Original article
Airway microbiota in patients with paediatric cystic fibrosis: Relationship with clinical status
Microbiota respiratoria en pacientes pediátricos con fibrosis quística: relación con la situación clínica
Antonia Sánchez-Bautistaa, Juan Carlos Rodríguez-Díaza,
, Inmaculada Garcia-Herediaa, Carmen Luna-Paredesb, Pedro J. Alcalá-Minagorrec
Corresponding author
a Department of Microbiology, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
b Pediatric Cystic Fibrosis Unit, Department of Pediatrics, Hospital Universitario Doce de Octubre, Madrid, Spain
c Department of Pediatrics, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain
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Alcalá-Minagorre" "autores" => array:5 [ 0 => array:3 [ "nombre" => "Antonia" "apellidos" => "Sánchez-Bautista" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Juan Carlos" "apellidos" => "Rodríguez-Díaz" "email" => array:1 [ 0 => "rodriguez_juadia@gva.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Inmaculada" "apellidos" => "Garcia-Heredia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Carmen" "apellidos" => "Luna-Paredes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "Pedro J." "apellidos" => "Alcalá-Minagorre" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Microbiology, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Pediatric Cystic Fibrosis Unit, Department of Pediatrics, Hospital Universitario Doce de Octubre, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Pediatrics, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Microbiota respiratoria en pacientes pediátricos con fibrosis quística: relación con la situación clínica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 793 "Ancho" => 1594 "Tamanyo" => 59113 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Relationship between the theoretical % of predicted value of forced expiratory volume in the first second (FEV1) and clusters determined by PCA for the microbiome composition. Kruskal–Wallis test for indenting samples (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.577).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Bronchopulmonary infection is the main prognostic determinant in patients with cystic fibrosis (CF). Traditional studies, using selective culture of respiratory samples, only identify a fraction of bacterial species involved at the stable stage and at the exacerbation of the disease.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> New massive sequencing techniques make possible to determine the composition of the microbiota in CF patients which includes a large number of species in addition to the pathogens traditionally considered responsible for respiratory infections (<span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>, <span class="elsevierStyleItalic">Haemophilus influenzae</span> and <span class="elsevierStyleItalic">Staphylococcus aureus</span>).<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> Changes have been described in the microbiome of the lower respiratory tract during the different stages of the disease, but interpretation of the significance of these changes is controversial, especially in the paediatric population.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3,4</span></a> The objective of this study was to correlate the clinical situation of a group of paediatric CF patients with the composition of their lung microbiota determined by massive sequencing techniques.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">A cross-sectional observational study was performed on induced sputum samples from 13 children between the ages of 6 and 17 years with clinically stable CF and known mutation in the <span class="elsevierStyleItalic">cftr</span> gene. Patients were recruited at the CF Unit of the Hospital Doce de Octubre in Madrid, a centre accredited for CF assistance. This study was approved by the Ethics Committee and informed written consent was obtained from parents or legal guardian of all subjects.</p><p id="par0015" class="elsevierStylePara elsevierViewall">During a scheduled outpatient visit a series of variables were recorded (age, gender, <span class="elsevierStyleItalic">cftr</span> mutation, extrapulmonary and pulmonary involvement, history of bacterial colonization, and treatments received). A sample of sputum induced by 7% hypertonic saline solution was obtained and frozen at −20<span class="elsevierStyleHsp" style=""></span>°C for subsequent processing. Nucleic acids were extracted and purified with the commercial system MolYsis™ (Molzym, Germany), which allows the selective lysis of human cells with their DNA in order to isolate bacterial DNA. Parallel cultures could not be performed, due to paucity of sample volume obtained in the majority of younger patients. Historical microbiology records of cultures in the last 6 months were used to determine the infection status with classical pathogens (chronic or intermittent) of patients. Massive sequencing was performed (two strands) with the Illumina MiSeq system (Illumina, USA) and sequences of 16S (V3 and V4) were obtained using the ssu-align and meta-rna programmes.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The sequences were quality-filtered using the Pyronoise<span class="elsevierStyleSup">®</span> programme and samples were compared with each other using the Unifrac programme. The bacterial taxonomy of each sample was assigned and we determined the absolute and relative abundance of species as well as the dominance and composition of bacterial communities in the samples obtained. In addition, the diversity of each sample (alpha diversity) was studied using the Shannon–Wiener index and the diversity among samples (beta diversity) using the Bray–Curtis distance and principal component analysis. Only sequences measuring between 250<span class="elsevierStyleHsp" style=""></span>bp and 500<span class="elsevierStyleHsp" style=""></span>bp with an end-trimming quality greater than 25 were analyzed and included in this study. The Operational Taxonomic Units (OTUs) were assigned using the RDP database (Ribosomal Database Project) for the <span class="elsevierStyleItalic">16S rRNA</span> gene. All the statistical analyses were done using the statistical software SPSS version 22.0 