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Diagnostic accuracy of exhaled nitric oxide in exercise-induced bronchospasm: Systematic review
Acurácia do óxido nítrico exalado no diagnóstico do broncoespasmos induzidos pelo exercício: Revisão sistemática
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Feitosa, A. Dornelas de Andrade, C.M.A. Reinaux, M.C.A. Britto" "autores" => array:4 [ 0 => array:4 [ "nombre" => "L.A.S." "apellidos" => "Feitosa" "email" => array:1 [ 0 => "larissa_asf@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Dornelas de Andrade" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "C.M.A." "apellidos" => "Reinaux" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "M.C.A." 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Bronchoconstriction occurs when there is a reduction of 10–15% in the forced expiratory volume in the first second (FEV<span class="elsevierStyleInf">1</span>) between 1 and 30<span class="elsevierStyleHsp" style=""></span>min after the test.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,5</span></a> However, although accurate, this test is complex, expensive, time consuming and requires specialized equipment and trained personnel.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a> There are risks and discomfort involved and some individuals may require medication and/or oxygen.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The measurement of exhaled nitric oxide (eNO) is described in the literature as an alternative to the exercise test for the diagnosis of EIB.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8–11</span></a> This is a non-invasive, fast, easy method that can be performed on adults and children over five years of age.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,10</span></a> Studies report the use of eNO for the adjustment of asthma medications, such as inhaled corticosteroids, as well as for the diagnosis of asthma.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,12,13</span></a> The test is also safe, it is not associated with risks such as inducing severe bronchospasm.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Considering the impact of exercise-induced asthma has on quality of life particularly in children,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> this systematic review of the literature was carried out to assess the accuracy of the measurement of exhaled nitric oxide for the diagnosis of this condition.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A systematic review was carried out of studies which have assessed the accuracy of eNO for the diagnosis of EIB, whatever the language of the study. The standard reference for diagnosis was the exercise test with spirometry.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The inclusion criteria were, primary studies which compared the diagnosis of exercised-induced asthma or bronchoconstriction using eNO with the exercise test, and which included the determination of sensitivity and specificity. Cross-sectional and longitudinal studies with participants of any age were included, provided the diagnostic tests were performed on the same day. Studies involving animals, subjects with associated co-morbidities (with the exception of rhinitis) or smokers were excluded.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Search strategy</span><p id="par0035" class="elsevierStylePara elsevierViewall">The studies were retrieved from the following databases: PubMed (1991 to August 2010), Latin American and Caribbean Health Sciences Literature (Lilacs) (1991 to August 2010), Scientific Electronic Library Online (SciELO) and SCOPUS. A general search strategy flexible enough to adapt to the characteristics of each database was used to identify studies which included the terms, exercise-induced asthma, exhaled nitric oxide and diagnosis.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The following strategy was used in the PubMed and SCOPUS databases: (Exhaled nitric oxide OR nitric oxide) AND (Exercise-Induced Asthma OR Exercise-Induced bronchoconstriction OR Exercise-Induced bronchospasm) AND (diagnosis OR Sensitivity and Specificity OR Diagnostic Techniques and Procedures); strategy used in the Lilacs database: (“Broncoespasmo Induzido por Exercício” OR “Asma induzida por exercício”) AND (“/diagnóstico” OR “Sensibilidade e Especificidade”) AND “Óxido Nítrico”; strategy used in the SciELO database: ASMA INDUZIDA PELO EXERCICIO or ASMA INDUZIDA POR EXERCICIO or BRONCOESPASMO INDUZIDO PELO EXERCICIO [Assunto] and DIAGNOSTICO or SENSIBILIDADE or ESPECIFICIDADE or ACURACIA [Assunto] and OXIDO NITRICO or OXIDO NITRICO EXALADO [Assunto]. From the primary studies retrieved, the bibliographic references were searched to be able to include further papers.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Two researchers independently analyzed the titles, abstracts and complete texts of the papers retrieved. Divergences were resolved by consensus with a third researcher. Data collection was done by the researchers independently. The data were extracted and computed in a data extraction form for each study. The data extracted were: name of authors, publication year, country, inclusion criteria, age of patients, number of patients, study design, the characteristics of standard test and the measurement of eNO, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) questions, the cutoff point of eNO levels, the number of true positives, true negatives, false positive and false negative patients. Review Manager program (RevMan, version 5.0.20) was used to analyze the data to obtain sensitivity and specificity values and respective 95% confidence intervals.