Alpha-1-Antitrypsin-Mangel (AATM) – Ein Expertenstatement

Dieses Statement wurde erstellt, um einen Überblick über Diagnostik und Therapie des Alpha-1-Antitrypsin-Mangels (AATM) zu erstellen. Die Erstellung des Dokuments wurde durch die Deutsche Gesellschaft für Pneumologie und die Deutsche Atemwegsliga initiiert. Es spiegelt die aktuelle Datenlage wider und bezieht sich auf die vorliegenden Leitlinien und Statements der internationalen und nationalen Fachgesellschaften. An der Erstellung sind deutsche, schweizerische und österreichische Alpha-1-Centren beteiligt.

Publication History

Article published online:
03 June 2020

• Literatur

• 1 Jeppsson JO. Amino acid substitution Glu leads to Lys alpha1-antitrypsin PiZ. FEBS Lett 1976; 65: 195-197
• 2 Carrell RW, Lomas DA. Alpha1-antitrypsin deficiency--a model for conformational diseases. N Engl J Med 2002; 346: 45-53
• 3 Beckman G, Stjernberg NL, Eklund A. Is the PiF allele of alpha 1-antitrypsin associated with pulmonary disease?. Clin Genet 1984; 25: 491-495
• 4 Hutchison DC. Alpha 1-antitrypsin deficiency in Europe: geographical distribution of Pi types S and Z. Respir Med 1998; 92: 367-377
• 5 Sveger T. Liver disease in alpha1-antitrypsin deficiency detected by screening of 200,000 infants. N Engl J Med 1976; 294: 1316-1321
• 6 Dahl M. et al. Change in lung function and morbidity from chronic obstructive pulmonary disease in alpha1-antitrypsin MZ heterozygotes: A longitudinal study of the general population. Ann Intern Med 2002; 136: 270-279
• 7 Blanco I. et al. Estimated numbers and prevalence of PI*S and PI*Z alleles of alpha1-antitrypsin deficiency in European countries. Eur Respir J 2006; 27: 77-84
• 8 Stoller JK. et al. Physical and social impact of alpha 1-antitrypsin deficiency: results of a survey. Cleve Clin J Med 1994; 61: 461-467
• 9 Greulich T. et al. An electronic nose can distinguish between different asthma phenotypes. Eur Respir J 2013; 42: P3551
• 10 ATS/ERS, American Thoracic Society/European Respiratory Society. statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med 2003; 168: 818-900
• 11 Sandhaus RA. et al. The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult. Chronic Obstr Pulm Dis 2016; 3: 668-682
• 12 Bals R. et al. Identification of individuals with alpha-1-antitrypsin deficiency by a targeted screening program. Respir Med 2007; 101: 1708-1714
• 13 Ferrarotti I. et al. Laboratory diagnosis of alpha1-antitrypsin deficiency. Transl Res 2007; 150: 267-274
• 14 Snyder MR. et al. Diagnosis of alpha-1-antitrypsin deficiency: An algorithm of quantification, genotyping, and phenotyping. Clin Chem 2006; 52: 2236-2242
• 15 Steiner SJ. et al. Serum levels of alpha1-antitrypsin predict phenotypic expression of the alpha1-antitrypsin gene. Dig Dis Sci 2003; 48: 1793-1796
• 16 Ferrarotti I. et al. Serum levels and genotype distribution of alpha1-antitrypsin in the general population. Thorax 2012; 67: 669-674
• 17 Greulich T. et al. European screening for alpha -antitrypsin deficiency in subjects with lung disease. Clin Respir J 2015;
• 18 Greulich T. et al. Real world evaluation of a novel lateral flow assay (AlphaKit(R) QuickScreen) for the detection of alpha-1-antitrypsin deficiency. Respir Res 2018; 19: 151
• 19 Miravitlles M. et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in alpha1-antitrypsin deficiency. Eur Respir J 2017; 50: 1700610
• 20 Piitulainen E, Mostafavi B, Tanash HA. Health status and lung function in the Swedish alpha 1-antitrypsin deficient cohort, identified by neonatal screening, at the age of 37-40 years. Int J Chron Obstruct Pulmon Dis 2017; 12: 495-500
• 21 Campos MA. et al. Clinical characteristics of subjects with symptoms of alpha1-antitrypsin deficiency older than 60 years. Chest 2009; 135: 600-608
