Effect of high dose inhaled corticosteroids on cell mediated immunity in patients with asthma

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Tuncel, P. Uysal, A.B. Hocaoglu, D.O. Erge, O. Karaman, N. Uzuner" "autores" => array:6 [ 0 => array:2 [ "nombre" => "T." "apellidos" => "Tuncel" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Uysal" ] 2 => array:2 [ "nombre" => "A.B." "apellidos" => "Hocaoglu" ] 3 => array:2 [ "nombre" => "D.O." "apellidos" => "Erge" ] 4 => array:2 [ "nombre" => "O." "apellidos" => "Karaman" ] 5 => array:2 [ "nombre" => "N." 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Pagán, A.J. Huertas, V. Iraola, H. Pinto, R. Martínez, M. Ramírez, M.D. Martos, J. Carnés" "autores" => array:8 [ 0 => array:2 [ "nombre" => "J.A." "apellidos" => "Pagán" ] 1 => array:2 [ "nombre" => "A.J." "apellidos" => "Huertas" ] 2 => array:2 [ "nombre" => "V." "apellidos" => "Iraola" ] 3 => array:2 [ "nombre" => "H." "apellidos" => "Pinto" ] 4 => array:2 [ "nombre" => "R." "apellidos" => "Martínez" ] 5 => array:2 [ "nombre" => "M." "apellidos" => "Ramírez" ] 6 => array:2 [ "nombre" => "M.D." "apellidos" => "Martos" ] 7 => array:2 [ "nombre" => "J." "apellidos" => "Carnés" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054611001261?idApp=UINPBA00004N" "url" => "/03010546/0000004000000002/v1_201304101104/S0301054611001261/v1_201304101104/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Effect of high dose inhaled corticosteroids on cell mediated immunity in patients with asthma" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "100" "paginaFinal" => "103" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "C. Lee, W.B. Klaustermeyer" "autores" => array:2 [ 0 => array:4 [ "nombre" => "C." "apellidos" => "Lee" "email" => array:1 [ 0 => "christina.h.lee@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "W.B." "apellidos" => "Klaustermeyer" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Department of Medicine, Division of Allergy and Immunology, VA Greater Los Angeles Healthcare System/University of California Los Angeles, Los Angeles, CA, United States" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "IntroductionAsthma is a variable and chronic inflammatory disease of the airways. The inflammatory disorder underlying asthma arises from the interaction of various cells including eosinophils, mast cells and T lymphocytes.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Thus, anti-inflammatory therapy, in the form of inhaled corticosteroids, is key in the management of persistent asthma.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> As the prevalence of asthma has been increasing, so has the use of inhaled corticosteroids, and at higher doses than previously prescribed early in its introduction.Recent studies have shown that inhaled corticosteroids have systemic effects on bone metabolism,<a class="elsevierStyleCrossRefs" href="#bib0015">3–8</a> hypothalamus–pituitary adrenal axis,<a class="elsevierStyleCrossRefs" href="#bib0045">9–15</a> on linear growth,<a class="elsevierStyleCrossRefs" href="#bib0080">16–18</a> and cataracts.<a class="elsevierStyleCrossRefs" href="#bib0095">19–21</a> Oral corticosteroids have an even more potent effect on these parameters, and additionally have been shown to suppress cell mediated immunity, increasing an individual's susceptibility of acquiring an opportunistic infection.<a class="elsevierStyleCrossRefs" href="#bib0110">22–31</a>It is unclear at this time whether high dose inhaled corticosteroids also suppress cell mediated immunity. Studies addressing this issue have been conflicting thus far.<a class="elsevierStyleCrossRefs" href="#bib0160">32–34</a> Currently there are no data to suggest increased incidence or course of fungal, viral or bacterial infections with the use of inhaled corticosteroids. However, there are rare cases that have been reported of reactivation of tuberculosis or viral infections associated with the use of inhaled corticosteroids.<a class="elsevierStyleCrossRefs" href="#bib0175">35–37</a> The US Food and Drug Administration has instructed the manufacturers of oral, injectable and inhaled corticosteroids to include the warning about the possible risk of tuberculosis and viral infections with the use of these agents.<a class="elsevierStyleCrossRef" href="#bib0190">38</a> However, the American Academy of Allergy and Immunology issued a position statement, stating that this warning is unwarranted.<a class="elsevierStyleCrossRef" href="#bib0195">39</a>The objective of our current study was to evaluate if there is a correlation between high dose inhaled corticosteroids and suppression of cell mediated immunity in asthmatics. This was accomplished by determining if there was a statistically significant higher incidence of impaired cellular immunity (as reflected in anergy or lower cumulative skin test scores to DTH testing) in patients with asthma who have already been receiving high dose inhaled fluticasone for >6 months compared to an age-matched control asthma population not on high dose inhaled corticosteroids.Materials and methodsStudy designEighteen volunteers with asthma between the ages of 42 and 67 were recruited for this cross-sectional study. Informed consent was obtained from each subject prior to entry into the study and the protocol was approved by the local Institutional Review Board (IRB B, VA Promise No. 0035). Exclusion criteria included subjects who have received systemic corticosteroids or immunosupressants in the past 6 months, patients with chronic diseases that may influence cell mediated immunity (autoimmune disease, malignancy or immunodeficiency), or patients with a significant infection in the past 6 months.Group A consisted of nine asthma patients who had been compliant with taking high dose inhaled corticosteroids (defined as fluticasone/salmeterol 500/50μg twice daily or fluticasone propionate 220μg two puffs twice daily) for at least 6 months duration.Group B consisted of nine volunteers with mild intermittent asthma who had been treated with albuterol as needed only, without exposure to inhaled corticosteroids.Cell mediated immunity was compared between volunteers of group A and group B by DTH skin testing. To account for differences that may be related to age, each volunteer in group A was age matched within 3 years to a volunteer in group B, resulting in a comparable spread of age between the two groups.DTH skin testing and interpretationDTH skin testing was performed in our study using the standard Mantoux technique. Intradermal injections of 0.1mL of candida (Candin; Allermed Laboratories; San Diego, CA, USA) and tetanus (Tetanus Toxoid USP; Aventis Pasteur) were placed on the volar aspect of the forearm. Results were read by a single blinded individual for all subjects 48h after placement using the ballpoint pen technique to measure the induration at each site. Orthogonal diameters were measured, and the average of these diameters was recorded. A mean induration of ≥2mm was considered positive. A cumulative skin test score was calculated by adding the mean diameters of positive reactions.Statistical analysisThe non-parametric Wilcoxon rank sum test and the parametric t test were both used to compute p values for comparing means between the inhaled corticosteroid group (group A) and the albuterol only (group B) in total skin test score for candida and tetanus individually, total skin test score for candida plus tetanus, as well as difference in incidence of anergy. A statistically significant result was defined as p<0.05. Means±SEM are reported.ResultsEighteen volunteer subjects completed this study. Subjects ranged in age from 42 to 67 years (mean, 57.11±6.6). One subject in the study was lost to follow up. There were no significant adverse events experienced in the 18 subjects who completed the study. The most common complaint was mild pruritis at the site of skin testing.<a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a> depict the sum of mean orthogonal diameters for candida and tetanus skin test score individually as well as for the candida plus tetanus total skin test score for the high dose inhaled corticosteroid group (group A) and no inhaled corticosteroid group (group B), respectively. The mean candida skin test score of 3.33±2.03mm and 4.33±1.76 in the inhaled corticosteroid group and albuterol only group, respectively, was not significantly different statistically (p=0.714 using t-test, p=0.594 using Wilcoxon rank sum test). The mean tetanus skin test score of 4.89±1.12 and 5.33±1.11 in the inhaled corticosteroid group and albuterol only group, respectively, was also not significantly different statistically (p=0.782 using t-test, p=0.721 using Wilcoxon rank sum test). Comparison of the mean candida plus tetanus total skin test score of 8.22±1.91 and 9.67±2.37 in the inhaled corticosteroid group and albuterol only group, respectively, showed no statistically significant difference (p=0.642 using t-test, p=0.824 using Wilcoxon rank sum test). Finally, there was no significant difference in the incidence of anergy between the two study groups. The largest mean difference in standard deviation (SD) units is a mean difference of 0.225 SD units for candida plus tetanus. To confirm that this difference is statistically significant with 80% power would require a sample size in excess of 300.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>DiscussionInhaled corticosteroids have been demonstrated to have adverse effects on bone metabolism, hypothalamus–pituitary adrenal axis, linear growth, and cataracts, like systemic corticosteroids, but to a lesser degree. However, studies evaluating whether inhaled corticosteroids impair cell mediated immunity have been conflicting and inconclusive thus far. An early study by Levy et al. found no suppression of cell mediated immunity in children with asthma treated with lower dose inhaled corticosteroids.