was read the article
array:23 [ "pii" => "S0300289624000012" "issn" => "03002896" "doi" => "10.1016/j.arbres.2023.12.017" "estado" => "S300" "fechaPublicacion" => "2024-03-01" "aid" => "3463" "copyright" => "SEPAR" "copyrightAnyo" => "2024" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2024;60:183-5" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S0300289624000036" "issn" => "03002896" "doi" => "10.1016/j.arbres.2024.01.002" "estado" => "S300" "fechaPublicacion" => "2024-03-01" "aid" => "3465" "copyright" => "SEPAR" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Arch Bronconeumol. 2024;60:186-90" "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">Scientific Letter</span>" "titulo" => "Methodology Employed to Develop the Airway Mucus Secretion Test (T-SEC): A Questionnaire to Evaluate Airway Mucus Hypersecretion in Patients With Asthma" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "186" "paginaFinal" => "190" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 3697 "Ancho" => 3341 "Tamanyo" => 1145325 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">T-SEC: English translation and original version in Spanish.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Esther Palones, Juan Luis García-Rivero, Carolina Cisneros, Carlos Almonacid-Sánchez, Luis Pérez-de Llano, Vicente Plaza, Astrid Crespo-Lessmann" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Esther" "apellidos" => "Palones" ] 1 => array:2 [ "nombre" => "Juan Luis" "apellidos" => "García-Rivero" ] 2 => array:2 [ "nombre" => "Carolina" "apellidos" => "Cisneros" ] 3 => array:2 [ "nombre" => "Carlos" "apellidos" => "Almonacid-Sánchez" ] 4 => array:2 [ "nombre" => "Luis" "apellidos" => "Pérez-de Llano" ] 5 => array:2 [ "nombre" => "Vicente" "apellidos" => "Plaza" ] 6 => array:2 [ "nombre" => "Astrid" "apellidos" => "Crespo-Lessmann" ] 7 => array:1 [ "colaborador" => "Sociedad Española de Neumología y Cirugía Torácica (SEPAR) Asthma Integrated Research Programme (PII) participants" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289624000036?idApp=UINPBA00003Z" "url" => "/03002896/0000006000000003/v3_202406110502/S0300289624000036/v3_202406110502/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0300289624000127" "issn" => "03002896" "doi" => "10.1016/j.arbres.2024.01.010" "estado" => "S300" "fechaPublicacion" => "2024-03-01" "aid" => "3474" "copyright" => "SEPAR" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Arch Bronconeumol. 2024;60:181-2" "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">Clinical Image</span>" "titulo" => "Pulmonary Artery Pseudoaneurysms in Cannonball Metastases" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "181" "paginaFinal" => "182" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 1735 "Ancho" => 2007 "Tamanyo" => 432769 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A, B) Cannonball metastases in both lungs on X-ray and thorax CT. (C) Maximum intensity projection image showing the largest pseudoaneurysm (arrow) and the terminal branches of the pulmonary artery (arrowheads). (D) The color intensity of the pseudoaneurysm indicated by the arrow in the color mapping obtained by thoracic CT fusion is the same as that of the right ventricle (*).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Esat Kaba, Merve Solak, Nur Hürsoy" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Esat" "apellidos" => "Kaba" ] 1 => array:2 [ "nombre" => "Merve" "apellidos" => "Solak" ] 2 => array:2 [ "nombre" => "Nur" "apellidos" => "Hürsoy" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289624000127?idApp=UINPBA00003Z" "url" => "/03002896/0000006000000003/v3_202406110502/S0300289624000127/v3_202406110502/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Peripheral Blood MxA Levels During a First Acute Wheezing Episode and the Link to Childhood Asthma" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">To the Director</span>," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "183" "paginaFinal" => "185" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Heidi Makrinioti, Kiara Homil, Pekka Hurme, Riku Erkkola, Lotta Kinnunen, Zhaozhong Zhu, Matti Waris, Carlos A. Camargo, Kohei Hasegawa, Tuomas Jartti" "autores" => array:10 [ 0 => array:4 [ "nombre" => "Heidi" "apellidos" => "Makrinioti" "email" => array:1 [ 0 => "cmakrynioti@mgh.harvard.edu" ] "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" => "Kiara" "apellidos" => "Homil" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Pekka" "apellidos" => "Hurme" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Riku" "apellidos" => "Erkkola" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Lotta" "apellidos" => "Kinnunen" "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" ] ] ] 5 => array:3 [ "nombre" => "Zhaozhong" "apellidos" => "Zhu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "Matti" "apellidos" => "Waris" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 7 => array:4 [ "nombre" => "Carlos A." "apellidos" => "Camargo" "sufijo" => "Jr." "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 8 => array:3 [ "nombre" => "Kohei" "apellidos" => "Hasegawa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 9 => array:3 [ "nombre" => "Tuomas" "apellidos" => "Jartti" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Paediatrics, Turku University Hospital and University of Turku, Turku, Finland" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Research Unit of Clinical Medicine, Medical Research Centre, University of Oulu, Oulu, Finland" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Paediatrics, Oulu University Hospital, Oulu, Finland" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Department of Clinical Microbiology, Turku University Hospital, Turku, Finland" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "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" => 1713 "Ancho" => 2508 "Tamanyo" => 214822 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A multi-panel graphical representation illustrating the key findings of the study.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Panel (A): Relationships of peripheral blood MxA levels with the development of asthma in infants hospitalized with a first wheezing episode. The fitted line represents a locally estimated scatterplot smoothed (loess) curve. The grey bar represents the range in which 95% of corresponding data are present.