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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A topic of interest in chronic obstructive pulmonary disease &#40;COPD&#41; is the identification of biomarkers that can be applied in the clinic&#46; The usefulness of eosinophil counts in blood for predicting future events&#44; such as exacerbations or death&#44; has been under discussion since several cohort studies reported discrepant results&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;6</span></a> However&#44; this biomarker predicts the effect of inhaled corticosteroids &#40;ICS&#41;&#44; in combination with bronchodilators&#44; in the prevention of exacerbations&#44;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> and for this reason&#44; the Spanish COPD guidelines &#40;GesEPOC&#41;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and the Global Initiative for Chronic Obstructive Lung Disease &#40;GOLD&#41;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> include it in their therapeutic algorithms&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The evidence comes essentially from clinical trials in which the biomarker is determined at the time of recruitment&#44; and the effect of the ICS is evaluated in short-term follow-up&#46; However&#44; these trials do not reproduce clinical practice conditions&#44; and decisions in this setting are often based on historical clinical data&#46; As eosinophil counts can vary over time&#44; and since the optimal cut-off point has not fully been clarified&#44; clinicians face some uncertainty with regard to the use of this marker&#44; particularly if there are discrepancies between the latest and the previous values&#44; or if the clinical laboratory tests were performed some time previously&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">For this reason&#44; we designed this study to assess the relationship between eosinophil counts and clinical events &#40;mortality and severe COPD exacerbations&#41; in conditions that reproduce our clinical practice&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">We retrospectively reviewed electronic medical records &#40;2009&#8211;2018&#41; from a dedicated COPD clinic in a second-level university hospital that included health data from all care levels&#44; providing reliable data on the outcome variables studied&#46; Complete blood counts performed when the patients were stable &#40;&#62;4 weeks from an exacerbation&#41; in the 5 years prior to the index date &#40;first visit&#41; were recorded&#46; The criterion for inclusion was a diagnosis of COPD according to GOLD in smokers of &#8805;10 pack-years&#44; with a follow-up of &#8805;12 months&#46; Exclusion criteria were not having &#8805;3 complete blood counts in the specified period&#44; alpha 1-antitrypsin deficiency&#44; concomitant diagnosis of other chronic respiratory disease&#44; chronic systemic steroid use&#44; and diseases that could alter the eosinophil count&#46; Subjects were divided into 3 groups&#58; &#40;A&#41;&#58; eosinophils always &#60;300&#47;&#956;L&#59; &#40;B&#41;&#58; variable counts&#44; above and below this value&#44; with less than 3 complete blood counts showing eosinophilia&#59; and &#40;C&#41;&#58; at least 3 complete blood counts with &#8805;300 eosinophils&#47;&#956;L&#46; The relationship between this classification and the risk of death or admission for COPD exacerbations after the index date was studied by constructing Kaplan-Meier curves and analyzing the Cox&#39;s proportional hazards model&#44; correcting for confounding variables&#46; An additional analysis was performed dividing persistently eosinopenic subjects &#40;&#8804;100 eosinophils&#47;&#956;L in all complete blood counts&#41; and non-eosinopenic subjects&#46; Receiver operating characteristic &#40;ROC&#41; curves were obtained for the maximum number of eosinophils determined in each patient&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We identified 758 subjects&#46; A total of 204 were excluded &#40;26&#37;&#41;&#44; as follows&#58; &#60;3 complete blood counts in stable phase &#40;164&#41;&#44; long-term administration of steroids &#40;20&#41;&#44; diagnosis of alpha-1 antitrypsin deficiency &#40;15&#41;&#44; leukemia &#40;2&#41;&#44; and pneumoconiosis &#40;3&#41;&#46; We studied 554 subjects with a follow-up of 58&#46;5&#8239;&#177;&#8239;26&#46;9 months&#58; Group A&#58; 228 subjects &#40;41&#46;1&#37;&#41;&#59; Group B&#58; 165 &#40;29&#46;7&#37;&#41;&#59; Group C&#58; 161 &#40;29&#37;&#41;&#46; Fifty-two &#40;9&#46;3&#37;&#41; had persistent eosinopenia&#46; There were no differences between groups in terms of age&#44; sex&#44; pack-year index&#44; percentage of active smokers&#44; spirometric values&#44; oxygen saturation&#44; body mass index&#44; comorbidity and BODEx indices&#44; or death rate&#44; nor in the percentage of subjects treated at the index date with ICS or other drugs for COPD&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the