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A critical appraisal on AIT in childhood asthma.

ABSTRACT: Abstract:Allergen immunotherapy (AIT) is the only disease-modifying treatment approved for allergic rhinitis and allergic asthma and represents a suitable therapeutic option, especially in childhood, to modify the progression of respiratory allergic diseases. Starting from the previous "generic class effect" evaluation, as testified by the numerous meta analyses, AIT is now considered a product-specific pathogenic-oriented treatment. Background:AIT was empirically proposed more than one century ago in the subcutaneous form (SCIT), but the IgE-mediated mechanism of allergy was elucidated only after 50 years of clinical use of the treatment. The sublingual administration (SLIT) was developed during the 1980 ties, to achieve an improvement in safety and convenience. While SCIT is approved in the United States for the treatment of asthmatic patients with more than 12 years, so far few trials evaluated the clinical efficacy and safety of SLIT in children with allergic asthma, although the indications and some aspects remain unclear. Certainly, due to compliance problems, the age below 3 years may be reasonably considered a practical contraindication. Conclusions:Given that some specific AIT products are effective and approved as drugs (AIFA, EMA, FDA), the use in children is still debated. Some aspects still need robust confirm: (a) the safety of AIT in asthma; (b) the optimal regimen of administration; (c) the role of AIT as preventative treatment for asthma development.

SUBMITTER: Ferrando M

PROVIDER: S-EPMC5839070 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A critical appraisal on AIT in childhood asthma.

Ferrando Matteo M Racca Francesca F Madeira Lorena Nascimento Girardi LNG Heffler Enrico E Passalacqua Giovanni G Puggioni Francesca F Stomeo Niccolò N Canonica Giorgio Walter GW

Clinical and molecular allergy : CMA 20180306

<h4>Abstract</h4>Allergen immunotherapy (AIT) is the only disease-modifying treatment approved for allergic rhinitis and allergic asthma and represents a suitable therapeutic option, especially in childhood, to modify the progression of respiratory allergic diseases. Starting from the previous "generic class effect" evaluation, as testified by the numerous meta analyses, AIT is now considered a product-specific pathogenic-oriented treatment.<h4>Background</h4>AIT was empirically proposed more th ...[more]

PMID: 29527129

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Project description:BackgroundInterleukin-6 (IL-6) contributes to numerous inflammatory, metabolic, and physiologic pathways of disease. We evaluated four IL-6 immunoassays in order to identify a reliable assay for studies of metabolic and physical function. Serial plasma samples from intravenous glucose tolerance tests (IVGTTs), with expected rises in IL-6 concentrations, were used to test the face validity of the various assays.Methods and findingsIVGTTs, administered to 14 subjects, were performed with a single infusion of glucose (0.3 g/kg body mass) at time zero, a single infusion of insulin (0.025 U/kg body mass) at 20 minutes, and frequent blood collection from time zero to 180 minutes for subsequent Il-6 measurement. The performance metrics of four IL-6 detection methods were compared: Meso Scale Discovery immunoassay (MSD), an Invitrogen Luminex bead-based multiplex panel (LX), an Invitrogen Ultrasensitive Luminex bead-based singleplex assay (ULX), and R&D High Sensitivity ELISA (R&D). IL-6 concentrations measured with MSD, R&D and ULX correlated with each other (Pearson Correlation Coefficients r = 0.47-0.94, p<0.0001) but only ULX correlated (r = 0.31, p = 0.0027) with Invitrogen Luminex. MSD, R&D, and ULX, but not LX, detected increases in IL-6 in response to glucose. All plasma samples were measurable by MSD, while 35%, 1%, and 4.3% of samples were out of range when measured by LX, ULX, and R&D, respectively. Based on representative data from the MSD assay, baseline plasma IL-6 (0.90 ± 0.48 pg/mL) increased significantly as expected by 90 minutes (1.29 ± 0.59 pg/mL, p = 0.049), and continued rising through 3 hours (4.25 ± 3.67 pg/mL, p = 0.0048).ConclusionThis study established the face validity of IL-6 measurement by MSD, R&D, and ULX but not LX, and the superiority of MSD with respect to dynamic range. Plasma IL-6 concentrations increase in response to glucose and insulin, consistent with both an early glucose-dependent response (detectable at 1-2 hours) and a late insulin-dependent response (detectable after 2 hours).