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Quality assessment</span><p id="par0050" class="elsevierStylePara elsevierViewall">The quality of the papers was assessed using the QUADAS, which is a validated questionnaire made up of 14 items.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The quality criteria were as follows: whether sample was representative of patient profile in clinical practice; clarity of the selection criteria for the participants; standard reference; time between evaluations with both methods; performance of all tests by the sample; independence of the tests; clarity of the protocols of the test studied and standard reference; blinding of the evaluators for both tests; information known to evaluators; non-interpretable results; and samples excluded. Two researchers were trained for the data extraction and use of QUADAS. Each item was identified as “yes”, “no” or “unclear”.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">Forty-eight studies were found in PubMed, eight in SCOPUS and none in either SciELO or Lilacs. One paper was found through the evaluation of the relevant references. Two papers were repeated which left 55 for analysis. <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> synthesizes the entire search process and paper selection.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Six papers met the eligibility criteria and 49 were excluded for the following reasons: 27 studies did not address accuracy; two did not compare eNO with exercise; seven were review articles; three did not use an acceptable standard reference; eight were not on EIB; and two were animal studies. The majority of studies that compared eNO with FEV<span class="elsevierStyleInf">1</span> values did not address diagnostic accuracy, as only two correlated the drop in FEV<span class="elsevierStyleInf">1</span> following exercise with baseline nitric oxide values. It was also impossible to construct a 2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>2 table, as these studies did not present mean eNO values in the groups that were positive and negative for EIB.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Six studies remained for analysis, involving a total of 672 individuals, 533 of whom were children and adolescents between 3.8 and 16 years of age. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> displays the results of the quality assessment of the studies. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> displays the characteristics of the studies. All studies were done in different countries. The age of patients ranged from 3.8 to 40 years old. There was a significant heterogeneity in sex (<span class="elsevierStyleItalic">X</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>56.44, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.000) and clinical spectrum (presence of asthma) (<span class="elsevierStyleItalic">X</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>504.00, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.000) between studies. The majority of the studies was cross-sectional and used a treadmill as the exercise challenge. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> summarizes the accuracy results. The cutoff point of eNO levels ranged from 7 to 50 according to subgroups and age of patients. The sensitivity ranged from 0.32 to 1 between studies. The specificity ranged from 0.32 to 0.80. The highest predictive value (PPV) was 100% and the lowest PPV was 16%. The highest negative predictive value (NPV) was 100% and the lowest NPV was 19%.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Methodological quality of papers</span><p id="par0070" class="elsevierStylePara elsevierViewall">All papers included individuals who had similar characteristics to those who would do these tests in clinical practice and all clearly defined the inclusion criteria. Malberg et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> were the only ones not to use the ideal standard reference test; however, this study was not considered of low quality, because the participants were too young for the use of spirometry as the evaluation method. All studies had a sufficient time period between evaluations, used the same tests for comparisons and described the eNO protocol. Only Berkman et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> failed to describe the exercise test in detail; however, this was the only study to state clearly that the evaluators were blinded to both the eNO and standard reference results. In the majority of studies, the evaluators had information compatible with clinical practice and there were no non-interpretable results. Only half of the studies gave a detailed explanation of the reasons for excluded samples.