Scientific Letter
Repeteability of Circulating Eosinophil Measures and Inhaled Corticosteroids Effect in Bronchiectasis. A Post Hoc Analysis of a Randomized Clinical Trial
Repetibilidad de las mediciones de eosinófilos circulantes y el efecto de los corticosteroides inhalados en las bronquiectasias. Un análisis a posteriori de un ensayo clínico aleatorizado
Miguel Angel Martinez-Garciaa,
, Tomás Posadasa, Giovanni Sotgiub, Francesco Blasic,d, Laura Saderib, Stefano Alibertic,d
Corresponding author
a Pneumology Department, Hospital Universitario i Politécnico La Fe, Valencia, Spain
b Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy
c University of Milan, Department of Pathophysiology and Transplantation, Milan, Italy
d Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy
Read
2593
Timeswas read the article
831
Total PDF
1762
Total HTML
Share statistics
array:23 [ "pii" => "S0300289620302064" "issn" => "03002896" "doi" => "10.1016/j.arbres.2020.06.005" "estado" => "S300" "fechaPublicacion" => "2020-10-01" "aid" => "2534" "copyright" => "SEPAR" "copyrightAnyo" => "2020" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2020;56:681-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:19 [ "pii" => "S0300289620300983" "issn" => "03002896" "doi" => "10.1016/j.arbres.2020.03.018" "estado" => "S300" "fechaPublicacion" => "2020-10-01" "aid" => "2449" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Arch Bronconeumol. 2020;56:684" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Director</span>" "titulo" => "Situación clínica de infección por SARS-CoV-2 en pacientes con carcinoma broncogénico: contexto actual" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:1 [ "paginaInicial" => "684" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "SARS-CoV-2 Infection in Patients with Lung Cancer: Current Clinical Context" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Jesús Isea de la Viña, Ana Laura Ortega Granados, Bernardino Alcázar-Navarrete" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Jesús" "apellidos" => "Isea de la Viña" ] 1 => array:2 [ "nombre" => "Ana Laura" "apellidos" => "Ortega Granados" ] 2 => array:2 [ "nombre" => "Bernardino" "apellidos" => "Alcázar-Navarrete" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1579212920302111" "doi" => "10.1016/j.arbr.2020.03.020" "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/S1579212920302111?idApp=UINPBA00003Z" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289620300983?idApp=UINPBA00003Z" "url" => "/03002896/0000005600000010/v2_202010270642/S0300289620300983/v2_202010270642/es/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0300289620302027" "issn" => "03002896" "doi" => "10.1016/j.arbres.2020.06.001" "estado" => "S300" "fechaPublicacion" => "2020-10-01" "aid" => "2530" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2020;56:679-81" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Hydroxychloroquine and Potential Drug Interactions in Older Adults" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "679" "paginaFinal" => "681" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La hidroxicloroquina y las posibles interacciones farmacológicas en ancianos" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Verónica Velasco-González, Ana Fernández-Araque, Maria Sainz-Gil, Natalia Jimeno, Luis H. Martín, Zoraida Verde" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Verónica" "apellidos" => "Velasco-González" ] 1 => array:2 [ "nombre" => "Ana" "apellidos" => "Fernández-Araque" ] 2 => array:2 [ "nombre" => "Maria" "apellidos" => "Sainz-Gil" ] 3 => array:2 [ "nombre" => "Natalia" "apellidos" => "Jimeno" ] 4 => array:2 [ "nombre" => "Luis H." "apellidos" => "Martín" ] 5 => array:2 [ "nombre" => "Zoraida" "apellidos" => "Verde" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289620302027?idApp=UINPBA00003Z" "url" => "/03002896/0000005600000010/v2_202010270642/S0300289620302027/v2_202010270642/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Repeteability of Circulating Eosinophil Measures and Inhaled Corticosteroids Effect in Bronchiectasis. A Post Hoc Analysis of a Randomized Clinical Trial" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "681" "paginaFinal" => "683" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Miguel Angel Martinez-Garcia, Tomás Posadas, Giovanni Sotgiu, Francesco Blasi, Laura Saderi, Stefano Aliberti" "autores" => array:6 [ 0 => array:4 [ "nombre" => "Miguel Angel" "apellidos" => "Martinez-Garcia" "email" => array:1 [ 0 => "mianmartinezgarcia@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Tomás" "apellidos" => "Posadas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Giovanni" "apellidos" => "Sotgiu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Francesco" "apellidos" => "Blasi" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Laura" "apellidos" => "Saderi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "Stefano" "apellidos" => "Aliberti" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Pneumology