Urinary leukotriene excretion profile in children with exercise-induced asthma compared with controls: A preliminary study

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Vieira, C. Lopes, A.M. Pereira, L. Araújo, A. Moreira, L. Delgado" "autores" => array:6 [ 0 => array:2 [ "nombre" => "T." "apellidos" => "Vieira" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Lopes" ] 2 => array:2 [ "nombre" => "A.M." "apellidos" => "Pereira" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Araújo" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Moreira" ] 5 => array:2 [ "nombre" => "L." 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"apellidos" => "Brockmann" "email" => array:1 [ 0 => "pbrockmann@med.puc.cl" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.A." "apellidos" => "Castro-Rodriguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "N.L." "apellidos" => "Holmgren" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "J." "apellidos" => "Cerda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "A." "apellidos" => "María Contreras" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "A." 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"apellidos" => "Bertrand" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Pediatrics, Pontificia Universidad Catolica de Chile, Santiago, Chile" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Public Health, Pontificia Universidad Catolica de Chile, Santiago, Chile" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Center of Medical Investigation, Pontificia Universidad Catolica de Chile, Santiago, Chile" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Pediatric Lung Function Laboratory, Pontificia Universidad Catolica de Chile, Santiago, Chile" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1036 "Ancho" => 1616 "Tamanyo" => 96620 ] ] "descripcion" => array:1 [ "en" => "Intraindividual changes in urinary LTE4 concentrations in controls." ] ] ] "textoCompleto" => "IntroductionExercise-induced symptoms are common among children with asthma. Coughing is the most common symptom associated with exercise, with a frequency of approximately 70–80% in untreated patients.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Exercise-induced symptoms produce limitations in daily activity<a class="elsevierStyleCrossRefs" href="#bib0010">2–4</a> and a poorer quality of life.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Therefore, early recognition of non-controlled exercise-induced asthma (EIA) may be important for adjustment of treatment and prevention of physical and psychological effects.<a class="elsevierStyleCrossRefs" href="#bib0025">5,6</a> Nevertheless, this assessment may be especially difficult in children using conventional methods like spirometry, peak flow or clinical symptoms.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> In recent years, markers of airway inflammation, such as fractional exhaled nitric oxide, induced sputum eosinophils and urinary leukotriene E4 (LTE4), have been studied and proposed for better assessment of the inflammatory state of children with asthma.<a class="elsevierStyleCrossRefs" href="#bib0040">8–10</a>Leukotrienes are among the most important cytokines involved in exercise-induced inflammatory response.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> They are products of arachidonic acid metabolism by the cyclooyxgenase 1/2 pathways.<a class="elsevierStyleCrossRefs" href="#bib0060">12–14</a> Since leukotriene E4 (LTE4) is the end product of all cysteinyl-LT metabolisms in the lung,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> measuring urinary leukotrienes may be an interesting option for assessing the inflammatory state in children with asthma.The role of leukotrienes in EIA has been evidenced by a sustained increase in their concentration 30–90min after exercise challenge in adults.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> However, in children with asthma, the specific profile of urinary leukotriene excretion and its association with the clinical severity of asthma has not yet been clarified.We aimed to determine if urinary LTE4 concentration shows a disease-specific pattern and could therefore be useful as a non-invasive marker to compare post exercise LTE4 urinary excretion in children with EIA versus healthy controls.MethodsChildren between 6 and 17 years of age with EIA (cases) and healthy children (controls) were enrolled prospectively in 2008. Cases were enrolled among children with physician diagnosed EIA (symptoms like wheezing, cough, or dyspnoea clearly associated with exercise<a class="elsevierStyleCrossRef" href="#bib0080">16</a>) who were routinely sent to our respiratory laboratory to perform an exercise challenge test (ECT). All children who presented any disease other than asthma; admitted active tobacco smoking; or had received long-term treatment with inhaled or oral corticosteroids, montelukast or antihistamines (the latter for at least seven days before the ECT), were excluded from this group. As controls, healthy volunteers (children of hospital co-workers) who were age-matched to cases were selected. In this group, children who presented any chronic underlying disease; admitted active smoking; or had used inhaled or oral corticosteroids, montelukast or antihistamines were also excluded. In both groups, children with any acute respiratory infection in the last three weeks were excluded.After explaining the purpose of the study, informed consent was obtained from parents and children. Age, gender and reported weekly hours of physical activity were assessed for both groups. Parents of cases were also asked about the use of medications, the date of the EIA diagnosis, visits to the emergency department and hospitalisation. Cases were classified as suffering from mild intermittent, mild persistent, moderate persistent or severe asthma according to the Global Initiative for Asthma Guidelines (<a href="http://www.ginasthma.org/">http://www.ginasthma.org</a>).The ECT was performed at the paediatric pulmonary function laboratory according to guidelines.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> In both groups (cases and controls) the ECT was conducted between 9am and 4pm under controlled environmental conditions (21°C and 45% relative humidity), in order to achieve standardisation of known factors that influence bronchial response to exercise.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Spirometry (Schiller SP 100®, Switzerland) was carried out with children standing and wearing a nose clip. At least three baseline spirometric measurements were performed in order to ensure appropriate acceptability and reproducibility of the test.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Subsequently, subjects performed a sub maximum effort, defined as a high intensity test of six minutes on a treadmill (Stracrac model ST-1600®) at 3.6miles/h and 10° elevation. Heart rate reached at least 80% of theoretical maximum for patient age (220 - age). This variable was monitored with a Polar F1TM fitness monitor placed around the thorax. Arterial saturation was monitored with Masimo RAD9® (Irvine, CA, USA) equipment. A nose clip was worn to ensure breathing through the mouth. After each spirometry, the children's breathing was monitored with a stethoscope to detect wheezing.Once the stimulus (exercise) was completed, spirometry was repeated at 1, 3, 5, 7, 10, 15 and 30min. Two or three spirometric manoeuvres were performed for each measurement, with a maximum difference of ±5% in forced expiratory volumen 1st second (FEV1). FEV1 and forced expiratory flow 25-75% (FEF25–75) was registered for each measurement, choosing the best corresponding FEV1 manoeuvre. After obtaining a fall in FEV1 from the baseline, we analysed the flow volume curve shape, which allowed testing for quality control of the spirometric effort. After the ECT, every child received 200mcg of salbutamol MDI using a breathing mask, and performed spirometry again to ensure the return to baseline values. ECT was considered positive if: (i) the decrease of FEV1 was >10% of baseline; or (ii) if wheezing and dyspnoea were determined.<a class="elsevierStyleCrossRef" href="#bib0080">16</a>Urine samples were collected immediately before starting the ECT. A second urine sample was collected 30min after finishing the ECT. Urine samples were then refrigerated at −70°C and saved until all samples were processed. LTE4 in urine was measured by ACETM Enzyme Immunoassay Kit® (Cayman Chemical, Ann Arbor, MI, USA), according to recommendations.