathway As per ERS 2017 guidelines, consider offering testing for AAT deficiency after appropriate counseling in family relatives of identified patients. E As per Alpha-1 2016 guidelines, provide genetic counseling and offer testing for AAT deficiency in adult siblings of patients with an abnormal AAT gene, whether heterozygote or homozygote. B Show 2 more Indications for testing, lung disease: As per ERS 2017 guidelines, consider testing for AAT deficiency in patients with bronchiectasis in the presence of basal emphysema or early onset airflow obstruction. As per ERS 2017 guidelines, test for AAT deficiency in all patients with COPD or adult-onset asthma. E As per Alpha-1 2016 guidelines: Test for AAT deficiency in all patients with COPD, regardless of age or ethnicity. B Test for AAT deficiency in all patients with unexplained bronchiectasis. B As per CTS 2012 guidelines: Consider obtaining targeted testing for AAT deficiency in patients with COPD diagnosed before 65 years of age or with a smoking history of < 20 pack-years. C Avoid obtaining targeted testing for AAT deficiency in patients with bronchiectasis or asthma. D Indications for testing (liver disease): test for AAT deficiency in all patients with unexplained chronic liver disease. B Indications for testing (vasculitis): test for AAT deficiency in all patients with granulomatosis with polyangiitis. B Indications for testing (panniculitis): test for AAT deficiency in all patients with necrotizing panniculitis. B 2. Diagnostic investigations AAT levels: As per ERS 2017 guidelines, obtain quantitative measurement of AAT levels in the blood to identify AAT deficiency. E As per Alpha-1 2016 guidelines, measure AAT level for advanced or confirmatory testing. Protein electrophoresis: As per ERS 2017 guidelines, obtain protein phenotyping by isoelectric focusing to identify variants where AAT is present in the sample including the rarer variants F, I, and P. E As per Alpha-1 2016 guidelines, obtain Pi-typing for advanced or confirmatory testing. Genetic testing: https://web.pathway.md/diseases/recnIrSPaCPOnucJJ 2/5 6/23/23, 2:19 AM Alpha-1 antitrypsin deficiency Pathway As per ERS 2017 guidelines, obtain genetic testing for AAT deficiency to support quantitative testing. E Show 2 more As per Alpha-1 2016 guidelines, obtain genotyping for at least the S and Z alleles for diagnostic testing of symptomatic patients. Obtain expanded genotyping for advanced or confirmatory testing. Pulmonary function testing: obtain initial complete lung function testing in all patients with AAT deficiency. B Chest imaging: obtain a baseline chest CT in newly diagnosed patients being symptomatic and/or having abnormal pulmonary function testing. B 3. Medical management Setting of care: manage patients with AAT deficiency in supervision by reference centers of excellence at a national or regional level. E Augmentation therapy: As per GOLD 2022 guidelines, consider initiating IV augmentation therapy to slow down the progression of emphysema in patients with AAT deficiency and COPD (with never or ex- smokers with an FEV in 1 second of 35-60% of predicted and patients with severe hereditary AAT deficiency with established emphysema being the most suitable candidates). C As per ERS 2017 guidelines: Initiate IV augmentation therapy to reduce the progression of emphysema in patients with severe AAT deficiency. E Insufficient evidence to support the use of augmentation therapy in PiSZ or PiMZ subjects or current smokers of any protein phenotype. I As per Alpha-1 2016 guidelines, initiate IV augmentation therapy in patients with AAT deficiency and an FEV in 1 second in the range of 30-65% of predicted. A Show 10 more As per CTS 2012 guidelines, consider initiating AAT augmentation therapy in non-smoking or ex-smoking patients with COPD with a FEV in 1 second in the range of 25-80% of predicted attributable to emphysema and documented low levels of AAT, i.e. 11 mcmol/L, receiving optimal pharmacological and nonpharmacological therapies, including comprehensive case management and pulmonary rehabilitation, for the benefits in CT lung density C and mortality. C 4. Nonpharmacologic interventions Smoking cessation: advise smoking cessation and avoidance of exposure to tobacco in patients with AAT deficiency. A https://web.pathway.md/diseases/recnIrSPaCPOnucJJ 3/5 6/23/23, 2:19 AM Alpha-1 antitrypsin deficiency Pathway 5. Surgical interventions Lung volume reduction surgery: As per ERS 2017 guidelines, consider performing surgical volume reduction and endobronchial valve placement in selected patients with AAT deficiency, with a careful appraisal of risks and benefits assessed by a multidisciplinary team experienced in lung volume reduction and AAT deficiency. E As per Alpha-1 2016 guidelines, do not perform lung volume reduction surgery in patients with COPD related to AAT deficiency. D Lung transplantation: recognize that patients with AAT deficiency generally have improved quality of life following lung transplantation, however insufficient evidence regarding the survival benefit of lung transplantation. E Liver transplantation: As per AASLD 2014 guidelines: Offer liver transplantation in patients with decompensated cirrhosis due to AAT deficiency. B Obtain pulmonary function testing and chest imaging to exclude lung disease in patients with AAT deficiency being evaluated for liver transplantation. B 6. Follow-up and surveillance Surveillance for lung disease: As per ERS 2017 guidelines, obtain annual pulmonary function testing including post- bronchodilator FEV in 1 second and gas transfer to monitor for disease progression. E Show 3 more As per Alpha-1 2016 guidelines: Obtain annual spirometry during follow-up of adult patients with AAT deficiency with normal baseline spirometry. B Do not obtain serial chest CT to monitor the progression of the disease. D Surveillance for liver disease: Obtain the following at annual intervals (or more frequently as indicated by clinical circumstances) to monitor for liver disease in patients with AAT deficiency: physical examination, including a focused examination for signs of liver disease liver ultrasound laboratory monitoring of AST, ALT, gamma-glutamyltransferase, albumin, bilirubin, INR, and platelets. B Surveillance for hepatocellular carcinoma: obtain surveillance for HCC in patients with AAT deficiency and cirrhosis. B References https://web.pathway.md/diseases/recnIrSPaCPOnucJJ 4/5 6/23/23, 2:19 AM Alpha-1 antitrypsin deficiency Pathway 1. Al B Benson, Michael I D'Angelica, Daniel E Abbott et al. Hepatobiliary Cancers, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. NCCN. 2022 Jul 15. Open 2. Robert A Sandhaus, Gerard Turino, Mark L Brantly et al. The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult. Chronic Obstr Pulm Dis. 2016 Jun 6;3 3 668 682. Open 3. Darcy D Marciniuk, P Hernandez, M Balter et al. Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2012 Mar- Apr;19 2 109 16. Open 4. Marc Miravitlles, Asger Dirksen, Ilaria Ferrarotti et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in 1 antitrypsin deficiency. Eur Respir J. 2017 Nov 30;50 5 1700610. Open 5. Paul Martin, Andrea DiMartini, Sandy Feng et al. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014 Mar;59 3 1144 65. Open 6. Polverino E, Goeminne PC, McDonnell MJ et al. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017 Sep 9;50 3 . pii: 1700629. Open 7. Alvar Agusti, Richard Beasley, Bartolome R. Celli et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: 2022 Report. GOLD. 2022. Open https://web.pathway.md/diseases/recnIrSPaCPOnucJJ 5/5