Skip to main content
SpringerLink
Log in

Genetische Ursache einer COPD

Alpha-1-Antitrypsin-Mangel: Pathophysiologie, Diagnostik und Therapie

  • cme fortbildung
  • Published:
Pneumo News Aims and scope

Zusammenfassung

Die chronisch obstruktive Lungenerkrankung (COPD) ist eine durch inhalative Noxen hervorgerufene chronische Erkrankung, deren Phänotyp neben Umwelteinflüssen auch durch genetische Ursachen wie einem Alpha-1-Antitrypsin(AAT)-Mangel beeinflusst wird, eine Genotypisierung kann mittels Polymerasekettenreaktion und Sequenzierung erfolgen. Um eine Progression der Erkrankung zu verlangsamen, kann AAT substituiert werden.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

1
2

Literatur

  1. https://www.atemwegsliga.de/copd.html?file=tl_files/eigene-dateien/copd/COPD-Leitlinie.pdf

  2. Laurell CB, Eriksson S. The electrophoretic alpha1-globulin pattern of serum in alpha1-antitrypsin deficiency. 1963. COPD. 2013;10 Suppl 1:3–8

    Article  Google Scholar 

  3. Konietzko N. [How Carl-Bertil Laurell and Sten Eriksson detected the alpha-1-antitrypsin deficiency 50 years ago and what then came—a somewhat headstrong and personal retrospection]. Pneumologie. 2013;67(10):562–6

    Article  CAS  Google Scholar 

  4. Blanco I, de Serres FJ, Fernandez-Bustillo E 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(1):77–84

    Article  CAS  Google Scholar 

  5. Lomas DA, and Parfrey H. Alpha1-antitrypsin deficiency. 4: Molecular pathophysiology. Thorax. 2004;59(6):529–35

    Article  CAS  Google Scholar 

  6. Greene CM, McElvaney NG. Z alpha-1 antitrypsin deficiency and the endoplasmic reticulum stress response. World J Gastrointest Pharmacol Ther. 2010;1(5):94–101

    Article  Google Scholar 

  7. Fairbanks KD, Tavill AS. Liver disease in alpha 1-antitrypsin deficiency: a review. Am J Gastroenterol. 2008;103(8):2136–41; quiz 42

    Article  CAS  Google Scholar 

  8. Kamimoto T, Shoji S, Hidvegi T et al. Intracellular inclusions containing mutant alpha1-antitrypsin Z are propagated in the absence of autophagic activity. J Biol Chem. 2006;281(7):4467–76

    Article  CAS  Google Scholar 

  9. Hidvegi T, Mirnics K, Hale P et al. Regulator of G Signaling 16 is a marker for the distinct endoplasmic reticulum stress state associated with aggregated mutant alpha1-antitrypsin Z in the classical form of alpha1-antitrypsin deficiency. J Biol Chem. 2007;282(38):27769–80

    Article  CAS  Google Scholar 

  10. Perlmutter DH. Clinical manifestations of alpha 1-antitrypsin deficiency. Gastroenterol Clin North Am. 1995;24(1):27–43

    CAS  PubMed  Google Scholar 

  11. Campbell EJ, Campbell MA, Boukedes SS et al. Quantum proteolysis by neutrophils: implications for pulmonary emphysema in alpha 1-antitrypsin deficiency. J Clin Invest. 1999;104(3):337–44

    Article  CAS  Google Scholar 

  12. Stockley RA. Alpha 1-antitrypsin: more than just deficiency. Thorax. 2004;59(5):363–4

    Article  CAS  Google Scholar 

  13. DeMeo DL, Silverman EK. Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk. Thorax. 2004;59(3):259–64

    Article  CAS  Google Scholar 

  14. Needham M, Stockley RA. Alpha 1-antitrypsin deficiency. 3: Clinical manifestations and natural history. Thorax. 2004;59(5):441–5

    Article  CAS  Google Scholar 

  15. Hersh CP, Dahl M, Ly NP et al. Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes: a meta-analysis. Thorax. 2004;59(10):843–9

    Article  CAS  Google Scholar 

  16. Brantly ML, Paul LD, Miller BH et al. Clinical features and history of the destructive lung disease associated with alpha-1-antitrypsin deficiency of adults with pulmonary symptoms. Am Rev Respir Dis. 1988;138(2):327–36