for Windows (SPSS Inc., 2013). The results were considered statistically significant when <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0025" class="elsevierStylePara elsevierViewall">All patients included had mutations associated with severe forms of CF and pancreatic insufficiency. Four out of the 13 patients (30.7%) exhibited severe respiratory involvement according to percentage of predicted forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s (FEV1%). According to current microbiological criteria,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> 92% of patients were chronic carriers of <span class="elsevierStyleItalic">S. aureus</span> and 43% chronic carriers of <span class="elsevierStyleItalic">P. aeruginosa</span>. None of the patients had a history of non-tuberculous mycobacteria infection in previous cultures. The main characteristics of the study subjects, variables associated with the disease, comorbidity and treatment received are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">A mean of 4048 sequences were obtained in each sample, 2332 (57.6%) of which were assigned. The number of genera in the 13 samples ranged between 9 and 26, with a mean of 14.92 (standard deviation of 4.80). Five genera were found in all the samples: <span class="elsevierStyleItalic">Staphylococcus</span> spp., <span class="elsevierStyleItalic">Streptococcus</span> spp., <span class="elsevierStyleItalic">Rothia</span> spp., <span class="elsevierStyleItalic">Granulicatella</span> spp., and <span class="elsevierStyleItalic">Gemella</span> spp. With the exception of the latter species, the relative abundance was >1% according to the criteria of phylogenetic composition (<span class="elsevierStyleItalic">core microbiome</span>), defined by Coburn et al.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Staphylococcus</span> spp. was the most abundant genus in 10 patients (76.92% of the total) and dominant<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> in 6 (46.15% of the total), whereas <span class="elsevierStyleItalic">Streptococcus</span> spp. was the most abundant and dominant species in 2 patients (15.38% of the total) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). <span class="elsevierStyleItalic">Haemophilus</span> spp. was detected in the microbiome of 3 patients (23.07% of the total). <span class="elsevierStyleItalic">Staphylococcus</span> spp. was present in all patients, with <span class="elsevierStyleItalic">S. aureus</span> being the most frequent species in all the samples, followed by <span class="elsevierStyleItalic">Staphylococcus epidermidis</span>. <span class="elsevierStyleItalic">Pseudomonas</span> spp. was detected only in 2 patients (15.38%), and in both cases accounted for less than 5% of the total number of genera. Fourteen genera only appeared in a maximum of one sample. <span class="elsevierStyleItalic">Stenotrophomonas</span> spp., <span class="elsevierStyleItalic">Achromobacter</span> spp., <span class="elsevierStyleItalic">Mycobacterium</span> spp. and <span class="elsevierStyleItalic">Burkholderia</span> spp. were not detected in any of the samples. The alpha diversity values, expressed as Shannon–Wiener indexes, ranged from 0.11 to 1.57, with a mean value of 1.00. When the 13 samples were compared using a principal component analysis (PCA) 3 clusters were found (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>a–c). Patients in group 1 exhibited the lowest alpha diversity, whereas those in group 3 exhibited the highest, and these differences were statistically significant (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.009) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). In addition to the greater number of species, there was a greater density of communities of <span class="elsevierStyleItalic">Staphylococcus</span> spp., a smaller number of colonies of <span class="elsevierStyleItalic">Streptococcus</span> spp. and <span class="elsevierStyleItalic">Actinomyces</span> spp. and a smaller absolute number of genera in group 1, although the differences were not statistically significant. No statistically significant associations were found between clinical variables and different diversity indexes. However, it was observed a trend between cluster defined by PCA and degree of respiratory involvement, defined by theoretical % FEV1 (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). Cluster 1, with the lowest alpha diversity, expressed by Shannon index, showed the lowest FEV1 values.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">New massive sequencing techniques provide a great amount of additional information in patients with CF. For example, certain bacterial species, whose clinical significance is not clear, may be detected by these new techniques but not by traditional procedures.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> Advances in molecular microbiology have shown that lung infection in CF is polymicrobial<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> and the pathogen abundance and type vary depending on the individual and on the disease stage.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">As described in other studies,<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">6,10,11</span></a><span class="elsevierStyleItalic">Staphylococcus</span> spp., <span class="elsevierStyleItalic">Streptococcus</span> spp. and other genera such as <span class="elsevierStyleItalic">Granulicatella</span> spp., <span class="elsevierStyleItalic">Gemella</span> spp., <span class="elsevierStyleItalic">Rothia</span> spp., and <span class="elsevierStyleItalic">Actinomyces</span> spp. were regularly detected in the respiratory tract of CF patients, and it was also observed a certain degree of variability among individuals in the structure, composition and diversity of the bacterial communities. By PCA analysis it was possible to establish clearly three distinct groups. These differences were found even though the group was homogeneous, delimited within an age group and with no apparent association with mutation type or other variables such as age or treatment administered.