European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma.

AIMS: Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. METHODS: MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. STAKEHOLDERS: Include patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors. RESULTS: MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. EU GRANTS 2018: MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). LESSONS LEARNT: (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.

EPOS2020: development strategy and goals for the latest European Position Paper on Rhinosinusitis.

BACKGROUND: The European Position Papers on Rhinosinusitis from 2005, 2007 and 2012 have had a measurable impact on the way this common condition with high impact on quality of life is managed around the world. EPOS2020 will be the latest iteration of the guideline, addressing new stakeholders and target users, presenting a summary of the latest literature and evolving treatment modalities, and formulating clear recommendations based on all available evidence. METHODOLOGY: Based on the AGREE II framework, this article demonstrates how the EPOS2020 steering group will address six key areas to ensure consistency in quality and presentation of information in the latest rhinosinusitis clinical practice guideline: scope and purpose; stakeholder involvement; rigour of development; clarity of presentation; recommendations and applicability; editorial independence. RESULTS: By analysing the guidance from AGREE II, we formulated a detailed development strategy for EPOS2020. We identify new stakeholders and target users and ratify the importance of patient involvement in the latest EPOS guideline. New and expanded areas of research to be addressed are highlighted. We confirm our intention to use mixed methodologies, combining evidence-based medicine with real life studies; when no evidence can be found, use Delphi rounds to achieve clear, inclusive recommendations. We also introduce new concepts for dissemination of the guideline, using Internet and social media to improve accessibility. CONCLUSION: This article is an introduction to the EPOS2020 project, and presents the key goals, core stakeholders, planned methodology and dissemination strategies for the latest version of this influential guideline.

MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence.

mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary.

Killing two birds with one stone? Association between tobacco and alcohol consumption.

OBJECTIVES: Tobacco and excessive alcohol consumption are addictive behaviours, listed among the 10 leading risk factors that cause death and disability in the world, and health consequences are greater if their consumption is combined. There is sparse empirical evidence on the variables that influence the simultaneous consumption of tobacco and alcohol. This study aims to identify the variables that influence the joint decision to consume alcohol and tobacco, and that encourage drinkers to smoke. STUDY DESIGN: The sample includes Portuguese adults, mainly aged 50 years and over, extracted from the Survey of Health, Ageing and Retirement in Europe, covering the year 2011. METHODS: We propose a bivariate probit model, which allows us to model simultaneously the two goods, accounting for potential correlation between smoking and drinking decisions. RESULTS: We identified the variables that influence joint consumption, and tobacco consumption among drinkers, which could be used as policy instruments to develop concerted policies. Prevention policies should focus on males, younger and more educated individuals, as well as on individuals with unhealthy eating habits, because these variables were statistically significant and increased joint consumption. In addition, these characteristics also should be regarded if we want to control tobacco consumption among alcohol consumers. CONCLUSIONS: The analysis of the interdependence between alcohol and tobacco use presented in this article may allow reducing their consumption with a common intervention, enabling policymakers to 'kill two birds with one stone' and to achieve extended health and economic gains.

The burden of osteoporotic hip fractures in Portugal: costs, health related quality of life and mortality.