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Urine LTE4 concentration was reported in pg/ml and standardised per mg/ml of creatinine. Therefore, all urinary LTE4 concentrations were reported as pg/mg of creatinine.This protocol was approved by the Ethics Committee of the Pontificia Universidad Católica de Chile and parents authorised their children's participation by signing informed consent forms.Statistical analysisIn this preliminary phase of the study, the objective was to compare LTE4's excretion profile in cases and controls. Statistical analyses were performed using statistical software (Statistical Package for the Social Sciences, Version 15 for Windows; SPSS; Chicago, IL, USA). A comparison of demographic and lung function variables between cases and controls was performed using the X2 test for categorical variables and the Mann–Whitney U-test for continuous variables. The distribution of urinary LTE4 concentrations was analysed before and after performing ECT. These distributions were compared between cases and controls using the Mann–Whitney U test. For each subject the change in urinary LTE4 concentrations after ECT (post ECT concentration−basal concentration) was calculated and its distribution was compared between groups using the Mann–Whitney U test. the correlations (non-parametric correlations) according to Spearman [rs] were estimated between changes in urinary LTE4 concentrations post ECT and pulmonary function variables or reported hours of physical activity. The Kruskal–Wallis test was used to investigate associations between changes in urinary LTE4 concentrations post ECT and clinical asthma severity. p-Values <0.05 were considered statistically significant.ResultsOf the 29 children initially recruited, four were excluded from the analysis. Two patients with EIA and one control were excluded because they were found to have previously received inhaled corticosteroids. An additional control subject was excluded for being an ex-smoker. Twenty-five subjects were finally analyzed, 10 with EIA (six boys) and 15 controls (11 boys). All of them completed the ECT successfully and reached the target heart rate. There were no differences between cases and controls in terms of age, weekly hours of physical activity, nor basal lung function. However, there were significantly higher decreases of FEV1 (%) after ECT among cases than controls (14 [8–59] vs. 1 [0–7], respectively, p<0.0001) (see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Among cases, four wheezed after full completion of ECT and required bronchodilator therapy in situ. After the ECT, all cases either developed a fall in FEV1 >10%, or had wheezing and had therefore, a positive ECT. In contrast to that, none of the controls developed such findings and all had therefore a negative ECT.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Children with EIA were classified as: mild intermittent (n=4); mild persistent (n=4); and moderate persistent (n=2). In this group, median (min–max) time of the asthma diagnosis was 0.23 (0–13) years; the number of asthma crises in the last year that needed treatment was one (1–6); the number of visits to the emergency department in the last year was one (0–8); and hospitalisations were zero (0–5).Baseline median (min–max) values of LTE4 concentrations [pg/mg creatinine] were similar between cases and controls (17.8 [7.6–90.2] vs. 17.2 [4.6–64.0], respectively, p=0.86). However, LTE4 concentrations post ECT were significantly higher among cases versus controls (23.8 [4.0–93] vs. 11.7 [0.1–25.1], respectively, p=0.02). Also, changes of LTE4 concentration pre and post ECT were significantly different among cases versus controls (2.5 [−32 to 43.3] vs. −13.5 [−46 to 11] in controls, p=0.03), <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. Individual changes in LTE4 concentrations in cases and controls are shown in <a class="elsevierStyleCrossRefs" href="#fig0010">Figs. 2 and 3</a>, respectively. There was a tendency towards higher changes in LTE4 concentration post ECT in children with more severe asthma (p=0.11), <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>There was no significant correlation between basal % predicted FEV1 and changes in LTE4 concentration in cases (rs=0.14) and controls (rs=0.12). Also, there was no significant correlation between absolute or predicted values of FVC, FEF25-75 and FEV1 and changes in LTE4 concentration pre and post ECT (all rs<0.20). There was a significant correlation between the maximum fall in FEV1 and changes in LTE4 concentration (rs=0.69) in cases but not in controls (rs=0.19). Correlation between changes in LTE4 concentration post ECT and weekly hours of physical activity was rs=0.09 (p=0.80) in cases, and rs=0.49 (p=0.05) in controls.DiscussionThis study demonstrated a different pattern in urinary LTE4 concentration post ECT in subjects with asthma compared to healthy children. As this response was observed within 30min of the running test, this may suggest a different and rapid pattern of LTE4 excretion after exercise in children with EIA compared to healthy controls. Interestingly, this response seems rapid enough to be assigned to the preceding exercise and could possibly be useful for the assessment of non-controlled inflammation in EIA.This pattern of LTE4 changes after exercise may reflect a specific and rapidmetabolism of inflammatory mediators in children with EIA. Interestingly, intraindividual changes showed that most of the healthy controls had a decrease in LTE4 concentration after ECT. In contrast to that, LTE4 concentration was stable in children with EIA, and increased in some cases.Nevertheless, there is conflicting evidence about changes in LTE4 after exercise. Kikawa et al. showed no significant differences between basal LTE4 concentration in children with asthma compared to healthy peers, but a significant increase only among asthmatics.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> On the other hand, others have shown no increased urinary excretion of LTE after exercise, nor an association with exercise-induced bronchospasm.<a class="elsevierStyleCrossRef" href="#bib0075">15</a>In adults, Reiss et al. showed an increase in urinary leukotrienes and an attenuation of that response using a leukotriene receptor antagonist in non-smoking asthmatic subjects.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> Also in adults, Taylor et al. showed no significant increase in urinary leukotrienes after exercise.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>However, in children with EIA the specific profile of urinary leukotrienes has not yet been clarified and studies that have assessed urinary excretion of leukotrienes after exercise are sparse. For example, Severien et al. showed that there was significantly higher urinary excretion of LTE4 in subjects with asthma compared to healthy controls.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Our results, similar to those of Kikawa et al.,<a class="elsevierStyleCrossRef" href="#bib0095">19</a> using another technique for LTE4 measure (i.e., radioimmunoassay), showed no significant changes in basal concentration of LTE4, and a significant difference in post-exercise change in LTE4 concentration between children with EIA and controls.An association of LTE4 concentrations and lung function has been summarized by a recent review.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> One study showed an association among LTE4 concentrations, a fall in FEV1, and a protection using leukotriene receptor antagonist in children.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> In contrast, we did not find a correlation between LTE4 concentration and FEV1. Interestingly, Kikawa et al. did not find any correlation either between LTE4 concentration after exercise and the degree of bronchoconstriction, although using maximum percentage decrease in the peak expiratory flow. This may be explained by either the presence of milder forms of asthma in the studied subjects, or even by a more precise recognition of non-controlled asthma by the LTE4 than FEV1. We also showed no correlation between hours of physical activity and changes in LTE4 concentration in children with EIA. This could be explained by diverse reasons, like different basal inflammatory conditions of the subjects or the subjective and possibly imprecise self-estimation of weekly hours of physical activity.