Asthma diagnosis and severity monitoring in primary school children: Essential role of sequential testing of exhaled nitric oxide

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Mahdaviani, P. Mehrian, A. Najafi, S. Khalilzadeh, S. Eslampanah, A. Nasri, M. Bakhshayesh Karam, N. Rezaei, A.A. Velayati" "autores" => array:9 [ 0 => array:2 [ "nombre" => "S.A." "apellidos" => "Mahdaviani" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Mehrian" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Najafi" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Khalilzadeh" ] 4 => array:2 [ "nombre" => "S." "apellidos" => "Eslampanah" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Nasri" ] 6 => array:2 [ "nombre" => "M. Bakhshayesh" "apellidos" => "Karam" ] 7 => array:2 [ "nombre" => "N." "apellidos" => "Rezaei" ] 8 => array:2 [ "nombre" => "A.A." "apellidos" => "Velayati" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054613001493?idApp=UINPBA00004N" "url" => "/03010546/0000004200000005/v1_201409050044/S0301054613001493/v1_201409050044/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0301054613001511" "issn" => "03010546" "doi" => "10.1016/j.aller.2013.04.005" "estado" => "S300" "fechaPublicacion" => "2014-09-01" "aid" => "525" "copyright" => "SEICAP" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Allergol Immunopathol (Madr). 2014;42:433-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 709 "formatos" => array:3 [ "EPUB" => 5 "HTML" => 452 "PDF" => 252 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Uncertain areas in the diagnosis of allergic bronchopulmonary aspergillosis in patients with asthma" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "433" "paginaFinal" => "438" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.R. Park, Y.H. Nam, S.K. Lee, K.H. Kim, M.S. Roh, H.W. Lee, I.H. Jeong, S.J. Um, C.H. Son" "autores" => array:9 [ 0 => array:2 [ "nombre" => "M.R." "apellidos" => "Park" ] 1 => array:2 [ "nombre" => "Y.H." "apellidos" => "Nam" ] 2 => array:2 [ "nombre" => "S.K." "apellidos" => "Lee" ] 3 => array:2 [ "nombre" => "K.H." "apellidos" => "Kim" ] 4 => array:2 [ "nombre" => "M.S." "apellidos" => "Roh" ] 5 => array:2 [ "nombre" => "H.W." "apellidos" => "Lee" ] 6 => array:2 [ "nombre" => "I.H." "apellidos" => "Jeong" ] 7 => array:2 [ "nombre" => "S.J." "apellidos" => "Um" ] 8 => array:2 [ "nombre" => "C.H." "apellidos" => "Son" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054613001511?idApp=UINPBA00004N" "url" => "/03010546/0000004200000005/v1_201409050044/S0301054613001511/v1_201409050044/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Asthma diagnosis and severity monitoring in primary school children: Essential role of sequential testing of exhaled nitric oxide" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "439" "paginaFinal" => "443" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "K.-S. Wan, W.-H. Chiu, W. Yang" "autores" => array:3 [ 0 => array:4 [ "nombre" => "K.-S." "apellidos" => "Wan" "email" => array:1 [ 0 => "DXD40@tpech.gov.tw" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "W.-H." "apellidos" => "Chiu" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "W." "apellidos" => "Yang" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Pediatrics, Taipei City Hospital, Renai Branch, Taiwan" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Colleges of Medicine, National Yang-Ming University, Taipei, Taiwan" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Pediatrics, Taipei City Hospital, Yangming Branch, Taiwan" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1572 "Ancho" => 2505 "Tamanyo" => 196093 ] ] "descripcion" => array:1 [ "en" => "There is statistically significant down-regulation among the three serial FeNO measurements (p<0.05) after ICS treatment with or without Singulair. However, the decreased FeNO in levels between the second and third measurements are not statistically significant." ] ] ] "textoCompleto" => "IntroductionAirway eosinophilia is considered a critical event in the pathogenesis of asthma. Eotaxin and RANTES have been implicated in the allergic inflammation associated with asthma by promoting the migration and activation of inflammatory cells, including eosinophils. Concentrations of these cytokines in exhaled breath condensates (EBC) have been significantly correlated with exhaled nitric oxide (FeNO) concentrations and serum eosinophil cationic protein (ECP) levels in asthmatics, particularly in unstable and steroid-naive stable asthmatics.<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a>Guidelines for asthma management suggest a stepwise approach to pharmacotherapy based on assessments of severity and control. However, the assessment of asthma control currently relies on surrogate measures like the frequency of symptoms or the frequency of use of short-acting β2-adrenergic agonists (SABA).<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a> Increased expression of inducible nitric oxide synthase and elevated FeNO levels are seen in asthmatic patients and have become increasingly recognised for their use in evaluating bronchial inflammation when monitoring anti-inflammatory treatment.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> Moreover, atopic individuals have increased FeNO levels, suggesting that atopy may be a co-determinant in FeNO production, although multivariate analysis has shown that atopy is not a significant predictor of FeNO levels in asthmatic patients.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>Exhaled nitric oxide has proven to be a marker of airway inflammation and has become a substantial part of clinical management of asthmatic in children due to its potential to predict possible exacerbation and for adjusting the dose of inhaled corticosteroids (ICS).<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Measuring FeNO enables an easy and rapid assessment of airway inflammation such that there is now an international consensus on this testing methodology.