Techniques and Procedures
Pharmacokinetics of α1-Antitrypsin Replacement Therapy in Severe Congenital Emphysema
Rafael Vidal Plaa,
, Nuria Padullés Zamorab, Ferran Sala Piñolb, Rosendo Jardi Margaleffc, Francisco Rodríguez Friasc, José Bruno Montoro Ronsanob
Corresponding author
ravidal@vhebron.net
Correspondence: Dr. R Vidal Pla. Servicio de Neumología. Hospital Universitario Vall d'Hebron. Pg. Vall d'Hebron. 119-129. 08035 Barcelona. España
Correspondence: Dr. R Vidal Pla. Servicio de Neumología. Hospital Universitario Vall d'Hebron. Pg. Vall d'Hebron. 119-129. 08035 Barcelona. España
Read
4305
Timeswas read the article
1835
Total PDF
2470
Total HTML
Share statistics
array:23 [ "pii" => "S1579212906605831" "issn" => "15792129" "doi" => "10.1016/S1579-2129(06)60583-1" "estado" => "S300" "fechaPublicacion" => "2006-10-01" "aid" => "60583" "copyright" => "Sociedad Española de Neumología y Cirugía Torácica (SEPAR)" "copyrightAnyo" => "2006" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Arch Bronconeumol. 2006;42:553-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2252 "formatos" => array:3 [ "EPUB" => 104 "HTML" => 1512 "PDF" => 636 ] ] "itemSiguiente" => array:18 [ "pii" => "S1579212906605843" "issn" => "15792129" "doi" => "10.1016/S1579-2129(06)60584-3" "estado" => "S300" "fechaPublicacion" => "2006-10-01" "aid" => "60584" "copyright" => "Sociedad Española de Neumología y Cirugía Torácica (SEPAR)" "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Arch Bronconeumol. 2006;42:557-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 3206 "formatos" => array:3 [ "EPUB" => 84 "HTML" => 2159 "PDF" => 963 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case Report</span>" "titulo" => "Airway-Centered Interstitial Fibrosis Associated With Exposure to Fumes From Cleaning Products" "tienePdf" => "en" "tieneTextoCompleto" => 0 "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "557" "paginaFinal" => "559" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Mario Serrano, Maria Molina-Molina, José Ramírez, Marcelo Sánchez, Antoni Xaubet" "autores" => array:5 [ 0 => array:3 [ "preGrado" => "Dr." "nombre" => "Mario" "apellidos" => "Serrano" ] 1 => array:2 [ "nombre" => "Maria" "apellidos" => "Molina-Molina" ] 2 => array:2 [ "nombre" => "José" "apellidos" => "Ramírez" ] 3 => array:2 [ "nombre" => "Marcelo" "apellidos" => "Sánchez" ] 4 => array:2 [ "nombre" => "Antoni" "apellidos" => "Xaubet" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212906605843?idApp=UINPBA00003Z" "url" => "/15792129/0000004200000010/v1_201305150229/S1579212906605843/v1_201305150229/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S157921290660582X" "issn" => "15792129" "doi" => "10.1016/S1579-2129(06)60582-X" "estado" => "S300" "fechaPublicacion" => "2006-10-01" "aid" => "60582" "copyright" => "Sociedad Española de Neumología y Cirugía Torácica (SEPAR)" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Arch Bronconeumol. 2006;42:541-52" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2134 "formatos" => array:3 [ "EPUB" => 92 "HTML" => 1480 "PDF" => 562 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special Article</span>" "titulo" => "Pneumonia Awareness Year, 2004: Scientific Impact Through Publications in A<span class="elsevierStyleSmallCaps">rchivos de</span> B<span class="elsevierStyleSmallCaps">ronconeumología</span>" "tienePdf" => "en" "tieneTextoCompleto" => 0 "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "541" "paginaFinal" => "552" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Olga Rajas Naranjo, Javier Aspa Marco" "autores" => array:2 [ 0 => array:3 [ "preGrado" => "Dra." "nombre" => "Olga Rajas" "apellidos" => "Naranjo" ] 1 => array:2 [ "nombre" => "Javier Aspa" "apellidos" => "Marco" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157921290660582X?idApp=UINPBA00003Z" "url" => "/15792129/0000004200000010/v1_201305150229/S157921290660582X/v1_201305150229/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Techniques and Procedures</span>" "titulo" => "Pharmacokinetics of α<span class="elsevierStyleInf">1</span>-Antitrypsin Replacement Therapy in Severe Congenital Emphysema" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "553" "paginaFinal" => "556" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Rafael Vidal Pla, Nuria Padullés Zamora, Ferran Sala Piñol, Rosendo Jardi Margaleff, Francisco Rodríguez Frias, José Bruno Montoro Ronsano" "autores" => array:6 [ 0 => array:5 [ "preGrado" => "Dr." "nombre" => "Rafael Vidal" "apellidos" => "Pla" "email" => array:1 [ 0 => "ravidal@vhebron.