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      Sublingual immunotherapy: World Allergy Organization position paper 2013 update

      , 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 22 , 21 , 23 , 24 , 25

      The World Allergy Organization Journal

      World Allergy Organization

      Sublingual immunotherapy, Allergen-specific immunotherapy, Mechanisms of SLIT, Safety of SLIT, Efficacy of SLIT, Clinical trials methodology in SLIT

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          We have prepared this document, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2013 Update”, according to the evidence-based criteria, revising and updating chapters of the originally published paper, “Sublingual Immunotherapy: World Allergy Organization Position Paper 2009”, available at http://www.waojournal.org. Namely, these comprise: “Mechanisms of sublingual immunotherapy;” “Clinical efficacy of sublingual immunotherapy” – reporting all the data of all controlled trials published after 2009; “Safety of sublingual immunotherapy” – with the recently published Grading System for adverse reactions; “Impact of sublingual immunotherapy on the natural history of respiratory allergy” – with the relevant evidences published since 2009; “Efficacy of SLIT in children” – with detailed analysis of all the studies; “Definition of SLIT patient selection” – reporting the criteria for eligibility to sublingual immunotherapy; “The future of immunotherapy in the community care setting”; “Methodology of clinical trials according to the current scientific and regulatory standards”; and “Guideline development: from evidence-based medicine to patients' views” – including the evolution of the methods to make clinical recommendations.

          Additionally, we have added new chapters to cover a few emerging crucial topics: “Practical aspects of schedules and dosages and counseling for adherence” – which is crucial in clinical practice for all treatments; “Perspectives and new approaches” – including recombinant allergens, adjuvants, modified allergens, and the concept of validity of the single products. Furthermore, “Raising public awareness about sublingual immunotherapy”, as a need for our patients, and strategies to increase awareness of allergen immunotherapy (AIT) among patients, the medical community, all healthcare stakeholders, and public opinion, are also reported in detail.

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          Most cited references 306

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          Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin.

          Lactobacilli are probiotic bacteria that are frequently tested in the management of allergic diseases or gastroenteritis. It is hypothesized that these probiotics have immunoregulatory properties and promote mucosal tolerance, which is in part mediated by regulatory T cells (Treg cells). On the basis of pathogenic or tissue-specific priming, dendritic cells (DC) acquire different T cell-instructive signals and drive the differentiation of naive T H cells into either T H 1, T H 2, or regulatory effector T cells. We studied in what way different species of lactobacilli prime human DCs for their ability to drive Treg cells. Human monocyte-derived DCs were cultured in vitro with lactobacilli of different species. Two different species of lactobacilli, Lactobacillus reuteri and Lactobacillus casei , but not Lactobacillus plantarum, prime monocyte-derived DCs to drive the development of Treg cells. These Treg cells produced increased levels of IL-10 and were capable of inhibiting the proliferation of bystander T cells in an IL-10-dependent fashion. Strikingly, both L reuteri and L casei , but not L plantarum , bind the C-type lectin DC-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN). Blocking antibodies to DC-SIGN inhibited the induction of the Treg cells by these probiotic bacteria, stressing that ligation of DC-SIGN can actively prime DCs to induce Treg cells. The targeting of DC-SIGN by certain probiotic bacteria might explain their beneficial effect in the treatment of a number of inflammatory diseases, including atopic dermatitis and Crohn's disease.
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            Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study.

            3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT. We evaluated the long-term clinical effect and the preventive effect of developing asthma 7-years after termination of SIT. One hundred and forty-seven subjects, aged 16-25 years with grass and/or birch pollen allergy was investigated 10 years after initiation of a 3-year course of SIT with standardized allergen extracts of grass and/or birch or no SIT respectively. Conjunctival provocations were performed outside the season and methacholine bronchial provocations were performed during the season and winter. Asthma was assessed by clinical evaluation. The significant improvements in rhinoconjunctivitis and conjunctival sensitivity persisted at the 10-year follow-up. Significantly less actively treated subjects had developed asthma at 10-year follow-up as evaluated by clinical symptoms [odds ratio 2.5 (1.1-5.9)]. Patients who developed asthma among controls were 24/53 and in the SIT group 16/64. The longitudinal treatment effect when adjusted for bronchial hyper-responsiveness and asthma status at baseline including all observations at 3, 5 and 10 years follow-up (children with or without asthma at baseline, n = 189; 511 observations) was statistically significant (P = 0.0075). The odds ratio for no-asthma was 4.6 95% CI (1.5-13.7) in favor of SIT. A 3-year course of SIT with standardized allergen extracts has shown long-term clinical effects and the potential of preventing development of asthma in children with allergic rhinoconjunctivitis up to 7 years after treatment. Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination.
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              Clinical management of asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) study.

