[Alpha-1 antitrypsin deficiency and spontaneous pneumothorax. Just a coincidence?] / Deficiencia de alfa-1 antitripsina y neumotórax espontáneo ¿solo una coincidencia?

Alpha-1 antitrypsin (AAT) deficiency is one of the most common inherited disorders with a higher incidence in patients with chronic obstructive pulmonary disease (COPD). Its prevalence in patients with spontaneous pneumothorax is unknown. The objective was to estimate the prevalence of AAT deficiency in patients with spontaneous pneumothorax. This was a prospective cross-sectional study, in patients with spontaneous pneumothorax, where those with secondary pneumothorax were excluded. Quantification of serum AAT by nephelometry and subsequent rapid genotyping (real time PCR) was performed, in order to detect the most prevalent deficiency alleles (Z and S) in those subjects with serum AAT concentrations = 120 mg/dl. Fifty-eight patients with primary spontaneous pneumothorax were included. The average age was 34 ± 13 years with male predominance (72%) and high prevalence of current and past smoking (60%). Twenty six percent of them (95% CI: 15-39) presented AAT serum concentrations = 120mg/dl. We found 7 deficiency variants (12%; IC 95%: 5-23%). One patient presented a severe Pi•ZZ form (1.7%), 3 were heterozygotes Z (5.2%) and 3 heterozygotes S (5.2%). The prevalence of AAT deficient variants was high in patients with spontaneous pneumothorax.

La deficiencia de alfa-1 antitripsina (AAT) es uno de los trastornos hereditarios más frecuentes y con mayor incidencia en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Se desconoce su prevalencia en aquellos con neumotórax espontáneo. El objetivo fue estimar la prevalencia de deficiencia de AAT en sujetos con neumotórax espontáneo. El estudio fue prospectivo y de corte transversal en pacientes con neumotórax espontáneo primario. Se excluyeron aquellos con neumotórax secundario. Se realizó cuantificación de AAT en suero por nefelometría y posterior genotipificación rápida (PCR en tiempo real) para detectar los alelos de deficiencia más prevalentes (Z y S) en aquellos con concentraciones séricas = 120 mg/dl. Se incluyeron 58 pacientes con neumotórax espontáneo primario. La edad promedio fue de 34 ± 13 años con predominio de sexo masculino (72%) y alta prevalencia de tabaquismo actual y pasado (60%). Del total, el 26% (IC95%: 15-39) presentó concentraciones de AAT = 120mg/dl. Encontramos 7 formas deficitarias (12%; IC 95%: 5-23%). Un paciente presentó una forma grave Pi•ZZ (1.7%), 3 fueron heterocigotos Z (5.2%) y 3 heterocigotos S (5.2%). La prevalencia de variantes deficitarias de AAT fue alta en este grupo con neumotórax espontáneo.

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

Deficiencia de alfa-1 antitripsina y neumotórax espontáneo. ¿Solo una coincidencia? / Alpha-1 antitrypsin deficiency and spontaneous pneumothorax. Just a coincidence?

Resumen La deficiencia de alfa-1 antitripsina (AAT) es uno de los trastornos hereditarios más frecuentes y con mayor incidencia en pacientes con enfermedad pulmonar obstructiva crónica (EPOC). Se desconoce su prevalencia en aquellos con neumotórax espontáneo. El objetivo fue estimar la prevalencia de deficiencia de AAT en sujetos con neumotórax espontáneo. El estudio fue prospectivo y de corte transversal en pacientes con neumotórax espontáneo primario. Se excluyeron aquellos con neumotórax secundario. Se realizó cuantificación de AAT en suero por nefelometría y posterior genotipificación rápida (PCR en tiempo real) para detectar los alelos de deficiencia más prevalentes (Z y S) en aquellos con concentraciones séricas ≤ 120 mg/dl. Se incluyeron 58 pacientes con neumotórax espontáneo primario. La edad promedio fue de 34 ± 13 años con predominio de sexo masculino (72%) y alta prevalencia de tabaquismo actual y pasado (60%). Del total, el 26% (IC95%: 15-39) presentó concentraciones de AAT ≤ 120mg/dl. Encontramos 7 formas deficitarias (12%; IC 95%: 5-23%). Un paciente presentó una forma grave Pi*ZZ (1.7%), 3 fueron heterocigotos Z (5.2%) y 3 heterocigotos S (5.2%). La prevalencia de variantes deficitarias de AAT fue alta en este grupo con neumotórax espontáneo.

