Skip to main content
SpringerLink
Log in

α1-Antitrypsin-Mangel in der COPD- und Emphysementstehung

Epidemiologie, Biologie und Klinik der COPD bei jungen Rauchern und Nichtrauchern

α1-antitrypsin deficiency in the development of COPD and emphysema

Epidemiology, biology and clinical presentation of COPD in young smokers and non-smokers

  • CME Weiterbildung · Zertifizierte Fortbildung
  • Published:
Der Pneumologe Aims and scope

Zusammenfassung

Die chronisch-obstruktive Lungenerkrankung (COPD) ist charakterisiert durch eine nichtreversible und typischerweise progrediente Atemwegsobstruktion und tritt überwiegend bei älteren Personen auf. Rauchen ist wichtigster Risikofaktor. Bis zu 25% der Patienten entwickeln jedoch ungewöhnlich früh eine COPD oder haben nie geraucht; hier bestehen oft diagnostische und therapeutische Unsicherheiten.

In dieser Übersicht werden Umweltfaktoren, genetische Dispositionen und Vorerkrankungen diskutiert, die in eine COPD münden können. Die Genetik der COPD ist komplex. Einzige gesicherte genetische Prädisposition ist der α1-Antitrypsin-Mangel (AATM): Mutationen des kodierenden Gens SERPINA1 bedingen Konformationsänderungen des Proteins, die zur Akkumulation von AAT in Leberzellen und zu einem Mangel im Organismus führen, der in der Lunge in einer frühen COPD resultieren kann. Rechtzeitige Identifikation des AATM und subsequente Lebensstiländerung können helfen, den Ausbruch der COPD hinauszuzögern.

Abstract

Chronic obstructive lung disease (COPD) is characterized by airflow limitation, which is typically progressive and irreversible. Tobacco smoking is the most important risk factor, leading primarily to development of COPD in older persons. However, there are many patients diagnosed with COPD (up to 25%) who have never smoked but nevertheless contract the disease at an unusually young age. In these cases, uncertainty often exists regarding diagnosis and therapy.

This review discusses environmental factors and genetic dispositions that contribute to the development of COPD, mainly focussing on α1-antitrypsin deficiency (AATD). There are many predisposing diseases or environmental factors besides smoking that may play a role in the pathogenesis of COPD. The genetics of COPD is very complex. The only accepted genetic predisposition resulting in COPD is AATD, which is based on a mutation of the encoding gene SERPINA1. Mutations of this gene result in conformational changes of AAT leading to an accumulation of the protein in hepatocytes and a deficiency in other organs. Because of deficiency of the lung, individuals are susceptible for the development of early COPD. Early identification of AATD with subsequent lifestyle changes and therapeutic interventions can help delay the onset of COPD.

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

Abb. 1
Abb. 2

Literatur

  1. Vogelmeier C, Buhl R, Criee CP et al (2007) Guidelines for the diagnosis and therapy of COPD issued by Deutsche Atemwegsliga and Deutsche Gesellschaft fur Pneumologie und Beatmungsmedizin. Pneumologie 61:e1–e40

    Article  CAS  PubMed  Google Scholar 

  2. Oswald NC, Medvei VC (1955) Chronic bronchitis; the effect of cigarette-smoking. Lancet 269:843–844

    Article  CAS  PubMed  Google Scholar 

  3. Kohansal R, Martinez-Camblor P, Agusti A et al (2009) The natural history of chronic airflow obstruction revisited: an analysis of the Framingham offspring cohort. Am J Respir Crit Care Med 180:3–10

    Article  PubMed  Google Scholar 

  4. Barnes PJ (2000) Chronic obstructive pulmonary disease. N Engl J Med 343:269–280

    Article  CAS  PubMed  Google Scholar 

  5. Burrows B, Knudson RJ, Cline MG et al (1977) Quantitative relationships between cigarette smoking and ventilatory function. Am Rev Respir Dis 115:195–205

    CAS  PubMed  Google Scholar 

  6. Buist AS, McBurnie MA, Vollmer WM et al (2007) International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet 370:741–750

    Article  PubMed  Google Scholar 

  7. Behrendt CE (2005) Mild and moderate-to-severe COPD in nonsmokers: distinct demographic profiles. Chest 128:1239–1244

    Article  PubMed  Google Scholar 

  8. Birring SS, Brightling CE, Bradding P et al (2002) Clinical, radiologic and induced sputum features of chronic obstructive pulmonary disease in nonsmokers: a descriptive study. Am J Respir Crit Care Med 166:1078–1083

