The hypothesis is that the low level of AAT or alternatively the low efficiency of the enzyme might determinate an unbalance of the equilibrium between protease and antiprotease promoting the destruction of the epithelium and the development of bronchiectasis.[9] Interestingly, our report presented both atopy and liver steatosis both conditions highly characterizing AAT deficiency, which can increase the susceptibility to the loss of lung function.[10] Another important issue is about the therapy of this patient. responsible for the S bandage obtained by isoelectrophocalization. This mutation was characterized by the substitution in the coding region of exon 3, of a guanine (G) for a thymine (T), generating the replacement of a glutamine (Gln) by an histidine (His) in codon 212 (cod 212 GlnCAG HisCAT), which corresponded to a new S allelic variant. Open in a separate window Figure 1 Computed tomography-scan section showing upper right lobe and medium lobe bronchiectasis This variant has not been previously described and has not been previously reported in the human gene mutation database. Furthermore, there are no frequency data in the Exome Sequencing Project, Exome Aggregation Consortium, and dbSNP databases. The new mutation was called S-Napoli. Discussion In our report, we have described in a patient with bronchiectasis a novel missense mutation in the heterozygous state, characterized by the substitution in the coding region of exon 3, of a guanine (G) for a thymine (T). This has generated the replacement of a glutamine (Gln) by a histidine (His) in codon 212 (cod 212 GlnCAG HisCAT), which corresponded to a new S allelic variant, probably leading to a dysfunctional protein. Interestingly, this is the second case in South Italy showing an AATD in a patient with bronchiectasis in the absence of emphysema. In fact, in a recent report, Carpagnano em et al. /em Bay 65-1942 R form [4] described a patient with a novel missense mutation Ile74Asn (c. 221T[A]) in heterozygous state on a M3 allele, affected by bronchiectasis in the absence of emphysema. This condition is not frequent as only a few case reports have been reported so far,[5,6] and a novel SERPINA-1 mutation causing alpha-1 antitrypsin deficiency in a patient with severe bronchiectasis and pulmonary embolism has been identified.[7] Furthermore, the association between bronchiectasis and AATD is not common as in a study on 1258 patients, only 0.6% of the population was affected.[8] However, we can only speculate within the association between AATD and bronchiectasis as in our Bay 65-1942 R form case, the AAT was at Bay 65-1942 R form lower limit. The hypothesis is that the low level of AAT or on the other hand the low effectiveness of the enzyme might determinate an unbalance of the equilibrium between protease and antiprotease advertising the destruction of the epithelium and the development of bronchiectasis.[9] Interestingly, our record presented both atopy and liver steatosis both conditions highly characterizing AAT deficiency, which can increase the susceptibility to the loss of lung function.[10] Another important issue is about the therapy of this patient. The patient Bay 65-1942 R form was not FGF19 treated as with Italy the rigid indicator for therapy in AAT deficiency is definitely AAT 80 mg/dl having a spirometric FEV1 value between 35% and 60%. Although it was shown that augmentation of therapy reduces the progression of emphysema,[11] no studies on the effects of augmentation therapy in individuals with bronchiectasis has been reported. The last issue is within the analysis of AATD. AATD is considered a rare genetic disease, possessing a prevalence of around 1/5000 in Europe. However, due to the large subdiagnosis, it is sensible to assume that it is not so rare. The AATD laboratory analysis is based on the use of biochemical and genetic methods for the recognition of AAT protein deficiency, and the characterization of SERPINA1 gene mutations that cause it. The spread of a sample collection management system that is simple and easy to use, such as AlphaKit?, allows.