Diagnostic flow chart for targeted detection of Alpha1-antitrypsin deficiency

Background: Alpha1-antitrypsin (AAT) deficiency is under-recognized, probably because many individuals affected show no clinical impairment. The targeted detection is a tool to increase its recognition. Methods: we prospectively submitted to AAT serum levels determination, phenotyping and, if doubtful, genotyping: (i) patients with the early onset of emphysema, emphysema in absence of recognized risk or pneumothorax (path P), antineutrophil cytoplasm antibodies (ANCA) positive vasculitis (path V), cervical artery dissection (path A), Periodic acid-Schiff (PAS) positive bodies in the liver cell or unexplained abnormal transaminase level (Path L) [index cases: IC] and (ii) subjects with lowserum alpha1-globulin (path e) and close relatives of patients with AAT deficiency (path r) [non index cases: NIC]. We determined and compared gender, age, AAT serum levels values, the ratio between AAT deficiency subjects identified and all subjects examined (identified/examined). Receiver operating characteristic (ROC) curve was plotted to find the best threshold for AAT serum levels. Results: Two hundred and eighty-five individuals were examined and 211 with AAT deficiency identified: 66 were IC and 145 NIC. The ratio identified/examined resulted 0.74. A serum level of 120 mg/dL was able to identify AAT deficiency with a specificity of 73% and a sensitivity of 97%. IC showed male prevalence (P ¼ 0:005), more advanced age (P ¼ 0:02), lower AAT serum levels (P ¼ 0:008).