Effectiveness of immunotherapy in children depends on place of living – A pilot study

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Urrutia-Pereira, D. Solé, N.A. Rosario, H.J.C. Neto, V. Acosta, C.F. Almendarez, M.M. Avalos, H. Badellino, F. Berroa, M. Álvarez-Castelló, A.J. Castillo, R.L. Castro-Almarales, M.M. De la Cruz, A.M. Cepeda, C. Fernandez, M. González-León, J. Lozano-Saenz, C. Sanchez-Silot, J.C. Sisul-Alvariza, M. Valentin-Rostan, R.O.S. Sarni" "autores" => array:21 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Urrutia-Pereira" ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Solé" ] 2 => array:2 [ "nombre" => "N.A." "apellidos" => "Rosario" ] 3 => array:2 [ "nombre" => "H.J.C." "apellidos" => "Neto" ] 4 => array:2 [ "nombre" => "V." "apellidos" => "Acosta" ] 5 => array:2 [ "nombre" => "C.F." "apellidos" => "Almendarez" ] 6 => array:2 [ "nombre" => "M.M." "apellidos" => "Avalos" ] 7 => array:2 [ "nombre" => "H." "apellidos" => "Badellino" ] 8 => array:2 [ "nombre" => "F." "apellidos" => "Berroa" ] 9 => array:2 [ "nombre" => "M." 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"apellidos" => "Sarni" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054616301495?idApp=UINPBA00004N" "url" => "/03010546/0000004500000003/v1_201704140223/S0301054616301495/v1_201704140223/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0301054616301574" "issn" => "03010546" "doi" => "10.1016/j.aller.2016.10.004" "estado" => "S300" "fechaPublicacion" => "2017-05-01" "aid" => "819" "copyright" => "SEICAP" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Allergol Immunopathol (Madr). 2017;45:265-71" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 10 "formatos" => array:2 [ "HTML" => 9 "PDF" => 1 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "The impact of age on serum allergen-specific IgE to inhaled molecular components" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "265" "paginaFinal" => "271" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 4294 "Ancho" => 2804 "Tamanyo" => 674417 ] ] "descripcion" => array:1 [ "en" => "Frequency of positive test for specific IgE for each allergen component according to the age of the patients: Der p1 (panel A), Bet v1 (panel B), Phl p1 (panel C), Fel d1 (panel D), Par j2 (panel E), Ole e1 (panel F), Cup a1 (panel G) and Can f1 (panel H). Patients were grouped according to their age as follows: early infancy (<2 years), preschool age (2 to <6 years), school-age (6 to <13 years), adolescence (13 to <18 years), 18–20 years, 21–30 years, 31–40 years, 41–50 years, 51–60 years, 61–70 years, 71 years and older." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.A. Tosca, M. Silvestri, R. Olcese, A. Pistorio, G.A. Rossi, G. Ciprandi" "autores" => array:6 [ 0 => array:2 [ "nombre" => "M.A." "apellidos" => "Tosca" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Silvestri" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Olcese" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Pistorio" ] 4 => array:2 [ "nombre" => "G.A." "apellidos" => "Rossi" ] 5 => array:2 [ "nombre" => "G." "apellidos" => "Ciprandi" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054616301574?idApp=UINPBA00004N" "url" => "/03010546/0000004500000003/v1_201704140223/S0301054616301574/v1_201704140223/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "Effectiveness of immunotherapy in children depends on place of living – A pilot study" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "272" "paginaFinal" => "275" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Pawlowski, J. Jerzynska, D. Podlecka, W. Stelmach, P. Majak, I. Stelmach" "autores" => array:6 [ 0 => array:3 [ "nombre" => "M." "apellidos" => "Pawlowski" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Jerzynska" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "D." "apellidos" => "Podlecka" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "W." "apellidos" => "Stelmach" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "P." "apellidos" => "Majak" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:4 [ "nombre" => "I." "apellidos" => "Stelmach" "email" => array:1 [ 0 => "alergol@kopernik.lodz.pl" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Allergology and Internal Medicine in Children, Copernicus Hospital, al. Pilsudskiego 71, 90-329 Lodz, Poland" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Social and Preventive Medicine, Medical University of Lodz, Lodz, Poland" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Clinical Department of Internal Medicine, Asthma and Alergology, Barlicki Hospital, ul. Kopcinskiego 22, Lodz, Poland" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2460 "Ancho" => 1575 "Tamanyo" => 213308 ] ] "descripcion" => array:1 [ "en" => "Comparison of the symptoms, drugs and total score after immunotherapy in children living in farm and city area." ] ] ] "textoCompleto" => "IntroductionThe protective effect of farming on asthma and atopy has been shown in numerous studies consistently across many parts of the world, and the beneficial effects of childhood farm exposure likely last until adulthood.<a class="elsevierStyleCrossRefs" href="#bib0055">1–3</a> It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins. A recently-published study by Schuijs et al., showed that chronic exposure to endotoxin or farm dust protects mice from developing asthma.<a class="elsevierStyleCrossRef" href="#bib0070">4</a> Allergen immunotherapy (AIT) is the only treatment of allergy modifying the immune response with the potential to change the natural history of allergic diseases in many atopic children. It seems that studies evaluating the efficacy of immunotherapy in large cohorts of allergic patients living in farm areas are needed in order to understand the influence of environment on immune response.The aim of this pilot study is to compare the clinical effectiveness of immunotherapy between children living in farm versus urban areas.Material and methodsThis was a retrospective analysis of 87 children living in farm area (n=42) and city area (n=45), aged 8–16, who completed three years of subcutaneous immunotherapy (dust mites, grasses, trees) in our allergy outpatient clinic due to allergic rhinitis and/or asthma, in years 2013–2015. Before immunotherapy there were no differences in asthma/allergic rhinitis severity between study groups. Children were considered as living in farm area if they lived on a farm run by their family and have everyday contact with farm animals or animal feed. All other children were considered as living in city area. Asthma/allergic rhinitis diagnosis was defined previously by the doctors according to GINA and ARIA guidelines.