Department, Hospital Universitario i Politécnico La Fe, Valencia, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Clinical Epidemiology and Medical Statistics Unit, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "University of Milan, Department of Pathophysiology and Transplantation, Milan, Italy" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Repetibilidad de las mediciones de eosinófilos circulantes y el efecto de los corticosteroides inhalados en las bronquiectasias. Un análisis <span class="elsevierStyleItalic">a posteriori</span> de un ensayo clínico aleatorizado" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2004 "Ancho" => 2912 "Tamanyo" => 297844 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Correlation graphs comparing 2-by-2 groups from circulating eosinophil baseline measures to 24-weeks follow-up measures. (B) Mean (standard deviation) eosinophils percentage counts at baseline, 4, 12 and 24 weeks in the studied groups. ICC: intraclass correlation coefficient; ICs: inhaled corticosteroids.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Peripheral eosinophils can increase in case of allergic, parasitic, or auto-immune disorders. Absolute and relative counts of peripheral eosinophils have been proposed to prescribe drugs in asthmatic patients and to assess their effectiveness.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> Their assessment was also suggested in individuals with chronic obstructive pulmonary disease (COPD). Eosinophils counts >300<span class="elsevierStyleHsp" style=""></span>cells/μL or >3% have been associated with a higher incidence and severity of exacerbations but with a better response to inhaled corticosteroids (ICs).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> On the other hand, counts <100<span class="elsevierStyleHsp" style=""></span>eosinophils/μL (<2%) has been associated with poor therapeutic response to ICs and a high incidence of adverse events (e.g., pneumonia).<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">There is very scarce literature on the role played by peripheral eosinophils in patients with bronchiectasis. It is known that bronchiectasis patients have a higher eosinophil counts in bronchial mucosa in comparison with healthy subjects and, sometimes, an eosinophilic pattern can be the predominant inflammatory cell type in the sputum.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a> Keeping into account the bactericidal activity of eosinophils,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> the prognostic value of bronchial bacterial infection and its association with eosinophil counts,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> and the potential immunosuppressive effect of ICs, an interaction between peripheral eosinophils and ICs treatment could be hypothesized also in bronchiectasis. Only one small study conducted by Aliberti et al. found that bronchiectasis patients treated with ICs can show a significant improvement of quality of life only when eosinophilia (at least 150<span class="elsevierStyleHsp" style=""></span>cells/L or ≥3%) is found.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Usually, baseline counts of circulating eosinophils in patients with clinical stability is used to predict long-term prognosis and therapeutic response, following the demonstration of a correlation between lung tissue and circulating eosinophil counts.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> However, peripheral eosinophils can fluctuate overtime because of their short half-life and diurnal variation (e.g., peak in the evening).<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a> Therefore, before their assessment as a biomarker in large studies in bronchiectasis, it is key to evaluate their time stability, as well as the role played by ICs at different dosages. A randomized controlled trial (RCT) published in 2008 evaluated the effectiveness of ICs in patients with bronchiectasis and performed repeated measures of eosinophils at different time-points.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The objective of the present study was to assess the variability of circulating eosinophils overtime retrieving data from that RCT, as well as to prove ICs effect on this variability when prescribed at different dosages.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The RCT recruited 132 patients with bronchiectasis diagnosed through high-resolution CT scan. Patients with cystic fibrosis, asthma, allergic bronchopulmonary aspergillosis, those exposed to systemic steroids or immunosuppressive therapy, or suffering from eosinophilic pulmonary or systemic diseases were excluded. Finally, 86 were randomized and followed-up for the entire duration of the study. All randomized patients were not exposed to ICs in the three months before their enrollment. A total of 28 patients did not receive ICs, 29 were treated with 250<span class="elsevierStyleHsp" style=""></span>μg of fluticasone propionate (FP) bid (medium doses), and 29 were exposed to 500 ug of FP bid (high doses) for 6 months. Blood collection was performed in the early morning and during a clinical stability state (≥4 weeks after an exacerbation).