    Article  CAS  Google Scholar 

  17. Carrell RW, Lomas DA. Alpha1-antitrypsin deficiency—a model for conformational diseases. N Engl J Med. 2002;346(1):45–53

    Article  CAS  Google Scholar 

  18. Stoller JK, Snider GL, Brantly ML et al. [American Thoracic Society/European Respiratory Society Statement: Standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency]. Pneumologie. 2005;59(1):36–68

    Article  CAS  Google Scholar 

  19. Silverman EK, Sandhaus RA. Clinical practice. Alpha1-antitrypsin deficiency. N Engl J Med. 2009;360(26):2749–57

    Article  CAS  Google Scholar 

  20. Eriksson S, Carlson J, Velez R. Risk of cirrhosis and primary liver cancer in alpha 1-antitrypsin deficiency. N Engl J Med. 1986;314(12):736–9.

    Article  CAS  Google Scholar 

  21. Nelson DR, Teckman J, Di Bisceglie AM et al. Diagnosis and management of patients with alpha1-antitrypsin (A1AT) deficiency. Clin Gastroenterol Hepatol. 2012;10(6):575–80

    Article  Google Scholar 

  22. Bowlus CL, Willner I, Zern MA et al. Factors associated with advanced liver disease in adults with alpha1-antitrypsin deficiency. Clin Gastroenterol Hepatol. 2005;3(4):390–6

    Article  CAS  Google Scholar 

  23. Silverman EK, Pierce JA, Province MA et al. Variability of pulmonary function in alpha-1-antitrypsin deficiency: clinical correlates. Ann Intern Med. 1989;111(12):982–91

    Article  CAS  Google Scholar 

  24. Seersholm N, Kok-Jensen A, Dirksen A. Survival of patients with severe alpha 1-antitrypsin deficiency with special reference to non-index cases. Thorax. 1994;49(7):695–8

    Article  CAS  Google Scholar 

  25. Parr DG, Stoel BC, Stolk J et al. Pattern of emphysema distribution in alpha1-antitrypsin deficiency influences lung function impairment. Am J Respir Crit Care Med. 2004;170(11):1172–8

    Article  Google Scholar 

  26. Gross B, Grebe M, Wencker M et al. New Findings in PiZZ alpha1-antitrypsin deficiency-related panniculitis. Demonstration of skin polymers and high dosing requirements of intravenous augmentation therapy. Dermatology. 2009;218(4):370–5

    Article  CAS  Google Scholar 

  27. Mahr AD, Edberg JC, Stone JH et al. Alpha(1)-antitrypsin deficiency-related alleles Z and S and the risk of Wegener’s granulomatosis. Arthritis Rheum. 2010;62(12):3760–7

    Article  CAS  Google Scholar 

  28. Stoller JK, Sandhaus RA, Turino G et al. Delay in diagnosis of alpha1-antitrypsin deficiency: a continuing problem. Chest. 2005;128(4):1989–94

    Article  CAS  Google Scholar 

  29. Greulich T, Ottaviani S, Bals R et al. Alpha1-antitrypsin deficiency - diagnostic testing and disease awareness in Germany and Italy. Respir Med. 2013;107(9):1400–8

    Article  Google Scholar 

  30. American Thoracic S, European Respiratory S. 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(7):818–900

    Article  Google Scholar 

  31. Bostrom S, Nilsson I. Telescopic suction tube for microsurgery. Acta Neurochir (Wien). 1992;118(3-4):162–3

    Article  CAS  Google Scholar 

  32. Costa X, Jardi R, Rodriguez F et al. Simple method for alpha1-antitrypsin deficiency screening by use of dried blood spot specimens. Eur Respir J. 2000;15(6):1111–5

    Article  CAS  Google Scholar 

  33. McElvaney NG, Burdon J, Holmes M et al. Long-term efficacy and safety of a1 proteinase inhibitor treatment for emphysema caused by severe a1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med. 2017 Jan;5(1):51–60

