First Argentine Study on Alpha-1 Antitrypsin Deficiency in Dried Blood Spot Samples From COPD Patients Primer estudio argentino del déficit de alfa-1-antitripsina en muestras de sangre seca de pacientes con enfermedad pulmonar obstructiva crónica (EPOC)

We welcome the cross-sectional, observational, case-finding study on alpha-1 antitrypsin deficiency (AATD) in 1002 individuals with COPD conducted by Sorroche et al. in Buenos Aires. This is the first study of its kind in Argentina.1 The authors set out to identify all genotypes associated with severe AATD (namely, Pi*ZZ and Pi*SZ) using an effective screening technique based on the quantification of alpha-1 antitrypsin (AAT) in dried blood. This was followed by hybridization probe genotyping to detect S and Z mutations in individuals with COPD and AAT concentrations below a cut-off level of 100 mg/dl (measured by immunonephelometry). The diagnostic technique enabled the investigators to detect nearly 22% of individuals with AAT levels below the cut-off value. Of these, 15 (1.5%) presented severe AATD associated with Pi*ZZ (12 cases, 1.3%) and Pi*SZ (3 cases, 0.2%) genotypes. The remaining 20% (60 cases) presented mild or moderate AATD associated with MS, SS, MZ genotypes and various uncharacterized heterozygous genotypes. Although these latter are not in themselves known to increase the risk of developing AATD-associated diseases, they can pass down S and Z and rare deficiency alleles. The results of this study suggest that far from being rare in Argentina, AATD is simply vastly under-diagnosed, as it is in nearly every other country in the world.2 The estimated incidence of Pi*S and Pi*Z in the Argentine population, made up of 97% of individuals with Spanish or Italian blood and 3% with Amerindian or mixed blood, is 33 and 6 per thousand inhabitants, respectively,3 a rate very similar to that found in Italy for these same alleles (Pi*S: 31 and Pi*Z: 8 per 1000).4 Although the study carried out by Sorroche et al. clearly has more strengths than weaknesses, some confounding variables acknowledged by the authors could, in aggregate, have partially