Expert Perspectives on the Management of Alpha 1-Antitrypsin Deficiency

Authors

  • Bebiana Conde Centro Hospitalar Trás-os-Montes e Alto Douro. Vila Real. Universidade de Trás-os-Montes e Alto Douro. Vila Real.
  • Filipa Costa Serviço de Pneumologia. Centro Hospitalar e Universitário de Coimbra. Coimbra.
  • Joana Gomes Serviço de Pneumologia. Centro Hospitalar e Universitário do Porto. Porto.
  • António Paulo Lopes Serviço de Pneumologia. Centro Hospitalar e Universitário de Coimbra. Coimbra.
  • Maria Alexandra Mineiro Serviço de Pneumologia. Centro Hospitalar Universitário Lisboa Central. Lisboa.
  • Orlando Rodrigues Serviço de Genética Médica. Hospital Pediátrico do Centro Hospitalar e Universitário de Coimbra. Coimbra.
  • Cristina Santos Serviço de Pneumologia. Centro Hospitalar e Universitário Lisboa Norte. Lisboa.
  • Luísa Semedo Serviço de Pneumologia. Centro Hospitalar Universitário Lisboa Central. Lisboa.
  • Maria Sucena Serviço de Pneumologia. Centro Hospitalar e Universitário do Porto. Porto.
  • Catarina Guimarães Serviço de Pneumologia. Hospital Senhora da Oliveira. Guimarães. https://orcid.org/0000-0001-9575-7898

DOI:

https://doi.org/10.20344/amp.18497

Keywords:

alpha 1-Antitrypsin, alpha 1-Antitrypsin Deficiency

Abstract

Alpha 1-antitrypsin deficiency is an inherited autosomal codominant disorder, which predisposes patients to lung and/or liver disease. Even though it is considered rare, it is one of the most frequent genetic disorders worldwide, albeit remaining underdiagnosed. Several organizations and societies, including the Portuguese Society of Pulmonology have been elaborating guidelines and recommendations for the diagnosis and management of alpha 1-antitrypsin deficiency. Nevertheless, some important matters are yet to be included in those, mainly due to lack of robust scientific evidence, and continue to represent a point of discussion. This article reviews some important scientific publications and expresses the perspectives of a group of Portuguese experts regarding the management of alpha 1-antitrypsin deficiency, namely in terms of the pre and neonatal diagnosis, the impact of the COVID-19 pandemic, the validity of replacement therapy in lung transplant-receiving, and finally, alternative strategies of alpha 1-antitrypsin deficiency treatment to improve the patients’ quality of life.

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References

Janciauskiene SM, Bals R, Koczulla R, Vogelmeier C, Kohnlein T, Welte T. The discovery of alpha1-antitrypsin and its role in health and disease. Respir Med. 2011;105:1129-39. DOI: https://doi.org/10.1016/j.rmed.2011.02.002

Radlovic N, Lekovic Z, Radlovic V, Simic D, Topic A, Ristic D, et al. Alpha-1-antitrypsin deficiency in children: clinical characteristics and diagnosis. Srp Arh Celok Lek. 2014;142:547-50. DOI: https://doi.org/10.2298/SARH1410547R

Cazzola M, Stolz D, Rogliani P, Matera MG. alpha1-Antitrypsin deficiency and chronic respiratory disorders. Eur Respir Rev. 2020;29:190073. DOI: https://doi.org/10.1183/16000617.0073-2019

Lopes AP, Mineiro MA, Costa F, Gomes J, Santos C, Antunes C, et al. Portuguese consensus document for the management of alpha-1-antitrypsin deficiency. Pulmonology.2018;24:S1-21. DOI: https://doi.org/10.1016/j.pulmoe.2018.09.004

Fraga JF, Sá A, Martins V, Calvino J, Pereira A, Quaresma M. Deficiência de alfa-1 antitripsina num grupo de crianças com patologia respiratória: experiência da consulta de Pediatria/Alergologia do hospital de Vila Real. Port J Ped. 2011;42:99-103.