UNLABELLED: The study rationale was to provide a detailed overview of the costs, quality of life and mortality of hip fractures in Portugal. Mean individual fracture-related costs were estimated at €13,434 [12,290; 14,576] for the first year and €5985 [4982; 7045] for the second year following the fracture. INTRODUCTION: Osteoporotic fractures represent a remarkable burden to health care systems and societies worldwide, which will tend to increase as life expectancy expands and lifestyle changes favour osteoporosis. The cost-effectiveness evaluation of intervention strategies demands accurate data on the epidemiological and economical reality to be addressed. METHODS: Information was collected retrospectively on consumption of resources and changes in quality of life attributable to fracture as well as mortality, regarding 186 patients randomly selected to represent the distribution of hip fractures in the Portuguese population, in terms of gender, age and geographical provenience. Data were cross-tabulated with socio-demographic variables and individual resource consumption to estimate the burden of disease. A societal perspective was adopted, including direct and indirect costs. Multivariate analyses were carried out to assess the main determinants of health-related quality of life (HrQoL). RESULTS: Mean individual fracture-related costs were estimated at €13,434 [12,290; 14,576] for the first year and €5985 [4982; 7045] for the second year following the fracture. In 2011 the economic burden attributable to osteoporotic hip fractures in Portugal could be estimated at €216 million. Mean reduction in HrQoL 12 months after fracture was estimated at 0.34. Regression analysis showed that age was associated with a higher loss of HrQoL, whereas education had the opposing effect. We observed 12 % excess mortality in the first year after hip fracture, when compared to the gender and age-matched general population. CONCLUSIONS: Results of this study indicate that osteoporotic hip fractures are, also in Portugal, despite its low incidence of fractures and cost per event, associated with a high societal burden, in terms of costs, loss in HrQoL and mortality. These data provide valuable input to the design and selection of fracture prevention strategies.

Haemodialysis in Diabetic Patients Modulates Inflammatory Cytokine Profile and T Cell Activation Status.

Diabetic nephropathy (DN) is a common complication in patients with diabetes, and most of them need renal replacement therapy such as haemodialysis (HD). These patients have a high tendency to develop infections and exhibit anomalies in the immune system. The objective of this study was to assess the expression of activation-related markers on T cells, as well as to quantify inflammatory cytokines, before and after a single HD session in DN patients. The study involved DN patients under HD treatment who signed an informed consent form. Blood samples before and after one HD session were collected, to analyse the expression of CD25, CD69 and CD71 in T cells. We also quantified IL-12p70, IL-8, IL-10, IL-1ß, TNF-α and IL-6 in serum samples using the cytometric bead array technique. After the HD session, there was an increase in the CD4/CD8 ratio due to significant alterations in both subsets. The relative percentage of CD25+ cells and CD8+ CD25+ increased significantly after the HD session, while the relative percentage of CD69 T cells decreased. There was a significant decrease in the CD25 mean fluorescence intensity values for CD4+ T, as well as in the case of CD71 in T cells after the HD session. Regarding cytokine synthesis, we found a significant increase in IL-10 and IL-6 and a decrease in IL-8 after HD session. This study showed that a HD session in DN patients affects the T cell activation status in the two major subpopulations and differentially modulates the production of inflammatory cytokines.

T cells in sputum of asthmatic patients are activated independently of disease severity or control

Background: T cells play an important role in bronchial asthma. Although airway CD4+ T cells have been extensively studied previously, there are hardly any studies relating CD8+ T cell activation and disease symptoms. Objectives: The aim of this study was to analyse the association between T cell activation in induced sputum T cells and asthma severity and control; and to evaluate T cell subpopulations in the same subgroups. Methods: Fifty allergic asthmatic patients were recruited and lung function testing was performed. Airway cells were obtained by sputum induction via inhalation of hypertonic saline solution. CD3, CD4, CD8, CD28, CD25 and CD69 were studied by flow cytometry in whole induced sputum and peripheral blood cells. Results: Total induced sputum T cells and CD8+ T cells had a higher relative percentage of the activation markers CD25 and CD69 in comparison with peripheral blood. In sputum, the relative percentage of CD25 was higher in CD4+ T cells when compared to CD8+ T cells and the reverse was true regarding CD69. However, neither disease severity nor control were associated with the relative percentage of CD25 or CD69 expression on T cells in sputum. Conclusions: Both CD4+ and CD8+ T cells are activated in the lungs and peripheral blood of asthmatic patients. However, with the possible exception of CD69+ CD8+ T lymphocytes in the sputum, there is no association between T cell activation phenotype in the target organ and disease severity or control (AU)

T cells in sputum of asthmatic patients are activated independently of disease severity or control.