Abstract Alpha-1 antitrypsin (AAT) deficiency is one of the most common inherited disorders with a higher incidence in patients with chronic obstructive pulmonary disease (COPD). Its prevalence in patients with spontaneous pneumothorax is unknown. The objective was to estimate the prevalence of AAT deficiency in patients with spontaneous pneumothorax. This was a prospective cross-sectional study, in patients with spontaneous pneumothorax, where those with secondary pneumothorax were excluded. Quantification of serum AAT by nephelometry and subsequent rapid genotyping (real time PCR) was performed, in order to detect the most prevalent deficiency alleles (Z and S) in those subjects with serum AAT concentrations ≤ 120 mg/dl. Fifty-eight patients with primary spontaneous pneumothorax were included. The average age was 34 ± 13 years with male predominance (72%) and high prevalence of current and past smoking (60%). Twenty six percent of them (95% CI: 15-39) presented AAT serum concentrations ≤ 120mg/dl. We found 7 deficiency variants (12%; IC 95%: 5-23%). One patient presented a severe Pi*ZZ form (1.7%), 3 were heterozygotes Z (5.2%) and 3 heterozygotes S (5.2%). The prevalence of AAT deficient variants was high in patients with spontaneous pneumothorax.

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.

Secondary Response to Chronic Respiratory Acidosis in Humans: A Prospective Study.

INTRODUCTION: The magnitude of the secondary response to chronic respiratory acidosis, that is, change in plasma bicarbonate concentration ([HCO3-]) per mm Hg change in arterial carbon dioxide tension (PaCO2), remains uncertain. Retrospective observations yielded Δ[HCO3-]/ΔPaCO2 slopes of 0.35 to 0.51 mEq/l per mm Hg, but all studies have methodologic flaws. METHODS: We studied prospectively 28 stable outpatients with steady-state chronic hypercapnia. Patients did not have other disorders and were not taking medications that could affect acid-base status. We obtained 2 measurements of arterial blood gases and plasma chemistries within a 10-day period. RESULTS: Steady-state PaCO2 ranged from 44.2 to 68.8 mm Hg. For the entire cohort, mean (± SD) steady-state plasma acid-base values were as follows: PaCO2, 52.8 ± 6.0 mm Hg; [HCO3-], 29.9 ± 3.0 mEq/l, and pH, 7.37 ± 0.02. Least-squares regression for steady-state [HCO3-] versus PaCO2 had a slope of 0.476 mEq/l per mm Hg (95% CI = 0.414-0.538, P < 0.01; r = 0.95) and that for steady-state pH versus PaCO2 had a slope of -0.0012 units per mm Hg (95% CI = -0.0021 to -0.0003, P = 0.01; r = -0.47). These data allowed estimation of the 95% prediction intervals for plasma [HCO3-] and pH at different levels of PaCO2 applicable to patients with steady-state chronic hypercapnia. CONCLUSION: In steady-state chronic hypercapnia up to 70 mm Hg, the Δ[HCO3-]/ΔPaCO2 slope equaled 0.48 mEq/l per mm Hg, sufficient to maintain systemic acidity between the mid-normal range and mild acidemia. The estimated 95% prediction intervals enable differentiation between simple chronic respiratory acidosis and hypercapnia coexisting with additional acid-base disorders.

