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Paolo Cameli,1 Maria Aliani,2 Elena Altieri,3 Pietro Bracciale,4 Luisa Brussino,5 Maria Filomena Caiaffa,6 Giorgio Walter Canonica,7,8 Cristiano Caruso,9 Stefano Centanni,10 Maria D’Amato,11 Fausto De Michele,12 Stefano Del Giacco,13 Fabiano Di Marco,14 Girolamo Pelaia,15 Paola Rogliani,16,17 Micaela Romagnoli,18 Pietro Schino,19 Jan Walter Schroeder,20 Gianenrico Senna,21 Alessandra Vultaggio,22 Marco Benci,23 Silvia Boarino,24 Francesco Menzella25 1Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; 2UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 3Reparto di Pneumologia, P.O. Garbagnate Milanese, Garbagnate Milanese (MI), Italy; 4Reparto di Pneumologia, Ospedale Ostuni, Ostuni (BR), Italy; 5Dipartimento di Scienze Mediche, Università degli Studi di Torino; SCDU Immunologia e Allergologia, AO Ordine Mauriziano Umberto I, Torino, Italy; 6Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 7Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy; 8Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano (MI), Italy; 9Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 10Respiratory Unit ASST Santi Paolo e Carlo, Department of Health Sciences Universita’ degli Studi di Milano, Milano, Italy; 11UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 12UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 13Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 14Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 15Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 16Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 17Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 18UOC Pneumologia, AULSS 2 Marca Trevigiana, Treviso, Italy; 19Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti (BA), Italy; 20Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 21Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 22Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 23Medical Affairs R&I, AstraZeneca, Milano, Italy; 24Medical Evidence R&I, AstraZeneca, Milano, Italy; 25Pulmonology Unit, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna (TV), ItalyCorrespondence: Paolo Cameli, Respiratory Diseases Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy, Email paolo.cameli@unisi.itPurpose: Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic treatment is a strategy adopted to optimize asthma control when patients show partial or no response to previous biologics.Patients and Methods: ANANKE is a retrospective, multicenter Italian study (NCT04272463). Here, we outline the characteristics and long-term clinical outcomes in naïve-to-biologics and biologics-experienced patients treated with benralizumab for up to 96 weeks. Bio-experienced patients were split into omalizumab and mepolizumab subsets according to the type of biologic previously used.Results: A total of 124 (76.5%) naïve and 38 (23.5%) bio-experienced patients were evaluated at index date; 13 patients (34.2%) switched from mepolizumab, 21 patients (55.3%) switched from omalizumab, and four patients (10.5%) received both biologics. The mepolizumab subset was characterized by the longest SEA duration (median of 4.6 years), the highest prevalence of chronic rhinosinusitis with nasal polyposis (CRSwNP) (76.5%), and the greatest oral corticosteroid (OCS) daily dosage (median of 25 mg prednisone equivalent). The omalizumab group showed the highest severe annual exacerbation rate (AER) (1.70). At 96 weeks, treatment with benralizumab reduced any and severe AER by more than 87% and 94%, respectively, across all groups. Lung function was overall preserved, with major improvements observed in the mepolizumab group, which also revealed a 100% drop of the median OCS dose. Asthma Control Test (ACT) score improved in the naïve group while its increment was more variable in bio-experienced patients; among these, a marked difference was noticed between omalizumab and mepolizumab subsets (median ACT score of 23.5 and 18, respectively).Conclusion: Benralizumab promotes durable and profound clinical benefits in naïve and bio-experienced groups, indicating that a nearly complete depletion of eosinophils is highly beneficial in the control of SEA, independently of previous biologic use.Keywords: benralizumab, asthma, eosinophils, switch, long-term