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>The aim of this study was to evaluate whether sequential FeNO testing could accurately reflect asthma severity and provide for successful stepwise therapy for asthmatic children.Materials and methodsA total of 22,083 first grade school children aged 6–7 years were included in this study. With the aid of their parents, current wheezing (within the last 12 months) was assessed using the ISAAC questionnaire. Sero-atopy was defined as a measurable specific IgE (≥0.35IU/ml) to any two of the common allergens tested in Taiwan: dust mites (der p, der f), blomia tropicalis, cat dander, dog dander, alternaria, and ragweed (Phadia ImmunoCAP system, Phadia AB, Sweden). Specific IgE tests were used for the students who met ISAAC wheezing criteria. The childhood asthma score was used to evaluate the pre-and post-treatment clinical features of the asthmatic children (cut off points: ≥21 controlled, =20 partly controlled, ≤19 uncontrolled, ≤12 very poor controlled). The Institutional Review Board (IRB) of Taipei City Hospital approved the study and all of the participants, their parents or guardians provided written informed consent.A sequence of FeNO measurements (MINO device) once every three months for one year was made for children who were diagnosed by a paediatric allergologist as seroatopy positive. All of the study participants received maintenance ICS (Flixotide 50μg; 2 puffs) with or without Singulair (5mg orally per day) depending on their asthmatic condition.A control group of 100 healthy students who met the exclusion criteria of no personal or family history of atopy, no history or symptoms of asthma and allergic rhinitis, never been diagnosed as asthmatic by a physician, and no corticosteroid or Singulair use in the last month also underwent FeNO measurements.The above procedures used on patients and controls have been done after informed consent had been obtained.ResultsA total of 22,083 grade 1 students were screened using the standardised ISAAC questionnaires to identify those who fulfilled the criteria for wheezing. Among the 279 students who met this criterion, 269 (96.4%) were sensitised to at least two common allergens in Taiwan and were diagnosed as asthmatic by a paediatric allergologist.Among the 269 allergic asthmatic children, 241 (89.6%) had elevated FeNO levels (>20ppb) and 28 (10%) had decreased levels (<20ppb). A total of 140 students who received ICS with or without Singulair treatment completed the series of FeNO testing (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The FeNO levels decreased in 121 students (86.4%) and increased in 19 students (13.6%), which were correlated with the changing of C-CAT (≥20ppb, ≤19ppb).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The 100 healthy students in the control group showed normal FeNO concentrations (<13ppb) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>DiscussionExhaled nitric oxide has been used as a surrogate measurement to determine the extent of airway inflammation in mild to moderate asthma. However, whether FeNo levels reflect disease activity in symptomatic asthmatics receiving low dose ICS with or without Singulair is uncertain. In the present study, the ability of sequential FeNO determinations to reflect asthma control over time was investigated in a regular clinical setting.In asthma, clinical symptoms and lung function are insensitive as regards reflecting the underlying airway inflammation. Monitoring this inflammatory process has only recently become available. FeNO is now recognised as a reliable surrogate marker of eosinophilic airway inflammation that offers the advantage of being completely non-invasive and very easy to obtain.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> Non-invasive markers are an attractive means for modifying therapy because they offer improved selection of active treatment based on an individual's response. Improved treatment titration using these markers is also better related to treatment outcomes.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>In addition, exercise-induced broncho-constriction (EIB) can be excluded with a 90% probability for asthmatic children with FeNO levels <20ppb without ICS treatment, and <12ppb for children with ICS treatment.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> For adult asthmatics, using a cut-off value of 40ppb has a 97% negative predictive value for a hand-held FeNO measurements (MINO) device.<a class="elsevierStyleCrossRefs" href="#bib0060">12,13</a> Another study showed that a cut-off of 32ppb of FeNO is a predictive factor for bronchial hyper-reactivity (BHR).<a class="elsevierStyleCrossRef" href="#bib0040">8</a> For paediatric asthma, the sensitivity, specificity, and positive and negative predictive values for the best cut-off point (19ppb) are 80%, 92%, 89%, and 86%, respectively, which is similar to those of eosinophil percentage when using a 2.7% cut-off (81%, 92%, 89%, and 85%, respectively).<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Moreover, a cut-off point of 22.9ppb FeNO has the best predictive value for exacerbations, with an 80% sensitivity and 60% specificity for children.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> In another study, optimal clinical control of infantile wheeze may be associated with control of bronchial inflammation when evaluated by FeNO measurements (FeNO>15ppb).<a class="elsevierStyleCrossRef" href="#bib0080">16</a>A key feature of FeNO in asthma therapy is that it can identify patients with difficult-to-treat asthma and the potential to respond to high doses of ICS or systemic steroids<a class="elsevierStyleCrossRef" href="#bib0085">17</a> because eosinophilic airway inflammation contributes to persistent airflow limitation in severe asthma.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> In general, FeNO levels can be a clinically useful measurement of asthma severity and may be used as an adjunct to spirometry to determine appropriate treatment plans.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> One study shows that FeNO levels do not exhibit circadian rhythms, as subjects with nocturnal asthma have high FeNO levels both at night and during the day.