Registros de enfermedades respiratorias en España: fundamentos y organización / Respiratory disease registries in Spain: fundamentals and organization

En el presente trabajo se describen las características generales, objetivos y aspectos organizativos de losregistros de enfermedades respiratorias existentes en España con el objetivo de dar a conocer su actividade incrementar su difusión.Se recoge información sobre los siguientes registros: Registro Español de Pacientes con Déficit de Alfa-1antitripsina, Registro Español de Bronquiectasias, Registro Internacional de Enfermedad Tromboembólica,Registro Español de Enfermedades de Origen Laboral, Registro Español de Hipertensión ArterialPulmonar, Registro de Mesotilioma Pleural, Registro Español de Tuberculosis y Estudio multicéntricoEspañol de Tumores Pulmonares Neuroendocrinos.Nuestro trabajo aporta información de cada uno de los citados registros.Cada registro ha recogido información clínica específica que aporta datos en situaciones reales, y completalos resultados obtenidos de los ensayos clínicos. Dicha información se ha difundido en publicacionestanto nacionales como internacionales y ha permitido la elaboración de varias normativas. Por tanto,las actividades llevadas a cabo por los profesionales vinculados a los registros han conseguido difundirel conocimiento sobre las enfermedades estudiadas propiciando el intercambio de información entregrupos(AU)

This present paper describes the general characteristics, objectives and organizational aspects of therespiratory disease registries in Spain with the aim to report their activities and increase their diffusion.The document compiles information on the following registries: the Spanish Registry of Patients withAlpha-1 Antitrypsin Deficiency, Spanish Registry of Bronchiectasis, International Registry of ThromboembolicDisease, Spanish Registry of Occupational Diseases, Spanish Registry of Pulmonary Artery Hypertension, Registry of Pleural Mesothelioma, Spanish Registry of Tuberculosis and Spanish MulticenterStudy of Neuroendocrine Pulmonary Tumors.Our paper provides information on each of the registries cited.Each registry has compiled specific clinical information providing data in real situations, and completesthe results obtained from clinical assays. Said information has been published both in national as well asinternational publications and has lead to the creation of various guidelines. Therefore, the activities of theprofessionals involved in the registries have spread the knowledge about the diseases studied, promotingthe exchange of information among workgroups(AU)

Diagnóstico del déficit de alfa 1-antitripsina: limitaciones de las pruebas de laboratorio de diagnóstico rápido / Diagnosis of Alpha-1 Antitrypsin Deficiency: Limitations of Rapid Diagnostic Laboratory Tests

El déficit hereditario de alfa 1-antitripsina ( 1-AT) predispone al desarrollo de enfisema pulmonar. Elobjetivo de este trabajo es evidenciar las limitaciones de algunos métodos de laboratorio utilizados en elestudio del déficit, cuya interpretación puede inducir a error en la detección de alelos poco frecuentes.Se describen dos casos clínicos: la paciente índice, que presentaba enfisema pulmonar con niveles de 1-AT inferiores a 12 mg/dL, catalogada erróneamente como homocigota de la variante alélica normalPI MM mediante un método de genotipificado rápido; la madre de la paciente, asintomática, con nivelesbajos (60 mg/dL), catalogada también como PI MM.La secuenciación del gen catalogó a la paciente índice como portadora del alelo nulo PI Clayton y deldeficitario PI Mmalton. La madre resultó portadora heterocigota PI Clayton/PI M.Los resultados ponen de relieve las dificultades de diagnóstico del déficit así como la necesidad deconsensuar métodos para este estudio(AU)

Hereditary alpha-1-antitrypsin ( 1-AT) deficiency predisposes to pulmonary emphysema. The objectiveof this study is to demonstrate the limitations of some laboratory methods used in the study of thedeficiency, and which may produce errors in interpretation and detection of uncommon alleles.Two clinical cases are described: the index patient, who had pulmonary emphysema with 1-AT levelsless than 12 mg/dL, was erroneously classified as a homozygote of the normal allelic variant PIMMusinga rapid genotype method; the mother of the patient, asymptomatic, with low levels (60 mg/dL), was alsoclassified as PI MM.The gene sequencing classified the index patient as a carrier of the PI Clayton null allele and PI Mmaltondeficient. The mother was a PI Clayton/PI heterozygote carrier.These results highlight the difficulties in diagnosing the deficiency, as the well as the need to reach aconsensus on methods for this study(AU)

[Respiratory disease registries in Spain: fundamentals and organization]. / Registros de enfermedades respiratorias en España: fundamentos y organización.

