BACKGROUND:The impact of grass pollen-induced allergic rhinitis (AR) on classroom/work productivity and activities can be assessed with a specific instrument: the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific (WPAI-AS). This study evaluated the relationships between the WPAI-AS and other outcome measures in AR.METHODS:Adolescents (aged 12-17) and adults (aged 18-65) consulting specialists for AR were enrolled in a four-week, multicentre, observational study. The management of AR was left to the physicians' discretion. Participants regularly rated the WPAI-AS, their symptoms (using the Rhinoconjunctivitis Total Symptom Score (RTSS) and a 0- to 100-mm visual analogue scale (VAS)) and quality of life (according to the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)).RESULTS:A total of 247 adolescents and 292 adults showed similar baseline impairments in classroom/work productivity and activities other than work. In both age groups, the WPAI-AS scores were moderately correlated with the RQLQ score and, to a lesser extent, with the VAS score and the RTSS. A multiple regression analysis indicated that the RQLQ score was a weak but statistically significant predictor of both impaired work/classroom productivity and daily activities. A 50-mm VAS cut-off categorized patients in whom AR had the greatest impact on productivity.CONCLUSIONS:Grass pollen-induced AR impairs work/classroom and daily activity to a similar extent in adults and adolescents. The weak-to-moderate correlations with AR symptom scores and quality-of-life scores suggest that a specific tool (such as the WPAI-AS) should be used to assess AR's impact on word/classroom productivity and daily activities.

BACKGROUND:The safety of allergen immunotherapy (AIT) in asthma has not always been sufficiently documented; accordingly, fear of asthma exacerbations has made physicians somewhat reluctant to prescribe AIT in this context. In a double-blind, placebo-controlled, randomized clinical trial, house dust mite (HDM) sublingual AIT was found to be efficacious in moderate, persistent asthma. The trial's safety results are now reported in detail.METHODS:Asthmatic adults were randomized 2 : 1 to twelve months of daily treatment with a sublingual solution of Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts or a placebo. Adverse events (AEs) at least possibly related to the investigational product were classified by the investigators as adverse drug reactions (ADRs).RESULTS:Overall, the patients in the safety analysis set (n = 484; active treatment: n = 322; placebo: n = 162) had mostly well-controlled, persistent asthma [mild in 290 patients (59.9%), moderate in 183 (37.8%) and severe in 11 (2.3%)]. No treatment-related serious AEs were reported. A total of 87.0% and 75.9% of the patients in the active and placebo groups, respectively, experienced at least one AE (mostly mild), and 78.9% and 48.1% experienced an ADR (mostly mild or moderate oral reactions). The incidence of asthma exacerbations (symptoms requiring a short course of oral corticosteroids) during the study was similar in the active treatment group (3.7%) and the placebo group (4.3%). There were no significant intergroup differences or intragroup changes over time in respiratory AEs, lung function or asthma-related quality of life.CONCLUSIONS:HDM sublingual AIT was safe and well tolerated in adult patients with mild-to-moderate, persistent asthma (ClinicalTrials.gov: NCT00660452).

Sublingual immunotherapy (SLIT) applied to type I respiratory allergies is commonly performed with natural allergen extracts. Herein, we developed a sublingual tablet made of pharmaceutical‐grade recombinant Bet v 1.0101 (rBet v 1) and investigated its clinical safety and efficacy in birch pollen (BP)‐allergic patients.

Precision medicine is a medical model aiming to deliver customised healthcare - with medical decisions, practices, and/or products tailored to the individual patient informed but not directed by guidelines. Allergen immunotherapy has unique immunological rationale, since the approach is tailored to the specific IgE spectrum of an individual and modifies the natural course of the disease as it has a persistent efficacy after completion of treatment. In this perspective Allergen Immunotherapy - AIT has to be presently considered a prototype of Precision Medicine. Precise information and biomarkers provided by systems medicine and network medicine will address the discovery of Allergen immunotherapy biomarkers for (i) identification of the causes, (ii) stratification of eligible patients for AIT and (iii) the assessment of AIT efficacy. This area of medical technology is evolving rapidly and, compelemented by e-health, will change the way we practice medicine. It will help to monitor patients' disease control and data for (i) patient stratification, (ii) clinical trials, (iii) monitoring the efficacy and safety of targeted therapies which are critical for reaching an appropriate reimbursement. Biomarkers associated with e-health combined with a clinical decision support system (CDSS) will change the scope of Allergen immunotherapy. The cost/effectiveness of Allergen immunotherapy is a key issue for successful implementation. It should include the long-term benefits in the pharmaco-economic evaluation, since no other allergy treatment has this specific characteristic. AIT is the prototype of current and future precision medicine.