    Article  CAS  Google Scholar 

  34. Stoller JK, Aboussouan LS. Alpha1-antitrypsin deficiency. Lancet. 2005;365(9478):2225–36

    Article  CAS  Google Scholar 

  35. Crystal RG. Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy. J Clin Invest. 1990;85(5):1343–52

    Article  CAS  Google Scholar 

  36. Ferrarotti I, Thun GA, Zorzetto M et al. Serum levels and genotype distribution of alpha1-antitrypsin in the general population. Thorax. 2012;67(8):669–74

    Article  Google Scholar 

  37. Wewers MD, Casolaro MA, Sellers SE et al. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. N Engl J Med. 1987;316(17):1055–62

    Article  CAS  Google Scholar 

  38. Stoller JK, Aboussouan LS. alpha1-Antitrypsin deficiency. 5: intravenous augmentation therapy: current understanding. Thorax. 2004;59(8):708–12

    Article  CAS  Google Scholar 

  39. Seersholm N, Wencker M, Banik 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(10):2260–3

    Article  CAS  Google Scholar 

  40. Tomashefski JF Jr., Crystal RG, Wiedemann HP et al. The bronchopulmonary pathology of alpha-1 antitrypsin (AAT) deficiency: findings of the Death Review Committee of the national registry for individuals with Severe Deficiency of Alpha-1 Antitrypsin. Hum Pathol. 2004;35(12):1452–61

    Article  CAS  Google Scholar 

  41. Wencker M, Fuhrmann B, Banik N 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(3):737–44

    Article  CAS  Google Scholar 

  42. Chapman KR, Stockley RA, Dawkins C et al. Augmentation therapy for alpha1 antitrypsin deficiency: a meta-analysis. COPD. 2009;6(3):177–84

    Article  Google Scholar 

  43. Dowson LJ, Guest PJ, Hill SL et al. High-resolution computed tomography scanning in alpha1-antitrypsin deficiency: relationship to lung function and health status. Eur Respir J. 2001;17(6):1097–104

    Article  CAS  Google Scholar 

  44. Dawkins PA, Dowson LJ, Guest PJ et al. Predictors of mortality in alpha1-antitrypsin deficiency. Thorax. 2003;58(12):1020–6

    Article  CAS  Google Scholar 

  45. Dirksen A, Dijkman JH, Madsen F et al. A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1468–72

    Article  CAS  Google Scholar 

  46. Dirksen A, Piitulainen E, Parr DG et al. Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha1-antitrypsin deficiency. Eur Respir J. 2009;33(6):1345–53

    Article  CAS  Google Scholar 

  47. Chapman KR, Burdon JG, Piitulainen E et al. Intravenous augmentation treatment and lung density in severe alpha1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;386(9991):360–8

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Innere Medizin V - Pneumologie, Allergologie, Beatmungs- und Umweltmedizin, Universitätsklinikum des Saarlandes, Kirrbergerstr. 1, 66421, Homburg/Saar, Deutschland

    Sebastian Fähndrich, Nikolas Bernhard,  Philipp Lepper &  Robert Bals

Authors
  1. Sebastian Fähndrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nikolas Bernhard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Philipp Lepper
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert Bals
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sebastian Fähndrich.

Additional information

Interessenkonflikt

Die Autoren erklären, dass sie sich bei der Erstellung des Beitrages von keinen wirtschaftlichen Interessen leiten ließen. SF und RB erhielten Reisekostenzuschüsse und Vortragshonorare der Firmen CSL Behring und Grifols. NB und PL geben an, dass kein Interessenkonflikt besteht. Der Verlag erklärt, dass die inhaltliche Qualität des Beitrags von zwei unabhängigen Gutachtern geprüft wurde. Werbung in dieser Zeitschriftenausgabe hat keinen Bezug zur CME-Fortbildung. Der Verlag garantiert, dass die CME-Fortbildung sowie die CME-Fragen frei sind von werblichen Aussagen und keiner-lei Produktempfehlungen enthalten. Dies gilt insbesondere für Präparate, die zur Therapie des dargestellten Krankheitsbildes geeignet sind.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fähndrich, S., Bernhard, N., Lepper, P. et al. Alpha-1-Antitrypsin-Mangel: Pathophysiologie, Diagnostik und Therapie. Pneumo News 10, 31–40 (2018). https://doi.org/10.1007/s15033-018-0813-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15033-018-0813-2

Search

Navigation