Evaluación del uso de corticoides inhalados en altas dosis para el tratamiento de crisis asmática / Evaluation of the Use of High-dose Inhaled Corticosteroids for the Treatment of Acute Asthma

Introducción: El asma es una enfermedad heterogénea caracterizada por la inflamación crónica de la vía aérea. Se caracteriza por síntomas respiratorios como sibilancias, disnea, opresión en el pecho, tos que varía en el tiempo y en la intensidad, además de presentar limitación variable al flujo aéreo. Afecta del 1 al 18% de la población mundial. Existe evidencia que sugiere que los corticoides inhalados pueden mostrar efectos terapéuticos tempranos (< 3 h). Esta rápida respuesta se encontraría vinculada a un efecto tópico (vasoconstricción de la mucosa de la vía aérea), debido a la potenciación del efecto adrenérgico por modificación de los receptores post-sinápticos. Materiales y métodos: Se realizó un estudio prospectivo, aleatorizado, analítico, longitudinal de cohorte y experimental, en pacientes con crisis de asma atendidos en la guardia externa del Hospital de Rehabilitación Respiratoria María Ferrer. Resultados: Se evaluó a un total de 71 pacientes en un período de 10 meses, todos ingresaron por el servicio de guardia del Hospital de Rehabilitación Respiratoria María Ferrer y accedieron a participar del protocolo firmando un consentimiento informado. Ambos grupos presentaron un 63% de respuesta significativa (FEV1 > 60%) a los 30 minutos de iniciado el tratamiento (p: 0.72). Al fnal del protocolo (180 minutos), el grupo control (salbutamol + bromuro de ipratropio) presentó 3 pacientes que no lograron el objetivo del FEV1 > 60% a comparación de 2 pacientes en el grupo tratado con corticoides inhalados a altas dosis (P: 0.97). Conclusión: Actualmente el uso de corticoides inhalados a altas dosis en crisis de asma es una opción terapéutica para pacientes con crisis moderadas a severas. Nuestro estudio no obtuvo valores significativos que apoyen el uso de esta medicación para reducir la incidencia de internaciones o mejorar significativamente la función pulmonar.

Introduction: Asthma is a heterogeneous disease characterized by chronic inflammation of the airways. Its more common respiratory symptoms such as wheezing, breathlessness, chest tightness and cough vary in time and intensity, in addition to displaying variable airflow limitation. Asthma affects 1 to 18% of the world population. Evidence suggests that inhaled corticosteroids may show early therapeutic effects (<3 hours). This quick response would be linked to a local effect (vessel constriction of the airway mucosa) due to the potentiation of the adrenergic effect that modifies the postsynaptic receptors. Materials and methods: A prospective, randomized, analytical and experimental longitudinal cohort study in patients with acute asthma treated at the emergency services of the Respiratory Rehabilitation Hospital Maria Ferrer, Buenos Aires. Results: A total of 71 patients were evaluated over a period of 10 months who had agreed to participate in the study by signing an informed consent. Both the study and the control groups had a 63% significant response (FEV1> 60%) within 30 minutes of starting treatment (p = 0.72). At the end of the observation (180 minutes), three patients of the control group (Salbutamol + ipratropium bromide) did not achieve the objective of FEV1> 60% compared to 2 patients in the study group treated with high-dose inhaled corticosteroids (P group: 0.97). Conclusion: Currently the use of high-dose inhaled corticosteroids in asthma attack is a therapeutic option for patients with moderate to severe crisis. The results of our study do not provide significant evidence in support of the use of this medication to reduce the incidence of hospitalizations or improve the lung function.

