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The purpose of this brief communication is to highlight emerging evidence to existing guidelines regarding potential benefits of supporting early, rather than delayed, peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma & Immunology, American Academy of Pediatrics, American College of Allergy, Asthma & Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Better management of allergic diseases needs a sharpened understanding of disease heterogeneity and mechanisms in relation to clinically significant outcomes. Phenotypes describing observable clinical and morphologic characteristics and unique responses to treatment have been developed; however, they do not relate to disease mechanisms. Recently, extended heterogeneous and disease-related metabolic, inflammatory, immunological, and remodeling pathways have been described, and reproducible patterns are defined as disease endotypes. An endotype might consist of several intricated mechanisms that cannot be clearly separated into "pure single molecular mechanism" thus being a "complex endotype." The description of an endotype may rely on biomarkers, which can be the signature of a complex underlying pathway or a key molecule associated with or directly playing a role in a particular disease endotype. The Th2 type inflammation can be defined as a complex endotype in asthma and linked to mechanisms of disease development and response to treatment and to disease outcomes such as exacerbations and remodeling. The type 2 complex endotype in allergies and asthma includes innate lymphoid cells, T helper 2 cells, tissue eosinophilia, and IgE production. Currently, emerging endotype-driven strategies in asthma, particularly the development of biologicals that target a single molecular pathway, are being focused for solving individualized clinical problems on disease outcomes. Progress is also being made for endotyping rhinitis, chronic rhinosinusitis, and atopic dermatitis.

The allergen challenge test has been the mainstay of diagnosis of allergic diseases for a long time since it offers a direct proof of the clinical relevance of a particular allergen for the allergic disease symptoms and severity. Standardisation and availability for daily practice (including safety issues) are still to be refined but most of the challenge tests have safely crossed the border from research tools to diagnostic tests available for daily practice for a well trained clinical staff., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy and Anaphylaxis Guidelines, managing patients with food allergy (FA) in the community, intend to provide guidance to reduce the risk of accidental allergic reactions to foods in the community. This document is intended to meet the needs of early-childhood and school settings as well as providers of non-prepackaged food (e.g., restaurants, bakeries, takeaway, deli counters, and fast-food outlets) and targets the audience of individuals with FA, their families, patient organizations, the general public, policymakers, and allergists. Food allergy is the most common trigger of anaphylaxis in the community. Providing children and caregivers with comprehensive information on food allergen avoidance and prompt recognition and management of allergic reactions are of the utmost importance. Provision of adrenaline auto-injector devices and education on how and when to use these are essential components of a comprehensive management plan. Managing patients at risk of anaphylaxis raises many challenges, which are specific to the community. This includes the need to interact with third parties providing food (e.g., school teachers and restaurant staff) to avoid accidental exposure and to help individuals with FA to make safe and appropriate food choices. Education of individuals at risk and their families, their peers, school nurses and teachers as well as restaurant and other food retail staff can reduce the risk of severe/fatal reactions. Increased awareness among policymakers may improve decision-making on legislation at local and national level., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