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">The measurement of eNO is an accurate negative predictor in the diagnosis of EIB in individuals with asthma or suspected EIB. As this test is easy to administer, is cheaper than the exercise test and can be administered to both children and adults without risk, it can be used as a screening tool for EIB. Thus, individuals with suspected EIB should have their eNO measured; if the value obtained is low, this condition can be ruled out. For patients with high eNO values, an exercise test should be performed to confirm the diagnosis of EIB.</p><p id="par0125" class="elsevierStylePara elsevierViewall">All papers included in this systematic review followed the recommendations of the American Thoracic Society from 1999 to 2005 regarding the protocol for the measurement of eNO.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18,19</span></a> The majority of studies used a flow rate of 50<span class="elsevierStyleHsp" style=""></span>ml/s and the online single-breath method for the measurement of eNO. Only two papers specified the ambient NO value,<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a> which was lower than five parts per billion (ppb), as recommended by the American Thoracic Society and the European Respiratory Society.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Among the six papers analyzed, only two reported the calibration of the eNO analyzer.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">As the clinical spectrum and sex of the groups was so heterogeneous, a meta-analysis of the studies was not considered appropriate. It was not possible to perform the heterogeneity evaluation for age and eNO cut off point because only one study described the mean and standard deviation of age and none of the studies provided these variables for eNO. It is possible that identifying an ideal cutoff point for the population studied will lead to greater accuracy in the use of eNO for the diagnosis of EIB. Thus, further studies should investigate the ideal cutoff point for adults and children with asthma, for those with allergies and those using inhaled corticosteroids.</p><p id="par0085" class="elsevierStylePara elsevierViewall">The best way to diagnose intolerance to exercise is for the subject to take exercise, ideally in the context in which the brochospasm has been observed.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> However, this type of diagnosis is difficult to perform in clinical practice and other diagnostic methods that reduce the evaluation time; risk and cost have obvious advantages.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Among the six papers analyzed, four involved children and adolescents. Higher cutoff points were used for children and adolescents (21<span class="elsevierStyleHsp" style=""></span>ppb) compared to adults. The same was true for individuals with asthma and allergies. Lower cutoff points should be employed for individuals who use inhaled corticosteroids, for, according to Silkoff et al.,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> the use of this medication for the treatment of asthma reduces eNO, as shown by the comparison of values before and after treatment. Another point to consider regarding the variability in the results is the issue of different temperature and humidity values, which may affect the prevalence of EIB and alter the predictive values of the tests in each study.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23,24</span></a> All the studies used were carried out in different countries and there were no information about the time of year in which the evaluations were carried out.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Five of the studies report sensitivity values ranging from 0.86 to 1.0.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7–11</span></a> However, these values were obtained at the cost of low specificity (0.31–0.7). Moreover, the studies that report high specificity values found low sensitivity values.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,17</span></a> Thus, the Youden Index was calculated to identify the studies with the best sensitivity and specificity relationship and only three studies achieved values above 0.5. These studies evaluated children using cutoff points of 12<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a> and 25<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleHsp" style=""></span>ppb.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Four of the six papers report a NPV above 88%, reaching as high as 100% in the study carried out by Lex et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Only the study by Elhalawani reports a low NPV, but reports a PPV of 100%. None of the other papers report a high PPV, which varied considerably among the different studies. For children between 3.8 and 7.8 years old, a cutoff point >28<span class="elsevierStyleHsp" style=""></span>ppb could be considered a ‘rule-in’ for EIB, with the highest PPV of 90% and specificity of 0.89. In children between 5 and 16 years old at a cutoff point <20 EIB can be ruled out with a NPV between 94 and 100%. For adults between 21 and 40 years old, a cutoff point <7 EIB can be ruled out with a NPV of 95% but a cutoff point >12 would be a ‘rule in’ for a PPV of 100%.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Quality of the systematic review</span><p id="par0105" class="elsevierStylePara elsevierViewall">The search for articles was sufficiently broad and carried out in four different databases. Emails were sent to all the authors whose studies were included to request unpublished papers. No restrictions were placed on the language or year of the studies. Only studies published since 1991 were selected, as this was the year in which the first paper on eNO in humans was published.