In alpha1-antitrypsin (AAT) deficiency the role of cigarette smoking as a risk factor for the development of emphysema is well known. It has been demonstrated that smoking patients with severe AAT deficiency (AATD) develop chronic obstructive pulmonary disease (COPD) earlier than non-smokers. Previous studies have focused on the differences between smoking and non-smoking individuals with severe AATD, finding that those who never smoked had better lung function with lower lung function decline, less respiratory symptoms and higher life expectancy and quality. Nonetheless, also never smokers patients with AATD can experience lung disease.
However, the population of Pi*ZZ non smoking patients is highly heterogeneous, ranging from healthy individuals found through family screening to severely ill patients with serious lung or liver impairment. Moreover, as of today studies involving large international cohorts are missing.