Original Article
Respiratory viral infections in a cohort of children during the first year of life and their role in the development of wheezing
Infecciones virales respiratorias en una cohorte de niños durante el primer año de vida y su papel en el desarrollo de sibilancias
Cristina Calvoa,
, Isabel Aguadoa, María Luz García-Garcíaa, Esther Ruiz-Chercolesb, Eloisa Díaz-Martinezc, Rosa María Albañild, Olga Campeloe, Antonio Olivasd, Luisa Muñóz-Gonzalezf, Francisco Pozog, Rosa Fernandez-Arroyoc, Adelaida Fernandez-Rincóna, Ana Calderong, Inmaculada Casasg, Working Group on Recurrent Wheezing ◊
Corresponding author
a Servicio de Pediatría, Hospital Severo Ochoa, Leganés, Madrid, Spain
b Centro de Salud María Jesús Hereza, Leganés, Madrid, Spain
c Centro de Salud Jaime Vera, Leganés, Madrid, Spain
d Centro de Salud Cuzco, Fuenlabrada, Madrid, Spain
e Centro de Salud Leganés Norte, Leganés, Madrid, Spain
f Centro de Salud María Ángeles Gómez López, Leganés, Madrid, Spain
g Laboratorio de Gripe y Virus Respiratorios, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain
Read
5818
Timeswas read the article
2332
Total PDF
3486
Total HTML
Share statistics
array:24 [ "pii" => "S2341287917301059" "issn" => "23412879" "doi" => "10.1016/j.anpede.2016.08.008" "estado" => "S300" "fechaPublicacion" => "2017-08-01" "aid" => "2143" "copyright" => "Asociación Española de Pediatría" "copyrightAnyo" => "2016" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2017;87:104-10" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1470 "formatos" => array:3 [ "EPUB" => 116 "HTML" => 954 "PDF" => 400 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S169540331630248X" "issn" => "16954033" "doi" => "10.1016/j.anpedi.2016.08.002" "estado" => "S300" "fechaPublicacion" => "2017-08-01" "aid" => "2143" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2017;87:104-10" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 5329 "formatos" => array:3 [ "EPUB" => 140 "HTML" => 3918 "PDF" => 1271 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Infecciones virales respiratorias en una cohorte de niños durante el primer año de vida y su papel en el desarrollo de sibilancias" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "104" "paginaFinal" => "110" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Respiratory viral infections in a cohort of children during the first year of life and their role in the development of wheezing" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2033 "Ancho" => 1424 "Tamanyo" => 110850 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Detección viral en infecciones respiratorias y en controles.</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">HRV, rinovirus; VRS, virus respiratorio sincitial; PIV, virus parainfluenza; HMPV, metapneumovirus humano; AD, adenovirus; FLU, virus influenza; HBoV: bocavirus humano.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Cristina Calvo, Isabel Aguado, María Luz García-García, Esther Ruiz-Chercoles, Eloisa Díaz-Martinez, Rosa María Albañil, Olga Campelo, Antonio Olivas, Luisa Muñóz-Gonzalez, Francisco Pozo, Rosa Fernandez-Arroyo, Adelaida Fernandez-Rincón, Ana Calderon, Inmaculada Casas" "autores" => array:15 [ 0 => array:2 [ "nombre" => "Cristina" "apellidos" => "Calvo" ] 1 => array:2 [ "nombre" => "Isabel" "apellidos" => "Aguado" ] 2 => array:2 [ "nombre" => "María Luz" "apellidos" => "García-García" ] 3 => array:2 [ "nombre" => "Esther" "apellidos" => "Ruiz-Chercoles" ] 4 => array:2 [ "nombre" => "Eloisa" "apellidos" => "Díaz-Martinez" ] 5 => array:2 [ "nombre" => "Rosa María" "apellidos" => "Albañil" ] 6 => array:2 [ "nombre" => "Olga" "apellidos" => "Campelo" ] 7 => array:2 [ "nombre" => "Antonio" "apellidos" => "Olivas" ] 8 => array:2 [ "nombre" => "Luisa" "apellidos" => "Muñóz-Gonzalez" ] 9 => array:2 [ "nombre" => "Francisco" "apellidos" => "Pozo" ] 10 => array:2 [ "nombre" => "Rosa" "apellidos" => "Fernandez-Arroyo" ] 11 => array:2 [ "nombre" => "Adelaida" "apellidos" => "Fernandez-Rincón" ] 12 => array:2 [ "nombre" => "Ana" "apellidos" => "Calderon" ] 13 => array:2 [ "nombre" => "Inmaculada" "apellidos" => "Casas" ] 14 => array:1 [ "colaborador" => "Grupo de Estudio de Sibilancias Recurrentes" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2341287917301059" "doi" => "10.1016/j.anpede.2016.08.008" "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/S2341287917301059?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S169540331630248X?idApp=UINPBA00005H" "url" => "/16954033/0000008700000002/v1_201707260014/S169540331630248X/v1_201707260014/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2341287917301035" "issn" => "23412879" "doi" => "10.1016/j.anpede.2016.10.013" "estado" => "S300" "fechaPublicacion" => "2017-08-01" "aid" => "2166" "copyright" => "Asociación Española de Pediatría" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "An Pediatr (Barc). 2017;87:111-3" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1340 "formatos" => array:3 [ "EPUB" => 125 "HTML" => 818 "PDF" => 397 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific Letter</span>" "titulo" => "Toxic shock syndrome in a paediatric intensive care unit over the last 15 years" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "111" "paginaFinal" => "113" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de <span class="elsevierStyleItalic">shock</span> tóxico en una unidad de cuidados intensivos pediátricos en los últimos 15 años" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Laura Butragueño Laiseca, Marina García Morín, Estíbaliz Barredo Valderrama, Andrés J. Alcaraz Romero" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Laura" "apellidos" => "Butragueño Laiseca" ] 1 => array:2 [ "nombre" => "Marina" "apellidos" => "García Morín" ] 2 => array:2 [ "nombre" => "Estíbaliz" "apellidos" => "Barredo Valderrama" ] 3 => array:2 [ "nombre" => "Andrés J." "apellidos" => "Alcaraz Romero" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1695403316302739" "doi" => "10.1016/j.anpedi.2016.10.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1695403316302739?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287917301035?idApp=UINPBA00005H" "url" => "/23412879/0000008700000002/v1_201707260017/S2341287917301035/v1_201707260017/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S234128791730100X" "issn" => "23412879" "doi" => "10.1016/j.anpede.2016.09.007" "estado" => "S300" "fechaPublicacion" => "2017-08-01" "aid" => "2158" "copyright" => "Asociación Española de Pediatría" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "An Pediatr (Barc). 2017;87:95-103" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1989 "formatos" => array:3 [ "EPUB" => 126 "HTML" => 1473 "PDF" => 390 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Vitamin D deficiency and morbimortality in critically ill paediatric patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "95" "paginaFinal" => "103" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Déficit de vitamina D y morbimortalidad en pacientes críticos pediátricos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Patricia García-Soler, Antonio Morales-Martínez, Vanessa Rosa-Camacho, Juan Antonio Lillo-Muñoz, Guillermo Milano-Manso" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Patricia" "apellidos" => "García-Soler" ] 1 => array:2 [ "nombre" => "Antonio" "apellidos" => "Morales-Martínez" ] 2 => array:2 [ "nombre" => "Vanessa" "apellidos" => "Rosa-Camacho" ] 3 => array:2 [ "nombre" => "Juan Antonio" "apellidos" => "Lillo-Muñoz" ] 4 => array:2 [ "nombre" => "Guillermo" "apellidos" => "Milano-Manso" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S169540331630265X" "doi" => "10.1016/j.anpedi.2016.09.