</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Panel (B): This Venn diagram describes the frequency of respiratory viruses detected in nasopharyngeal aspirates from infants in the VINKU2 analytical sub-cohort (i.e., <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>106 in total). The left circle (i.e., yellow) includes RSV-positive cases. The middle circle (i.e., light blue) includes cases positive as solo or a coinfection for human metapneumovirus, influenza, parainfluenza, adenovirus, or bocavirus, but not RSV or rhinovirus (RV). The right circle (i.e., pink) includes RV-positive cases. The intersections between the left, middle, and right circles include three groups; the RSV-other viruses coinfections, the RSV-RV-double positive cases, and the RSV-RV-other viruses coinfections. Similarly, the intersections between the right, middle, and left circles include three groups; the RSV-other viruses coinfections, the RSV-RV-double positive cases, and the RSV-RV-other viruses coinfections.</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Panel (C): The violin plots depict statistically significant differences in mean peripheral blood MxA levels (i.e., in microgram/ml) in infants hospitalized with an RV-only (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>47) as compared to an RSV-only (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9) first wheezing episode (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05), as well as in infants hospitalized with an RV-only (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>47) as compared to RV-coinfections (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21) first wheezing episode (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). The RV-coinfections group is consistent with the description followed in the Venn diagram in Panel (B). Comparisons have been made with the Mann–Whitney <span class="elsevierStyleItalic">U</span> test.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">MxA, myxovirus resistance protein 1; RSV, respiratory syncytial virus; RV, rhinovirus.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Severe wheezing episodes (i.e., wheezing illnesses requiring hospitalisation) in early life are associated with an increased risk of childhood asthma.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">1,2</span></a> In terms of pathophysiology, this association is primarily ascribed to an interplay between environmental factors (e.g., respiratory viruses) and host innate immune responses,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">3</span></a> while interferons (IFN) and IFN-stimulated genes (ISG) are considered to play a key role in the latter.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a> These mediators limit respiratory virus replication early on, thereby preventing chronic airway inflammation, a key feature of asthma.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a> There are more than one thousand ISGs, but attention has focused on the myxovirus resistance (Mx) genes, since the expression of these genes and their products (e.g., IFNs) have a broad inhibitory role in terms of respiratory virus replication and may act prior to genome replication at an early post-entry step of the respiratory virus life cycle.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">5,6</span></a> Specifically, some structural analyses have shown that Mx proteins interact with viral ribonucleoprotein complexes. The affinity of this interaction may be low, possibly explaining the broad target specificity of Mx proteins. However, the interaction between low-affinity Mx protein and viral ribonucleoprotein can trigger the assembly of Mx proteins into oligomers and the subsequent disassembly of viral target structures.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> The current understanding is that in infants and older children with severe respiratory viral infections, high peripheral blood MxA (i.e., the protein encoded by the <span class="elsevierStyleItalic">MX1</span> gene) levels indicate viral rather than bacterial pathogens.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">8</span></a> This increase in <span class="elsevierStyleItalic">MX1</span> expression has also been confirmed in an age-dependent manner in children presenting with a wheezing exacerbation.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">9</span></a> However, no evidence is yet available to suggest a link between peripheral blood MxA levels in early-life wheezing illnesses and the risk of developing asthma.</p><p id="par0010" class="elsevierStylePara elsevierViewall">To identify the evidence, we analysed biological data from the Viral Inception of Asthma (VINKU2) study, the design of which is described elsewhere.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">10</span></a> The VINKU2 cohort inclusion criteria were age 3–23 months, delivery at 36 weeks of gestation or older, first wheezing episode (based on parental report and confirmed from medical records), ongoing signs of lower respiratory tract symptoms (cough, noisy breathing, or wheezing), and written informed consent from a caregiver. Since the exposure of interest for this paper was peripheral blood MxA levels, our analytical cohort consisted of 106 infants with available peripheral blood MxA data. MxA protein was detected in diluted 1:20 blood samples using ELISA. A multiplex polymerase chain reaction (PCR) test was used for the detection of rhinovirus (RV) A and B, respiratory syncytial virus (RSV) A and B, parainfluenza virus types 1–3, human metapneumovirus, adenovirus, coronavirus (229E, NL63, OC43, and HKU1), and influenza A and B virus from frozen samples. Human bocavirus-1 was analysed by using PCR and serology, as previously described.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">10</span></a> The primary outcome was the development of asthma by the age of 8 years, documented in either a physician report or healthcare insurance registries. These data were successfully obtained from 86 (81%) of 106 infants. As an exploratory outcome, we investigated whether peripheral blood MxA was secreted at different levels in children with only RV or only RSV illness. Potential confounders (i.e., age, history of eczema, parental asthma, and treatment with prednisolone) were accounted for in the model. The role of smoking in the home was investigated as a possible effect modifier.