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> Cell mediated immunity was evaluated with immune parameters including differential white blood count, T and B cell numbers, T helper and suppressor counts, T cell mitogenic transformation, and IL-1 and IL-2 secretion.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> Recently, two studies evaluated the effects of high dose inhaled corticosteroids on cell mediated immunity. Sharma et al. showed suppression of cell mediated immunity determined by delayed hypersensitivity skin testing (using Multi-test) in nine healthy patients after 4 weeks of high dose inhaled fluticasone compared to baseline.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> However, this study was faulted for using Multi-test, as the American Thoracic Society does not recommend multipuncture devices for DTH testing due to the possibility of administering inconsistent amounts of antigen (17). England et al. conversely showed no suppression of cell mediated immunity determined by delayed hypersensitivity skin testing (using standard Mantoux technique) in 18 healthy subjects after 4 weeks of high dose inhaled fluticasone compared to baseline testing.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> However, it is important to evaluate DTH testing in asthmatics (not healthy volunteers) receiving inhaled corticosteroids for a longer duration.In our present study, patients with asthma treated with high dose inhaled corticosteroids for at least 6 months did not have reduced cellular immunity in comparison to asthma patients taking albuterol as needed only without inhaled corticosteroids. There was no statistically significant difference for cell mediated immunity by DTH testing using the Mantoux technique. At this time, there are no data to suggest increased incidence or altered course of fungal, viral or bacterial infections with the use of inhaled corticosteroids. There are only rare case reports of reactivation of tuberculosis or viral infections associated with the use of inhaled corticosteroids.<a class="elsevierStyleCrossRefs" href="#bib0175">35–37</a> Our findings are in agreement with those of England et al. who found no suppression of cell mediated immunity after 28 days of treatment with high dose inhaled corticosteroids. However, we do acknowledge that there is a wide spread of values obtained in our study, the significance of which is unclear due to the small number of subjects. Further studies with larger numbers of asthma patients followed prospectively with DTH testing both before and after 6 months of therapy may be warranted.FundingResearch conducted at VA Greater Los Angeles Healthcare System; Los Angeles, CA. Research non-funded and approved by local IRB Board.Conflicts of interestDr. Lee and Dr. Klaustermeyer have no conflicts of interest to disclose." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres86097" "titulo" => array:6 [ 0 => "Abstract" 1 => "Background" 2 => "Study objectives" 3 => "Methods" 4 => "Results" 5 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec74261" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "DTH skin testing and interpretation" ] ] ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Funding" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of interest" ] 9 => array:2 [ "identificador" => "xack31872" "titulo" => "Acknowledgement" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-08-12" "fechaAceptado" => "2011-11-07" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec74261" "palabras" => array:5 [ 0 => "Asthma" 1 => "Cell mediated immunity" 2 => "Delayed type hypersensitivity skin test" 3 => "Infection" 4 => "Inhaled corticosteroids" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "BackgroundCell mediated immunity is suppressed by systemic corticosteroids. Inhaled corticosteroids have been shown to affect parameters including bone metabolism, hypothalamus–pituitary adrenal axis, linear growth, and lead to the development of cataracts. However, it is unclear if high dose inhaled corticosteroid therapy affects cell mediated immunity. Study objectivesTo evaluate if asthma patients taking high dose inhaled corticosteroids chronically have reduced cell mediated immunity compared to asthma patients not taking inhaled corticosteroids. MethodsEighteen asthmatic subjects participated in this cross-sectional study. Cell mediated immunity was evaluated in nine patients who had been taking high dose inhaled corticosteroids for >6 months and nine patients not taking inhaled corticosteroids. Cell mediated immunity was evaluated by delayed type hypersensitivity (DTH) skin testing with intradermal placement of candida and tetanus antigens. ResultsThere was no significant difference in DTH skin test results between the high dose inhaled corticosteroid and no corticosteroid treated asthma group. ConclusionPatients with asthma taking high dose inhaled corticosteroids chronically (>6 months) did not have significantly greater impaired cell mediated immunity than patients not taking inhaled corticosteroids in this study." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Subject \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Candida (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" 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title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.72 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SEM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.91 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165453.png" ] ] ] ] "descripcion" => array:1 [ "en" => "DTH skin test results (millimetres of induration) evaluating cell mediated immunity in the inhaled corticosteroid group." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Subject \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Candida (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Tetanus (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Candida+tetanus (mm) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mean \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.67 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SEM \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.37 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab165452.png" ] ] ] ] "descripcion" => array:1 [ "en" => "DTH skin test results (millimetres of induration) evaluating cell mediated immunity in the no inhaled corticosteroid group." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:39 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "National Asthma Education and Prevention Program Expert Panel Report 3: guidelines for the diagnosis and management of asthma; 2003." ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glucocorticoid therapy for asthma: clinical pharmacology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "S.J. Szefler" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "1991" "volumen" => "88" "paginaInicial" => "147" "paginaFinal" => "165" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1880315" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Beclomethasone inhalation decreases serum osteocalcin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E.M. Pouw" 1 => "M.F. Prummel" 2 => "H. Oosting" 3 => "C.M. Roos" 4 => "E. Endert" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "BMJ" "fecha" => "1991" "volumen" => "302" "paginaInicial" => "627" "paginaFinal" => "628" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2012877" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Decreased bone mineral density in premenopausal asthma patients receiving long-term inhaled steroid therapy for asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Ip" 1 => "K. Lam" 2 => "L. Yam" 3 => "A. Kung" 4 => "M. Ng" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "1994" "volumen" => "105" "paginaInicial" => "1722" "paginaFinal" => "1727" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8205866" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of dose and dosing schedule of inhaled budesonide on bone turnover" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.H. Toogood" 1 => "B.H. Jennings" 2 => "A.B. Hodsman" 3 => "J. Baskerville" 4 => "L.I. Fraher" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "1991" "volumen" => "88" "paginaInicial" => "572" "paginaFinal" => "580" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1918724" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled corticosteroid use and bone mineral density in patients with asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C.A. Wong" 1 => "L.J. Walsh" 2 => "C.J. Smith" 3 => "A.F. Wisniewski" 4 => "S.A. Lewis" 5 => "R. Hubbard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(00)02138-3" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2000" "volumen" => "355" "paginaInicial" => "1399" "paginaFinal" => "1403" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10791523" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled corticosteroid and hip fracture: a population based case–control study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R.B. Hubbard" 1 => "C.J. Smith" 2 => "L. Smeeth" 3 => "T.W. Harrison" 4 => "A.E. Tattersfield" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200206-606OC" "Revista" => array:6 [ "tituloSerie" => "Am J Resp Crit Care Med" "fecha" => "2002" "volumen" => "166" "paginaInicial" => "1563" "paginaFinal" => "1566" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12406825" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of