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S169540331630265X?idApp=UINPBA00005H" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S234128791730100X?idApp=UINPBA00005H" "url" => "/23412879/0000008700000002/v1_201707260017/S234128791730100X/v1_201707260017/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Respiratory viral infections in a cohort of children during the first year of life and their role in the development of wheezing" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "104" "paginaFinal" => "110" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Cristina Calvo, Isabel Aguado, María Luz García-García, Esther Ruiz-Chercoles, Eloisa Díaz-Martinez, Rosa María Albañil, Olga Campelo, Antonio Olivas, Luisa Muñóz-Gonzalez, Francisco Pozo, Rosa Fernandez-Arroyo, Adelaida Fernandez-Rincón, Ana Calderon, Inmaculada Casas" "autores" => array:15 [ 0 => array:4 [ "nombre" => "Cristina" "apellidos" => "Calvo" "email" => array:1 [ 0 => "ccalvorey@ono.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" => "Isabel" "apellidos" => "Aguado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "María Luz" "apellidos" => "García-García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Esther" "apellidos" => "Ruiz-Chercoles" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Eloisa" "apellidos" => "Díaz-Martinez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "Rosa María" "apellidos" => "Albañil" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 6 => array:3 [ "nombre" => "Olga" "apellidos" => "Campelo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 7 => array:3 [ "nombre" => "Antonio" "apellidos" => "Olivas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 8 => array:3 [ "nombre" => "Luisa" "apellidos" => "Muñóz-Gonzalez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 9 => array:3 [ "nombre" => "Francisco" "apellidos" => "Pozo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 10 => array:3 [ "nombre" => "Rosa" "apellidos" => "Fernandez-Arroyo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 11 => array:3 [ "nombre" => "Adelaida" "apellidos" => "Fernandez-Rincón" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 12 => array:3 [ "nombre" => "Ana" "apellidos" => "Calderon" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 13 => array:3 [ "nombre" => "Inmaculada" "apellidos" => "Casas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 14 => array:2 [ "colaborador" => "Working Group on Recurrent Wheezing" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">◊</span>" "identificador" => "fn0005" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital Severo Ochoa, Leganés, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Salud María Jesús Hereza, Leganés, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Centro de Salud Jaime Vera, Leganés, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Centro de Salud Cuzco, Fuenlabrada, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Centro de Salud Leganés Norte, Leganés, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Centro de Salud María Ángeles Gómez López, Leganés, Madrid, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Laboratorio de Gripe y Virus Respiratorios, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Infecciones virales respiratorias en una cohorte de niños durante el primer año de vida y su papel en el desarrollo de sibilancias" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2033 "Ancho" => 1424 "Tamanyo" => 114890 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Viral detection in respiratory infections and controls. hRV, human rhinovirus; RSV, respiratory syncytial virus; PIV, parainfluenza virus; hMPV, human metapneumovirus; AD, adenovirus; FLU, virus influenza; hBoV: human bocavirus.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acute respiratory infections (ARIs) are a major reason for health care use in infants and constitute a substantial economic burden.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">1,2</span></a> Although infections in this age group are most frequently of a viral aetiology,<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">3,4</span></a> inappropriate antibiotic use continues to be widespread. Techniques based on the polymerase chain reaction (PCR) have made the aetiological diagnosis of ARIs possible in children, and made us aware of the high prevalence of asymptomatic viral infections.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5,6</span></a> Respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and influenza virus (FLU) have been clearly identified as respiratory pathogens, and more recent studies have been analysing the role of other viruses such rhinovirus (RV) and human bocavirus (hBoV), although the high prevalence of coinfection with other respiratory viruses or their detection in asymptomatic patients pose challenges to the interpretation of these positive results.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">It is known that children with severe RSV infection that require hospitalisation are at high risk of developing asthma in the long term, even as late as age 18 years, as Sigurs et al. demonstrated.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">9</span></a> There is also evidence of an increased risk of recurrent wheezing up to age 5 years in infants hospitalised due to bronchiolitis associated to hMPV.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">10</span></a> There are fewer studies in children that have not been admitted to hospital, among which we would like to mention the classic studies by Stein et al., who analysed an unselected cohort and found that milder infections by RSV also increased the risk of developing wheezing.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">11</span></a> In recent years, the role of RV as a long-term predictor of future asthma has also been investigated. A study of particular interest on the subject is that of Lemanske et al.,<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> whose cohort of infants that had a RV infection with wheezing in the first year of life were at increased risk of having developed wheezing by age 3 years, with an odds ratio of 10. Most of the studies that assess the risk of developing asthma or wheezing have been conducted in selected high-risk populations.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">13,14</span></a> Furthermore, little is known about mild viral respiratory infections managed in outpatient settings in relation to the future development of wheezing, not to mention asymptomatic viral infections, although it is generally assumed that risk increases with increasing severity. The objective of our prospective study was to analyse asymptomatic and symptomatic infections of varying severity in a cohort of newborns during the first year of life and assess their role in the development of recurrent wheezing. Our secondary objective was to analyse the aetiology and clinical characteristics of these infections.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Recruitment of newborns and study design</span><p id="par0015" class="elsevierStylePara elsevierViewall">We conducted a prospective cohort study in newborns to analyse the association between past viral infections of varying severity and the development of recurrent wheezing. We requested the participation of all newborns delivered in four health care centres in the Área Sur health zone of Madrid during their first neonatal visit (7–14 days of life). The parents or guardians signed an informed consent form and completed a questionnaire of epidemiological data (history of asthma and atopy in the family, exposure to tobacco smoke, pregnancy and delivery data, number of siblings). Nasopharyngeal aspirate (NPA) specimens were collected during this visit and routine checkups performed at ages 2, 4, 6 and 12 months. Furthermore, if the infants developed respiratory symptoms, they were evaluated by a paediatrician, with collection of an additional NPA sample.