Feasibility of a genotyping system for the diagnosis of alpha1 antitrypsin deficiency: a multinational cross-sectional analysis.

INTRODUCTION: Currently, strategies for improving alpha1 antitrypsin deficiency (AATD) diagnosis are needed. Here we report the performance of a multinational multiplex-based genotyping test on dried blood spots and buccal swabs sent by post or courier and with web registration for subjects with suspected AATD in Argentina, Brazil, Chile, Colombia, Spain, and Turkey. METHODS: This was an observational, cross-sectional analysis of samples from patients with suspected AATD from March 2018 to January 2022. Samples were coded on a web platform and sent by post or courier to the central laboratory in Northern Spain. Allele-specific genotyping for the 14 most common mutations was carried out with the A1AT Genotyping Test (Progenika-Grifols, Spain). SERPINA1 gene sequencing was performed if none of the mutations were found or one variant was detected in heterozygous status and the AAT serum level was < 60 mg/dl, or if requested by the clinician in charge. RESULTS: The study included 30,827 samples: 30,458 (94.7%) with final results after direct genotyping and 369 (1.1%) with additional gene sequencing. Only 0.3% of the samples were not processed due to their poor quality. The prevalence of the most frequent allele combinations was MS 14.7%, MZ 8.6%, SS 1.9%, SZ 1.9%, and ZZ 0.9%. Additionally, 70 cases with new mutations were identified. Family screening was conducted in 2.5% of the samples. Samples from patients with respiratory diseases other than COPD, including poorly controlled asthma or bronchiectasis, also presented AATD mutations. CONCLUSIONS: Our results confirm the viability of this diagnostic system for genotyping AATD conducted simultaneously in different countries. The system has proved satisfactory and can improve the timely diagnosis of AATD.

Prevalencia de déficit de alfa-1 antitripsina en pacientes con EPOC en Argentina. Estudio DAAT.AR / Prevalence of Alpha-1 Antitrypsin Deficiency in COPD Patients in Argentina. The DAAT.AR Study

INTRODUCCIÓN: Existe subdiagnóstico del déficit grave de alfa-1 antitripsina (DAAT) a pesar de la recomendación de realizar la determinación de AAT en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). OBJETIVO: Estimar la prevalencia de DAAT en pacientes con EPOC ajustada a la población del estudio de prevalencia de EPOC en la Argentina (EPOC.AR). MATERIAL Y MÉTODOS: Estudio prospectivo multicéntrico de corte transversal en población ≥ 30 años de edad con diagnóstico de EPOC. Cuantificación de AAT por toma de sangre capilar en gota seca y posterior genotipificación en aquellos sujetos con concentraciones < 1,5 mg/dl en sangre capilar en gota seca (< 80 mg/dl sérica). Se definió DAAT como la detección de las variantes ZZ o SZ por genotipificación. Se tomó la población del estudio EPOC.AR para calcular la prevalencia local ajustada. RESULTADOS: Se incluyeron 3.254 pacientes (544 con AAT < 80 mg/dl) con diagnóstico espirométrico de EPOC. La prevalencia de DAAT en la población total del estudio fue de 1,29% (IC 95% 0,93-1,74), de los cuales un 0,92% (IC 95% 0,62-1,31) fueron Pi*ZZ y un 0,37% (IC 95% 0,19-0,64) Pi*SZ. La prevalencia ajustada de DAAT en pacientes con EPOC (≥ 40 años) fue de 0,83% (IC 95% 0,23-2,08). Encontramos asociación negativa de DAAT con la edad (OR 0,94; IC 95% 0,90-0,98; p = 0,006), el consumo de tabaco (OR 0,98; IC 95% 0,96-0,99; p = 0,009) y el VEF1% (OR 0,95; IC 95% 0,91-0,99; p = 0,015). CONCLUSIONES: Se estima que la prevalencia de DAAT en la población adulta con EPOC en Argentina es del 0,83%, lo cual podría representar 17.000 casos en nuestro país

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is still underdiagnosed, despite the recommendation to determine AAT in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To estimate the prevalence of AATD in COPD patients adjusted according to the population of the COPD prevalence study in Argentina (EPOC.AR). MATERIAL AND METHODS: This was a multicenter prospective cross-sectional study of a population aged ≥ 30 years of age diagnosed with COPD, involving AAT quantification in dry blood spot and subsequent genotyping in subjects with < 1.5 mg/dL AAT in dry blood spot (< 80 mg/dL in serum). AAT was defined as the detection of variants ZZ or SZ on genotyping. The EPOC.AR study population was used to calculate local adjusted prevalence. RESULTS: We included 3,254 patients (544 with AAT < 80 mg/dL) with a spirometric diagnosis of COPD. The prevalence of AATD in the total study population was 1.29% (95% CI 0.93-1.74), of which 0.92% (95% CI 0.62-1.31) were Pi*ZZ and 0.37% (95% CI 0.19-0.64) Pi*SZ. The adjusted prevalence of AATD in COPD patients ≥ 40 years of age was 0.83% (95% CI 0.23-2.08). We found that AATD was negatively associated with age (OR 0.94; 95% CI 0.90-0.98; P = .006), smoking habit (OR 0.98; 95% CI 0.96-0.99; P = .009), and FEV1% (OR 0.95; 95% CI 0.91-0.99; P = .015). CONCLUSIONS: The prevalence of AATD in the adult population with COPD in Argentina is estimated to be 0.83%, which could represent 17,000 cases in our country

Elucidating the mechanism of action of alpha-1-antitrypsin using retinal pigment epithelium cells exposed to high glucose. Potential use in diabetic retinopathy.