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> All papers selected were evaluated by two researchers in an independent fashion. Meta-analysis was not possible, as the studies were carried out with different cutoff points. The authors were contacted by email for a new analysis of the cutoff point, but there was no response. The present review systematically followed the QUADAS<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> criteria. All these factors contributed to the quality of the systematic review and validity of the study.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Implications for clinical practice and research</span><p id="par0110" class="elsevierStylePara elsevierViewall">eNO is a simple, noninvasive method that can help reduce the number of people having to do an exercise test combined with spirometry. Individuals with a negative diagnosis determined by the measurement of eNO can be considered as not having EIB, whereas those with a positive result should be sent to do the exercise test to confirm the diagnosis. In clinical practice, this method can be used for both the diagnosis of this condition and the administration of medication when necessary, especially among individuals with asthma. The ideal cutoff point for the diagnosis of EIB depends on the population studied, as eNO varies among healthy individuals, those using corticosteroids, those with asthma and those with allergies and also varies between children and adults. Thus, further studies with large samples are needed to standardize the ideal cutoff points of eNO in different populations.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conclusion</span><p id="par0115" class="elsevierStylePara elsevierViewall">The measurement of eNO seems to be an effective test to ‘rule-in’ or rule out EIB in some specific groups. EIB is a strong possibility where there is a cutoff point >28 for children under 8 years old and a cutoff point >12 for adults. EIB could be ruled out with a cutoff point <20 for children between 5 and 16 years old and with a cutoff point <7 for adults. To standardize the ideal cutoff points of eNO in different subgroups of patients more studies with large samples are needed. The measurement of eNO for the diagnosis of EIB could be considered mainly an accurate negative predictor of this condition, but it is not possible to confirm the diagnosis with certainty in positive cases without an exercise test combined with spirometry. Therefore, the measurement of eNO levels could be an important tool for safely avoiding the exercise test when the result is negative, reducing costs and the personal impact of this disease.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0120" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:2 [ "identificador" => "xres547815" "titulo" => array:5 [ 0 => "Abstract" 1 => "Introduction" 2 => "Methods" 3 => "Results" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec565696" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres547816" "titulo" => "Resumo" ] 3 => array:2 [ "identificador" => "xpalclavsec565695" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Search strategy" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Quality assessment" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Results" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Methodological quality of papers" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Quality of the systematic review" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Implications for clinical practice and research" ] 13 => array:2 [ "identificador" => "sec0050" "titulo" => "Conclusion" ] 14 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interest" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-10-06" "fechaAceptado" => "2012-01-29" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec565696" "palabras" => array:4 [ 0 => "Exercise-induced asthma" 1 => "Diagnosis" 2 => "Sensitivity and specificity" 3 => "Nitric oxide" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec565695" "palabras" => array:4 [ 0 => "Asma induzida por exercício" 1 => "diagnóstico" 2 => "sensibilidade e especificidade" 3 => "óxido nítrico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span><span class="elsevierStyleSectionTitle">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The gold-standard method for the diagnosis of exercise-induced bronchospasm (EIB) is an exercise test combined with spirometry. However, this test is expensive, time consuming and requires specialized equipment and trained personnel. Exhaled nitric oxide (eNO) is a fast, easy, noninvasive method for the diagnosis of EIB. The aim of the present study was to assess the accuracy of the measurement of eNO for the diagnosis of EIB through a systematic review of the literature.</p></span> <span><span class="elsevierStyleSectionTitle">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A search was carried out in the PubMed, Lilacs, SciELO and SCOPUS databases by two independent researchers.