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "Nuria Padullés" "apellidos" => "Zamora" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] 2 => array:3 [ "nombre" => "Ferran Sala" "apellidos" => "Piñol" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] 3 => array:3 [ "nombre" => "Rosendo Jardi" "apellidos" => "Margaleff" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff3" ] ] ] 4 => array:3 [ "nombre" => "Francisco Rodríguez" "apellidos" => "Frias" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff3" ] ] ] 5 => array:3 [ "nombre" => "José Bruno" "apellidos" => "Montoro Ronsano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Universitario Vall d'Hebron, Barcelona, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Servicio de Farmacia, Hospital Universitario Vall d'Hebron, Barcelona, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Servicio de Bioquímica, Hospital Universitario Vall d'Hebron, Barcelona, Spain" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff3" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence: Dr. R Vidal Pla. Servicio de Neumología. Hospital Universitario Vall d'Hebron. Pg. Vall d'Hebron. 119-129. 08035 Barcelona. España" ] ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2005-10-20" "fechaAceptado" => "2005-11-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec154202" "palabras" => array:5 [ 0 => "Emphysema" 1 => "α<span class="elsevierStyleInf">1</span>-antitrypsin" 2 => "Pharmacokinetics" 3 => "Duration of protection" 4 => "Replacement therapy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec154201" "palabras" => array:5 [ 0 => "Enfisema" 1 => "Alfa-1-antitripsina" 2 => "Farmacocinética" 3 => "Tiempo de cobertura" 4 => "Tratamiento sustitutivo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p class="elsevierStyleSimplePara elsevierViewall">α<span class="elsevierStyleInf">1</span>-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.</p> <span class="elsevierStyleSectionTitle">Material and Methods</span><p class="elsevierStyleSimplePara elsevierViewall">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.</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">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.</p><p class="elsevierStyleSimplePara elsevierViewall">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.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">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.</p>" ] "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p class="elsevierStyleSimplePara elsevierViewall">El déficit de alfa-1-antitripsina (AAT) es una enfermedad genética autosómica codominante, que predispone a enfermedad pulmonar obstructiva crónica y enfisema. El tratamiento especifico 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 dias. El objetivo de este trabajo ha sido evaluar el com-portamiento 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 alternatives.</p> <span class="elsevierStyleSectionTitle">Material y métodos</span><p class="elsevierStyleSimplePara elsevierViewall">El analisis farmacocinético de la AAT se realizó mediante el ajuste de 4 pares de valores concentracion/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, segun el modelo propuesto y los valores de los parámetros obtenidos en el estudio.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">Los pacientes presentaban las caracteristicas demograficas siguientes: 5 varones y 4 mujeres, peso medio de 69 kg (intervalo, 59-84 kg) y dosis media de AAT por infusion de 12,06 g (intervalo: 11-15 g). El volumen medio (± desviación estándar) de infusión fue de 516.67 ± 88.17 ml.</p><p class="elsevierStyleSimplePara elsevierViewall">La vida media de la AAT fue de 8,7 dias, y el volumen de distribución de 127,6 ml/kg. La pauta de tratamiento actual (180 mg/kg cada 21 dias) 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 dias fueron del 82 y el 100%, respectivamente. Para 60 mg/kg cada 7 dias fue del 100%, en ambos casos.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">La caracterización del comportamiento farmacocinético de la AAT ha permitido evaluar el tiempo de cobertura de las diversas pautas de tratamiento y estable-cer como más adecuada la de 120 mg/kg cada 14 dias.</p>" ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "<p class="elsevierStyleNotepara">Work financed in part by the FUCAP Almirall Prodesfarma grant, 2004.