inhaled corticosteroids and risk of fracture" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R. Hubbard" 1 => "A. Tattersfield" 2 => "C. Smith" 3 => "J. West" 4 => "L. Smeeth" 5 => "A. Fletcher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.130.4.1082" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2006" "volumen" => "130" "paginaInicial" => "1082" "paginaFinal" => "1088" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17035441" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diurnal cortisol secretion during therapy with inhaled beclomethasone dipropionate in children with asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. Tabachnik" 1 => "Z. Zadik" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Pediatr" "fecha" => "1991" "volumen" => "118" "paginaInicial" => "294" "paginaFinal" => "297" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1993964" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Integrate plasma cortisol concentration in children with asthma receiving long term inhaled corticosteroids" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Phillip" 1 => "M. Aviram" 2 => "E. Leiberman" 3 => "Z. Zadik" 4 => "Y. Giat" 5 => "J. Levy" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pediatr Pulmonol" "fecha" => "1992" "volumen" => "12" "paginaInicial" => "84" "paginaFinal" => "89" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1315017" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic bioavailability and potency of high dose inhaled corticosteroids" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D. Wales" 1 => "H. Makker" 2 => "J. Kane" 3 => "P. McDowell" 4 => "R. O’Driscoll" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "1999" "volumen" => "115" "paginaInicial" => "1278" "paginaFinal" => "1284" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10334140" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dose response effect for adrenal suppression with repeated twice daily inhaled fluticasone propionate and triamcinolone acetonide in adult asthmatics" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.M. Wilson" 1 => "L.C. McFarlane" 2 => "B.J. Lipworth" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.156.4.97-03029" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1997" "volumen" => "156" "paginaInicial" => "1274" "paginaFinal" => "1277" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9351634" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic adverse effects of inhaled corticosteroid therapy: a systemic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "B.J. Lipworth" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Intern Med" "fecha" => "1999" "volumen" => "159" "paginaInicial" => "941" "paginaFinal" => "955" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10326936" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patient" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "T.B. Casale" 1 => "H.S. Nelson" 2 => "W.E. Stricker" 3 => "H. Raff" 4 => "K.B. Newman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1081-1206(10)62918-3" "Revista" => array:6 [ "tituloSerie" => "Ann Allergy Asthma Immunol" "fecha" => "2001" "volumen" => "87" "paginaInicial" => "379" "paginaFinal" => "385" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11730179" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of long term inhaled corticosteroid on adrenal function in a patient with asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. White" 1 => "T. Crisalida" 2 => "H. Li" 3 => "A. Economides" 4 => "M. Kaliner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1081-1206(10)60911-8" "Revista" => array:6 [ "tituloSerie" => "Ann Allergy Asthma Immunol" "fecha" => "2006" "volumen" => "96" "paginaInicial" => "437" "paginaFinal" => "444" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16597078" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Growth of asthmatic children during treatment with budesonide: a double blind trial" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "O.D. Wolthers" 1 => "S. Pedersen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "BMJ" "fecha" => "1991" "volumen" => "303" "paginaInicial" => "163" "paginaFinal" => "165" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1878641" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of asthma and its treatment on growth: four year follow up of cohort of children from general practices in Tayside, Scotland" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. McCowan" 1 => "R.G. Neville" 2 => "G.E. Thomas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "BMJ" "fecha" => "1998" "volumen" => "316" "paginaInicial" => "668" "paginaFinal" => "672" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9522793" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of long term treatment with inhaled budesonide on adult height in children with asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L. Agertoft" 1 => "S. Pedersen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM200010123431502" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2000" "volumen" => "343" "paginaInicial" => "1064" "paginaFinal" => "1069" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11027740" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of inhaled corticosteroids and risk of cataracts" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.G. Cumming" 1 => "P. Mitchell" 2 => "S.R. Leeder" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199707033370102" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1997" "volumen" => "337" "paginaInicial" => "8" "paginaFinal" => "14" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9203425" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of inhaled corticosteroid use with cataract in elderly patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Garbe" 1 => "S. Suissa" 2 => "J. 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Fletcher" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Br J Opthalmol" "fecha" => "2003" "volumen" => "87" "paginaInicial" => "1247" "paginaFinal" => "1251" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Complications associated with immunosuppressive therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.I. Min" 1 => "A.P. Monaco" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pharmacotherapy" "fecha" => "1991" "volumen" => "11" "paginaInicial" => "119S" "paginaFinal" => "125S" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1745617" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunosuppressive effects and infections associated with corticosteroid therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G. Mukwaya" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Pediatr Infect Dis J" "fecha" => "1988" "volumen" => "7" "paginaInicial" => "499" "paginaFinal" => "504" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3043365" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberculosis emerging in patients treated with corticosteroids" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "O.C. Haanes" 1 => "A. 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Gopalan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med" "fecha" => "1996" "volumen" => "100" "paginaInicial" => "186" "paginaFinal" => "192" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8629653" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberculin skin testing of hospitalized patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K.F. Woeltje" 1 => "C.M. Kilo" 2 => "K. Johnson" 3 => "J. Primack" 4 => "V.J. Fraser" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Infect Control Hosp Epidemiol" "fecha" => "1997" "volumen" => "18" "paginaInicial" => "561" "paginaFinal" => "565" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9276237" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Skin testing with Mycobacterium avium to identify infection with M avium complex in patients with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Pinto-Powell" 1 => "K.N. Olivier" 2 => "B.J. Marsh" 3 => "S. Donaldson" 4 => "H. Worth-Parker" 5 => "W. Boyle" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "1996" "volumen" => "22" "paginaInicial" => "560" "paginaFinal" => "562" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8852979" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glucocorticosteroids 2: the clinical responses" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "H.N. Claman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Hosp Pract" "fecha" => "1983" "volumen" => "7" "paginaInicial" => "143" "paginaFinal" => "151" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Corticosteroid-mediated immunoregulation in man" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "T.R. Cupps" 1 => "A.S. Fauci" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Immunol Rev" "fecha" => "1982" "volumen" => "65" "paginaInicial" => "133" "paginaFinal" => "147" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6214495" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanisms of glucocorticoid action on immune processes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.E. Parrillo" 1 => "A.S. Fauci" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev.pa.19.040179.001143" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Pharmacol Toxicol" "fecha" => "1979" "volumen" => "19" "paginaInicial" => "179" "paginaFinal" => "201" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/222199" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of prolonged use of inhaled steroids on the cellular immunity of children with asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Levy" 1 => "I. Zalkinder" 2 => "O. Kuperman" 3 => "A. Skibin" 4 => "R. Apte" 5 => "J.E. Bearman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "1995" "volumen" => "95" "paginaInicial" => "806" "paginaFinal" => "812" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7722159" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of high-dose inhaled fluticasone propionate via spacer on cell-mediated immunity in healthy volunteers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.C. Sharma" 1 => "D. Stevens" 2 => "L. Casey" 3 => "S. Kesten" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2000" "volumen" => "118" "paginaInicial" => "1042" "paginaFinal" => "1048" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11035675" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High dose inhaled fluticasone and delayed hypersensitivity skin testing" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R.W. England" 1 => "J.S. Nugent" 2 => "K.W. Grathwohl" 3 => "L. Hagan" 4 => "J.M. Quinn" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2003" "volumen" => "123" "paginaInicial" => "1014" "paginaFinal" => "1017" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12684288" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical pulmonary tuberculosis in an asthmatic patient using a steroid aerosol" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.J. Horton" 1 => "S.L. Spector" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "1977" "volumen" => "71" "paginaInicial" => "540" "paginaFinal" => "542" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/852327" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulmonary tuberculosis in patients treated with inhaled beclomethasone" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "W.A. Shaikh" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Allergy" "fecha" => "1992" "volumen" => "47" "paginaInicial" => "327" "paginaFinal" => "330" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1443454" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Severe chickenpox after intranasal use of corticosteroids" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.J. Abzug" 1 => "M.F. Cotton" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Pediatr" "fecha" => "1993" "volumen" => "123" "paginaInicial" => "577" "paginaFinal" => "579" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8410510" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "FDA Medical Bulletin 1991;3." ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Position statement: inhaled glucocorticoids and severe viral infections" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "American Academy of Allergy and Immunology" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "1993" "paginaInicial" => "223" "paginaFinal" => "228" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7410746" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:3 [ "identificador" => "xack31872" "titulo" => "Acknowledgement" "texto" => "The authors would like to thank Jeffrey Gornbein, DrPH, SBCC for statistical computation support." ] ] ] "idiomaDefecto" => "en" "url" => "/03010546/0000004000000002/v1_201304101104/S0301054611003594/v1_201304101104/en/main.assets" "Apartado" => array:4 [ "identificador" => "5554" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/03010546/0000004000000002/v1_201304101104/S0301054611003594/v1_201304101104/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054611003594?idApp=UINPBA00004N"]

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C. Lee

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christina.h.lee@hotmail.com

Corresponding author.

, W.B. Klaustermeyer

Department of Medicine, Division of Allergy and Immunology, VA Greater Los Angeles Healthcare System/University of California Los Angeles, Los Angeles, CA, United States

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    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Effect of high dose inhaled corticosteroids on cell mediated immunity in patients with asthma"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Asthma is a variable and chronic inflammatory disease of the airways&#46; The inflammatory disorder underlying asthma arises from the interaction of various cells including eosinophils&#44; mast cells and T lymphocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Thus&#44; anti-inflammatory therapy&#44; in the form of inhaled corticosteroids&#44; is key in the management of persistent asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> As the prevalence of asthma has been increasing&#44; so has the use of inhaled corticosteroids&#44; and at higher doses than previously prescribed early in its introduction&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Recent studies have shown that inhaled corticosteroids have systemic effects on bone metabolism&#44;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;8</span></a> hypothalamus&#8211;pituitary adrenal axis&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;15</span></a> on linear growth&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;18</span></a> and cataracts&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#8211;21</span></a> Oral corticosteroids have an even more potent effect on these parameters&#44; and additionally have been shown to suppress cell mediated immunity&#44; increasing an individual&#39;s susceptibility of acquiring an opportunistic infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#8211;31</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">It is unclear at this time whether high dose inhaled corticosteroids also suppress cell mediated immunity&#46; Studies addressing this issue have been conflicting thus far&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32&#8211;34</span></a> Currently there are no data to suggest increased incidence or course of fungal&#44; viral or bacterial infections with the use of inhaled corticosteroids&#46; However&#44; there are rare cases that have been reported of reactivation of tuberculosis or viral infections associated with the use of inhaled corticosteroids&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35&#8211;37</span></a> The US Food and Drug Administration has instructed the manufacturers of oral&#44; injectable and inhaled corticosteroids to include the warning about the possible risk of tuberculosis and viral infections with the use of these agents&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> However&#44; the American Academy of Allergy and Immunology issued a position statement&#44; stating that this warning is unwarranted&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The objective of our current study was to evaluate if there is a correlation between high dose inhaled corticosteroids and suppression of cell mediated immunity in asthmatics&#46; This was accomplished by determining if there was a statistically significant higher incidence of impaired cellular immunity &#40;as reflected in anergy or lower cumulative skin test scores to DTH testing&#41; in patients with asthma who have already been receiving high dose inhaled fluticasone for &#62;6 months compared to an age-matched control asthma population not on high dose inhaled corticosteroids&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Study design</span><p id="par0025" class="elsevierStylePara elsevierViewall">Eighteen volunteers with asthma between the ages of 42 and 67 were recruited for this cross-sectional study&#46; Informed consent was obtained from each subject prior to entry into the study and the protocol was approved by the local Institutional Review Board &#40;IRB B&#44; VA Promise No&#46; 0035&#41;&#46; Exclusion criteria included subjects who have received systemic corticosteroids or immunosupressants in the past 6 months&#44; patients with chronic diseases that may influence cell mediated immunity &#40;autoimmune disease&#44; malignancy or immunodeficiency&#41;&#44; or patients with a significant infection in the past 6 months&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Group A consisted of nine asthma patients who had been compliant with taking high dose inhaled corticosteroids &#40;defined as fluticasone&#47;salmeterol 500&#47;50<span class="elsevierStyleHsp" style=""></span>&#956;g twice daily or fluticasone propionate 220<span class="elsevierStyleHsp" style=""></span>&#956;g two puffs twice daily&#41; for at least 6 months duration&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Group B consisted of nine volunteers with mild intermittent asthma who had been treated with albuterol as needed only&#44; without exposure to inhaled corticosteroids&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Cell mediated immunity was compared between volunteers of group A and group B by DTH skin testing&#46; To account for differences that may be related to age&#44; each volunteer in group A was age matched within 3 years to a volunteer in group B&#44; resulting in a comparable spread of age between the two groups&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">DTH skin testing and interpretation</span><p id="par0045" class="elsevierStylePara elsevierViewall">DTH skin testing was performed in our study using the standard Mantoux technique&#46; Intradermal injections of 0&#46;1<span class="elsevierStyleHsp" style=""></span>mL of candida &#40;Candin&#59; Allermed Laboratories&#59; San Diego&#44; CA&#44; USA&#41; and tetanus &#40;Tetanus Toxoid USP&#59; Aventis Pasteur&#41; were placed on the volar aspect of the forearm&#46; Results were read by a single blinded individual for all subjects 48<span class="elsevierStyleHsp" style=""></span>h after placement using the ballpoint pen technique to measure