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>Guidelines for asthma management suggest a stepwise pharmacotherapeutic approach based on assessments of asthma severity and control. FeNO analysis has been proposed as an easy tool for use in adjustments in asthma therapy.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> A recent study has shown significant independent relationships between higher FeNO levels and increasing SABA use and oral corticosteroid courses, confirmed by linear trend analyses. Thus, FeNO measurements may be a complementary tool to help clinicians assess asthma burden.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> Moreover, children who receive FeNO-guided treatment use prednisolone less often than children whose treatment is based on symptoms.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> FeNO can be used to identify sputum eosinophil counts ≥3% with reasonable accuracy, although thresholds vary according to ICS dose, smoking, and atopy.<a class="elsevierStyleCrossRef" href="#bib0110">22</a>The present study shows that FeNO is a non-invasive tool for the diagnosis and monitoring of allergic-type asthma in children. Its positive predictive rate is about 89.6%, which is similar to other reports in literature. However, there is a 10% negative predictive rate. Using serial FeNO monitoring for the treated asthma children (n=140), FeNO levels (86.4%, n=121) continually decreased after the appropriate ICS with or without Singulair treatment (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). This is comparable with the successfully reduced dosage of ICS and Singulair (ICS dosage from 50μg twice per day to 50μg daily in children with or without Singulair use, while Singulair 40 was withdrawn in 62 cases) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>There are 19 students with increased FeNO concentrations, which may have been due to poor compliance to anti-inflammatory drugs, or from respiratory infections. Interestingly, the necessity for oral corticosteroid use for the group with decreased FeNO levels is less than that in the group with increased FeNO levels (49.5%, n=6 vs. 63.2%, n=12).In conclusion, sequential FeNO monitoring is a simple, time- and resource-efficient tool for asthma control and for guiding optimal anti-inflammatory asthma therapy in children.Ethical disclosuresPatients’ data protectionThe authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.Right to privacy and informed consentThe authors have obtained the informed consent of the patients and/or subjects mentioned in the article. The author for correspondence is in possession of this document.Protection of human subjects and animals in researchThe authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration. The authors confirmed the research meets ethical guidelines and it has been proved by the IRB of Taipei City Hospital.Conflict of interestsThere are no conflicts of interest that may be inherent in their submission." "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:2 [ "identificador" => "xres368099" "titulo" => array:5 [ 0 => "Abstract" 1 => "Background" 2 => "Methods" 3 => "Results" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec347275" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 6 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Patients’ data protection" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Right to privacy and informed consent" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Protection of human subjects and animals in research" ] ] ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-02-13" "fechaAceptado" => "2013-04-11" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec347275" "palabras" => array:4 [ 0 => "Asthma" 1 => "Exhaled nitric oxide" 2 => "Monitor" 3 => "Treatment" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "BackgroundChronic eosinophilic airway inflammation, airflow limitation, and airway hyper-responsiveness are the mainstays of asthma diagnosis. The increased levels of exhaled nitric oxide (FeNO) in asthma are closely related to the extent of airway inflammation. Sequential measurement of FeNO concentrations may accurately predict asthma severity and guide therapeutic decisions. MethodsA total of 22,083 grade 1 students in Taipei city primary schools were screened for wheezing episodes using the International Study of Asthma and Allergies in Childhood questionnaire (ISAAC) questionnaires while their sero-atopic conditions were confirmed by Fluorescent Enzyme Immune Assay (FEIA). All students with allergies were tested by FeNO electrochemical test. 100 age-matched healthy students were used as control group (FeNO levels<25ppb). ResultsFrom the 2650 students (12%) initially included via the wheezing criteria, 2065 (78.0%) were confirmed to have allergy by FEIA (sensitisation to at least two common aero-allergens in Taiwan) and diagnosed by a paediatric allergologist. Among them, 1852 (89.6%) had elevated FeNO values (>25ppb) and 266 (10%) had FeNO values<25ppb. Using the GINA guidelines, 140 mild-to-moderate asthma students who had received inhaled corticosteroids (ICS) with or without Singulair treatment completed serial FeNO testing every three months for one year. The FeNO levels decreased in 121 students (86.4%) and increased in 19 students (13.6%), which was compatible to changing childhood asthma control score and response to step-down treatment, respectively. ConclusionFeNO is an easy, used non-invasive tool for the diagnosis of allergic asthma. Sequential FeNO testing can accurately reflect asthma severity and provide for successful stepwise therapy for asthmatic children." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1572 "Ancho" => 2505 "Tamanyo" => 196093 ] ] "descripcion" => array:1 [ "en" => "There is statistically significant down-regulation among the three serial FeNO measurements (p<0.05) after ICS treatment with or without Singulair. However, the decreased FeNO in levels between the second and third measurements are not statistically significant." ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" 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, mean±SD \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.0±0.35 \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">Male, n (%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 (56.6%) \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">Female, n (%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (41.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Comorbidity, n (%)</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">Allergic rhinitis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 (56.4%) \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">Atopic dermatitis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (10.7%) \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">Gastro-oesophageal reflux \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 (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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\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">ISAAC wheezing criteria met \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \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">Childhood asthma control test, mean±SD \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.13±2.10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inhaled allergen-specific IgE</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">Dermatophagoides pteronyssinus \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">127 (91%) \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">Dermatophagoides farinae \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">116 (82.8%) \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">German cockroach \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 (15%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\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">Initial FeNO level \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.31±13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prescribed anti-asthmatic medication</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">Inhaled corticosteroids (ICS), n (%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85 (60.7%) \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">ICS plus antileukotriene, n (%) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55 (39.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab553480.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Characteristics of the study participants (n=140)." ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Abbreviations: Fractional exhaled nitric oxide (FeNO); inhaled nitric oxide (ICS)." "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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \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">ICS plus Singulair (n=73) \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">ICS only (n=48) \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">FeNO levels decreased \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">84.9% (62) \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">83.3% (40) \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">FeNO levels increased \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">15.1% (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">16.7% (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">Decrease ICS 50μg \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">79.5% (53) \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">83.3% (40) \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">Withdraw Singulair 5mg \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">64.5% (40) \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">– \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab553479.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results of inhaled corticosteroid with or without Singulair treatment in mild to moderate asthmatic primary schoolchildren with sequential exhaled nitric oxide monitoring." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:22 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "RANTES in exhaled breath condensate of stable and unstable asthma patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Z. 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K.-S. Wana,b,

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DXD40@tpech.gov.tw

Corresponding author.

, W.-H. Chiub, W. Yangb,c

a Department of Pediatrics, Taipei City Hospital, Renai Branch, Taiwan

b Colleges of Medicine, National Yang-Ming University, Taipei, Taiwan

c Department of Pediatrics, Taipei City Hospital, Yangming Branch, Taiwan

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    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Asthma diagnosis and severity monitoring in primary school children&#58; Essential role of sequential testing of exhaled nitric oxide"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">There is statistically significant down-regulation among the three serial FeNO measurements &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41; after ICS treatment with or without Singulair&#46; However&#44; the decreased FeNO in levels between the second and third measurements are not statistically significant&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Airway eosinophilia is considered a critical event in the pathogenesis of asthma&#46; Eotaxin and RANTES have been implicated in the allergic inflammation associated with asthma by promoting the migration and activation of inflammatory cells&#44; including eosinophils&#46; Concentrations of these cytokines in exhaled breath condensates &#40;EBC&#41; have been significantly correlated with exhaled nitric oxide &#40;FeNO&#41; concentrations and serum eosinophil cationic protein &#40;ECP&#41; levels in asthmatics&#44; particularly in unstable and steroid-naive stable asthmatics&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Guidelines for asthma