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:20 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Key current clinical issues in alpha-1-antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J Stoller" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Respir Care" "fecha" => "2003" "volumen" => "48" "paginaInicial" => "1216" "paginaFinal" => "1221" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14651762" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alpha-1-antitrypsin deficiency 6: new and emerging treatments for alpha-1-antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R Sandhaus" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2003.006551" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2000" "volumen" => "59" "paginaInicial" => "904" "paginaFinal" => "909" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15454659" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "American Thoracic Society/European Respiratory Society Statement: standards for the diagnosis and management of individuals with alpha-1-antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Anonymous" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.168.7.818" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2003" "volumen" => "168" "paginaInicial" => "818" "paginaFinal" => "900" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14522813" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alpha-1-antitrypsin deficiency 5: intravenous augmentation therapy: current understanding" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "JK Stoller" 1 => "LS Aboussouan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2003.006544" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2004" "volumen" => "59" "paginaInicial" => "708" "paginaFinal" => "712" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15282394" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Usefulness of a national registry of alpha-1-antitrypsin deficiency. The Spanish experience" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M Miravitlles" 1 => "R Vidal" 2 => "JC Barros-Tizón" 3 => "A Bustamente" 4 => "PP España" 5 => "F Casas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Respir Med" "fecha" => "1998" "volumen" => "92" "paginaInicial" => "1181" "paginaFinal" => "1187" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9926146" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular basis of alpha-1-antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M Brantly" 1 => "T Nukiwa" 2 => "RG Crystal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "1988" "volumen" => "84" "paginaInicial" => "13" "paginaFinal" => "31" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3289385" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Replacement therapy for alpha-1-antitrypsin deficiency associated with emphysema" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "MD Wewers" 1 => "MA Casolaro" 2 => "SE Sellers" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "N Engl Med" "fecha" => "1987" "volumen" => "316" "paginaInicial" => "1055" "paginaFinal" => "1062" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Replacement therapy for alpha-1-antitrypsin deficiency associated with emphysema" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "MD Wewers" 1 => "MA Casolano" 2 => "SE Sellers" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM198704233161704" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1987" "volumen" => "316" "paginaInicial" => "1055" "paginaFinal" => "1062" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3494198" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Augmentation therapy with alpha-1-antitrypsin: patterns of use and adverse events" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "JK Stoller" 1 => "R Fallat" 2 => "MD Schluchter" 3 => "RG Brian" 4 => "JT Connor" 5 => "N Gross" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2003" "volumen" => "123" "paginaInicial" => "1425" "paginaFinal" => "1434" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12740257" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biochemical efficacy and safety on monthly augmentation therapy for alpha-1-antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "RC Hubbard" 1 => "S Sellers" 2 => "D Czerski" 3 => "L Stephens" 4 => "RG Crystal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "1988" "volumen" => "260" "paginaInicial" => "1259" "paginaFinal" => "1264" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3261353" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estado