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Intraclass correlation coefficient (ICC) (95%CI) was computed to assess eosinophilic counts stability, comparing baseline values with those recorded after 1, 3, and 6 months. Values ranging from 0.41 to 0.60 represented a moderate concordance, whereas those >0.60 a good concordance.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> Normal distribution of the variables was assessed by the Kolmogorov–Smirnov test. Pearson correlation coefficient was calculated. To assess the effect of the ICs on eosinophil counts changes, an ANOVA for repeated measures with the Bonferroni correction for multiple comparisons was performed. In 25 (7.8%) cases a multiple imputation method by chained equations was implemented under the assumption that missing data were missing randomly. A <span class="elsevierStyleItalic">p</span>-value <0.05 was considered statistically significant. Statistical computations were performed with the statistical package SPSS (version 20.0).</p><p id="par0035" class="elsevierStylePara elsevierViewall">86 patients [mean (SD) age: 69.5 (8.9) years; 64% were women] were randomly selected. 21% were infected by <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>. At baseline mean (SD) FEV<span class="elsevierStyleInf">1</span> was 1403 (557) mL, and mean (SD) eosinophil percentage was 2.97 (1.3) %. A total of 74.4% and 41.8% patients had an eosinophil percentage of >2% and >3% at baseline, respectively, whereas 74.4% and 34.9% after 6 months of therapy. No statistically significant differences were found between the three groups.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows higher ICC values in cases of closer measurements until 12 weeks, but lower in those at 24 weeks. Those results are confirmed by the correlation analysis showed in the same figure. 81% and 48.6% of patients did not change their eosinophil percentage >2% and >3% after 6 months, respectively. There were no differences between eosinophil percentage counts between groups at any time (<span class="elsevierStyleItalic">p</span> values between 0.31 and 0.69 at baseline, 4,12 and 24 weeks). Finally, it was not proved any significant effect of ICs treatment or its doses over time (intergroup <span class="elsevierStyleItalic">p</span> value: 0.83).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">The results found in patients with bronchiectasis overlap those found in COPD patients. A study on 27,557 patients with stable COPD showed an ICC of 0.61.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> However, a post hoc analysis of TRISTAN proved variability between baseline and 24- and 52-week values.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> Moreover, in our study >80% of patients remained with >2% of eosinophils at 6 months of follow-up, but less than 50% remained with >3% compare with baseline data, as it was also found in COPD.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> Similarly, although circulating eosinophils seem to be a good biomarker for the assessment of the effectiveness of ICs in preventing exacerbations,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> their values is not affected by ICs in COPD patients.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> The results of this study highlight the necessity of performing repeated measures of eosinophils in the design of long-term studies to assess the role of this biomarker in clinical outcomes and treatment effectiveness in bronchiectasis.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, moderate to good concordance between baseline and follow-up eosinophil counts was showed in patients with bronchiectasis. However, this concordance can decrease at six months but it is not affected by ICs treatment or its doses.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Previous presentations</span><p id="par0055" class="elsevierStylePara elsevierViewall">This data have not been presented in any scientific congress or meeting</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0060" class="elsevierStylePara elsevierViewall">This study has no funding.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Previous presentations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2004 "Ancho" => 2912 "Tamanyo" => 297844 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Correlation graphs comparing 2-by-2 groups from circulating eosinophil baseline measures to 24-weeks follow-up measures. (B) Mean (standard deviation) eosinophils percentage counts at baseline, 4, 12 and 24 weeks in the studied groups. ICC: intraclass correlation coefficient; ICs: inhaled corticosteroids.