• 22 Seersholm N, Kok-Jensen A. Clinical features and prognosis of life time non-smokers with severe alpha 1-antitrypsin deficiency. Thorax 1998; 53: 265-268
• 23 Tobin MJ, Cook PJ, Hutchison DC. Alpha 1 antitrypsin deficiency: the clinical and physiological features of pulmonary emphysema in subjects homozygous for Pi type Z. A survey by the British Thoracic Association. Br J Dis Chest 1983; 77: 14-27
• 24 Piitulainen E, Eriksson S. Decline in FEV1 related to smoking status in individuals with severe alpha1-antitrypsin deficiency (PiZZ). Eur Respir J 1999; 13: 247-251
• 25 Janus ED, Phillips NT, Carrell RW. Smoking, lung function, and alpha 1-antitrypsin deficiency. Lancet 1985; 1: 152-154
• 26 Stoller JK. et al. Mortality in individuals with severe deficiency of alpha1-antitrypsin: findings from the National Heart, Lung, and Blood Institute Registry. Chest 2005; 127: 1196-1204
• 27 Dawkins PA. et al. Predictors of mortality in alpha1-antitrypsin deficiency. Thorax 2003; 58: 1020-1026
• 28 Horvath I. et al. Diagnosis and management of alpha1-antitrypsin deficiency in Europe: an expert survey. ERJ Open Res 2019; 5: 00171-2018
• 29 Miravitlles M. et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in alpha1-antitrypsin deficiency. Eur Respir J 2017; 50: pii: 1700610
• 30 Vogelmeier C. et al. Guideline for the Diagnosis and Treatment of COPD Patients – Issued by the German Respiratory Society and the German Atemwegsliga in Cooperation with the Austrian Society of Pneumology. Pneumologie 2018; 72: 253-308
• 31 Singh D. et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur Respir J 2019; 53: pii: 1900164
• 32 Dirksen A. et al. Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency. Eur Respir J 2009; 33: 1345-1353
• 33 Chapman KR. et al. Augmentation therapy for alpha1 antitrypsin deficiency: a meta-analysis. COPD 2009; 6: 177-184
• 34 Stockley RA. et al. Therapeutic efficacy of alpha-1 antitrypsin augmentation therapy on the loss of lung tissue: an integrated analysis of 2 randomised clinical trials using computed tomography densitometry. Respir Res 2010; 11: 136
• 35 Gotzsche PC, Johansen HK. Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease. Cochrane Database Syst Rev 2010; 09: CD007851
• 36 Dirksen A. et al. A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy. Am J Respir Crit Care Med 1999; 160: 1468-1472
• 37 Chapman KR. et al. Intravenous augmentation treatment and lung density in severe alpha1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 386: 360-368
• 38 McElvaney NG. et al. Long-term efficacy and safety of alpha1 proteinase inhibitor treatment for emphysema caused by severe alpha1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med 2017; 5: 51-60
• 39 Stoller JK. et al. Biochemical efficacy and safety of a new pooled human plasma alpha(1)-antitrypsin, Respitin. Chest 2002; 122: 66-74
• 40 Stocks JM. et al. Multi-center study: the biochemical efficacy, safety and tolerability of a new alpha1-proteinase inhibitor, Zemaira. COPD 2006; 3: 17-23
• 41 Stocks JM. et al. Pharmacokinetic comparability of Prolastin(R)-C to Prolastin(R) in alpha(1)-antitrypsin deficiency: a randomized study. BMC Clin Pharmacol 2010; 10: 13
• 42 Campos MA. et al. Safety and pharmacokinetics of 120 mg/kg versus 60 mg/kg weekly intravenous infusions of alpha-1 proteinase inhibitor in alpha-1 antitrypsin deficiency: a multicenter, randomized, double-blind, crossover study (SPARK). COPD 2013; 10: 687-695
• 43 Sandhaus RA. et al. Biochemical efficacy and safety of a new, ready-to-use, liquid alpha-1-proteinase inhibitor, GLASSIA (alpha1-proteinase inhibitor (human), intravenous). COPD 2014; 11: 17-25
• 44 The Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. Am J Respir Crit Care Med 1998; 158: 49-59