Recomendaciones prácticas para el manejo de la crisis asmática en pacientes adultos / Practical Recommendations for the Management of Acute Asthma in Adult Patients

Las exacerbaciones de asma pueden ser graves y ponen en riesgo la vida de los pacientes. En estos casos es fundamental reconocer signos y síntomas de riesgo, incluyendo la medición de la obstrucción al flujo aéreo y la oximetría de pulso, con la finalidad de objetivar la gravedad de la crisis. La administración adecuada del tratamiento incluyendo broncodilatadores, corticoesteroides y oxigenoterapia permite revertir la obstrucción bronquial y preservar la vida del paciente. A pesar de estas premisas básicas en el manejo de la crisis asmática, en nuestro medio se ha detectado recurrentemente una atención defciente de estos eventos. El contar con recomendaciones de fácil implementación, adecuadas a las necesidades locales y desarrolladas por médicos especialistas en medicina respiratoria podría mejorar la calidad de atención de estos pacientes. Con este objetivo se realizó una revisión bibliográfica clasificando la información según el grado de evidencia. Los resultados fueron evaluados por un panel de expertos y se desarrolló un algoritmo de manejo del asma aguda. El algoritmo propone una evaluación inicial en base a signos de severidad, datos de medición del flujo aéreo (FEV1 y/o FPE) y oximetría de pulso que permitirán clasificar las exacerbaciones según su grado de severidad e indicar detalladamente los pasos terapéuticos a seguir en cada caso, como así también los criterios de internación y alta. El uso de estas recomendaciones permitirá una mejor distribución de recursos y optimización del tratamiento de los pacientes atendidos por exacerbaciones de asma.

Asthma exacerbations can be severe and life threatening. In order to assess in a correct and objective way the severity of the exacerbation, it is essential to recognize risk signs and symptoms, including the measurement of airflow obstruction and pulse oximetry. Proper treatment including bronchodilators, corticosteroids, and oxygen can reverse bronchial obstruction and preserve patient's life. Despite these basic facts, inappropriate care in the management of acute asthma events is frequent in Argentina. Recommendations developed by specialists in respiratory medicine, which are easy to implement and adapted to local needs, could improve the quality of care of these patients. In order to accomplish these goals, an exhaustive review of the literature was conducted and the information was classified according to the degree of evidence. The results were evaluated by a panel of experts and an algorithm for the management of acute asthma was designed. This algorithm proposes an initial assessment based on asthma severity including measurement of airflow obstruction (FEV1 and/or PF) and pulse oximetry. Thus, it allows classifying exacerbations by degree of severity, leading to appropriate sequential therapeutic options as well as criteria for admission and discharge. The use of these recommendations is intended to allow a correct management of asthma exacerbations in Argentina and an optimized use of medical resources.

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.

Timoma y miastenia gravis: algunas reflexiones / Thymoma and myasthenia gravis: some reflections

La miastenia gravis es un desorden autoinmune cuyo espectro de síntomas abarca desde la debilidad ocular hasta la depresión respiratoria. Por tanto, debe tratarse como tal asociando corticoides e inmunosupresores, de ser necesario, a los fines de obtener estabilidad clínica al momento del procedimiento quirúrgico. Ello es independiente de la presencia o no de un timoma. La paciente presentaba síntomas bulbares (afectación de músculos orofaríngeos y fonatorios), perteneciendo al menos a un estadío IIb de la clasificación Clínica de Osserman, lo que implicaba que tal vez las condiciones clínicas en las cuales fue llevada a cirugía no fueron las más adecuadas, y pudieron motivar las complicaciones posteriores

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)

Acid-base patterns in acute severe asthma.

