https://doi.org/10.4081/monaldi.2021.1883
Z-alpha1-antitrypsin polymers and small airways disease: a new paradigm in alfa-1 anti-trypsin deficiency-related COPD development?
Published: June 8, 2021
Abstract Views: 3336
PDF: 1109
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
The presence of Alpha1-Antitrypsin (AAT) polymers, known to promote a sustained pro-inflammatory activity, has been previously demonstrated in bronchial biopsies of subjects with Z-AAT deficiency (AATD) suggesting a possible role in the development of COPD through a small airway disease impairment. The study aimed to assess the presence of small airways dysfunction and the potential correlation with the presence of Z-AAT polymers obtained by Exhaled Breath Condensate (EBC) collection in PiZZ subjects, as compared with matched healthy PiMM subjects. We enrolled 19 asymptomatic, never smoker subjects: 9 PiZZ and 10 PiMM as controls, without obstructive ventilatory defect (i.e., normal FEV1/VC% ratio). All subjects underwent complete pulmonary function tests (PFT). EBC was collected in all subjects. ELISA test was applied to search for Z-AAT polymers. The PiZZ subjects showed normal lung volumes and DLCO values. However, in comparison with PiMM subjects, the single breath test N2 wash-out revealed significant differences regarding the phase III slope (1.45±0.35 N2/L vs. 0.96±0.40 N2/L) (p<0.02) in the PiZZ subjects, while the closing volume/vital capacity ratio (14.3±4.5 % vs. 11.3±6.3 %) was not significantly increased. The ELISA test detected the presence of Z-AAT polymers in 44% of PiZZ patients. Asymptomatic, never smoker PiZZ subjects with normal spirometry and lung diffusion capacity showed airways impairment when compared to PiMM subjects. Although Z-AAT polymers were found only in 44% of PiZZ subjects, these findings suggest the possibility that chronic bronchiolitis can develop as a result of the long-term pro-inflammatory activity of Z-AAT polymers in subjects with Z-related AATD.
Blanco I, Bueno P, Diego I, et al. Alpha-1 anti-trypsin Pi? Z gene frequency and Pi?ZZ genotype numbers worldwide: an update. Int J Chron Obstruct Pulmon Dis 2017;12:561-69.
DOI: https://doi.org/10.2147/COPD.S125389
Strnad P, McElvaney NG, Lomas DA. Alpha1-antitrypsin deficiency. N Engl J Med 2020;382:1443-55.
DOI: https://doi.org/10.1056/NEJMra1910234
Franciosi AN, Carroll TP, McElvaney NG.Franciosi AN, et al. Pitfalls and caveats in alpha1- antitrypsin deficiency testing: a guide for clinicians. Lancet Respir Med 2019;7:1059-67.
DOI: https://doi.org/10.1016/S2213-2600(19)30141-9
Ferrarotti I, Ottaviani S, De Silvestri A, Corsico AG. Update on alpha(1)-antitrypsin deficiency. Breathe (Sheff) 2018;14:e17-e24.
DOI: https://doi.org/10.1183/20734735.015018
Janciauskiene S, Welte T. Well known and less well known functions of alpha-1 anti-trypsin: its role in chronic obstructive pulmonary disease and other disease developments. Ann Am Thorac Soc 2016;13:S280-8.
DOI: https://doi.org/10.1513/AnnalsATS.201507-468KV
Greene CM, Marciniak SJ, Teckman J, et al. α1-antitrypsin deficiency. Nat Rev Dis Primers 2016;2:16051.
DOI: https://doi.org/10.1038/nrdp.2016.51
Stoller JK, Aboussouan LS. A review of α1-antitrypsin deficiency. Am J Respir Crit Care Med 2011;185:246-59.
DOI: https://doi.org/10.1164/rccm.201108-1428CI
Eriksson S, Carlson J, Velez R. Risk of cirrhosis and primary liver cancer in alpha1-antitrypsin deficiency. N Engl J Med 1986;314:736-9.
DOI: https://doi.org/10.1056/NEJM198603203141202
Hussain M, Mieli-Vergani G, Mowat AP. Alpha1-antitrypsin deficiency and liver disease: clinical presentation, diagnosis and treatment. J Inherit Metab Dis 1991;14:497-511.
DOI: https://doi.org/10.1007/BF01797920
Pini L, Paoletti G, Heffler E, et al. Alpha1-antitrypsin deficiency and asthma. Curr Opin Allergy Clin Immunol 2021;21:46-51.
DOI: https://doi.org/10.1097/ACI.0000000000000711
Vizzardi E, Corda L, Sciatti E, et al. Echocardiographic evaluation in subjects with α1-antitrypsin deficiency. Eur J Clin Invest 2015;45:949-54.
DOI: https://doi.org/10.1111/eci.12492
Vizzardi E, Corda L, Pezzali N, et al. Elastic properties of theascending aorta in patients with ?1-antitrypsin deficiency (Z homozygotes). Heart 2012;98:1354-8.