This present paper describes the general characteristics, objectives and organizational aspects of the respiratory disease registries in Spain with the aim to report their activities and increase their diffusion. The document compiles information on the following registries: the Spanish Registry of Patients with Alpha-1 Antitrypsin Deficiency, Spanish Registry of Bronchiectasis, International Registry of Thromboembolic Disease, Spanish Registry of Occupational Diseases, Spanish Registry of Pulmonary Artery Hypertension, Registry of Pleural Mesothelioma, Spanish Registry of Tuberculosis and Spanish Multi-center Study of Neuroendocrine Pulmonary Tumors. Our paper provides information on each of the registries cited. Each registry has compiled specific clinical information providing data in real situations, and completes the results obtained from clinical assays. Said information has been published both in national as well as international publications and has lead to the creation of various guidelines. Therefore, the activities of the professionals involved in the registries have spread the knowledge about the diseases studied, promoting the exchange of information among workgroups.

[Diagnosis of alpha-1 antitrypsin deficiency: limitations of rapid diagnostic laboratory tests]. / Diagnóstico del déficit de alfa 1-antitripsina: limitaciones de las pruebas de laboratorio de diagnóstico rápido.

Hereditary alpha-1-antitrypsin (α1-AT) deficiency predisposes to pulmonary emphysema. The objective of this study is to demonstrate the limitations of some laboratory methods used in the study of the deficiency, and which may produce errors in interpretation and detection of uncommon alleles. Two clinical cases are described: the index patient, who had pulmonary emphysema with α1-AT levels less than 12 mg/dL, was erroneously classified as a homozygote of the normal allelic variant PI MM using a rapid genotype method; the mother of the patient, asymptomatic, with low levels (60 mg/dL), was also classified as PI MM. The gene sequencing classified the index patient as a carrier of the PI Clayton null allele and PI Mmalton deficient. The mother was a PI Clayton/PI heterozygote carrier. These results highlight the difficulties in diagnosing the deficiency, as the well as the need to reach a consensus on methods for this study.

[Pharmacokinetics of alpha1-antitrypsin replacement therapy in severe congenital emphysema]. / Farmacocinética de la alfa-1-antitripsina utilizada en el tratamiento sustitutivo del enfisema congénito grave.

OBJECTIVE: Alpha1-antitrypsin (AAT) deficiency is a codominant autosomal genetic disorder that predisposes a patient to chronic obstructive pulmonary disease and emphysema. Specific treatment is systemic, consisting of intravenous infusion of AAT. The protocol currently recommended by the Spanish Registry is infusion of 180 mg/kg every 21 days. The objective of this study was to assess the pharmacokinetic behavior of AAT and estimate the level of protection, defined as the percentage of time that the AAT plasma concentration was above the assumed protective threshold of 50 mg/dL with the usual protocol and with other alternative ones. MATERIAL AND METHODS: Plasma concentrations at 4 times were analyzed for 9 patients to profile the pharmacokinetics of AAT. The data were fitted to a single compartment open model with the WinNonlin software package. The duration of protection was estimated by simulating the evolution of AAT plasma activity over time according to the model constructed based on data recorded in the study. RESULTS: Five men and 4 women (mean weight, 69 kg; range, 59-84 kg) were given a mean AAT dose of 12.06 g (range, 11-15 g). The mean (SD) volume infused was 516.67 (88.17) mL. The half-life of AAT was 8.7 days and the volume of distribution was 127.6 mL/kg. The currently recommended treatment protocol (180 mg/kg every 21 days) gave a level of protection of 67% (considering 60 mg/dL to be protective threshold) or 76% (for a threshold of 50 mg/dL). Protection values for the alternative protocol of 120 mg/kg every 14 days were 82% and 100%, respectively. For the alternative protocol of 60 mg/kg every 7 days, protection was 100% for both thresholds. CONCLUSIONS: Profiling the pharmacokinetic behavior of AAT has enabled the coverage time to be assessed for several treatment protocols. The regimen of 120 mg/kg every 14 days had the most appropriate profile.