management suggest a stepwise approach to pharmacotherapy based on assessments of severity and control&#46; However&#44; the assessment of asthma control currently relies on surrogate measures like the frequency of symptoms or the frequency of use of short-acting &#946;2-adrenergic agonists &#40;SABA&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> Increased expression of inducible nitric oxide synthase and elevated FeNO levels are seen in asthmatic patients and have become increasingly recognised for their use in evaluating bronchial inflammation when monitoring anti-inflammatory treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Moreover&#44; atopic individuals have increased FeNO levels&#44; suggesting that atopy may be a co-determinant in FeNO production&#44; although multivariate analysis has shown that atopy is not a significant predictor of FeNO levels in asthmatic patients&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Exhaled nitric oxide has proven to be a marker of airway inflammation and has become a substantial part of clinical management of asthmatic in children due to its potential to predict possible exacerbation and for adjusting the dose of inhaled corticosteroids &#40;ICS&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Measuring FeNO enables an easy and rapid assessment of airway inflammation such that there is now an international consensus on this testing methodology&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this study was to evaluate whether sequential FeNO testing could accurately reflect asthma severity and provide for successful stepwise therapy for asthmatic children&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materials and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A total of 22&#44;083 first grade school children aged 6&#8211;7 years were included in this study&#46; With the aid of their parents&#44; current wheezing &#40;within the last 12 months&#41; was assessed using the ISAAC questionnaire&#46; Sero-atopy was defined as a measurable specific IgE &#40;&#8805;0&#46;35<span class="elsevierStyleHsp" style=""></span>IU&#47;ml&#41; to any two of the common allergens tested in Taiwan&#58; dust mites &#40;der p&#44; der f&#41;&#44; <span class="elsevierStyleItalic">blomia tropicalis</span>&#44; cat dander&#44; dog dander&#44; <span class="elsevierStyleItalic">alternaria</span>&#44; and ragweed &#40;Phadia ImmunoCAP system&#44; Phadia AB&#44; Sweden&#41;&#46; Specific IgE tests were used for the students who met ISAAC wheezing criteria&#46; The childhood asthma score was used to evaluate the pre-and post-treatment clinical features of the asthmatic children &#40;cut off points&#58; &#8805;21 controlled&#44; &#61;20 partly controlled&#44; &#8804;19 uncontrolled&#44; &#8804;12 very poor controlled&#41;&#46; The Institutional Review Board &#40;IRB&#41; of Taipei City Hospital approved the study and all of the participants&#44; their parents or guardians provided written informed consent&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">A sequence of FeNO measurements &#40;MINO device&#41; once every three months for one year was made for children who were diagnosed by a paediatric allergologist as seroatopy positive&#46; All of the study participants received maintenance ICS &#40;Flixotide 50<span class="elsevierStyleHsp" style=""></span>&#956;g&#59; 2 puffs&#41; with or without Singulair &#40;5<span class="elsevierStyleHsp" style=""></span>mg orally per day&#41; depending on their asthmatic condition&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">A control group of 100 healthy students who met the exclusion criteria of no personal or family history of atopy&#44; no history or symptoms of asthma and allergic rhinitis&#44; never been diagnosed as asthmatic by a physician&#44; and no corticosteroid or Singulair use in the last month also underwent FeNO measurements&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The above procedures used on patients and controls have been done after informed consent had been obtained&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">A total of 22&#44;083 grade 1 students were screened using the standardised ISAAC questionnaires to identify those who fulfilled the criteria for wheezing&#46; Among the 279 students who met this criterion&#44; 269 &#40;96&#46;4&#37;&#41; were sensitised to at least two common allergens in Taiwan and were diagnosed as asthmatic by a paediatric allergologist&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Among the 269 allergic asthmatic children&#44; 241 &#40;89&#46;6&#37;&#41; had elevated FeNO levels &#40;&#62;20<span class="elsevierStyleHsp" style=""></span>ppb&#41; and 28 &#40;10&#37;&#41; had decreased levels &#40;&#60;20<span class="elsevierStyleHsp" style=""></span>ppb&#41;&#46; A total of 140 students who received ICS with or without Singulair treatment completed the series of FeNO testing &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The FeNO levels decreased in 121 students &#40;86&#46;4&#37;&#41; and increased in 19 students &#40;13&#46;6&#37;&#41;&#44; which were correlated with the changing of C-CAT &#40;&#8805;20<span class="elsevierStyleHsp" style=""></span>ppb&#44; &#8804;19<span class="elsevierStyleHsp" style=""></span>ppb&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The 100 healthy students in the control group showed normal FeNO concentrations &#40;&#60;13<span class="elsevierStyleHsp" style=""></span>ppb&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">Exhaled nitric oxide has been used as a surrogate measurement to determine the extent of airway inflammation in mild to moderate asthma&#46; However&#44; whether FeNo levels reflect disease activity in symptomatic asthmatics receiving low dose ICS with or without Singulair is uncertain&#46; In the present study&#44; the ability of sequential FeNO determinations to reflect asthma control over time was investigated in a regular clinical setting&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">In asthma&#44; clinical symptoms and lung function are insensitive