BACKGROUND: Alpha-1-antitrypsin is a protein involved in avoidance of different processes that are seen in diabetic retinopathy pathogenesis. These processes include apoptosis, extracellular matrix remodeling and damage of vessel walls and capillaries. Furthermore, because of its anti-inflammatory effects, alpha-1-antitrypsin has been proposed as a possible therapeutic approach for diabetic retinopathy. Our group tested alpha-1-antitrypsin in a type 1 diabetes mouse model and observed a reduction of inflammation and retinal neurodegeneration. Thus, shedding light on the mechanism of action of alpha-1-antitrypsin at molecular level may explain how it works in the diabetic retinopathy context and show its potential for use in other retinal diseases. METHODS: In this work, we evaluated alpha-1-antitrypsin in an ARPE-19 human cell line exposed to high glucose. We explored the expression of different mediators on signaling pathways related to pro-inflammatory cytokines production, glucose metabolism, epithelial-mesenchymal transition and other proteins involved in the normal function of retinal pigment epithelium by RT-qPCR and Western Blot. RESULTS: We obtained different expression patterns for evaluated mediators altered with high glucose exposure and corrected with the use of alpha-1-antitrypsin. CONCLUSIONS: The expression profile obtained in vitro for the evaluated proteins and mRNA allowed us to explain our previous results obtained on mouse models and to hypothesize how alpha-1-antitrypsin hinder diabetic retinopathy progression on a complex network between different signaling pathways. GENERAL SIGNIFICANCE: This network helps to understand the way alpha-1-antitrypsin works in diabetic retinopathy and its scope of action.

Prevalence of Alpha-1 Antitrypsin Deficiency in COPD Patients in Argentina. The DAAT.AR Study. / Prevalencia de déficit de alfa-1 antitripsina en pacientes con EPOC en Argentina. Estudio DAAT.AR.

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is still underdiagnosed, despite the recommendation to determine AAT in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To estimate the prevalence of AATD in COPD patients adjusted according to the population of the COPD prevalence study in Argentina (EPOC.AR). MATERIAL AND METHODS: This was a multicenter prospective cross-sectional study of a population aged≥30 years of age diagnosed with COPD, involving AAT quantification in dry blood spot and subsequent genotyping in subjects with<1.5mg/dL AAT in dry blood spot (<80mg/dL in serum). AAT was defined as the detection of variants ZZ or SZ on genotyping. The EPOC.AR study population was used to calculate local adjusted prevalence. RESULTS: We included 3,254 patients (544 with AAT<80mg/dL) with a spirometric diagnosis of COPD. The prevalence of AATD in the total study population was 1.29% (95% CI 0.93-1.74), of which 0.92% (95% CI 0.62-1.31) were Pi*ZZ and 0.37% (95% CI 0.19-0.64) Pi*SZ. The adjusted prevalence of AATD in COPD patients≥40 years of age was 0.83% (95% CI 0.23-2.08). We found that AATD was negatively associated with age (OR 0.94; 95% CI 0.90-0.98; P=.006), smoking habit (OR 0.98; 95% CI 0.96-0.99; P=.009), and FEV1% (OR 0.95; 95% CI 0.91-0.99; P=.015). CONCLUSIONS: The prevalence of AATD in the adult population with COPD in Argentina is estimated to be 0.83%, which could represent 17,000 cases in our country.

Alpha-1-antitrypsin ameliorates inflammation and neurodegeneration in the diabetic mouse retina.

Diabetic retinopathy (DR) is the most common cause of blindness in the working age population. Early events of DR are accompanied by neurodegeneration of the inner retina resulting in ganglion cell loss. These findings together with reduced retinal thickness are observed within the first weeks of experimental DR. Besides, an inflammatory process is triggered in DR in which the innate immune response plays a relevant role. Alpha 1 antitrypsin (AAT), an inhibitor of serine proteases, has shown anti-inflammatory properties in several diseases. We aimed at evaluating the use of AAT to prevent the early changes induced by DR. Diabetic AAT-treated mice showed a delay on ganglion cell loss and retinal thinning. These animals showed a markedly reduced inflammatory status. AAT was able to preserve systemic and retinal TNF-α level similar to that of control mice. Furthermore, retinal macrophages found in the AAT-treated diabetic mouse exhibited M2 profile (F4/80+CD206+) together with an anti-inflammatory microenvironment. We thus demonstrated that AAT-treated mice show less retinal neurodegenerative changes and have reduced levels of systemic and retinal TNF-α. Our results contribute to shed light on the use of AAT as a possible therapeutic option in DR.

Recomendaciones de vacunación en adultos con enfermedades respiratorias: Documento de la Asociación Argentina de Medicina Respiratoria para los neumonólogos / Recommendations on Vaccination for Adults with Respiratory Diseases. Document of the Argentina Association of Respiratory Medicine for Pulmonologists