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>We hypothesize that under certain conditions, like exercise, leukotriene-associated inflammation has a specific pattern in children with EIA, and this may mark a difference with healthy children, among whom there is no such inflammation. Furthermore, we found in the present study, that children with more severe EIA, according to a widely used clinical classification (i.e., Global Initiative for Asthma Guidelines), showed higher levels of change in urinary concentration of LTE4 post ECT. While some have found similar results,<a class="elsevierStyleCrossRefs" href="#bib0110">22,24</a> others have found no correlation between leukotriene concentration and asthma severity.<a class="elsevierStyleCrossRefs" href="#bib0045">9,13,25</a> This fact may be of special clinical interest, considering that using montelukast may be useful in patients with EIA with such high leukotriene excretion levels.In order to better understand the role of leukotrienes in asthma, different metabolites (i.e., leukotriene B4, C4, D4 or E4) have been investigated in sputum, exhaled condensate and urine.<a class="elsevierStyleCrossRefs" href="#bib0050">10,26</a> For the present study, urinary LTE4 was chosen as a marker of inflammation, as it has recently shown specific functions in patients with asthma, suggesting an important role for this molecule in inflammation.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> In addition, urinary LTE4 could be easily obtained in school-aged children from single urine samples. Previously, techniques for assessing urinary LTE4, such as reversed-phase high-performance liquid chromatography, radioimmunoassay, or enzyme immunoassay have been used.<a class="elsevierStyleCrossRefs" href="#bib0095">19,21</a> Qiu et al. showed that enzyme immunoassay significantly correlated with what was usually considered the gold standard (i.e., reversed-phase high-performance liquid chromatography).<a class="elsevierStyleCrossRef" href="#bib0135">27</a> To our knowledge, the present study represents the first comparison in LTE4 concentration after exercise using enzyme immunoassay in children with this specific form of asthma (i.e., EIA).The present study has some potential limitations. First, we measured only one sample of LTE4 from all subjects 30min after the ECT. It is possible that obtaining more samples of each subject, in order to establish the optimal excretion time, would have shown further differences in LTE4 excretion between the groups. Notwithstanding that, we demonstrated a significant difference in the concentration of LTE4 post ECT under the same sampling conditions between cases and healthy controls. Another limitation of this preliminary phase may have been the sample size, although it was based on previous studies.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> However, we hypothesize that associations obtained between urinary LTE4 concentration and lung function or clinical severity could be strengthened with a larger sample, which may be designed based on this results. Moreover, intraindividual changes showed that LTE4 concentrations after ECT in subjects with EIA often remained stable and increased in some cases.Further studies should confirm if assessment of changes in LTE4 concentration after exercise could be helpful in directing a specific treatment in children with EIA. A strength of the present study was the use of an ECT that strictly followed the recommendation of the American Thoracic Society (ATS) recommendation, considering that only one out of nine protocols of ECT published after 2000 (and none published before) followed these guidelines.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Due to the pattern of urinary LTE4 excretion in subjects with EIA in our study, we think that methods for its detection in a clinical setting could be helpful for adjusting short-term and long-term treatment. We speculate that assessment of changes in personal concentration of LTE4 could be more reliable than the absolute value of a single measurement.In conclusion, urinary LTE4 excretion after exercise has a different pattern (i.e. higher changes) in children with EIA compared to controls. Assessment of urinary LTE4 using enzyme immunoassay could be a promising non-invasive alternative for optimising therapy in children with EIA.Conflict of interestThe authors have no competing interests to declare. The authors alone are responsible for the content and writing of the paper." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres86110" "titulo" => array:5 [ 0 => "Abstract" 1 => "Background" 2 => "Methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec74274" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xpalclavsec74275" "titulo" => "Abbreviations" ] 3 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 4 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 5 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interest" ] 9 => array:2 [ "identificador" => "xack31879" "titulo" => "Acknowledgments" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-02-13" "fechaAceptado" => "2011-03-29" "PalabrasClave" => array:1 [ "en" => array:2 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec74274" "palabras" => array:5 [ 0 => "Inflammation" 1 => "Exercise" 2 => "Paediatric" 3 => "Asthma" 4 => "Lung function" ] ] 1 => array:4 [ "clase" => "abr" "titulo" => "Abbreviations" "identificador" => "xpalclavsec74275" "palabras" => array:9 [ 0 => "EIA" 1 => "ECT" 2 => "FEF 25-75" 3 => "FEV1" 4 => "FVC" 5 => "LTE 4" 6 => "Max" 7 => "Min" 8 => "rs" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "BackgroundLeukotrienes are among the most important mediators associated with inflammatory responses in patients with exercise induced asthma (EIA). The aim of this study was to investigate the impact of exercise on the urinary leukotriene profile. Hence, we compared post exercise changes of urinary leukotriene E4 (LTE4) concentration between children with EIA and healthy controls. MethodsTen children with EIA and 15 controls were enrolled. Both groups underwent a standardised exercise challenge test (ECT). LTE4 concentration was measured in urine samples obtained pre and post ECT, using enzyme immunoassay and adjusted by urinary creatinine concentrations. ResultsMedian (minimum–maximum) pre ECT concentration of LTE4 was 17.82 (7.58–90.23pg/ml) in EIA and 17.24 (4.64–64.02pg/ml) in controls, p=0.86. LTE4 concentration post ECT were 23.37 (4.02–93.00pg/ml) in EIA and 11.74 (0.13–25.09pg/ml) in controls, p=0.02. Changes of LTE4 concentration post ECT were 2.54 (−31.98 to 43.31pg/ml) in cases and −13.53 (−46.00 to 11.02pg/ml) in controls, p=0.03. There was no significant correlation between basal predicted FEV1 [%] and changes in LTE4 concentration in cases (i.e., rs=0.14) nor controls (i.e., rs=0.12). There was a tendency towards more pronounced changes in LTE4 concentration post ECT in children with moderate/mild persistent asthma compared to those with mild but intermittent asthma. ConclusionsChildren with EIA had significantly higher changes of urinary LTE4 concentrations post ECT compared to healthy controls. Urinary measurement of LTE4 may be an interesting and non-invasive option to assess control of EIA in children." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1313 "Ancho" => 1657 "Tamanyo" => 67237 ] ] "descripcion" => array:1 [ "en" => "Comparison of changes in urinary LTE4 concentration post-ECT between cases and controls." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1023 "Ancho" => 1595 "Tamanyo" => 64362 ] ] "descripcion" => array:1 [ "en" => "Intraindividual changes in urinary LTE4 concentrations in cases." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1036 "Ancho" => 1616 "Tamanyo" => 96620 ] ] "descripcion" => array:1 [ "en" => "Intraindividual changes in urinary LTE4 concentrations in controls." ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Gender is expressed as n; all other variables as median (min–max).ECT: exercise challenge test; FEF 25–77: forced expiratory flow 25–75%; FEV1: forced expiratory volume in 1st second; FVC: forced vital capacity." "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Cases (n=10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Controls (n=15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">p-Value \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Girls/boys \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4/6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4/11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.79 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age [years] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.1 (7.6–15.