</p></span> <span><span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Fifty-six papers were found. Following the application of the eligibility criteria to the title, abstract and text, six papers remained for analysis. There was a significant heterogeneity in sex (<span class="elsevierStyleItalic">X</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>56.44, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.000) and clinical spectrum (<span class="elsevierStyleItalic">X</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>504.00, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.000) between studies. In children between 3.8 and 7.8 years old a cutoff point >28<span class="elsevierStyleHsp" style=""></span>ppb EIB can be ruled in and in children between 5 and 16 years old at a cutoff point <20<span class="elsevierStyleHsp" style=""></span>EIB can be ruled out. For adults a cutoff point <7<span class="elsevierStyleHsp" style=""></span>EIB can be ruled out and it can be ruled in with a cutoff point >12. Four papers reported negative predictive values above 88%.</p></span> <span><span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The measurement of eNO seems to be effective for ruling in and ruling out EIB in some specific groups. Therefore, the meansurement of eNO levels could be an important tool to safely avoid the need for an exercise test when the result is negative, reducing the individual and economic impact of this disease.</p></span>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Introdução: O método padrão de ouro para o diagnóstico de broncoespasmos induzidos por exercício (BIE) é a prova de esforço combinada com a espirometria. Contudo, esta prova é dispendiosa, demorada e requer equipamento específico e pessoal especializado. O óxido nítrico exalado (eNO) é um método rápido, simples e não invasivo para o diagnóstico de BIE. O objectivo do presente estudo foi o de aferir a acurácia do eNO para o diagnóstico do BIE através da revisão sistemática da literatura. Métodos: Foi efectuada uma pesquisa nas bases de dados PubMed, Lilacs, SciELO e SCOPUS por dois investigadores independentes. Resultados: Foram encontrados 56 artigos e após as exclusões pelo título, resumo e texto, restaram 6 artigos para análise. Foi encontrada heterogeneidade significativa entre os estudos quanto ao sexo (X2=56,44; p=0,000) e ao espectro clínico (X2 =504,00; p=0,000). Em crianças com idades entre os 3,8 e os 7,8 anos o ponto de corte >28 ppb pode considerar o BIE presente, e em crianças com idades entre os 5 e os 16 anos o ponto de corte <20 BIE poderá excluir essa afecção. Para adultos o BIE poderá ser excluído quando o ponto de corte for <7 BIE e o ponto de corte >12 poderá considerar a presença da doença. Quatro artigos registaram valores preditores negativos acima dos 88%. Conclusão: A avaliação do eNO parece ser eficaz na inclusão ou na exclusão de BIE em alguns grupos específicos. Assim sendo, a avaliação dos níveis de eNO poderá ser uma ferramenta segura para evitar a necessidade da prova de esforço nos casos negativos, reduzindo a impacto individual e económico desta doença.</p></span>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1533 "Ancho" => 1639 "Tamanyo" => 141072 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Flow diagram of the study inclusion process.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">QUADAS: Quality Assessment of Diagnostic Accuracy Studies.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">QUADAS \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Malberg2009 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Ramser2008 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Lex2007 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Buchvald2005 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Berkman2005 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Elhalawani2003 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Was the spectrum of patients representative of the patients who will receive the test in practice? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Were selection criteria clearly described? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Is the reference standard likely to correctly classify the target condition? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Is the time between reference standard and index test short enough to be reasonably sure that the target condition did not change between the two tests? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Did the whole sample or a random selection of the sample receive verification using a reference standard of diagnosis? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Did patients receive the same reference standard regardless of the index test result? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Was the reference standard independent of the index test ? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Was the execution of the index test described in sufficient detail to permit replication of the test? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Was the execution of the reference standard described in sufficient detail to permit its replication? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Were the index test results interpreted without knowledge of the results of the reference standard? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Were the reference standard results interpreted without knowledge of the results of the index test? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Unclear \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Were the same clinical data available when test results were interpreted as would be available when the test is used in practice? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Were uninterpretable/intermediate test results reported? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Were withdrawals from the study explained? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab884817.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Quality of studies.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Min–max: minimum–maximum; F/M: female/male; min: minutes; EIB: exercise induced bronchospasm; ATS: American Thorax Society; ml/s: milliliters/seconds; NO: nitric oxide; FEV1: forced expiratory flow in the first second; ERS: European Respiratory Society; HR: heart rate; ppb: parts per billion.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AuthorsYearCountry \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Inclusion criteria \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age (years)Min–max \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">F/M \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total sample \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">EIB cases \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study design \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Standard test \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Exhaled nitric oxide \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Malmberg2009Finland \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Suspected of asthma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.8–7.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22/62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54 (64%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Case–control. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Impulse oscillometry (basal, 5, 20<span class="elsevierStyleHsp" style=""></span>min pos-exercise; EIB +: ↑ 40% airway resistance).Free running (Haby et al., 1995).Time/intensity: not reported. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reference: ATS, 1999.Flow: 50±5<span class="elsevierStyleHsp" style=""></span>ml/s.Environment NO: not reported.Method: not reported.Calibration: not reported. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Ramser2008Swiss \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Suspected of EIB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6–16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73/96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">169 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 (12%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cross-sectional. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Espirometry.FEV1<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>15%.Treadmill (ERS, 1997)7–10<span class="elsevierStyleHsp" style=""></span>min/submaximal HR. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reference: ATS/ERS, 2005.Flow: 50<span class="elsevierStyleHsp" style=""></span>ml/s.Environment NO: not reported.Method: <span class="elsevierStyleItalic">on-line</span>, <span class="elsevierStyleItalic">single-breath</span>.Calibration: not reported. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Lex2007Germany \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asmathic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5–16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33/52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (14%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cross-sectional. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Espirometry (basal, 5, 10<span class="elsevierStyleHsp" style=""></span>min pos-exercise).FEV1<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>15%.Treadmill (ATS, 2000)7<span class="elsevierStyleHsp" style=""></span>min/submaximal HR. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reference: ERS/ATS, 2001.Flow: 50<span class="elsevierStyleHsp" style=""></span>ml/s.Environment NO<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>5<span class="elsevierStyleHsp" style=""></span>ppb.Method: <span class="elsevierStyleItalic">on-line</span>, <span class="elsevierStyleItalic">single-breath</span>.Calibration: yes. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Buchvald2005Denmark \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Asmathic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7–16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39–72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 (27%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cross-sectional. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Espirometry (basal, 1, 3, 5, 15, 20<span class="elsevierStyleHsp" style=""></span>min pos-exercise).FEV1<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>15%.Treadmill (ATS, 2000).6<span class="elsevierStyleHsp" style=""></span>min/Submaximal HR. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reference: ATS, 1999; ERS, 1997.Flow: 50<span class="elsevierStyleHsp" style=""></span>ml/s.Environment NO: not reported.Method: <span class="elsevierStyleItalic">on-line</span>, <span class="elsevierStyleItalic">single-breath</span>.Calibration: not reported. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Berkman2005Israel \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Suspected of asthma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21.9–29.3 (mean) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37/48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (27%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Longitudinal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Espirometry.FEV1: not reported.Exercise test (Avital et al., 1995; Godfrey et al., 1999).Time/intensity: not reported. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reference: ATS, 1999.Flow: 250<span class="elsevierStyleHsp" style=""></span>ml/s.Environment NO<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>ppb.Method: not reported.Calibration: yes. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Elhalawani2003United States \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Suspected of EIB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18–40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14/35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (14%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Cross-sectional \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Espirometry (basal, 5, 10, 15, 20, 25, 30<span class="elsevierStyleHsp" style=""></span>min pos-exercise).FEV1<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>15%.Treadmill.14<span class="elsevierStyleHsp" style=""></span>min/85% maximal HR. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reference: ATS, 1999.Flow: 50<span class="elsevierStyleHsp" style=""></span>ml/s.Environment NO: not reported.Method: <span class="elsevierStyleItalic">on-line</span>.Calibration: not reported. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab884815.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Characteristics of included studies.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ppb: parts per billion; CI: confidence interval; PPV: preditive positive value; NPV: negative preditive value.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AuthorYear \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total sample \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">EIB cases \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cut off (ppb) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Sensitivity (95%CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Especificity (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Youden index \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">%PPV \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">%NPV \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Malmberg2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54 (64%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.41 (0.28–0.55) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.89 (0.73–0.98) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.50 (0.36–0.64) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.79 (0.61–0.92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Ramser2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">169 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 (12%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.86 (0.64–0.97) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.32 (0.24–0.40) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">94 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.64 (0.38–0.82) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.66 (0.58–0.74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.50 (0.26–0.70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.78 (0.70–0.84) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.36 (0.18–0.62) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.86 (0.79–0.91) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.32 (0.15–0.57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.88 (0.82–0.93) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Lex2007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (14%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (0.74–1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.58 (0.45–0.69) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Buchvald2005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 (27%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.71 (0.42–0.91) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.76 (0.59–0.88) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.93 (0.68–0.99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.59 (0.43–0.74) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Berkman2005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 (27%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.91 (0.72–0.99) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.70(0.58–0.81) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Elhalawani2003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7 (14%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (0.59–1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.31(0.18–0.47) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab884816.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Results of included studies.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:25 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "American Academy of Allergy Asthma & Immunology Work Group report: exercise-induced asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Weiler" 1 => "S. Bonini" 2 => "R. Coifman" 3 => "T. Craig" 4 => "L. Delgado" 5 => "M. Capao-Filipe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2007.02.041" "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2007" "volumen" => "119" "paginaInicial" => "1349" "paginaFinal" => "1358" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17433829" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Asma induzida pelo exercício: aspectos atuais e recomendações" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "O. Laitano" 1 => "F. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 7 | 15 |