El neumonólogo de adultos acostumbra a prescribir vacunas. Este documento hecho por expertos en aspectos de la especialidad que involucran vacunar a pacientes con enfermedades respiratorias, perteneciente a la Asociación Argentina de Medicina Respiratoria, resumió la información disponible proponiendo una participación activa en la vacunación contra influenza (VAG), neumococo (VAN), pertusis y zoster. El Ministerio de Salud (MSAL) en Argentina, como el CDC y su comité de consulta sobre inmunización (ACIP) en Estados Unidos, elaboran calendarios y recomendaciones para vacunación. La ACIP recomienda la VAG a mayores de 6 meses sin contraindicaciones; el MSAL a mayores de 65 años y a quienes tengan comorbilidades (incluye enfermedades respiratorias y tabaquismo) o contacto con personas vulnerables. La clásica VAN polisacárida de 23 serotipos es recomendada para adultos con riesgo de enfermedad invasiva, incluyendo a mayores de 65 años, revacunando a los inmunosuprimidos y una única vez a los mayores de 65 que hubieran sido vacunados 5 años antes o más; la ACIP recomienda dar la VAN conjugada de 13 serotipos, más inmunogénica, secuencialmente con la polisacárida de 23, en adultos con factores de riesgo y en mayores de 65 años. Sugerimos usarla en menores de 65 con comorbilidad respiratoria. El neumonólogo debe recordar al menos 2 vacunas más: dar el refuerzo decenal contra difteria y tétanos (DT) en mayores de 18, una vez con vacuna triple acelular (difteria, pertusis y tétanos) protegiendo contra pertusis y reduciendo su transmisión. El herpes zoster produce un rash cutáneo vesicular doloroso. Uno cada 2 mayores de 85 sufrirán al menos un ataque de herpes zoster. La vacuna reduce más del 50% la incidencia y más del 60% la neuralgia post herpética; el ACIP la recomienda en mayores de 60 años. Un gran número de los pacientes con afecciones pulmonares crónicas tienen esa edad.

The pulmonologist uses to prescribe vaccines to adult patients. Experts of the Argentina Association of Respiratory Medicine who are specialists in areas involving vaccination of patients with respiratory diseases prepared this document which summarizes the available information and proposes an active prescription of the infuenza, pneumococcus, pertussis and herpes zoster vaccinations. The Ministry of Health in Argentina as the CDC and its Advisory Committee on Immunization Practices (ACIP) in the USA, made recommendations on vaccination indications and schedules. The ACIP recommends influenza vaccination to persons older than 6 months of age without any contraindication. The Ministry of Health recommends this vaccination to persons over 65 years of age, to those with morbidities (including respiratory diseases and smoking habit) and to persons in contact with high risk people. The classic 23-valent polysaccharide pneumococcal vaccine is recommended for adults at risk of invasive disease, including persons over 65 years of age. Revaccination is recommended to immunosuppressed patients and persons over 65 years of age at 5-year intervals. The ACIP recommends vaccination with the 13-valent serotypes polysaccharide pneumococcal vaccine, which is more immunogenic, sequentially with the 23-valent vaccine in adults with risk factors and over 65 years of age. We suggest this practice in patients under 65 years of age with respiratory morbidities. The pulmonologist must remember at least two other vaccines: a booster vaccination every 10 years of diphtheria and tetanus vaccine to persons over 18 years of age, and once the triple acellular vaccine (diphtheria, pertussis and tetanus) to protect against pertussis and reduce transmission. Herpes zoster (shingles) causes a painful vesicular rash; 50% of persons over 85 years suffer at least one bout of herpes zoster. The vaccine reduces more than 50% incidence and more than 60% postherpetic neuralgia. This vaccine is recommended by ACIP for persons over 60 years. In this age group there are many patients with chronic lung conditions.

Déficit de alfa 1 antitripsina en pacientes con EPOC: estudio de corte transversal / Alpha-1 Antitrypsin Deficiency in COPD Patients: A Cross-Sectional Study

Introducción: El déficit de alfa 1 antitripsina (DAAT) es un desorden genético asociado a enfermedad pulmonar obstructiva crónica (EPOC) en edad temprana y enfermedad hepática. A su vez, es una condición altamente subdiagnosticada, lo que haría necesario el desarrollo de programas de cribado para identificar a pacientes afectados, ya que el diagnóstico podría promover intervenciones específicas como cese tabáquico, estudio de familiares, consejo genético y uso de terapia de reemplazo. Objetivo: Estimar la prevalencia de DAAT grave en pacientes con EPOC mediante la cuantificación de la proteína en sangre seca de forma rutinaria y posterior genotipado de aquellos pacientes con concentraciones por debajo de un umbral establecido. Materiales y métodos: Estudio de corte transversal de pacientes adultos con diagnóstico de EPOC que consultaron al Hospital Dr. Antonio Cetrángolo (Buenos Aires, Argentina) entre 2009 y 2012. La participación en el estudio consistió en la toma de una muestra de sangre por punción capilar del pulpejo del dedo para la determinación de las concentraciones de alfa 1 antitripsina (AAT), evaluación clínica y evaluación de función pulmonar. En los pacientes con déficit, se determinó adicionalmente el genotipo. Resultados: Un total de 1.002 pacientes fueron evaluados, de los cuales 785 (78,34%) tuvieron un valor normal de AAT, mientras que en 217 (21,66%) se detectó un déficit de concentración de AAT; a este último subgrupo se les realizó genotipado posterior, que arrojó: 15 (1,5%, IC 95% 0,75-2,25) pacientes con genotipo asociado a DAAT grave, de los cuales 12 ZZ (1,2%, IC 95% 0,52-1,87) y 3 SZ (0,3%, IC 95% 0-0,64). Los 202 pacientes restantes se clasificaron como: 29 heterocigotos Z (2,89%, IC 95% 1,86-3,93), 25 heterocigotos S (2,5%, IC 95% 1,53-3,46) y 4 SS (0,4%, IC 95% 0,01-0,79). Por otra parte, en 144 pacientes (14,37%, IC 95% 12,2-16,54) no se llegó a un diagnóstico definitivo. Conclusión: La estrategia utilizada con concentración sérica inicial de AAT según la proteína en sangre seca y posterior genotipado resultó adecuada como primera aproximación a un programa de cribado de DAAT grave, ya que se logró el diagnóstico definitivo en un 87% de los pacientes. Sin embargo, no se obtuvieron resultados por razones logísticas en el 13% restante. La implementación de técnicas para fenotipado en proteína en sangre seca permitirá corregir este significativo problema en esta etapa. Creemos que los resultados obtenidos avalarían su aplicación para la detección DAAT en poblaciones de pacientes con EPOC en cumplimiento de las recomendaciones de las guías nacionales e internacionales