Laura Tenero,1 Rachele Vaia,2 Giuliana Ferrante,1 Matteo Maule,3 Laura Venditto,1 Giorgio Piacentini,1 Gianenrico Senna,2,3 Marco Caminati3 1Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Clinic, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 3Department of Medicine, University of Verona, Verona, ItalyCorrespondence: Marco Caminati, Department of Medicine, University of Verona, Piazzala L.A. Scuro, 10, Verona, 37134, Italy, Email marco.caminati@univr.itAbstract: Allergic rhinitis (AR) is a common upper airways inflammatory condition especially in paediatric population; its burden potentially impacts on quality of life, quality of sleep and daily performance, which can be difficult to perceive but not less relevant in the middle-long term. The present review aims to provide an updated overview on AR epidemiology, diagnosis and with a special focus on its connections with bronchial asthma. In fact, when considering asthmatic pediatric population, AR is probably the most important risk factor for asthma onset and the most impactful extra-bronchial determinant of asthma control. Under this perspective, allergen immunotherapy (AIT) should always be considered in the light of a precision medicine approach. In fact, AIT does represent a unique opportunity to specifically interfere with AR immunological background, improve both AR and bronchial asthma control and prevent allergic disease evolution. Verifying the patient’s eligibility to that option should be considered as a priority for every physician managing children suffering from AR, especially when associated with bronchial asthma.Keywords: asthma, asthma control, rhinitis, immunotherapy, personalized medicine

Gianenrico Senna,1,2 Maria Aliani,3 Elena Altieri,4 Pietro Bracciale,5 Luisa Brussino,6 Maria Filomena Caiaffa,7 Paolo Cameli,8 Giorgio Walter Canonica,9,10 Cristiano Caruso,11 Maria D’Amato,12 Fausto De Michele,13 Stefano Del Giacco,14 Fabiano Di Marco,15 Francesco Menzella,16 Girolamo Pelaia,17 Paola Rogliani,18,19 Micaela Romagnoli,20 Pietro Schino,21 Jan Walter Schroeder,22 Alessandra Vultaggio,23 Sara Rizzoli,24 Alessandro Zullo,24 Silvia Boarino,25 Marilena Palmisano,26 Alessandra Rossi,26 Gianfranco Vitiello,26 Stefano Centanni27 1Department of Medicine, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, Verona University Hospital, Verona, Italy; 3UO Pneumologia e Pneumologia Riabilitativa, ICS Maugeri, IRCCS Bari, Bari, Italy; 4Reparto di Pneumologia, P.O., Garbagnate Milanese, Italy; 5Reparto di Pneumologia, Ospedale Ostuni, Ostuni, BR, Italy; 6Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I, Torino, Italy; 7Cattedra e Scuola di Allergologia e Immunologia Clinica, Dipartimento di Scienze Mediche, Università di Foggia, Foggia, Italy; 8Respiratory Diseases and Lung Transplantation, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Italy; 9Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy; 10Personalized Medicine Center: Asthma and Allergology, Humanitas Research Hospital, Rozzano, MI, Italy; 11Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy; 12UOSD Malattie Respiratorie “Federico II”, Ospedale Monaldi, AO Dei Colli, Napoli, Italy; 13UOC Pneumologia e Fisiopatologia Respiratoria, AORN A. Cardarelli, Napoli, Italy; 14Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 15Department of Health Sciences, Università Degli Studi Di Milano, Pneumologia, ASST Papa Giovanni XXIII, Bergamo, Italy; 16UOC Pneumologia, Ospedale “S. Valentino”, AULSS 2 Marca Trevigiana, Montebelluna, TV, Italy; 17Dipartimento di Scienze della Salute, Università Magna Graecia, Catanzaro, Italy; 18Division of Respiratory Medicine, University Hospital “Tor Vergata”, Roma, Italy; 19Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Roma, Italy; 20UOC Pneumologia, ULSS 2 Marca Trevigiana, Treviso, Italy; 21Fisiopatologia Respiratoria, Ospedale Generale Regionale, Ente Ecclesiastico “F. Miulli”, Acquaviva delle Fonti, BA, Italy; 22Allergy and Clinical Immunology, ASST Grande Ospedale Metropolitano Niguarda, Milano, Italy; 23Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Firenze, Italy; 24Medineos Observational Research - An IQVIA Company, Modena, Italy; 25Medical Evidence R&I, AstraZeneca, Milano, Italy; 26Medical Affairs R&I, AstraZeneca, Milano, Italy; 27Respiratory Unit, ASST Santi Paolo e Carlo, Department of Health Sciences, Università degli Studi di Milano, Milano, ItalyCorrespondence: Marilena Palmisano, Medical Affairs R&I, AstraZeneca, Milano, Italy, Email marilena.palmisano@astrazeneca.comPurpose: Benralizumab effectively reduces severe eosinophilic asthma (SEA) exacerbations in patients with a wide range of baseline blood eosinophil count (BEC). Patients included in real-world studies are often characterized by high mean/median BEC, while patients with BEC close to 300 cells/mm3 are poorly represented. This post hoc analysis from the Italian study ANANKE aims to define the clinical features and corroborate the efficacy of benralizumab in real world in the BEC 300– 450 cells/mm3 subset of patients.Patients and Methods: Post hoc analysis of the Italian, multicenter, observational, retrospective real-life study ANANKE (NCT04272463). Baseline clinical and laboratory characteristics were collected in the 12 months prior to benralizumab treatment and presented for a BEC 300– 450 cells/mm3 subgroup of patients. Change over time of BEC, annualized exacerbation rate (AER), asthma control (ACT), lung function and oral corticosteroid (OCS) use at 16, 24 and 48 weeks after benralizumab introduction were collected.Results: A total of 164 patients were analyzed, 34 of whom with a BEC of 300– 450 cells/mm3. This subgroup was more likely to be female (64.7%), with lower rates of severe exacerbations at baseline when compared to the total population (0.69 vs 1.01). After 48 weeks of benralizumab treatment, the BEC 300– 450 subset showed similar reductions in AER (− 94.8% vs − 92.2%) and OCS use (median dose reduction of 100% in both groups), as well as improvement in ACT score (median scores 22.5 vs 22) and lung function (pre-BD FEV1: +200 mL vs +300 mL) when compared to the total population. No discontinuations for safety reasons were registered.Conclusion: At baseline, apart from lower severe exacerbation rate, the BEC 300– 450 cells/mm3 subset of patients is comparable to the total population prescribed with benralizumab. In this real-life study, benralizumab is as effective in BEC 300– 450 patients as in the total population.Keywords: severe eosinophilic asthma, blood eosinophil count, benralizumab, observational, real-world evidence, real-life

Silvia Tognella,1 Claudio Micheletto,2 Alessandro Roggeri,3 Guido Polese,4 Denise Artioli,1 Gianenrico Senna,5 Marco Caminati,5,6 Daniela Paola Roggeri3 1Pulmonology Unit, Mater Salutis Hospital, Legnago (Verona), Italy; 2Pulmonology Unit, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; 3ProCure Solutions, Nembro, Bergamo, Italy; 4Pulmonology Unit, Magalini Hospital, Villafranca (Verona), Italy; 5Asthma Center and Allergy Unit, Verona University Hospital, Verona, Italy; 6Department of Medicine, Allergy and Clinical Immunology Section, University of Verona and Verona University Hospital, Verona, 37134, ItalyCorrespondence: Alessandro RoggeriProCure Solutions, Via Camozzi 1/C, Nembro, 24027, BG, ItalyTel +39 035 521121Email alessandro.roggeri@procuresolutions.itPurpose: A Regional Technical Commission was set in 2017 by Veneto region (Italy) to provide opinions and recommendations on drug prescriptions and to implement treatment-pathway guidelines for severe asthma. In this observational study, we describe the first structured, integrated, multidisciplinary, patient-centered outpatient clinic for the care of severe-asthma patients in Italy, and characterize patients referring to the center for specialist visits.Patients and Methods: To characterize patients that accessed the outpatient clinic in 2018, data on demographic characteristics, treatments, severity of asthma, phenotypes, and relevant comorbidities by phenotype were collected. Use of biologic agents and indicators of the performance of the outpatient clinic were described.Results: A structured multidisciplinary outpatient pathway for taking charge of patients