</p><p id="par0020" class="elsevierStylePara elsevierViewall">We considered children with specimens collected during routine well-child checkups healthy controls, even if they presented with isolated rhinorrhoea. We defined asymptomatic infection as detection of a virus in the NPA of one of these patients. We defined clinically significant respiratory infection as a case that met the clinical criteria for respiratory infection presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. We defined “first detected viral infection” as PCR detecting a respiratory virus in a sample for the first time in the life of a child, whether the infection was asymptomatic, symptomatic and managed at the outpatient level, or symptomatic and requiring hospital admission.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clinical manifestations of respiratory infection</span><p id="par0025" class="elsevierStylePara elsevierViewall">When a child met the criteria for respiratory infection described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, the paediatrician conducted an evaluation, a clinical data form was completed, and a NPA sample collected. If the infant required admission to hospital, data for the most relevant variables were also collected in another form. Isolated rhinorrhoea was not considered a symptomatic respiratory infection. We differentiated between the following forms of respiratory infection: upper respiratory tract infection, defined as infection meeting the criteria specified in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> in the absence of respiratory distress or wheezing. We defined bronchiolitis as the first episode of respiratory infection that manifested with respiratory distress and wheezing. Subsequent episodes of similar characteristics were classified as recurrent wheezing. Episodes manifesting with inspiratory dyspnoea and wheezing were classified as laryngotracheobronchitis. Laryngitis was defined as inspiratory dyspnoea without wheezing. We defined pneumonia as evidence of focal infiltrates or consolidation in chest radiography in the absence of wheezing.</p><p id="par0030" class="elsevierStylePara elsevierViewall">We classified all infections requiring hospital admission as severe, and the rest as mild.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Sample collection</span><p id="par0035" class="elsevierStylePara elsevierViewall">When the requisite criteria were met, a NPA sample was collected and kept at 4<span class="elsevierStyleHsp" style=""></span>°C to await transportation to the Influenza and Respiratory Viruses Laboratory of the Centro Nacional de Microbiología (National Centre of Microbiology). In hospitalised patients, the NPA sample was collected between 7 and 8<span class="elsevierStyleHsp" style=""></span>AM of the morning following admission and kept refrigerated until it was transported.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Virology testing</span><p id="par0040" class="elsevierStylePara elsevierViewall">Three RT-nested PCR assays were used to test for 16 respiratory viruses. Reverse transcription (RT) and the first amplification reaction were performed with OneStep RT-PCR kits (Qiagen). Influenza A, B and C were detected by a previously described PCR assay.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a> A second multiplex PCR assay was used to detect parainfluenza virus (PIV) 1 through 4, coronavirus 229E and OC43, enterovirus and RV.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a> The presence of RSV-A and B, hMPV, hBoV and adenovirus (ADV) was assessed with a third RT-nested PCR assay using the BRQ method.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">We have expressed discrete data as percentages and continuous data as mean and standard deviation. We compared clinical and laboratory characteristics using the Student's <span class="elsevierStyleItalic">t</span>, Mann–Whitney <span class="elsevierStyleItalic">U</span>, chi-square and Fisher exact tests. We defined statistical significance as a <span class="elsevierStyleItalic">P</span>-value of less than .05 in any of the tests. The statistical analysis was performed with the Statistical Package for the Social Sciences (SPSS) version 13.0.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Epidemiological characteristics of the cohort</span><p id="par0050" class="elsevierStylePara elsevierViewall">We recruited a total of 302 infants at birth, of which 55.3% were male (167), 80% born to Spanish parents, and 14% of Latin-American ancestry. Thirty-five percent of infants were exposed to tobacco smoke; 36% of mothers and 37% of fathers had asthma and/or atopy. Only 2 patients were born preterm at a gestational age of 33 weeks. All infants but 7 completed the yearlong followup. Those 7 patients did not attend the 12-month checkup, but we contacted their paediatricians to obtain information about their clinical outcomes, so they were ultimately included in the analysis.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Virology specimens and results</span><p id="par0055" class="elsevierStylePara elsevierViewall">A total of 1,239 samples were collected, 1,005 during routine visits and 288 when a respiratory infection was suspected. Of the samples collected during the well-child checkups, 30.8% (310) tested positive, while viruses were detected in 77.8% of respiratory infection cases (224/288), <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001 (odds ratio, 3; 95% confidence interval, 2.4–3.8). The frequency of viral detection in asymptomatic children (healthy controls) increased proportionally with age from 20.8% in newborns aged 15 days to up to 42% in infants aged 12 months. The virus identified most frequently was RV, found in 82% (254) of cases. Other viruses were found in a small proportion of cases: ADV (9.7%), PIV (4.2%), hBoV (3.2%), hMPV (2.9%), FLU (2.2%) and RSV (1.6%) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">First detected viral infection and patient outcomes</span><p id="par0060" class="elsevierStylePara elsevierViewall">Of the 302 infants included in the study, 239 (79%) had at least one positive viral detection in the first year of life (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The virus detected most frequently was RV (181 samples, 71%), followed by PIV (6.3%), ADV (5%) and RSV (6%). Coinfections were only detected in 21 cases (8.8%). The mean age at detection of the first viral infection was 3.4 months (SD, 2.8). The first detected viral infection was associated with upper respiratory tract infections in 45 patients (20%), bronchiolitis in 19 (8.5%) while remaining 159 samples (70%) corresponded to asymptomatic patients and had been collected during routine well-child checkups.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">We analysed the outcomes of infants that had at least one positive specimen, and found that 27 (11%) developed recurrent wheezing in the first year of life (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD, 2.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.2 episodes; range, 2–5) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Rhinovirus was the first virus detected in 18 patients (66%), of who 14 (52%) were asymptomatic at the time of the specimen collection (routine checkup). The mean age of infants that developed recurrent wheezing with their first positive viral detection was 2 months (SD, 1.3; all but three were at least 3 months old). Ten of the 27 infants with episodes of bronchiolitis required admission (37%). The most frequently involved virus was RV, both in mild bronchiolitis cases managed at the outpatient level (11/17, 69%) and in severe cases that required hospitalisation (7/10, 70%).