BACKGROUND: T cells play an important role in bronchial asthma. Although airway CD4+ T cells have been extensively studied previously, there are hardly any studies relating CD8+ T cell activation and disease symptoms. OBJECTIVES: The aim of this study was to analyse the association between T cell activation in induced sputum T cells and asthma severity and control; and to evaluate T cell subpopulations in the same subgroups. METHODS: Fifty allergic asthmatic patients were recruited and lung function testing was performed. Airway cells were obtained by sputum induction via inhalation of hypertonic saline solution. CD3, CD4, CD8, CD28, CD25 and CD69 were studied by flow cytometry in whole induced sputum and peripheral blood cells. RESULTS: Total induced sputum T cells and CD8+ T cells had a higher relative percentage of the activation markers CD25 and CD69 in comparison with peripheral blood. In sputum, the relative percentage of CD25 was higher in CD4+ T cells when compared to CD8+ T cells and the reverse was true regarding CD69. However, neither disease severity nor control were associated with the relative percentage of CD25 or CD69 expression on T cells in sputum. CONCLUSIONS: Both CD4+ and CD8+ T cells are activated in the lungs and peripheral blood of asthmatic patients. However, with the possible exception of CD69+ CD8+ T lymphocytes in the sputum, there is no association between T cell activation phenotype in the target organ and disease severity or control.

Demographic, laboratory and clinical characterisation of adult portuguese asthmatic patients.

BACKGROUND: Asthma is a heterogeneous chronic inflammatory condition characterised by reversible airway obstruction and hyperresponsiveness associated with underlying bronchial inflammation and structural changes. It represents an increasing health problem and is a huge burden on the patients, their families and society. The aim of the study was to characterise the adult asthmatic population attending a Hospital Allergy Clinic between the years of 2003 and 2006. METHODS: Clinical files from the Allergy Outpatient Clinic of Cova da Beira Hospital were sequentially studied. The total population analysed included 335 female and 130 male asthmatic patients. Bronchial asthma was characterised by clinical history, skin prick testing to aeroallergens, determination of total and specific IgE and lung function testing, and classified according to international guidelines. RESULTS: Of the patients studied, 70 % had allergic asthma, and 30 % had non-allergic asthma. When compared to allergic asthma, non-allergic asthma was more frequently associated with older age, perennial symptoms and female gender. More allergic than non-allergic asthma patients also had rhinitis and the reverse was true regarding drug allergy and oesophageal reflux. Grass pollen and mites were the major sensitisers for allergic asthmatics. The sensitisation profile was significantly different between urban- and rural-based asthmatic patients regarding tree pollen, fungi and moulds. CONCLUSIONS: In this population, rhinitis was more frequently associated with allergic than with non-allergic asthma. The two types of asthma did not differ in clinical severity or changes in lung function. Sensitisation profiles were different between the urban and rural patients.

Demographic, laboratory and clinical characterisation of adult portuguese asthmatic patients / Caracterızacıón demográfıca, analítıca y clínıca de pacıentes asmátıcos adultos portugueses

Background: Asthma is a heterogeneous chronic inflammatory condition characterised by reversible airway obstruction and hyperresponsiveness associated with underlying bronchial inflammation and structural changes. It represents an increasing health problem and is a huge burden on the patients, their families and society. The aim of the study was to characterise the adult asthmatic population attending a Hospital Allergy Clinic between the years of 2003 and 2006. Methods: Clinical files from the Allergy Outpatient Clinic of Cova da Beira Hospital were sequentially studied. The total population analysed included 335 female and 130 male asthmatic patients. Bronchial asthma was characterised by clinical history, skin prick testing to aeroallergens, determination of total and specific IgE and lung function testing, and classified according to international guidelines. Results: Of the patients studied, 70 % had allergic asthma, and 30 % had non-allergic asthma. When compared to allergic asthma, non-allergic asthma was more frequently associated with older age, perennial symptoms and female gender. More allergic than non-allergic asthma patients also had rhinitis and the reverse was true regarding drug allergy and oesophageal reflux. Grass pollen and mites were the major sensitisers for allergic asthmatics. The sensitisation profile was significantly different between urban- and rural-based asthmatic patients regarding tree pollen, fungi and moulds. Conclusions: In this population, rhinitis was more frequently associated with allergic than with non-allergic asthma. The two types of asthma did not differ in clinical severity or changes in lung function. Sensitisation profiles were different between the urban and rural patients

