Advertisement

Lung Disease of Alpha-1 Antitrypsin Deficiency

  • Robert A. SandhausEmail author
Part of the Respiratory Medicine book series (RM)

Abstract

Lung disease is the most commonly identified clinical manifestation of alpha-1 antitrypsin deficiency (AATD) and is usually characterized by pulmonary emphysema and/or bronchiectasis (Silverman and Sandhaus, N Engl J Med 360(26):2749–57, 2009). It also represents the most common reason that an adult is tested for AATD (The Alpha 1-Antitrypsin Deficiency Registry Study Group, Chest 106(4):1223–32, 1994). This bias toward testing individuals with lung disease that is of unexplained severity or age of onset has led to the potentially mistaken impression that most individuals with AATD suffer from precocious lung disease. In fact, the percentage of individuals with AATD who suffer from pulmonary problems is currently not known, and most collections of individuals diagnosed with this genetic condition reveal an average age not that dissimilar from patients with non-AATD chronic obstructive pulmonary disease (COPD) (Campos et al., Chest 128(3):1179–86, 2005). The importance of diagnosing AATD-related lung disease is centered around family genetic counseling and the availability of specific therapy.

Keywords

Alpha-1 antitrypsin Alpha-1 antitrypsin deficiency Emphysema Bronchiectasis Augmentation Elastase Tobacco 