The majority of patients seeking medical advice for allergic diseases are first seen in a primary care setting. Correct diagnosis with identification of all offending allergens is an absolute prerequisite for appropriate management of allergic disease by the general practitioner. Allergy diagnostic tests recommended for use in primary care are critically reviewed in accordance with the significant workload in a primary care setting. Simplified pathways for recognition and diagnosis of allergic diseases are proposed, that should be further adapted to local (national) conditions., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Food allergies can have serious physical, social, and financial consequences. This systematic review examined ways to prevent the development of food allergy in children and adults., Methods: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after studies, interrupted time series studies, and prospective cohort studies. Experts were consulted for additional studies. There were no language or geographic restrictions. Two reviewers appraised the studies using appropriate tools. Data were not suitable for meta-analysis due to heterogeneity, so were narratively synthesized., Results: Seventy-four studies were included, one-third of which were of high quality. There was no good evidence to recommend that pregnant or breastfeeding women should change their diet or take supplements to prevent allergies in infants at high or normal risk. There were mixed findings about the preventive benefits of breastfeeding for infants at high or normal risk, but there was evidence to recommend avoiding cow's milk and substituting with extensively or partially hydrolyzed whey or casein formulas for infants at high risk for the first 4 months. Soy milk and delaying the introduction of solid foods beyond 4 months did not have preventive benefits in those at high or normal risk. There was very little evidence about strategies for preventing food allergy in older children or adults., Conclusions: There is much to learn about preventing food allergy, and this is a priority given the high societal and healthcare costs involved., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Allergic reactions to food can have serious consequences. This systematic review summarizes evidence about the immediate management of reactions and longer-term approaches to minimize adverse impacts., Methods: Seven bibliographic databases were searched from their inception to September 30, 2012, for systematic reviews, randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials, controlled before-and-after and interrupted time series studies. Experts were consulted for additional studies. There was no language or geographic restrictions. Two reviewers critically appraised the studies using the appropriate tools. Data were not suitable for meta-analysis due to heterogeneity so were narratively synthesized., Results: Eighty-four studies were included, but two-thirds were at high risk of potential bias. There was little evidence about acute management for non-life-threatening reactions. H1-antihistamines may be of benefit, but this evidence was in part derived from studies on those with cross-reactive birch pollen allergy. Regarding long-term management, avoiding the allergenic food or substituting an alternative was commonly recommended, but apart from for infants with cow's milk allergy, there was little high-quality research on this management approach. To reduce symptoms in children with cow's milk allergy, there was evidence to recommend alternatives such as extensively hydrolyzed formula. Supplements such as probiotics have not proved helpful, but allergen-specific immunotherapy may be disease modifying and therefore warrants further exploration., Conclusions: Food allergy can be debilitating and affects a significant number of people. However, the evidence base about acute and longer-term management is weak and needs to be strengthened as a matter of priority., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Allergen-specific immunotherapy (SIT) is the only available curative treatment of allergic diseases. Recent evidence provided a plausible explanation to its multiple mechanisms inducing both rapid desensitization and long-term allergen-specific immune tolerance, and suppression of allergic inflammation in the affected tissues. During SIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T cells, which suppress proliferative and cytokine responses against the allergen of interest. Regulatory T cells are characterized by IL-10 and TGF-beta secretion and expression of important cell surface suppressive molecules such as cytotoxic T lymphocyte antigen-4 and programmed death-1 that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Regulatory T cells and particularly IL-10 also have an influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies. In addition, development of allergen-specific B regulatory cells that produce IL-10 and develop into IgG4 producing plasma cells represent essential players in peripheral tolerance. These findings together with the new biotechnological approaches create a platform for development of the advanced vaccines. Moreover, reliable biomarkers could be selected and validated with the intention to select the patients who will benefit most from this immune-modifying treatment. Thus, allergen-SIT could provide a complete cure for a larger number of allergic patients and novel preventive approaches need to be elaborated.