Kaplan&#8211;Meier curves for mortality and the risk of a first admission for COPD exacerbation&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the results of the Cox analysis for both events&#46; Classification using the cut-off point of 300 eosinophils was not associated with differences in the risk of death or admission&#46; Patients with persistent eosinopenia presented a higher risk of death &#40;HR&#58; 1&#46;70&#59; 95&#37; CI&#58; 1&#46;03&#8211;2&#46;79&#59; p&#8239;&#61;&#8239;0&#46;03&#41; but not of admission&#46; The area under the ROC curve for the maximum number of eosinophils to predict mortality or hospitalization was 0&#46;51 &#40;95&#37; CI&#58; 0&#46;47&#8211;0&#46;56&#41; and 0&#46;50 &#40;95&#37; CI&#58; 0&#46;45&#8211;0&#46;54&#41;&#44; respectively&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">This study illustrates the difficulties of using the eosinophil count in the clinic&#46; In a quarter of the subjects&#44; no previous complete blood count results &#40;or very few&#41; were available&#44; or elements that might alter results were identified&#46; Only one third have persistent eosinophilia&#44; in line with previous studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;11</span></a> The maximum interval between obtaining a complete blood count and using the results to guide treatment is not clearly defined in either GOLD or GesEPOC&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> Considering that COPD treatment is decided in all areas&#44; including primary care&#44; it is not realistic to expect a recent complete blood count &#40;CBC&#41; in each case&#44; and we believe that clinicians rely on previous historical values that are not always recent&#46; In our study&#44; classification according to historical figures&#44; based on the cut-off point recommended by GesEPOC&#44; was not associated with major clinical events&#44; and the ROC curve for the maximum number of eosinophils indicates that using another cut-off point would not have changed the results&#46; However&#44; patients with persistently very low eosinophil counts had a higher risk of mortality&#44; but this finding that must be interpreted cautiously given the size of the sample&#46; We must recognize that the usefulness of this biomarker lies in predicting the effect of ICS in preventing exacerbations&#44; although this factor could not be judged in this study due to its limitations&#44; since prescription data were only available from the first visit&#44; and not on subsequent developments&#46; In spite of that and other limitations &#40;risk of information bias and clear selection bias due to scope of the study conduct&#41;&#44; we believe that our findings underline the advisability of carrying out studies that reproduce real-world practice&#44; in order to make more precise recommendations on how to incorporate this biomarker in the clinic&#44; and we believe these results will be interesting to our community&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Golpe R&#44; et al&#46; Recuento de eosin&#243;filos en sangre y eventos centrados en el paciente con enfermedad pulmonar obstructiva cr&#243;nica en pr&#225;ctica asistencial real&#46; Arch Bronconeumol&#46; 2020&#59;56&#58;129&#8211;130&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Kaplan&#8211;Meier curves for &#40;1&#41; mortality and &#40;2&#41; admission for COPD exacerbations &#40;A&#41;&#58; eosinophil count always &#60;300&#47;&#956;L&#59; &#40;B&#41;&#58; variable eosinophil counts&#59; &#40;C&#41;&#58; at least 3 complete blood counts with &#8805;300 eosinophils&#47;&#956;L&#46;</p>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">BMI&#58; body mass index&#59; SpO<span class="elsevierStyleInf">2</span>&#58; Oxygen saturation by pulse oximetry&#46;</p>"
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                  \t\t\t\t">0&#46;96&#8211;0&#46;98&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">BMI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Charlson index&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;25&#8211;1&#46;52&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">0&#46;87&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;57&#8211;1&#46;33&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;54&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">1&#46;03&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">0&#46;83&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">1&#46;12&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">0&#46;73&#8211;1&#46;73&nbsp;\t\t\t\t\t\t\n
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Scientific Letter
Plasma eosinophil count and patient-centered events in chronic obstructive pulmonary disease in real-life clinical practice
Recuento de eosinófilos en sangre y eventos centrados en el paciente con enfermedad pulmonar obstructiva crónica en práctica asistencial real
Rafael Golpe
Corresponding author
rafael.golpe.gomez@sergas.es

Corresponding author.