and for administration and monitoring of biological agents was developed. A total of 146 patients accessed the outpatient clinic in 2018: 62.3% had uncontrolled asthma upon admission and 27.4% were already being treated with biologic agents. Among patients with uncontrolled asthma, 66% had severe uncontrolled asthma, 22% had moderate–severe uncontrolled asthma, and 12% had mild–moderate uncontrolled asthma. Main asthma phenotypes in uncontrolled-asthma patients were allergic (58% of patients), eosinophilic (22%), allergic plus eosinophilic (10%) and non-atopic asthma (10%). Among patients affected by severe asthma, 47% had allergic asthma, 28% had eosinophilic asthma, 13% had allergic plus eosinophilic asthma, and 12% had non-atopic asthma. Nasal polyps were more frequent in eosinophilic and allergic plus eosinophilic asthma, while gastro-esophageal reflux disease was more frequent in non-atopic asthma.Conclusion: This structure of an outpatient clinic for the treatment of severe asthma, with its dedicated pathway and multidisciplinary approach, may allow a stricter control of asthma and optimization of therapies, as well as minimization of drug misuse.Keywords: asthma, severe, multidisciplinary, outpatient

Marco Caminati,1 Rachele Vaia,1 Fabiana Furci,2 Gabriella Guarnieri,3 Gianenrico Senna1,2 1Department of Medicine, University of Verona, Verona, Italy; 2Allergy Unit and Asthma Center, University of Verona and Verona University Hospital, Verona, Italy; 3Respiratory Pathophysiology Unit, Department of Cardiological, Thoracic and Vascular Sciences, University of Padua, Padua, ItalyCorrespondence: Marco CaminatiDepartment of Medicine, University of Verona and Verona University Hospital, Piazzala L.A. Scuro 10, Verona, 37134, ItalyEmail marco.caminati@univr.itAbstract: The recent scientific research has provided clinicians with the tools for substantially upgrading the standard of care in the field of bronchial asthma. Nevertheless, satisfactory asthma control still remains an unmet need worldwide. Identifying the major determinants of poor control in different asthma severity levels represents the first step towards the improvement of the overall patients’ management. The present review aims to provide an overview of the main unmet needs in asthma control and of the potential tools for overcoming the issue. Implementing a personalized medicine approach is essential, not only in terms of pharmacological treatments, biologic drugs or sophisticated biomarkers. In fact, exploring the complex profile of each patient, from his inflammation phenotype to his preferences and expectations, may help in filling the gap between the big potential of currently available treatments and the overall unsatisfactory asthma control. Telemedicine and e-health technologies may provide a strategy to both optimize disease assessment on a regular basis and enhance patients’ empowerment in managing their asthma. Increasing patients’ awareness as well as the physicians’ knowledge about asthma phenotypes and treatment options besides corticosteroid probably represent the key and more difficult goals of all the players involved in asthma management at every level.Keywords: asthma, asthma control, severe asthma, mild to moderate asthma, telemedicine, personalized medicine

Francesca Puggioni,1,2 Luisa Brussino,3 Giorgio Walter Canonica,1,2 Francesco Blasi,4,5 Pierluigi Paggiaro,6 Marco Caminati,7,8 Manuela Latorre,6 Enrico Heffler,1,2 Gianenrico Senna7,8 On behalf of the Severe Asthma Network in Italy (SANI) group1Personalized Medicine, Asthma and Allergy – Humanitas Clinical and Research Center, IRCCS – Rozzano (MI), Milan, Italy; 2Department of Biomedical Sciences, Humanitas University – Pieve Emanuele (MI), Milan, Italy; 3Dipartimento di Scienze Mediche, SSDDU Allergologia e Immunologia Clinica, Università degli Studi di Torino, AO Ordine Mauriziano Umberto I – Torino, Torino, Italy; 4Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; 5Internal Medicine Department, Respiratory Unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy; 6Department of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa, Pisa, Italy; 7Department of Medicine, University