Introduction: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with early onset chronic obstructive pulmonary disease (COPD) and liver disease. It is also a highly under-diagnosed condition. As early diagnosis could prompt specific interventions such as smoking cessation, testing of family members, genetic counselling and use of replacement therapy, screening programs are needed to identify affected patients. Objective: To estimate the prevalence of severe AATD in COPD patients by routine dried blood spot testing and subsequent genotyping in patients with alpha-1 antitrypsin (AAT) levels below an established threshold. Materials and methods: Cross-sectional study of adult COPD patients attending the Hospital Dr. Antonio Cetrángolo (Buenos Aires, Argentina) between 2009 and 2012. The study consisted of capillary blood collection via finger stick to determine AAT levels, clinical evaluation and lung function tests. Genotype was determined in AAT-deficient patients. Results: A total of 1,002 patients were evaluated, of whom 785 (78.34%) had normal AAT levels, while low AAT levels were found in 217 (21.66%). Subsequent genotyping of the latter sub-group found: 15 (1.5%, 95% CI 0.75-2.25) patients with a genotype associated with severe AATD, of whom 12 were ZZ (1.2%, 95% CI 0.52-1.87) and 3 SZ (0.3%, 95% CI 0-0.64). The remaining 202 patients were classified as: 29 Z heterozygotes (2.89%, 95% CI 1.86-3.93), 25 S heterozygotes (2.5%, 95% CI 1.53-3.46) and 4 SS (0.4%, 95% CI 0.01-0.79). A definitive diagnosis could not be reached in 144 patients (14.37%, 95% CI 12.2-16.54). Conclusion: The strategy using an initial serum AAT level obtained by dried blood spot testing and subsequent genotyping was a satisfactory initial approach to a screening program for severe AAT, as a definitive diagnosis was achieved in 87% of patients. However, results were not obtained for logistical reasons in the remaining 13%. This major obstacle may be overcome by the use of dried blood spot phenotyping techniques. We believe this approach for detecting AATD in COPD patients, in compliance with national and international guidelines, is supported by our results

Alpha-1 Antitrypsin Deficiency in COPD Patients: A Cross-Sectional Study.

INTRODUCTION: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder associated with early onset chronic obstructive pulmonary disease (COPD) and liver disease. It is also a highly under-diagnosed condition. As early diagnosis could prompt specific interventions such as smoking cessation, testing of family members, genetic counselling and use of replacement therapy, screening programs are needed to identify affected patients. OBJECTIVE: To estimate the prevalence of severe AATD in COPD patients by routine dried blood spot testing and subsequent genotyping in patients with alpha-1 antitrypsin (AAT) levels below an established threshold. MATERIALS AND METHODS: Cross-sectional study of adult COPD patients attending the Hospital Dr. Antonio Cetrángolo (Buenos Aires, Argentina) between 2009 and 2012. The study consisted of capillary blood collection via finger stick to determine AAT levels, clinical evaluation and lung function tests. Genotype was determined in AAT-deficient patients. RESULTS: A total of 1,002 patients were evaluated, of whom 785 (78.34%) had normal AAT levels, while low AAT levels were found in 217 (21.66%). Subsequent genotyping of the latter sub-group found: 15 (1.5%, 95% CI 0.75-2.25) patients with a genotype associated with severe AATD, of whom 12 were ZZ (1.2%, 95% CI 0.52-1.87) and 3 SZ (0.3%, 95% CI 0-0.64). The remaining 202 patients were classified as: 29 Z heterozygotes (2.89%, 95% CI 1.86-3.93), 25 S heterozygotes (2.5%, 95% CI 1.53-3.46) and 4 SS (0.4%, 95% CI 0.01-0.79). A definitive diagnosis could not be reached in 144 patients (14.37%, 95% CI 12.2-16.54). CONCLUSION: The strategy using an initial serum AAT level obtained by dried blood spot testing and subsequent genotyping was a satisfactory initial approach to a screening program for severe AAT, as a definitive diagnosis was achieved in 87% of patients. However, results were not obtained for logistical reasons in the remaining 13%. This major obstacle may be overcome by the use of dried blood spot phenotyping techniques. We believe this approach for detecting AATD in COPD patients, in compliance with national and international guidelines, is supported by our results.

¿El déficit de alfa1 antitripsina es el culpable? / Is alpha1 antitrypsin deficiency the guilty?

He tenido la oportunidad de leer detenidamente el artículo de la Dra. Silvia Quadrelli y Justine Dibarboure acerca de la enfermedad y muerte de Federico Chopin. Ha sido muy apasionante y educativo recorrer tan detallada crónica de la vida y obra de uno de los mayores exponentes de la música clásica de todos los tiempos, así como la discusión sobre la causa de su fallecimiento con los diagnósticos diferenciales planteados

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.

