Z-alpha1-antitrypsin polymers and small airways disease: a new paradigm in COPD development?

Introduction: The presence of Alpha1-Antitrypsin (AAT) polymers that are pro-inflammatory has been previously demonstrated in bronchial biopsies of subjects with Z-AAT deficiency (Respir Res, 2014 Sep 14;15:112), suggesting a possible role in the development of COPD.Aim: The aim of the study was 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, comparing with matched healthy PiMM subjects.Methods: We enrolled 17 asymptomatic non-smoker subjects: 9 PiZZ and 8 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 PiZZ patients. ELISA test was applied to search for Z-AAT polymers.Results: 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 (1.5{ extpm}0.4 N2/L vs 1.1{ extpm}0.3 N2/L) and the closing volume/vital capacity ratio (14.3{ extpm}4.5 % vs 9.5{ extpm}5.3 %) (p<0.05) in the PiZZ subjects. The ELISA test detected the presence of Z-AAT polymers in 4 PiZZ patients. No correlations were found between polymers levels and any functional respiratory parameter.Conclusions: PiZZ subjects showed small airways dysfunction when compared to PiMM subjects. Surprisingly, Z-AAT polymers were found only in 4 PiZZ subjects; this is probably due to the sample methodology. New studies are needed to evaluate the correlation between bronchial Z-AAT polymers and small airway impairment in subjects with Z-AAT deficiency.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 965.This abstract was presented at the 2020 ERS International Congress, in session { extquotedblleft}Respiratory viruses in the "pre COVID-19" era{ extquotedblright}.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).