Correspondence.

BACKGROUND:The efficacy and safety of sublingual immunotherapy in house dust mite-induced asthma have yet to be firmly established. We report the results of a double-blind, placebo-controlled, randomized clinical trial performed in mainland China.METHODS:After a three-month baseline period, 484 asthmatic adults were randomized 2 : 1 to 12 months of daily treatment with either an aqueous, standardized, 300 index of reactivity mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae extracts or a placebo. The primary efficacy criterion was well-controlled asthma for at least 16 of the last 20 weeks of treatment.RESULTS:In the active (n = 308) and placebo (n = 157) groups, well-controlled asthma was achieved by 85.4% and 81.5% of the patients, respectively (P = 0.244). A subsequent post hoc analysis by asthma severity revealed significant clinical benefits in actively treated subjects with moderate, persistent asthma at baseline [401-800 μg budesonide/day (n = 175)], with greater achievement of well-controlled asthma (80.5% and 66.1% for the active treatment and placebo groups, respectively; P = 0.021) and totally controlled asthma (54.0% and 33.9%, respectively, P = 0.008), a higher percentage of patients with an asthma control questionnaire score < 0.75 (56.6% and 40.0%, respectively; P = 0.039) and a greater mean reduction in inhaled corticosteroid use (218.5 μg and 126.2 μg, respectively; P = 0.004). The active vs placebo differences in disease control and corticosteroid use were not significant for mild, persistent asthma. No treatment-related serious adverse events were reported.CONCLUSIONS:Sublingual mite allergen immunotherapy was well tolerated in adult asthmatics and effectively controlled disease in patients with moderate (but not mild) persistent asthma (ClinicalTrials.gov: NCT00660452).

BACKGROUND:The minimally important difference (MID) has been defined as the smallest improvement considered worthwhile by a patient. The MID has not been estimated for the Rhinoconjunctivitis Total Symptom Score (RTSS).METHODS:In a prospective multicentre study, patients consulting for grass-pollen-induced allergic rhinitis (AR) recorded a 15-point global rating of change scale (GRCS) score and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score on a weekly basis and the individual symptom scores comprising the RTSS on a daily basis over two consecutive weeks. The MID in the RTSS was determined with anchor-based methods (using the GRCS and the RQLQ) and a distribution-based method [based on the RTSS' standard deviation (SD)].RESULTS:The study population comprised 806 patients (253 children, 250 adolescents and 303 adults). During the first week of the study, the mean ± SD RTSSs for these age groups were 6.5 ± 3.3, 6.8 ± 3.4 and 7.0 ± 3.4, respectively. For an improvement of 2 points in the GRCS or 0.5 points in the RQLQ score, the regression analysis yielded MIDs in the RTSS of 1.24 ± 0.17 and 1.12 ± 0.14 in children, 1.33 ± 0.14 and 1.20 ± 0.13 in adolescents and 1.13 ± 0.14 and 0.89 ± 0.12 in adults, respectively. When applying distribution-based methods, the MID ranged from 1.09 to 1.13 (based on 0.33 SDs of the first-week RTSS) and from 1.22 to 1.40 (based on 0.5 SDs of the difference in RTSSs between the first and second weeks).CONCLUSION:The MID in the RTSS was consistently estimated as 1.1-1.3 (and could conceivably be rounded to 1) in patients with grass-pollen-induced AR.

L'immunothérapie par voie sublinguale est une autre voie de traitement vaccinal aux allergènes. Les essais cliniques en double insu chez l'adulte ont été favorables pour plusieurs allergènes dont les pollens (graminées, pariétaires, olivier etc.) et les acariens. Seules quatre études en double insu contre placebo ont été réalisées chez l'enfant. Le protocole n'a pas toujours été identique. Les indications s'adressaient surtout à la rhinite et/ou à l'asthme. Les allergènes utilisés étaient les pollens de pariétaire, d'olivier et les acariens. Les résultats ont été appréciés sur les scores cliniques et médicamenteux, sur les paramètres biologiques tels que les IgE spécifiques, IgG4 spécifiques et l'ECP. Seules la première et la quatrième étude ont donné des résultats statistiquement favorables. L'efficacité clinique et biologique a été fonction de la dose cumulative de l'allergène, y compris de la qualité protéinique de l'extrait allergénique. L'avenir immédiat de l'immunothérapie en général s'oriente vers des traitements inhibiteurs de la sensibilisation à l'allergène, par l'utilisation de vaccins DNA, l'inhibition de la réponse IgE par un vaccin anti-IgE, l'inhibition de la libération des médiateurs et également l'utilisation de la cytokine IL18 codée au niveau du tissu pulmonaire. Ces traitements immunothérapiques du troisième millénaire sont déjà en phase II et III d'essais cliniques. L'immunothérapie allergénique (ITa) ou vaccination aux allergènes consiste en l'administration de doses progressivement croissantes d'un allergène à un sujet allergique jusqu'à une dose efficace, améliorant la symptomatologie associée à l'exposition consécutive à l'allergène causal ou responsable.

