Normativas de diagnóstico y tratamiento del déficit de alfa-1 antitripsina / Guidelines on Diagnosis and Treatment of Alpha-1 Antitrypsin Deficiency

El déficit de alfa-1 antitripsina (AAT) es una condición hereditaria rara y raramente diagnosticada en todo el mundo, incluida Argentina. El infradiagnóstico es fundamentalmente debido a que muchos médicos desconocen su existencia, diagnóstico y tratamiento. Por ello, la Asociación Argentina de Medicina Respiratoria encomendó a un grupo de expertos la elaboración de la presente normativa. La AAT es una glicoproteína secretada por el hígado, muy abundante en sangre, tejidos y fluidos corporales, cuya función principal consiste en inhibir la elastasa del neutrófilo y otras serin proteasas, confiriendo al suero humano más del 90% de su capacidad antiproteasa. El déficit de AAT deriva de mutaciones del gen de la SERPINA1, y se manifiesta clínicamente por enfisema pulmonar, cirrosis hepática y, con menor frecuencia, por paniculitis, vasculitis sistémicas y posiblemente otras enfermedades. El déficit grave de AAT afecta mayoritariamente a individuos de raza caucasiana y tiene su máxima prevalencia (1:2.000-1:5.000 individuos) en el norte, oeste y centro de Europa. En EEUU y Canadá, la prevalencia es de 1: 5.000-10.000, y es 5 veces menor en países latinoamericanos, incluida Argentina, donde se estima que puede haber unos 18.000 individuos con genotipos deficientes graves SZ y ZZ, la inmensa mayoría sin diagnosticar. Sospechar la enfermedad resulta clave para medir la concentración sérica de AAT y completar el diagnóstico con la determinación del fenotipo o genotipo ante concentraciones bajas. La detección de casos permite la puesta en práctica del consejo genético, el chequeo de familiares consanguíneos y, en casos seleccionados, la aplicación de terapia sustitutiva.

The alpha-1 antitrypsin (AAT) deficiency is a rare hereditary condition which is rarely diagnosed in the world, including Argentina. Underdiagnosis is mainly due to lack of knowledge of its diagnosis and treatment by many physicians. For this reason, the Argentine Association of Respiratory Medicine convened a group of experts to develop the present guidelines. AAT is a glycoprotein secreted by the liver; it reaches high levels in blood, body tissues and fluids. Its main function is to inhibit the neutrophil elastase and other serum proteases providing 90% of human serine antiprotease activity. The AAT deficiency is produced by mutations of the SERPINA1 gene. Its clinical manifestations are pulmonary emphysema, liver cirrhosis, and less often panniculitis, systemic vasculitis and possibly other conditions. The severe AAT deficiency affects mainly Caucasian individuals. The highest prevalence, ranging from 1 in 2000 to 1 in 5000 population is observed in northern, western and central Europe. In the USA and Canada, the prevalence varies from 1 in 5000 to 1 in 10000 population. It is 5 times less frequent in Latin American countries. It is estimated that in Argentina there may be 18000 cases with severe deficiency of SZ y ZZ genotypes, most of them undiagnosed. It is crucial to suspect the disease in order to measure the serum AAT concentration, and, if the concentrations are low, to confirm the diagnosis with the phenotype or genotype determinations. Case detection allows genetic advice, control of blood-related relatives and in selected cases, replacement therapy.

Intralipid Infusions Effect on Nutrophil Elastase Level in Newborns

PURPOSE: Parenteral nutrition is given to infants who tempararily cannot take oral feeding adequately. A lipid emulsion is added to the parenteral to supply essential fatty acids. In neonatal sepsis, elastase from azuropilic granules of the neutrophils is released and rapidly bound to alpha1-Proteinase Inhibitor(alpha1-PI). The lipid emulsion has been noted to markedly inhibit chemotaxis of neutrophils, so we to measured the levels of Elastase-alpha1-Proteinase Inhibitor(E-alpha1-PI) complex to evaluate the effect of intralipid infusions on the neutrophil in newborns with sepsis. METHODS: This study evaluated 8 patients with neonatal sepsis and 12 normal newborns. We measured E-alpha1-PI complex levels in the serum of these patients by ELISA methods. RESULTS: Before infusion with lipid solution, patients with neonatal sepsis had significantly increased levels of E-alpha1-PI complex in comparison with those of vaginally delivered normal newborns. E-alpha1-PI complex levels were significantly decreased after lipid infusions of 0.5g/kg per day, but there was no further significant decrease with higher doses of the infusate. CONCLUSION: We observed the suppression neutrophil elastase levels by lipid infusions in newborn with sepsis. These results suggest that there were no appropriate chemotatic effects of neutrophil in newborn with sepsis. Therefore, we considered whether the lipid infusion was stopped if the newborn with sepsis was infused parenteral nutrition with intralipid.

The Effect of Alpha-1-Proteinase Inhibi-tor on Serums in Rats Exposed to Ozone and Cigarette Smoke / 环境与健康杂志

This paper reports the effect of alpha-1-proteinase inhibitor on serums in rats exposed to ozone and cigarette somke. The result shows that the activity of alpha-1-proteinase inhibitor on serums may be decreased by exposing rats to ozone and cig-arett somke. When ozone content is up to 1.2?0.lPPm, the activity of alpha-1-prot-einase inhibitor may by obviously decreased.