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Bronchodilator Efficacy of Combined Salmeterol and Tiotropium in Patients With Chronic Obstructive Pulmonary Disease
A. Baloira Villar
, C. Vilariño Pombo
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adolfobalo@eresmas.com
Correspondence: Dr. A. Baloira Villar. Sección de Neumología. Complexo Hospitalario de Pontevedra. Mourente. 36071 Pontevedra. España
Correspondence: Dr. A. Baloira Villar. Sección de Neumología. Complexo Hospitalario de Pontevedra. Mourente. 36071 Pontevedra. España
Sección de Neumología, Complexo Hospitalario de Pontevedra, Mourente, Pontevedra, Spain
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Barrueco, C. Jiménez Ruiz, L. Palomo, M. Torrecilla, P. Romero, J.A. Riesco" "autores" => array:6 [ 0 => array:3 [ "preGrado" => "Dr." "nombre" => "M." "apellidos" => "Barrueco" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Jiménez Ruiz" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Palomo" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Torrecilla" ] 4 => array:2 [ "nombre" => "P." "apellidos" => "Romero" ] 5 => array:2 [ "nombre" => "J.A." "apellidos" => "Riesco" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S157921290660414X?idApp=UINPBA00003Z" "url" => "/15792129/0000004100000003/v1_201305150210/S157921290660414X/v1_201305150210/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S1579212906604126" "issn" => "15792129" "doi" => "10.1016/S1579-2129(06)60412-6" "estado" => "S300" "fechaPublicacion" => "2005-03-01" "aid" => "60412" "copyright" => "Sociedad Española de Neumología y Cirugía Torácica (SEPAR)" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Arch Bronconeumol. 2005;41:125-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2213 "formatos" => array:3 [ "EPUB" => 112 "HTML" => 1464 "PDF" => 637 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Importance of Routine Mediastinal Staging in Women With Nonsmall Cell Lung Cancer" "tienePdf" => "en" "tieneTextoCompleto" => 0 "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "125" "paginaFinal" => "129" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.L. Martín de Nicolás, A. Gómez-Caro Andrés, F.J. Moradiellos Díez, V. Díaz-Hellín, O. Gigirey Castro, E. Larrú Cabrero, J.A. Pérez Antón, C. Marrón Fernández" "autores" => array:8 [ 0 => array:2 [ "nombre" => "J.L." "apellidos" => "Martín de Nicolás" ] 1 => array:3 [ "preGrado" => "Dr." "nombre" => "A." "apellidos" => "Gómez-Caro Andrés" ] 2 => array:2 [ "nombre" => "F.J." "apellidos" => "Moradiellos Díez" ] 3 => array:2 [ "nombre" => "V." "apellidos" => "Díaz-Hellín" ] 4 => array:2 [ "nombre" => "O." "apellidos" => "Gigirey Castro" ] 5 => array:2 [ "nombre" => "E." "apellidos" => "Larrú Cabrero" ] 6 => array:2 [ "nombre" => "J.A." "apellidos" => "Pérez Antón" ] 7 => array:2 [ "nombre" => "C. Marrón" "apellidos" => "Fernández" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212906604126?idApp=UINPBA00003Z" "url" => "/15792129/0000004100000003/v1_201305150210/S1579212906604126/v1_201305150210/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Articles</span>" "titulo" => "Bronchodilator Efficacy of Combined Salmeterol and Tiotropium in Patients With Chronic Obstructive Pulmonary Disease" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "130" "paginaFinal" => "134" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Baloira Villar, C. Vilariño Pombo" "autores" => array:2 [ 0 => array:5 [ "preGrado" => "Dr." "nombre" => "A." "apellidos" => "Baloira Villar" "email" => array:1 [ 0 => "adolfobalo@eresmas.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Vilariño Pombo" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Sección de Neumología, Complexo Hospitalario de Pontevedra, Mourente, Pontevedra, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence: Dr. A. Baloira Villar. Sección de Neumología. Complexo Hospitalario de Pontevedra. Mourente. 