<a class="elsevierStyleCrossRefs" href="#bib0075">5,6</a>An AIT efficacy questionnaire<a class="elsevierStyleCrossRef" href="#bib0085">7</a> has been designed to be filled in by the allergy specialist during a regular immunotherapy visit (based on the medical documentation) before and after AIT. The form includes evaluation of severity of symptoms related to asthma, rhinitis and conjunctivitis, as well as the intake and dosing of allergy and asthma medication. Each component was evaluated for a minimum score −2 (deterioration after AIT) and maximum score of +2 points (significant improvement after AIT). Total score reflected the average score for symptoms and drugs intake – a minimum score −2 (deterioration after AIT) and maximum score of +2 points (significant improvement after AIT).The study was approved by the Ethical Committee of Medical University of LODZ, Lodz, Poland and a written consent was obtained from all the mothers before commencement of the study.Statistical methodsDuring analysis of our data we used Chi square test to determine the difference between nominal variables. The associations between dependent, dichotomic variable and groups of independent variables (presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) were analysed using logistic regression. First, logistic regression was used to assess the relationship between dependent variables and each one of the independent variables–univariate model. A stepwise forward procedure was then used to select variables. Predictors with p levels of at least 0.1 estimated in univariate models were included into multivariate regression analyses. All statistical analyses were performed using StatSoft Statistica for Windows, release 8.0 (StatSoft, Inc., Tulsa, USA). p<0.05 was used as the definition of statistical significance.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>ResultsEighty-seven children were included in the analysis. Clinical characteristics are given in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.We observed significantly higher improvement in total score among children from farm area compared to children from city area (p<0.001). Between-group differences in symptoms and drug scores did not reached the level of significance. (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>In the next step dichotomised all scores (according to the following formula: 1 – significant improvement and 0 – others) and included as dependent variables into three different models of logistic regression analysis. Multivariate logistic regression analysis (adjustment for the effect of gender and type of allergy) showed that living in farm areas was independently associated with significant improvement in total score after immunotherapy (OR: 10.9; 95%CI: 3.7–32.2). Changed in symptoms and drug scores were not associated with place of living of our patients.DiscussionOur study is the first showing differences between efficacy of immunotherapy in children living in farm and city areas. After adjustment for the effect of gender and type of allergy we showed that living in farm area was independently associated with significant improvement in total score (symptoms+drugs use) after immunotherapy.In the present study, treatment with AIT in all groups resulted in overall clinical improvement, however more children living in farm area responded better to AIT treatment based on the reduction in symptom-medication score (total score). The above phenomenon has not been described before in the literature. Keeping in mind a general rule that the effectiveness of immunotherapy depends on the modification of immune regulation, our findings are highly attractive especially in the light of the latest study by Schuijs et al. recently published.<a class="elsevierStyleCrossRef" href="#bib0070">4</a> They showed that chronic exposure to low-dose endotoxin or farm dust protects mice from developing house dust mite-induced asthma. Endotoxin reduced epithelial cell cytokines that activate dendritic cells, thus suppressing type 2 immunity to house dust mites (HDMs).<a class="elsevierStyleCrossRef" href="#bib0070">4</a> Their findings demonstrate that LPS protection blunts the innate immune response to HDMs, which they and others previously found to be driven by Toll-like receptor 4 on epithelial cells.<a class="elsevierStyleCrossRefs" href="#bib0090">8,9</a> Ege et al. identified 15 genes with strong interactions for asthma or atopy in relation to farming, contact with cows and straw, or consumption of raw farm milk.<a class="elsevierStyleCrossRef" href="#bib0100">10</a> They concluded that common genetic polymorphisms are unlikely to moderate the protective influence of the farming environment on childhood asthma and atopy, but rarer variants, particularly of the glutamate receptor may do so. The explanation for our phenomenon may be found in potential interaction of immunotherapy and environmental farm exposures on the immunology system. However, this is a retrospective pilot study based on our observation, therefore we cannot be sure if farm children's symptoms improved from immunotherapy or it was because of living on a farm and exposure to endotoxin or both. The current analysis of the better AIT effectiveness in the farm population has shown the protective influence of environmental exposures on asthma and allergic rhinitis in our children. Given the retrospective design and limited statistical power of our study, these findings should be interpreted with caution before being replicated in prospective large cohort studies.Financial informationThis study was funded by grant 503/2-056-01/503-01 from the Medical University of Lodz, Poland.Conflict of interestThere is no conflict of interest.Ethical disclosuresConfidentiality of dataThe authors declare that no patient data appears in this article.Right to privacy and informed consentThe authors declare that no patient data appears in this article.Protection of human subjects and animals in researchThe authors declare that no experiments were performed on humans or animals for this investigation." 