the induration at each site&#46; Orthogonal diameters were measured&#44; and the average of these diameters was recorded&#46; A mean induration of &#8805;2<span class="elsevierStyleHsp" style=""></span>mm was considered positive&#46; A cumulative skin test score was calculated by adding the mean diameters of positive reactions&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">The non-parametric Wilcoxon rank sum test and the parametric <span class="elsevierStyleItalic">t</span> test were both used to compute <span class="elsevierStyleItalic">p</span> values for comparing means between the inhaled corticosteroid group &#40;group A&#41; and the albuterol only &#40;group B&#41; in total skin test score for candida and tetanus individually&#44; total skin test score for candida plus tetanus&#44; as well as difference in incidence of anergy&#46; A statistically significant result was defined as <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46; Means<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SEM are reported&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">Eighteen volunteer subjects completed this study&#46; Subjects ranged in age from 42 to 67 years &#40;mean&#44; 57&#46;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;6&#41;&#46; One subject in the study was lost to follow up&#46; There were no significant adverse events experienced in the 18 subjects who completed the study&#46; The most common complaint was mild pruritis at the site of skin testing&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a> depict the sum of mean orthogonal diameters for candida and tetanus skin test score individually as well as for the candida plus tetanus total skin test score for the high dose inhaled corticosteroid group &#40;group A&#41; and no inhaled corticosteroid group &#40;group B&#41;&#44; respectively&#46; The mean candida skin test score of 3&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;03<span class="elsevierStyleHsp" style=""></span>mm and 4&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;76 in the inhaled corticosteroid group and albuterol only group&#44; respectively&#44; was not significantly different statistically &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;714 using <span class="elsevierStyleItalic">t</span>-test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;594 using Wilcoxon rank sum test&#41;&#46; The mean tetanus skin test score of 4&#46;89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;12 and 5&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;11 in the inhaled corticosteroid group and albuterol only group&#44; respectively&#44; was also not significantly different statistically &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;782 using <span class="elsevierStyleItalic">t</span>-test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;721 using Wilcoxon rank sum test&#41;&#46; Comparison of the mean candida plus tetanus total skin test score of 8&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;91 and 9&#46;67<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;37 in the inhaled corticosteroid group and albuterol only group&#44; respectively&#44; showed no statistically significant difference &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;642 using <span class="elsevierStyleItalic">t</span>-test&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;824 using Wilcoxon rank sum test&#41;&#46; Finally&#44; there was no significant difference in the incidence of anergy between the two study groups&#46; The largest mean difference in standard deviation &#40;SD&#41; units is a mean difference of 0&#46;225 SD units for candida plus tetanus&#46; To confirm that this difference is statistically significant with 80&#37; power would require a sample size in excess of 300&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">Inhaled corticosteroids have been demonstrated to have adverse effects on bone metabolism&#44; hypothalamus&#8211;pituitary adrenal axis&#44; linear growth&#44; and cataracts&#44; like systemic corticosteroids&#44; but to a lesser degree&#46; However&#44; studies evaluating whether inhaled corticosteroids impair cell mediated immunity have been conflicting and inconclusive thus far&#46; An early study by Levy et al&#46; found no suppression of cell mediated immunity in children with asthma treated with lower dose inhaled corticosteroids&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Cell mediated immunity was evaluated with immune parameters including differential white blood count&#44; T and B cell numbers&#44; T helper and suppressor counts&#44; T cell mitogenic transformation&#44; and IL-1 and IL-2 secretion&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> Recently&#44; two studies evaluated the effects of high dose inhaled corticosteroids on cell mediated immunity&#46; Sharma et al&#46; showed suppression of cell mediated immunity determined by delayed hypersensitivity skin testing &#40;using Multi-test&#41; in nine healthy patients after 4 weeks of high dose inhaled fluticasone compared to baseline&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> However&#44; this study was faulted for using Multi-test&#44; as the American Thoracic Society does not recommend multipuncture devices for DTH testing due to the possibility of administering inconsistent amounts of antigen &#40;17&#41;&#46; England et al&#46; conversely showed no suppression of cell mediated immunity determined by delayed hypersensitivity skin testing &#40;using standard Mantoux technique&#41; in 18 healthy subjects after 4 weeks of high dose inhaled fluticasone compared to baseline testing&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> However&#44; it is important to evaluate DTH testing in asthmatics &#40;not healthy volunteers&#41; receiving inhaled corticosteroids for a longer duration&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">In our present study&#44; patients with asthma treated with high dose inhaled corticosteroids for at least 6 months did not have reduced cellular immunity in comparison to asthma patients taking albuterol as needed only without inhaled corticosteroids&#46; There was no statistically significant difference for cell mediated immunity by DTH testing using the Mantoux technique&#46; At this time&#44; there are no data to suggest increased incidence or altered course of fungal&#44; viral or bacterial infections with the use of inhaled corticosteroids&#46; There are only rare case reports of reactivation of tuberculosis or viral infections associated with the use of inhaled corticosteroids&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35&#8211;37</span></a> Our findings are in agreement with those of England et al&#46; who found no suppression of cell mediated immunity after 28 days of treatment with high dose inhaled corticosteroids&#46; However&#44; we do acknowledge that there is a wide spread of values obtained in our study&#44; the significance of which is unclear due to the small number of subjects&#46; Further studies with larger numbers of asthma patients followed prospectively with DTH testing both before and after 6 months of therapy may be warranted&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Funding</span><p id="par0075" class="elsevierStylePara elsevierViewall">Research conducted at VA Greater Los Angeles Healthcare System&#59; Los Angeles&#44; CA&#46; Research non-funded and approved by local IRB Board&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">Dr&#46; Lee and Dr&#46; Klaustermeyer have no conflicts of interest to disclose&#46;</p></span></span>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Cell mediated immunity is suppressed by systemic corticosteroids&#46; Inhaled corticosteroids have been shown to affect parameters including bone metabolism&#44; hypothalamus&#8211;pituitary adrenal axis&#44; linear growth&#44; and lead to the development of cataracts&#46; However&#44; it is unclear if high dose inhaled corticosteroid therapy affects cell mediated immunity&#46;</p> <span class="elsevierStyleSectionTitle">Study objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To evaluate if asthma patients taking high dose inhaled corticosteroids chronically have reduced cell mediated immunity compared to asthma patients not taking inhaled corticosteroids&#46;</p> <span class="elsevierStyleSectionTitle">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Eighteen asthmatic subjects participated in this cross-sectional study&#46; Cell mediated immunity was evaluated in nine patients who had been taking high dose inhaled corticosteroids for &#62;6 months and nine patients not taking inhaled corticosteroids&#46; Cell mediated immunity was evaluated by delayed type hypersensitivity &#40;DTH&#41; skin testing with intradermal placement of candida and tetanus antigens&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">There was no significant difference in DTH skin test results between the high dose inhaled corticosteroid and no corticosteroid treated asthma group&#46;</p> <span class="elsevierStyleSectionTitle">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Patients with asthma taking high dose inhaled corticosteroids chronically &#40;&#62;6 months&#41; did not have significantly greater impaired cell mediated immunity than patients not taking inhaled corticosteroids in this study&#46;</p>"
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                  """
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              "imagenFichero" => array:1 [
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        "descripcion" => array:1 [
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      1 => array:7 [