as regards reflecting the underlying airway inflammation&#46; Monitoring this inflammatory process has only recently become available&#46; FeNO is now recognised as a reliable surrogate marker of eosinophilic airway inflammation that offers the advantage of being completely non-invasive and very easy to obtain&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Non-invasive markers are an attractive means for modifying therapy because they offer improved selection of active treatment based on an individual&#39;s response&#46; Improved treatment titration using these markers is also better related to treatment outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In addition&#44; exercise-induced broncho-constriction &#40;EIB&#41; can be excluded with a 90&#37; probability for asthmatic children with FeNO levels &#60;20<span class="elsevierStyleHsp" style=""></span>ppb without ICS treatment&#44; and &#60;12<span class="elsevierStyleHsp" style=""></span>ppb for children with ICS treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> For adult asthmatics&#44; using a cut-off value of 40<span class="elsevierStyleHsp" style=""></span>ppb has a 97&#37; negative predictive value for a hand-held FeNO measurements &#40;MINO&#41; device&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a> Another study showed that a cut-off of 32<span class="elsevierStyleHsp" style=""></span>ppb of FeNO is a predictive factor for bronchial hyper-reactivity &#40;BHR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> For paediatric asthma&#44; the sensitivity&#44; specificity&#44; and positive and negative predictive values for the best cut-off point &#40;19<span class="elsevierStyleHsp" style=""></span>ppb&#41; are 80&#37;&#44; 92&#37;&#44; 89&#37;&#44; and 86&#37;&#44; respectively&#44; which is similar to those of eosinophil percentage when using a 2&#46;7&#37; cut-off &#40;81&#37;&#44; 92&#37;&#44; 89&#37;&#44; and 85&#37;&#44; respectively&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Moreover&#44; a cut-off point of 22&#46;9<span class="elsevierStyleHsp" style=""></span>ppb FeNO has the best predictive value for exacerbations&#44; with an 80&#37; sensitivity and 60&#37; specificity for children&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In another study&#44; optimal clinical control of infantile wheeze may be associated with control of bronchial inflammation when evaluated by FeNO measurements &#40;FeNO<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>ppb&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">A key feature of FeNO in asthma therapy is that it can identify patients with difficult-to-treat asthma and the potential to respond to high doses of ICS or systemic steroids<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> because eosinophilic airway inflammation contributes to persistent airflow limitation in severe asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> In general&#44; FeNO levels can be a clinically useful measurement of asthma severity and may be used as an adjunct to spirometry to determine appropriate treatment plans&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> One study shows that FeNO levels do not exhibit circadian rhythms&#44; as subjects with nocturnal asthma have high FeNO levels both at night and during the day&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Guidelines for asthma management suggest a stepwise pharmacotherapeutic approach based on assessments of asthma severity and control&#46; FeNO analysis has been proposed as an easy tool for use in adjustments in asthma therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> A recent study has shown significant independent relationships between higher FeNO levels and increasing SABA use and oral corticosteroid courses&#44; confirmed by linear trend analyses&#46; Thus&#44; FeNO measurements may be a complementary tool to help clinicians assess asthma burden&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Moreover&#44; children who receive FeNO-guided treatment use prednisolone less often than children whose treatment is based on symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> FeNO can be used to identify sputum eosinophil counts &#8805;3&#37; with reasonable accuracy&#44; although thresholds vary according to ICS dose&#44; smoking&#44; and atopy&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The present study shows that FeNO is a non-invasive tool for the diagnosis and monitoring of allergic-type asthma in children&#46; Its positive predictive rate is about 89&#46;6&#37;&#44; which is similar to other reports in literature&#46; However&#44; there is a 10&#37; negative predictive rate&#46; Using serial FeNO monitoring for the treated asthma children &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>140&#41;&#44; FeNO levels &#40;86&#46;4&#37;&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>121&#41; continually decreased after the appropriate ICS with or without Singulair treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; This is comparable with the successfully reduced dosage of ICS and Singulair &#40;ICS dosage from 50<span class="elsevierStyleHsp" style=""></span>&#956;g twice per day to 50<span class="elsevierStyleHsp" style=""></span>&#956;g daily in children with or without Singulair use&#44; while Singulair 40 was withdrawn in 62 cases&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">There are 19 students with increased FeNO concentrations&#44; which may have been due to poor compliance to anti-inflammatory drugs&#44; or from respiratory infections&#46; Interestingly&#44; the necessity for oral corticosteroid use for the group with decreased FeNO levels is less than that in the group with increased FeNO levels &#40;49&#46;5&#37;&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6 vs&#46; 63&#46;2&#37;&#44; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>12&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">In conclusion&#44; sequential FeNO monitoring is a simple&#44; time- and resource-efficient tool for asthma