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.D. Pavord" 1 => "S. Korn" 2 => "P. Howarth" 3 => "E.R. Bleecker" 4 => "R. Buhl" 5 => "O.N. Keene" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(12)60988-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2012" "volumen" => "380" "paginaInicial" => "651" "paginaFinal" => "659" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22901886" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0085" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood eosinophil counts, exacerbations, and response to the addition of inhaled fluticasone furoate to vilanterol in patients with chronic obstructive pulmonary disease: a secondary analysis of data from two parallel randomised controlled trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Pascoe" 1 => "N. Locantore" 2 => "M.T. Dransfield" 3 => "N.C. Barnes" 4 => "I.D. Pavord" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(15)00106-X" "Revista" => array:6 [ "tituloSerie" => "Lancet Respir Med" "fecha" => "2015" "volumen" => "3" "paginaInicial" => "435" "paginaFinal" => "442" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25878028" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0090" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood eosinophil count and pneumonia risk in patients with chronic obstructive pulmonary disease: a patient-level meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "I.D. Pavord" 1 => "S. Lettis" 2 => "A. Anzueto" 3 => "N. Barnes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(16)30148-5" "Revista" => array:6 [ "tituloSerie" => "Lancet Respir Med" "fecha" => "2016" "volumen" => "4" "paginaInicial" => "731" "paginaFinal" => "741" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27460163" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0095" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of non-invasive modalities for assessing inflammation in patients with non-cystic fibrosis bronchiectasis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Tsikrika" 1 => "K. Dimakou" 2 => "A.I. Papaioannou" 3 => "Hillas 4" 4 => "L. Thanos" 5 => "K. Kostikas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cyto.2017.08.005" "Revista" => array:6 [ "tituloSerie" => "Cytokine" "fecha" => "2017" "volumen" => "99" "paginaInicial" => "281" "paginaFinal" => "286" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28863927" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0100" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antibacterial properties of eosinophil major basic protein and eosinophil cationic protein" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R.I. Lehrer" 1 => "D. Szklarek" 2 => "A. Barton" 3 => "T. Ganz" 4 => "K.J. Hamann" 5 => "G.J. Gleich" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Immunol (Baltimore, Md: 1950)" "fecha" => "1989" "volumen" => "142" "paginaInicial" => "4428" "paginaFinal" => "4434" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0105" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood and sputum eosinophils in COPD; relationship with bacterial load" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "U. Kolsum" 1 => "G.C. Donaldson" 2 => "R. Singh" 3 => "B.L. Barker" 4 => "V. Gupta" 5 => "L. George" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Respir Res" "fecha" => "2017" "volumen" => "18" "paginaInicial" => "88" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0110" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood eosinophils predict inhaled fluticasone response to bronchiectasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Aliberti" 1 => "G. Sotgiu" 2 => "F. Blasi" 3 => "L. Saderi" 4 => "T. Posadas" 5 => "M.A. Martinez-Garcia" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/13993003.00453-2020" "Revista" => array:3 [ "tituloSerie" => "Eur Resp J" "fecha" => "2020" "itemHostRev" => array:3 [ "pii" => "S1470204512700803" "estado" => "S300" "issn" => "14702045" ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0115" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute exacerbations of chronic obstructive pulmonary disease: identification of biologic clusters and their biomarkers" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Bafadhel" 1 => "S. McKenna" 2 => "S. Terry" 3 => "V. Mistry" 4 => "C. Reid" 5 => "P. Haldar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201104-0597OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2011" "volumen" => "184" "paginaInicial" => "662" "paginaFinal" => "671" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21680942" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0120" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Asthma outcomes: biomarkers" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.J. Szefler" 1 => "S. Wenzel" 2 => "R. Brown" 3 => "S.C. Erzurum" 4 => "J.V. Fahy" 5 => "R.G. Hamilton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2011.12.979" "Revista" => array:8 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2012" "volumen" => "129" "numero" => "Suppl. 