The incidence, prevalence and costs of allergy have increased substantially in recent decades in many parts of Europe. The dominant model of allergy care within Europe is at the moment specialist-based. This model will become unsustainable and undeliverable with increasing disease prevalence. One solution to increase provision of allergy services is to diversify the providers. A new model for the provision of allergy care in the community with the general practitioner at the forefront is proposed. Pre- and postgraduate allergy education and training, implementation of pathways of care, allergy specialization and political will to generate resources and support are essential to achieve this new model. In parallel the holistic view of allergic diseases should be maintained, including assessment of severity and risk, psychological factors and health-care related costs in the context of the patient-centered decision making process., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The standard of care for allergies within a primary care (PC) setting has a strong influence on disease prevention and control, quality of life, and patient satisfaction. The level of knowledge of allergic diseases and the accessibility to regular follow-up are essential. EAACI and IPCRG conducted a survey to evaluate the actual status of care for allergic diseases in PC. Access to allergy and asthma specialist treatment was identified as the greatest 'unmet need'. The average waiting time between a referral and being seen in a public health service is usually >6 weeks. Referring the patients to an 'organ' specialist is much easier compared with referral to an allergist. Most PCPs have access to blood tests for total and specific IgE. Skin prick testing is available in only half of the cases, while provocation tests, allergen quantification in homes, and a dietician service are even less available. 20.6% of practices do not have access to allergy tests at all. Other issues raised were low political or general public awareness, lack of understanding by the patients of their allergic disease, the need to invest in PC, and to achieve sufficient competence at the appropriate level of care., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Asthma and obesity are chronic multifactorial conditions that are associated with gene-environment interaction and immune function. Although the data are not fully consistent, it seems that obesity increases the risk of asthma and compromises asthma control., Objective: To investigate the impact that weight changes have on asthma., Methods: We carried out a systematic review of three large biomedical databases. Studies were scrutinized and critically appraised according to agreed exclusion and inclusion criteria. Quality assessment of eligible papers was conducted using the GRADE method. Meta-analyses of comparable studies were carried out., Results: Thirty studies met the eligibility criteria of the review. Interventions were limited to dietary manipulation in three studies, one of which also used anti-obesity drugs, and bariatric surgery in four. All the other studies reported observational data. Becoming obese increased the odds for incident asthma by 1.82 (95% CI 1.47, 2.25) in adults and 1.98 (95% CI 0.71, 5.52) in children. Weight loss was associated with significant improvement in mean scores for symptoms, rescue medication score, and asthma exacerbations in the only randomized controlled trial. Similarly, evidence gathered from observational studies, with follow-up ranging between 8 weeks to 1 year, and from changes 1 year after bariatric surgery showed improvements in all asthma control-related outcomes. Changes in lung function were reported in one randomized controlled and eight observational studies of asthmatic subjects, with conflicting results. Either improvement after weight loss, decline with weight gain, or no effects at all were reported. Changes in airway inflammation and responsiveness were reported only by observational studies., Conclusion: Weight increases above the obesity threshold significantly increase the risk of asthma. The available studies show weak evidence of benefits from weight reduction on asthma outcomes., (© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Background: H1-antihistamines are recommended as the first-line symptomatic treatment of allergic rhinitis. The objective of this study was to evaluate the effects of rupatadine (RUP) versus desloratadine (DES) in subjects with seasonal allergic rhinitis (SAR)., Method: To assess the efficacy and safety of RUP in SAR in comparison with placebo (PL) and DES. A randomized, double-blind, multicenter, international, and PL-controlled study was carried out. The main selection criteria included SAR patients over 12 years old with a positive prick test to a relevant seasonal allergen for the geographic area. Symptomatic patients at screening with a nasal symptom sum score of ≥6 points (nasal discharge, nasal obstruction, sneezing, and nasal pruritus), a non-nasal score of ≥3 points (ocular pruritus, ocular redness, and tearing eyes), and a rhinorrhea score of ≥2 points with laboratory test results and electrocardiography within acceptable limits were included in the study. Change from baseline in the total symptom-score (T7SS) over the 4-week treatment period (reflective evaluation) was considered the primary efficacy variable. Secondary efficacy measures included total nasal symptom score (T4NSS) and conjunctival symptom score (T3NNSS), both of which are reflective and instantaneous evaluations. Furthermore questions related to quality of life (eg, sleep disturbances or impairment of daily activities) have also been evaluated. Safety was assessed according to adverse events reported, as well as laboratory and electrocardiography controls., Results: A total of 379 patients were randomized, of which 356 were included and allocated to PL (n = 122), RUP (n = 117), or DES (n = 117). Mean change of T7SS over the 4-week treatment period was significantly reduced in the RUP (-46.1%, P = 0.03) and DES (-48.9%, P = 0.01) groups, compared with PL. Similarly, RUP and DES were comparable and significantly superior to PL for all secondary endpoints, including nasal and conjunctival symptoms and patients' and investigator's overall clinical opinions. Symptom score evaluation (both reflective and instantaneous evaluations) throughout the treatment period showed a progressive and maintained significant improvement with both treatments at day 7 (P = 0.01), day 14 (P = 0.007), and day 21 (P = 0.01) in comparison with PL. Adverse events were scarce and were similar in both treatment groups. Electrocardiography (QTc) and lab test results did not show any relevant findings., Conclusion: RUP is a very good choice for SAR due to its contribution to the improvement of nasal (including obstruction) and non-nasal symptoms to a similar degree as DES.

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.