36071 Pontevedra. España" ] ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2004-03-24" "fechaAceptado" => "2004-03-31" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key Words" "identificador" => "xpalclavsec153978" "palabras" => array:4 [ 0 => "Chronic obstructive pulmonary disease (COPD)" 1 => "Salmeterol" 2 => "Tiotropium" 3 => "Spirometry" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec153977" "palabras" => array:4 [ 0 => "Enfermedad pulmonar obstructiva crónica (EPOC)" 1 => "Salmeterol" 2 => "Tiotropio" 3 => "Espirometría" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p class="elsevierStyleSimplePara elsevierViewall">Bronchodilators are still the most effective drugs for controlling the symptoms of chronic obstructive pulmonary disease (COPD). Tiotropium bromide, a long-acting anticholinergic drug, has recently been added to the therapeutic arsenal for the disease. To date, there have been no studies combining 2 long-acting bronchodilators. The aim of the present trial was to determine whether the combination of salmeterol and tiotropium improved lung function in COPD patients more than either of them alone.</p> <span class="elsevierStyleSectionTitle">Patients and methods</span><p class="elsevierStyleSimplePara elsevierViewall">Twenty-two patients (20 men) diagnosed with COPD, with a mean age of 64 years, were enrolled in this cross-over trial. Active smokers were excluded. Mean (SD) forced expiratory volume in 1 second (FEV<span class="elsevierStyleInf">1</span>) was 43% (14%) of predicted. All patients were experienced in the use of inhalers. The following 3 therapeutic combinations were randomly assigned to be administered for a 1-week period: <span class="elsevierStyleItalic">a</span>) fluticasone (500 μg/12 h), salmeterol (50 μg/12 h) and placebo; <span class="elsevierStyleItalic">b</span>) fluticasone, tiotropium (18 μg/24 h), and placebo; and <span class="elsevierStyleItalic">c</span>) fluticasone, salmeterol, and tiotropium. At the end of each period, forced spirometry was performed before inhalation of the therapeutic combination (between 8:30 AM and 9:30 AM) and 2 hours after inhalation. Throughout the week, morning peak flow rates measured immediately before inhalation were recorded, and there was a 48-hour wash-out period between each therapeutic combination.</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">All the patients completed the protocol. There were no significant differences in preinhalation or postinhalation FEV<span class="elsevierStyleInf">1</span> with salmeterol compared to tiotropium (preinhalation FEV<span class="elsevierStyleInf">1</span>, 1.17 [0.55] L compared to 1.19 [0.49] L; postinhalation FEV<span class="elsevierStyleInf">1</span>, 1.32 [0.65] L compared to 1.29 [0.61] L). In all cases postinhalation FEV<span class="elsevierStyleInf">1</span> was significantly higher than preinhalation FEV<span class="elsevierStyleInf">1</span>. The combination of fluticasone, salmeterol, and tiotropium proved superior to the other 2 combinations with respect to both preinhalation FEV1 and postinhalation FEV<span class="elsevierStyleInf">1</span> (preinhalation FEV<span class="elsevierStyleInf">1</span>, 1.32 [0.56] L, [<span class="elsevierStyleItalic">P</span> <.03 in both comparisons]; postinhalation FEV<span class="elsevierStyleInf">1</span>, 1.49 [0.68] L [<span class="elsevierStyleItalic">P</span> <.001 in both comparisons]). Peak flow rate was also significantly higher with the combination of the 2 bronchodilators (345 L/min compared to 291 L/min and 311 mL, respectively [<span class="elsevierStyleItalic">P</span> <.04 in both cases]). There were no notable side effects.