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Allergen immunotherapy (AIT) is the only treatment of allergy modifying the immune response with the potential to change the natural history of allergic diseases. It seems that studies evaluating the efficacy of immunotherapy in large cohorts of allergic patients living in farm areas are needed to understand the influence of environment on immune response during AIT.Aim. To compare the clinical effectiveness of immunotherapy between children living in farm versus urban areas. Materials and methodsThis was a retrospective analysis of 87 children living in farm area (n=42) and city area (n=45), aged 8–16, who completed three years of subcutaneous immunotherapy due to allergic rhinitis/asthma. An AIT efficacy questionnaire has been designed to be filled in by the allergy specialist during a regular immunotherapy visit before and after AIT. ResultsWe observed significantly higher improvement in total score among children from farm area compared to children from city area (p<0.001). Between-group differences in symptoms and drug scores did not reached the level of significance. Multivariate logistic regression analysis (adjustment for the effect of gender and type of allergy) showed that living in farm areas was independently associated with significant improvement in total score after immunotherapy (OR: 10.9; 95%CI: 3.7–32.2). ConclusionThe current analysis of the better AIT effectiveness in the farm population has shown the protective influence of environmental exposures on asthma and allergic rhinitis in our children." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2460 "Ancho" => 1575 "Tamanyo" => 213308 ] ] "descripcion" => array:1 [ "en" => "Comparison of the symptoms, drugs and total score after immunotherapy in children living in farm and city area." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">City area (n=45)</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Farm area (n=42)</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Total group (n=87)</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \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">N \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">% \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">N \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">% \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">N \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">% \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 " colspan="7" align="left" valign="top">Gender</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female \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">44.4 \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">50.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male \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">55.6 \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">50.0 \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><td class="td" title="table-entry " align="char" valign="top">52.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">Type of allergy</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Seasonal \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">63.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Perennial \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36.6 \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">59.5 \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">48.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">Clinical symptoms<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deterioration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lack of change \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.1 \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">13.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Improvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Significant improvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40.0 \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">54.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">Drug use<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deterioration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lack of change \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Improvement \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">44.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Significant improvement \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">26.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42.9 \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">34.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top">Total score<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deterioration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Lack of change \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.5 \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">11.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Improvement \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">57.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Significant improvement \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">26.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">78.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1392754.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "Change from baseline after three years of allergen immunotherapy." ] ] ] "descripcion" => array:1 [ "en" => "Clinical characteristics of study sample." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gene–environment interactions in asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E. von Mutius" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2008.10.046" "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2009" "volumen" => "123" "paginaInicial" => "3" "paginaFinal" => "11" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19130922" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "August" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Living on a farm: impact on asthma induction and clinical course" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. von Mutius" 1 => "K. Radon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.iac.2008.03.010" "Revista" => array:6 [ "tituloSerie" => "Immunol Allergy Clin North Am" "fecha" => "2008" "volumen" => "28" "paginaInicial" => "631" "paginaFinal" => "647" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18572111" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0065" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of immunotherapy for treatment of allergic asthma in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.H. Alzakar" 1 => "A.M. 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M. Pawlowskia, J. Jerzynskaa, D. Podleckaa, W. Stelmachb, P. Majakc, I. Stelmacha,