Farmacocinética de la alfa-1-antitripsina utilizada en el tratamiento sustitutivo del enfisema congénito grave / Pharmacokinetics of alpha1-antitrypsin replacement therapy in severe congenital emphysema

Objetivo: El déficit de alfa-1-antitripsina (AAT) es una enfermedad genética autosómica codominante, que predispone a enfermedad pulmonar obstructiva crónica y enfisema. El tratamiento específico consiste en la administración intravenosa sistemática de AAT. La pauta de tratamiento actual recomendada por el Registro Español es de 180 mg/kg cada 21 días. El objetivo de este trabajo ha sido evaluar el comportamiento farmacocinético de la AAT y estimar el grado de cobertura, definido como el porcentaje de tiempo que la concentración plasmática de AAT se sitúa en valores superiores a 50 mg/dl, valor considerado como protector, de la pauta de tratamiento habitual y otras pautas alternativas. Material y métodos: El análisis farmacocinético de la AAT se realizó mediante el ajuste de 4 pares de valores concentración/tiempo, de 9 pacientes, a un modelo farmacocinético monocompartimental abierto empleando el paquete informático Win-Nonlin. La estimación del tiempo de cobertura se efectuó mediante la simulación de la evolución de la actividad plasmática de la AAT, en función del tiempo, según el modelo propuesto y los valores de los parámetros obtenidos en el estudio. Resultados: Los pacientes presentaban las características demográficas siguientes: 5 varones y 4 mujeres, peso medio de 69 kg (intervalo, 59-84 kg) y dosis media de AAT por infusión de 12,06 g (intervalo, 11-15 g). El volumen medio (± desviación estándar) de infusión fue de 516,67 ± 88,17 ml. La vida media de la AAT fue de 8,7 días, y el volumen de distribución de 127,6 ml/kg. La pauta de tratamiento actual (180 mg/kg cada 21 días) presentó un porcentaje de cobertura del 67% (considerando que 60 mg/dl es el valor protector) o del 76% (para 50 mg/dl), y los porcentajes para la pauta alternativa de 120 mg/kg cada 14 días fueron del 82 y el 100%, respectivamente. Para 60 mg/kg cada 7 días fue del 100% en ambos casos. Conclusiones: La caracterización del comportamiento farmacocinético de la AAT ha permitido evaluar el tiempo de cobertura de las diversas pautas de tratamiento y establecer como más adecuada la de 120 mg/kg cada 14 días

Objective: alpha1-antitrypsin (AAT) deficiency is a codominant autosomal genetic disorder that predisposes a patient to chronic obstructive pulmonary disease and emphysema. Specific treatment is systemic, consisting of intravenous infusion of AAT. The protocol currently recommended by the Spanish Registry is infusion of 180 mg/kg every 21 days. The objective of this study was to assess the pharmacokinetic behavior of AAT and estimate the level of protection, defined as the percentage of time that the AAT plasma concentration was above the assumed protective threshold of 50 mg/dL with the usual protocol and with other alternative ones. Material and methods: Plasma concentrations at 4 times were analyzed for 9 patients to profile the pharmacokinetics of AAT. The data were fitted to a single compartment open model with the WinNonlin software package. The duration of protection was estimated by simulating the evolution of AAT plasma activity over time according to the model constructed based on data recorded in the study. Results: Five men and 4 women (mean weight, 69 kg; range, 59-84 kg) were given a mean AAT dose of 12.06 g (range, 11-15 g). The mean (SD) volume infused was 516.67 (88.17) mL. The half-life of AAT was 8.7 days and the volume of distribution was 127.6 mL/kg. The currently recommended treatment protocol (180 mg/kg every 21 days) gave a level of protection of 67% (considering 60 mg/dL to be protective threshold) or 76% (for a threshold of 50 mg/dL). Protection values for the alternative protocol of 120 mg/kg every 14 days were 82% and 100%, respectively. For the alternative protocol of 60 mg/kg every 7 days, protection was 100% for both thresholds. Conclusions: Profiling the pharmacokinetic behavior of AAT has enabled the coverage time to be assessed for several treatment protocols. The regimen of 120 mg/kg every 14 days had the most appropriate profile