References

  1. 1.
    Stoller JK, Aboussouan LS. A review of alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2012;185(3):246–59.PubMedCrossRefGoogle Scholar
  2. 2.
    DeMeo DL, Campbell EJ, Brantly ML, Barker AF, Eden E, McElvaney NG, et al. Heritability of lung function in severe alpha-1 antitrypsin deficiency. Hum Hered. 2009;67(1):38–45.PubMedCrossRefGoogle Scholar
  3. 3.
    Mayer AS, Stoller JK, Vedal S, Ruttenber AJ, Strand M, Sandhaus RA, et al. Risk factors for symptom onset in PI*Z alpha-1 antitrypsin deficiency. Int J Chron Obstruct Pulmon Dis. 2006;1(4):485–92.PubMedCentralPubMedGoogle Scholar
  4. 4.
    Dowson LJ, Guest PJ, Hill SL, Holder RL, Stockley RA. High-resolution computed tomography scanning in alpha1-antitrypsin deficiency: relationship to lung function and health status. Eur Respir J. 2001;17(6):1097–104.PubMedCrossRefGoogle Scholar
  5. 5.
    Parr DG, Guest PG, Reynolds JH, Dowson LJ, Stockley RA. Prevalence and impact of bronchiectasis in alpha1-antitrypsin deficiency. Am J Respir Crit Care Med. 2007;176(12):1215–21.PubMedCrossRefGoogle Scholar
  6. 6.
    Elzouki AN, Segelmark M, Wieslander J, Eriksson S. Strong link between the alpha 1-antitrypsin PiZ allele and Wegener’s granulomatosis. J Intern Med. 1994;236(5):543–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Laurell C-B, Eriksson S. The electrophoretic alpha-1-globulin pattern of serum in alpha-1 antitrypsin deficiency. Scan J Clin Lab Invest. 1963;15:132–40.CrossRefGoogle Scholar
  8. 8.
    Gross P, Babyak MA, Tolker E, Kaschak M. Enzymatically produced pulmonary emphysema; a preliminary report. J Occup Med. 1964;6:481–4.PubMedGoogle Scholar
  9. 9.
    Snider GL, Hayes JA, Franzblau C, Kagan HM, Stone PS, Korthy AL. Relationship between elastolytic activity and experimental emphysema-induced properties of papain preparations. Am Rev Respir Dis. 1974;110(3):254–62.PubMedCrossRefGoogle Scholar
  10. 10.
    Blackwood CE, Hosannah Y, Perman E, Keller S, Mandl I. Experimental emphysema in rats: elastolytic titer of inducing enzyme as determinant of the response. Proc Soc Exp Biol Med. 1973;144(2):450–4.PubMedCrossRefGoogle Scholar
  11. 11.
    Janoff A, Scherer J. Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes. J Exp Med. 1968;128(5):1137–55.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Janoff A. Inhibition of human granulocyte elastase by serum alpha-1-antitrypsin. Am Rev Respir Dis. 1972;105(1):121–2.PubMedGoogle Scholar
  13. 13.
    Pannell R, Johnson D, Travis J. Isolation and properties of human plasma alpha-1-proteinase inhibitor. Biochemistry. 1974;13(26):5439–45.PubMedCrossRefGoogle Scholar
  14. 14.
    Laurell CB. Is emphysema in alpha 1-antitrypsin deficiency a result of autodigestion? Scand J Clin Lab Invest. 1971;28(1):1–3.PubMedCrossRefGoogle Scholar
  15. 15.
    Janoff A, Carp H. Possible mechanisms of emphysema in smokers: cigarette smoke condensate suppresses protease inhibition in vitro. Am Rev Respir Dis. 1977;116(1):65–72.PubMedGoogle Scholar
  16. 16.
    Janoff A, Carp H, Lee DK, Drew RT. Cigarette smoke inhalation decreases alpha 1-antitrypsin activity in rat lung. Science. 1979;206(4424):1313–4.PubMedCrossRefGoogle Scholar
  17. 17.
    Fregonese L, Stolk J, Frants RR, Veldhuisen B. Alpha-1 antitrypsin null mutations and severity of emphysema. Respir Med. 2008;102(6):876–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Gadek JE, Klein HG, Holland PV, Crystal RG. Replacement therapy of alpha 1-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects. J Clin Invest. 1981;68(5):1158–65.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Wewers MD, Casolaro MA, Sellers SE, Swayze SC, McPhaul KM, Wittes JT, et al. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. N Engl J Med. 1987;316(17):1055–62.PubMedCrossRefGoogle Scholar
  20. 20.
    Tan L, Dickens JA, Demeo DL, Miranda E, Perez J, Rashid ST, et al. Circulating polymers in alpha1-antitrypsin deficiency. Eur Respir J. 2014;43(5):1501–4.PubMedCrossRefGoogle Scholar
  21. 21.
    Parmar JS, Mahadeva R, Reed BJ, Farahi N, Cadwallader KA, Keogan MT, et al. Polymers of alpha(1)-antitrypsin are chemotactic for human neutrophils: a new paradigm for the pathogenesis of emphysema. Am J Respir Cell Mol Biol. 2002;26(6):723–30.PubMedCrossRefGoogle Scholar
  22. 22.
    McElvaney NG, Stoller JK, Buist AS, Prakash UB, Brantly ML, Schluchter MD, Alpha 1-Antitrypsin Deficiency Registry Study Group, et al. Baseline characteristics of enrollees in the National Heart, Lung and Blood Institute registry of alpha 1-antitrypsin deficiency. Chest. 1997;111(2):394–403.PubMedCrossRefGoogle Scholar
  23. 23.
    Lieberman J, Winter B, Sastre A. Alpha 1-antitrypsin Pi-types in 965 COPD patients. Chest. 1986;89(3):370–3.PubMedCrossRefGoogle Scholar
  24. 24.
    Rahaghi FF, Sandhaus RA, Strange C, Hogarth DK, Eden E, Stocks JM, et al. The prevalence of alpha-1 antitrypsin deficiency among patients found to have airflow obstruction. COPD. 2012;9(4):352–8.PubMedGoogle Scholar
  25. 25.
    Yang P, Wentzlaff KA, Katzmann JA, Marks RS, Allen MS, Lesnick TG, et al. Alpha1-antitrypsin deficiency allele carriers among lung cancer patients. Cancer Epidemiol Biomarkers Prev. 1999;8(5):461–5.PubMedGoogle Scholar
  26. 26.
    Silverman EK, Sandhaus RA. Clinical practice. Alpha1-antitrypsin deficiency. N Engl J Med. 2009;360(26):2749–57.PubMedCrossRefGoogle Scholar
  27. 27.
    Campos MA, Alazemi S, Zhang G, Wanner A, Salathe M, Baier H, et al. Exacerbations in subjects with alpha-1 antitrypsin deficiency receiving augmentation therapy. Respir Med. 2009;103(10):1532–9.PubMedCrossRefGoogle Scholar
  28. 28.
    The Alpha 1-Antitrypsin Deficiency Registry Study Group. A registry of patients with severe deficiency of alpha 1-antitrypsin. Design and methods. Chest. 1994;106(4):1223–32.CrossRefGoogle Scholar
  29. 29.
    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(1):49–59.CrossRefGoogle Scholar
  30. 30.
    Seersholm N, Wencker M, Banik N, Viskum K, Dirksen A, Kok-Jensen A, 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.PubMedCrossRefGoogle Scholar
  31. 31.
    Wencker M, Fuhrmann B, Banik N, Konietzko N. 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.PubMedCrossRefGoogle Scholar
  32. 32.
    Dirksen A, Dijkman JH, Madsen F, Stoel B, Hutchison DC, Ulrik CS, 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.PubMedCrossRefGoogle Scholar
  33. 33.
    Stockley RA, Parr DG, Piitulainen E, Stolk J, Stoel BC, Dirksen A. 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.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Chapman KR, Burdon JGW, Piitulainen E, Sandhaus RA, Seersholm N, Stocks JM. Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. The Lancet. 2015. doi: 10.1016/S0140-6736(15)60860-1
  35. 35.
    Campos MA, Alazemi S, Zhang G, Wanner A, Sandhaus RA. Effects of a disease management program in individuals with alpha-1 antitrypsin deficiency. COPD. 2009;6(1):31–40.PubMedCrossRefGoogle Scholar
  36. 36.
    Hersh CP, Dahl M, Ly NP, Berkey CS, Nordestgaard BG, Silverman EK. Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes: a meta-analysis. Thorax. 2004;59(10):843–9.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Molloy K, Hersh CP, Morris VB, Carroll TP, O’Connor CA, Lasky-Su JA, et al. Clarification of the risk of chronic obstructive pulmonary disease in alpha1-antitrypsin deficiency PiMZ heterozygotes. Am J Respir Crit Care Med. 2014;189(4):419–27.PubMedCrossRefGoogle Scholar
  38. 38.
    Campos MA, Wanner A, Zhang G, Sandhaus RA. Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and 2003. Chest. 2005;128(3):1179–86.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Pulmonary, Critical Care, and Sleep, National Jewish HealthDenverUSA

Personalised recommendations