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alergol@kopernik.lodz.pl

Corresponding author.

a Department of Allergology and Internal Medicine in Children, Copernicus Hospital, al. Pilsudskiego 71, 90-329 Lodz, Poland

b Department of Social and Preventive Medicine, Medical University of Lodz, Lodz, Poland

c Clinical Department of Internal Medicine, Asthma and Alergology, Barlicki Hospital, ul. Kopcinskiego 22, Lodz, Poland

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The protective effect of farming on asthma and atopy has been shown in numerous studies consistently across many parts of the world&#44; and the beneficial effects of childhood farm exposure likely last until adulthood&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#8211;3</span></a> It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins&#46; A recently-published study by Schuijs et al&#46;&#44; showed that chronic exposure to endotoxin or farm dust protects mice from developing asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Allergen immunotherapy &#40;AIT&#41; is the only treatment of allergy modifying the immune response with the potential to change the natural history of allergic diseases in many atopic children&#46; It seems that studies evaluating the efficacy of immunotherapy in large cohorts of allergic patients living in farm areas are needed in order to understand the influence of environment on immune response&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The aim of this pilot study is to compare the clinical effectiveness of immunotherapy between children living in farm versus urban areas&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material and methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">This was a retrospective analysis of 87 children living in farm area &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42&#41; and city area &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#44; aged 8&#8211;16&#44; who completed three years of subcutaneous immunotherapy &#40;dust mites&#44; grasses&#44; trees&#41; in our allergy outpatient clinic due to allergic rhinitis and&#47;or asthma&#44; in years 2013&#8211;2015&#46; Before immunotherapy there were no differences in asthma&#47;allergic rhinitis severity between study groups&#46; Children were considered as living in farm area if they lived on a farm run by their family and have everyday contact with farm animals or animal feed&#46; All other children were considered as living in city area&#46; Asthma&#47;allergic rhinitis diagnosis was defined previously by the doctors according to GINA and ARIA guidelines&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">An AIT efficacy questionnaire<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> has been designed to be filled in by the allergy specialist during a regular immunotherapy visit &#40;based on the medical documentation&#41; before and after AIT&#46; The form includes evaluation of severity of symptoms related to asthma&#44; rhinitis and conjunctivitis&#44; as well as the intake and dosing of allergy and asthma medication&#46; Each component was evaluated for a minimum score &#8722;2 &#40;deterioration after AIT&#41; and maximum score of &#43;2 points &#40;significant improvement after AIT&#41;&#46; Total score reflected the average score for symptoms and drugs intake &#8211; a minimum score &#8722;2 &#40;deterioration after AIT&#41; and maximum score of &#43;2 points &#40;significant improvement after AIT&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The study was approved by the Ethical Committee of Medical University of LODZ&#44; Lodz&#44; Poland and a written consent was obtained from all the mothers before commencement of the study&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Statistical methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">During analysis of our data we used Chi square test to determine the difference between nominal variables&#46; The associations between dependent&#44; dichotomic variable and groups of independent variables &#40;presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41; were analysed using logistic regression&#46; First&#44; logistic regression was used to assess the relationship between dependent variables and each one of the independent variables&#8211;univariate model&#46; A stepwise forward procedure was then used to select variables&#46; Predictors with <span class="elsevierStyleItalic">p</span> levels of at least 0&#46;1 estimated in univariate models were included into multivariate regression analyses&#46; All statistical analyses were performed using StatSoft Statistica for Windows&#44; release 8&#46;0 &#40;StatSoft&#44; Inc&#46;&#44; Tulsa&#44; USA&#41;&#46; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was used as the definition of statistical significance&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">Eighty-seven children were included in the analysis&#46; Clinical characteristics are given in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">We observed significantly higher improvement in total score among children from farm area compared to children from city area &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Between-group differences in symptoms and drug scores did not reached the level of significance&#46; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">In the next step dichotomised all scores &#40;according to the following formula&#58; 1 &#8211; significant improvement and 0 &#8211; others&#41; and included as dependent variables into three different models of logistic regression analysis&#46; Multivariate logistic regression analysis &#40;adjustment for the effect of gender and type of allergy&#41; showed that living in farm areas was independently associated with significant improvement in total score after immunotherapy &#40;OR&#58; 10&#46;9&#59; 95&#37;CI&#58; 3&#46;7&#8211;32&#46;2&#41;&#46; Changed in symptoms and drug scores were not associated with place of living of our patients&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Our study is the first showing differences between efficacy of immunotherapy in children living in farm and city areas&#46; After adjustment for the effect of gender and type of allergy we showed that living in farm area was independently associated with significant improvement in total score &#40;symptoms<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>drugs use&#41; after immunotherapy&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In the present study&#44; treatment with AIT in all groups resulted in overall clinical improvement&#44; however more children living in farm area responded better to AIT treatment based on the reduction in symptom-medication score &#40;total score&#41;&#46; The above phenomenon has not been described before in the literature&#46; Keeping in mind a general rule that the effectiveness of immunotherapy depends on the modification of immune regulation&#44; our findings are highly attractive especially in the light of the latest study by Schuijs et al&#46; recently published&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> They showed that chronic exposure to low-dose endotoxin or farm dust protects mice from developing house dust mite-induced asthma&#46; Endotoxin reduced epithelial cell cytokines that activate dendritic cells&#44; thus suppressing type 2 immunity to house dust mites &#40;HDMs&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Their findings demonstrate that LPS protection blunts the innate immune response to HDMs&#44; which they and others previously found to be driven by Toll-like receptor 4 on epithelial cells&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> Ege et al&#46; identified 15 genes with strong interactions for asthma or atopy in relation to farming&#44; contact with cows and