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.6 (7.2–17.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weekly hours of physical activity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5 (0–8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.0 (0–12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.85 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FEV1 predicted [%] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">118 (85–150) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">123 (88–136) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FVC predicted) [%] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">116 (88–155) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">116 (85–135) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FEF25–75 predicted [%] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">99 (67–139) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">97 (68–144) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Maximum fall of FEV1 after ECT [%] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14.0 (8–59) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0 (0–7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.0001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Time for maximum fall in FEV1 [min] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.0 (1–3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.0 (0–7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.17 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165479.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison of demographic and pulmonary function variables between cases and controls." ] ] 4 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "All results given as median (min–max).Kruskal–Wallis test between asthma severity groups: p-value=0.11.LTE4: leukotriene E4; ECT: exercise challenge test." "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Asthma severity classification \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Change in urinary LTE4 concentration [pg/mg] after exercise test \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No asthma (n=15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−15.3 (−81.3; +13.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mild intermittent (n=4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−4.1 (−17.7; +109.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mild persistent (n=4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+9.1 (−103.4; +15.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate persistent (n=2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+12.6 (+8.4; +16.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165478.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison of changes in urinary LTE4 concentration after ECT stratified by asthma severity." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:27 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exercise-induced asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.H. 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P.E. Brockmanna,

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pbrockmann@med.puc.cl

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, J.A. Castro-Rodrigueza, N.L. Holmgrena, J. Cerdab, A. María Contrerasc, A. Moyad, P.J. Bertranda

a Department of Pediatrics, Pontificia Universidad Catolica de Chile, Santiago, Chile

b Department of Public Health, Pontificia Universidad Catolica de Chile, Santiago, Chile

c Center of Medical Investigation, Pontificia Universidad Catolica de Chile, Santiago, Chile

d Pediatric Lung Function Laboratory, Pontificia Universidad Catolica de Chile, Santiago, Chile

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Exercise-induced symptoms are common among children with asthma&#46; Coughing is the most common symptom associated with exercise&#44; with a frequency of approximately 70&#8211;80&#37; in untreated patients&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Exercise-induced symptoms produce limitations in daily activity<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#8211;4</span></a> and a poorer quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Therefore&#44; early recognition of non-controlled exercise-induced asthma &#40;EIA&#41; may be important for adjustment of treatment and prevention of physical and psychological effects&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a> Nevertheless&#44; this assessment may be especially difficult in children using conventional methods like spirometry&#44; peak flow or clinical symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> In recent years&#44; markers of airway inflammation&#44; such as fractional exhaled nitric oxide&#44; induced sputum eosinophils and urinary leukotriene E4 &#40;LTE4&#41;&#44; have been studied and proposed for better assessment of the inflammatory state of children with asthma&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#8211;10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Leukotrienes are among the most important cytokines involved in exercise-induced inflammatory response&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> They are products of arachidonic acid metabolism by the cyclooyxgenase 1&#47;2 pathways&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#8211;14</span></a> Since leukotriene E4 &#40;LTE4&#41; is the end product of all cysteinyl-LT metabolisms in the lung&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> measuring urinary leukotrienes may be an interesting option for assessing the inflammatory state in children with asthma&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The role of leukotrienes in EIA has been evidenced by a sustained increase in their concentration 30&#8211;90<span class="elsevierStyleHsp" style=""></span>min after exercise challenge in adults&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> However&#44; in children with asthma&#44; the specific profile of urinary leukotriene excretion and its association with the clinical severity of asthma has not yet been clarified&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">We aimed to determine if urinary LTE4 concentration shows a disease-specific pattern and could therefore be useful as a non-invasive marker to compare post exercise LTE4 urinary excretion in children with EIA versus healthy controls&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">Children between 6 and 17 years of age with EIA &#40;cases&#41; and healthy children &#40;controls&#41; were enrolled prospectively in 2008&#46; Cases were enrolled among children with physician diagnosed EIA &#40;symptoms like wheezing&#44; cough&#44; or dyspnoea clearly associated with exercise<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>&#41; who were routinely sent to our respiratory laboratory to perform an exercise challenge test &#40;ECT&#41;&#46; All children who presented any disease other than asthma&#59; admitted active tobacco smoking&#59; or had received long-term treatment with inhaled or oral corticosteroids&#44; montelukast or antihistamines &#40;the latter for at least seven days before the ECT&#41;&#44; were excluded from this group&#46; As controls&#44; healthy volunteers &#40;children of hospital co-workers&#41; who were age-matched to cases were selected&#46; In this group&#44; children who presented any chronic underlying disease&#59; admitted active smoking&#59; or had used inhaled or oral corticosteroids&#44; montelukast or antihistamines were also excluded&#46; In both groups&#44; children with any acute respiratory infection in the last three weeks were excluded&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">After explaining the purpose of the study&#44; informed consent was obtained from parents and children&#46; Age&#44; gender and reported weekly hours of physical activity were assessed for both groups&#46; Parents of cases were also asked about the use of medications&#44; the date of the EIA diagnosis&#44; visits to the emergency department and hospitalisation&#46; Cases were classified as suffering from mild intermittent&#44; mild persistent&#44; moderate persistent or severe asthma according to the Global Initiative for Asthma Guidelines &#40;<a href="http://www.ginasthma.org/">http&#58;&#47;&#47;www&#46;ginasthma&#46;org</a>&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The ECT was performed at the paediatric pulmonary function laboratory according to guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> In