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Clinical records showed that less than a half (38%) of our patients were chronic carriers of <span class="elsevierStyleItalic">P. aeruginosa</span> as determined by the traditional culture, while the great majority were carriers of <span class="elsevierStyleItalic">S. aureus</span>, which coincides with the findings of other studies performed on this age group.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> It is remarkable that the genus <span class="elsevierStyleItalic">Pseudomonas</span> spp. was detected in the microbiome of only two patients of our sample. In another study performed with bronchoalveolar lavage samples from children with CF, it was reported that <span class="elsevierStyleItalic">P. aeruginosa</span> was also detected in the culture but not in the molecular analysis of the microbiota.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> This apparent discrepancy may be due to the magnification of Gram-negative bacilli usually found with traditional culture methods.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> As these methods are intentionally selective, they are unable to detect the vast majority of the microbioma components. The amount of <span class="elsevierStyleItalic">P. aeruginosa</span> in the airway microbiota progressively increases, especially at the beginning of adulthood and tends to predominate over other species, with a resulting decrease in the amount of <span class="elsevierStyleItalic">Staphylococcus</span> spp., due to the antagonism between the two genera.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> The existence of this inverse relationship is supported by the fact that prophylactic treatment to prevent colonization by <span class="elsevierStyleItalic">S. aureus</span> may lead to an increase in the incidence and prevalence of infection due to <span class="elsevierStyleItalic">P. aeruginosa</span>.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">When the microbiome in the different samples was compared using a principal components analysis (PCA), there was a clearly different group with a higher density of <span class="elsevierStyleItalic">Staphylococcus</span> spp. as opposed to the other two groups in which there was a higher density of <span class="elsevierStyleItalic">Actinomyces</span> spp. and <span class="elsevierStyleItalic">Streptococcus</span> spp. There was a smaller absolute number of genera and lower alpha diversity expressed as a Shannon index in the group with the higher density of <span class="elsevierStyleItalic">Staphylococcus</span> spp. This inversely proportional relationship between <span class="elsevierStyleItalic">Staphylococcus</span> spp. and alpha diversity has been reported in other studies.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> On other hand, the predominance of <span class="elsevierStyleItalic">Streptococcus</span> spp. is associated with a microbiome of greater diversity,<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> which usually occurs in patients in whom there is less progression of lung disease. In our study, a microbiome with low alpha diversity, dominated by <span class="elsevierStyleItalic">Staphylococcus</span> spp. and with less number of genera found in non-CF children seems to be in relationship with lower values of FEV1, but without statistically significant differences.</p><p id="par0060" class="elsevierStylePara elsevierViewall">An association between deteriorated lung function and alpha diversity has been described in cross-sectional studies.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> The diversity of bacterial communities in healthy individuals is greater than that in CF patients.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> This loss of diversity in CF occurs progressively with age and lung disease.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> The microbiome of infants and toddlers without lung damage appears to be dominated by <span class="elsevierStyleItalic">Streptococcus</span> spp. and anaerobic genera such as <span class="elsevierStyleItalic">Prevotella</span> spp. and <span class="elsevierStyleItalic">Veionella</span> spp.,<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> as in children without CF. Despite the lack of longitudinal studies, diversity seems to increase during the first decade of life, a period when lung function is usually relatively conserved.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> The diversity begins to decrease from adolescence to adulthood in parallel with lung function parameters and airway remodelling due to progression of the disease.</p><p id="par0065" class="elsevierStylePara elsevierViewall">New microbiological methods reveal a high number of anaerobic microorganisms in the airways of CF patients.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> The role played by these organisms is not clear, and it is not known whether they are commensal organisms with a certain protective effect against traditional pathogens. In our study, as occurs in other studies of patients with CF<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> and in patients with persistent lung infections such as chronic obstructive pulmonary disease,<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> a small number of <span class="elsevierStyleItalic">Streptococcus</span> spp. and <span class="elsevierStyleItalic">Actinomyces</span> spp. seems to be in relationship with a worsening of respiratory parameters. In our study, the genus <span class="elsevierStyleItalic">Mycobacterium</span> spp. was not detected. This may be due to the fact that non-tuberculous mycobacteria are mainly found in long term CF patients, over 15 years old,<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">25,26</span></a> whereas in our sample the majority of patients were younger individuals. Some authors consider that sputum samples are not suitable for studying the lower airway microbiota.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> However, other studies have shown that the contact of the sample with oral bacteria has a discrete relevance in lower airway microbiota composition analysis.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Implementation of the new methodologies suggest that disruption of the ecological balance of microbial communities in the lungs, loss of mutualism, and the emergence of competing species may be determining factors in a variety of respiratory diseases such as CF.