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Recurrent wheezing episodes (at least one following the initial bronchiolitis) occurred in 58.3% of infants in who the first viral detection corresponded to a severe infection that required admission, compared to 8.6% of infants whose first detection corresponded to a mild infection managed at the outpatient level or an asymptomatic infection (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001; odds ratio, 2.18; 95% CI, 1.05–4.5). A total of 5 infants received montelukast or budesonide during the followup (18%, 3 admitted to hospital and 2 managed at outpatient level at first positive viral detection). There were no differences in the family history of asthma or atopy between children with and without recurrent wheezing.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Characteristics of infections managed in outpatient and inpatient settings</span><p id="par0075" class="elsevierStylePara elsevierViewall">There were 288 episodes of infection managed in outpatient settings that corresponded to 160 infants (53% of the total sample) who had between 1 and 6 episodes each (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD, 1.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1). The most frequent symptoms were: fever in 90 cases (38%), rhinorrhoea in 224 (96%), cough in 223 (96%), respiratory distress in 51 (21%) and nonspecific symptoms in 35 (15%). The most frequent diagnoses were upper respiratory tract infection (147, 51%) and bronchiolitis (48, 16%), with a lesser incidence of recurrent wheezing, laryngitis and pneumonia. Only 2 patients had infiltrates on radiologic examination, and both required hospital admission during the followup. The viruses detected in these infections were RV in 127 cases (55.8%), followed by PIV (13%), RSV (12.5%), hMPV (8.9%) and FLU (8%) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The causative agent of upper respiratory tract infection was RV in 61% of cases, followed by PIV (13%) and ADV (11%). When it came to bronchiolitis, RV was detected in 53%, RSV in 25% and hMPV in 8% of cases.</p><p id="par0080" class="elsevierStylePara elsevierViewall">We analysed a total of 19 hospital admissions corresponding to 14 infants (14/302; 4.6% of the cohort; 5.8% of infants with a positive viral detection). Five patients were admitted more than twice in the first year of life. Fifty-eight percent of admitted patients (11) were female. The mean age of admission was 3.6 months (SD, 2.5 months; range, 6 days–8 months). Forty-two percent presented with fever (mean, 38.6<span class="elsevierStyleHsp" style=""></span>°C; SD, 0.9<span class="elsevierStyleHsp" style=""></span>°C) lasting 3.5 days (SD, 2). Sixty-eight percent (13/19 episodes) required oxygen supplementation for a mean of 5 days (SD, 3). Twenty-six percent (5/19) had infiltrates detected by radiology. The diagnoses were bronchiolitis in 12 cases (63%), wheezing episode in 3 (15%), upper respiratory tract infection in 3 and pneumonia in 1. Only 3 infants received antibiotics. Respiratory syncytial virus was detected in 42% of the cases and RV in 52%. Viral coinfection was detected in 4 cases.</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">A considerable number of infants test positive for at least one respiratory virus in the first year of life, and we observed a percentage of 79% in our cohort. More than half of the cohort experienced at least one symptomatic infection treated at the outpatient level, with a mean of 1.6 symptomatic infections a year (range, 1–6), while approximately 5% required hospital admission. Rhinovirus was the virus detected most frequently in symptomatic (43%) as well as asymptomatic (25%) infants.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Eleven percent of the infants with positive virology results went on to develop recurrent wheezing in the first year of life, but the risk was much higher in patients that required admission due to bronchiolitis (58%; odds ratio, 2.18) compared to patients whose first infection was mild or asymptomatic.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Our data are consistent with the findings of the study conducted by Rhedin et al., who analysed a group of paediatric outpatients with respiratory infections and a group of asymptomatic controls. Rhedin et al. detected respiratory viruses in 72.3% of cases (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>151) and 35.4% of controls (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>74) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.001). Rhinovirus was the virus identified most frequently in both cases and controls (47.9 and 21.5%, respectively).<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">6</span></a> Although infections by RV are common, a recent study that used nucleotide sequencing demonstrated that the prolonged presence of rhinovirus RNA in the respiratory tract following an upper respiratory tract infection is rare in healthy infants (<5%). In these infants, the detection of RV RNA in repeat samples at least 30 days apart most likely corresponded to new infections.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">17</span></a> Another study found that the detection of the same virus strain more than 2 weeks apart was unusual.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a> In our study, we found that RV was detected in a significant proportion of infants that were classified as healthy (routine vaccination visit), probably because we did not take isolated rhinorrhoea into account, and this is a frequent symptom in children that does not contraindicate vaccination. However, it is possible that rhinorrhoea is actually a presenting symptom in mild RV infections. Unfortunately, we have no data on the percentage of infants considered healthy controls that had rhinorrhoea as the sole symptom. This is consistent with the hypothesis of Jartti et al. according to which RV always causes an actual infection, which may or may not be clinically relevant.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">5</span></a> Although there are authors like Jansen et al.,<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">19</span></a> who found a higher RV load in children with acute symptomatic infections compared to asymptomatic children, or Utokaparch et al.,<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">20</span></a> who detected significantly higher RV loads in infections of the lower respiratory tract, there are others, like Takeyama et al.,<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a> who have not found a correlation between viral load and disease severity in RV infections. At any rate, the clinical significance of viral loads in respiratory samples is not well established, and we did not measure viral loads in our patients.</p><p id="par0100" class="elsevierStylePara elsevierViewall">We also ought to highlight the small percentage of coinfections found in our cohort (8.8%), as other case series, including previous studies by our research group, found a percentages of coinfection of up to 46% in hospitalised children with rhinovirus infections.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">22</span></a> We believe that the age of our patients (a substantial proportion of the specimens were collected from infants aged less than 6 months) and our decision to include mild and asymptomatic infections with positive virology may account for the low proportion of coinfection.</p><p id="par0105" class="elsevierStylePara elsevierViewall">In a cohort study of 140 newborns with a design similar to our own, Van der Gugten et al.