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Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by restricted airflow. The best-documented genetic factor is alpha-1 antitrypsin (AAT). AAT is encoded by the SERPINA1 gene. The PiZ (rs28929474) and PiS (rs17580) variants are believed to cause severe AAT deficiency and are linked to a high risk of developing COPD. This study sought to identify whether genetic polymorphisms rs28929474 and rs17580 are associated with COPD susceptibility and lung function values in a Mexican mestizo population., Methods: In this study, 558 smokers were included, of whom 279 had COPD and 279 did not (smokers without COPD - SWC). The PiS and PiZ variants were genotyped by allelic discrimination. Independent populations and lung function values were compared using the Kruskal-Wallis test. A bivariate logistic regression analysis was also conducted., Results: Stage I and iv COPD patients showed significant differences in the frequencies of both heterozygous genotypes compared to SWC. For PiS, individuals with the heterozygous genotype AT demonstrated a decreased FEV1/FVC ratio compared to subjects with the homozygous genotype AA (P=0.037). A significant association was found between the FEV1/FVC ratio and genotype AA for PiS (OR=0.982, β coefficient=-0.019, 95% CI=0.966-0.997)., Conclusions: COPD-causing AAT deficiency risk alleles exist at a very low frequency among Mexican mestizo population. Although they are not directly linked in our study population with disease susceptibility, these risk alleles are associated with poorer lung function measurements. It is important to characterize how often these genetic risk variants occur in other Latin American populations., (Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.)

Introduction: The present study intends to describe the characteristics of patients diagnosed with severe alpha-1 antitrypsin deficiency (AATD) in Spain, to observe the rate of decline in forced expiratory volume in 1 second (FEV1) with and without substitutive therapy, and to identify factors associated with a rapid rate of decline in FEV1., Method: A retrospective study of the evolution of individuals with AATD was carried out based on data collected from the Spanish registry. The primary response variable was the annual rate of decline in FEV1, calculated using the baseline and last postbronchodilator FEV1 values in an endpoint analysis., Results: 303 patients with severe AATD and Pi ZZ phenotype were identified. Follow-up spirometric data were collected for 117 subjects. Being a smoker or ex-smoker versus never smoker (odds ratio [OR]=10.31; 95% confidence interval (CI)=1.8-58.8; p=0.008) and having a higher baseline postbronchodilator FEV1 (% predicted) (OR=1.03; 95% CI=1.005-1.06; p=0.018) were independently associated with a more rapid rate of decline in FEV1. There was also a trend towards a relationship between low body mass index (BMI) and a greater rate of deterioration in lung function (OR=1.14; 95% CI=0.98-1.33; p=0.085)., Conclusion: Being a smoker or ex-smoker, greater baseline lung function, and low BMI were the main risk factors associated with an accelerated rate of decline in FEV1. This finding warrants the close observation of younger patients with a better-preserved FEV1., (Copyright © 2011 SEPAR. Published by Elsevier Espana. All rights reserved.)

The objective of this study was to determine whether high concentrations of circulating interleukin-6 (IL-6) and/or the soluble receptor of IL-6 (SRIL-6) may mediate systemic inflammatory activity in patients with alpha-1 antitrypsin deficiency (AATD). To that end we assessed serum concentrations of IL-6 and SRIL-6 for 7 patients with AATD in stable phase. The patients' mean age was 51 years (SD 5.2); mean FEV1% was 35.5% (SD 15%). IL-6 and SRIL-6 concentrations were compared with those of 23 non-AATD patients with COPD but with similar changes in lung function (mean age 63 years, SD 10.1; FEV1% 38.3%, SD 11%). The AADT patients had mean IL-6 concentrations of 4.7 pg/mL (interquartile range [IR( 4.0) and RSIL-6 levels of 129.1 ng/mL (IR 31.5). The COPD patients had IL-6 concentrations of 4.1 pg/mL (IR 4.2) and SRIL-6 levels of 140.8 ng/mL (IR 71). No significant differences between the AADT group and the COPD group were observed for either cytokine (non-parametric Mann Whitney U test, p > 0.05). Only one AADT patient had an IL-6 concentration that was higher than normal. In conclusion, the serum IL-6 and SRIL-6 concentrations of patients with AADT are not different from those of patients with COPD, similarly altered respiratory function and normal alpha-1 antitrypsin levels. These results do not point to a role for alpha-1 antitrypsin in systemic inflammatory stimulation in patients with AADT.