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Background: Abnormal breathing patterns may cause characteristic symptoms and impair quality of life. In a cross-sectional survey 29% of adults treated for asthma in primary care had symptoms suggestive of dysfunctional breathing (DB), more likely to be female and younger, with no differences for severity of asthma. No clear risk factors were demonstrated for DB in asthma, nor the impact of asthma medication was evaluated. The objective of this study was to describe the DB phenotype in adults with asthma treated in a specialised asthma centre., Methods: Adult patients aged 17-65 with diagnosed asthma were screened for DB using the Nijmegen questionnaire (positive predictive score >23) and confirmed by progressive exercise testing. The following were evaluated as independent risk factors for DB in the multiple regression analysis: female sex; atopy, obesity, active smoker, moderate/severe rhinitis, psychopathology, GERD, arterial hypertension; severe asthma, asthma duration > 5 years, lack of asthma control, fixed airway obstruction, fast lung function decline, frequent exacerbator and brittle asthma phenotypes; lack of ICS, use of LABA or LTRA., Results: 91 adults with asthma, mean age 35.04 ±1.19 years, 47(51.65%) females were evaluated. 27 (29.67%) subjects had a positive screening score on Nijmegen questionnaire and 16(17.58%) were confirmed by progressive exercise testing as having DB. Independent risk factors for DB were psychopathology (p = 0.000002), frequent exacerbator asthma phenotype (p = 0.01) and uncontrolled asthma (p < 0.000001)., Conclusion: Dysfunctional breathing is not infrequent in asthma patients and should be evaluated in asthma patients presenting with psychopathology, frequent severe asthma exacerbations or uncontrolled asthma. Asthma medication (ICS, LABA or LTRA) had no significant relation with dysfunctional breathing.

Asthma phenotypes have been developed to address the complexities of the disease. However, owing to a lack of longitudinal studies, little is known about the onset as well as the stability of phenotypes. Distinguishing phenotypes with regard to the severity or duration of the disease is essential. A phenotype covers the clinically relevant properties of the disease, but does not show the direct relationship to disease etiology and pathophysiology. Different pathogenetic mechanisms might cause similar asthma symptoms and might be operant in a certain phenotype. These putative mechanisms are addressed by the term 'endotype'. Classification of asthma based on endotypes provides advantages for epidemiological, genetic, and drug-related studies. A successful definition of endotypes should link key pathogenic mechanisms with the asthma phenotype. Thus, the identification of corresponding molecular biomarkers for individual pathogenic mechanism underlying phenotypes or subgroups within a phenotype is important. Whether newly defined asthma endotypes predict the individual course of asthma has to be validated in longitudinal studies. The accurate endotyping reflects natural history of asthma and should help to predict treatment response. Thus, understanding asthma endotypes might be useful in clinical practice., (© 2012 John Wiley & Sons A/S.)

Objective: The aim of this study was to evaluate the predictive value of lung function and fraction of exhaled nitric oxide (FeNO) for difficult asthma in children., Patients and Methods: Children with asthma referred to an asthma clinic for uncontrolled persistent asthma on inhaled corticosteroids (ICSs) alone or in combination with a long-acting beta2-agonist and/or a leukotriene receptor antagonist were followed in a prospective 1-year study to identify difficult asthma. At the end of the study period, difficult asthma was considered for children with persistent asthma symptoms and/or frequent moderate/severe asthma exacerbations despite regular intake of ICSs (beclomethasone or equivalent) > 800 microg/d for at least 3 months, after correcting for adherence to treatment, inhalation technique, and comorbidities and after implementing an individualized treatment plan. The difficult asthma phenotype was characterized using a multidimensional approach combining clinical features and pathophysiologic features (lung function and inflammation). Unfavorable lung function trend (persistent airway obstruction and fluctuations in forced expiratory volume in the first second of alpha > 0.5) and persistently high FeNO levels (> 45 ppb despite increasing ICS doses) were analyzed as risk factors for difficult asthma in the logistic regression analysis together with male sex, atopy, concurrent severe rhinitis, obesity, psychopathology, exposure to tobacco smoke, low socioeconomic status, lack of adherence to treatment, and persistent bronchodilator response., Results: Forty-six asthmatic children (34 males, 74%) with a mean (SEM) age of 7.55 (3.04) years were enrolled. After 1 year, 24 children (52%) were labeled as having difficult asthma. Independent risk factors for difficult asthma were persistently high FeNO (P = .04), obesity (P = .04), and severe rhinitis (P = .03)., Conclusions: Persistently high FeNO predicts difficult asthma in children, while unfavorable lung function trend does not.

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies., (Copyright © 2012 S. Karger AG, Basel.)