<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">29,30</span></a> More studies must be performed in order to determine whether changes observed in the microbiome of patients with CF play a causal role in the evolution of pulmonary disease, or are only a consequence of the progression of the disease and the antibiotic treatments received. In first premise, the studies must offer data that allow interventions on airway microbiome with positive repercussion in the clinical evolution of CF.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Funding</span><p id="par0075" class="elsevierStylePara elsevierViewall">This work has been funded with a grant from the foundation <span class="elsevierStyleGrantSponsor" id="gs1">Navarro Tripodi</span>.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">Nothing to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1155347" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1082907" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1155346" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1082906" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 10 => array:2 [ "identificador" => "xack394292" "titulo" => "Acknowledgments" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-02-23" "fechaAceptado" => "2018-05-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1082907" "palabras" => array:4 [ 0 => "Cystic fibrosis" 1 => "Lung microbiome" 2 => "Paediatric patients" 3 => "Lung disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1082906" "palabras" => array:4 [ 0 => "Fibrosis quística" 1 => "Pulmón" 2 => "Edad pediátrica" 3 => "Enfermedad pulmonar" ] ] ] ] "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">New massive sequencing techniques make it possible to determine the composition of airway microbiota in patients with cystic fibrosis (CF). However, the relationship between the composition of lung microbiome and the clinical status of paediatric patients is still not fully understood.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A cross-sectional observational study was conducted on induced sputum samples from children with CF and known mutation in the CFTR gene. The bacterial sequences of the 16SrRNA gene were analyzed and their association with various clinical variables studied.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Analysis of the 13 samples obtained showed a core microbiome made up of <span class="elsevierStyleItalic">Staphylococcus</span> spp., <span class="elsevierStyleItalic">Streptococcus</span> spp., <span class="elsevierStyleItalic">Rothia</span> spp., <span class="elsevierStyleItalic">Gemella</span> spp. and <span class="elsevierStyleItalic">Granulicatella</span> spp., with a small number of <span class="elsevierStyleItalic">Pseudomonas</span> spp. The cluster of patients with less biodiversity were found to exhibit a greater number of sequences of <span class="elsevierStyleItalic">Staphylococcus</span> spp., mainly <span class="elsevierStyleItalic">Staphylococcus aureus</span> (<span class="elsevierStyleItalic">p</span> 0.009) and a greater degree of lung damage.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">An airway microbiome with greater biodiversity may be an indicator of less pronounced disease progression, in which case new therapeutic interventions that prevent reduction in non-pathogenic species of the airway microbiota should be studied.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "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 nuevas técnicas de secuenciación masiva permiten determinar la composición de la microbiota de las vías respiratorias en pacientes con fibrosis quística (FQ). Sin embargo, la relación entre la composición de la microbiota pulmonar y el estado clínico de los pacientes pediátricos todavía no se ha establecido bien.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realizó un estudio transversal observacional en muestras de esputo inducido de niños con FQ y mutación conocida en el gen CFTR. Se analizaron las secuencias bacterianas del gen 16SrRNA y se estudió su asociación con diversas variables clínicas.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El análisis de las 13 muestras obtenidas mostró un microbioma central compuesto por <span class="elsevierStyleItalic">Staphylococcus</span> spp., <span class="elsevierStyleItalic">Streptococcus</span> spp., <span class="elsevierStyleItalic">Rothia</span> spp., <span class="elsevierStyleItalic">Gemella</span> spp. y <span class="elsevierStyleItalic">Granulicatella</span> spp., con un pequeño número de <span class="elsevierStyleItalic">Pseudomonas</span> spp. Se descubrió que el grupo de pacientes con menos biodiversidad mostraba un mayor número de secuencias de <span class="elsevierStyleItalic">Staphylococcus</span> spp., principalmente <span class="elsevierStyleItalic">Staphylococcus aureus</span> (p 0,009) y un mayor daño de la función pulmonar.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La mayor biodiversidad del microbioma de vía respiratoria puede ser un indicador de menor progresión de la enfermedad, en cuyo caso deben estudiarse nuevas intervenciones terapéuticas que prevengan la disminución de especies no patógenas.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1769 "Ancho" => 2165 "Tamanyo" => 342918 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Relative abundance for the detected genera in all samples studied.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2593 "Ancho" => 3008 "Tamanyo" => 271989 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">(a) Principal component analysis (PCA) for the microbiome composition of the samples; (b) dendrogram; (c) Venn diagram.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 778 "Ancho" => 1546 "Tamanyo" => 56117 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Relationship between clusters determined by PCA for the microbiome composition and alpha diversity expressed by the Shanon index. Kruskal–Wallis test for independent samples (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.009).