Z-alpha1-antitrypsin polymers and small airways disease: a new paradigm in alfa-1 anti-trypsin deficiency-related COPD development?

https://doi.org/10.4081/monaldi.2021.1883

Authors

  • Laura Pini | laura.pini@unibs.it Respiratory Medicine Unit, ASST-Spedali Civili di Brescia; Department of Clinical and Experimental Sciences, University of Brescia, Italy. https://orcid.org/0000-0002-5958-0228
  • Laura Tiberio Department of Molecular and Translational Medicine, University of Brescia, Italy. https://orcid.org/0000-0003-0482-9898
  • Marianna Arici Department of Clinical and Experimental Sciences, University of Brescia, Italy. https://orcid.org/0000-0001-9698-1680
  • Luciano Corda Respiratory Medicine Unit, ASST-Spedali Civili di Brescia, Italy.
  • Jordan Giordani Department of Clinical and Experimental Sciences, University of Brescia, Italy. https://orcid.org/0000-0002-5958-0228
  • Elena Bargagli Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy. https://orcid.org/0000-0002-8351-3703
  • Claudio Tantucci Respiratory Medicine Unit, ASST-Spedali Civili di Brescia; Department of Clinical and Experimental Sciences, University of Brescia, Italy.

Abstract

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.

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Published
2021-06-08
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Section
Pneumology - Original Articles
Supporting Agencies
University of Brescia
Keywords:
Alpha-1 anti-trypsin; polimers; small airways; AATD; AAT
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How 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, June. https://doi.org/10.4081/monaldi.2021.1883.

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