Lung disease in never smokers with severe alpha1-antitrypsin deficiency: The EARCO Registry.

The role of smoking as a risk factor for the development of emphysema in alpha1-antitrypsin deficiency (AATD) is well known. Nonetheless, also never smokers (NS) with severe AATD can experience lung disease, ranging from healthy individuals diagnosed through family screening to patients with serious lung impairment. The aim of our cross-sectional, observational study was to better characterise the population of NS PI*ZZ patients and to analyse their clinical features, using data from the European Alpha-1 Research Collaboration (EARCO)International Registry. A total of 1355 PI*ZZ individuals were analysed, of whom 701 (51.7%) were ever smokers (S) and 654 (48.3%) NS. S were more frequently males (60.9% vs 39.9%; p<0.001) and had lower FEV1(%) (57.6% (SD=29.1) vs 87.6% (SD=25.9); p<0.001), but age distribution was similar. Chronic obstructive pulmonary disease and emphysema were more frequent in S compared with NS (92.6% vs 64.3%; p<0.001), but bronchiectasis were more frequent in NS (23.2% vs 16.2%; p=0.001). A total of 353 (26.1%) patients were under augmentation therapy, of whom 260 (37.1%) S and 93 (14.3%) NS. Among NS, 456 (69.9%) were index cases (IC), 196 (30.1%) were non index cases (NIC). IC were older than NIC (mean age 59.9 (SD=12.0) vs 54.4 (SD=11.3) years; p<0.001) and had lower FEV1(%) (83.4% (SD=27.3) vs 97.5% (SD=19.4); p<0.001), but there were no differences in sex distribution. Of the 93 NS on augmentation, 13 (6.7%) were NIC. NS PI*ZZ in EARCO had frequent lung disease, but milder than S. However, bronchiectasis were more frequent in NS. NS and NIC were younger and had preserved lung function, although some of them were on augmentation therapy.