BACKGROUND AND OBJECTIVES: Acid-base status in acute severe asthma (ASA) remains undefined; some studies report complete absence of metabolic acidosis, whereas others describe it as present in one fourth of patients or more. Conclusion discrepancies would therefore appear to derive from differences in assessment methodology. Only a systematic approach centering on patient clinical findings can correctly establish true acid-base disorder prevalence levels. METHODS: This study examines acid-base patterns in ASA (314 patients), taking into account both natural history of disease and treatment, in patients free of other diseases altering acid-base status. Data were collected from patients admitted for ASA without prior history of chronic bronchitis, emphysema, kidney or liver disease, heart failure, uncontrolled diabetes mellitus or gastrointestinal illness. Informed consent was obtained for all patients, after study protocol approval by the Institutional Review Board. RESULTS: Arterial blood gases, plasma electrolytes, lactate levels, and FEV(1) were measured on arrival. Severe airway obstruction was found with FEV(1) values of 25.6 ± 10.0%, substantial hypoxemia (PaO(2) 66.1 ± 11.9 mmHg) and increased A-a O(2) gradient (39.3 ± 12.3 mmHg) breathing room air. While respiratory alkalosis occurred in patients with better preservation of FEV1, respiratory acidosis was observed with more severe airway obstruction, as was increased lactate in the majority of patients, independent of PaO(2) and PaCO(2) levels. CONCLUSIONS: Predominant acid-base patterns observed in ASA in this patient population included primary hypocapnia, or less frequently, primary hypercapnia. Lactic acidosis occurred in 11% of patients and presented consistently as a mixed acid-base disorder. These findings suggest lactic acidosis results from the combined effects of both ASA and medication-related sympathetic effects.

A rare case of respiratory disorders associated with two autosomal recessive diseases and male infertility.

The study of nasal ciliary beat frequency (CBF) and ultrastructure may contribute to the understanding of pathognomonic cases of male infertility associated with defects in sperm motility. This study was designed to report a particular case of male infertility, characterized by the association of two respiratory autosomal recessive genetic diseases (alpha-1-antitrypsin deficiency [AAT-D] and primary ciliary dyskinesia [PCD]). A 39-year-old patient with complete sperm immotility, AAT-D, and bronchiectasis was studied in the Laboratory of Male Fertility, the Department of Urology, the Respiratory Center of a Pediatric Hospital, and in the Department of Clinical Medicine of a Rehabilitation Respiratory Hospital. Family history, physical examination, hormonal analysis, microbial assays, semen analysis, nasal ciliary function, and structure study by digital high-speed video photography and transmission electron microscopy are described. A noninvasive nasal biopsy to retrieve ciliated epithelium lining the inferior surface of the inferior nasal turbinates was performed and CBF was determined. Beat pattern was slightly curved and rigid, not wide, and metacronic in all the observed fields analyzed. CBF was 8.2 Hz in average (reference value, 10-15 Hz) Ultrastructural assay revealed absence of the inner dynein arms in 97% of the cilia observed. The final infertility accurate diagnosis was achieved by the study of nasal CBF and ultrastructure contributing to the patient health management and genetic counseling while deciding fatherhood. Beyond this particular case, the present report may open a new field of studies in male infertility, mainly in cases of asthenozoospermia.

Factores de pronóstico y resultados a largo plazo de timomas tratados quirúrgicamente en una cohorte de pacientes argentinos / Prognostic factors and long-term results of surgically treated thymoma in a cohort of patients Argentine