3" "paginaInicial" => "S9" "paginaFinal" => "S23" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22386512" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0163445312001302" "estado" => "S300" "issn" => "01634453" ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0125" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled steroids improve quality of life in patients with steady-state bronchiectasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.A. Martinez-Garcia" 1 => "M. Perpiña" 2 => "P. Román" 3 => "J.J. Soler-Cataluña" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Resp Med" "fecha" => "2006" "volumen" => "100" "paginaInicial" => "1623" "paginaFinal" => "1632" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0130" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical biostatistics LIV. The biostatistics of concordance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.S. Kramer" 1 => "A.R. Feinstein" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Clin Pharmacol Ther" "fecha" => "1981" "paginaInicial" => "111" "paginaFinal" => "123" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0135" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood eosinophil levels in COPD patients in the UK Clinical Practice Research Datalink (CPRD)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Landis" 1 => "R. Suruki" 2 => "K. Bonar" 3 => "E. Hilton" 4 => "C. Compton" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2016" "volumen" => "193" "paginaInicial" => "A6329" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0140" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood eosinophils and inhaled corticosteroid/long-acting beta-2 agonist efficacy in COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "I.D. Pavord" 1 => "S. Lettis" 2 => "N. Locantore" 3 => "S. Pascoe" 4 => "P.W. Jones" 5 => "J.A. Wedzicha" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2015-207021" "Revista" => array:7 [ "tituloSerie" => "Thorax" "fecha" => "2016" "volumen" => "71" "paginaInicial" => "118" "paginaFinal" => "125" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26585525" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0213005X17303087" "estado" => "S300" "issn" => "0213005X" ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0145" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eosinophilic inflammation in COPD: prevalence and clinical characteristics" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Singh" 1 => "U. Kolsum" 2 => "C.E. Brightling" 3 => "N. Locantore" 4 => "A. Agusti" 5 => "R. Tal-Singer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00162414" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2014" "volumen" => "44" "paginaInicial" => "1697" "paginaFinal" => "1700" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25323230" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0150" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reassessing the role of eosinophils as a biomarker in chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Tine" 1 => "D. Biondini" 2 => "U. Semenzato" 3 => "E. Bazzan" 4 => "M.G. Cosio" 5 => "M. Saetta" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Clin Med" "fecha" => "2019" "volumen" => "8" "paginaInicial" => "962" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/03002896/0000005600000010/v2_202010270642/S0300289620302064/v2_202010270642/en/main.assets" "Apartado" => array:4 [ "identificador" => "86148" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Cartas cientificas" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/03002896/0000005600000010/v2_202010270642/S0300289620302064/v2_202010270642/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289620302064?idApp=UINPBA00003Z" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 5 | 8 |
| 2024 October | 51 | 29 | 80 |
| 2024 September | 55 | 15 | 70 |
| 2024 August | 101 | 44 | 145 |
| 2024 July | 57 | 20 | 77 |
| 2024 June | 69 | 29 | 98 |
| 2024 May | 95 | 26 | 121 |
| 2024 April | 48 | 30 | 78 |
| 2024 March | 49 | 14 | 63 |
| 2024 February | 47 | 33 | 80 |
| 2023 October | 9 | 2 | 11 |
| 2023 March | 17 | 3 | 20 |
| 2023 February | 72 | 22 | 94 |
| 2023 January | 63 | 54 | 117 |
| 2022 December | 98 | 44 | 142 |
| 2022 November | 117 | 41 | 158 |
| 2022 October | 92 | 39 | 131 |
| 2022 September | 62 | 38 | 100 |
| 2022 August | 75 | 50 | 125 |
| 2022 July | 58 | 58 | 116 |
| 2022 June | 69 | 43 | 112 |
| 2022 May | 75 | 40 | 115 |
| 2022 April | 122 | 35 | 157 |
| 2022 March | 149 | 50 | 199 |
| 2022 February | 48 | 27 | 75 |
| 2021 November | 1 | 1 | 2 |
| 2021 June | 2 | 2 | 4 |
| 2021 April | 1 | 2 | 3 |
| 2021 February | 1 | 2 | 3 |
| 2021 January | 1 | 2 | 3 |
| 2020 December | 1 | 0 | 1 |
| 2020 November | 3 | 0 | 3 |
| 2020 October | 42 | 21 | 63 |
| 2020 September | 1 | 2 | 3 |
| 2020 August | 1 | 2 | 3 |
| 2020 July | 7 | 6 | 13 |
Show all