Avec l’éviction des allergènes, l’immunothérapie spécifique (ITS) est le seul traitement curatif pour les maladies allergiques. Les conditions d’application de l’ITS sont d’abord l’identification des allergènes en cause, à partir des résultats des tests d’allergie et de l’histoire clinique, mais aussi la stabilisation de la maladie. L’application de l’ITS chez les patients polysensibilisés avec une maladie allergique grave difficile à contrôler par un traitement optimal est un défi majeur. Nous rapportons le cas d’une jeune fille de 16 ans, atteinte d’une rhinite et d’un asthme sévère attribué aux acariens (Dermatophagoides pteronyssinus et Dermatophagoides farinae), pollens de graminées et squames de chat. L’adjonction d’omaluzimab au traitement optimal préétabli a permis de contrôler la maladie et d’initier l’immunothérapie spécifique sublinguale (ITSL). L’ITSL a été bien tolérée pendant et après l’arrêt de l’omaluzimab, et a conduit à un contrôle total de la maladie allergique [fonction respiratoire, clinique et tests immuno-allergologiques] qui a persisté après l’arrêt du traitement par omalizumab. Plusieurs études ont montré que l’omalizumab a augmenté la tolérance et l’efficacité de l’ITS chez les patients souffrant d’allergies respiratoires et aux venins d’hyménoptères. Cependant, dans la plupart des études, le traitement par omalizumab devait être maintenu pendant l’ITS. Nos résultats chez une jeune fille polysensibilisée souffrant d’asthme sévère, sont en accord avec ceux de quelques autres études montrant que le pré-traitement par omalizumab pourrait conduire à la tolérance et à l’efficacité de l’ITS. En outre, ils montrent également que l’ITS peut agir en synergie avec l’omalizumab et poursuivre seule l’induction des mécanismes d’immunoregulation.The avoidance of allergens and allergen-specific immunotherapy (AIT) are the only curative treatments of allergic diseases. This requires identification of the offending allergens based on the clinical history and the results of allergy tests, but also on prior attempts to stabilize the disease with drugs. AIT in polysensitized patients with severe allergic diseases which are difficult to control is a major challenge. We report the case of a 16-year-old girl with rhinitis and severe asthma attributed to mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae), grass pollen and cat dander. The addition of Omaluzimab to the pre-established optimal treatment helped to control the disease and allowed us to initiate sublingual immunotherapy (SLIT). SLIT was well tolerated during Omaluzimab administration and also after the drug was discontinued, and the treatment led to complete control of her allergic disease (symptoms, respiratory function and immunoassays). Several studies have shown that omalizumab increases tolerance to and efficacy of AIT in patients with respiratory and hymenoptera venom allergies. However, in most studies, omalizumab treatment was maintained during AIT. Our results in this young polysensitized girl with severe asthma agree with results reported in other studies which showed that pretreatment with omalizumab could lead to better tolerance and efficacy of AIT. Moreover, it was also reported that AIT can act synergistically with omalizumab and involves only the induction mechanisms of immune-regulation.

L'immunothérapie par voie sublinguale est une autre voie de traitement vaccinal aux allergènes. Les essais cliniques en double insu chez l'adulte ont été favorables pour plusieurs allergènes dont les pollens (graminées, pariétaires, olivier etc.) et les acariens. Seules quatre études en double insu contre placebo ont été réalisées chez l'enfant. Le protocole n'a pas toujours été identique. Les indications s'adressaient surtout à la rhinite et/ou à l'asthme. Les allergènes utilisés étaient les pollens de pariétaire, d'olivier et les acariens. Les résultats ont été appréciés sur les scores cliniques et médicamenteux, sur les paramètres biologiques tels que les IgE spécifiques, IgG4 spécifiques et l'ECP. Seules la première et la quatrième étude ont donné des résultats statistiquement favorables. L'efficacité clinique et biologique a été fonction de la dose cumulative de l'allergène, y compris de la qualité protéinique de l'extrait allergénique. L'avenir immédiat de l'immunothérapie en général s'oriente vers des traitements inhibiteurs de la sensibilisation à l'allergène, par l'utilisation de vaccins DNA, l'inhibition de la réponse IgE par un vaccin anti-IgE, l'inhibition de la libération des médiateurs et également l'utilisation de la cytokine IL18 codée au niveau du tissu pulmonaire. Ces traitements immunothérapiques du troisième millénaire sont déjà en phase II et III d'essais cliniques. L'immunothérapie allergénique (ITa) ou vaccination aux allergènes consiste en l'administration de doses progressivement croissantes d'un allergène à un sujet allergique jusqu'à une dose efficace, améliorant la symptomatologie associée à l'exposition consécutive à l'allergène causal ou responsable.