A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors., (© 2010 John Wiley & Sons A/S.)

Background: There are few data on asthma risk factors and phenotypes in patients with seasonal allergic rhinitis (SAR)., Methods: Thirty-three children (mean age, 8.27 ± 1.77 years) and 82 adults (mean age, 34.12 ± 10.59 years) with SAR were evaluated for asthma (history, reversibility of bronchial obstruction, increased inhaled nitric oxide). The following asthma risk factors were considered in the multiple regression analysis: male sex, family history of asthma, breastfeeding < 2 months, passive/active smoking, obesity, pets/molds exposure, high total serum immunoglobulin E (IgE), polysensitization (sensitized to 3 seasonal pollens with different structure), mixed sensitization (seasonal and perennial allergens), severe rhinitis (according to the Allergic Rhinitis and its Impact on Asthma guidelines), and lack of allergen-specific immunotherapy (SIT) for rhinitis preceding asthma diagnosis. Asthma phenotypes were characterized using the k-means clustering (silhouette method for cluster validation)., Results: Asthma was diagnosed in 22 (66.7%) children and in 57 (69.5%) adults with SAR. Independent risk factors for asthma were lack of SIT preceding asthma diagnosis, both for children (P = 0.008132) and adults (P = 0.000017), and mixed sensitization for children (P = 0.035694). Asthma phenotypes identified in children according to the associated risk factors were: breastfeeding < 2 months and severe rhinitis in 16 (63.6%) patients; male, polysensitized, and severe rhinitis in 8 (36.4%) patients. Asthma phenotypes in adults were: polysensitization and severe rhinitis in 30 (52.6%) patients; male, exposure to pets, and severe rhinitis in 11 (19.3%) patients; and high total serum IgE and polysensitization in 16 (28.1%) patients., Conclusion: Lack of SIT is an independent risk factor for asthma both in children and adults with SAR, whereas polysensitization is a risk factor only for children. The dominant asthma phenotype in children with SAR is breastfeeding < 2 months and severe rhinitis. In adults with SAR, the dominant asthma phenotype is polysensitization and severe rhinitis.

The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients’ values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.

Background: IL-17 expression was found to be associated with many inflammatory diseases in humans, such as rheumatoid arthritis, asthma, systemic lupus erythematosus and allograft rejection and many in vitro studies have indicated a proinflammatory function for IL-17., Objective: Prognostic value of increased serum IL-17 in asthma patients., Methods: Serum IL-17 (ELISA) was measured in 85 asthma patients (pts), mean age 46.99 +/- 14.1 years, 61% females, 23 mild persistent, 26 moderate persistent and 36 severe persistent asthma. Using multiple regression analysis (STATISTICA 7), increased serum IL-17 (>20 pg/ml) was tested as risk factor for severe asthma in comparison with "traditional" risk factors: smoke, NSAID intolerance, obesity, chronic rhinosinusitis, blood eosinophilia, FEV(1) at baseline < 50% predicted (low FEV(1))., Results: Medium serum IL-17 values were 14.21 pg/ml in mild asthma, 12.22 pg/ml in moderate asthma and 24.72 pg/ml in severe asthma. IL-17 values > 20 pg/ml were encountered in 3(13%) mild asthma pts (p < 0.001 vs. severe asthma), 2(8%) moderate asthma pts. (p < 0.001 vs. severe asthma), and in 11(31%) severe asthma pts. For severe asthma multiple regression analysis revealed as independent risk factors IL-17 (p = 0.000290), NSAID intolerance (p = 0.000585) and low FEV(1) (p = 0.000059)., Conclusions: IL-17 is increased in severe asthma compared to mild/moderate forms of the disease and values above 20 pg/ml are an independent risk factor for severe asthma., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Bilastine is a new non-sedative H(1) receptor antagonist, indicated for the treatment of allergic rhinitis (AR) (seasonal and perennial)., Objective: To assess and compare the efficacy and safety of bilastine 20 mg vs. cetirizine 10 mg and placebo in relieving the symptoms of seasonal allergic rhinitis (SAR)., Methods: Overall, 683 SAR patients, aged 12-70 years, were randomized to a double-blind treatment with bilastine 20 mg, cetirizine 10 mg or placebo, once daily for 14 days, in 61 centres across Europe. Patients recorded reflective (over the past 12 h) and instantaneous nasal (obstruction, rhinorrhoea, itching and sneezing) and non-nasal (ocular tearing, redness and itching) symptom scores (NSS and NNSS, respectively) twice daily, according to a pre-determined severity scale to provide reflective and instantaneous total symptom scores (TSS). The primary efficacy measure was the area under curve (AUC) of reflective TSS over 14 days of treatment (TSS-AUC(0-14 days)). Secondary efficacy measures included mean change from baseline in TSS, NSS and NNSS; discomfort caused by AR; and investigator's clinical global impression of the treatment. Safety was assessed according to adverse events (AEs), laboratory tests and electrocardiograms., Results: The mean TSS-AUC(0-14 days) (score x day) was reduced in bilastine- and cetirizine-treated groups to a similar and significantly greater extent, compared with placebo (76.5, 72.3 and 100.6, respectively; P<0.001). Similarly, bilastine and cetirizine were comparable and significantly superior to placebo for all secondary outcomes. While all treatments were well tolerated and the AE profiles of bilastine and placebo were similar, significantly fewer patients in the bilastine-treated group experienced somnolence (1.8%; P<0.001) and fatigue (0.4%; P=0.02) than patients in the cetirizine-treated group (7.5% and 4.8%, respectively)., Conclusions: Bilastine 20 mg once daily was significantly superior to placebo and comparable to cetirizine 10 mg in relieving symptoms of SAR, although it demonstrated a significantly better AE profile than cetirizine.