</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 793 "Ancho" => 1594 "Tamanyo" => 59113 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Relationship between the theoretical % of predicted value of forced expiratory volume in the first second (FEV1) and clusters determined by PCA for the microbiome composition. Kruskal–Wallis test for indenting samples (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.577).</p>" ] ] 4 => 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=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Median<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD (range) or <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><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="elsevierStyleItalic">Number of patients</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 \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="elsevierStyleItalic">Age in years</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.9 (7 to 17.2) \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="elsevierStyleItalic">Female/male</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7/6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">cfrt mutation</span></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>Delta F508 homozygous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (23.1) \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>Delta F508/other mutation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (46.1) \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>Other mutations non Delta F508 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (30.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Extrapulmonary disease</span></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>Pancreatic insufficiency \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (100) \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">z</span>-Score of body max index \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.85 (−1.70 to 0.50) \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>Liver disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (53.8) \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>Sinus involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (23.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Bronchopulmonary disease</span></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>FEV1 value [% theoretical value] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65.23% ±22.0 [32–108] \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>Radiological bronchiectasis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (100) \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>Exacerbation last 6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (61.5) \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>Intermittent oxygen therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (15.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Previous colonization</span></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">S. aureus</span> carrier \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (92.3) \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">P. aeruginosa</span> carrier \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (42.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Therapy</span></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>Nebulized antibiotics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (76.9) \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>Colisitin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (53.8) \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>Colistin<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>aztreonam \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (15.4) \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>Tobramycin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (7.7) \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>Long-term macrolide therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (76.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1972358.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Demographic characteristics of patients and clinical variables of the disease.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "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" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genus \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Relative abundance >1%<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Most abundant genus<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dominant genus<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Maximun abundance relative<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><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="elsevierStyleItalic">Staphylococcus</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64.3 \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="elsevierStyleItalic">Streptococcus</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.02 \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="elsevierStyleItalic">Rothia</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.5 \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="elsevierStyleItalic">Granulicatella</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1972359.png" ] ] ] "notaPie" => array:4 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Number of samples in which the relative abundance was greater than 1%.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Number of samples where this genus was the most abundant.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Number of samples where this genus was the dominant (more frequent genus in the sample and twice more frequent than the next most abundant genus, according to the definition of Coburn et al.).</p>" ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "d" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Maximum relative abundance obtained (%).</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Comparison between the genera constituting the microbiome core.