SMALL AIRWAYS DISEASE AND Z-ALPHA1-ANTITRYPSIN POLYMERS: IS THERE A CORRELATION?

PURPOSE: 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 (1.50.4 N2/L vs 1.10.3 N2/L) and the closing volume/vital capacity ratio (14.34.5 % vs 9.55.3 %) (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. CLINICAL IMPLICATIONS: 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.