, David Dacal, Pilar Sanjuán-López, Irene Martín-Robles, Luis A. Pérez-de-Llano
Servicio de Neumología, Hospital Universitario Lucus Augusti, Lugo, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A topic of interest in chronic obstructive pulmonary disease &#40;COPD&#41; is the identification of biomarkers that can be applied in the clinic&#46; The usefulness of eosinophil counts in blood for predicting future events&#44; such as exacerbations or death&#44; has been under discussion since several cohort studies reported discrepant results&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#8211;6</span></a> However&#44; this biomarker predicts the effect of inhaled corticosteroids &#40;ICS&#41;&#44; in combination with bronchodilators&#44; in the prevention of exacerbations&#44;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a> and for this reason&#44; the Spanish COPD guidelines &#40;GesEPOC&#41;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> and the Global Initiative for Chronic Obstructive Lung Disease &#40;GOLD&#41;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> include it in their therapeutic algorithms&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The evidence comes essentially from clinical trials in which the biomarker is determined at the time of recruitment&#44; and the effect of the ICS is evaluated in short-term follow-up&#46; However&#44; these trials do not reproduce clinical practice conditions&#44; and decisions in this setting are often based on historical clinical data&#46; As eosinophil counts can vary over time&#44; and since the optimal cut-off point has not fully been clarified&#44; clinicians face some uncertainty with regard to the use of this marker&#44; particularly if there are discrepancies between the latest and the previous values&#44; or if the clinical laboratory tests were performed some time previously&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">For this reason&#44; we designed this study to assess the relationship between eosinophil counts and clinical events &#40;mortality and severe COPD exacerbations&#41; in conditions that reproduce our clinical practice&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">We retrospectively reviewed electronic medical records &#40;2009&#8211;2018&#41; from a dedicated COPD clinic in a second-level university hospital that included health data from all care levels&#44; providing reliable data on the outcome variables studied&#46; Complete blood counts performed when the patients were stable &#40;&#62;4 weeks from an exacerbation&#41; in the 5 years prior to the index date &#40;first visit&#41; were recorded&#46; The criterion for inclusion was a diagnosis of COPD according to GOLD in smokers of &#8805;10 pack-years&#44; with a follow-up of &#8805;12 months&#46; Exclusion criteria were not having &#8805;3 complete blood counts in the specified period&#44; alpha 1-antitrypsin deficiency&#44; concomitant diagnosis of other chronic respiratory disease&#44; chronic systemic steroid use&#44; and diseases that could alter the eosinophil count&#46; Subjects were divided into 3 groups&#58; &#40;A&#41;&#58; eosinophils always &#60;300&#47;&#956;L&#59; &#40;B&#41;&#58; variable counts&#44; above and below this value&#44; with less than 3 complete blood counts showing eosinophilia&#59; and &#40;C&#41;&#58; at least 3 complete blood counts with &#8805;300 eosinophils&#47;&#956;L&#46; The relationship between this classification and the risk of death or admission for COPD exacerbations after the index date was studied by constructing Kaplan-Meier curves and analyzing the Cox&#39;s proportional hazards model&#44; correcting for confounding variables&#46; An additional analysis was performed dividing persistently eosinopenic subjects &#40;&#8804;100 eosinophils&#47;&#956;L in all complete blood counts&#41; and non-eosinopenic subjects&#46; Receiver operating characteristic &#40;ROC&#41; curves were obtained for the maximum number of eosinophils determined in each patient&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We identified 758 subjects&#46; A total of 204 were excluded &#40;26&#37;&#41;&#44; as follows&#58; &#60;3 complete blood counts in stable phase &#40;164&#41;&#44; long-term administration of steroids &#40;20&#41;&#44; diagnosis of alpha-1 antitrypsin deficiency &#40;15&#41;&#44; leukemia &#40;2&#41;&#44; and pneumoconiosis &#40;3&#41;&#46; We studied 554 subjects with a follow-up of 58&#46;5&#8239;&#177;&#8239;26&#46;9 months&#58; Group A&#58; 228 subjects &#40;41&#46;1&#37;&#41;&#59; Group B&#58; 165 &#40;29&#46;7&#37;&#41;&#59; Group C&#58; 161 &#40;29&#37;&#41;&#46; Fifty-two &#40;9&#46;3&#37;&#41; had persistent eosinopenia&#46; There were no differences between groups in terms of age&#44; sex&#44; pack-year index&#44; percentage of active smokers&#44; spirometric values&#44; oxygen saturation&#44; body mass index&#44; comorbidity and BODEx indices&#44; or death rate&#44; nor in the percentage