of Verona, Verona, Italy; 8Allergy Unit and Asthma Center, Verona University Hospital, Verona, Verona, ItalyCorrespondence: Enrico HefflerPersonalized Medicine, Asthma and Allergy, Istituto Clinico Humanitas, Milan, ItalyTel +39 0288247013Fax + 39 0282246484Email enrico.heffler@hunimed.euPurpose: Patients with uncontrolled asthma despite high doses of inhaled corticosteroid therapy plus another controller are defined as severe asthmatics. Tiotropium bromide respimat (TBR) is the only long-acting muscarinic antagonists (LAMA) approved for severe asthma. The aim of this study was to explore the frequency of severe asthmatics treated with TBR and characterize their clinical features in a real-life, registry-based setting.Materials and Methods: Baseline data from the Severe Asthma Network in Italy (SANI) registry have been analyzed to determine the use of TBR and other LAMA, and to compare clinical, functional and inflammatory features associated with the use of LAMA.Results: Among a total of 698 enrolled patients, 35.9% were treated with LAMA (23.3% TBR, 4.5% tiotropium bromide handihaler, 4.5% aclidinium, 3.4% glycopyrronium bromide 0.3% umeclidinium bromide). Age of asthma onset was higher in patients taking LAMA, whom, compared to others were more frequently former smokers. They also had a higher annual exacerbation rate, experienced worst asthma control, worst disease-related quality of life and poorer lung function. Bronchiectasis was more frequently found in LAMA users (25.9% vs 13.1%).Conclusion: TBR is still underused in severe asthma in a real-life setting, while a relevant proportion of patients are treated with other LAMA that are not approved for severe asthma treatment. Patients taking LAMA have features characteristic of even more severe asthma.Keywords: severe asthma, registry, long-acting muscarinic antagonists, real-ligfe

Marco Caminati,1,2 Diego Bagnasco,3 Rachele Vaia,2 Gianenrico Senna11Asthma Center and Allergy Unit, Verona University Hospital, Verona, Italy; 2Department of Medicine, School of Specialization in Allergy and Clinical Immunology, University of Verona, Verona, Italy; 3Allergy & Respiratory Diseases, DIMI Department of Internal Medicine, University of Genoa, Genoa, ItalyAbstract: In the last decades, the increasing evidence concerning inflammation mechanisms underlying severe eosinophilic asthma has highlighted new potential therapeutic targets and has paved the way to new selective biologic drugs. Understanding the mechanism of action and the clinical outcomes of a particular drug along with the clinical and biological characteristics of the patient population for which that drug was intended may ensure appropriate selection of patients that will respond to that drug. Under this perspective, the present review will focus on the mechanisms of action and clinical evidence of benralizumab as a treatment option for severe eosinophilic asthma, in order to provide a concise overview and a reference for clinical practice. Benralizumab is a fully humanized afucosylated IgG1κ mAb that binds to an epitope on IL-5 Rα, and inhibits IL-5 signaling. Benralizumab also sustains antibody-directed cell-mediated cytotoxicity (ADCC) of eosinophils and basophils and consequently depletes IL-5Rα-expressing cells. As a result, it is responsible for a substantial depletion of blood, tissue, and bone marrow eosinophilia. This unique mechanism of action may account for a more complete and rapid action profile. Randomized clinical trials have demonstrated that benralizumab provides an optimal safety profile, and is able to significantly reduce asthma exacerbations, oral steroid intake, and to improve lung function. Some clinical predictors of enhanced clinical response to benralizumab have also been identified, including: a level of blood eosinophils ≥300 μL−1, oral steroids use, the presence of nasal polyposis, FVC

Abstract In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century. The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients’ Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients’ organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels. Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.