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">23</span></a> found that RV infections manifesting with wheezing in the first year of life were a risk factor for developing recurrent wheezing in the future. Although they did not assess the severity of acute episodes, mild infections without wheezing were not associated with an increased risk of recurrent wheezing. These authors reached the conclusions we have reached based on our cohort, in which infections by RV or RSV that were sufficiently severe to cause bronchiolitis requiring hospital admission were a risk factor for developing wheezing as early as the first year of life. The followup of our cohort in the immediate future will allow us to learn whether the risk of wheezing continues to be higher in early childhood. As Lemanske et al. suggested,<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">12</span></a> the severity of infection is a risk factor for the development of asthma and recurrent wheezing. Various studies have demonstrated that severe bronchiolitis associated to RV infection increase the risk of asthma, but as we commented above, these studies were conducted in selected populations.<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">24–26</span></a> Our case series, which analysed symptomatic and asymptomatic infections and severity at an early age (less than 3 months in most first episodes) in an unselected population contributes a broader picture on the subject.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Although our study has strengths, such as its unselected sample and testing for all respiratory viruses (as opposed to only the most prevalent) and for the presence of asymptomatic infection, we ought to comment on certain methodological aspects. We did not collect weekly samples to study viral shedding and its duration, and we also did not perform genotyping of RV. The duration of followup was short, and the number of patients with recurrent wheezing small. Nevertheless, we believe that the association found in the study is worth considering, and that we will be able to reach broader conclusions in upcoming years. Until then, we can state that respiratory infections in the first months of life that are severe enough to require hospitalisation are a risk factor for the development of recurrent wheezing.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding</span><p id="par0115" class="elsevierStylePara elsevierViewall">This study was partially funded by the Fondo de Investigaciones Sanitarias (<span class="elsevierStyleGrantSponsor" id="gs1">Health Research Fund</span>), project PI12/0129; the 2011 Research Grant of the Asociación Española de Pediatría (<span class="elsevierStyleGrantSponsor" id="gs2">Spanish Association of Paediatrics [AEP]</span>); and the 2011 Research Grant of the Sociedad Española de Neumología Pediátrica (<span class="elsevierStyleGrantSponsor" id="gs3">Spanish Society of Paediatric Pulmonology</span>).</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflict of interests</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres874564" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec862956" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres874563" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec862955" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Recruitment of newborns and study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinical manifestations of respiratory infection" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Sample collection" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Virology testing" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Epidemiological characteristics of the cohort" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Virology specimens and results" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "First detected viral infection and patient outcomes" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Characteristics of infections managed in outpatient and inpatient settings" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-05-19" "fechaAceptado" => "2016-08-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec862956" "palabras" => array:6 [ 0 => "Respiratory infections" 1 => "Viral infections" 2 => "Asymptomatic infections" 3 => "Rhinovirus" 4 => "Wheezing" 5 => "Infants" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec862955" "palabras" => array:6 [ 0 => "Infecciones respiratorias" 1 => "Infecciones virales" 2 => "Infecciones asintomáticas" 3 => "Rinovirus" 4 => "Sibilancias" 5 => "Lactantes" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">It is known that infants with viral respiratory infections severe enough to require hospital admission have a high risk of developing recurrent wheezing. Few data have been published on unselected populations. The main aim of this study was to analyse symptomatic and asymptomatic respiratory viral infections during the first year of life in a cohort of infants, recruited at birth, and the development of recurrent wheezing.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A total of 302 newborns were recruited. A nasopharyngeal aspirate was taken when the patients had a respiratory infection, as well as in the visits for vaccination at 2, 4, 6, and 12 months. RT-nested PCR assays were performed to detect 16 viruses.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 1293 samples were analysed (1005 healthy controls and 288 respiratory infections). Samples taken during routine check-ups were positive in 30.8% of cases, while those with respiratory infection were positive in 77.8%, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001 (OR: 3, 95% CI: 2.4–3.8). A total of 239 (79%) infants had at least 1 positive respiratory viral infection detected. The most frequent virus (71%) was rhinovirus (RV). Recurrent wheezing was found in 27 (11%) children during their first year of life (1.2 episodes, SD 2.9). Recurrent wheezing was present in 58.3% of patients admitted to hospital during their first viral infection, vs. 8.6% of infants when the first infection was mild or who had asymptomatic viral detection, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001 (OR: 2.18; 95% CI: 1.05–4.5).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In our series, severe respiratory infections leading to hospitalisation in the first months of life are risk factors for developing wheezing, but not in the case of mild RV infections.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Las infecciones respiratorias virales que requieren hospitalización parecen conferir riesgo de desarrollar sibilancias recurrentes, pero existen pocos datos publicados en poblaciones no seleccionadas por tener factores de riesgo. Nuestro objetivo principal fue analizar si las infecciones respiratorias virales sintomáticas y asintomáticas, de diferente gravedad, durante el primer año de vida en una cohorte de recién nacidos, suponen un mayor riesgo de sibilancias recurrentes.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 302 recién nacidos. Se recogió aspirado nasofaríngeo a los niños cuando presentaron una infección respiratoria y de forma periódica en los controles de salud (2, 4, 6 y 12 meses). Se estudiaron 16 virus respiratorios mediante reacción en cadena de polimerasa (PCR).</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se analizaron 1.293 muestras (1.005 controles de salud y 288 infecciones respiratorias). El 30,8% de las muestras tomadas en los controles de salud fueron positivas, frente a un 77,8% en las infecciones respiratorias, p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001 (OR: 3, IC 95%: 2,4-3,8). Un total de 239 (79%) lactantes tuvieron al menos una detección viral positiva durante el primer año de vida. El virus más frecuentemente identificado (71%) fue el rinovirus (RV). En 27 lactantes (11%) se detectaron sibilancias recurrentes durante su primer año de vida (2,9 DE: 1,2 episodios). El 58,3% de los lactantes cuya primera infección respiratoria requirió hospitalización desarrollaron sibilancias de repetición, frente al 8,6% de los niños cuya primera infección fue leve o asintomática, p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001 (OR: 2,18; lC 95%: 1,05-4,5).