Los timomas representan el tumor más frecuente del mediastino anterior. El objetivo del trabajo es presentar las características clínico patológicas de los timomas tratados quirúrgicamente desde enero de 1971 hasta diciembre del 2008 en el Hospital de Rehabilitación Respiratoria María Ferrer, e investigar los factores que afectan la supervivencia. De los 131 casos analizados, 11 fueron perdidos de seguimiento (6%); de los restantes 120, 26 se hallaban fallecidos al final del estudio (21.7%). Se analizaron las siguientes variables: edad, sexo, síntomas de miastenia gravis al momento del diagnóstico, estadificación de Masaoka(1994) del tumor original, clasificación histológica de la OMS (1999), radioterapia postoperatoria y evolución clínica de la miastenia gravis según la clasificación modificada de Osserman. Fueron analizados 66 hombres (54%) y 56 mujeres (46%), con una mediana de edad de 48 años (rango13-78); 78 presentaban miastenia gravis al momento del diagnóstico (64%), y el 97% de ellos persistían sintomáticos luego del tratamiento quirúrgico. En el análisis univariado, la presencia de miastenia gravis al momento del diagnóstico (HR 0.527, IC 95% 0.243 - 1.141, p = 0.10), la evolución clínica de la enfermedad (HR 18.81, IC 95% 4.070 - 86.886,p = 0.000) y el estadio de Masaoka (HR 2.044, IC 95% 0.934 - 4.474, p = 0.074) se asociaron significativamente con la frecuencia de la muerte en pacientes con timoma. En el análisis multivariado, ese valor resultó ser casi 7 veces mayor en timomas invasores que en los estadios I y II (HR 7.272, IC 95% 2.19 - 24.11, p = 0.001), mientras que la radioterapia adyuvante disminuyó en un 79% este riesgo en nuestra población (HR 0.214 IC 95% 0.0648 - 0.7085, p= 0.12)...

Thymomas are neoplasias originating from epithelial cellsof the thymus. The aim is to present a serie of surgicallytreated thymomas at the Hospital de Rehabilitación Respi -ratoria María Ferrer from January 1971 to December 2008and to determine which factors affected the survival ofthese patients during the follow-up time. All patients withdiagnostic of thymoma surgically treated were included.A total of 131 cases were analized, 11 of which were lostto follow-up (6%); of the remaining 120, 26 were dead atthe end of the study (21.7%). The following variables wereanalyzed: age, gender, symptoms of myasthenia gravis atthe time of diagnosis, staging of Masaoka (1994) of theoriginal tumor, the 1999 WHO classification, postoperativeradiotherapy treatment and clinical course of myastheniagravis defined by the modified Osserman classification.Out of the 120 patients studied, 66 were men (54%) and 56female (46%), with a median age of 48 years old (range 13-78); 78/120 had myasthenia gravis at the time of diagnosis(64%), and 97% of them had persistent symptoms aftersurgical treatment. In univariate analysis, symptoms ofmyasthenia gravis at the time of diagnosis (HR 0.527, 95%CI 0.243 - 1.141, p = 0.10), clinical course of myastheniaaccording to the Osserman classification (HR 18.81, CI95% 4.070 - 86.886, p = 0.000) and staging of Masaoka(HR 2.044, 95% CI 0.934-4.474, p = 0.074) showed a signi -ficant association with the frequency of death in patientswith thymoma. In multivariate analysis, the risk of deathin patients with invasive thymomas proved to be almost7 times higher than in stages I and II (HR 7.272, 95% CI2.19 - 24.11, p = 0.001), whereas the postoperative adjuvanttherapy decreased 79% this risk in our population (HR0.214, 95% CI 0.0648 - 0.7085, p = 0.012)...

Infecciones y otros problemas de salud en usuarios de pasta base de cocaina en un centro asistencial de Buenos Aires, Argentina / Infections and other health problems among coca paste users at a drug treatment center in Buenos Aires, Argentina

INTRODUCCIÓN: la pasta base de cocaína (PBC) es una forma fumable de cocaína de creciente utilización entre los jóvenes. OBJETIVO: describir el patrón de consumo de drogas, las seroprevalencias de VIH, hepatitis B (VHB), hepatitis C (VHC), sífilis y otrosproblemas de salud en usuarios de PBC en un centro asistencial de Argentina. MÉTODO: se incluyeron voluntarios mayores de 18 años, asistidos en el Centro Nacional de Reeducación Social (CENARESO)en el período 2006-2007, que consumieron PBC en los 6 meses anteriores a la entrevista y que nunca utilizaron drogas inyectables. Se aplicó un cuestionario estructurado, se tomó una muestra de sangre para serología de VIH, VHB, VHC y sífilis, y se analizó una sub-muestra de radiografías de tórax. RESULTADOS: más de la mitad de los 146 voluntarios manifestó haber fumado PBC varias veces por semana. Los participantes eran también consumidores frecuentes de cocaína en polvo (64%), cannabis (80,8%) y tranquilizantes (44,5%). Los principales problemas de salud auto-percibidos como consecuencia del consumo de PBC fueron las lesiones orales y la pérdida de peso. El 4,3% de los voluntarios resultó VIH-positivo. Las prevalencias de infección por sífilis, VHB y VHC fueron 2,7%, 5,5%, y 5,5%, respectivamente. El 16% estaba coinfectado con uno o más de los agentes estudiados. DISCUSIÓN: la prevalencia de infecciones, unida a otros problemas de salud de los usuarios de PBC, indica la necesidad de nuevas investigaciones a fin de diseñar intervenciones preventivas y terapéuticas apropiadas