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">DTH skin test results &#40;millimetres of induration&#41; evaluating cell mediated immunity in the no inhaled corticosteroid group&#46;</p>"
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      "titulo" => "References"
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        0 => array:2 [
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            0 => array:3 [
              "identificador" => "bib0005"
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                0 => array:1 [
                  "referenciaCompleta" => "National Asthma Education and Prevention Program Expert Panel Report 3&#58; guidelines for the diagnosis and management of asthma&#59; 2003&#46;"
                ]
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            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glucocorticoid therapy for asthma&#58; clinical pharmacology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "S&#46;J&#46; Szefler"
                          ]
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1991"
                        "volumen" => "88"
                        "paginaInicial" => "147"
                        "paginaFinal" => "165"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1880315"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Beclomethasone inhalation decreases serum osteocalcin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46;M&#46; Pouw"
                            1 => "M&#46;F&#46; Prummel"
                            2 => "H&#46; Oosting"
                            3 => "C&#46;M&#46; Roos"
                            4 => "E&#46; Endert"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "1991"
                        "volumen" => "302"
                        "paginaInicial" => "627"
                        "paginaFinal" => "628"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2012877"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Decreased bone mineral density in premenopausal asthma patients receiving long-term inhaled steroid therapy for asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Ip"
                            1 => "K&#46; Lam"
                            2 => "L&#46; Yam"
                            3 => "A&#46; Kung"
                            4 => "M&#46; Ng"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "1994"
                        "volumen" => "105"
                        "paginaInicial" => "1722"
                        "paginaFinal" => "1727"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8205866"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of dose and dosing schedule of inhaled budesonide on bone turnover"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "J&#46;H&#46; Toogood"
                            1 => "B&#46;H&#46; Jennings"
                            2 => "A&#46;B&#46; Hodsman"
                            3 => "J&#46; Baskerville"
                            4 => "L&#46;I&#46; Fraher"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
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                        "paginaInicial" => "572"
                        "paginaFinal" => "580"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1918724"
                            "web" => "Medline"
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                ]
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              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled corticosteroid use and bone mineral density in patients with asthma"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46;A&#46; Wong"
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                            2 => "C&#46;J&#46; Smith"
                            3 => "A&#46;F&#46; Wisniewski"
                            4 => "S&#46;A&#46; Lewis"
                            5 => "R&#46; Hubbard"
                          ]
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                      ]
                    ]
                  ]
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                    0 => array:2 [
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                        "tituloSerie" => "Lancet"
                        "fecha" => "2000"
                        "volumen" => "355"
                        "paginaInicial" => "1399"
                        "paginaFinal" => "1403"
                        "link" => array:1 [
                          0 => array:2 [
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                  ]
                ]
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              "identificador" => "bib0035"
              "etiqueta" => "7"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Inhaled corticosteroid and hip fracture&#58; a population based case&#8211;control study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
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                            4 => "A&#46;E&#46; Tattersfield"
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                    0 => array:2 [
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                        "tituloSerie" => "Am J Resp Crit Care Med"
                        "fecha" => "2002"
                        "volumen" => "166"
                        "paginaInicial" => "1563"
                        "paginaFinal" => "1566"
                        "link" => array:1 [
                          0 => array:2 [
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              "identificador" => "bib0040"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Use of inhaled corticosteroids and risk of fracture"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "R&#46; Hubbard"
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                            2 => "C&#46; Smith"
                            3 => "J&#46; West"
                            4 => "L&#46; Smeeth"
                            5 => "A&#46; Fletcher"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.130.4.1082"
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                        "tituloSerie" => "Chest"
                        "fecha" => "2006"
                        "volumen" => "130"
                        "paginaInicial" => "1082"
                        "paginaFinal" => "1088"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17035441"
                            "web" => "Medline"
                          ]
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              ]
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              "identificador" => "bib0045"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Diurnal cortisol secretion during therapy with inhaled beclomethasone dipropionate in children with asthma"
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                          "etal" => false
                          "autores" => array:2 [
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
                        "fecha" => "1991"
                        "volumen" => "118"
                        "paginaInicial" => "294"
                        "paginaFinal" => "297"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1993964"
                            "web" => "Medline"
                          ]
                        ]
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              "identificador" => "bib0050"
              "etiqueta" => "10"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Integrate plasma cortisol concentration in children with asthma receiving long term inhaled corticosteroids"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            2 => "E&#46; Leiberman"
                            3 => "Z&#46; Zadik"
                            4 => "Y&#46; Giat"
                            5 => "J&#46; Levy"
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                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Pulmonol"
                        "fecha" => "1992"
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                        "paginaInicial" => "84"
                        "paginaFinal" => "89"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1315017"
                            "web" => "Medline"
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              "identificador" => "bib0055"
              "etiqueta" => "11"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Systemic bioavailability and potency of high dose inhaled corticosteroids"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "D&#46; Wales"
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                            4 => "R&#46; O&#8217;Driscoll"
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                        ]
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
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                        "tituloSerie" => "Chest"
                        "fecha" => "1999"
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                        "paginaInicial" => "1278"
                        "paginaFinal" => "1284"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10334140"
                            "web" => "Medline"
                          ]
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              "identificador" => "bib0060"
              "etiqueta" => "12"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Dose response effect for adrenal suppression with repeated twice daily inhaled fluticasone propionate and triamcinolone acetonide in adult asthmatics"