Abstract Allergy today is a public health concern of pandemic proportions, affecting more than 150 million people in Europe alone. In view of epidemiological trends, the European Academy of Allergy and Clinical Immunology (EAACI) predicts that within the next few decades, more than half of the European population may at some point in their lives experience some type of allergy. Not only do allergic patients suffer from a debilitating disease, with the potential for major impact on their quality of life, career progression, personal development and lifestyle choices, but they also constitute a significant burden on health economics and macroeconomics due to the days of lost productivity and underperformance. Given that allergy triggers, including urbanization, industrialization, pollution and climate change, are not expected to change in the foreseeable future, it is imperative that steps are taken to develop, strengthen and optimize preventive and treatment strategies. Allergen specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease. Years of basic science research, clinical trials, and systematic reviews and meta-analyses have convincingly shown that allergen specific immunotherapy can achieve substantial results for patients, improving the allergic individuals’ quality of life, reducing the long-term costs and burden of allergies, and changing the course of the disease. Allergen specific immunotherapy not only effectively alleviates allergy symptoms, but it has a long-term effect after conclusion of the treatment and can prevent the progression of allergic diseases. Unfortunately, allergen specific immunotherapy has not yet received adequate attention from European institutions, including research funding bodies, even though this could be a most rewarding field in terms of return on investments, translational value and European integration and, a field in which Europe is recognized as a worldwide leader. Evaluation and surveillance of the full cost of allergic diseases is still lacking and further progress is being stifled by the variety of health systems across Europe. This means that the general population remains unaware of the potential use of allergen specific immunotherapy and its potential benefits. We call upon Europe’s policy-makers to coordinate actions and improve individual and public health in allergy by: Promoting awareness of the effectiveness of allergen specific immunotherapy Updating national healthcare policies to support allergen specific immunotherapy Prioritising funding for allergen specific immunotherapy research Monitoring the macroeconomic and health economic parameters of allergy Reinforcing allergy teaching in medical disciplines and specialties The effective implementation of the above policies has the potential for a major positive impact on European health and well-being in the next decade.

Este trabalho apresenta os primeiros resultados do esforço conjunto de várias instituições, organizadas em torno da rede Geoma (Rede Temática de Pesquisa em Modelagem Ambiental da Amazônia) para avançar a compreensão dos novos padrões e processos de estruturação do território nas novas frentes no sul do Pará, analisando padrões de desmatamento e os processos que dão origem a esses padrões. Busca-se, aqui, produzir os subsídios necessários para o desenho de políticas públicas responsáveis, que não privilegiem um único aspecto do problema, como a abertura de estradas, por exemplo. Aponta-se, então, a partir desses primeiros resultados, que apenas uma solução integrada que procure estruturar os principais agentes e processos na cadeia produtiva seria possível para minorar os efeitos do desmatamento e nortear o desenvolvimento integrado para a região, com benefícios para a floresta e para as populações que ali vivem.This work presents the first results achieved through an interdisciplinary and multi-institutional effort conduct by the Geoma Network, aiming to advance in the comprehension of the new frontiers in the South of the Pará State, in the Amazonian region, by examining the new patterns of deforestation and the underlying processes that are generating them. Our objective is to product information aiding to draw responsible public policies considering not only one dimension of the problem like roads infra-structure, as usual. Based on the analysis presented here we pointed out that only an integrated solution, that considers the main actors and the organization of economical processes in the productive chains over the region, would be capable to minimize the effects of deforestation and would drive an integrated development policy to the region bringing benefits to forest conservation and the local population.