Editorial
β2-agonists in asthma: the strange case of Dr Jekyll and Mr Hyde
β2-agonistas en asma: el extraño caso del Dr Jekyll y Mr Hyde
Read
2282
Timeswas read the article
798
Total PDF
1484
Total HTML
Share statistics
array:23 [ "pii" => "S1579212920300239" "issn" => "15792129" "doi" => "10.1016/j.arbr.2019.07.010" "estado" => "S300" "fechaPublicacion" => "2020-04-01" "aid" => "2222" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Arch Bronconeumol. 2020;56:204-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:18 [ "pii" => "S0300289619303047" "issn" => "03002896" "doi" => "10.1016/j.arbres.2019.07.003" "estado" => "S300" "fechaPublicacion" => "2020-04-01" "aid" => "2222" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Arch Bronconeumol. 2020;56:204-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 101 "formatos" => array:2 [ "HTML" => 68 "PDF" => 33 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "β<span class="elsevierStyleInf">2</span>-agonistas en asma: el extraño caso del Dr. Jekyll y Mr. Hyde" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "204" "paginaFinal" => "205" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "β<span class="elsevierStyleInf">2</span>-Agonists in Asthma: The Strange case of Dr. Jekyll and Mr. Hyde" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Xavier Muñoz, Christian Romero-Mesones, María Jesús Cruz" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Xavier" "apellidos" => "Muñoz" ] 1 => array:2 [ "nombre" => "Christian" "apellidos" => "Romero-Mesones" ] 2 => array:2 [ "nombre" => "María Jesús" "apellidos" => "Cruz" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1579212920300239" "doi" => "10.1016/j.arbr.2019.07.010" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212920300239?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289619303047?idApp=UINPBA00003Z" "url" => "/03002896/0000005600000004/v3_202007180720/S0300289619303047/v3_202007180720/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S1579212920300628" "issn" => "15792129" "doi" => "10.1016/j.arbr.2019.07.013" "estado" => "S300" "fechaPublicacion" => "2020-04-01" "aid" => "2232" "copyright" => "SEPAR" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Arch Bronconeumol. 2020;56:206-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Organization of Home Mechanical Ventilation in Europe: A Plea for Uniformity and Accreditation" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "206" "paginaFinal" => "207" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Manejo de la ventilación mecánica domiciliaria en Europa: Tiempo de unificar y acreditar" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "João Carlos Winck" "autores" => array:1 [ 0 => array:2 [ "nombre" => "João Carlos" "apellidos" => "Winck" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S030028961930314X" "doi" => "10.1016/j.arbres.2019.07.012" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S030028961930314X?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212920300628?idApp=UINPBA00003Z" "url" => "/15792129/0000005600000004/v1_202004040736/S1579212920300628/v1_202004040736/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S1579212920300227" "issn" => "15792129" "doi" => "10.1016/j.arbr.2019.06.017" "estado" => "S300" "fechaPublicacion" => "2020-04-01" "aid" => "2217" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Arch Bronconeumol. 2020;56:201-3" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Diaphragmatic Ultrasound: An Innovative Tool Has Become Routine" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "201" "paginaFinal" => "203" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ecografía diafragmática: una herramienta de novedosa a rutinaria" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 455 "Ancho" => 1750 "Tamanyo" => 146172 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0040" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Diaphragmatic dome in 2D and M modes and anatomical measurements of dome movement in A) movement in tidal volume, B) movement in vital capacity, and C) sniff maneuvers.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Javier Sayas-Catalán, Ana Hernández-Voth, María Victoria Villena-Garrido" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Javier" "apellidos" => "Sayas-Catalán" ] 1 => array:2 [ "nombre" => "Ana" "apellidos" => "Hernández-Voth" ] 2 => array:2 [ "nombre" => "María Victoria" "apellidos" => "Villena-Garrido" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0300289619302959" "doi" => "10.1016/j.arbres.2019.06.020" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289619302959?