Antecedentes: el asma es un estado inflamatorio crónico heterogéneo, caracterizado por la obstrucción reversible de las vías aéreas e hiperreactividad asociada con la subyacente inflamación bronquial y cambios estructurales. Representa un creciente problema de salud y es una gran carga para los pacientes, sus familias y la sociedad. El objetivo de este estudio ha sido caracterizar la población de asmáticos adultos atendidos en el Clínica de Alergia del Hospital entre los años 2003 y 2006. Métodos: se estudió la documentación de los pacientes asistidos en el Ambulatorio de la Clínica de Alergia del Hospital Cova da Beira. El total de población analizada comprende 335 mujeres y 130 hombres. El asma bronquial se diagnóstico por la historia clínica, las pruebas cutáneas con aeroalergenos, la determinación de IgE total y específica y la función pulmonar, clasificándolos de acuerdo con las guías internacionales. Resultados: de los pacientes estudiados, el 70% tenían asma alérgica, y el 30% asma no alérgica. Comparando ambos grupos, el asma no alérgica estuvo asociada con mayor frecuencia con los pacientes de mayor edad, el género femenino y los síntomas perennes. Más pacientes con asma alérgica que no alérgica, también tenían rinitis, y lo contrario se observó con la alergia a medicamentos o el reflujo gastroesofágico. El polen de gramíneas y los ácaros del polvo fueron los alergenos más frecuentes en los asmáticos alérgicos. El perfil de sensibilización a polen de árboles, hongos y ácaros, fue significativamente distinto en los pacientes de la ciudad y los del área rural. Conclusiones: en esta población, la rinitis fue más frecuentemente asociada con el asma alérgica. Los dos tipos de asma no difieren en cuanto a la graveada o los cambios en la función pulmonar. Los perfiles de sensibilización fueron diferentes en el área urbana y en la rural

Functional and phenotypic characterization of CD8+CD28+ and CD28- T cells in atopic individuals sensitized to Dermatophagoides pteronyssinus.

BACKGROUND: CD8+ T suppressor cells may play a role in immunoregulation. Recent studies have characterized this population by the lack of the CD28 molecule. These CD8+CD28 T cells differ phenotypically and functionally from CD8 + CD28 + T cells. Little is known about CD8 + CD28 cells in atopy. Our aim was to analyze the phenotype and functional properties of CD8 + CD28T cells in atopic and non-atopic individuals. METHODS: Peripheral blood mononuclear cells (PBMC) were obtained after density gradient centrifugation. CD8 + CD28 and CD8 + CD28 + T cells were isolated using immunomagnetic beads. Relative percentages of these cells and expression of several phenotypic markers were analyzed by flow cytometry. Proliferation was assessed by thymidine incorporation in isolated populations and in co-cultures with PBMC using Dermatophagoides pteronyssinus as stimulus. Cytokine synthesis was evaluated in culture supernatants by cytometric bead array. RESULTS: The relative percentages of CD8+CD28 T cells and their phenotypic expression in atopic and non-atopic volunteers were not significantly different. However, CD8 + CD28 T cells showed greater proliferation than did CD8+CD28+ T cells when stimulated with D. pteronyssinus, although cytokine synthesis patterns were similar. CD8+CD28 co-cultures with PBMC showed greater proliferation than CD8+CD28+ T cell co-cultures, but cytokine synthesis patterns were not different. CONCLUSIONS: Our data confirm phenotypic and functional differences between CD28+ and CD28 T cells, irrespective of atopic status. Purified human CD8+CD28 T cells, freshly isolated from peripheral blood, do not have suppressor properties on allergen-specific proliferation or on cytokine synthesis in PBMC.