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">In terms of improvement in lung function, the combination of salmeterol and tiotropium together with fluticasone is more effective in patients with moderate-to-severe COPD than either of the 2 bronchodilators administered alone.</p>" ] "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p class="elsevierStyleSimplePara elsevierViewall">LOS broncodilatadores continúan siendo los fármacos más eficaces para el control de los síntomas de la enfermedad pulmonar obstructiva crónica (EPOC). Recien-temente se ha añadido un anticolinérgico de acción larga, el bromuro de tiotropio, al arsenal terapéutico de esta enfermedad. No existen estudios que hayan asociado 2 broncodilatadores de acción sostenida. El objetivo de este estudio ha sido comprobar si la asociación de salmeterol y tiotropio a pacientes con EPOC mejora la función pulmonar respecto a cuando se administran aislados.</p> <span class="elsevierStyleSectionTitle">Pacientes Y Métodos</span><p class="elsevierStyleSimplePara elsevierViewall">Se incluyó en el estudio a 22 pacientes diagnosticados de EPOC (20 varones), con una edad media de 64 años. Se excluyó a los fumadores activos. El volumen espira-torio forzado en el primer segundo (FEV<span class="elsevierStyleInf">1</span>) medio (± desviación estándar) fue un 43 ± 14% del teórico. Todos los pacientes tenían amplia experiencia en el uso de los dispositivos de inhalación. Se realizaron 3 combinaciones terapéuticas de forma aleatoria durante una semana: <span class="elsevierStyleItalic">a</span>) fluticasona (500 μg/12 h), salmeterol (50 μg/12 h) y placebo; <span class="elsevierStyleItalic">b</span>) fluticasona, tiotropio (18 μg/24 h) y placebo, y <span class="elsevierStyleItalic">c</span>) fluticasona, salmeterol y tiotropio. Al final de cada período se realizó una espirometría forzada entre las 8.30 y las 9.00 h, antes de la inhalación de la combinación y 2 h después de ésta. Durante toda la semana se recogió el pico de flujo ma-tutino inmediatamente antes de la inhalación de los fármacos, dejando 48 h de lavado entre cada asociación.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">Todos los pacientes finalizaron el protocolo. No hubo diferencias significativas en el FEV<span class="elsevierStyleInf">1</span> tanto valle como postinhalación con salmeterol y tiotropio (FEV<span class="elsevierStyleInf">1</span> valle: 1,17 ± 0,55 frente a 1,19 ± 0,49 l; FEV<span class="elsevierStyleInf">1</span> postinhalación: 1,32 ± 0,65 frente a 1,29 ± 0,61 l). En todos los casos el FEV<span class="elsevierStyleInf">1</span> postinhalación fue significativamente superior al FEV<span class="elsevierStyleInf">1</span> valle. La combinación de fluticasona, salmeterol y tiotropio se mostró superior a las otras 2 tanto en el FEV<span class="elsevierStyleInf">1</span> valle como postinhalación (FEV1 valle: 1,32 ± 0,56 l, p < 0,03 en ambos casos; FEV<span class="elsevierStyleInf">1</span> postinhalación: 1,49 ± 0,68 l, p < 0,001 en los 2 casos). El pico de flujo también fue significativamente mayor con la combinación de los 2 broncodilatadores (345 frente a 291 l/m y 311 l/m, respectivamente; p < 0,04 en ambos casos). No hubo efectos secundarios reseñables.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">La asociación de salmeterol y tiotropio unidos a fluticasona en pacientes con EPOC de grado mode-rado-grave es más eficaz en términos de mejoría funcional respiratoria que cualquiera de los 2 broncodilatadores dados de forma aislada.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estudio IBERPOC en España: prevalencia de síntomas respiratorios habituales y de limitación crónica al flujo aéreo" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V Sobradillo" 1 => "M Miravitlles" 2 => "CA Jiménez" 3 => "R Gabriel" 4 => "JL Viejo" 5 => "JF Masa" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Bronconeumol." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 4 | 7 |