Several studies reported the appearance of asthma and autoimmune conditions in the same patient, but the clinical significance of this association was not yet assessed. One hundred asthmatic patients were observed for one year evolution with death, severe exacerbations, intake of > 1000 micrograms of beclometasone or equivalent (high ICS) and FEV1 decline >100 ml, in relation with ANA (ELISA), sputum and blood eosinophilia (EO), NSAID intolerance, BMI >25, chronic rhinosinusitis, smoking status and FEV1 <30% predicted (low FEV1). After 1 year of observation, there were 5 deaths, 28 severe asthma exacerbations requiring hospitalisations, 24 cases requiring high inhaled corticosteroid intake, and 19 patients with fast FEV1 decline (>100 ml/year). Multiple regression analysis pointed out several different independent risk factors for severe asthma evolution: for death presence of ANA (P=0.037), NSAID intolerance (P<0.001) and low FEV1 (P=0.021); for evolution with severe exacerbations ANA (p=0.011), sputum EO (P<0.001), smoking (P=0.044) and NSAID intolerance (P=0.022); for high ICS intake ANA (P=0.036), sputum EO (P=0.026) and low FEV1 (P=0.006); for FEV1 decline >100 ml ANA (P=0.006), sputum EO (P=0.037), BMI>25 (P=0.046) and NSAID intolerance (P=0.017). The presence of ANA is an independent risk factor in asthma for evolution with death, severe exacerbations, high inhaled corticosteroid intake and FEV1 decline >100 ml.

Background: With the current increasing incidence of allergies worldwide, new treatments showing efficacy and long term safety are needed for chronic conditions such as persistent allergic rhinitis (PER). New generation H1-antihistamines have demonstrated anti-allergic properties, which could possibly enhance their effectiveness in long-term periods of treatment., Objective: To investigate the efficacy of rupatadine, in controlling symptoms of PER over a 12-week period., Methods: A randomized, double blind, parallel-group, placebo-controlled study was carried out in patients aged older than 12 years with PER. Main inclusion criteria were: instantaneous total symptom score (i6TSS) >or=45, nasal obstruction score or=2 as moderate during the first visit. The primary efficacy endpoint was the 12-week average change from baseline of the patients' i6TSS., Results: In all, 736 patients were selected. Of them, 543 (73.8%) were randomized in three different groups: placebo (n = 185), cetirizine (n = 175) and rupatadine (n = 183). Rupatadine (P = 0.008) but not cetirizine (P = 0.07) statistically reduced the baseline i6TSS vs placebo (47.8%, 44.7% and 38.8%, respectively), after 12 weeks. Onset of action was observed at the first 24 h for both treatments (rupatadine vs placebo, P = 0.013; cetirizine vs placebo, P = 0.015). Furthermore, instantaneous total nasal symptoms score (iTNSS) (including nasal blockage) mean change from baseline showed a significant reduction with rupatadine 10 mg in comparison with placebo, along all treatment duration of 12 weeks. Study treatments were well tolerated., Conclusion: Rupatadine significantly relieves symptoms of PER, providing a rapid onset of action and maintains its effects over a long period of 12-weeks.