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212920300227?idApp=UINPBA00003Z" "url" => "/15792129/0000005600000004/v1_202004040736/S1579212920300227/v1_202004040736/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "β<span class="elsevierStyleInf">2</span>-agonists in asthma: the strange case of Dr Jekyll and Mr Hyde" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "204" "paginaFinal" => "205" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Xavier Muñoz, Christian Romero-Mesones, María Jesús Cruz" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Xavier" "apellidos" => "Muñoz" "email" => array:1 [ 0 => "xmunoz@vheron.net" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Christian" "apellidos" => "Romero-Mesones" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "María Jesús" "apellidos" => "Cruz" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Neumologia, Hospital Universitario Vall d’Hebron, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "CIBER Enfermedades Respiratorias (CibeRes), Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Biología Celular, Fisiología e Inmunología, Universitat Autònoma de Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "β<span class="elsevierStyleInf">2</span>-agonistas en asma: el extraño caso del Dr Jekyll y Mr Hyde" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Bronchial asthma is a major public health problem, affecting more than 300 million people worldwide, and its prevalence is steadily rising in most developed countries.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Current strategies in the management of patients with asthma are focused on achieving disease control. ®<span class="elsevierStyleInf">2</span>-agonists play an important role in this regard. These drugs are classified according to the duration of the bronchodilator effect, and short-acting ®<span class="elsevierStyleInf">2</span>-agonists (SABA) are distinguished from long-acting ®<span class="elsevierStyleInf">2</span>-agonists (LABA) when the effect lasts for 12 h, or even longer in the case of ultra-LABAs.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Despite the enormous benefit of ®2-agonists in the treatment of asthma (Dr. Jekyll), major alarms concerning their use have been raised since they were first introduced (Mr. Hyde). Indeed, an increase in mortality associated with the use of SABA<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> had already been reported as early as the 1960s, and in 1979, a peak of 4.1/100,000 asthma deaths per year in a population aged between 5 and 34 years was observed in New Zealand.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> While this increase in mortality was associated with overuse of these drugs, their use in monotherapy also appears to be a determinant factor. Currently, concerns have shifted to LABA, the use which was already questioned in 1993, when a trend towards an increase in mortality in asthmatic patients treated with salmeterol was observed.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> This trend was confirmed by the results of the SMART study, which found that mortality was 4.4 times higher in patients receiving salmeterol compared to placebo.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> This increase in mortality associated with LABA was also reported in 2006 in a meta-analysis that included results from 19 randomized placebo-controlled studies.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In this context, the FDA analyzed approximately 61,000 cases and concluded that the risk of an asthma-related serious adverse event e.g. death, intubation, or hospital admission was 2.8 times higher per 1,000 patients treated with LABA compared to those who did not receive these products.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Given the questions raised by these results and the observation that these adverse effects did not appear to occur if the LABA was administered concomitantly with inhaled corticosteroids, the FDA demanded that the 4 large companies producing LABA (AstraZeneca, GlaxoSmithKline, Merck, and Novartis) conduct 5 studies, 4 in adolescents/adults and 1 in a pediatric population, comparing patients randomized to receive inhaled corticosteroids + LABA versus inhaled corticosteroids in monotherapy at a fixed dose during 6 months. The individual results of these studies,<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8–11</span></a> together with the pooled analysis of all outcomes,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> seem to indicate that the administration of LABA in asthmatic patients is safe provided they are given in combination with inhaled corticosteroids and at doses not exceeding 50 μg/12 h salmeterol or 9 μg/12 h formoterol.