actual del tratamiento sustitutivo en el enfisema congénito por déficit de alfa-1-antitripsina. Informe del Registro Nacional" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M Miravitlles" 1 => "R Vidal" 2 => "JC Barros-Tirón" 3 => "A Bustamante" 4 => "PP España" 5 => "F Casas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Bronconeumol" "fecha" => "1999" "volumen" => "35" "paginaInicial" => "446" "paginaFinal" => "454" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10596342" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Survival and FEV<span class="elsevierStyleInf">1</span> decline in individuals with severe deficiency of alpha-1-antitrypsin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "The Alpha-1-Antitrypsin Deficiency Registry Study Group" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.158.1.9712017" "Revista" => array:7 [ "tituloSerie" => "Am J Resp Crit Care Med" "fecha" => "1998" "volumen" => "158" "paginaInicial" => "49" "paginaFinal" => "59" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9655706" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673605673412" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term treatment of alpha-1-antitrypsin deficiency-related pulmonary emphysema with human alpha-1-antitrypsin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M Wencker" 1 => "N Banik" 2 => "R Buhl" 3 => "R Seidel" 4 => "N Konietzko" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "1998" "volumen" => "11" "paginaInicial" => "428" "paginaFinal" => "433" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9551749" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A randomized clinical trial of alpha-1-antitrypsin augmentation therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A Dirksen" 1 => "JH Dijkman" 2 => "F Madsen" 3 => "B Stoel" 4 => "D Hutchison" 5 => "C Ulrik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.160.5.9901055" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1999" "volumen" => "160" "paginaInicial" => "1468" "paginaFinal" => "1472" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10556107" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Augmentation therapy reduces frequency of lung infections in antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J Lieberman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2000" "volumen" => "118" "paginaInicial" => "1480" "paginaFinal" => "1485" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11083705" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Longitudinal follow-up of patients with alpha-1-antitrypsin protease inhibitor deficiency before and during therapy with IV alpha-1-protease inhibitor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M Wenchker" 1 => "B Fuhrmann" 2 => "N Banik" 3 => "N Konietzko" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2001" "volumen" => "119" "paginaInicial" => "737" "paginaFinal" => "744" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11243951" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Does alpha-1-antitrypsin therapy slow the annual decline in FEV<span class="elsevierStyleInf">1</span>, in patients with severe hereditary alpha-1-antitrypsin deficiency?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N Seersholm" 1 => "M Wencker" 2 => "N Banik" 3 => "K Viskum" 4 => "A Dirksen" 5 => "A Kok-Jensen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "1997" "volumen" => "10" "paginaInicial" => "2260" "paginaFinal" => "2263" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9387950" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pharmacokinetic study of alpha-1-antitrypsin infusion in alpha-1-antitryspin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "AF Barker" 1 => "I Iwata-Morgan" 2 => "L Oveson" 3 => "R Roussel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "1997" "volumen" => "112" "paginaInicial" => "607" "paginaFinal" => "613" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9315791" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of augmentation therapy on bronchial inflammation in alpha-1-antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "RA Stockley" 1 => "DL Bayley" 2 => "I Unsal" 3 => "LJ Dowson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.2109013" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2002" "volumen" => "165" "paginaInicial" => "1494" "paginaFinal" => "1498" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12045122" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alpha-1-antitrypsin