    Article  PubMed  Google Scholar 

  9. Pena VS, Miravitlles M, Gabriel R et al (2000) Geographic variations in prevalence and underdiagnosis of COPD: results of the IBERPOC multicentre epidemiological study. Chest 118:981–989

    Article  CAS  PubMed  Google Scholar 

  10. Sezer H, Akkurt I, Guler N et al (2006) A case-control study on the effect of exposure to different substances on the development of COPD. Ann Epidemiol 16:59–62

    Article  PubMed  Google Scholar 

  11. Boy E, Bruce N, Delgado H (2002) Birth weight and exposure to kitchen wood smoke during pregnancy in rural Guatemala. Environ Health Perspect 110:109–114

    CAS  PubMed  Google Scholar 

  12. Murray CJ, Lopez AD, Jamison DT (1994) The global burden of disease in 1990: summary results, sensitivity analysis and future directions. Bull World Health Organ 72:495–509

    CAS  PubMed  Google Scholar 

  13. Andreas S, Batra A, Behr J et al (2008) Guidelines for smoking cessation in patients with COPD issued by the Deutsche Gesellschaft fur Pneumologie und Beatmungsmedizin. Pneumologie 62:255–272

    Article  CAS  PubMed  Google Scholar 

  14. Balmes J, Becklake M, Blanc P et al (2003) American thoracic society statement: Occupational contribution to the burden of airway disease. Am J Respir Crit Care Med 167:787–797

    Article  PubMed  Google Scholar 

  15. Salvi SS, Barnes PJ (2009) Chronic obstructive pulmonary disease in non-smokers. Lancet 374:733–743

    Article  PubMed  Google Scholar 

  16. Birath G, Caro J, Malmberg R et al (1966) Airways obstruction in pulmonary tuberculosis. Scand J Respir Dis 47:27–36

    CAS  PubMed  Google Scholar 

  17. Snider GL, Doctor L, Demas TA et al (1971) Obstructive airway disease in patients with treated pulmonary tuberculosis. Am Rev Respir Dis 103:625–640

    CAS  PubMed  Google Scholar 

  18. Orie NG (1961) Correlations of emphysema and asthmatic constitution. Acta Allergol 16:407–409

    CAS  PubMed  Google Scholar 

  19. Haldar P, Pavord ID (2007) Noneosinophilic asthma: a distinct clinical and pathologic phenotype. J Allergy Clin Immunol 119:1043–1052

    Article  CAS  PubMed  Google Scholar 

  20. Fairbairn AS, Reid DD (1948) Air pollution and other local factors in respiratory disease. Br J Prev Soc Med 12:94–103

    Google Scholar 

  21. Sunyer J (2001) Urban air pollution and chronic obstructive pulmonary disease: a review. Eur Respir J 17:1024–1033

    Article  CAS  PubMed  Google Scholar 

  22. Hegewald MJ, Crapo RO (2007) Socioeconomic status and lung function. Chest 132:1608–1614

    Article  PubMed  Google Scholar 

  23. Kabesch M, Kauffmann F, von Mutius E (2006) New ways in respiratory genetics. Eur Respir J 28:1079–1080

    Article  CAS  PubMed  Google Scholar 

  24. Silverman EK, Palmer LJ, Mosley JD et al (2002) Genomewide linkage analysis of quantitative spirometric phenotypes in severe early-onset chronic obstructive pulmonary disease. Am J Hum Genet 70:1229–1239

    Article  CAS  PubMed  Google Scholar 

  25. Wan ES, Silverman EK (2009) Genetics of COPD and emphysema. Chest 136:859–866

    Article  PubMed  Google Scholar 

  26. Ganrot PO, Laurell CB, Eriksson S (1967) Obstructive lung disease and trypsin inhibitors in alpha-1-antitrypsin deficiency. Scand J Clin Lab Invest 19:205–208

    Article  CAS  PubMed  Google Scholar 

  27. Blanco I, Serres FJ de, Fernandez-Bustillo E et al (2006) Estimated numbers and prevalence of PI*S and PI*Z alleles of alpha1-antitrypsin deficiency in European countries. Eur Respir J 27:77–84

    Article  CAS  PubMed  Google Scholar 

  28. Stockley RA, Luisetti M, Miravitlles M et al (2007) Ongoing research in Europe: Alpha One International Registry (AIR) objectives and development. Eur Respir J 29:582–586

    Article  CAS  PubMed  Google Scholar 

  29. DeMeo DL, Silverman EK (2004) Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk. Thorax 59:259–264

    Article  CAS  PubMed  Google Scholar 

  30. American Thoracic Society; European Respiratory Society (2003) 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 168:818–900