• 45 Seersholm N. et al. Does alpha1-antitrypsin augmentation therapy slow the annual decline in FEV1 in patients with severe hereditary alpha1-antitrypsin deficiency? Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL) alpha1-AT study group. Eur Respir J 1997; 10: 2260-2263
• 46 Stoller JK. et al. Augmentation therapy with alpha1-antitrypsin: patterns of use and adverse events. Chest 2003; 123: 1425-1434
• 47 Wencker M. et al. Longitudinal follow-up of patients with alpha(1)-protease inhibitor deficiency before and during therapy with IV alpha(1)-protease inhibitor. Chest 2001; 119: 737-744
• 48 Tonelli AR. et al. Alpha-1-antitrypsin augmentation therapy in deficient individuals enrolled in the Alpha-1 Foundation DNA and Tissue Bank. Int J Chron Obstruct Pulmon Dis 2009; 4: 443-452
• 49 Barros-Tizon JC. et al. Reduction of severe exacerbations and hospitalization-derived costs in alpha-1-antitrypsin-deficient patients treated with alpha-1-antitrypsin augmentation therapy. Ther Adv Respir Dis 2012; 6: 67-78
• 50 Wewers MD. et al. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. N Engl J Med 1987; 316: 1055-1062
• 51 Schmidt EW. et al. Replacement therapy for alpha-1-protease inhibitor deficiency in PiZ subjects with chronic obstructive lung disease. Am J Med 1988; 84: 63-69
• 52 Barker AF. et al. Replacement therapy for hereditary alpha1-antitrypsin deficiency. A program for long-term administration. Chest 1994; 105: 1406-1410
• 53 Barker AF. et al. Pharmacokinetic study of alpha1-antitrypsin infusion in alpha1-antitrypsin deficiency. Chest 1997; 112: 607-613
• 54 Miravitlles M. et al. Evaluation of replacement therapy in emphysema caused by alpha 1-antitrypsin deficiency. Arch Bronconeumol 1994; 30: 479-484
• 55 Schwaiblmair M, Vogelmeier C, Fruhmann G. Long-term augmentation therapy in twenty patients with severe alpha-1-antitrypsin deficiency -- three-year follow-up. Respiration 1997; 64: 10-15
• 56 Wencker M. et al. Long-term therapy of alpha 1-antitrypsin-deficiency-associated pulmonary emphysema with human alpha 1-antitrypsin. Pneumologie 1998; 52: 545-552
• 57 Wencker M. et al. Long-term treatment of alpha1-antitrypsin deficiency-related pulmonary emphysema with human alpha1-antitrypsin. Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL)-alpha1-AT-study group. Eur Respir J 1998; 11: 428-433
• 58 Campos MA. et al. Exacerbations in subjects with alpha-1 antitrypsin deficiency receiving augmentation therapy. Respir Med 2009; 103: 1532-1539
• 59 Subramanian DR. et al. Assessment of pulmonary neutrophilic inflammation in emphysema by quantitative positron emission tomography. Am J Respir Crit Care Med 2012; 186: 1125-1132
• 60 Ma S. et al. The Effect of Alpha-1 Proteinase Inhibitor on Biomarkers of Elastin Degradation in Alpha-1 Antitrypsin Deficiency: An Analysis of the RAPID/RAPID Extension Trials. Chronic Obstr Pulm Dis 2016; 4: 34-44
• 61 Fahndrich S. et al. Exacerbations and duration of smoking abstinence are associated with the annual loss of FEV1 in individuals with PiZZ alpha-1-antitrypsin deficiency. Respir Med 2017; 129: 8-15
• 62 Dowson LJ. et al. High-resolution computed tomography scanning in alpha1-antitrypsin deficiency: relationship to lung function and health status. Eur Respir J 2001; 17: 1097-1104
• 63 Dawkins P. et al. Mortality in alpha-1-antitrypsin deficiency in the United Kingdom. Respir Med 2009; 103: 1540-1547
• 64 Green CE. et al. Lung density associates with survival in alpha 1 antitrypsin deficient patients. Respir Med 2016; 112: 81-87
• 65 Campos MA. et al. The Biological Effects of Double-Dose Alpha-1 Antitrypsin Augmentation Therapy: A Pilot Study. Am J Respir Crit Care Med 2019; 200: 318-326
• 66 Kohnlein T. et al. Expert statement for augmentation therapy in patients with alpha-1 antitrypsin deficiency. Pneumologie 2014; 68: 492-495