augmentation therapy for alpha-1-antitrypsin deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "RC Hubbard" 1 => "RG Crystal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "1988" "volumen" => "84" "paginaInicial" => "52" "paginaFinal" => "62" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3289387" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15792129/0000004200000010/v1_201305150229/S1579212906605831/v1_201305150229/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/15792129/0000004200000010/v1_201305150229/S1579212906605831/v1_201305150229/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212906605831?idApp=UINPBA00003Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 3 | 7 |
| 2024 October | 28 | 24 | 52 |
| 2024 September | 24 | 24 | 48 |
| 2024 August | 48 | 57 | 105 |
| 2024 July | 21 | 24 | 45 |
| 2024 June | 30 | 27 | 57 |
| 2024 May | 29 | 28 | 57 |
| 2024 April | 21 | 33 | 54 |
| 2024 March | 18 | 15 | 33 |
| 2024 February | 21 | 19 | 40 |
| 2023 March | 2 | 3 | 5 |
| 2023 February | 14 | 16 | 30 |
| 2023 January | 20 | 28 | 48 |
| 2022 December | 21 | 32 | 53 |
| 2022 November | 16 | 28 | 44 |
| 2022 October | 21 | 26 | 47 |
| 2022 September | 19 | 28 | 47 |
| 2022 August | 57 | 39 | 96 |
| 2022 July | 52 | 38 | 90 |
| 2022 June | 71 | 22 | 93 |
| 2022 May | 22 | 32 | 54 |
| 2022 April | 27 | 27 | 54 |
| 2022 March | 21 | 33 | 54 |
| 2022 February | 20 | 24 | 44 |
| 2022 January | 13 | 29 | 42 |
| 2021 December | 14 | 47 | 61 |
| 2021 November | 22 | 51 | 73 |
| 2021 October | 17 | 50 | 67 |
| 2021 September | 16 | 55 | 71 |
| 2021 August | 12 | 28 | 40 |
| 2021 July | 12 | 24 | 36 |
| 2021 June | 17 | 39 | 56 |
| 2021 May | 11 | 23 | 34 |
| 2021 April | 33 | 58 | 91 |
| 2021 March | 31 | 22 | 53 |
| 2021 February | 12 | 13 | 25 |
| 2021 January | 10 | 11 | 21 |
| 2020 December | 6 | 12 | 18 |
| 2020 November | 5 | 9 | 14 |
| 2020 October | 9 | 11 | 20 |
| 2020 September | 7 | 4 | 11 |
| 2020 August | 10 | 13 | 23 |
| 2020 July | 14 | 18 | 32 |
| 2020 June | 6 | 3 | 9 |
| 2020 May | 22 | 16 | 38 |
| 2020 April | 17 | 16 | 33 |
| 2020 March | 4 | 12 | 16 |
| 2020 February | 18 | 18 | 36 |
| 2020 January | 15 | 16 | 31 |
| 2019 December | 8 | 16 | 24 |
| 2019 November | 19 | 9 | 28 |
| 2019 October | 8 | 8 | 16 |
| 2019 September | 12 | 10 | 22 |
| 2019 August | 27 | 10 | 37 |
| 2019 July | 32 | 15 | 47 |
| 2019 June | 5 | 4 | 9 |
| 2019 May | 11 | 11 | 22 |
| 2019 April | 9 | 17 | 26 |
| 2019 March | 11 | 17 | 28 |
| 2019 February | 7 | 7 | 14 |
| 2019 January | 6 | 8 | 14 |
| 2018 December | 9 | 13 | 22 |
| 2018 November | 8 | 13 | 21 |
| 2018 October | 21 | 20 | 41 |
| 2018 September | 9 | 7 | 16 |
| 2018 May | 4 | 0 | 4 |
| 2018 April | 4 | 6 | 10 |
| 2018 March | 8 | 6 | 14 |
| 2018 February | 4 | 8 | 12 |
| 2018 January | 3 | 7 | 10 |
| 2017 December | 6 | 8 | 14 |
| 2017 November | 3 | 3 | 6 |
| 2017 October | 1 | 5 | 6 |
| 2017 September | 4 | 7 | 11 |
| 2017 August | 7 | 12 | 19 |
| 2017 July | 3 | 5 | 8 |
| 2017 June | 8 | 12 | 20 |
| 2017 May | 4 | 5 | 9 |
| 2017 April | 1 | 4 | 5 |
| 2017 March | 1 | 5 | 6 |
| 2017 February | 0 | 1 | 1 |
| 2017 January | 3 | 0 | 3 |
| 2016 December | 14 | 5 | 19 |
| 2016 November | 15 | 12 | 27 |
| 2016 October | 20 | 11 | 31 |
| 2016 September | 12 | 3 | 15 |
| 2016 August | 14 | 2 | 16 |
| 2016 July | 11 | 3 | 14 |
| 2016 March | 2 | 0 | 2 |
| 2015 December | 2 | 0 | 2 |
| 2015 October | 53 | 14 | 67 |
| 2015 September | 39 | 9 | 48 |
| 2015 August | 32 | 16 | 48 |
| 2015 July | 42 | 8 | 50 |
| 2015 June | 30 | 8 | 38 |
| 2015 May | 40 | 9 | 49 |
| 2015 April | 33 | 4 | 37 |
| 2015 March | 28 | 10 | 38 |
| 2015 February | 27 | 7 | 34 |
| 2015 January | 21 | 6 | 27 |
| 2014 December | 29 | 6 | 35 |
| 2014 November | 29 | 5 | 34 |
| 2014 October | 52 | 9 | 61 |
| 2014 September | 32 | 11 | 43 |
| 2014 August | 34 | 12 | 46 |
| 2014 July | 33 | 10 | 43 |
| 2014 June | 59 | 14 | 73 |
| 2014 May | 36 | 9 | 45 |
| 2014 April | 44 | 5 | 49 |
| 2014 March | 52 | 13 | 65 |
| 2014 February | 38 | 9 | 47 |
| 2014 January | 26 | 7 | 33 |
| 2013 December | 37 | 9 | 46 |
| 2013 November | 31 | 8 | 39 |
| 2013 October | 29 | 12 | 41 |
| 2013 September | 35 | 7 | 42 |
| 2013 August | 41 | 16 | 57 |
| 2013 July | 44 | 15 | 59 |
| 2013 June | 31 | 7 | 38 |
| 2013 May | 33 | 8 | 41 |
| 2013 April | 34 | 6 | 40 |
| 2013 March | 10 | 3 | 13 |
Show all