    Article  Google Scholar 

  31. Mahadeva R, Lomas DA (1998) Genetics and respiratory disease. 2. Alpha 1-antitrypsin deficiency, cirrhosis and emphysema. Thorax 53:501–505

    Article  CAS  PubMed  Google Scholar 

  32. McElvaney NG, Stoller JK, Buist AS et al (1997) Baseline characteristics of enrollees in the national heart, lung and blood institute registry of alpha 1-antitrypsin deficiency. Alpha 1-antitrypsin deficiency registry study group. Chest 111:394–403

    Article  CAS  PubMed  Google Scholar 

  33. Bals R, Koczulla R, Kotke V et al (2007) Identification of individuals with alpha-1-antitrypsin deficiency by a targeted screening program. Respir Med 101:1217–1218

    Article  Google Scholar 

  34. anonymous (1997) Alpha 1-antitrypsin deficiency: memorandum from a WHO meeting. Bull World Health Organ 75:397–415

    Google Scholar 

  35. Magnussen H, Goeckenjan G, Kohler D et al (2001) Guidelines to long-term oxygen therapy. Pneumologie 55:454–464

    Article  CAS  PubMed  Google Scholar 

  36. Tutic M, Bloch KE, Lardinois D et al (2004) Long-term results after lung volume reduction surgery in patients with alpha1-antitrypsin deficiency. J Thorac Cardiovasc Surg 128:408–413

    Article  PubMed  Google Scholar 

  37. Sandhaus RA (2004) alpha1-antitrypsin deficiency. 6: new and emerging treatments for alpha1-antitrypsin deficiency. Thorax 59:904–909

    Article  CAS  PubMed  Google Scholar 

  38. Wencker M, Banik N, Buhl R et al (1998) 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 11:428–433

    Article  CAS  PubMed  Google Scholar 

  39. Alpha-1-Antitrypsin Deficiency Registry Study Group (1998) Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. The alpha-1-antitrypsin deficiency registry study group. Am J Respir Crit Care Med 158:49–59

    Google Scholar 

  40. Wencker M, Fuhrmann B, Banik N et al (2001) Longitudinal follow-up of patients with alpha(1)-protease inhibitor deficiency before and during therapy with IV alpha(1)-protease inhibitor. Chest 119:737–744

    Article  CAS  PubMed  Google Scholar 

  41. Seersholm N, Wencker M, Banik N et al (1997) 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 10:2260–2263

    Article  CAS  PubMed  Google Scholar 

  42. Dirksen A, Dijkman JH, Madsen F et al (1999) A randomized clinical trial of alpha(1)-antitrypsin augmentation therapy. Am J Respir Crit Care Med 160:1468–1472

    CAS  PubMed  Google Scholar 

  43. Dirksen A, Piitulainen E, Parr DG et al (2009) Exploring the role of CT densitometry: a randomised study of augmentation therapy in alpha-1 antitrypsin deficiency. Eur Respir J 33(6):1345–1353

    Article  CAS  PubMed  Google Scholar 

  44. Hersh CP, Dahl M, Ly NP et al (2004) Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes: a meta-analysis. Thorax 59:843–849

    Article  CAS  PubMed  Google Scholar 

  45. Koczulla R, Bittkowski N, Andress J et al (2008) The German registry of individuals with alpha-1-antitrypsin deficiency – a source for research on patient care. Pneumologie 62:655–658

    Article  CAS  PubMed  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Wissenschaftliche Projekte des Klinikums werden seit 2003 von der Firma Bayer Healthcare/Talecris Biotherapeutics gefördert. RB erhielt Vortragshonorare und Reisesponsoring durch diese Firmen. Die Präsentation des Themas ist unabhängig und die Darstellung des Inhalts produktneutral.

Author information

Authors and Affiliations

  1. Klinik für Innere Medizin mit Schwerpunkt Pneumologie, Onkologie und Immunologie, Universitätsklinikum Gießen und Marburg – Standort Marburg, Philipps-Universität Marburg, Baldingerstr. 1, 35043, Marburg, Deutschland

    S. Schroth &  R. Bals

Authors
  1. S. Schroth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Bals
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Bals.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schroth, S., Bals, R. α1-Antitrypsin-Mangel in der COPD- und Emphysementstehung. Pneumologe 7, 49–58 (2010). https://doi.org/10.1007/s10405-009-0381-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10405-009-0381-6

Schlüsselwörter

Keywords

Search

Navigation