The sustained efficacy (i.e., after 3 treatment years) of discontinuous treatment with 300IR sublingual tablet of 5-grass pollen allergen extract, initiated 4 or 2 months before each grass pollen season and continued for its duration, has been demonstrated in an ongoing 5-year study. Here we report the persistence of efficacy during the first post-treatment pollen season. 633 adults were randomized to placebo or 300IR pre- and co-seasonally for three grass pollen seasons starting 4 months[4M] or 2 months[2M] prior to the season each year. Patients were followed during the subsequent, treatment-free, season. Primary endpoint for post treatment efficacy was the Average Adjusted Symptom Score (AASS). Secondary efficacy criteria included overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score. AASS and overall RQLQ score were analyzed using an ANCOVA model. Statistically significant differences compared to Placebo in mean AASS during the Year 4 pollen period were observed for both 300IR(4M) and 300IR(2M). 300IR(4M): difference in LS Means -1.14 (95% CI: [[[Unsupported Character - Codename ­]]2.03, -0.26], p = 0.0114), relative LS Mean difference from Placebo -22.9%. 300IR (2M): difference in LS Means -1.43 (95% CI: [-2.32, -0.53]), p = 0.0019), relative LS Mean difference from Placebo -28.5%. Active treatment groups also showed statistically significant LS Mean differences in changes from baseline in overall RQLQ score (p≤0.0001). There were no serious drug-related post-treatment adverse events. The long-term efficacy of 300IR sublingual tablets of grass pollen allergen extract was demonstrated during the first post-treatment pollen season. This persistent improvement was clinically meaningful to patients.