| 2024 October | 42 | 32 | 74 |
| 2024 September | 52 | 28 | 80 |
| 2024 August | 80 | 34 | 114 |
| 2024 July | 44 | 31 | 75 |
| 2024 June | 45 | 42 | 87 |
| 2024 May | 32 | 38 | 70 |
| 2024 April | 50 | 25 | 75 |
| 2024 March | 36 | 31 | 67 |
| 2024 February | 33 | 24 | 57 |
| 2024 January | 28 | 26 | 54 |
| 2023 December | 26 | 30 | 56 |
| 2023 November | 29 | 33 | 62 |
| 2023 October | 23 | 32 | 55 |
| 2023 September | 27 | 28 | 55 |
| 2023 August | 27 | 27 | 54 |
| 2023 July | 17 | 29 | 46 |
| 2023 June | 21 | 16 | 37 |
| 2023 May | 43 | 28 | 71 |
| 2023 April | 26 | 21 | 47 |
| 2023 March | 74 | 19 | 93 |
| 2023 February | 44 | 21 | 65 |
| 2023 January | 24 | 13 | 37 |
| 2022 December | 58 | 20 | 78 |
| 2022 November | 63 | 36 | 99 |
| 2022 October | 50 | 28 | 78 |
| 2022 September | 27 | 24 | 51 |
| 2022 August | 43 | 41 | 84 |
| 2022 July | 39 | 42 | 81 |
| 2022 June | 22 | 30 | 52 |
| 2022 May | 34 | 40 | 74 |
| 2022 April | 31 | 35 | 66 |
| 2022 March | 30 | 37 | 67 |
| 2022 February | 26 | 27 | 53 |
| 2022 January | 24 | 37 | 61 |
| 2021 December | 22 | 46 | 68 |
| 2021 November | 34 | 34 | 68 |
| 2021 October | 26 | 35 | 61 |
| 2021 September | 23 | 30 | 53 |
| 2021 August | 21 | 28 | 49 |
| 2021 July | 15 | 18 | 33 |
| 2021 June | 20 | 18 | 38 |
| 2021 May | 38 | 41 | 79 |
| 2021 April | 43 | 89 | 132 |
| 2021 March | 60 | 17 | 77 |
| 2021 February | 52 | 13 | 65 |
| 2021 January | 18 | 12 | 30 |
| 2020 December | 23 | 8 | 31 |
| 2020 November | 53 | 25 | 78 |
| 2020 October | 23 | 14 | 37 |
| 2020 September | 63 | 25 | 88 |
| 2020 August | 69 | 21 | 90 |
| 2020 July | 101 | 26 | 127 |
| 2020 June | 92 | 26 | 118 |
| 2020 May | 95 | 19 | 114 |
| 2020 April | 55 | 13 | 68 |
| 2020 March | 51 | 14 | 65 |
| 2020 February | 83 | 18 | 101 |
| 2020 January | 83 | 23 | 106 |
| 2019 December | 79 | 23 | 102 |
| 2019 November | 72 | 13 | 85 |
| 2019 October | 87 | 28 | 115 |
| 2019 September | 88 | 18 | 106 |
| 2019 August | 144 | 20 | 164 |
| 2019 July | 139 | 15 | 154 |
| 2019 June | 162 | 11 | 173 |
| 2019 May | 168 | 13 | 181 |
| 2019 April | 155 | 23 | 178 |
| 2019 March | 243 | 13 | 256 |
| 2019 February | 201 | 18 | 219 |
| 2019 January | 204 | 18 | 222 |
| 2018 December | 123 | 4 | 127 |
| 2018 November | 50 | 0 | 50 |
| 2018 October | 50 | 8 | 58 |
| 2018 September | 29 | 7 | 36 |
| 2018 August | 42 | 30 | 72 |
| 2018 July | 47 | 14 | 61 |
| 2018 June | 58 | 14 | 72 |
| 2018 May | 51 | 18 | 69 |
| 2018 April | 129 | 20 | 149 |
| 2018 March | 70 | 22 | 92 |
| 2018 February | 14 | 8 | 22 |
| 2018 January | 24 | 11 | 35 |
| 2017 December | 40 | 15 | 55 |
| 2017 November | 42 | 13 | 55 |
| 2017 October | 44 | 6 | 50 |
| 2017 September | 43 | 28 | 71 |
| 2017 August | 59 | 23 | 82 |
| 2017 July | 49 | 17 | 66 |
| 2017 June | 32 | 15 | 47 |
| 2017 May | 47 | 24 | 71 |
| 2017 April | 14 | 5 | 19 |
| 2017 March | 14 | 7 | 21 |
| 2017 February | 16 | 9 | 25 |
| 2017 January | 16 | 4 | 20 |
| 2016 December | 12 | 12 | 24 |
| 2016 November | 17 | 9 | 26 |
| 2016 October | 14 | 16 | 30 |
| 2016 September | 4 | 4 | 8 |
| 2016 August | 5 | 5 | 10 |
| 2016 July | 7 | 8 | 15 |
| 2016 June | 0 | 5 | 5 |
| 2016 May | 0 | 5 | 5 |
| 2016 April | 19 | 3 | 22 |
| 2016 March | 57 | 12 | 69 |
| 2016 February | 43 | 13 | 56 |
| 2016 January | 30 | 12 | 42 |
| 2015 December | 48 | 11 | 59 |
| 2015 November | 25 | 9 | 34 |
| 2015 October | 24 | 8 | 32 |
| 2015 September | 29 | 10 | 39 |
| 2015 August | 40 | 14 | 54 |
| 2015 July | 22 | 6 | 28 |
| 2015 June | 29 | 7 | 36 |
| 2015 May | 42 | 8 | 50 |
| 2015 April | 32 | 6 | 38 |
| 2015 March | 28 | 8 | 36 |
| 2015 February | 36 | 10 | 46 |
| 2015 January | 41 | 14 | 55 |
| 2014 December | 51 | 16 | 67 |
| 2014 November | 55 | 10 | 65 |
| 2014 October | 52 | 17 | 69 |
| 2014 September | 80 | 15 | 95 |
| 2014 August | 48 | 18 | 66 |
| 2014 July | 52 | 18 | 70 |
| 2014 June | 40 | 10 | 50 |
| 2014 May | 60 | 15 | 75 |
| 2014 April | 59 | 14 | 73 |
| 2014 March | 49 | 16 | 65 |
| 2014 February | 54 | 15 | 69 |
| 2014 January | 60 | 14 | 74 |
| 2013 December | 47 | 16 | 63 |
| 2013 November | 55 | 17 | 72 |
| 2013 October | 46 | 19 | 65 |
| 2013 September | 49 | 23 | 72 |
| 2013 August | 61 | 25 | 86 |
| 2013 July | 69 | 25 | 94 |
| 2013 June | 54 | 17 | 71 |
| 2013 May | 68 | 24 | 92 |
| 2013 April | 70 | 35 | 105 |
| 2013 March | 62 | 37 | 99 |
| 2013 February | 63 | 31 | 94 |
| 2013 January | 60 | 35 | 95 |
| 2012 December | 43 | 32 | 75 |
| 2012 November | 49 | 20 | 69 |
| 2012 October | 38 | 20 | 58 |
| 2012 September | 23 | 60 | 83 |
| 2012 January | 126 | 0 | 126 |
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