Project description:Background Tobacco use is a leading preventable cause of morbidity and mortality globally. Clinical practice guidelines for the treatment of tobacco use dependence are of varied scope and quality, making it challenging for users to select and apply recommendations. Objective The study objective is to identify and critically appraise the quality of existing clinical practice guidelines for tobacco cessation. Setting The study occurred between collaborative academic institutions located in Qatar and New Zealand. Methods A systematic literature search was performed for the period 2006-2018 through the following databases: PubMed, EMBASE, CINAHL, ISI Web of Science, Scopus, National Guideline Clearing House, Campbell Library, Health System Evidence, Joanna Briggs Institute Evidence-Based Practice Database, Academic Search Complete, ProQuest, PROSPERO, and Google Scholar. Relevant professional societies' and health agencies' websites were also searched. Two reviewers independently extracted and assessed guidelines' quality using Appraisal of Guidelines, Research and Evaluation II (AGREE II) instrument. Main outcome measure Standardized domain scores according to the AGREE II instrument. Results 7741 hits were identified. After removing duplicates and screening, 24 guidelines were included. Highest guideline quality was for National Institute for Health and Care Excellence (NICE) guideline with an overall ranking score of 87.56% and least quality was for Japanese Circulation Society Joint Working Group with an overall score of 29.34%. Domain 4 of AGREE II (clarity of presentation) had the highest average quality score (70.95%), while the lowest average quality scores were for Domain 2 (Rigour of Development) (50.21%) and Domain 5 (Applicability) (45.05%). Conclusion Seven guidelines were judged to be of high quality (overall score of ≥ 70%). Future guidelines for tobacco dependence treatment should use rigorous methods of development and provide applicable recommendations.

Project description:Background: Nasal epithelia are emerging as a proxy measure of gene expression of the airway epithelium in asthma. We hypothesized that epigenetic marks regulate gene expression of the nasal epithelia and consequently may provide a novel target for allergic asthma. Methods: We compared genomic DNA methylation patterns and gene expression in African American children with persistent atopic asthma [N=36] versus healthy controls [N=36]. Results were validated in an independent population of asthmatics [N=30]. Results: We identified 186 genes with significant methylation changes, either as regions (differentially methylated regions [DMRs]) or single CpGs (differentially methylated probes [DMPs]) after adjustment for age, gender, race/ethnicity, batch effects, inflation, and multiple comparisons (false discovery rate-adjusted q<0.05). Genes differentially methylated include those with established roles in asthma and atopy, components of the extracellular matrix, genes related to immunity, cell adhesion, epigenetic regulation, and airway obstruction. The methylation changes are large (median 9.5%, range: 2.6-29.5% methylation change) and similar in magnitude to those observed in malignancies. Hypo- and hyper-methylated genes were associated with increased and decreased gene expression respectively (P<2.8x10-6 for DMRs and P<7.8x10-10 for DMPs). Quantitative analysis of methylation-expression relationships in 53 differentially expressed genes demonstrated that 32 (60%) have significant (q<0.05) methylation-expression relationships within 5kb of the gene. 10 loci selected based on the relevance to asthma, magnitude of methylation change, and asthma specific methylation-expression relationships were validated in an independent cohort of children with asthma. Conclusions: Our findings that epigenetic marks in respiratory epithelia are associated with allergic asthma in inner-city children provide new targets for biomarker development, and novel approaches to understanding disease pathogenesis. case control design with nasal epithelial cells from 36 atopic asthmatic and 36 nonatopic nonasthmatic children from the inner city

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A critical appraisal on AIT in childhood asthma.

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A critical appraisal on AIT in childhood asthma.

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