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">11</span></a> Recruited patients were screened for respiratory viral infections, as described previously.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">10</span></a> We examined the between-groups differences in the infants’ baseline characteristics and virology, using the Mann–Whitney <span class="elsevierStyleItalic">U</span> test and Chi-square tests as appropriate.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Of 106 infants hospitalized with a first wheezing episode, the median age was 12 months and 33% were girls (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). After adjusting for confounders, we observed that a 1 unit (μg/ml) increase in MxA levels was associated with a 4.7-fold chance of developing asthma by the age of 8 years (adjusted OR 4.7, 95% CI 1.2–18.9; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.042) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). This association was not modified by smoking in the home (<span class="elsevierStyleItalic">p</span>-interaction<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.99). The frequency of respiratory viruses detected in this analytical cohort can be seen in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B. The exploratory analysis showed that infants with RV infection only had significantly lower peripheral blood MxA levels than infants with RSV-only and with RSV-RV coinfections (both <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05, respectively) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). The statistical analysis and figures were produced using R Version 4.2.3 and STATA/BE 17.0 software.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">To the best of our knowledge, this is the first study of infants hospitalised with a first wheezing episode that suggests that peripheral blood MxA levels are associated with a high risk of childhood asthma. This observation is interesting, particularly following evidence from birth cohort studies showing that <span class="elsevierStyleItalic">MX1</span> polymorphisms may be associated with an increased risk of asthma exacerbations at school age.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">7,12</span></a> If these data can be confirmed in a larger cohort providing additional evidence of specificity, sensitivity and positive predictive value, peripheral blood MxA could be proposed as a biomarker for childhood asthma. This could prove beneficial, given that peripheral blood MxA levels can be readily identified in point-of-care testing.</p><p id="par0025" class="elsevierStylePara elsevierViewall">We also analysed the available respiratory virus data for RSV-only and RV-only positive groups, and for groups with RSV-RV coinfection. Interestingly, despite the limited sample size, our results in RSV- and RV-only positive groups are in line with reported observational and mechanistic evidence.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">8,13</span></a> To be more precise, we noted among infants hospitalised with a first wheezing episode that those who tested positive for RSV alone showed the highest MxA levels. A similar trend in RSV-positive children was also observed in a Swedish study.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">8</span></a> Furthermore, mechanistic data have shown that in RV infection, ciliated epithelial cells express lower levels of ISGs, possibly through a mechanism that facilitates RV replication.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> This reported mechanism could possibly explain our findings in infants positive for RV only. While we would expect an association between reduced ISG expression and increased asthma risk, this association seems to be more complex than expected. For instance, data from a multicentre bronchiolitis study reveal that infants with RSV-positive bronchiolitis and increased IFN transcription (e.g., linked to probable increased ISG expression) in their nasal airway samples were actually at a greater risk of developing asthma during their school years than infants with RSV-bronchiolitis and reduced IFN transcription in nasal airway samples.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">3</span></a> Further study is needed to clarify if this is related to the respiratory virus type. Another factor that needs to be considered is the timing (i.e., how many days since the onset of symptoms) in the context of the wheezing illness hospitalisation. For example, we know that in adult patients with asthma, IFN expression in response to respiratory virus stimulation is lower than in control patients.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">14</span></a> Nevertheless, recent evidence from an in vitro model showed that IFN deficiency may be associated with increased respiratory virus replication and a subsequent increase in IFN and ISG expression.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">15</span></a> Furthermore, infection with different respiratory viruses may be associated with diverse immune responses in the context of a wheezing illness.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">16</span></a> In this study, we have taken a different approach to the definition of respiratory virus aetiology for analytical purposes. For example, in the statistical analysis, we opted to analyse data by “virus-only-positive” groups based on emerging evidence indicating that respiratory viral coinfections, within the scope of a lower respiratory viral illness, may define groups with unique pathophysiological characteristics.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">17</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Despite its strengths, our study also has several potential limitations. Firstly, the study size in terms of the primary outcome is limited (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>86), although we did observe a significant association between peripheral blood MxA and asthma development up to the age of 8 years. Our study findings provide preliminary evidence that warrants further testing in a larger cohort. Secondly, this study does not have data on asthma phenotypes. The sample size was too small to derive a firm conclusion as to whether peripheral blood MxA could be a more specific marker of childhood asthma development in children with RSV-positive wheezing illnesses. The initial findings from our analysis, however, indicate that this concept should be examined in a larger group of patients.