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A worldwide increase in prevalence of allergic diseases has led to adaptations in national and international health care systems. ARIA (Allergic Rhinitis and Its Impact on Asthma) initiative develops internationally applicable guidelines for allergic respiratory diseases. In collaboration with international initiatives, ARIA offers updates of real-life integrated care pathways (ICPs) for digitally assisted, integrated, and individualized treatment of allergic rhinitis (AR). This article presents certain aspects of the health care system in Kuwait with reference to the management of AR and the objective of introducing ICPs and adopting the latest ARIA recommendations. Guidelines for ICPs include aspects of patients and health care providers and cover key areas of management of AR. This model of guidelines supports real-life health care better than traditional models. ARIA recommendations will be locally integrated in the health care system with the aim of improving both pharmacotherapy and allergy immunotherapy.

Introduction Sublingual immunotherapy (SLIT) with birch pollen extract has been shown to be an efficacious treatment of allergic rhinitis (AR). An as-yet unanswered question is whether and how clinical benefit translates into patient benefit, i.e. what benefit patients derive from this treatment. Methods This 1-year, open, prospective, multicenter, non-interventional study conducted in 75 German centers measured patient-relevant benefit of birch pollen SLIT (Staloral® Birch) using the questionnaire “Patient Benefit Index for Allergic Rhinitis (PBI-AR)”. At treatment onset, patients rated the importance of 25 treatment needs; after the first birch pollen season on treatment, goal achievement was evaluated. A preference-weighted benefit index was calculated and its association with gender, asthma, allergy status, and severity of AR symptoms was determined. Results Mean age of the 291 adult patients was 38.8 years; 58.4% were female. The most important treatment goals were to “be able to stay outdoors without symptoms” (87.3% quite or very important), “no longer have a runny or stuffed-up nose” (86.9%), and “be able to breathe through your nose more freely” (86.9%). The treatment goals with the highest benefit ratings (referring to those patients to whom the respective goal applied) were to “have confidence in the therapy” (60.5% has helped “quite” or “very much”), “have an easily applicable treatment” (55.6%), and “be able to breathe through my nose more freely” (51.7%). The average PBI-AR global score was 2.19 (SD 1.04) (0–4; with 4 indicating maximum benefit). No significant differences in PBI-AR global score or subscales were found between men and women, poly- and monoallergic patients, or patients with severe versus mild rhinoconjunctivitis. Patients with asthma reported relevant but lower benefit than patients without asthma. Conclusion After 1 year of birch pollen SLIT treatment, patients reported considerable benefit, mainly due to a reduction of physical symptoms and treatment burden.

Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2 are receptors that act in co-stimulatory and coinhibitory immune responses. Signaling the PD-1/PD-L1 or PD-L2 pathway is essential to regulate the inflammatory responses to infections, autoimmunity, and allergies, and it has been extensively studied in cancer. Allergic diseases include asthma, rhinoconjunctivitis, atopic dermatitis, drug allergy, and anaphylaxis. These overactive immune responses involve IgE-dependent activation and increased CD4+ T helper type 2 (Th2) lymphocytes. Recent studies have shown that PD-L1 and PD-L2 act to regulate T-cell activation and function. However, the main role of PD-1 and its ligands is to balance the immune response; however, the inflammatory process of allergic diseases is poorly understood. These immune checkpoint molecules can function as a brake or a kick-start to regulate the adaptive immune response. These findings suggest that PD-1 and its ligands may be a key factor in studying the exaggerated response in hypersensitivity reactions in allergies. This review summarizes the current understanding of the role of PD-1 and PD-L1 and PD-L2 pathway regulation in allergic diseases and how this immunomodulatory pathway is currently being targeted to develop novel therapeutic immunotherapy.

Allergic asthma often coexists with different pathological conditions, called multimorbidities, that are mostly of allergic nature and share a common underlying inflammatory pathophysiological mechanism. Multimorbidities of allergic asthma may influence asthma control, its severity, and patients' response to treatment, and contribute to the overall socioeconomic burden of the disease. Immunoglobulin E (IgE) is known to play a central role in the pathogenesis of various allergic diseases, including asthma. Thus, IgE-mediated immunologic pathways present an attractive target for intervention in asthma and multimorbidities. In this review, we discuss the most frequently reported IgE-mediated multimorbidities in allergic asthma, including allergic rhinitis, rhinoconjunctivitis, atopic dermatitis, vernal keratoconjunctivitis, chronic rhinosinusitis with nasal polyps, food allergies, and allergic bronchopulmonary aspergillosis. Omalizumab is a recombinant humanized monoclonal antibody against IgE and has been in use to treat allergic asthma for more than a decade. We comprehensively review the clinical evidence for omalizumab in the treatment of the aforementioned multimorbidities in allergic asthma. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology

Allergic rhinitis is one of the most common human diseases and causes a deterioration of the quality of life. The prevalence of allergic rhinitis in the Russian Federation and in the world has increased significantly. The main pharmacological group in the treatment of allergic rhinitis is the 2nd generation antihistamines with high affinity for H1-receptors. The article presents an overview of the new representative of the abovementioned group of drugs - the drug bilastine (Nixar®).