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En nuestra serie, las infecciones respiratorias virales graves en los primeros meses de vida supusieron un factor de riesgo para desarrollar sibilancias recurrentes. No ocurrió lo mismo con las infecciones respiratorias leves.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:2 [ 0 => array:3 [ "etiqueta" => "◊" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Members of the Working Group on Recurrent Wheezing are listed in <a class="elsevierStyleCrossRef" href="#sec0080">Appendix A</a>.</p>" "identificador" => "fn0005" ] 1 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Calvo C, Aguado I, García-García ML, Ruiz-Chercoles E, Díaz-Martinez E, Albañil RM, et al. Infecciones virales respiratorias en una cohorte de niños durante el primer año de vida y su papel en el desarrollo de sibilancias. An Pediatr (Barc). 2017;87:104–110.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0125" class="elsevierStylePara elsevierViewall">Luis Carlos Aragón: Centro de Salud Leganés Norte, Leganés, Madrid, Spain.</p> <p id="par0130" class="elsevierStylePara elsevierViewall">Ana María Berroya: Centro de Salud Leganés Norte, Leganés, Madrid, Spain.</p> <p id="par0135" class="elsevierStylePara elsevierViewall">Laura Carretero: entro de Salud Leganés Norte, Leganés, Madrid, Spain.</p> <p id="par0140" class="elsevierStylePara elsevierViewall">José María de Cea: Department of Paediatrics, Hospital Severo Ochoa, Leganés, Madrid, Spain.</p> <p id="par0145" class="elsevierStylePara elsevierViewall">Sandra García-Estevez: Centro de Salud Leganés Norte, Leganés, Madrid, Spain.</p> <p id="par0150" class="elsevierStylePara elsevierViewall">Gema García-Ron: Centro de Salud María Jesús Hereza, Leganés, Madrid, Spain.</p> <p id="par0155" class="elsevierStylePara elsevierViewall">Mónica Gonzalez-Esguevillas: Centro de Salud María Jesús Hereza, Leganés, Madrid, Spain.</p> <p id="par0160" class="elsevierStylePara elsevierViewall">Carmen Luján: Centro de Salud Jaime Vera, Leganés, Madrid, Spain.</p> <p id="par0165" class="elsevierStylePara elsevierViewall">Mar Molinero: Influenza and Respiratory Viruses Laboratory, Centro Nacional de Microbiología, Instituto de Salud Carlos <span class="elsevierStyleSmallCaps">III</span>, Madrid, Spain.</p> <p id="par0170" class="elsevierStylePara elsevierViewall">Fermín Vinaixa: Centro de Salud Leganés Norte, Leganés, Madrid, Spain.</p>" "etiqueta" => "Appendix A" "titulo" => "Working Group on Recurrent Wheezing" "identificador" => "sec0080" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2033 "Ancho" => 1424 "Tamanyo" => 114890 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Viral detection in respiratory infections and controls. hRV, human rhinovirus; RSV, respiratory syncytial virus; PIV, parainfluenza virus; hMPV, human metapneumovirus; AD, adenovirus; FLU, virus influenza; hBoV: human bocavirus.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 771 "Ancho" => 1613 "Tamanyo" => 102793 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">First positive viral detection and associated clinical diagnosis.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 925 "Ancho" => 1579 "Tamanyo" => 66779 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Severity of disease associated to the first positive viral test result in infants that developed recurrent wheezing.</p>" ] ] 3 => 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:1 [ "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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">At least 2 of the following</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Fever</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Rhinorrhoea</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cough</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Tachypnoea/respiratory distress</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Nonspecific nonrespiratory symptoms (at least 2 out of 5)</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Vomiting \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Refusal to feed \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Diarrhoea \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Lethargy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Irritability \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1475955.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Clinical criteria for the diagnosis of respiratory infection.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0135" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The economic burden of noninfluenza-related viral respiratory tract infection in the United States" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.M. Fendrick" 1 => "A.S. Monto" 2 => "B. Nightengale" 3 => "M. Sarnes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "2003" "volumen" => "163" "paginaInicial" => "487" "paginaFinal" => "494" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12588210" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0140" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Viruses associated with acute respiratory infections and influenza-like illness among outpatients from the Influenza Incidence Surveillance Project, 2010–2011" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Fowlkes" 1 => "A. Giorgi" 2 => "D. Erdman" 3 => "J. Temte" 4 => "K. Goodin" 5 => "S. di Lonardo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/infdis/jit806" "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "2014" "volumen" => "209" "paginaInicial" => "1715" "paginaFinal" => "1725" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24338352" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0145" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Detection of new respiratory viruses in infants hospitalized with bronchiolitis. A three year prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Calvo" 1 => "F. Pozo" 2 => "M.L. García-García" 3 => "M. Sanchez" 4 => "M. Lopez-Valero" 5 => "P. Pérez-Breña" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1651-2227.2010.01714.x" "Revista" => array:6 [ "tituloSerie" => "Acta Paediatr" "fecha" => "2010" "volumen" => "99" "paginaInicial" => "883" "paginaFinal" => "887" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20163373" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0150" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Respiratory syncytial virus-associated hospitalizations among children less than 24 months of age" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.B. Hall" 1 => "G.A. Weinberg" 2 => "A.K. Blumkin" 3 => "K.M. Edwards" 4 => "M.A. Staat" 5 => "A.F. Schultz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1542/peds.2013-0303" "Revista" => array:6 [ "tituloSerie" => "Pediatrics" "fecha" => "2013" "volumen" => "132" "paginaInicial" => "e341" "paginaFinal" => "e348" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23878043" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0155" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Indentification of respiratory viruses in asymptomatic subjects: aymptomatic respiratory viral infections" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "T. Jartti" 1 => "L. Jartti" 2 => "V. Peltola" 3 => "M. Waris" 4 => "O. Ruuskanen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/INF.0b013e31817e695d" "Revista" => array:7 