Normativas de diagnóstico y tratamiento del déficit de alfa-1 antitripsina

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.(AU)

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.(AU)

Frecuencia de trastornos respiratorios del sueño en pacientes con enfermedad difusa del parénquima pulmonar / Frecuency of sleep related disorders in patients with diffuse lung diseases

Introducción: Los pacientes con enfermedad pulmonar difusa (EPD) a menudo presentan fragmentación del sueño con microdespertares frecuentes. En este grupo de pacientes, la desaturación nocturna de oxígeno es frecuente con una prevalencia de 50- 80%. Se agrava en el sueño REM y se asocia con una menor calidad de vida, pudiendo contribuir al daño vascular a largo plazo. La presencia de apneas obstructivas del sueño (AOS) se presenta en el 20% de la población adulta general. Objetivos: Describir las características de los parámetros respiratorios clínicos y fisiológicos y la frecuencia de los trastornos respiratorios del sueño (TRS), especialmente de AOS, en pacientes con EPD. Materiales y métodos: Se incluyeron prospectivamente pacientes con diagnóstico establecido de EPD que consultaron en un hospital especializado en enfermedades respiratorias entre julio de 2010 y enero de 2012. Se les realizó polisomnografía (PSG) y estudio de función pulmonar (CVF y DLCO). Resultados: Se estudiaron 41 pacientes con edad promedio de 61.5 ± 12.6 años. El 54% eran hombres (n = 22). Los diagnósticos de EPD fueron neumonía intersticial usual (NIU) en el 70.7%, neumonía intersticial no específica (NINE) en el 14.6%, neumonitis por hipersensibilidad (NHS) en el 9.8% y proteinosis alveolar pulmonar (PAP) en el 4.8%. El índice de masa corporal (IMC) medio fue 29.4 ± 4.4 kg/m². En el 80% fue = 25 y en el 41% = 30. La CVF media fue de 2.18 ± 0.7 l y 64.8 ± 16.8 del porcentaje del predictivo. La DLCO ajustada a la Hb media fue de 10.3±3.6 ml/mmHg/min y 46.9 ± 14 del porcentaje del valor predictivo. Con respecto a la PSG, la SpO2 basal media fue de 93.9 ±3.4%, la saturación media durante el sueño fue 89.8 ±7% y en el 39% de los casos la SpO2 media era < 90%. En el 90% de los casos la SpO>2 mínima durante el sueño fue menor de 90%. El 34% de los casos presentaba CT 90 (tiempo con SpO2 < 90%) > 50%. De los 13 pacientes con SpO2 basal despierto > 95%, 3 presentaron un CT90 = 20% yv de los 27 pacientes con SpO2 basal > 92%, 10 cursaban con un CT90 = 20%.v Del total de los pacientes, el 48.8% presentaba AOS. El índice de apneas-hipoapneasv (IAH) medio fue 11.4 y el 20% de los pacientes presentó IAH = 15. Con respecto a la escala de somnolencia de Epworth (ESE), el 45% de los pacientes conv AOS presentaba una ESE = 10, que resultó significativamente mayor en comparación conv el grupo sin AOS. Del grupo de pacientes con IAH = 15, el 62.5% presentaban ESE < 10. Conclusiones: Un número importante de pacientes sin hipoxemia en reposo presentan desaturación durante el sueño. En este estudio, la frecuencia de AOS fue del 48.8%. Además, el grupo de pacientes con EPD con AOS presentó mayor compromiso oximétrico medido a través de CT90. Globalmente, el grupo de pacientes con AOS presentaba mayores valores de FVC (71.25% vs 58.67 p = 0.019).

Background: Patients with interstitial lung disease (ILD) often have sleep fragmentation with frequent arousals. In this group of patients, nocturnal oxygen desaturation is common, with a prevalence of 50-80%. It is worse in Rapid Eye Movement (REM) sleep, is associated with reduced quality of life and can contribute to long-term vascular damage. The presence of obstructive sleep apnea (OSA) occurs in 20% of the general adult population. Aims: To describe the characteristics of clinical and physiological respiratory parameters and frequency of respiratory sleep disorders (RSD), especially OSA, in patients with ILD. Materials and Methods: We prospectively included ILD patients who attended a specialized hospital between July 2010 and January 2012. Polysomnography (PSG) and study of pulmonary function: Forced Vital Capacity (FVC) and Diffusing Lung Capacity for Carbon Monoxide (DLCO) were performed. Results: We studied 41 patients with a mean age of 61.5 ± 12.6 years. 54% were male (n = 22). ILD diagnoses were usual interstitial pneumonia (UIP) in 70.7%, nonspecific interstitial pneumonia (NSIP) in 14.6%, hypersensitivity pneumonitis (HP) in 9.8% and pulmonary alveolar proteinosis (PAP) in 4.8%. The body mass index (BMI) was 29.4 ± 4.4 kg/m²; it was = 25 in 80% of patients and = 30 in 41%. The mean FVC was 2.18 ± 0.7 l and 64.8 ± 16.8 in the percentage of predictive value. The DLCO adjusted to Hb mean was 10.3 ± 3.6 ml/mmHg/min and 46.9 ± 14 in the percentage of predictive value. Regarding the PSG, the mean baseline SpO2 was 93.9 ± 3.4%, the mean saturation during sleep was 89.8 ± 7%, and the mean SpO2 was < 90% in 39% of cases. In 90% of cases the minimum SpO2 during sleep was less than 90%; 34% of patients had CT 90 (time with SpO2 < 90%) > 50%. In 13 patients with baseline SpO2 > 95%, 3 had CT90 = 20% and 10 of the 27 patients with basal SpO2 > 92%, had CT90 = 20%. Of all patients, 48.8% had OSA. The mean apnea-hypopnea index ...