Kats-Ugurlu G, Hogeveen M, Driessen A, van den Ouweland AM, Hulsbergen-van de Kaa C. Diagnosis of alpha-1-antitrypsin deficiency in bleeding disorder-related neonatal death. Eur J Pediatr. 2011;170:103-6. DOI: https://doi.org/10.1007/s00431-010-1280-x

Stoller JK, Hupertz V, Aboussouan LS. Alpha-1 Antitrypsin Deficiency. In Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJ, Gripp KW, et al, editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2006.

Mahr AD, Edberg JC, Stone JH, Hoffman GS, St Clair EW, Specks U, et al. Alpha(1)-antitrypsin deficiency-related alleles Z and S and the risk of Wegener’s granulomatosis. Arthritis Rheum. 2010;62:3760-7. DOI: https://doi.org/10.1002/art.27742

Vianello A, Caminati M, Senna G, Arcolaci A, Chieco-Bianchi F, Ferrarotti I, et al. Effect of α 1 antitrypsin deficiency on lung volume decline in severe asthmatic patients undergoing biologic therapy. J Allergy Clin Immunol Pract. 2021;9:1414-6. DOI: https://doi.org/10.1016/j.jaip.2020.12.061

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;176:1215-21. DOI: https://doi.org/10.1164/rccm.200703-489OC

Rodrigues JF, Mineiro A, Reis A, Ventura DG, Fernandez-Llimos F, Costa F, et al. Alpha-1 antitrypsin deficiency: principles of care. Acta Med Port. 2020;33:433-9. DOI: https://doi.org/10.20344/amp.12950

Orphanet. Alpha-1-antitrypsin deficiency. [accessed 2021 Sep 27]. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=60.

EARCO. European Alpha-1 Research Collaboration website. [accessed 2021 Sep 27]. Available from: https://www.ersnet.org/science-andresearch/clinical-research-collaboration-application-programme/earcoeuropean-alpha-1-research-collaboration/.

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;168:818-900. DOI: https://doi.org/10.1164/rccm.168.7.818

Miravitlles M, Dirksen A, Ferrarotti I, Koblizek V, Lange P, Mahadeva R, et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in alpha1-antitrypsin deficiency. Eur Respir J.2017;50:1700610. DOI: https://doi.org/10.1183/13993003.00610-2017

Casas F, Blanco I, Martinez MT, Bustamante A, Miravitlles M, Cadenas S, et al. Indications for active case searches and intravenous alpha-1 antitrypsin treatment for patients with alpha-1 antitrypsin deficiency chronic pulmonary obstructive disease: an update. Arch Bronconeumol. 2015;51:185-92. DOI: https://doi.org/10.1016/j.arbr.2014.12.006

Sandhaus RA, Turino G, Brantly ML, Campos M, Cross CE, Goodman K, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis. 2016;3:668-82. DOI: https://doi.org/10.15326/jcopdf.3.3.2015.0182

Balderacchi AM, Barzon V, Ottaviani S, Corino A, Zorzetto M, Wencker M, et al. Comparison of different algorithms in laboratory diagnosis of alpha1-antitrypsin deficiency. Clin Chem Lab Med. 2021;59:1384-91. DOI: https://doi.org/10.1515/cclm-2020-1881

Burdelski M. Diagnostic, preventive, medical and surgical management of alpha 1-antitrypsin deficiency in childhood. Acta Paediatr Suppl. 1994;393:33-6. DOI: https://doi.org/10.1111/j.1651-2227.1994.tb13205.x

Gynaecologists RCoOa. Amniocentesis and Chorionic Villus Sampling. 2010. [accessed 2021 Sep 27]. Available from: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg8/.

Teckman J, Pardee E, Howell RR, Mannino D, Sharp RR, Brantly M, et al. Appropriateness of newborn screening for alpha1-antitrypsin deficiency. J Pediatr Gastroenterol Nutr. 2014;58:199-203. DOI: https://doi.org/10.1097/MPG.0000000000000196

Yang C, Chapman KR, Wong A, Liu M. alpha1-Antitrypsin deficiency and the risk of COVID-19: an urgent call to action. Lancet Respir Med. 2021;9:337-9. DOI: https://doi.org/10.1016/S2213-2600(21)00018-7