of subjects treated at the index date with ICS or other drugs for COPD&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the Kaplan&#8211;Meier curves for mortality and the risk of a first admission for COPD exacerbation&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the results of the Cox analysis for both events&#46; Classification using the cut-off point of 300 eosinophils was not associated with differences in the risk of death or admission&#46; Patients with persistent eosinopenia presented a higher risk of death &#40;HR&#58; 1&#46;70&#59; 95&#37; CI&#58; 1&#46;03&#8211;2&#46;79&#59; p&#8239;&#61;&#8239;0&#46;03&#41; but not of admission&#46; The area under the ROC curve for the maximum number of eosinophils to predict mortality or hospitalization was 0&#46;51 &#40;95&#37; CI&#58; 0&#46;47&#8211;0&#46;56&#41; and 0&#46;50 &#40;95&#37; CI&#58; 0&#46;45&#8211;0&#46;54&#41;&#44; respectively&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">This study illustrates the difficulties of using the eosinophil count in the clinic&#46; In a quarter of the subjects&#44; no previous complete blood count results &#40;or very few&#41; were available&#44; or elements that might alter results were identified&#46; Only one third have persistent eosinophilia&#44; in line with previous studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;11</span></a> The maximum interval between obtaining a complete blood count and using the results to guide treatment is not clearly defined in either GOLD or GesEPOC&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> Considering that COPD treatment is decided in all areas&#44; including primary care&#44; it is not realistic to expect a recent complete blood count &#40;CBC&#41; in each case&#44; and we believe that clinicians rely on previous historical values that are not always recent&#46; In our study&#44; classification according to historical figures&#44; based on the cut-off point recommended by GesEPOC&#44; was not associated with major clinical events&#44; and the ROC curve for the maximum number of eosinophils indicates that using another cut-off point would not have changed the results&#46; However&#44; patients with persistently very low eosinophil counts had a higher risk of mortality&#44; but this finding that must be interpreted cautiously given the size of the sample&#46; We must recognize that the usefulness of this biomarker lies in predicting the effect of ICS in preventing exacerbations&#44; although this factor could not be judged in this study due to its limitations&#44; since prescription data were only available from the first visit&#44; and not on subsequent developments&#46; In spite of that and other limitations &#40;risk of information bias and clear selection bias due to scope of the study conduct&#41;&#44; we believe that our findings underline the advisability of carrying out studies that reproduce real-world practice&#44; in order to make more precise recommendations on how to incorporate this biomarker in the clinic&#44; and we believe these results will be interesting to our community&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Golpe R&#44; et al&#46; Recuento de eosin&#243;filos en sangre y eventos centrados en el paciente con enfermedad pulmonar obstructiva cr&#243;nica en pr&#225;ctica asistencial real&#46; Arch Bronconeumol&#46; 2020&#59;56&#58;129&#8211;130&#46;</p>"
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Eosinophil group C<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                          "etal" => true
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                            2 => "J&#46;L&#46; Curtis"
                            3 => "C&#46;M&#46; Doerschuk"
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                        "tituloSerie" => "Lancet Respir Med"
                        "fecha" => "2017"
                        "volumen" => "5"
                        "paginaInicial" => "956"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29146301"
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                          "etal" => true
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                            0 => "R&#46;S&#46; Zeiger"
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                            3 => "M&#46; Schatz"
                            4 => "Q&#46; Li"
                            5 => "D&#46;B&#46; Khatry"
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                    0 => array:1 [
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                        "tituloSerie" => "J Allergy Clin Inmunol Pract"
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                            3 => "J&#46; Vestbo"
                            4 => "B&#46;G&#46; Nordestgaard"
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Article information
ISSN: 15792129
Original language: English
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