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Emerging bacterial pathogens and changing concepts of bacterial pathogenesis in cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.D. Parkins" 1 => "R.A. Floto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcf.2015.03.012" "Revista" => array:6 [ "tituloSerie" => "J Cyst Fibros" "fecha" => "2015" "volumen" => "14" "paginaInicial" => "293" "paginaFinal" => "304" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25881770" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0160" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The cystic fibrosis lower airways microbial metagenome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Moran Losada" 1 => "P. Chouvarine" 2 => "M. Dorda" 3 => "S. Hedtfeld" 4 => "S. Mielke" 5 => "A. Schulz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/23120541.00096-2015" "Revista" => array:6 [ "tituloSerie" => "ERJ Open Res" "fecha" => "2016" "volumen" => "2" "paginaInicial" => "00096" "paginaFinal" => "02015" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27730195" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0165" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.B. Frayman" 1 => "D.S. Armstrong" 2 => "R. Carzino" 3 => "T.W. Ferkol" 4 => "K. Grimwood" 5 => "G.A. Storch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2016-209279" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2017" "volumen" => "72" "paginaInicial" => "1104" "paginaFinal" => "1112" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28280235" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0170" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Airway microbiota across age and disease spectrum in cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.T. Zemanick" 1 => "B.D. Wagner" 2 => "C.E. Robertson" 3 => "R.C. Ahrens" 4 => "J.F. Chmiel" 5 => "J.P. Clancy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/13993003.00832-2017" "Revista" => array:5 [ "tituloSerie" => "Eur Respir J" "fecha" => "2017" "volumen" => "50" "paginaInicial" => "1700832" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29146601" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0175" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "en representación del Grupo Español de Consenso del Tratamiento Antimicrobiano en el Paciente con Fibrosis Quística Spanish consensus on the prevention and treatment of <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> bronchial infections in cystic fibrosis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Cantón" 1 => "L. Máiz" 2 => "A. Escribano" 3 => "C. Olveira" 4 => "A. Oliver" 5 => "O. Asensio" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.arbres.2014.09.021" "Revista" => array:6 [ "tituloSerie" => "Arch Bronconeumol" "fecha" => "2015" "volumen" => "51" "paginaInicial" => "140" "paginaFinal" => "150" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25614377" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0180" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung microbiota across age and disease stage in cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Coburn" 1 => "P.W. Wang" 2 => "J. Diaz Caballero" 3 => "S.T. Clark" 4 => "V. Brahma" 5 => "S. Donaldson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/srep10241" "Revista" => array:5 [ "tituloSerie" => "Sci Rep" "fecha" => "2015" "volumen" => "5" "paginaInicial" => "10241" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25974282" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0185" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The microbiome and the respiratory tract" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.P. Dickson" 1 => "J.R. Erb-Downward" 2 => "F.J. Martinez" 3 => "G.B. Huffnagle" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev-physiol-021115-105238" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Physiol" "fecha" => "2016" "volumen" => "78" "paginaInicial" => "481" "paginaFinal" => "504" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26527186" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0190" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sputum DNA sequencing in cystic fibrosis: non-invasive access to the lung microbiome and to pathogen details" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Feigelman" 1 => "C.R. Kahlert" 2 => "F. Baty" 3 => "F. Rassouli" 4 => "R.L. Kleiner" 5 => "P. Kohler" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s40168-017-0234-1" "Revista" => array:5 [ "tituloSerie" => "Microbiome" "fecha" => "2017" "volumen" => "5" "paginaInicial" => "20" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28187782" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0195" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Initial acquisition and succession of the cystic fibrosis lung microbiome is associated with disease progression in infants and preschool children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.S. Muhlebach" 1 => "B.T. Zorn" 2 => "C.R. Esther" 3 => "J.E. Hatch" 4 => "C.P. Murray" 5 => "L. Turkovic" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.ppat.1006798" "Revista" => array:5 [ "tituloSerie" => "PLoS Pathog" "fecha" => "2018" "volumen" => "14" "paginaInicial" => "e1006798" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29346420" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0200" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acquisition and adaptation of the airway microbiota in the early life of cystic fibrosis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. Boutin" 1 => "A.H. Dalpke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s40348-016-0067-1" "Revista" => array:6 [ "tituloSerie" => "Mol Cell Pediatr" "fecha" => "2017" "volumen" => "4" "paginaInicial" => "1" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28097632" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673609610692" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0205" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The microbiota in bronchoalveolar lavage from young children with chronic lung disease includes taxa present in both the oropharynx and nasopharynx" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.L. Marsh" 1 => "M. Kaestli" 2 => "A.B. Chang" 3 => "M.J. Binks" 4 => "C.E. Pope" 5 => "L.R. Hoffman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s40168-016-0182-1" "Revista" => array:5 [ "tituloSerie" => "Microbiome" "fecha" => "2016" "volumen" => "4" "paginaInicial" => "37" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27388563" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0210" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changing