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                        0 => array:2 [
                          "etal" => false
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                    0 => array:2 [
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                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1997"
                        "volumen" => "156"
                        "paginaInicial" => "1274"
                        "paginaFinal" => "1277"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9351634"
                            "web" => "Medline"
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                        "tituloSerie" => "Arch Intern Med"
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                        "paginaInicial" => "941"
                        "paginaFinal" => "955"
                        "link" => array:1 [
                          0 => array:2 [
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                      "doi" => "10.1016/S1081-1206(10)62918-3"
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                        "tituloSerie" => "Ann Allergy Asthma Immunol"
                        "fecha" => "2001"
                        "volumen" => "87"
                        "paginaInicial" => "379"
                        "paginaFinal" => "385"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11730179"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of long term inhaled corticosteroid on adrenal function in a patient with asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; White"
                            1 => "T&#46; Crisalida"
                            2 => "H&#46; Li"
                            3 => "A&#46; Economides"
                            4 => "M&#46; Kaliner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1081-1206(10)60911-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol"
                        "fecha" => "2006"
                        "volumen" => "96"
                        "paginaInicial" => "437"
                        "paginaFinal" => "444"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16597078"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Growth of asthmatic children during treatment with budesonide&#58; a double blind trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "O&#46;D&#46; Wolthers"
                            1 => "S&#46; Pedersen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "1991"
                        "volumen" => "303"
                        "paginaInicial" => "163"
                        "paginaFinal" => "165"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1878641"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of asthma and its treatment on growth&#58; four year follow up of cohort of children from general practices in Tayside&#44; Scotland"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46; McCowan"
                            1 => "R&#46;G&#46; Neville"
                            2 => "G&#46;E&#46; Thomas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "1998"
                        "volumen" => "316"
                        "paginaInicial" => "668"
                        "paginaFinal" => "672"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9522793"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of long term treatment with inhaled budesonide on adult height in children with asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "L&#46; Agertoft"
                            1 => "S&#46; Pedersen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM200010123431502"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2000"
                        "volumen" => "343"
                        "paginaInicial" => "1064"
                        "paginaFinal" => "1069"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11027740"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of inhaled corticosteroids and risk of cataracts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46;G&#46; Cumming"
                            1 => "P&#46; Mitchell"
                            2 => "S&#46;R&#46; Leeder"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJM199707033370102"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "1997"
                        "volumen" => "337"
                        "paginaInicial" => "8"
                        "paginaFinal" => "14"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9203425"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association of inhaled corticosteroid use with cataract in elderly patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "E&#46; Garbe"
                            1 => "S&#46; Suissa"
                            2 => "J&#46; Lelorier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "1998"
                        "volumen" => "280"
                        "paginaInicial" => "539"
                        "paginaFinal" => "543"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9707144"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A population based case-controlled study of cataracts and inhaled corticosteroids"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "L&#46; Smeeth"
                            1 => "M&#46; Boulis"
                            2 => "R&#46; Hubbard"
                            3 => "A&#46;E&#46; Fletcher"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Br J Opthalmol"
                        "fecha" => "2003"
                        "volumen" => "87"
                        "paginaInicial" => "1247"
                        "paginaFinal" => "1251"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Complications associated with immunosuppressive therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;I&#46; Min"
                            1 => "A&#46;P&#46; Monaco"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacotherapy"
                        "fecha" => "1991"
                        "volumen" => "11"
                        "paginaInicial" => "119S"
                        "paginaFinal" => "125S"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1745617"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunosuppressive effects and infections associated with corticosteroid therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "G&#46; Mukwaya"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Infect Dis J"
                        "fecha" => "1988"
                        "volumen" => "7"
                        "paginaInicial" => "499"
                        "paginaFinal" => "504"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3043365"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberculosis emerging in patients treated with corticosteroids"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "O&#46;C&#46; Haanes"
                            1 => "A&#46; Bergmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Respir"
                        "fecha" => "1983"
                        "volumen" => "64"
                        "paginaInicial" => "294"
                        "paginaFinal" => "297"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Reversion and reconversion rate of tuberculin skin reactions in correlation with the use of prednisone"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Bovornkitti"
                            1 => "P&#46; Kangsadal"
                            2 => "P&#46; Sathirapat"
                            3 => "P&#46; Oonsombatti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Dis Chest"
                        "fecha" => "1960"
                        "volumen" => "38"
                        "paginaInicial" => "51"
                        "paginaFinal" => "53"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13803423"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberculin skin test reactivity&#44; anergy&#44; and HIV infection in hospitalized patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;M&#46; Janis"
                            1 => "D&#46;W&#46; Allen"
                            2 => "M&#46;J&#46; Glesby"
                            3 => "L&#46;A&#46; Carey"
                            4 => "L&#46;M&#46; Mundy"
                            5 => "R&#46; Gopalan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med"
                        "fecha" => "1996"
                        "volumen" => "100"
                        "paginaInicial" => "186"
                        "paginaFinal" => "192"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8629653"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tuberculin skin testing of hospitalized patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "K&#46;F&#46; Woeltje"
                            1 => "C&#46;M&#46; Kilo"
                            2 => "K&#46; Johnson"
                            3 => "J&#46; Primack"
                            4 => "V&#46;J&#46; Fraser"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Infect Control Hosp Epidemiol"
                        "fecha" => "1997"
                        "volumen" => "18"
                        "paginaInicial" => "561"
                        "paginaFinal" => "565"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9276237"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Skin testing with <span class="elsevierStyleItalic">Mycobacterium avium</span> to identify infection with <span class="elsevierStyleItalic">M avium</span> complex in patients with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Pinto-Powell"
                            1 => "K&#46;N&#46; Olivier"
                            2 => "B&#46;J&#46; Marsh"
                            3 => "S&#46; Donaldson"