both groups &#40;cases and controls&#41; the ECT was conducted between 9<span class="elsevierStyleHsp" style=""></span>am and 4<span class="elsevierStyleHsp" style=""></span>pm under controlled environmental conditions &#40;21<span class="elsevierStyleHsp" style=""></span>&#176;C and 45&#37; relative humidity&#41;&#44; in order to achieve standardisation of known factors that influence bronchial response to exercise&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Spirometry &#40;Schiller SP 100<span class="elsevierStyleSup">&#174;</span>&#44; Switzerland&#41; was carried out with children standing and wearing a nose clip&#46; At least three baseline spirometric measurements were performed in order to ensure appropriate acceptability and reproducibility of the test&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Subsequently&#44; subjects performed a sub maximum effort&#44; defined as a high intensity test of six minutes on a treadmill &#40;Stracrac model ST-1600<span class="elsevierStyleSup">&#174;</span>&#41; at 3&#46;6<span class="elsevierStyleHsp" style=""></span>miles&#47;h and 10&#176; elevation&#46; Heart rate reached at least 80&#37; of theoretical maximum for patient age &#40;220 - age&#41;&#46; This variable was monitored with a Polar F1<span class="elsevierStyleSup">TM</span> fitness monitor placed around the thorax&#46; Arterial saturation was monitored with Masimo RAD9<span class="elsevierStyleSup">&#174;</span> &#40;Irvine&#44; CA&#44; USA&#41; equipment&#46; A nose clip was worn to ensure breathing through the mouth&#46; After each spirometry&#44; the children&#39;s breathing was monitored with a stethoscope to detect wheezing&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Once the stimulus &#40;exercise&#41; was completed&#44; spirometry was repeated at 1&#44; 3&#44; 5&#44; 7&#44; 10&#44; 15 and 30<span class="elsevierStyleHsp" style=""></span>min&#46; Two or three spirometric manoeuvres were performed for each measurement&#44; with a maximum difference of &#177;5&#37; in forced expiratory volumen 1st second &#40;FEV<span class="elsevierStyleInf">1</span>&#41;&#46; FEV<span class="elsevierStyleInf">1</span> and forced expiratory flow 25-75&#37; &#40;FEF<span class="elsevierStyleInf">25&#8211;75</span>&#41; was registered for each measurement&#44; choosing the best corresponding FEV<span class="elsevierStyleInf">1</span> manoeuvre&#46; After obtaining a fall in FEV<span class="elsevierStyleInf">1</span> from the baseline&#44; we analysed the flow volume curve shape&#44; which allowed testing for quality control of the spirometric effort&#46; After the ECT&#44; every child received 200<span class="elsevierStyleHsp" style=""></span>mcg of salbutamol MDI using a breathing mask&#44; and performed spirometry again to ensure the return to baseline values&#46; ECT was considered positive if&#58; &#40;i&#41; the decrease of FEV<span class="elsevierStyleInf">1</span> was &#62;10&#37; of baseline&#59; or &#40;ii&#41; if wheezing and dyspnoea were determined&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Urine samples were collected immediately before starting the ECT&#46; A second urine sample was collected 30<span class="elsevierStyleHsp" style=""></span>min after finishing the ECT&#46; Urine samples were then refrigerated at &#8722;70<span class="elsevierStyleHsp" style=""></span>&#176;C and saved until all samples were processed&#46; LTE4 in urine was measured by ACETM Enzyme Immunoassay Kit<span class="elsevierStyleSup">&#174;</span> &#40;Cayman Chemical&#44; Ann Arbor&#44; MI&#44; USA&#41;&#44; according to recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Urine LTE4 concentration was reported in pg&#47;ml and standardised per mg&#47;ml of creatinine&#46; Therefore&#44; all urinary LTE4 concentrations were reported as pg&#47;mg of creatinine&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">This protocol was approved by the Ethics Committee of the Pontificia Universidad Cat&#243;lica de Chile and parents authorised their children&#39;s participation by signing informed consent forms&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">In this preliminary phase of the study&#44; 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was calculated and its distribution was compared between groups using the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; the correlations &#40;non-parametric correlations&#41; according to Spearman &#91;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span>&#93; were estimated between changes in urinary LTE4 concentrations post ECT and pulmonary function variables or reported hours of physical activity&#46; The Kruskal&#8211;Wallis test was used to investigate associations between changes in urinary LTE4 concentrations post ECT and clinical asthma severity&#46; <span class="elsevierStyleItalic">p</span>-Values &#60;0&#46;05 were considered statistically significant&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">Of the 29 children initially recruited&#44; four were excluded from the analysis&#46; Two patients with EIA and one control were excluded because they were found to have previously received inhaled corticosteroids&#46; An additional control subject was excluded for being an ex-smoker&#46; Twenty-five subjects were finally analyzed&#44; 10 with EIA &#40;six boys&#41; and 15 controls &#40;11 boys&#41;&#46; All of them completed the ECT successfully and reached the target heart rate&#46; There were no differences between cases and controls in terms of age&#44; weekly hours of physical activity&#44; nor basal lung function&#46; However&#44; there were significantly higher decreases of FEV<span class="elsevierStyleInf">1</span> &#40;&#37;&#41; after ECT among cases than controls &#40;14 &#91;8&#8211;59&#93; vs&#46; 1 &#91;0&#8211;7&#93;&#44; respectively&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41; &#40;see <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; Among cases&#44; four wheezed after full completion of ECT and required bronchodilator therapy in situ&#46; After the ECT&#44; all cases either developed a fall in FEV<span class="elsevierStyleInf">1</span> &#62;10&#37;&#44; or had wheezing and had therefore&#44; a positive ECT&#46; In contrast to that&#44; none of the controls developed such findings and all had therefore a negative ECT&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Children with EIA were classified as&#58; mild intermittent &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#59; mild persistent &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#59; and moderate persistent &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&#46; In this group&#44; median &#40;min&#8211;max&#41; time of the asthma diagnosis was 0&#46;23 &#40;0&#8211;13&#41; years&#59; the number of asthma crises in the last year that needed treatment was one &#40;1&#8211;6&#41;&#59; the number of visits to the emergency department in the last year was one &#40;0&#8211;8&#41;&#59; and hospitalisations were zero &#40;0&#8211;5&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Baseline median &#40;min&#8211;max&#41; values of LTE4 concentrations &#91;pg&#47;mg creatinine&#93; were similar between cases and controls &#40;17&#46;8 &#91;7&#46;6&#8211;90&#46;2&#93; vs&#46; 17&#46;2 &#91;4&#46;6&#8211;64&#46;0&#93;&#44; respectively&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;86&#41;&#46; However&#44; LTE4 concentrations post ECT were significantly higher among cases versus controls &#40;23&#46;8 &#91;4&#46;0&#8211;93&#93; vs&#46; 11&#46;7 &#91;0&#46;1&#8211;25&#46;1&#93;&#44; respectively&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41;&#46; Also&#44; changes of LTE4 concentration pre and post ECT were significantly different among cases versus controls &#40;2&#46;5 &#91;&#8722;32 to 43&#46;3&#93; vs&#46; &#8722;13&#46;5 &#91;&#8722;46 to 11&#93; in controls&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#44; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; Individual changes in LTE4 concentrations in cases and controls are shown in <a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#44; respectively&#46; There was a tendency towards higher changes in LTE4 concentration post ECT in children with more severe asthma &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;11&#41;&#44; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">There was no significant correlation between basal &#37; predicted FEV<span class="elsevierStyleInf">1</span> and changes in LTE4 concentration in cases &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;14&#41; and controls &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;12&#41;&#46; Also&#44; there was no significant correlation between absolute or predicted values of FVC&#44; FEF25-75 and FEV<span class="elsevierStyleInf">1</span> and changes in LTE4 concentration pre and post ECT &#40;all <span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;20&#41;&#46; There was a significant correlation between the maximum fall in FEV<span class="elsevierStyleInf">1</span> and changes in LTE4 concentration &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;69&#41; in cases but not in controls &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;19&#41;&#46; Correlation between changes in LTE4 concentration post ECT and weekly hours of physical activity was <span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;09 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;80&#41; in cases&#44; and <span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;49 &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; in controls&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">This study demonstrated a different pattern in urinary LTE4 concentration post ECT in subjects with asthma compared to healthy children&#46; As this response was observed within 30<span class="elsevierStyleHsp" style=""></span>min of the running test&#44; this may suggest a different and rapid pattern of LTE4 excretion after exercise in children with EIA compared to healthy controls&#46; Interestingly&#44; this response seems rapid enough to be assigned to the preceding exercise and could possibly be useful for the assessment of non-controlled inflammation in EIA&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">This pattern of LTE4 changes after exercise may reflect a specific and rapidmetabolism of inflammatory mediators in children with EIA&#46; Interestingly&#44; intraindividual changes showed that most of the healthy controls had a decrease in LTE4 concentration after ECT&#46; In contrast to that&#44; LTE4 concentration was stable in children with EIA&#44; and increased in some cases&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Nevertheless&#44; there is conflicting evidence about changes in LTE4 after exercise&#46; Kikawa et al&#46; showed no significant differences between basal LTE4 concentration in children with asthma compared to healthy peers&#44; but a significant increase only among asthmatics&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> On the other hand&#44; others have shown no increased urinary excretion of LTE after exercise&#44; nor an association with exercise-induced bronchospasm&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">In adults&#44; Reiss et al&#46; showed an increase in urinary leukotrienes and an attenuation of that response using a leukotriene receptor antagonist in non-smoking asthmatic subjects&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Also in adults&#44; Taylor et al&#46; showed no significant increase in urinary leukotrienes after exercise&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">However&#44; in children with EIA the specific profile of urinary leukotrienes has not yet been clarified and studies that have assessed urinary excretion of leukotrienes after exercise are sparse&#46; For example&#44; Severien et al&#46; showed that there was significantly higher urinary excretion of LTE4 in subjects with asthma compared to healthy controls&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Our results&#44; similar to those of Kikawa et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> using another technique for LTE4 measure &#40;i&#46;e&#46;&#44; radioimmunoassay&#41;&#44; showed no significant changes in basal concentration of LTE4&#44; and a significant difference in post-exercise change in LTE4 concentration between children with EIA and controls&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">An association of LTE4 concentrations and lung function has been summarized by a recent review&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> One study showed an association among LTE4 concentrations&#44; a fall in FEV<span class="elsevierStyleInf">1</span>&#44; and a protection using leukotriene receptor antagonist in children&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> In contrast&#44; we did not find a correlation between LTE4 concentration and FEV<span class="elsevierStyleInf">1</span>&#46; Interestingly&#44; Kikawa et al&#46; did not find any correlation either between LTE4 concentration after exercise and the degree of bronchoconstriction&#44; although using maximum percentage decrease in the peak expiratory flow&#46; This may be explained by either the presence of milder forms of asthma in the studied subjects&#44; or even by a more precise recognition of non-controlled asthma by the LTE4 than FEV<span class="elsevierStyleInf">1</span>&#46; We also showed no correlation between hours of physical activity and changes in LTE4 concentration in children with EIA&#46; This could be explained by diverse reasons&#44; like different basal inflammatory conditions of the subjects or the subjective and possibly imprecise self-estimation of weekly hours of physical activity&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">We hypothesize that under certain conditions&#44; like exercise&#44; leukotriene-associated inflammation has a specific pattern in children with EIA&#44; and this may mark a difference with healthy children&#44; among whom there is no such inflammation&#46; Furthermore&#44; we found in the present study&#44; that children with more severe EIA&#44; according to a widely used clinical classification &#40;i&#46;e&#46;&#44; Global Initiative for Asthma Guidelines&#41;&#44; showed higher levels of change in urinary concentration of LTE4 post ECT&#46; While some have found similar results&#44;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;24</span></a> others have found no correlation between leukotriene concentration and asthma severity&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;13&#44;25</span></a> This fact may be of special clinical interest&#44; considering that using montelukast may be useful in patients with EIA with such high leukotriene excretion levels&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">In order to better understand the role of leukotrienes in asthma&#44; different metabolites &#40;i&#46;e&#46;&#44; leukotriene B4&#44; C4&#44; D4 or E4&#41; have been investigated in sputum&#44; exhaled condensate and urine&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;26</span></a> For the present study&#44; urinary LTE4 was chosen as a marker of inflammation&#44; as it has recently shown specific functions in patients with asthma&#44; suggesting an important role for this molecule in inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In addition&#44; urinary LTE4 could be easily obtained in school-aged children from single urine samples&#46; Previously&#44; techniques for assessing urinary LTE4&#44; such as reversed-phase high-performance liquid chromatography&#44; radioimmunoassay&#44; or enzyme immunoassay have been used&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;21</span></a> Qiu et al&#46; showed that enzyme immunoassay significantly correlated with what was usually considered the gold standard &#40;i&#46;e&#46;&#44; reversed-phase high-performance liquid chromatography&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> To our knowledge&#44; the present study represents the first comparison in LTE4 concentration after exercise using enzyme immunoassay in children with this specific form of asthma &#40;i&#46;e&#46;&#44; EIA&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The present study has some potential limitations&#46; First&#44; we measured only one sample of LTE4 from all subjects 30<span class="elsevierStyleHsp" style=""></span>min after the ECT&#46; It is possible that obtaining more samples of each subject&#44; in order to establish the optimal excretion time&#44; would have shown further differences in LTE4 excretion between the groups&#46; Notwithstanding that&#44; we demonstrated a significant difference in the concentration of LTE4 post ECT under the same sampling conditions between cases and healthy controls&#46; Another limitation of this preliminary phase may have been the sample size&#44; although it was based on previous studies&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> However&#44; we hypothesize