control and for guiding optimal anti-inflammatory asthma therapy in children&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Ethical disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Patients&#8217; data protection</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Right to privacy and informed consent</span><p id="par0105" class="elsevierStylePara elsevierViewall">The authors have obtained the informed consent of the patients and&#47;or subjects mentioned in the article&#46; The author for correspondence is in possession of this document&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Protection of human subjects and animals in research</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration&#46; The authors confirmed the research meets ethical guidelines and it has been proved by the IRB of Taipei City Hospital&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflict of interests</span><p id="par0115" class="elsevierStylePara elsevierViewall">There are no conflicts of interest that may be inherent in their submission&#46;</p></span></span>"
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        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Chronic eosinophilic airway inflammation&#44; airflow limitation&#44; and airway hyper-responsiveness are the mainstays of asthma diagnosis&#46; The increased levels of exhaled nitric oxide &#40;FeNO&#41; in asthma are closely related to the extent of airway inflammation&#46; Sequential measurement of FeNO concentrations may accurately predict asthma severity and guide therapeutic decisions&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A total of 22&#44;083 grade 1 students in Taipei city primary schools were screened for wheezing episodes using the International Study of Asthma and Allergies in Childhood questionnaire &#40;ISAAC&#41; questionnaires while their sero-atopic conditions were confirmed by Fluorescent Enzyme Immune Assay &#40;FEIA&#41;&#46; All students with allergies were tested by FeNO electrochemical test&#46; 100 age-matched healthy students were used as control group &#40;FeNO levels<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>25<span class="elsevierStyleHsp" style=""></span>ppb&#41;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">From the 2650 students &#40;12&#37;&#41; initially included via the wheezing criteria&#44; 2065 &#40;78&#46;0&#37;&#41; were confirmed to have allergy by FEIA &#40;sensitisation to at least two common aero-allergens in Taiwan&#41; and diagnosed by a paediatric allergologist&#46; Among them&#44; 1852 &#40;89&#46;6&#37;&#41; had elevated FeNO values &#40;&#62;25<span class="elsevierStyleHsp" style=""></span>ppb&#41; and 266 &#40;10&#37;&#41; had FeNO values<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>25<span class="elsevierStyleHsp" style=""></span>ppb&#46; Using the GINA guidelines&#44; 140 mild-to-moderate asthma students who had received inhaled corticosteroids &#40;ICS&#41; with or without Singulair treatment completed serial FeNO testing every three months for one year&#46; The FeNO levels decreased in 121 students &#40;86&#46;4&#37;&#41; and increased in 19 students &#40;13&#46;6&#37;&#41;&#44; which was compatible to changing childhood asthma control score and response to step-down treatment&#44; respectively&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">FeNO is an easy&#44; used non-invasive tool for the diagnosis of allergic asthma&#46; Sequential FeNO testing can accurately reflect asthma severity and provide for successful stepwise therapy for asthmatic children&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleItalic">Age&#44; years&#44; mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD</span>&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="left" valign="\n
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                  \t\t\t\t">6&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;35&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"><span class="elsevierStyleItalic">Male&#44; n &#40;&#37;&#41;</span>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">82 &#40;56&#46;6&#37;&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Female&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \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">58 &#40;41&#46;4&#37;&#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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Comorbidity&#44; n &#40;&#37;&#41;</span></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"><span class="elsevierStyleHsp" style=""></span>Allergic rhinitis&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79 &#40;56&#46;4&#37;&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Atopic dermatitis&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;10&#46;7&#37;&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gastro-oesophageal reflux&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0 &#40;0&#37;&#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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">ISAAC wheezing criteria met</span>&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="left" valign="\n
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                  \t\t\t\t">Positive&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"><span class="elsevierStyleItalic">Childhood asthma control test&#44; mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD</span>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#46;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;10&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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Inhaled allergen-specific IgE</span></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"><span class="elsevierStyleHsp" style=""></span>Dermatophagoides pteronyssinus&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">127 &#40;91&#37;&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dermatophagoides farinae&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">116 &#40;82&#46;8&#37;&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>German cockroach&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;15&#37;&#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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Initial FeNO level</span>&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;31<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Prescribed anti-asthmatic medication</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Inhaled corticosteroids &#40;ICS&#41;&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">85 &#40;60&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>ICS plus antileukotriene&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55 &#40;39&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; Fractional exhaled nitric oxide &#40;FeNO&#41;&#59; inhaled nitric oxide &#40;ICS&#41;&#46;</p>"