INTRODUCTION: cocaine paste is a smokable form of cocaine increasingly used among young people. OBJECTIVE:to describe patterns of drugs, seroprevalences of HIV, hepatitis B (HBV), hepatitis C (HCV), syphilis and other health problems among coca paste users assisted at a drug treatment center in Argentina. METHOD: volunteers, eighteen-year-old and olderassisted at the National Center for Social Re-education (CENARESO)during 2006-2007, who had consumed coca paste over the past 6 months previous to the interview and had never injected drugs, were selected. A structured questionnaire wasused and blood was drawn to test HIV, HBV, HCV and syphilis. A sub-sample of thorax X-rays was analyzed. RESULTS: morethan half of the 146 volunteers had smoked coca paste severaltimes a week. The use of other drugs was frequently associated: sniffed cocaine 64%, cannabis 80,8%, and tranquilizers 44,5. Oral lesions and lost of weight were referred as health problems stemming from coca paste use. Out of the 146 volunteers, 4.3%resulted HIV-positive. Prevalences of infection for syphilis, HBV, and HCV were 2,7%, 5,5% and 5,5%, respectively. 16% wasco-infected with one or more infectious agents. DISCUSSION: the prevalence of infections detected, along with other clinical problems found among this coca paste users, show the need for further research, in order to design proper preventive and therapeutic interventions

Decline of outpatient asthma management in Argentina.

BACKGROUND AND OBJECTIVES: To assess management of adult patients admitted with acute asthma and compare the results obtained with a similar study 5 years earlier. METHODS: A cross-sectional survey of 211 consecutive patients admitted to hospital during a 12-month period was conducted. Patients were surveyed using a validated management questionnaire and the results compared with those of the previous survey. RESULTS: There were 211 patients in the present survey and patient demographics were similar in both populations studied. Comparison of the previous to the current survey showed significant differences in predicted FEV(1)% at admission (30.2 +/- 10.7 vs 23.9 +/- 8.9, respectively, P < 0.001), and the average number of hospital admissions in the year prior to the survey (0.7 +/- 1.2 vs 1.3 +/- 0.7, P < 0.0001). In the present survey, more patients changed their medication after acute exacerbation and more received an action plan. Compared with the previous survey, there were no significant differences between the mean number of emergency department visits, need for mechanical ventilation, number of patients prescribed inhaled corticosteroids and other related variables. CONCLUSION: Compared with the previous study the severity of asthma at the time of admission was worse. Some of the recommended international asthma management programmes appear to have been followed.

[Argentine consensus of non-invasive ventilation]. / Consenso argentino de ventilación no invasiva.