that associations obtained between urinary LTE4 concentration and lung function or clinical severity could be strengthened with a larger sample&#44; which may be designed based on this results&#46; Moreover&#44; intraindividual changes showed that LTE4 concentrations after ECT in subjects with EIA often remained stable and increased in some cases&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Further studies should confirm if assessment of changes in LTE4 concentration after exercise could be helpful in directing a specific treatment in children with EIA&#46; A strength of the present study was the use of an ECT that strictly followed the recommendation of the American Thoracic Society &#40;ATS&#41; recommendation&#44; considering that only one out of nine protocols of ECT published after 2000 &#40;and none published before&#41; followed these guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Due to the pattern of urinary LTE4 excretion in subjects with EIA in our study&#44; we think that methods for its detection in a clinical setting could be helpful for adjusting short-term and long-term treatment&#46; We speculate that assessment of changes in personal concentration of LTE4 could be more reliable than the absolute value of a single measurement&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In conclusion&#44; urinary LTE4 excretion after exercise has a different pattern &#40;i&#46;e&#46; higher changes&#41; in children with EIA compared to controls&#46; Assessment of urinary LTE4 using enzyme immunoassay could be a promising non-invasive alternative for optimising therapy in children with EIA&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors have no competing interests to declare&#46; The authors alone are responsible for the content and writing of the paper&#46;</p></span></span>"
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          "titulo" => array:5 [
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            1 => "Background"
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            4 => "Conclusions"
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          "titulo" => "Keywords"
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          "identificador" => "xpalclavsec74275"
          "titulo" => "Abbreviations"
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        3 => array:2 [
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          "titulo" => "Introduction"
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          "titulo" => "Methods"
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        5 => array:2 [
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          "titulo" => "Statistical analysis"
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        6 => array:2 [
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          "titulo" => "Results"
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        7 => array:2 [
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          "titulo" => "Discussion"
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        8 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Conflict of interest"
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        9 => array:2 [
          "identificador" => "xack31879"
          "titulo" => "Acknowledgments"
        ]
        10 => array:1 [
          "titulo" => "References"
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    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2011-02-13"
    "fechaAceptado" => "2011-03-29"
    "PalabrasClave" => array:1 [
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec74274"
          "palabras" => array:5 [
            0 => "Inflammation"
            1 => "Exercise"
            2 => "Paediatric"
            3 => "Asthma"
            4 => "Lung function"
          ]
        ]
        1 => array:4 [
          "clase" => "abr"
          "titulo" => "Abbreviations"
          "identificador" => "xpalclavsec74275"
          "palabras" => array:9 [
            0 => "EIA"
            1 => "ECT"
            2 => "FEF 25-75"
            3 => "FEV<span class="elsevierStyleInf">1</span>"
            4 => "FVC"
            5 => "LTE 4"
            6 => "Max"
            7 => "Min"
            8 => "<span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span>"
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    "resumen" => array:1 [
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Leukotrienes are among the most important mediators associated with inflammatory responses in patients with exercise induced asthma &#40;EIA&#41;&#46; The aim of this study was to investigate the impact of exercise on the urinary leukotriene profile&#46; Hence&#44; we compared post exercise changes of urinary leukotriene E4 &#40;LTE4&#41; concentration between children with EIA and healthy controls&#46;</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Ten children with EIA and 15 controls were enrolled&#46; Both groups underwent a standardised exercise challenge test &#40;ECT&#41;&#46; LTE4 concentration was measured in urine samples obtained pre and post ECT&#44; using enzyme immunoassay and adjusted by urinary creatinine concentrations&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Median &#40;minimum&#8211;maximum&#41; pre ECT concentration of LTE4 was 17&#46;82 &#40;7&#46;58&#8211;90&#46;23<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; in EIA and 17&#46;24 &#40;4&#46;64&#8211;64&#46;02<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; in controls&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;86&#46; LTE4 concentration post ECT were 23&#46;37 &#40;4&#46;02&#8211;93&#46;00<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; in EIA and 11&#46;74 &#40;0&#46;13&#8211;25&#46;09<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; in controls&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#46; Changes of LTE4 concentration post ECT were 2&#46;54 &#40;&#8722;31&#46;98 to 43&#46;31<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; in cases and &#8722;13&#46;53 &#40;&#8722;46&#46;00 to 11&#46;02<span class="elsevierStyleHsp" style=""></span>pg&#47;ml&#41; in controls&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#46; There was no significant correlation between basal predicted FEV<span class="elsevierStyleInf">1</span> &#91;&#37;&#93; and changes in LTE4 concentration in cases &#40;i&#46;e&#46;&#44; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;14&#41; nor controls &#40;i&#46;e&#46;&#44; <span class="elsevierStyleItalic">r</span><span class="elsevierStyleInf">s</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;12&#41;&#46; There was a tendency towards more pronounced changes in LTE4 concentration post ECT in children with moderate&#47;mild persistent asthma compared to those with mild but intermittent asthma&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Children with EIA had significantly higher changes of urinary LTE4 concentrations post ECT compared to healthy controls&#46; Urinary measurement of LTE4 may be an interesting and non-invasive option to assess control of EIA in children&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Comparison of changes in urinary LTE4 concentration post-ECT between cases and controls&#46;</p>"