DOI: https://doi.org/10.1136/heartjnl-2012-302144
Pini L, Peroni M, Zanotti C, et al. Investigating the link between Alpha-1 antitrypsin deficiency and abdominal aortic aneurysms. Ann Vasc Surg 2021;77:195-201.
DOI: https://doi.org/10.1016/j.avsg.2021.05.064
Lomas DA, Parfrey H. α1-Antitrypsin deficiency: Molecular pathophysiology. Thorax 2004;59:529-35.
DOI: https://doi.org/10.1136/thx.2003.006528
Gooptu B, Lomas DA. Polymers and inflammation: disease mechanisms of the serpinopathies; J Exp Med 2008;205:1529-34.
DOI: https://doi.org/10.1084/jem.20072080
Luisetti M, Seersholm N. α1-Antitrypsin deficiency: Epidemiology of α1-antitrypsin deficiency. Thorax 2004;59164-9.
DOI: https://doi.org/10.1136/thorax.2003.006494
Lomas DA, Mahadeva R. Alpha1-antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy. J Clin Invest 2002;110:1585-90.
DOI: https://doi.org/10.1172/JCI0216782
Lomas DA, Evans DL, Finch JT, Carrell RW. The mechanism of Z alpha1-antitrypsin accumulation in the liver. Nature 1992;357:605-7.
DOI: https://doi.org/10.1038/357605a0
Parmar JS, Mahadeva R, Reed BJ, et al. Polymers of alpha-1 anti-trypsin are chemotactic for human neutrophils: a new paradigm for the pathogenesis of emphysema. Am J Respir Cell Mol Biol 2002;26:723-30.
DOI: https://doi.org/10.1165/ajrcmb.26.6.4739
Koo HK, Vasilescu DM, Booth S, et al. Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study. Lancet Respir Med 2018;6:591-602.
DOI: https://doi.org/10.1016/S2213-2600(18)30196-6
Yanai M, Sekizawa K, Ohrui T, et al. Site of airway obstruction in pulmonary disease: direct measurement of intrabronchial pressure. J Appl Physiol 1992;72:1016-23.
DOI: https://doi.org/10.1152/jappl.1992.72.3.1016
Kim, Rogers TJ, Criner GJ. New concepts in the pathobiology of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2008;5:478.
DOI: https://doi.org/10.1513/pats.200802-014ET
Taraseviciene-Stewart L, Voekel NF. Molecular pathogenesis of emphysema. J Clin Invest 2008;118:394.
DOI: https://doi.org/10.1172/JCI31811
Hogg JC, Timens W. The pathology of chronic obstructive pulmonary disease. Ann Rev Path Mech Dis 2009;4:435-59.
DOI: https://doi.org/10.1146/annurev.pathol.4.110807.092145
Tantucci C, Bottone D, Levi G, et al. Respiratory function, autonomic dysfunction, and systemic inflammation are closely linked in patients with COPD and tidal flow limitation: An exploratory study. Respir Physiol Neurobiol 2021;284:103565.
DOI: https://doi.org/10.1016/j.resp.2020.103565
Uccelli S, Pini L, Bottone D, et al. Dyspnea during night-time and at early morning in patients with stable COPD is associated with supine tidal expiratory flow limitation. Int J Chron Obstruct Pulmon Dis 2020;15:2549-58.
DOI: https://doi.org/10.2147/COPD.S269346
Burgel PR. The role of small airways in obstructive airway diseases. Eur Respir Rev 2011;20:23-33.
DOI: https://doi.org/10.1183/09059180.00010410
Stockley JA, Cooper BG, Stockley RA, Sapey E. Small airways disease: time for a revisit? Int J Chron Obstruct Pulmon Dis 2017;12:2343-53.
DOI: https://doi.org/10.2147/COPD.S138540
Tantucci C, Pini L. Inhaled corticosteroids in COPD: Trying to make a long story short. Int J Chron Obstruct Pulmon Dis 2020;15:821-9.
DOI: https://doi.org/10.2147/COPD.S233462
Bazzan E, Tin M, Biondini D, et al. Alpha1-Antitrypsin polymerizes in alveolar macrophages of smokers with and without alpha1-antitrypsin deficiency. Chest 2018;154:607-16.
DOI: https://doi.org/10.1016/j.chest.2018.04.039
Pini L, Tiberio L, Venkatesan N, et al. The role of bronchial epithelial cells in the pathogenesis of COPD in Z-alpha-1 antitrypsin deficiency. Respir Res 2014;15:112.
DOI: https://doi.org/10.1186/s12931-014-0112-3
Corda L, Bertella E, Pini L, et al. Diagnostic flow chart for targeted detection of alpha1- antitrypsin deficiency. Respir Med 2006;100:463-70.
DOI: https://doi.org/10.1016/j.rmed.2005.06.009
Pini L, Corda L, Malerba M, et al. Alpha 1-antitrypsin deficiency: the Brescia clinical study. Recent Prog Med 2000;91:352-61.