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "2008" "volumen" => "27" "paginaInicial" => "1103" "paginaFinal" => "1107" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18978518" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1699258X14000606" "estado" => "S300" "issn" => "1699258X" ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0160" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical utility of PCR for common viruses in acute respiratory illness" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Rhedin" 1 => "A. Lindstrand" 2 => "M. Rotzén-Östlund" 3 => "T. Tolfvenstam" 4 => "L. Ohrmalm" 5 => "M.R. Rinder" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1542/peds.2013-3042" "Revista" => array:6 [ "tituloSerie" => "Pediatrics" "fecha" => "2014" "volumen" => "133" "paginaInicial" => "e538" "paginaFinal" => "e545" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24567027" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0165" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human bocavirus detection in nasopharyngeal aspirates of children without clinical symptoms of respiratory infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.L. García-García" 1 => "C. Calvo" 2 => "F. Pozo" 3 => "P. Pérez-Breña" 4 => "S. Quevedo" 5 => "T. Bracamonte" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/INF.0b013e3181626d2a" "Revista" => array:6 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "2008" "volumen" => "27" "paginaInicial" => "358" "paginaFinal" => "360" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18316984" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0170" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High incidence of human bocavirus infection in children in Spain" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "F. Pozo" 1 => "M.L. García-García" 2 => "C. Calvo" 3 => "I. Cuesta" 4 => "P. Pérez-Breña" 5 => "I. Casas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcv.2007.08.010" "Revista" => array:6 [ "tituloSerie" => "J Clin Virol" "fecha" => "2007" "volumen" => "40" "paginaInicial" => "224" "paginaFinal" => "228" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17904416" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0175" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Sigurs" 1 => "F. Ajassim" 2 => "B. Kjellman" 3 => "P.D. Robinson" 4 => "F. Sigurbergsson" 5 => "R. Bjarnason" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2009.121582" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2010" "volumen" => "65" "paginaInicial" => "1045" "paginaFinal" => "1052" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20581410" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0180" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human metapneumovirus bronchiolitis in infancy is an important risk factor for asthma at age 5" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.L. García-García" 1 => "C. Calvo" 2 => "I. Casas" 3 => "T. Bracamonte" 4 => "A. Rellán" 5 => "F. Gozalo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ppul.20597" "Revista" => array:6 [ "tituloSerie" => "Pediatr Pulmonol" "fecha" => "2007" "volumen" => "42" "paginaInicial" => "458" "paginaFinal" => "464" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17427899" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0185" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.T. Stein" 1 => "D. Sherrill" 2 => "W.J. Morgan" 3 => "C.J. Holberg" 4 => "M. Halonen" 5 => "L.M. Taussig" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(98)10321-5" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "1999" "volumen" => "354" "paginaInicial" => "541" "paginaFinal" => "545" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10470697" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0190" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rhinovirus illnesses during infancy predict subsequent childhood wheezing" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.F. Lemanske" 1 => "D.J. Jackson" 2 => "R.E. Gangnon" 3 => "M.D. Evans" 4 => "Z. Li" 5 => "P.A. Shult" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2005.06.024" "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2005" "volumen" => "116" "paginaInicial" => "571" "paginaFinal" => "577" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16159626" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0195" "etiqueta" => "13" "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:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2008" "volumen" => "178" "paginaInicial" => "667" "paginaFinal" => "672" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18565953" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0200" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rhinovirus induced wheezing in infancy — the first sign of childhood asthma?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Kotaniemi-Syrjänen" 1 => "R. Vainionpää" 2 => "T.M. Reijonen" 3 => "M. Waris" 4 => "K. Korhonen" 5 => "M. Korppi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2003" "volumen" => "111" "paginaInicial" => "66" "paginaFinal" => "71" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12532098" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0205" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Simultaneous detection of influenza A, B, and C viruses, respiratory syncytial virus, and adenoviruses in clinical samples by multiplex reverse transcription nested-PCR assay" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.T. Coiras" 1 => "P. Perez-Brena" 2 => "M.L. Garcia" 3 => "I. Casas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jmv.10255" "Revista" => array:6 [ "tituloSerie" => "J Med Virol" "fecha" => "2003" "volumen" => "69" "paginaInicial" => "132" "paginaFinal" => "144" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12436489" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0210" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Simultaneous detection of fourteen respiratory viruses in clinical specimens by two multiplex reverse transcription nested-PCR assays" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.T. Coiras" 1 => "J.C. Aguilar" 2 => "M.L. Garcia" 3 => "I. Casas" 4 => "P. Pérez-Breña" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jmv.20008" "Revista" => array:6 [ "tituloSerie" => "J Med Virol" "fecha" => "2004" "volumen" => "72" "paginaInicial" => "484" "paginaFinal" => "495" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14748074" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0215" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Duration of rhinovirus shedding in the upper respiratory tract in the first year of life" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.J. Loeffelholz" 1 => "R. Trujillo" 2 => "R.B. Pyles" 3 => "A.L. Miller" 4 => "P. Alvarez-Fernandez" 5 => "D.L. Pong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1542/peds.2014-2132" "Revista" => array:6 [ "tituloSerie" => "Pediatrics" "fecha" => "2014" "volumen" => "134" "paginaInicial" => "1144" "paginaFinal" => "1150" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25404719" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0220" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serial viral infections in infants with recurrent respiratory illnesses" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "T. Jartti" 1 => "W.M. Lee" 2 => "T. Pappas" 3 => "M. Evans" 4 => "R.F. Lemanske Jr." 5 => "J.E. Gern" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00161907" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2008" "volumen" => "32" "paginaInicial" => "314" "paginaFinal" => "320" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18448489" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0225" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Frequent