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          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Gender is expressed as <span class="elsevierStyleItalic">n</span>&#59; all other variables as median &#40;min&#8211;max&#41;&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">ECT&#58; exercise challenge test&#59; FEF 25&#8211;77&#58; forced expiratory flow 25&#8211;75&#37;&#59; FEV<span class="elsevierStyleInf">1</span>&#58; forced expiratory volume in 1st second&#59; FVC&#58; forced vital capacity&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">Cases &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Controls &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-Value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Girls&#47;boys&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#47;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age &#91;years&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;1 &#40;7&#46;6&#8211;15&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;6 &#40;7&#46;2&#8211;17&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Weekly hours of physical activity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&#46;5 &#40;0&#8211;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;0 &#40;0&#8211;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEV<span class="elsevierStyleInf">1</span> predicted &#91;&#37;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">118 &#40;85&#8211;150&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">123 &#40;88&#8211;136&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FVC predicted&#41; &#91;&#37;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">116 &#40;88&#8211;155&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">116 &#40;85&#8211;135&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FEF25&#8211;75 predicted &#91;&#37;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99 &#40;67&#8211;139&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97 &#40;68&#8211;144&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Maximum fall of FEV<span class="elsevierStyleInf">1</span> after ECT &#91;&#37;&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">14&#46;0 &#40;8&#8211;59&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&#46;0 &#40;0&#8211;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#60;0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Time for maximum fall in FEV<span class="elsevierStyleInf">1</span> &#91;min&#93;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3&#46;0 &#40;1&#8211;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&#46;0 &#40;0&#8211;7&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;17&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Asthma severity classification&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Change in urinary LTE4 concentration &#91;pg&#47;mg&#93; after exercise test&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8722;15&#46;3 &#40;&#8722;81&#46;3&#59; &#43;13&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#8722;4&#46;1 &#40;&#8722;17&#46;7&#59; &#43;109&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Mild persistent &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#43;9&#46;1 &#40;&#8722;103&#46;4&#59; &#43;15&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Moderate persistent &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#43;12&#46;6 &#40;&#43;8&#46;4&#59; &#43;16&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparison of changes in urinary LTE4 concentration after ECT stratified by asthma severity&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:27 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Exercise-induced asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "K&#46;H&#46; Carlsen"
                            1 => "K&#46;C&#46; Carlsen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Paediatr Respir Rev"
                        "fecha" => "2002"
                        "volumen" => "3"
                        "numero" => "June"
                        "paginaInicial" => "154"
                        "paginaFinal" => "160"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12297065"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Physical activity in urban school-aged children with asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "D&#46;M&#46; Lang"
                            1 => "A&#46;M&#46; Butz"
                            2 => "A&#46;K&#46; Duggan"
                            3 => "J&#46;R&#46; Serwint"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Pediatrics"
                        "fecha" => "2004"
                        "volumen" => "113"
                        "numero" => "April"
                        "paginaInicial" => "e341"
                        "paginaFinal" => "e346"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15060265"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Exercise-induced asthma as perceived by pediatric patients and their parents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Brockmann"
                            1 => "D&#46; Fodor"
                            2 => "S&#46; Caussade"
                            3 => "E&#46; Campos"
                            4 => "P&#46; Bertrand"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "/S0034-98872006000600010"
                      "Revista" => array:7 [
                        "tituloSerie" => "Rev Med Chil"
                        "fecha" => "2006"
                        "volumen" => "134"
                        "numero" => "June"
                        "paginaInicial" => "743"
                        "paginaFinal" => "748"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17130949"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Physical activity and physical self-concept&#58; comparison between children with and without asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46;C&#46; Chiang"
                            1 => "J&#46;L&#46; Huang"
                            2 => "L&#46;S&#46; Fu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2648.2006.03873.x"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Adv Nurs"
                        "fecha" => "2006"
                        "volumen" => "54"
                        "numero" => "June"
                        "paginaInicial" => "653"
                        "paginaFinal" => "662"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16796657"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
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            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Exercise-induced asthma is associated with impaired quality of life among children with asthma in Japan"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Kojima"
                            1 => "Y&#46; Ohya"
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Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2011.03.012

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	1	0	1
2024 October	20	7	27
2024 September	14	8	22
2024 August	14	7	21
2024 July	8	9	17
2024 June	23	5	28
2024 May	11	10	21
2024 April	9	3	12
2024 March	22	5	27
2024 February	27	10	37
2024 January	5	2	7
2023 December	17	8	25
2023 November	18	5	23
2023 October	26	12	38
2023 September	26	2	28
2023 August	14	9	23
2023 July	28	7	35
2023 June	24	3	27
2023 May	29	2	31
2023 April	34	5	39
2023 March	21	3	24
2023 February	21	6	27
2023 January	16	7	23
2022 December	16	5	21
2022 November	15	4	19
2022 October	17	7	24
2022 September	12	7	19
2022 August	12	9	21
2022 July	9	9	18
2022 June	8	6	14
2022 May	18	8	26
2022 April	22	6	28
2022 March	12	9	21
2022 February	12	5	17
2022 January	30	9	39
2021 December	16	11	27
2021 November	11	6	17
2021 October	14	11	25
2021 September	10	11	21
2021 August	9	10	19
2021 July	4	9	13
2021 June	12	8	20
2021 May	14	5	19
2021 April	23	14	37
2021 March	14	15	29
2021 February	9	8	17
2021 January	4	4	8
2020 December	1	2	3
2020 October	0	1	1
2020 July	0	2	2
2020 June	0	1	1
2020 May	0	2	2
2020 February	0	1	1
2020 January	0	4	4
2019 December	0	4	4
2019 November	0	2	2
2019 September	0	4	4
2019 July	0	2	2
2019 June	0	11	11
2019 May	0	32	32
2019 April	0	10	10
2019 March	0	3	3
2019 January	0	4	4
2018 February	0	0	0
2018 January	6	0	6
2017 December	8	0	8
2017 November	7	5	12
2017 October	6	2	8
2017 September	6	2	8
2017 August	7	2	9
2017 July	5	1	6
2017 June	8	4	12
2017 May	18	2	20
2017 April	7	0	7
2017 March	17	15	32
2017 February	11	1	12
2017 January	11	0	11
2016 December	12	2	14
2016 November	7	3	10
2016 October	25	2	27
2016 September	12	2	14
2016 August	15	4	19
2016 July	12	2	14
2016 June	17	6	23
2016 May	9	7	16
2016 April	9	9	18
2016 March	10	13	23
2016 February	13	13	26
2016 January	11	14	25
2015 December	14	13	27
2015 November	15	11	26
2015 October	24	12	36
2015 September	11	5	16
2015 August	11	1	12
2015 July	1	3	4
2015 June	5	2	7
2015 May	10	1	11
2015 April	12	7	19
2015 March	5	2	7
2015 February	8	3	11
2015 January	22	2	24
2014 December	22	3	25
2014 November	15	5	20
2014 October	17	3	20
2014 September	24	2	26
2014 August	10	2	12
2014 July	14	2	16
2014 June	7	1	8
2014 May	11	1	12
2014 April	5	4	9
2014 March	35	7	42
2014 February	40	5	45
2014 January	52	11	63
2013 December	57	9	66
2013 November	23	8	31
2013 October	31	8	39
2013 September	32	4	36
2013 August	35	14	49
2013 July	33	13	46
2013 June	23	2	25
2013 May	23	5	28
2013 April	15	9	24
2013 March	20	8	28
2013 February	11	6	17
2013 January	7	2	9
2012 December	8	3	11
2012 November	0	3	3
2012 October	2	1	3
2012 September	3	2	5
2012 April	491	0	491

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Allergologia et Immunopathologia is no longer published on Elsevier since the 2021 year.Transferred to Codon Publications

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