epidemiology of the respiratory bacteriology of patients with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.L. Salsgiver" 1 => "A.K. Fink" 2 => "E.A. Knapp" 3 => "J.J. LiPuma" 4 => "K.N. Olivier" 5 => "B.C. Marshall" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.15-0676" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2015" "volumen" => "149" "paginaInicial" => "390" "paginaFinal" => "400" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26203598" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0215" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.K. Harris" 1 => "M.A. De Groote" 2 => "S.D. Sagel" 3 => "E.T. Zemanick" 4 => "R. Kapsner" 5 => "C. Penvari" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Proc Natl Acad Sci U S A" "fecha" => "2007" "volumen" => "18" "paginaInicial" => "20529" "paginaFinal" => "20533" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0220" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sputum microbiota in moderate versus severe patients with COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Galiana" 1 => "E. Aguirre" 2 => "J.C. Rodriguez" 3 => "A. Mira" 4 => "M. Santibañez" 5 => "I. Candela" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00191513" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2014" "volumen" => "43" "paginaInicial" => "1787" "paginaFinal" => "1790" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24311775" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0225" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The dynamics of disease progression in cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F.R. Adler" 1 => "T.G. Liou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0156752" "Revista" => array:6 [ "tituloSerie" => "PLOS ONE" "fecha" => "2016" "volumen" => "11" "paginaInicial" => "e0156752" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27248696" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0002939413003346" "estado" => "S300" "issn" => "00029394" ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0230" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prophylactic anti-staphylococcal antibiotics for cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.R. Smyth" 1 => "M. Rosenfeld" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/14651858.CD001912.pub4" "Revista" => array:5 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2017" "volumen" => "4" "paginaInicial" => "CD001912" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28417451" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0235" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antibiotic therapy alters lung microbiome in pediatric cystic fibrosis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "L. Kramná" 1 => "K. Vilimovská" 2 => "D. De" 3 => "D. Pavel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2016" "editorial" => "European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Congress; EP0194" "editorialLocalizacion" => "Amsterdam, The Netherlands" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0240" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Data mining of lung microbiota in cystic fibrosis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Li" 1 => "C. Hao" 2 => "L. Ren" 3 => "Y. Xiao" 4 => "J. Wang" 5 => "X. Qin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0164510" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2016" "volumen" => "11" "paginaInicial" => "e0164510" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27741283" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0245" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pyrosequencing unveils cystic fibrosis lung microbiome differences associated with a severe lung function decline" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Bacci" 1 => "P. Paganin" 2 => "L. Lopez" 3 => "C. Vanni" 4 => "C. Dalmastri" 5 => "C. Cantale" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0156807" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2016" "volumen" => "11" "paginaInicial" => "e0156807" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27355625" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0250" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The airway microbiota in early cystic fibrosis lung disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.B. Frayman" 1 => "D.S. Armstrong" 2 => "K. Grimwood" 3 => "S.C. Ranganathan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ppul.23782" "Revista" => array:6 [ "tituloSerie" => "Pediatr Pulmonol" "fecha" => "2017" "volumen" => "52" "paginaInicial" => "1384" "paginaFinal" => "1404" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28815937" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0255" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The airway microbiota in early cystic fibrosis lung disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.B. Frayman" 1 => "D.S. Armstrong" 2 => "K. Grimwood" 3 => "S.C. Ranganathan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ppul.23782" "Revista" => array:2 [ "tituloSerie" => "Pediatr Pulmonol" "fecha" => "2017" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0260" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Rosenfeld" 1 => "R.L. Gibson" 2 => "S. Mcnamara" 3 => "J. Emerson" 4 => "J.L. Burns" 5 => "R. Castile" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pediatr Pulmonol" "fecha" => "2015" "volumen" => "32" "paginaInicial" => "356" "paginaFinal" => "366" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11596160" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0265" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fluctuations in airway bacterial communities associated with clinical states and disease stages in cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.A. Carmody" 1 => "L.J. Caverly" 2 => "B.K. Foster" 3 => "M.A.M. Rogers" 4 => "L.M. Kalikin" 5 => "R.H. Simon" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "PLOS ONE" "fecha" => "2018" "volumen" => "13" "paginaInicial" => "e 0194060" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0270" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reduced bacterial colony count of anaerobic bacteria is associated