Allergy and allergic diseases represent a major health problem not only in industrialized ‘modern’ societies, but worldwide. There has been an epidemic increase in prevalence of allergic diseases in the last few decades with 10–30% of the population affected. Apart from individual suffering, because of their life-threatening or chronic course, these diseases present a high socioeconomic burden. In many countries, patient care of affected individuals is insufficient and/or inadequate. In spite of great progress in research into the causes and treatment of allergy in the last decades, there are still many problems to be solved in moving to reach our goals of more effective therapies and eventual prevention (1–3). Therefore, a group of 40 scientists and clinicians from four continents and all fields of allergy and related disciplines gathered under the sponsorship of the Christine-Kühne Center of Allergy Research and Education (CK-CARE) in Davos, Switzerland from 17 to 20 July 2011 for the first ‘Global Allergy Forum’. Under the topic ‘Allergy and Allergic Diseases: Barriers to Cure’, the participants formed five working groups to discuss and define the most urgent problems in the field and seek solutions and recommend an action plan. There are numerous unmet clinical needs and millions of patients are undertreated or not treated with the most appropriate methods. Accessibility to and affordability of effective therapeutic regimens are not provided in many countries. The development of innovative therapies is slow compared to most other fields of medicine. Allergic diseases encompass broad fields of medicine and show a wide heterogeneity involving different organs such as eyes, respiratory tract, gut, and skin. Diseases include rhinoconjunctivitis, asthma, anaphylaxis, eczema, urticaria, and angioedema as well as drug and food allergies. Allergic diseases show variability in severity and clinical course which at the moment are only poorly defined. Much better definition of the subtypes of allergic patients (phenotyping) appears crucial and very much needed to address the right therapy to the right patient. A new integrative approach is needed to understand how a complex network of immunological, genetic, and environmental factors leads to a complex allergic phenotype (1). Action should be taken at various levels and through existing doctors, scientists, and lay organizations to solve these problems. The global expertise from clinical allergists, immunologists, microbiologists, biologists, nutritionists, epidemiologists, bio-informaticians, psychologists, and environmental researchers should be merged to develop focused transdisciplinary research strategies toward sustainable preventive programs and new therapeutic options. J. Ring: Christine Kühne-Center of Allergy Research and Education (CK-CARE), Department Dermatology and Allergy, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany C. Akdis: Christine Kühne-Center of Allergy Research and Education (CK-CARE), Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland H. Behrendt: Christine Kühne-Center of Allergy Research and Education (CK-CARE), ZAUM – Zentrum Allergie und Umwelt (Center for Allergy and Environment), Technische Universitaet Muenchen, Munich, Germany R.-P. Lauener: Christine Kühne-Center of Allergy Research and Education (CK-CARE), Children's Allergy & Asthma Hospital, Hochgebirgsklinik Davos, Davos, Switzerland; Zurich University Children's Hospital, Zurich, Switzerland G. Schäppi: Christine Kühne-Center of Allergy Research and Education (CK-CARE), Davos, Switzerland M. Akdis: Immunodermatology, Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland W. Ammann: Global Risk Forum GRF Davos, Davos, Switzerland O. de Beaumont: Stallergenes S.A., Antony, France T. Bieber: Klinik und Poliklinik für Dermatologie University, Bonn, Germany J. Bienenstock: Departments of Pathology and Molecular Medicine, McMaster University, Brain-Body Institute, Hamilton, Ontario, Canada K. Blaser: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland B. Bochner: Division of Allergy and Clinical Immunology, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland, USA J. Bousquet: Service des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, Montpellier, France R. Crameri: Molecular Allergology, Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos, Switzerland A. Custovic: Respiratory Research Group, University of Manchester, Manchester, United Kingdom C. Czerkinsky: International Vaccine Institute, Seoul, Korea U. Darsow, M. Ollert, C. Traidl-Hoffmann: Department Dermatology and Allergy, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany J. Denburg: Division of Clinical Immunology and Allergy, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada J. Drazen: New England Journal of Medicine, Boston, Massachusetts, USA E.-M. de Villiers: Abteilung Tumorvirus-Charakterisierung, University of Heidelberg, Heidelberg, Germany A. Fire: Departments of Pathology and Genetics, Stanford University School of Medicine, Stanford, California, USA S. Galli: Department of Pathology and Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA T. Haahtela: Department of Allergy, Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland H. zur Hausen: Deutsches Krebsforschungszentrum, Heidelberg, Germany S. Hildemann: Global Clinical Operations Europe-I, Eastern Europe, Middle East & Africa, Merck & Co., Merck, Darmstadt, Germany S. Holgate: III Division, Faculty of Medicine, University of Southampton, United Kingdom P. Holt: Telethon Institute for Child Health Research and Centre for child Health Research, The University of Western Australia, Perth, Australia T. Jakob: Allergy Research Group, Dept. of Dermatology, University Medical Center Freiburg, Freiburg, Germany A. Jung, G. Menz: Hochgebirgsklinik Davos, Davos, Switzerland M. Kemeny: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, China H. Koren: Environmental Health, LLC, Durham, North Carolina, USA D. Leung: Pediatric Allergy-Immunology, National Jewish Medical and Research Center, Denver, Colorado, USA R. Lockey: Division of Allergy and Clinical Immunology, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida, USA G. Marone: Department of Clinical Immunology and Allergy, School of Medicine, University of Naples Federico II, Naples, Italy M. Mempel: Department of Dermatology, Venereology und Allergy, Universitätsmedizin Göttingen, Göttingen, Germany B. Menné: Global Change and Health, World Health Organization, Rome, Italy U. Mueller: Allergiestation Medizinische Klinik, Spital Netz Bern, Zieglerspital, Bern, Switzerland E. von Mutius: Dr. von Hauner Children's Hospital, Ludwig Maximilian University Munich, Munich, Germany L. O'Mahony: Molecular Immunology, Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland R. Pawankar: Nippon Medical School, Tokyo, Japan H. Renz: Abteilung für Klinische Chemie und Zentrallaboratorium, Marburg, Germany T. Platts-Mills: Department of Medicine, Allergy & Immunology, Asthma & Allergy Disease Center, Charlottesville, Virginia, USA C. Roduit: Pediatric Allergy and Immunology, University Children's Hospital of Zurich, Zurich, Switzerland C. Schmidt-Weber: ZAUM – Zentrum Allergie und Umwelt (Center of Allergy and Environment), Technische Universität and Helmholtz Zentrum München, Munich, Germany U. Wahn: Klinik für Pädiatrie, Charité, Universitätsmedizin Berlin, Germany E. Rietschel: Wissenschaftsgemeinschaft Gottfried Wilhelm Leibniz, Berlin, Germany