Shapira G, Shomron N, Gurwitz D. Ethnic differences in alpha-1 antitrypsin deficiency allele frequencies may partially explain national differences in COVID-19 fatality rates. FASEB J. 2020;34:14160-5. DOI: https://doi.org/10.1096/fj.202002097

Faria N, Ines Costa M, Gomes J, Sucena M. Alpha-1 antitrypsin deficiency severity and the risk of COVID-19: a Portuguese cohort. Respir Med. 2021;181:106387. DOI: https://doi.org/10.1016/j.rmed.2021.106387

Janciauskiene S, Wilkens M. COVID-19 infection in patients with alpha-1-antitrypsin deficiency. 2020. [accessed 2021 Sep 20]. Available from: breath-hannover.de/en/news-media/news/news-details.html?tx_news_pi1%5Bnews5D=509&cHash=c4d03f11e02767dd75c9b9726a8bf6be.

Alqahtani JS, Oyelade T, Aldhahir AM, Mendes RG, Alghamdi SM, Miravitlles M, et al. Reduction in hospitalised COPD exacerbations during COVID-19: a systematic review and meta-analysis. PLoS One. 2021;16:e0255659. DOI: https://doi.org/10.1371/journal.pone.0255659

Chapman KR, Burdon JG, Piitulainen E, Sandhaus RA, Seersholm N, Stocks JM, et al. Intravenous augmentation treatment and lung density in severe alpha1 antitrypsin deficiency (RAPID): a randomised, doubleblind, placebo-controlled trial. Lancet. 2015;386:360-8. DOI: https://doi.org/10.1016/S0140-6736(15)60860-1

McElvaney NG, Burdon J, Holmes M, Glanville A, Wark PA, Thompson PJ, 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. DOI: https://doi.org/10.1016/S2213-2600(16)30430-1

Zamora M. Surgery for patients with Alpha 1 Antitrypsin Deficiency: a review. Am J Surg. 2019;218:639-47. DOI: https://doi.org/10.1016/j.amjsurg.2018.10.019

Kleinerova J, Ging P, Rutherford C, Lawrie I, Winward S, Eaton D, et al. The withdrawal of replacement therapy and outcomes in alpha-1 antitrypsin deficiency lung transplant recipients. Eur Respir J. 2019;53:1900055. DOI: https://doi.org/10.1183/13993003.00055-2019

Conrad A, Janciauskiene S, Kohnlein T, Fuge J, Ivanyi P, Tudorache I, et al. Impact of alpha 1-antitrypsin deficiency and prior augmentation therapy on patients’ survival after lung transplantation. Eur Respir J. 2017;50:1700962. DOI: https://doi.org/10.1183/13993003.00962-2017

Banga A, Gildea T, Rajeswaran J, Rokadia H, Blackstone EH, Stoller JK. The natural history of lung function after lung transplantation for alpha(1)-antitrypsin deficiency. Am J Respir Crit Care Med. 2014;190:274-81. DOI: https://doi.org/10.1164/rccm.201401-0031OC

Ravichandran BR, Feist AA, Magana MM, Reed S, Lane JR, Yung G. Alpha-1 proteinase inhibitors post-lung transplantation: a single center experience. J Heart Lung Transplant. 2013;32:S1-330. DOI: https://doi.org/10.1016/j.healun.2013.01.783

Lewis EC. Expanding the clinical indications for alpha(1)-antitrypsin therapy. Mol Med. 2012;18:957-70. DOI: https://doi.org/10.2119/molmed.2011.00196

Campos MA, Geraghty P, Holt G, Mendes E, Newby PR, Ma S, et al. The biological effects of double-dose alpha-1 antitrypsin augmentation therapy. a pilot clinical trial. Am J Respir Crit Care Med. 2019;200:318-26. DOI: https://doi.org/10.1164/rccm.201901-0010OC

Yang C, Keshavjee S, Liu M. Alpha-1 antitrypsin for COVID-19 treatment: dual role in antiviral infection and anti-inflammation. Front Pharmacol. 2020;11:615398. DOI: https://doi.org/10.3389/fphar.2020.615398

Ataya A. Recurrence of emphysema post-lung transplantation in a patient with alpha 1 antitrypsin deficiency (AATD). Respir Med Case Rep. 2020;31:101309. DOI: https://doi.org/10.1016/j.rmcr.2020.101309