Bayley DL, Abusriwil H, Ahmad A, Stockley RA. Validation of assays for inflammatory mediators in exhaled breath condensate. Eur Respir J 2008;31:943-8.
DOI: https://doi.org/10.1183/09031936.00081707
Koczulla AR, Noeske S, Herr C, et al. Alpha-1 anti-trypsin is elevated in exhaled breath condensate and serum in exacerbated COPD patients. Respir Med 2012;106:120-6.
DOI: https://doi.org/10.1016/j.rmed.2011.06.015
Supporting Agencies
University of BresciaHow to Cite
Pini, Laura, Laura Tiberio, Marianna Arici, Luciano Corda, Jordan Giordani, Elena Bargagli, and Claudio Tantucci. 2021. “Z-Alpha1-Antitrypsin Polymers and Small Airways Disease: A New Paradigm in Alfa-1 Anti-Trypsin Deficiency-Related COPD Development?”. Monaldi Archives for Chest Disease 91 (4). https://doi.org/10.4081/monaldi.2021.1883.
Copyright (c) 2021 The Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Bhaskar Kakarla, Bronchocele, a common but underrecognized condition: a systematic review , Monaldi Archives for Chest Disease: Vol. 93 No. 1 (2023)
- Federico Raimondi, Caterina Conti, Luca Novelli, Francesco Tarantini, Giuseppe Ciaravino, Piermario Scuri, Aurelia Grosu, Daniela Chinaglia, Lorenzo S.C. Grazioli, Andrea Gianatti, Ferdinando L. Lorini, Michele Senni, Fabiano Di Marco, A 57-year-old man with rapidly progressive pulmonary hypertension , Monaldi Archives for Chest Disease: Vol. 92 No. 1 (2022)
- Sunil Mahavar, Princy Tyagi, Abhishek Agrawal, Sudhir Bhandari, Subrata Banerjee, Raman Sharma, Prakash Keshwani, Clinical and epidemiological profile of Indian COVID-19 patients from Jaipur: a descriptive study , Monaldi Archives for Chest Disease: Vol. 91 No. 2 (2021)
- Vasiliki Epameinondas Georgakopoulou, Dimitrios Mermigkis, Despoina Melemeni, Aikaterini Gkoufa, Christos Damaskos, Nikolaos Garmpis, Anna Garmpi, Nikolaos Trakas, Xanthi Tsiafaki, Cytomegalovirus pneumonia in an immunocompetent host with primary ciliary dyskinesia: A case report , Monaldi Archives for Chest Disease: Vol. 91 No. 3 (2021)
- Konstantinos Kapriniotis, Angelina Bania, Savvas Lampridis, Georgios Geropoulos, Sofoklis Mitsos, Fleur Monk, David A. Moore, Nikolaos Panagiotopoulos, Metastatic mandibular ameloblastoma of the lung ten years after primary resection: A rare case report , Monaldi Archives for Chest Disease: Vol. 91 No. 2 (2021)
- Barun Kumar, Ashwin Kodliwadmath, Amar Upadhyay, Anupam Singh, Nanda N, Apparently normal epicardial coronaries in a patient with inferior wall myocardial infarction on the background of mild coronavirus disease-2019: take a second look! , Monaldi Archives for Chest Disease: Vol. 91 No. 3 (2021)
- Cleante Scarduelli, Francesco Inglese, Massimiliano Beccaria, Fabio Spreafico, Martina Garuti, Antonietta Pecoriello, Giulia Cervi, Graziana Greco, Sara Scarduelli, Giuseppe Lucchini, Giuseppe De Donno, Claudio Borghi, Pulmonary embolism in patients with severe COVID-19 treated with intermediate- to full-dose enoxaparin: A retrospective study , Monaldi Archives for Chest Disease: Vol. 91 No. 3 (2021)
- Shayan Shahid, Kausar Jabeen, Nousheen Iqbal, Joveria Farooqi, Muhammad Irfan, Respiratory pathogens in patients with acute exacerbation of non-cystic fibrosis bronchiectasis from a developing country , Monaldi Archives for Chest Disease: Vol. 91 No. 2 (2021)
- Mansi Gupta, Pranav Ish, Shibdas Chakrabarti, Manas Kamal Sen, Prabhakar Mishra, Jagdish Chander Suri, Diagnostic accuracy and feasibility of portable sleep monitoring in patients with obstructive sleep apnea: Re-exploring the utility in the current COVID-19 pandemic , Monaldi Archives for Chest Disease: Vol. 92 No. 1 (2022)
- Ana Martins da Costa, Rafael Teixeira, Eduardo M. Vilela, Ana Tavares, Susana Torres, Francisco Sampaio, Madalena Teixeira, Ricardo Fontes-Carvalho, José Pedro Nunes, Suppression of tumorigenicity 2 after exercise: a systematic review , Monaldi Archives for Chest Disease: Vol. 92 No. 1 (2022)
<< < 4 5 6 7 8 9 10 11 12 > >>
You may also start an advanced similarity search for this article.