Functional and phenotypic characterization of CD8+CD28+ and CD28­ T cells in atopic individuals sensitized to Dermatophagoides pteronyssinus / Caracterización funcional y fenotípica de las células CD8+CD28+ y CD28¯ en individuos atópicos sensibilizados a Dermatophagoides pteroyissinus

Background: CD8+ T suppressor cells may play a role in immunoregulation. Recent studies have characterized this population by the lack of the CD28 molecule. These CD8+CD28– T cells differ phenotypically and functionally from CD8 + CD28 + T cells. Little is known about CD8 + CD28– cells in atopy. Our aim was to analyze the phenotype and functional properties of CD8 + CD28–T cells in atopic and non-atopic individuals. Methods: Peripheral blood mononuclear cells (PBMC) were obtained after density gradient centrifugation. CD8 + CD28– and CD8 + CD28 + T cells were isolated using immunomagnetic beads. Relative percentages of these cells and expression of several phenotypic markers were analyzed by flow cytometry. Proliferation was assessed by thymidine incorporation in isolated populations and in co-cultures with PBMC using Dermatophagoides pteronyssinusas stimulus. Cytokine synthesis was evaluated in culture supernatants by cytometric bead array. Results:The relative percentages of CD8+CD28– T cells and their phenotypic expression in atopic and non-atopic volunteers were not significantly different. However, CD8 + CD28– T cells showed greater proliferation than did CD8+CD28+ T cells when stimulated with D. pteronyssinus, although cytokine synthesis patterns were similar. CD8+CD28– co-cultures with PBMC showed greater proliferation than CD8+CD28+ T cell co-cultures, but cytokine synthesis patterns were not different. Conclusions: Our data confirm phenotypic and functional differences between CD28+ and CD28– T cells, irrespective of atopic status. Purified human CD8+CD28– T cells, freshly isolated from peripheral blood, do not have suppressor properties on allergen-specific proliferation or on cytokine synthesis in PBMC

Antecedentes: Células T CD8+ supresoras pueden tener un papel en inmunoregulación. Estudios recientes han demonstrado la falta de expresión de la molécula CD28 en esta población. Estas células T CD28− son diferentes fenotipica y funcionalmente de las células T CD28+. Se sabe muy poco de las células T CD8+CD28− en atopia. Nuestro objectivo ha sido analisar el fenótipo y función de células T CD8+CD28− en individuos atópicos y no atópicos. Métodos: Células mononucleares de la sangre periférica (CMSP) fueron obtenidas por gradiente de densidad. Células T CD8+CD28− y CD28+ fueran aisladas con cuentas inmunomagnéticas. Sus porcentages relativos y la expresión de varios marcadores fenotípicos fueran analizados con citometria de flujo. La proliferación fue estudiada por incorporación de timidina en las poblaciones aisladas y en co-culturas con CMSP, con Der p como estímulo. La sintesis de citocinas fue evaluada en los sobrenadantes de culturas por CBA. Resultados: Los porcentages relativos de células T CD8+CD28− y su expresión fenotípica no fueran distinctas entre atópicos y no atópicos. Las células T CD8+CD28− proliferaran mas que las células CD28+ quando estimuladas con Der p, aunque los padrones de síntesis de citocinas fueran similares. Co-culturas de células T CD8+CD28− con CMSP proliferaran mas que las co-culturas de células T CD8+CD28+ con las mismas células, pero los padrones de sintesis de citocinas no fueran diferentes. Conclusiones: Nuestros resultados confirman diferencias fenotípicas y funcionales entre células T CD28+ y CD28−, independientemente de la atopia. Células T CD8+CD28− humanas recientemente aisladas de la sangre periférica, no presentan propiedades supresoras sobre la proliferación o la sintesis de citocinas induzidas por alergenos en CMSP