Unlabelled: The vasooclusive features of scleroderma are attributed to the vessel wall anomalies, while platelet's intervention is less studied., Aim: platelet activation markers (PAM) pattern and significance in systemic sclerosis., Design: 20 scleroderma patients with severe Raynaud phenomenon, under aspirin treatment, were evaluated by quantitative flow-cytometry for PAM (P-selectin, GPIIbIIIa, CD40L) in correlation with scleroderma activity and severity, systemic endothelial dysfunction (flow-mediated vasodilatation), systemic inflammation (serum CRP and IL-6) and cold-provocation test. Associated autoantibodies (ANCA, antiTPO, anticardiolipin, antiplatelet, antimitochondrial antibodies) were evaluated in relation to IL-6., Results: PAM were expressed in 11 (55%) cases: P-selectin in 5 (45.45%), GPIIbIIIa in 1 (9.1%), combined P-selectin and GPIIbIIIa in 5 (45.45%), CD40L in 0 cases. Scleroderma patients expressing PAM had increased incidence of disease activity and severity. There was no correlation between PAM and systemic endothelial dysfunction. CRP increased in 14(70%) cases was correlated with P-selectin and GPIIbIIIa expression (r = 0.28). Normal IL6 present in 19 (90.9%) cases was correlated with lack of CD40L expression (r = 0.69) and with low autoantibodies incidence (r = 0.69 for ANCA, 0.55 for anti TPO and antiplatelet, 0.39 for anti cardiolipin, 0.45 for antimitochondrial). After cold provocation test PAM were significantly lost and were not expressed de novo., Conclusions: In systemic scleroderma platelet activation markers are correlated with disease activity and severity and increased CRP and are not correlated with systemic endothelial dysfunction or exposure to cold. Normal IL-6 was correlated with lack of CD40L expression and with low incidence of associated autoantibodies.

Background: Major antibiotic trials targeting Chlamydia Pneumoniae or the pathogen burden in acute coronary syndromes reported conflicting data. Only a minor impact of antibiotic treatment on major cardiovascular events (MACE) incidence was demonstrated in some studies., Methods and Results: 109 unstable angina patients were randomised in: group C receiving conventional treatment, group R treated with Rovamycine 12 days 4.5 MUI iv /day as add-on therapy, group R1 treated with Rovamycine 12 days 4.5 MUI iv/day followed by 6 MUI/day per os for another 12 days add on treatment. Randomisation into the therapeutical groups was independent of the serological status for Chlamydia pneumoniae. The primary adverse end-points of the study were the incidence of major cardiovascular events at 3 months, 6 months and at 4 years and the 4 years cumulated end-point rate. Secondary adverse end-points were the incidence of recurrent stable angina at 3 and 6 months and the incidence of increased serum levels of C reactive protein and fibrinogen at 3 and 6 months. Statistics used multiple regression analysis and Chi square test. At 6 months the incidence of unstable angina with readmission was significantly lower in groups R and R1 compared to group C (p < 0.001, respective p < 0.0001) and significantly lower in group R1 compared to group R (p < 0.0001). The incidence of nonfatal myocardial infarction at 6 months was significantly lower in groups R and R1 compared to group C (p < 0.0001). The incidence of cardiovascular death was significantly lower in group R1 compared to group C and R (p < 0.001). At 4 years the incidence of unstable angina with readmission and the cumulated end point rate were significantly reduced in groups R and R1 compared to group C. The 3 months incidence of increased serum levels of C reactive protein was significantly decreased in group R1 compared to groups C and R (p<0.001). The 3 months incidence of increased serum levels of fibrinogen was significantly lower in groups R and R1 compared to group C (p<0.002, respectively p<0.001)., Conclusions: In patients with unstable angina Rovamycine as add-on treatment to the conventional treatment lead to a significant decrease of MACE incidence at 6 months and to a significant decrease in the 4 years incidence of unstable angina with readmission. The beneficial effect of Rovamycine was parallel to the decrease in serum inflammations markers concentration.