straw&#44; or consumption of raw farm milk&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> They concluded that common genetic polymorphisms are unlikely to moderate the protective influence of the farming environment on childhood asthma and atopy&#44; but rarer variants&#44; particularly of the glutamate receptor may do so&#46; The explanation for our phenomenon may be found in potential interaction of immunotherapy and environmental farm exposures on the immunology system&#46; However&#44; this is a retrospective pilot study based on our observation&#44; therefore we cannot be sure if farm children&#39;s symptoms improved from immunotherapy or it was because of living on a farm and exposure to endotoxin or both&#46; The current analysis of the better AIT effectiveness in the farm population has shown the protective influence of environmental exposures on asthma and allergic rhinitis in our children&#46; Given the retrospective design and limited statistical power of our study&#44; these findings should be interpreted with caution before being replicated in prospective large cohort studies&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Financial information</span><p id="par0060" class="elsevierStylePara elsevierViewall">This study was funded by grant <span class="elsevierStyleGrantNumber" refid="gs1">503&#47;2-056-01&#47;503-01</span> from the <span class="elsevierStyleGrantSponsor" id="gs1">Medical University of Lodz</span>&#44; Poland&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">There is no conflict of interest&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Ethical disclosures</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Confidentiality of data</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Right to privacy and informed consent</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Protection of human subjects and animals in research</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this investigation&#46;</p></span></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">It is considered that farm areas protect young patients from allergy and asthma due to high exposure to endotoxins&#46; Allergen immunotherapy &#40;AIT&#41; is the only treatment of allergy modifying the immune response with the potential to change the natural history of allergic diseases&#46; It seems that studies evaluating the efficacy of immunotherapy in large cohorts of allergic patients living in farm areas are needed to understand the influence of environment on immune response during AIT&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Aim&#46; To compare the clinical effectiveness of immunotherapy between children living in farm versus urban areas&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This was a retrospective analysis of 87 children living in farm area &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42&#41; and city area &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#44; aged 8&#8211;16&#44; who completed three years of subcutaneous immunotherapy due to allergic rhinitis&#47;asthma&#46; An AIT efficacy questionnaire has been designed to be filled in by the allergy specialist during a regular immunotherapy visit before and after AIT&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We observed significantly higher improvement in total score among children from farm area compared to children from city area &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; Between-group differences in symptoms and drug scores did not reached the level of significance&#46; Multivariate logistic regression analysis &#40;adjustment for the effect of gender and type of allergy&#41; showed that living in farm areas was independently associated with significant improvement in total score after immunotherapy &#40;OR&#58; 10&#46;9&#59; 95&#37;CI&#58; 3&#46;7&#8211;32&#46;2&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The current analysis of the better AIT effectiveness in the farm population has shown the protective influence of environmental exposures on asthma and allergic rhinitis in our children&#46;</p></span>"
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleItalic">Type of allergy</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Seasonal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Perennial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleItalic">Clinical symptoms</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Deterioration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lack of change&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Significant improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleItalic">Drug use</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Deterioration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lack of change&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Significant improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">34&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleItalic">Total score</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Deterioration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lack of change&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Significant improvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">78&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of study sample&#46;</p>"
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            0 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Gene&#8211;environment interactions in asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "E&#46; von Mutius"
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                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2008.10.046"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2009"
                        "volumen" => "123"
                        "paginaInicial" => "3"
                        "paginaFinal" => "11"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19130922"
                            "web" => "Medline"
                          ]
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            1 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "August"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Living on a farm&#58; impact on asthma induction and clinical course"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46; von Mutius"
                            1 => "K&#46; Radon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.iac.2008.03.010"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunol Allergy Clin North Am"
                        "fecha" => "2008"
                        "volumen" => "28"
                        "paginaInicial" => "631"
                        "paginaFinal" => "647"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18572111"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy of immunotherapy for treatment of allergic asthma in children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "R&#46;H&#46; Alzakar"
                            1 => "A&#46;M&#46; Alsamarai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2500/aap.2010.31.3353"
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy Asthma Proc"
                        "fecha" => "2010"
                        "volumen" => "31"
                        "paginaInicial" => "324"
                        "paginaFinal" => "330"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20819323"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "September 4"
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells"
                      "autores" => array:1 [
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                          "etal" => true
                          "autores" => array:6 [
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Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2016.08.016