</p><p id="par0020" class="elsevierStylePara elsevierViewall">However, it is becoming increasing common to see LABA escalation in clinical practice simultaneously with the escalation of doses of inhaled corticosteroids, without taking into account these safety limits and the inherent risk of overdosing these drugs. Moreover, few benefits in terms of efficacy have been reported with these dose increases. However, questions are being raised as to whether these dose increases might predispose to a greater number of exacerbations. While Wofe et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> did not find a greater number of exacerbations in patients treated with formoterol 24 μg/12 h compared to patients treated with lower doses, Mann et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> reported that doses of 24 μg/day were associated with a 4.5% risk of developing a serious asthma exacerbation, whereas the risk was only 2% if doses of 12 μg/day were used. LABAs are currently used in patients with moderate or severe asthma. However, the latest update of the GINA guidelines<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> states that the combination of budesonide/formoterol can be used on-demand in patients with mild asthma. This recommendation is based on the SYGMA 1<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and SYGMA 2<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> studies, sponsored by Astra-Zeneca, which reported that patients with mild asthma receiving budesonide 200 μg + formoterol 6 μg on-demand had fewer exacerbations than patients receiving terbutaline on-demand. Although this treatment schedule was not inferior in terms of preventing exacerbations, when compared with budesonide 200 demand had fewer exacerbations g twice a day + terbutaline on-demand it was inferior in terms of asthma control. These results have recently been reproduced in a real-world study (also sponsored by Astra-Zeneca) without the limitations imposed by clinical trials.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Extreme caution is needed when choosing this therapeutic option, and to avoid awakening Mr. Hyde the dose should probably not exceed 18 demand had fewer exacerbations g/day.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The reason why ®<span class="elsevierStyleInf">2</span>-adrenergic receptors have this double personality is unknown, although the data seem to point to their action on ®<span class="elsevierStyleInf">2</span>-adrenergic receptors in the bronchial smooth muscle. In this respect, genetic variants, such as the 9 different ®<span class="elsevierStyleInf">2</span>-adrenergic receptor polymorphisms identified, could explain this effect. Variable expression after the stimulation of protein receptors such as EPAC or arrestins could also be the cause. Either way, our efforts should be directed at ensuring, above all, that these drugs are never administered in monotherapy; in fact, they should be contraindicated in patients with asthma unless they are administered in conjunction with inhaled corticosteroids.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> We must also raise awareness among all medical professionals treating patients with asthma that the established safe doses must not be exceeded. The combinations of LABA and inhaled corticosteroids that are so helpful in avoiding monotherapy may be dangerous if they are progressively escalated without taking into account the maximum safe dose for LABA.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Robert Louis Stevenson published <span class="elsevierStyleItalic">The Strange Case of Dr Jekyll and Mr Hyde</span> in 1886. A few years before that, in 1860, Sir Henry Hyde Salter opened the door to the treatment of asthma with ®-agonists when he observed that bronchial smooth muscle contraction was the main cause of obstruction in these patients.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Any relationship between both Mr. Hydes is purely coincidental.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0035" class="elsevierStylePara elsevierViewall">Xavier Muñoz has received honoraria as a speaker, scientific advisor, and participant in clinical studies from (in alphabetical order): AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Mundifarma, Novartis, and Teva.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-06-14" "fechaAceptado" => "2019-07-10" "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:19 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Pocket guide for asthma management and prevention. Update 2019. <a target="_blank" href="http://www.ginasthma.org">www.ginasthma.org</a>." ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Geographical variations in the epidemics of asthma deaths" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P. Fraser" 1 => "R. Doll" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/jech.25.1.34" "Revista" => array:6 [ "tituloSerie" => "Br J Prev Soc Med" "fecha" => "1971" "volumen" => "25" "paginaInicial" => "34" "paginaFinal" => "36" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5551231" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The short and long-term effects of β2-agonists" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.R. Sear" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "editores" => "S.T.Holgate, K.F.Austen, L.M.Lichtenstein" "titulo" => "Asthma: physiology, immunopharmacology, and treatment" "paginaInicial" => "359" "paginaFinal" => "374" "serieFecha" => "1993" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serevent nationwide