              Asthma management guidelines provide recommendations for the optimum control of asthma. This survey assessed the current levels of asthma control as reported by patients, which partly reflect the extent to which guideline recommendations are implemented. Current asthma patients were identified by telephone by screening 73,880 households in seven European countries. Designated respondents were interviewed on healthcare utilization, symptom severity, activity limitations and asthma control. Current asthma patients were identified in 3,488 households, and 2,803 patients (80.4%) completed the survey. Forty-six per cent of patients reported daytime symptoms and 30% reported asthma-related sleep disturbances, at least once a week. In the past 12 months, 25% of patients reported an unscheduled urgent care visit, 10% reported one or more emergency room visits and 7% reported overnight hospitalization due to asthma. In the past 4 weeks, more patients had used prescription quick-relief medication (63%) than inhaled corticosteroids (23%). Patient perception of asthma control did not match their symptom severity; approximately 50% of patients reporting severe persistent symptoms also considered their asthma to be completely or well controlled. The current level of asthma control in Europe falls far short of the goals for long-term asthma management. Patients' perception of asthma control is different from their actual asthma control.

                Author and article information

                World Allergy Organ J
                World Allergy Organ J
                The World Allergy Organization Journal
                World Allergy Organization
                28 March 2014
                : 7
                : 1
                : 6
                [1 ]Respiratory and Allergy Clinic, DIMI—Department of Internal Medicine, University of Genoa, IRCCS Aou San Martino, Largo Rosanna Benzi 10, Genoa 1-16132, Italy
                [2 ]Department of Medicine, Nova Southeastern University, College of Osteopathic Medicine, Davie Florida, USA
                [3 ]Division of Allergy, Department of Pediatrics, Nippon Medical School, Tokyo, Japan
                [4 ]Research Center for Respiratory Medicine (CIMER), Catholic University, Fundación LIBRA, Córdoba, Argentina
                [5 ]Department of Pediatrics and Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA
                [6 ]Department of Medicine, Second University of Naples, Institute of Translational Pharmacology, Italian National Research Council, Rome, Italy
                [7 ]Centre Hospitalier Regional Universitaire de Montpellier, Université de Montpellier, Montpellier, France
                [8 ]Section of Allergy and Clinical Immunology, Imperial College of London, National Heart and Lung Institute, Royal Brompton Hospital, London, UK
                [9 ]Allergy and Respiratory Diseases Clinic, Department of Internal Medicine, University of Genoa, Genova, Italy
                [10 ]Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College of London, London, UK
                [11 ]Department of Allergology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
                [12 ]Allergy Department, Hospital Medica Sur, Mexico City, Mexico
                [13 ]National Jewish Health, University of Colorado – Denver School of Medicine, Denver, Colorado, USA
                [14 ]Allergy and Respiratory Diseases, IRCCS San Martino IST, University of Genoa, Genova, Italy
                [15 ]Center for Rhinology and Allergology Wiesbaden, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany
                [16 ]Pediatric Allergy and Immunology Division, Hospital de Clínicas, Federal University of Parana, Curitiba, Brazil
                [17 ]Academic Centre of Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
                [18 ]Children’s Mercy Hospital, University of Missouri – Kansas City School of Medicine, Kansas City, Missouri
                [19 ]Allergy Unit, Department of Dermatology, University Hospital of Zürich, Zürich, Switzerland
                [20 ]Allergy Unit, Verona General Hospital, Verona, Italy
                [21 ]Department of Paediatrics, University Children’s Medical Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
                [22 ]Department of Clinical Allergology and Pulmonary Diseases, University of Turku, Finland, and Allergy Clinic, Terveystalo, Turku, Finland
                [23 ]Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
                [24 ]Department of Pediatric Pneumology and Immunology, Charité, Humboldt University, Berlin, Germany
                [25 ]The Allergy and Asthma Institute, Islamabad, Pakistan
                Copyright © 2014 Canonica et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.



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