Frecuencia de trastornos respiratorios del sueño en pacientes con enfermedad difusa del parénquima pulmonar / Frecuency of sleep related disorders in patients with diffuse lung diseases

Introducción: Los pacientes con enfermedad pulmonar difusa (EPD) a menudo presentan fragmentación del sueño con microdespertares frecuentes. En este grupo de pacientes, la desaturación nocturna de oxígeno es frecuente con una prevalencia de 50- 80%. Se agrava en el sueño REM y se asocia con una menor calidad de vida, pudiendo contribuir al daño vascular a largo plazo. La presencia de apneas obstructivas del sueño (AOS) se presenta en el 20% de la población adulta general. Objetivos: Describir las características de los parámetros respiratorios clínicos y fisiológicos y la frecuencia de los trastornos respiratorios del sueño (TRS), especialmente de AOS, en pacientes con EPD. Materiales y métodos: Se incluyeron prospectivamente pacientes con diagnóstico establecido de EPD que consultaron en un hospital especializado en enfermedades respiratorias entre julio de 2010 y enero de 2012. Se les realizó polisomnografía (PSG) y estudio de función pulmonar (CVF y DLCO). Resultados: Se estudiaron 41 pacientes con edad promedio de 61.5 ± 12.6 años. El 54% eran hombres (n = 22). Los diagnósticos de EPD fueron neumonía intersticial usual (NIU) en el 70.7%, neumonía intersticial no específica (NINE) en el 14.6%, neumonitis por hipersensibilidad (NHS) en el 9.8% y proteinosis alveolar pulmonar (PAP) en el 4.8%. El índice de masa corporal (IMC) medio fue 29.4 ± 4.4 kg/m². En el 80% fue = 25 y en el 41% = 30. La CVF media fue de 2.18 ± 0.7 l y 64.8 ± 16.8 del porcentaje del predictivo. La DLCO ajustada a la Hb media fue de 10.3±3.6 ml/mmHg/min y 46.9 ± 14 del porcentaje del valor predictivo. Con respecto a la PSG, la SpO2 basal media fue de 93.9 ±3.4%, la saturación media durante el sueño fue 89.8 ±7% y en el 39% de los casos la SpO2 media era < 90%. En el 90% de los casos la SpO>2 mínima durante el sueño fue menor de 90%. El 34% de los casos presentaba CT 90 (tiempo con SpO2 < 90%) > 50%. De los 13 pacientes con SpO2 basal despierto > 95%, 3 presentaron un CT90 = 20% yv de los 27 pacientes con SpO2 basal > 92%, 10 cursaban con un CT90 = 20%.v Del total de los pacientes, el 48.8% presentaba AOS. El índice de apneas-hipoapneasv (IAH) medio fue 11.4 y el 20% de los pacientes presentó IAH = 15. Con respecto a la escala de somnolencia de Epworth (ESE), el 45% de los pacientes conv AOS presentaba una ESE = 10, que resultó significativamente mayor en comparación conv el grupo sin AOS. Del grupo de pacientes con IAH = 15, el 62.5% presentaban ESE < 10. Conclusiones: Un número importante de pacientes sin hipoxemia en reposo presentan desaturación durante el sueño. En este estudio, la frecuencia de AOS fue del 48.8%. Además, el grupo de pacientes con EPD con AOS presentó mayor compromiso oximétrico medido a través de CT90. Globalmente, el grupo de pacientes con AOS presentaba mayores valores de FVC (71.25% vs 58.67 p = 0.019).(AU)

Background: Patients with interstitial lung disease (ILD) often have sleep fragmentation with frequent arousals. In this group of patients, nocturnal oxygen desaturation is common, with a prevalence of 50-80%. It is worse in Rapid Eye Movement (REM) sleep, is associated with reduced quality of life and can contribute to long-term vascular damage. The presence of obstructive sleep apnea (OSA) occurs in 20% of the general adult population. Aims: To describe the characteristics of clinical and physiological respiratory parameters and frequency of respiratory sleep disorders (RSD), especially OSA, in patients with ILD. Materials and Methods: We prospectively included ILD patients who attended a specialized hospital between July 2010 and January 2012. Polysomnography (PSG) and study of pulmonary function: Forced Vital Capacity (FVC) and Diffusing Lung Capacity for Carbon Monoxide (DLCO) were performed. Results: We studied 41 patients with a mean age of 61.5 ± 12.6 years. 54% were male (n = 22). ILD diagnoses were usual interstitial pneumonia (UIP) in 70.7%, nonspecific interstitial pneumonia (NSIP) in 14.6%, hypersensitivity pneumonitis (HP) in 9.8% and pulmonary alveolar proteinosis (PAP) in 4.8%. The body mass index (BMI) was 29.4 ± 4.4 kg/m²; it was = 25 in 80% of patients and = 30 in 41%. The mean FVC was 2.18 ± 0.7 l and 64.8 ± 16.8 in the percentage of predictive value. The DLCO adjusted to Hb mean was 10.3 ± 3.6 ml/mmHg/min and 46.9 ± 14 in the percentage of predictive value. Regarding the PSG, the mean baseline SpO2 was 93.9 ± 3.4%, the mean saturation during sleep was 89.8 ± 7%, and the mean SpO2 was < 90% in 39% of cases. In 90% of cases the minimum SpO2 during sleep was less than 90%; 34% of patients had CT 90 (time with SpO2 < 90%) > 50%. In 13 patients with baseline SpO2 > 95%, 3 had CT90 = 20% and 10 of the 27 patients with basal SpO2 > 92%, had CT90 = 20%. Of all patients, 48.8% had OSA. The mean apnea-hypopnea index ...(AU)

Neumonía aguda grave de la comunidad en menores de 65 años sin comorbilidades conocidas previamente: estudio multicéntrico retrospectivo / Severe community acquired pneumonia in healthy adults: a multicenter retrospective study