surveillance study: comparison of salmeterol with salbutamol in asthmatic patients who require regular bronchodilator treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "W. Castle" 1 => "R. Fuller" 2 => "J. Hall" 3 => "J. Palmer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.306.6884.1034" "Revista" => array:7 [ "tituloSerie" => "BMJ" "fecha" => "1993" "volumen" => "306" "paginaInicial" => "1034" "paginaFinal" => "1037" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8098238" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022395614002337" "estado" => "S300" "issn" => "00223956" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The salmeterol multicenter asthma research trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "H.S. Nelson" 1 => "S.T. Weiss" 2 => "E.R. Bleecker" 3 => "S.W. Yancey" 4 => "P.M. Dorinsky" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Chest" "fecha" => "2006" "volumen" => "129" "paginaInicial" => "15" "paginaFinal" => "26" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Meta-analysis: effect of longacting beta-agonists on severe asthma exacerbations and asthma related deaths" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S.R. Salpeter" 1 => "N.S. Buckle" 2 => "T.M. Ormisto" 3 => "E.E. Salpeter" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/0003-4819-144-12-200606200-00126" "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2006" "volumen" => "144" "paginaInicial" => "904" "paginaFinal" => "912" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16754916" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-acting beta-agonists and adverse asthma events meta-analysis statistical briefing package for joint meeting of the pulmonary-allergy drugs advisory committee, drug safety and risk management advisory committee and paediatric advisory committee on Desember 10-11, 2008" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.S. Levenson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "titulo" => "Quantitative safety and pharmacoepidemiology group, United States Food and Drug Administration" "fecha" => "2008" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serious asthma events with fluticasone plus salmeterol versus fluticasone alone" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.A. Stempel" 1 => "I.H. Raphiou" 2 => "K.M. Kral" 3 => "A.M. Yeakey" 4 => "A.H. Emmett" 5 => "C.M. Prazma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1511049" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2016" "volumen" => "374" "paginaInicial" => "1822" "paginaFinal" => "1830" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26949137" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serious asthma events with budesonide plus formoterol vs. budesonide alone" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.P. Peters" 1 => "E.R. Bleecker" 2 => "G.W. Canonica" 3 => "Y.B. Park" 4 => "R. Ramirez" 5 => "S. Hollis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1511190" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2016" "volumen" => "375" "paginaInicial" => "850" "paginaFinal" => "860" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27579635" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serious asthma outcomes with mometasone fluorate plus formoterol versus mometasone alone" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.I.J. Weinstein" 1 => "D. Gates" 2 => "N. Ryan" 3 => "W. Mok" 4 => "S.J. Lane" 5 => "I. Agache" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2017" "volumen" => "195" "paginaInicial" => "A7612" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety of adding salmeterol to fluticasone propionate in children with asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.A. Stempel" 1 => "S.J. Szefler" 2 => "S. Pedersen" 3 => "R.S. Zeiger" 4 => "A.M. Yeakey" 5 => "L.A. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1606356" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2016" "volumen" => "375" "paginaInicial" => "840" "paginaFinal" => "849" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27579634" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined analysis of asthma safety trials of long-acting β2-agonists" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "W.W. Busse" 1 => "E.D. Bateman" 2 => "A.L. Caplan" 3 => "H.W. Kelly" 4 => "P.M. O’Byrne" 5 => "K.F. Rabe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1716868" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2018" "volumen" => "378" "paginaInicial" => "2497" "paginaFinal" => "2505" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29949492" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Formoterol, 24 µg bid, and serious asthma exacerbations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Wofe" 1 => "C. Laforce" 2 => "B. Friedman" 3 => "W. Sokol" 4 => "D. Till" 5 => "G. Della Cioppa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.129.1.27" "Revista" => array:7 [ "tituloSerie" => "Chest" "fecha" => "2006" "volumen" => "129" "paginaInicial" => "27" "paginaFinal" => "38" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16424410" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S2215036617301025" "estado" => "S300" "issn" => "22150366" ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serious asthma exacerbations in asthmatics treated with high-dose formoterol" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Mann" 1 => "B. Chowdhury" 2 => "E. Sullivan" 3 => "R. Nicklas" 4 => "R. Anthracite" 5 => "R.J. Meyer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.124.1.70" "Revista" => array:6 [ "tituloSerie" => "Chest." "fecha" => "2003" "volumen" => "124" "paginaInicial" => "70" "paginaFinal" => "74" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12853504" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled combined budesonide-formoterol as needed in mild asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.M. O’Byrne" 1 => "J.M. FitzGerald" 2 => "E.D. Bateman" 3 => "P.J. Barnes" 4 => "N. Zhong" 5 => "C. Keen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1715274" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2018" "volumen" => "378" "paginaInicial" => "1865" "paginaFinal" => "1876" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29768149" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "As-needed budesonide-formoterol versus maintenance budesonide in mild asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.D. Bateman" 1 => "H.K. Reddel" 2 => "P.M. O’Byrne" 3 => "P.J. Barnes" 4 => "N. Zhong" 5 => "C. Keen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1715275" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2018" "volumen" => "378" "paginaInicial" => "1877" "paginaFinal" => "1887" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29768147" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Controlled trial of budesonide-formoterol as needed for mild asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Beasley" 1 => "M. Holliday" 2 => "H.K. Reddel" 3 => "I. Braithwaite" 4 => "S. Ebmeier" 5 => "R.J. Hancox" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1901963" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med." "fecha" => "2019" "volumen" => "380" "paginaInicial" => "2020" "paginaFinal" => "2030" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31112386" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "GINA 2019: a fundamental change in asthma management" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.K. Reddel" 1 => "J.M. FitzGerald" 2 => "E.D. Bateman" 3 => "L.B. Bacharier" 4 => "A. Becker" 5 => "G. Brusselle" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/13993003.01184-2018" "Revista" => array:4 [ "tituloSerie" => "Eur Respir J" "fecha" => "2019" "volumen" => "53" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30705126" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Henry Hyde Salter (1823-71): a biographical sketch" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. Sakula" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.40.12.887" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "1985" "volumen" => "40" "paginaInicial" => "887" "paginaFinal" => "888" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3913047" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15792129/0000005600000004/v1_202004040736/S1579212920300239/v1_202004040736/en/main.assets" "Apartado" => array:4 [ "identificador" => "45360" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Editorials" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15792129/0000005600000004/v1_202004040736/S1579212920300239/v1_202004040736/en/main.pdf?idApp=UINPBA00003Z&text.app=https://www.archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212920300239?idApp=UINPBA00003Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 61 | 24 | 85 |
| 2024 September | 58 | 25 | 83 |
| 2024 August | 94 | 42 | 136 |
| 2024 July | 64 | 36 | 100 |
| 2024 June | 75 | 49 | 124 |
| 2024 May | 97 | 54 | 151 |
| 2024 April | 61 | 48 | 109 |
| 2024 March | 59 | 39 | 98 |
| 2024 February | 62 | 29 | 91 |
| 2024 January | 5 | 1 | 6 |
| 2023 December | 7 | 0 | 7 |
| 2023 November | 2 | 0 | 2 |
| 2023 October | 4 | 0 | 4 |
| 2023 September | 3 | 0 | 3 |
| 2023 August | 4 | 0 | 4 |
| 2023 July | 5 | 0 | 5 |
| 2023 June | 4 | 0 | 4 |
| 2023 May | 2 | 0 | 2 |
| 2023 April | 6 | 0 | 6 |
| 2023 March | 22 | 2 | 24 |
| 2023 February | 70 | 18 | 88 |
| 2023 January | 50 | 31 | 81 |
| 2022 December | 94 | 28 | 122 |
| 2022 November | 85 | 23 | 108 |
| 2022 October | 102 | 41 | 143 |
| 2022 September | 49 | 29 | 78 |
| 2022 August | 47 | 41 | 88 |
| 2022 July | 47 | 54 | 101 |
| 2022 June | 39 | 37 | 76 |
| 2022 May | 38 | 40 | 78 |
| 2022 April | 49 | 38 | 87 |
| 2022 March | 55 | 42 | 97 |
| 2022 February | 22 | 17 | 39 |
| 2022 January | 11 | 0 | 11 |
| 2021 December | 17 | 4 | 21 |
| 2021 November | 6 | 0 | 6 |
| 2021 August | 1 | 0 | 1 |
| 2020 July | 1 | 0 | 1 |
| 2020 June | 2 | 4 | 6 |
| 2020 April | 4 | 2 | 6 |
Show all