detection of respiratory viruses without symptoms: toward defining clinically relevant cutoff values" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.R. Jansen" 1 => "J. Wieringa" 2 => "S.M. Koekkoek" 3 => "C.E. Visser" 4 => "D. Pajkrt" 5 => "R. Molenkamp" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JCM.02094-10" "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "2011" "volumen" => "49" "paginaInicial" => "2631" "paginaFinal" => "2636" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21543571" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0230" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The relationship between respiratory viral loads and diagnosis in children presenting to a pediatric hospital emergency department" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Utokaparch" 1 => "D. Marchant" 2 => "J.V. Gosselink" 3 => "J.E. McDonough" 4 => "E.E. Thomas" 5 => "J.C. Hogg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/INF.0b013e3181ff2fac" "Revista" => array:6 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "2011" "volumen" => "30" "paginaInicial" => "e18" "paginaFinal" => "e23" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20980931" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0235" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rhinovirus load and disease severity in children with lower respiratory tract infections" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Takeyama" 1 => "K. Hashimoto" 2 => "M. Sato" 3 => "T. Sato" 4 => "S. Kanno" 5 => "K. Takano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jmv.23306" "Revista" => array:6 [ "tituloSerie" => "J Med Virol" "fecha" => "2012" "volumen" => "84" "paginaInicial" => "1135" "paginaFinal" => "1142" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22585733" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0240" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of rhinovirus C respiratory infections in sick and healthy children in Spain" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Calvo" 1 => "I. Casas" 2 => "M.L. García-García" 3 => "F. Pozo" 4 => "N. Reyes" 5 => "N. Cruz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/INF.0b013e3181d7a708" "Revista" => array:6 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "2010" "volumen" => "29" "paginaInicial" => "717" "paginaFinal" => "720" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20305581" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0245" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human rhinovirus and wheezing: short and long-term associations in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.C. Van der Gugten" 1 => "M.M. van der Zalm" 2 => "C. Uiterwaal" 3 => "B. Wilbrink" 4 => "J.W.A. Rossen" 5 => "C.K. van der Ent" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/INF.0b013e318290620e" "Revista" => array:6 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "2013" "volumen" => "32" "paginaInicial" => "827" "paginaFinal" => "833" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23584579" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0250" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Response to infections in patients with asthma and atopic disease: an epiphenomenon or reflection of host susceptibility?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K.M. James" 1 => "R.S. Peebles Jr." 2 => "T.V. Hartert" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2012.05.056" "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2012" "volumen" => "130" "paginaInicial" => "343" "paginaFinal" => "351" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22846746" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0255" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rhinovirus-induced bronchiolitis and asthma development" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T. Jartti" 1 => "M. Korppi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1399-3038.2011.01170.x" "Revista" => array:6 [ "tituloSerie" => "Pediatr Allergy Immunol" "fecha" => "2011" "volumen" => "22" "paginaInicial" => "350" "paginaFinal" => "355" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21535176" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0260" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Midulla" 1 => "A. Pierangeli" 2 => "G. Cangiano" 3 => "E. Bonci" 4 => "S. Salvadei" 5 => "C. Scagnolari" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00188210" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2012" "volumen" => "39" "paginaInicial" => "396" "paginaFinal" => "402" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21852336" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000008700000002/v1_201707260017/S2341287917301059/v1_201707260017/en/main.assets" "Apartado" => array:4 [ "identificador" => "26005" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000008700000002/v1_201707260017/S2341287917301059/v1_201707260017/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287917301059?idApp=UINPBA00005H" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 9 | 15 |
| 2024 October | 30 | 53 | 83 |
| 2024 September | 51 | 29 | 80 |
| 2024 August | 61 | 44 | 105 |
| 2024 July | 47 | 33 | 80 |
| 2024 June | 56 | 29 | 85 |
| 2024 May | 47 | 31 | 78 |
| 2024 April | 61 | 29 | 90 |
| 2024 March | 42 | 36 | 78 |
| 2024 February | 41 | 29 | 70 |
| 2024 January | 42 | 28 | 70 |
| 2023 December | 22 | 20 | 42 |
| 2023 November | 30 | 21 | 51 |
| 2023 October | 24 | 24 | 48 |
| 2023 September | 16 | 29 | 45 |
| 2023 August | 31 | 17 | 48 |
| 2023 July | 33 | 36 | 69 |
| 2023 June | 24 | 32 | 56 |
| 2023 May | 33 | 23 | 56 |
| 2023 April | 25 | 18 | 43 |
| 2023 March | 55 | 28 | 83 |
| 2023 February | 45 | 12 | 57 |
| 2023 January | 27 | 19 | 46 |
| 2022 December | 61 | 30 | 91 |
| 2022 November | 68 | 29 | 97 |
| 2022 October | 69 | 47 | 116 |
| 2022 September | 33 | 42 | 75 |
| 2022 August | 45 | 77 | 122 |
| 2022 July | 37 | 54 | 91 |
| 2022 June | 32 | 34 | 66 |
| 2022 May | 32 | 43 | 75 |
| 2022 April | 40 | 37 | 77 |
| 2022 March | 58 | 56 | 114 |
| 2022 February | 30 | 22 | 52 |
| 2022 January | 43 | 39 | 82 |
| 2021 December | 85 | 37 | 122 |
| 2021 November | 57 | 36 | 93 |
| 2021 October | 63 | 71 | 134 |
| 2021 September | 39 | 37 | 76 |
| 2021 August | 36 | 45 | 81 |
| 2021 July | 35 | 44 | 79 |
| 2021 June | 43 | 36 | 79 |
| 2021 May | 57 | 64 | 121 |
| 2021 April | 134 | 98 | 232 |
| 2021 March | 54 | 35 | 89 |
| 2021 February | 56 | 21 | 77 |
| 2021 January | 49 | 42 | 91 |
| 2020 December | 50 | 22 | 72 |
| 2020 November | 37 | 25 | 62 |
| 2020 October | 60 | 14 | 74 |
| 2020 September | 52 | 26 | 78 |
| 2020 August | 28 | 21 | 49 |
| 2020 July | 46 | 25 | 71 |
| 2020 June | 39 | 14 | 53 |
| 2020 May | 35 | 25 | 60 |
| 2020 April | 32 | 15 | 47 |
| 2020 March | 35 | 25 | 60 |
| 2020 February | 33 | 23 | 56 |
| 2020 January | 21 | 15 | 36 |
| 2019 December | 59 | 18 | 77 |
| 2019 November | 18 | 9 | 27 |
| 2019 October | 26 | 26 | 52 |
| 2019 September | 23 | 13 | 36 |
| 2019 August | 51 | 17 | 68 |
| 2019 July | 28 | 23 | 51 |
| 2019 June | 18 | 33 | 51 |
| 2019 May | 45 | 21 | 66 |
| 2019 April | 71 | 33 | 104 |
| 2019 March | 30 | 32 | 62 |
| 2019 February | 42 | 24 | 66 |
| 2019 January | 33 | 23 | 56 |
| 2018 December | 43 | 17 | 60 |
| 2018 November | 88 | 41 | 129 |
| 2018 October | 97 | 23 | 120 |
| 2018 September | 62 | 19 | 81 |
| 2018 August | 2 | 0 | 2 |
| 2018 July | 3 | 0 | 3 |
| 2018 June | 2 | 0 | 2 |
| 2018 May | 2 | 0 | 2 |
| 2018 April | 17 | 0 | 17 |
| 2018 March | 22 | 0 | 22 |
| 2018 February | 14 | 0 | 14 |
| 2018 January | 16 | 0 | 16 |
| 2017 December | 34 | 0 | 34 |
| 2017 November | 24 | 0 | 24 |
| 2017 October | 23 | 0 | 23 |
| 2017 September | 20 | 0 | 20 |
| 2017 July | 0 | 5 | 5 |
Show all