</p><p id="par0035" class="elsevierStylePara elsevierViewall">To summarise, this is the first study to demonstrate a link between peripheral blood MxA levels in infants hospitalised with a first wheezing episode and the development of childhood asthma. The findings are preliminary but significant and warrant further investigation in a larger group of patients. This evidence, when validated, may help design a crucial strategy for the prevention of childhood asthma, which remains a public health priority.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of Interests</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests.</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 "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1713 "Ancho" => 2508 "Tamanyo" => 214822 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A multi-panel graphical representation illustrating the key findings of the study.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Panel (A): Relationships of peripheral blood MxA levels with the development of asthma in infants hospitalized with a first wheezing episode. The fitted line represents a locally estimated scatterplot smoothed (loess) curve. The grey bar represents the range in which 95% of corresponding data are present.</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Panel (B): This Venn diagram describes the frequency of respiratory viruses detected in nasopharyngeal aspirates from infants in the VINKU2 analytical sub-cohort (i.e., <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>106 in total). The left circle (i.e., yellow) includes RSV-positive cases. The middle circle (i.e., light blue) includes cases positive as solo or a coinfection for human metapneumovirus, influenza, parainfluenza, adenovirus, or bocavirus, but not RSV or rhinovirus (RV). The right circle (i.e., pink) includes RV-positive cases. The intersections between the left, middle, and right circles include three groups; the RSV-other viruses coinfections, the RSV-RV-double positive cases, and the RSV-RV-other viruses coinfections. Similarly, the intersections between the right, middle, and left circles include three groups; the RSV-other viruses coinfections, the RSV-RV-double positive cases, and the RSV-RV-other viruses coinfections.</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Panel (C): The violin plots depict statistically significant differences in mean peripheral blood MxA levels (i.e., in microgram/ml) in infants hospitalized with an RV-only (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>47) as compared to an RSV-only (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9) first wheezing episode (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05), as well as in infants hospitalized with an RV-only (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>47) as compared to RV-coinfections (<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>21) first wheezing episode (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). The RV-coinfections group is consistent with the description followed in the Venn diagram in Panel (B). Comparisons have been made with the Mann–Whitney <span class="elsevierStyleItalic">U</span> test.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">MxA, myxovirus resistance protein 1; RSV, respiratory syncytial virus; RV, rhinovirus.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Note</span>: Data are <span class="elsevierStyleItalic">N</span> (%) of children unless otherwise indicated.</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">MxA: myxovirus resistance protein 1; RSV: respiratory syncytial virus.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Patient Characteristics \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Overall(<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>106) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Asthma by Age of 8 Years<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>(<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>86)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"><span class="elsevierStyleItalic">p</span>-Value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Yes(<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>33; 38.4%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">No(<span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>53; 61.6%) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Demographics</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Age (months) median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11.96 (6.7–16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.3 (8.55–11.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.8 (11.1–14.01) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Female sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">35 (33%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (24%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (43%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.07 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>History of eczema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 (28%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (36%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (25%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Parental asthma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47 (44%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (55%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 (42%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.24 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Parental smoking \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 (28%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (33%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (36%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.81 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Peripheral blood cytokine levels</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MxA levels (μg/L) median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">281 (181–474) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">314 (242–684) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">212 (157–383) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.015 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="5" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Respiratory virus data</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>RSV-only \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (8%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.96 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>RSV-rhinovirus only \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (7.5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (9%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.54 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rhinovirus-only \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47 (44%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 (48%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 (43%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.65 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Virus-only (other)<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (5%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (6%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.94 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3564716.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Physician report or data from healthcare insurance registries for asthma at any point during an 8-year follow-up.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Infections with a single respiratory virus agent other than RSV and rhinovirus (i.e., human metapneumovirus, influenza, parainfluenza, adenovirus, or bocavirus).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Demographic Characteristics and Respiratory Virus Detection in the VINKU2 Analytical Sub-cohort (i.e., <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>106 in total) and Participants With Complete Asthma Diagnostic Data Asthma Diagnosis by the Age of 8 Years (i.e., <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>86 in Total).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bib0090" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early life rhinovirus wheezing, allergic sensitization, and asthma risk at adolescence" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.J. Rubner" 1 => "D.J. Jackson" 2 => "M.D. Evans" 3 => "R.E. Gangnon" 4 => "C.J. Tisler" 5 => "T.E. Pappas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2016.03.049" "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2017" "volumen" => "139" "paginaInicial" => "501" "paginaFinal" => "507" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27312820" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0095" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.J. Jackson" 1 => "R.E. Gangnon" 2 => "M.D. Evans" 3 => "K.A. Roberg" 4 => "E.L. Anderson" 5 => "T.E. Pappas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200802-309OC" "Revista" => array:5 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2008" "volumen" => "178" "paginaInicial" => "667" "paginaFinal" => "672" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0100" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Integrated omics endotyping of infants with respiratory syncytial virus bronchiolitis and risk of childhood asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Raita" 1 => "M. Perez-Losada" 2 => "R.J. Freishtat" 3 => "B. Harmon" 4 => "J.M. Mansbach" 5 => "P.A. Piedra" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41467-021-23859-6" "Revista" => array:5 [ "tituloSerie" => "Nat Commun" "fecha" => "2021" "volumen" => "12" "paginaInicial" => "3601" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34127671" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0105" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.G. Holt" 1 => "D. Mok" 2 => "D. Panda" 3 => "L. Renn" 4 => "G. Fabozzi" 5 => "N.H. deKlerk" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2018.08.035" "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2019" "volumen" => "143" "paginaInicial" => "1176" "paginaFinal" => "1182.e5" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30217468" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0110" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Induction of MxA gene expression by influenza A virus requires type I or type III interferon signaling" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Holzinger" 1 => "C. Jorns" 2 => "S. Stertz" 3 => "S. Boisson-Dupuis" 4 => "R. Thimme" 5 => "M. Weidmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JVI.00546-06" "Revista" => array:6 [ "tituloSerie" => "J Virol" "fecha" => "2007" "volumen" => "81" "paginaInicial" => "7776" "paginaFinal" => "7785" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17494065" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0115" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interferon-stimulated genes: a complex web of host defenses" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "W.M. Schneider" 1 => "M.D. Chevillotte" 2 => "C.M. Rice" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev-immunol-032713-120231" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Immunol" "fecha" => "2014" "volumen" => "32" "paginaInicial" => "513" "paginaFinal" => "545" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24555472" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0120" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mx proteins: antiviral gatekeepers that restrain the uninvited" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Verhelst" 1 => "P. Hulpiau" 2 => "X. Saelens" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/MMBR.00024-13" "Revista" => array:6 [ "tituloSerie" => "Microbiol Mol Biol Rev" "fecha" => "2013" "volumen" => "77" "paginaInicial" => "551" "paginaFinal" => "566" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24296571" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0125" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children – the TREND study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Rhedin" 1 => "A. Eklundh" 2 => "M. Ryd-Rinder" 3 => "V. Peltola" 4 => "M. Waris" 5 => "J. Gantelius" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cmi.2022.05.008" "Revista" => array:6 [ "tituloSerie" => "Clin Microbiol Infect" "fecha" => "2022" "volumen" => "28" "paginaInicial" => "1251" "paginaFinal" => "1257" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35597507" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0130" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased lymphoid MxA expression in acute asthma exacerbation in children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Itazawa" 1 => "Y. Adachi" 2 => "H. Imamura" 3 => "Y. Okabe" 4 => "J. Yamamoto" 5 => "Y. Onoue" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1034/j.1398-9995.2001.00312.x" "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "2001" "volumen" => "56" "paginaInicial" => "895" "paginaFinal" => "898" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11551256" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0135" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Short- and long-term efficacy of prednisolone for first acute rhinovirus-induced wheezing episode" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Jartti" 1 => "R. Nieminen" 2 => "T. Vuorinen" 3 => "P. Lehtinen" 4 => "T. Vahlberg" 5 => "J. Gern" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2014.07.001" "Revista" => array:3 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2015" "volumen" => "135" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0140" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Direct and second hand cigarette smoke exposure and development of childhood asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S.H. Gopal" 1 => "S. Mukherjee" 2 => "S.K. Das" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.15436/2378-6841.16.1122" "Revista" => array:4 [ "tituloSerie" => "J Environ Health Sci" "fecha" => "2016" "volumen" => "2" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29399637" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0145" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic associations with viral respiratory illnesses and asthma control in children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.A. Loisel" 1 => "G. Du" 2 => "T.S. Ahluwalia" 3 => "C.J. Tisler" 4 => "M.D. Evans" 5 => "R.A. Myers" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/cea.12642" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2016" "volumen" => "46" "paginaInicial" => "112" "paginaFinal" => "124" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26399222" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0150" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rhinovirus C causes heterogeneous infection and gene expression in airway epithelial cell subsets" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Basnet" 1 => "C. Mohanty" 2 => "Y.A. Bochkov" 3 => "R.A. Brockman-Schneider" 4 => "C. Kendziorski" 5 => "J.E. Gern" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.mucimm.2023.01.008" "Revista" => array:6 [ "tituloSerie" => "Mucosal Immunol" "fecha" => "2023" "volumen" => "16" "paginaInicial" => "386" "paginaFinal" => "398" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36796588" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0155" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of deficient type III interferon-lambda production in asthma exacerbations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Contoli" 1 => "S.D. Message" 2 => "V. Laza-Stanca" 3 => "M.R. Edwards" 4 => "P.A.B. Wark" 5 => "N.W. Bartlett" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nm1462" "Revista" => array:6 [ "tituloSerie" => "Nat Med" "fecha" => "2006" "volumen" => "12" "paginaInicial" => "1023" "paginaFinal" => "1026" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16906156" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0160" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In vivo bronchial epithelial interferon responses are augmented in asthma on day 4 following experimental rhinovirus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Farne" 1 => "L. Lin" 2 => "D.J. Jackson" 3 => "M. Rattray" 4 => "A. Simpson" 5 => "A. Custovic" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2021-217389" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2022" "volumen" => "77" "paginaInicial" => "929" "paginaFinal" => "932" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35790388" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0165" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cytokine expression in rhinovirus- vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Hurme" 1 => "M. Komulainen" 2 => "M. Tulkki" 3 => "A. Leino" 4 => "B. Rückert" 5 => "R. Turunen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fimmu.2022.1044621" "Revista" => array:5 [ "tituloSerie" => "Front Immunol" "fecha" => "2022" "volumen" => "13" "paginaInicial" => "1044621" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36451824" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0170" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coinfection by influenza A virus and respiratory syncytial virus produces hybrid virus particles" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Haney" 1 => "S. Vijayakrishnan" 2 => "J. Streetley" 3 => "K. Dee" 4 => "D.M. Goldfarb" 5 => "M. Clarke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41564-022-01242-5" "Revista" => array:6 [ "tituloSerie" => "Nat Microbiol" "fecha" => "2022" "volumen" => "7" "paginaInicial" => "1879" "paginaFinal" => "1890" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36280786" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/03002896/0000006000000003/v3_202406110502/S0300289624000012/v3_202406110502/en/main.assets" "Apartado" => array:4 [ "identificador" => "93560" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Scientific Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/03002896/0000006000000003/v3_202406110502/S0300289624000012/v3_202406110502/en/main.pdf?idApp=UINPBA00003Z&text.app=https://www.archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289624000012?idApp=UINPBA00003Z" ]
Year/Month | Html | Total | |
---|---|---|---|
2024 September | 1 | 0 | 1 |
2024 June | 1 | 0 | 1 |
2024 May | 1 | 2 | 3 |
2024 April | 4 | 1 | 5 |
2024 March | 47 | 6 | 53 |
2024 February | 46 | 34 | 80 |
2024 January | 49 | 30 | 79 |