Objetivo: analizar las características epidemiológicas, clínicas y de estudios complementarios en pacientes jóvenes y sanos con neumonía aguda grave de la comunidad (NACG). Material y Método: evaluación retrospectiva de historias clínicas de adultos menores de 65 años, sin comorbilidades, internados con NACG entre 1998 y 2008. Resultados: se identificaron 40 pacientes (M/F = 0.48), edad promedio 37.8 ± 14.1años (16-61). El 42.5% requirió ventilación mecánica y el 57.5% inotrópicos. La PaO2/FiO2 inicial fue 203.6 ± 91.4 mmHg (50-366.7) y las anomalías de laboratorio más frecuentesincluyeron anemia, leucocitosis, hipoalbuminemia y urea y creatinina elevadas. El tratamiento antibiótico empírico consistió en ceftriaxona o ß-lactámico/inhibidor de ß-lactamasas (BL) + macrólido en el 70% de los casos. La etiología se reveló en el 50%,los patógenos y su frecuencia fueron: Streptococcus Pneumoniae, 35%; Leptospira, 15%; Hantavirus y Mycoplasma pneumoniae, 10% y Legionella pneumophila, Pneumocystisjirovecii, Histoplasma capsulatum, Klebsiella pneumoniae, Haemophilus influenzae BL (-) y Staphylococcus aureus sensible a meticilina, 5%. El 77.5% de los pacientes presentócomplicaciones, las más frecuentes fueron shock, insuficiencia respiratoria, insuficiencia renal aguda y derrame pleural. Ocho pacientes presentaron comorbilidades desconocidas,incluyendo HIV positivo, diabetes mellitus, asma, insuficiencia cardíaca e hipotiroidismo. La mortalidad fue 12.5%. Hipotensión arterial diastólica, taquicardia, requerimiento dehemodiálisis y tratamiento inadecuado se asociaron independientemente a mortalidad. Conclusiones: el 20% de los menores de 65 años con NACG, presumiblemente sanos, tenían comorbilidades. El patógeno más frecuente fue neumococo y la mortalidad se asoció a la gravedad de la sepsis e inadecuación del tratamiento.

Aims: to analyze epidemiologic, clinical and other abnormalities in healthy young adults with severe community acquired pneumonia (SCAP). Methods: retrospective analysis of clinical records of adults younger than 65 years, with SCAP and without previously known comorbidities, admitted from 1998 to 2008. Results: forty patients were included (M/F = 0.48), age 37.8 ± 14.1 years (range 16 - 61). Mechanical ventilation was used in 42.5% and vasopressors in 57.5% of patients. Initial PaO2/FIO2 ratio was 203.6 ± 91.4 mmHg (50 - 366.7); frequent laboratory abnormalities included: anemia, leukocytosis, hypoalbuminemia and high urea and creatinine levels.The empiric antimicrobial therapy was ceftriaxone or ß-lactam/ß - lactamases (BL) inhibitor plus macrolide in 70% of cases. The etiology was established in 50%; the specific pathogens were: Streptococcus pneumoniae, 35%; Leptospira, 15%; Hantavirus and Mycoplasma pneumoniae, 10%; and Legionella pneumophila, Pneumocystisjirovecii, Histoplasma capsulatum, Klebsiella pneumoniae, Haemophilus influenzae BL (-) and methicillin susceptible Staphylococcus aureus, 5%. Complications were present in 77.5% including shock, respiratory failure, acute renal failure and pleural effusion.Eight patients presented previously unknown comorbidities including HIV infection, diabetes mellitus, asthma, congestive cardiac failure and hypothyroidism. Mortality was 12.5 %. Diastolic arterial hypotension, taquichycardia, requirement of hemodialysis and inadequate therapy were significantly associated to mortality. Conclusions: 20% of young and presumably healthy adults with SCAP had comorbidities. S. pneumoniae was the commonest pathogen; mortality was associated with severity of sepsis and inadequate therapy.

Sleep disordered breathing and daytime sleepiness are associated with poor academic performance in teenagers. A study using the Pediatric Daytime Sleepiness Scale (PDSS).

STUDY OBJECTIVES: Inadequate sleep and sleep disordered breathing (SDB) can impair learning skills. Questionnaires used to evaluate sleepiness in adults are usually inadequate for adolescents. We conducted a study to evaluate the performance of a Spanish version of the Pediatric Daytime Sleepiness Scale (PDSS) and to assess the impact of sleepiness and SDB on academic performance. DESIGN: A cross-sectional survey of students from 7 schools in 4 cities of Argentina. MEASUREMENTS: A questionnaire with a Spanish version of the PDSS was used. Questions on the occurrence of snoring and witnessed apneas were answered by the parents. Mathematics and language grades were used as indicators of academic performance. PARTICIPANTS: The sample included 2,884 students (50% males; age: 13.3 +/- 1.5 years) RESULTS: Response rate was 85%; 678 cases were excluded due to missing data. Half the students slept <9 h per night on weekdays. The mean PDSS value was 15.74 +/- 5.93. Parental reporting of snoring occurred in 511 subjects (23%); snoring was occasional in 14% and frequent in 9%. Apneas were witnessed in 237 cases (11%), being frequent in 4% and occasional in 7%. Frequent snorers had higher mean PDSS scores than occasional or nonsnorers (18 +/- 5, 15.7 +/- 6 and 15.5 +/- 6, respectively; P < 0.001). Reported snoring or apneas and the PDSS were significant univariate predictors of failure and remained significant in multivariate logistic regression analysis after adjusting for age, sex, body mass index, specific school attended, and sleep habits. CONCLUSIONS: Insufficient hours of sleep were prevalent in this population. The Spanish version of the PDSS was a reliable tool in middle-school-aged children. Reports of snoring or witnessed apneas and daytime sleepiness as measured by PDSS were independent predictors of poor academic performance.

