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      Approach to Patients with Severe Asthma: a Consensus Statement from the Respiratory Care Experts’ Input Forum (RC-EIF), Iran

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          Abstract

          Challenges in the assessment, diagnosis and management of severe, difficult-to-control asthma are increasingly regarded as clinical needs yet unmet. The assessments required to determine asthma severity, comorbidities and confounding factors, disease phenotypes and optimal treatment are among the controversial issues in the field.

          The respiratory care experts’ input forum (RC-EIF), comprised of an Iranian panel of experts, reviewed the definition, appraised the available guidelines and provided a consensus for evaluation and treatment of severe asthma in adults.

          A systematic literature review followed by discussions during and after the forum, yielded the present consensus. The expert panel used the appraisal of guidelines for research and evaluation-II (AGREE-II) protocol to define an initial locally-adapted strategy for the management of severe asthma.

          Severe asthma is considered a heterogeneous condition with various phenotypes. Issues such as assessment of difficult-to-control asthma, phenotyping, the use of blood and sputum eosinophil count, exhaled nitric oxide to guide therapy, the position of anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty as well as the use of established, recently-developed and evolving treatment approaches were discussed and unanimously agreed upon in the panel.

          A systematic approach is required to ensure proper diagnosis, evaluate compliance, and to identify comorbidities and triggering factors in severe asthma. Phenotyping helps select optimized treatment. The treatment approach laid down by the Global Initiative for Asthma (GINA) needs to be followed, while the benefit of using biological therapies should be weighed against the cost and safety concerns.

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          Most cited references163

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          AGREE II: advancing guideline development, reporting and evaluation in health care.

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            Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial.

            Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab. We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophilic inflammation. They were randomly assigned (in a 1:1:1:1 ratio) to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg) or matched placebo (100 mL 0·9% NaCl) with a central telephone-based system and computer-generated randomly permuted block schedule stratified by whether treatment with oral corticosteroids was required. Patients received 13 infusions at 4-week intervals. The primary outcome was the rate of clinically significant asthma exacerbations, which were defined as validated episodes of acute asthma requiring treatment with oral corticosteroids, admission, or a visit to an emergency department. Patients, clinicians, and data analysts were masked to treatment assignment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01000506. 621 patients were randomised: 159 were assigned to placebo, 154 to 75 mg mepolizumab, 152 to 250 mg mepolizumab, and 156 to 750 mg mepolizumab. 776 exacerbations were deemed to be clinically significant. The rate of clinically significant exacerbations was 2·40 per patient per year in the placebo group, 1·24 in the 75 mg mepolizumab group (48% reduction, 95% CI 31-61%; p<0·0001), 1·46 in the 250 mg mepolizumab group (39% reduction, 19-54%; p=0·0005), and 1·15 in the 750 mg mepolizumab group (52% reduction, 36-64%; p<0·0001). Three patients died during the study, but the deaths were not deemed to be related to treatment. Mepolizumab is an effective and well tolerated treatment that reduces the risk of asthma exacerbations in patients with severe eosinophilic asthma. GlaxoSmithKline. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              T-helper type 2-driven inflammation defines major subphenotypes of asthma.

              T-helper type 2 (Th2) inflammation, mediated by IL-4, IL-5, and IL-13, is considered the central molecular mechanism underlying asthma, and Th2 cytokines are emerging therapeutic targets. However, clinical studies increasingly suggest that asthma is heterogeneous. To determine whether this clinical heterogeneity reflects heterogeneity in underlying molecular mechanisms related to Th2 inflammation. Using microarray and polymerase chain reaction analyses of airway epithelial brushings from 42 patients with mild-to-moderate asthma and 28 healthy control subjects, we classified subjects with asthma based on high or low expression of IL-13-inducible genes. We then validated this classification and investigated its clinical implications through analyses of cytokine expression in bronchial biopsies, markers of inflammation and remodeling, responsiveness to inhaled corticosteroids, and reproducibility on repeat examination. Gene expression analyses identified two evenly sized and distinct subgroups, "Th2-high" and "Th2-low" asthma (the latter indistinguishable from control subjects). These subgroups differed significantly in expression of IL-5 and IL-13 in bronchial biopsies and in airway hyperresponsiveness, serum IgE, blood and airway eosinophilia, subepithelial fibrosis, and airway mucin gene expression (all P < 0.03). The lung function improvements expected with inhaled corticosteroids were restricted to Th2-high asthma, and Th2 markers were reproducible on repeat evaluation. Asthma can be divided into at least two distinct molecular phenotypes defined by degree of Th2 inflammation. Th2 cytokines are likely to be a relevant therapeutic target in only a subset of patients with asthma. Furthermore, current models do not adequately explain non-Th2-driven asthma, which represents a significant proportion of patients and responds poorly to current therapies.
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                Author and article information

                Journal
                Tanaffos
                Tanaffos
                Tanaffos
                Tanaffos
                Tanaffos
                National Research Institute of Tuberculosis and Lung Disease
                1735-0344
                2345-3729
                2015
                : 14
                : 2
                : 73-94
                Affiliations
                [1 ]Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
                [2 ]Lung Disease Research Center, Mashhad University of Medical Science, Mashhad, Iran
                [3 ]Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [4 ]Advanced Thoracic Research Center, Pulmonary and Critical Care Department, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
                [5 ]Department of Pulmonology, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran
                [6 ]Department of Internal Medicine, Pulmonary and Critical Care Division, Mazandaran University of Medical Sciences, Sari, Iran
                [7 ]Allergy Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
                [8 ]Department of Internal Medicine, Division of Pulmonology, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
                [9 ]Department of Internal Medicine, Pulmonary Division, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
                [10 ]Behphar Scientific Committee, Behphar Group, Tehran, Iran
                [11 ]Respiratory-Care Experts’ Input Forum, Mortaz Hospital, Yazd, Iran
                [12 ]Department of Pulmonology, Artesh University of Medical Sciences, Tehran, Iran
                [13 ]Department of Pulmonary Medicine, Imam Khomeini hospital, Urmia University of Medical Sciences, Urmia, Iran
                [14 ]Department of Internal medicine, Division of Pulmonary and Critical Care Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
                [15 ]Department of Pulmonary Diseases, Qazvin University of Medical Sciences, Qazvin, Iran
                [16 ]Department of Pulmonary Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [17 ]Clinical Research & Development Center, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                [18 ]Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
                [19 ]Division of Pulmonology, Department of Internal Medicine, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
                Author notes
                Correspondence to: Torabi-Nami M, Address: Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran, Email address: torabinami@ 123456sums.ac.ir
                Article
                tanaffos-14-73
                4629434
                26528362
                2523cbc0-53b2-4590-9b00-1295aba61234
                Copyright© 2015 National Research Institute of Tuberculosis and Lung Disease

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

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                Categories
                Review Article

                severe asthma,definition,comorbidities,treatment,phenotyping,consensus statement,iran

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