| 2024 October | 32 | 19 | 51 |
| 2024 September | 24 | 12 | 36 |
| 2024 August | 59 | 31 | 90 |
| 2024 July | 23 | 18 | 41 |
| 2024 June | 33 | 21 | 54 |
| 2024 May | 40 | 25 | 65 |
| 2024 April | 21 | 18 | 39 |
| 2024 March | 21 | 14 | 35 |
| 2024 February | 17 | 20 | 37 |
| 2023 March | 5 | 2 | 7 |
| 2023 February | 16 | 18 | 34 |
| 2023 January | 17 | 28 | 45 |
| 2022 December | 20 | 23 | 43 |
| 2022 November | 20 | 28 | 48 |
| 2022 October | 18 | 37 | 55 |
| 2022 September | 14 | 28 | 42 |
| 2022 August | 19 | 29 | 48 |
| 2022 July | 22 | 39 | 61 |
| 2022 June | 16 | 39 | 55 |
| 2022 May | 19 | 37 | 56 |
| 2022 April | 14 | 21 | 35 |
| 2022 March | 17 | 33 | 50 |
| 2022 February | 17 | 29 | 46 |
| 2022 January | 18 | 35 | 53 |
| 2021 December | 20 | 36 | 56 |
| 2021 November | 35 | 46 | 81 |
| 2021 October | 49 | 37 | 86 |
| 2021 September | 24 | 40 | 64 |
| 2021 August | 30 | 29 | 59 |
| 2021 July | 22 | 27 | 49 |
| 2021 June | 26 | 33 | 59 |
| 2021 May | 19 | 23 | 42 |
| 2021 April | 85 | 48 | 133 |
| 2021 March | 16 | 23 | 39 |
| 2021 February | 12 | 19 | 31 |
| 2021 January | 11 | 13 | 24 |
| 2020 December | 7 | 8 | 15 |
| 2020 November | 5 | 19 | 24 |
| 2020 October | 9 | 12 | 21 |
| 2020 September | 8 | 11 | 19 |
| 2020 August | 13 | 11 | 24 |
| 2020 July | 10 | 15 | 25 |
| 2020 June | 6 | 4 | 10 |
| 2020 May | 17 | 15 | 32 |
| 2020 April | 18 | 14 | 32 |
| 2020 March | 14 | 16 | 30 |
| 2020 February | 21 | 20 | 41 |
| 2020 January | 17 | 13 | 30 |
| 2019 December | 20 | 13 | 33 |
| 2019 November | 5 | 11 | 16 |
| 2019 October | 9 | 7 | 16 |
| 2019 September | 11 | 15 | 26 |
| 2019 August | 12 | 5 | 17 |
| 2019 July | 12 | 21 | 33 |
| 2019 June | 9 | 24 | 33 |
| 2019 May | 14 | 13 | 27 |
| 2019 April | 20 | 24 | 44 |
| 2019 March | 14 | 31 | 45 |
| 2019 February | 4 | 15 | 19 |
| 2019 January | 5 | 17 | 22 |
| 2018 December | 15 | 23 | 38 |
| 2018 November | 13 | 13 | 26 |
| 2018 October | 15 | 17 | 32 |
| 2018 September | 11 | 17 | 28 |
| 2018 May | 2 | 0 | 2 |
| 2018 April | 6 | 11 | 17 |
| 2018 March | 3 | 10 | 13 |
| 2018 February | 4 | 8 | 12 |
| 2018 January | 5 | 10 | 15 |
| 2017 December | 5 | 12 | 17 |
| 2017 November | 3 | 13 | 16 |
| 2017 October | 5 | 14 | 19 |
| 2017 September | 0 | 8 | 8 |
| 2017 August | 9 | 23 | 32 |
| 2017 July | 2 | 1 | 3 |
| 2017 June | 8 | 43 | 51 |
| 2017 May | 7 | 19 | 26 |
| 2017 April | 4 | 8 | 12 |
| 2017 March | 2 | 11 | 13 |
| 2017 February | 3 | 2 | 5 |
| 2017 January | 1 | 5 | 6 |
| 2016 December | 12 | 9 | 21 |
| 2016 November | 15 | 8 | 23 |
| 2016 October | 19 | 14 | 33 |
| 2016 September | 9 | 12 | 21 |
| 2016 August | 8 | 5 | 13 |
| 2016 July | 7 | 13 | 20 |
| 2016 March | 1 | 0 | 1 |
| 2016 February | 1 | 0 | 1 |
| 2015 December | 3 | 0 | 3 |
| 2015 October | 52 | 1 | 53 |
| 2015 September | 41 | 17 | 58 |
| 2015 August | 56 | 20 | 76 |
| 2015 July | 49 | 9 | 58 |
| 2015 June | 36 | 12 | 48 |
| 2015 May | 55 | 21 | 76 |
| 2015 April | 41 | 21 | 62 |
| 2015 March | 34 | 19 | 53 |
| 2015 February | 34 | 18 | 52 |
| 2015 January | 43 | 19 | 62 |
| 2014 December | 32 | 10 | 42 |
| 2014 November | 42 | 8 | 50 |
| 2014 October | 46 | 13 | 59 |
| 2014 September | 51 | 12 | 63 |
| 2014 August | 43 | 11 | 54 |
| 2014 July | 60 | 9 | 69 |
| 2014 June | 83 | 14 | 97 |
| 2014 May | 63 | 11 | 74 |
| 2014 April | 76 | 14 | 90 |
| 2014 March | 92 | 16 | 108 |
| 2014 February | 69 | 12 | 81 |
| 2014 January | 56 | 12 | 68 |
| 2013 December | 47 | 11 | 58 |
| 2013 November | 41 | 14 | 55 |
| 2013 October | 42 | 18 | 60 |
| 2013 September | 38 | 11 | 49 |
| 2013 August | 31 | 9 | 40 |
| 2013 July | 41 | 14 | 55 |
| 2013 June | 22 | 9 | 31 |
| 2013 May | 26 | 10 | 36 |
| 2013 April | 25 | 7 | 32 |
| 2013 March | 6 | 2 | 8 |
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