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	2	0	2
2024 October	17	2	19
2024 September	15	5	20
2024 August	15	5	20
2024 July	10	4	14
2024 June	8	3	11
2024 May	10	3	13
2024 April	19	6	25
2024 March	15	4	19
2024 February	14	6	20
2024 January	9	9	18
2023 December	25	5	30
2023 November	12	5	17
2023 October	16	9	25
2023 September	9	5	14
2023 August	24	6	30
2023 July	15	4	19
2023 June	6	4	10
2023 May	17	3	20
2023 April	14	0	14
2023 March	23	3	26
2023 February	15	3	18
2023 January	29	3	32
2022 December	19	5	24
2022 November	25	7	32
2022 October	17	10	27
2022 September	18	6	24
2022 August	14	8	22
2022 July	22	5	27
2022 June	25	13	38
2022 May	26	11	37
2022 April	38	7	45
2022 March	33	6	39
2022 February	32	12	44
2022 January	50	9	59
2021 December	56	9	65
2021 November	32	15	47
2021 October	30	20	50
2021 September	22	16	38
2021 August	11	6	17
2021 July	11	13	24
2021 June	25	16	41
2021 May	24	17	41
2021 April	47	23	70
2021 March	74	8	82
2021 February	17	12	29
2021 January	19	7	26
2020 December	1	0	1
2020 July	0	1	1
2018 February	3	0	3
2017 June	1	0	1
2017 May	3	0	3
2017 April	2	0	2
2016 December	0	2	2

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

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

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