Iskender I, Sakamoto J, Nakajima D, Lin H, Chen M, Kim H, et al. Human alpha1-antitrypsin improves early post-transplant lung function: preclinical studies in a pig lung transplant model. J Heart Lung Transplant. 2016;35:913-21. DOI: https://doi.org/10.1016/j.healun.2016.03.006

Lopez-Campos JL, Carrasco Hernandez L, Caballero Eraso C. Implications of a change of paradigm in alpha1 antitrypsin deficiency augmentation therapy: from biochemical to clinical efficacy. J Clin Med. 2020;9:2526. DOI: https://doi.org/10.3390/jcm9082526

U.S. Food & Drug Administration. The voice of the patient: patientfocused drug development for alpha-1 antitrypsin deficiency. 2015. [accessed 2021 Sep 30]. Available from: http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm326192.htm.

Horvath I, Canotilho M, Chlumsky J, Chorostowska-Wynimko J, Corda L, Derom E, et al. Diagnosis and management of alpha1-antitrypsin deficiency in Europe: an expert survey. ERJ Open Res. 2019;5:00171-2018. DOI: https://doi.org/10.1183/23120541.00171-2018

Annunziata A, Lanza M, Coppola A, Andreozzi P, Spinelli S, Fiorentino G. Alpha-1 antitrypsin deficiency: home therapy. Front Pharmacol. 2021;12:575402. DOI: https://doi.org/10.3389/fphar.2021.575402

Greulich T, Chlumsky J, Wencker M, Vit O, Fries M, Chung T, et al. Safety of biweekly alpha1-antitrypsin treatment in the RAPID programme. Eur Respir J. 2018;52:1800897. DOI: https://doi.org/10.1183/13993003.00897-2018

Soy D, de la Roza C, Lara B, Esquinas C, Torres A, Miravitlles M. Alpha-1-antitrypsin deficiency: optimal therapeutic regimen based on population pharmacokinetics. Thorax. 2006;61:1059-64. DOI: https://doi.org/10.1136/thx.2005.057943

Oyesiku JO. Home treatment of haemophilia patients with inhibitors. Haemophilia. 2011;17:173-8. DOI: https://doi.org/10.1111/j.1365-2516.2010.02418.x

Caballero T, Sala-Cunill A, Cancian M, Craig TJ, Neri S, Keith PK, et al. Current status of implementation of self-administration training in various regions of Europe, Canada and the USA in the management of hereditary angioedema. Int Arch Allergy Immunol. 2013;161:S10-6. DOI: https://doi.org/10.1159/000351233

Ochs HD, Gupta S, Kiessling P, Nicolay U, Berger M, Subcutaneous IgG Study Group. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol. 2006;26:265-73. DOI: https://doi.org/10.1007/s10875-006-9021-7

Sandhaus R, Boyd B. Alpha 1 antitrypsin therapy: a satisfaction survey of individuals self-administering. Am J Respir Crit Care Med. 2018;A46:A1758.

Sandhaus RA, Strange C, Zanichelli A, Skalvoll K, Koczulla AR, Stockley RA. Improving the lives of patients with alpha-1 antitrypsin deficiency. Int J Chron Obstruct Pulmon Dis. 2020;15:3313-22. DOI: https://doi.org/10.2147/COPD.S276773

Global A-. Alpha-1 Global calls for home treatment throughout the European Union. 2020. [accessed 2021 Oct 07]. Available from: http://alpha-1global.org/en/alpha-1-global-calls-for-home-treatmentthroughout-the-european-union/.

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Published

2022-07-18

How to Cite

1.
Conde B, Costa F, Gomes J, Lopes AP, Mineiro MA, Rodrigues O, Santos C, Semedo L, Sucena M, Guimarães C. Expert Perspectives on the Management of Alpha 1-Antitrypsin Deficiency. Acta Med Port [Internet]. 2022 Jul. 18 [cited 2024 Mar. 29];36(1):49-54. Available from: https://actamedicaportuguesa.com/revista/index.php/amp/article/view/18497

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Review Articles