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">84&#46;9&#37; &#40;62&#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">15&#46;1&#37; &#40;11&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Decrease ICS 50<span class="elsevierStyleHsp" style=""></span>&#956;g&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">79&#46;5&#37; &#40;53&#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">83&#46;3&#37; &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Withdraw Singulair 5<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">64&#46;5&#37; &#40;40&#41;&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Results of inhaled corticosteroid with or without Singulair treatment in mild to moderate asthmatic primary schoolchildren with sequential exhaled nitric oxide monitoring&#46;</p>"
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      "titulo" => "References"
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                    0 => array:2 [
                      "titulo" => "RANTES in exhaled breath condensate of stable and unstable asthma patients"
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                          "etal" => false
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                            0 => "Z&#46; Zietkowski"
                            1 => "M&#46;M&#46; Tomasiak"
                            2 => "R&#46; Skiepko"
                            3 => "A&#46; Bodzenta-Lukaszyk"
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                    0 => array:2 [
                      "doi" => "10.1016/j.rmed.2008.03.010"
                      "Revista" => array:7 [
                        "tituloSerie" => "Respir Med"
                        "fecha" => "2008"
                        "volumen" => "102"
                        "paginaInicial" => "1198"
                        "paginaFinal" => "1202"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18603420"
                            "web" => "Medline"
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                        "itemHostRev" => array:3 [
                          "pii" => "S0022399913003279"
                          "estado" => "S300"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Eotaxin-1 in exhaled breath condensate of stable and unstable asthma patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Z&#46; Zietkowski"
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                            3 => "E&#46; Zietkowska"
                            4 => "A&#46; Bodzenta-Lukaszyk"
                          ]
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                    0 => array:2 [
                      "doi" => "10.1186/1465-9921-11-110"
                      "Revista" => array:5 [
                        "tituloSerie" => "Respir Res"
                        "fecha" => "2010"
                        "volumen" => "11"
                        "paginaInicial" => "110"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20704746"
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Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2013.04.007

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	1	0	1
2024 October	13	4	17
2024 September	12	19	31
2024 August	10	8	18
2024 July	10	3	13
2024 June	14	3	17
2024 May	8	5	13
2024 April	14	9	23
2024 March	13	6	19
2024 February	18	4	22
2024 January	26	10	36
2023 December	29	11	40
2023 November	13	12	25
2023 October	15	5	20
2023 September	6	4	10
2023 August	11	3	14
2023 July	12	6	18
2023 June	9	5	14
2023 May	15	2	17
2023 April	8	5	13
2023 March	12	5	17
2023 February	9	9	18
2023 January	10	7	17
2022 December	13	7	20
2022 November	19	6	25
2022 October	12	5	17
2022 September	10	11	21
2022 August	16	9	25
2022 July	10	10	20
2022 June	12	4	16
2022 May	10	11	21
2022 April	13	12	25
2022 March	13	11	24
2022 February	13	7	20
2022 January	12	6	18
2021 December	7	12	19
2021 November	9	17	26
2021 October	9	18	27
2021 September	11	11	22
2021 August	10	7	17
2021 July	9	6	15
2021 June	8	9	17
2021 May	15	7	22
2021 April	18	28	46
2021 March	4	9	13
2021 February	14	11	25
2021 January	13	10	23
2020 December	1	1	2
2020 November	0	1	1
2020 September	0	1	1
2020 July	0	1	1
2020 May	0	1	1
2020 April	0	2	2
2020 January	0	2	2
2019 December	0	2	2
2019 November	0	2	2
2019 September	0	1	1
2019 July	0	1	1
2019 June	0	4	4
2019 May	0	12	12
2018 February	10	1	11
2018 January	2	3	5
2017 December	4	0	4
2017 November	6	3	9
2017 October	6	4	10
2017 September	7	8	15
2017 August	13	2	15
2017 July	13	2	15
2017 June	8	3	11
2017 May	15	2	17
2017 April	11	0	11
2017 March	14	13	27
2017 February	15	4	19
2017 January	18	3	21
2016 December	34	7	41
2016 November	23	1	24
2016 October	35	7	42
2016 September	15	4	19
2016 August	17	2	19
2016 July	5	1	6
2016 June	18	3	21
2016 May	14	5	19
2016 April	17	9	26
2016 March	17	12	29
2016 February	9	10	19
2016 January	16	10	26
2015 December	10	7	17
2015 November	18	6	24
2015 October	20	6	26
2015 September	10	4	14
2015 May	1	3	4
2015 April	0	3	3
2015 March	1	2	3
2015 February	1	1	2
2015 January	0	2	2
2014 December	0	2	2
2014 November	0	5	5
2014 October	0	2	2
2014 September	2	1	3

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

Indexed in:

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