Non-invasive ventilation (NIV) is nowadays increasingly used. The significant decrease in tracheal intubation related complications makes it particularly attractive in patients with moderately acute respiratory failure (ARF) who still have some degree of respiratory autonomy. It has also been used to support patients with chronic respiratory failure. However, final outcomes are variable according to the conditions which determined its application. This Consensus was performed in order to review the evidence supporting the use of positive pressure NIV. The patho-physiological background of NIV and the equipment required technology are described. Available evidence clearly suggests benefits of NIV in acute exacerbation of chronic obstructive pulmonary disease (COPD) and in cardiogenic pulmonary edema (Recommendation A). When considering ARF in the setting of acute respiratory distress syndrome results are uncertain, unless dealing with immunosupressed patients (Recommendation B). Positive results are also shown in weaning of mechanical ventilation (MV), particularly regarding acute exacerbation of COPD patients (Recommendation A). An improved quality of life in chronic respiratory failure and a longer survival in restrictive disorders has also been shown (Recommendation B) while its benefit in stable COPD patients is still controversial (Recommendation C). NIV should be performed according to pre-established standards. A revision of NIV related complications is performed and the cost-benefit comparison with invasive MV is also considered.

Adequacy of outpatient management of asthma patients admitted to a state hospital in Argentina.

OBJECTIVE: The aim of this study was to assess chronic outpatient management of adult patients admitted with asthma. METHODOLOGY: A cross-sectional survey was conducted of 98 consecutive asthma admissions to a specialized pulmonary State Hospital in Buenos Aires, Argentina, over a 12-month period. Patients were surveyed, within 48 h of admission, with a previously validated questionnaire which deals with chronic outpatient management and measures taken by patients or physicians to treat symptoms during asthma exacerbations. RESULTS: FEV1% predicted was 30.2 +/- 10.7. Mean admission rate and emergency department (ED) visits in the previous year were 0.7 +/- 1.2 and 4.6 +/- 5.1, respectively. A total of 96, 65 and 9% of the patients had been treated previously in the ED, admitted to hospital or mechanically ventilated, respectively. Only 62% had been prescribed inhaled corticosteroids (IC) by their physician; 38% had been prescribed nebulized beta agonists (Nbeta2) and 68% a metered dose inhaler (MDIbeta2). Inhaled beta2-agonist usage during acute exacerbations over the 24 h prior to admission was 14.4 +/- 7.4 puffs for MDIbeta2 and 8.6 +/- 5.4 occasions for Nbeta2. Only 11% of the patients were able to perform all the steps of the MDI inhalation technique correctly. An action plan had been provided by their physicians to 43% of patients, while 58% changed their medication on their own. Only three patients had a peak flow meter (PFM) prescribed. ED was used by 26% for their routine care. No health insurance coverage was available to 75.5% of the patients. CONCLUSIONS: Underuse of IC, poor MDI inhalation technique, and low prescription of an action plan was common and a PFM was seldom prescribed. During exacerbations, many patients changed their medication spontaneously and MDIbeta2 underuse was observed.

Consenso argentino de ventilación no invasiva. / [Argentine consensus of non-invasive ventilation]

Non-invasive ventilation (NIV) is nowadays increasingly used. The significant decrease in tracheal intubation related complications makes it particularly attractive in patients with moderately acute respiratory failure (ARF) who still have some degree of respiratory autonomy. It has also been used to support patients with chronic respiratory failure. However, final outcomes are variable according to the conditions which determined its application. This Consensus was performed in order to review the evidence supporting the use of positive pressure NIV. The patho-physiological background of NIV and the equipment required technology are described. Available evidence clearly suggests benefits of NIV in acute exacerbation of chronic obstructive pulmonary disease (COPD) and in cardiogenic pulmonary edema (Recommendation A). When considering ARF in the setting of acute respiratory distress syndrome results are uncertain, unless dealing with immunosupressed patients (Recommendation B). Positive results are also shown in weaning of mechanical ventilation (MV), particularly regarding acute exacerbation of COPD patients (Recommendation A). An improved quality of life in chronic respiratory failure and a longer survival in restrictive disorders has also been shown (Recommendation B) while its benefit in stable COPD patients is still controversial (Recommendation C). NIV should be performed according to pre-established standards. A revision of NIV related complications is performed and the cost-benefit comparison with invasive MV is also considered.