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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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Rationale This study aims to determine a relationship between short-term exposure to Particulate Matter and Fine Particulate Matter (PM10 and PM2.54) and the Emergency Department (ED) visit's trend for COPD Exacerbation. Visits' outcomes were also evaluated. The analysis has been conducted in Brescia, a city recognized for being one of the most important European industrial realities and one with the most complex environmental issues. Methods For this study, a dedicated database with data exclusively focused on COPD Exacerbation-related ED admissions has been created. Starting from January 1 st , 2014, to January 2016, 431 ED admission records for COPD Exacerbation have been collected. Data for the Particulate Matter daily mean concentrations were collected from the Environmental Protection Regional Agency (ARPA) and added to the database. Finally, a timeseries analysis with distributed day-lag has been conducted, and the results have been expressed in terms of Relative Risk (RR) and Relative Risk Increase (ER) for COPD Exacerbation-related ED visits and/or hospitalizations, over a 10µg/m3 increase in PM10 or PM2.5 concentration. Results A significant association for both PM10 and PM2.5 with the risk of ED visits and/or hospitalization for COPD Exacerbation. In lag0-1, increases of 10µg/m3 in PM10 concentration corresponded to a RR(IC95%) for ED visit of 1.06, while, for PM2.5, corresponded to 1.08 (p<0.05). At lag0-5, the RR(IC95%) corresponded to 1.06 and 1.09 for PM10 and PM2.5 respectively (p<0.05). Considering the hospitalizations, similar results have been found, with a RR of 1.07 and 1.10 in lag0-1; 1.07 and 1.11 in lag0-5. Conclusions Our findings increase the knowledge regarding the shortterm effects of exposure to Particulate Matter on the respiratory system. This study could also provide reliable data to monitor ED visits and outcomes over time.