                            4 => "H&#46; Worth-Parker"
                            5 => "W&#46; Boyle"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "1996"
                        "volumen" => "22"
                        "paginaInicial" => "560"
                        "paginaFinal" => "562"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8852979"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glucocorticosteroids 2&#58; the clinical responses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "H&#46;N&#46; Claman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Hosp Pract"
                        "fecha" => "1983"
                        "volumen" => "7"
                        "paginaInicial" => "143"
                        "paginaFinal" => "151"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Corticosteroid-mediated immunoregulation in man"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "T&#46;R&#46; Cupps"
                            1 => "A&#46;S&#46; Fauci"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunol Rev"
                        "fecha" => "1982"
                        "volumen" => "65"
                        "paginaInicial" => "133"
                        "paginaFinal" => "147"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6214495"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Mechanisms of glucocorticoid action on immune processes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;E&#46; Parrillo"
                            1 => "A&#46;S&#46; Fauci"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1146/annurev.pa.19.040179.001143"
                      "Revista" => array:6 [
                        "tituloSerie" => "Annu Rev Pharmacol Toxicol"
                        "fecha" => "1979"
                        "volumen" => "19"
                        "paginaInicial" => "179"
                        "paginaFinal" => "201"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/222199"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of prolonged use of inhaled steroids on the cellular immunity of children with asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Levy"
                            1 => "I&#46; Zalkinder"
                            2 => "O&#46; Kuperman"
                            3 => "A&#46; Skibin"
                            4 => "R&#46; Apte"
                            5 => "J&#46;E&#46; Bearman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1995"
                        "volumen" => "95"
                        "paginaInicial" => "806"
                        "paginaFinal" => "812"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7722159"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of high-dose inhaled fluticasone propionate via spacer on cell-mediated immunity in healthy volunteers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "K&#46;C&#46; Sharma"
                            1 => "D&#46; Stevens"
                            2 => "L&#46; Casey"
                            3 => "S&#46; Kesten"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2000"
                        "volumen" => "118"
                        "paginaInicial" => "1042"
                        "paginaFinal" => "1048"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11035675"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "High dose inhaled fluticasone and delayed hypersensitivity skin testing"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46;W&#46; England"
                            1 => "J&#46;S&#46; Nugent"
                            2 => "K&#46;W&#46; Grathwohl"
                            3 => "L&#46; Hagan"
                            4 => "J&#46;M&#46; Quinn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
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                        "fecha" => "2003"
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                        "paginaInicial" => "1014"
                        "paginaFinal" => "1017"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12684288"
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                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical pulmonary tuberculosis in an asthmatic patient using a steroid aerosol"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;J&#46; Horton"
                            1 => "S&#46;L&#46; Spector"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "1977"
                        "volumen" => "71"
                        "paginaInicial" => "540"
                        "paginaFinal" => "542"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/852327"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pulmonary tuberculosis in patients treated with inhaled beclomethasone"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "W&#46;A&#46; Shaikh"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Allergy"
                        "fecha" => "1992"
                        "volumen" => "47"
                        "paginaInicial" => "327"
                        "paginaFinal" => "330"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1443454"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0185"
              "etiqueta" => "37"
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                0 => array:2 [
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                      "titulo" => "Severe chickenpox after intranasal use of corticosteroids"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46;J&#46; Abzug"
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                    ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pediatr"
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                        "volumen" => "123"
                        "paginaInicial" => "577"
                        "paginaFinal" => "579"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8410510"
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                    ]
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                ]
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              "identificador" => "bib0195"
              "etiqueta" => "39"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Position statement&#58; inhaled glucocorticoids and severe viral infections"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "American Academy of Allergy and Immunology"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1993"
                        "paginaInicial" => "223"
                        "paginaFinal" => "228"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7410746"
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                    ]
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              ]
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Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2011.11.001

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	13	1	14
2024 October	50	6	56
2024 September	49	4	53
2024 August	51	6	57
2024 July	81	6	87
2024 June	61	4	65
2024 May	36	4	40
2024 April	96	6	102
2024 March	61	4	65
2024 February	71	8	79
2024 January	78	10	88
2023 December	55	11	66
2023 November	68	22	90
2023 October	93	15	108
2023 September	69	5	74
2023 August	53	9	62
2023 July	79	5	84
2023 June	53	5	58
2023 May	112	1	113
2023 April	101	2	103
2023 March	103	4	107
2023 February	72	9	81
2023 January	71	6	77
2022 December	67	8	75
2022 November	42	12	54
2022 October	29	16	45
2022 September	23	15	38
2022 August	22	6	28
2022 July	13	12	25
2022 June	13	4	17
2022 May	14	7	21
2022 April	19	7	26
2022 March	18	10	28
2022 February	20	6	26
2022 January	15	11	26
2021 December	14	9	23
2021 November	9	7	16
2021 October	13	17	30
2021 September	9	11	20
2021 August	6	11	17
2021 July	10	11	21
2021 June	16	8	24
2021 May	16	7	23
2021 April	28	13	41
2021 March	8	4	12
2021 February	13	11	24
2021 January	11	8	19
2020 December	1	0	1
2020 August	0	1	1
2020 July	0	1	1
2020 May	0	1	1
2020 April	0	1	1
2020 March	0	1	1
2020 February	0	1	1
2020 January	0	4	4
2019 December	0	3	3
2019 June	0	9	9
2019 May	0	19	19
2019 April	0	4	4
2019 March	0	1	1
2019 February	0	1	1
2019 January	0	1	1
2018 December	0	7	7
2018 February	7	0	7
2018 January	12	1	13
2017 December	9	0	9
2017 November	8	3	11
2017 October	16	2	18
2017 September	17	0	17
2017 August	15	1	16
2017 July	21	2	23
2017 June	9	1	10
2017 May	18	6	24
2017 April	15	10	25
2017 March	12	18	30
2017 February	15	3	18
2017 January	19	2	21
2016 December	12	1	13
2016 November	14	1	15
2016 October	30	3	33
2016 September	35	10	45
2016 August	18	3	21
2016 July	15	3	18
2016 June	15	4	19
2016 May	14	5	19
2016 April	20	13	33
2016 March	8	5	13
2016 February	15	13	28
2016 January	11	7	18
2015 December	15	4	19
2015 November	13	5	18
2015 October	17	7	24
2015 September	16	4	20
2015 August	39	2	41
2015 July	18	5	23
2015 June	12	3	15
2015 May	17	2	19
2015 April	21	8	29
2015 March	16	9	25
2015 February	11	2	13
2015 January	21	4	25
2014 December	27	3	30
2014 November	15	3	18
2014 October	26	6	32
2014 September	30	4	34
2014 August	22	2	24
2014 July	4	2	6
2014 June	12	0	12
2014 May	10	2	12
2014 April	12	1	13
2014 March	37	6	43
2014 February	49	6	55
2014 January	13	5	18
2013 December	31	10	41
2013 November	82	5	87
2013 October	71	10	81
2013 September	56	9	65
2013 August	90	5	95
2013 July	108	17	125
2013 June	15	4	19
2013 May	25	5	30
2013 April	14	10	24
2013 March	11	6	17
2013 February	8	6	14
2013 January	8	4	12
2012 December	3	2	5
2012 November	1	4	5
2012 October	1	2	3
2012 September	1	1	2
2012 March	752	0	752

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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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