with a worsening in lung clearance index and inflammation in cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. O’Neill" 1 => "J.M. Bradley" 2 => "E. Johnston" 3 => "S. McGrath" 4 => "L. McIlreavey" 5 => "S. Rowan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0126980" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "e0126980" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25992575" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0275" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nontuberculous mycobacteria in cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K. Kolnik" 1 => "G. Kirkpatrick" 2 => "B.S. Quon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s40506-016-0092-6" "Revista" => array:6 [ "tituloSerie" => "Curr Treat Options Infect Dis" "fecha" => "2016" "volumen" => "8" "paginaInicial" => "259" "paginaFinal" => "274" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28035194" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0280" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Scandinavian cystic fibrosis study consortium (SCFSC) epidemiology of nontuberculous mycobacteria among patients with cystic fibrosis in Scandinavia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Qvist" 1 => "M. Gilljam" 2 => "B. Jönsson" 3 => "D. Taylor-Robinson" 4 => "S. Jensen-Fangel" 5 => "M. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcf.2014.08.002" "Revista" => array:6 [ "tituloSerie" => "J Cyst Fibros" "fecha" => "2015" "volumen" => "14" "paginaInicial" => "46" "paginaFinal" => "52" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25178871" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0285" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of microbiomes from different niches of upper and lower airways in children and adolescents with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Boutin" 1 => "S.Y. Graeber" 2 => "M. Weitnauer" 3 => "J. Panitz" 4 => "M. Stahl" 5 => "D. Clausznitzer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0116029" "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "e0116029" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25629612" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0290" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Respiratory microbiota: addressing clinical questions, informing clinical practice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G.B. Rogers" 1 => "D. Shaw" 2 => "R.L. Marsh" 3 => "M.P. Carroll" 4 => "D.J. Serisier" 5 => "K.D. Bruce" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2014-205826" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2015" "volumen" => "70" "paginaInicial" => "74" "paginaFinal" => "81" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25035125" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0295" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cystic fibrosis airway microbiome: overturning the old, opening the way for the new" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.A. O’Toole" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JB.00561-17" "Revista" => array:5 [ "tituloSerie" => "J Bacteriol" "fecha" => "2018" "volumen" => "200" "paginaInicial" => "e00561-17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29084859" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0300" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "e00158-17" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Host–microbe interactions in airway disease: toward disease mechanisms and novel therapeutic strategies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E.K. Cope" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "mSystems" "fecha" => "2018" "volumen" => "3" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack394292" "titulo" => "Acknowledgments" "texto" => "<p id="par0085" class="elsevierStylePara elsevierViewall">To Dr. Gloria García Hernández, for a lifetime of dedication to the care of children with cystic fibrosis.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/2529993X/0000003700000003/v1_201902260607/S2529993X19300292/v1_201902260607/en/main.assets" "Apartado" => array:4 [ "identificador" => "63564" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/2529993X/0000003700000003/v1_201902260607/S2529993X19300292/v1_201902260607/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2529993X19300292?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 5 | 1 | 6 |
| 2024 September | 9 | 2 | 11 |
| 2024 August | 12 | 3 | 15 |
| 2024 July | 8 | 3 | 11 |
| 2024 June | 7 | 3 | 10 |
| 2024 May | 16 | 4 | 20 |
| 2024 April | 10 | 3 | 13 |
| 2024 March | 14 | 4 | 18 |
| 2024 February | 18 | 1 | 19 |
| 2024 January | 5 | 1 | 6 |
| 2023 December | 8 | 3 | 11 |
| 2023 November | 15 | 2 | 17 |
| 2023 October | 24 | 2 | 26 |
| 2023 September | 16 | 3 | 19 |
| 2023 August | 20 | 0 | 20 |
| 2023 July | 6 | 1 | 7 |
| 2023 June | 23 | 0 | 23 |
| 2023 May | 39 | 2 | 41 |
| 2023 April | 40 | 0 | 40 |
| 2023 March | 26 | 0 | 26 |
| 2023 February | 33 | 2 | 35 |
| 2023 January | 32 | 2 | 34 |
| 2022 December | 14 | 2 | 16 |
| 2022 November | 49 | 5 | 54 |
| 2022 October | 52 | 7 | 59 |
| 2022 September | 38 | 9 | 47 |
| 2022 August | 26 | 6 | 32 |
| 2022 July | 6 | 4 | 10 |
| 2022 June | 8 | 4 | 12 |
| 2022 May | 18 | 6 | 24 |
| 2022 April | 10 | 6 | 16 |
| 2022 March | 8 | 4 | 12 |
| 2022 February | 9 | 4 | 13 |
| 2022 January | 36 | 5 | 41 |
| 2021 December | 33 | 8 | 41 |
| 2021 November | 24 | 11 | 35 |
| 2021 October | 25 | 5 | 30 |
| 2021 September | 24 | 8 | 32 |
| 2021 August | 6 | 7 | 13 |
| 2021 July | 12 | 5 | 17 |
| 2021 June | 11 | 6 | 17 |
| 2021 May | 18 | 7 | 25 |
| 2021 April | 21 | 17 | 38 |
| 2021 March | 21 | 7 | 28 |
| 2021 February | 20 | 10 | 30 |
| 2021 January | 34 | 5 | 39 |
| 2020 December | 8 | 6 | 14 |
| 2020 November | 10 | 7 | 17 |
| 2020 October | 12 | 4 | 16 |
| 2020 September | 12 | 10 | 22 |
| 2020 August | 9 | 6 | 15 |
| 2020 July | 5 | 8 | 13 |
| 2020 June | 12 | 5 | 17 |
| 2020 May | 9 | 5 | 14 |
| 2020 April | 9 | 1 | 10 |
| 2020 March | 18 | 6 | 24 |
| 2020 February | 9 | 4 | 13 |
| 2020 January | 15 | 0 | 15 |
| 2019 December | 11 | 6 | 17 |
| 2019 November | 8 | 2 | 10 |
| 2019 October | 10 | 2 | 12 |
| 2019 September | 6 | 6 | 12 |
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