Ventilación no invasiva en pacientes con exacerbacion de EPOC / Non invasive positive pressure ventilation in patients with COPD exacerbation

Se realizó un estudio prospectivo sobre la utilización de la ventilación mecánica no invasiva (VNI) en pacientes internados en Clínica Médica Neumonológica por exacerbación de la enfermedad pulmonar obstructiva crónica (EPOC), con el objetivo de evaluar la evolución, los cambios gasométricos, las comorbilidades y la mortalidad de los pacientes internados. Desde enero 2000 a enero 2003 ingresaron al estudio 39 pacientes, evaluados según normas internacionales en 54 internaciones, siendo clasificados como de grado grave y muy grave, dado que la medición del volumen espiratorio forzado en un segundo (VEF1) era del 26%. Veintinueve pacientes (74.4%) presentaron alguna comorbilidad. Como consecuencia de la aplicación de la VNI, el pH se incrementó entre la primera y tercera medición. El pH promedio inicial fue de 7.25 llegando a 7.33 a las 2 horas y a 7.39 al alta, en tanto que la pCO2 con promedio inicial de 83.8 mm Hg llegó a 67.8 mm Hg y 54.2 mm Hg en el mismo período. Treinta y cinco de los 39 pacientes fueron dados de alta con un período de internación promedio de 13.6 días. Cuatro pacientes (10.3%) fallecieron. Se concluye que con la aplicación de la VNI en pacientes con exacerbación de EPOC, el pH y la PaCO2 cambian significativamente en las muestras sucesivas, y que la adecuada capacitación del equipo de salud puede permitir el tratamiento de estos pacientes en áreas de menor complejidad. Deben ser tenidas en cuenta las posibles complicaciones que pueden sufrir los pacientes durante la internación, que pueden requerir la aplicación de ventilación invasiva.

This is a prospective study on the implementation of the non-invasive positive pressure ventilation (NPPV) to treat respiratory failure resulting from exacerbation of chronic obstructive pulmonary disease (COPD) in patients hospitalized in a Pneumological Unit. From January 2000 to January 2003, 39 patients were included during 54 different exacerbation events after being evaluated under international standards. They were classified as severe and very severe patients on the basis of their FEV1 values of 26%. Twenty nine patients presented co-morbidities. As a consequence of the NPPV treatment, the pH values increased between the first and last register as well as the pCO2 dropped in the same period. The initial mean pH values were 7.25 reaching mean values of 7.33 at 2 hours and 7.39 at the discharge; the corresponding pCO2 mean values were 83.8 mmHg, 67.8 mmHg and 54.2 mmHg. Thirty five patients out of 39 were discharged after a mean hospitalization length of 13.6 days. Four patients died. Apropriate training of health care staff in general facilities could allow the implementation of NPPV in addition to usual medical care to treat exacerbation of COPD. High morbidity situations could arise during hospitalization, so invasive ventilation must be necessary.

Ventilación no invasiva en pacientes con exacerbacion de EPOC / Non invasive positive pressure ventilation in patients with COPD exacerbation

Se realizó un estudio prospectivo sobre la utilización de la ventilación mecánica no invasiva (VNI) en pacientes internados en Clínica Médica Neumonológica por exacerbación de la enfermedad pulmonar obstructiva crónica (EPOC), con el objetivo de evaluar la evolución, los cambios gasométricos, las comorbilidades y la mortalidad de los pacientes internados. Desde enero 2000 a enero 2003 ingresaron al estudio 39 pacientes, evaluados según normas internacionales en 54 internaciones, siendo clasificados como de grado grave y muy grave, dado que la medición del volumen espiratorio forzado en un segundo (VEF1) era del 26%. Veintinueve pacientes (74.4%) presentaron alguna comorbilidad. Como consecuencia de la aplicación de la VNI, el pH se incrementó entre la primera y tercera medición. El pH promedio inicial fue de 7.25 llegando a 7.33 a las 2 horas y a 7.39 al alta, en tanto que la pCO2 con promedio inicial de 83.8 mm Hg llegó a 67.8 mm Hg y 54.2 mm Hg en el mismo período. Treinta y cinco de los 39 pacientes fueron dados de alta con un período de internación promedio de 13.6 días. Cuatro pacientes (10.3%) fallecieron. Se concluye que con la aplicación de la VNI en pacientes con exacerbación de EPOC, el pH y la PaCO2 cambian significativamente en las muestras sucesivas, y que la adecuada capacitación del equipo de salud puede permitir el tratamiento de estos pacientes en áreas de menor complejidad. Deben ser tenidas en cuenta las posibles complicaciones que pueden sufrir los pacientes durante la internación, que pueden requerir la aplicación de ventilación invasiva.(AU)

This is a prospective study on the implementation of the non-invasive positive pressure ventilation (NPPV) to treat respiratory failure resulting from exacerbation of chronic obstructive pulmonary disease (COPD) in patients hospitalized in a Pneumological Unit. From January 2000 to January 2003, 39 patients were included during 54 different exacerbation events after being evaluated under international standards. They were classified as severe and very severe patients on the basis of their FEV1 values of 26%. Twenty nine patients presented co-morbidities. As a consequence of the NPPV treatment, the pH values increased between the first and last register as well as the pCO2 dropped in the same period. The initial mean pH values were 7.25 reaching mean values of 7.33 at 2 hours and 7.39 at the discharge; the corresponding pCO2 mean values were 83.8 mmHg, 67.8 mmHg and 54.2 mmHg. Thirty five patients out of 39 were discharged after a mean hospitalization length of 13.6 days. Four patients died. Apropriate training of health care staff in general facilities could allow the implementation of NPPV in addition to usual medical care to treat exacerbation of COPD. High morbidity situations could arise during hospitalization, so invasive ventilation must be necessary.(AU)