This study analyzed the predictive power of sociodemographic (age, sex) and medical variables (months since diagnosis and in treatment, immunotherapy, number of environmental allergens, food allergies or atopic dermatitistypes) on the quality of life of patients with rhinoconjunctivitis and bronchial asthma, using models based on comparative qualitative fuzzy analysis to compare them according to the pathology(s). Retrospective cross-sectional design.Sixty-four adolescents (65.60% boys) diagnosed with rhinoconjunctivitis and/or bronchial asthma aged between 12 and 16 years old (M= 14.02; SD = 1.45). The data were collected between February 2019 and January 2020 using the Brief Disease Perception Questionnaire (B-IPQ), the Adolescent Rhinoconjunctivitis Quality of Life Questionnaire (AdolRQoLQ) and the Respiratory Disease Questionnaire Self-administered and Standardized Chronicle (CRQ-SAS). Qualitative comparative analysis models (QCA) were used. In the QCA models, the various combinations indicated that the variables that predicted a higher quality of life for both rhinocojuntivitis symptoms and respiratory symptoms were receiving longer-term immunotherapy and a perceived lower threat of the disease. The consistencies of the models vary between 23-29%. In conclusion, the patients' QoL was explained by the presence of longer-term immunotherapy and a less threatening perception of the disease. Therefore, early multidisciplinary diagnosis and treatment is important.

Background: As in many fields of medical care, the coronavirus disease 2019 (COVID-19) resulted in an increased uncertainty regarding the safety of allergen immunotherapy (AIT). Therefore, the European Academy of Allergy and Clinical Immunology (EAACI) aimed to analyze the situation in different countries and systematically collect all information available regarding tolerability and possible amendments in daily practice of sublingual AIT (SLIT), subcutaneous AIT (SCIT) for inhalant allergies and venom AIT.Method: Under the framework of the EAACI, a panel of experts in the field of AIT coordinated by the Immunotherapy Interest Group (IT IG) set-up a web-based retrospective survey (SurveyMonkey®) including 27 standardized questions on practical and safety aspects on AIT in worldwide clinical routine. Results: 417 respondents providing AIT to their patients in daily routine answered the survey. For patients (without any current symptoms to suspect COVID-19), 60% of the respondents informed of not having initiated SCIT (40% venom AIT, 35% SLIT) whereas for the maintenance phase of AIT, SCIT was performed by 75% of the respondents (74% venom AIT, 89% SLIT). No tolerability concern arises from this preliminary analysis. 16 physicians reported having performed AIT despite (early) symptoms of COVID-19 and/or a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Conclusions: This first international retrospective survey in atopic diseases investigated practical aspects and tolerability of AIT during the COVID-19 pandemic and gave no concerns regarding reduced tolerability under real-life circumstances. However, the data indicate an undertreatment of AIT, which may be temporary, but could have a long-lasting negative impact on the clinical care of allergic patients. Keywords: COVID-19, allergen immunotherapy (AIT), SARS-CoV-2, practicability, survey, safety, pandemic

Adolescent and young adult (AYA) patients need additional support, while they experience the challenges associated with their age. They need specific training to learn the knowledge and skills required to confidently self-manage their allergies and/or asthma. Transitional care is a complex process, which should address the psychological, medical, educational and vocational needs of AYA in the developmentally appropriate way. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline to provide evidence-based recommendations for healthcare professionals to support the transitional care of AYA with allergy and/or asthma. This guideline was developed by a multidisciplinary working panel of experts and patient representatives based on two recent systematic reviews. It sets out a series of general recommendations on operating a clinical service for AYA, which include the following: (a) starting transition early (11-13 years), (b) using a structured, multidisciplinary approach, (c) ensuring AYA fully understand their condition and have resources they can access, (d) active monitoring of adherence and (e) discussing any implications for further education and work. Specific allergy and asthma transition recommendations include (a) simplifying medication regimes and using reminders; (b) focusing on areas where AYA are not confident and involving peers in training AYA patients; (c) identifying and managing psychological and socio-economic issues impacting disease control and quality of life; (d) enrolling the family in assisting AYA to undertake self-management; and (e) encouraging AYA to let their friends know about their allergies and asthma. These recommendations may need to be adapted to fit into national healthcare systems.

The prevalence of ocular allergies has been increasing worldwide for the past several decades. The geographical distribution and hot spots of rhinoconjunctivitis have been documented in a global survey by the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC indicated that Africa, Latin America, and Japan were notable for their high prevalence of rhinoconjunctivitis. The outcomes of follow-up studies of regional differences and the characteristics of allergic conjunctivitis are summarized in this review. Currently, comorbid diseases and socioeconomic and environmental factors, including climate and air pollution, are proposed to contribute to the regional differences in the prevalence of allergic conjunctivitis. Of them, rhinitis has been shown repeatedly to be significantly associated with allergic conjunctivitis. Their mechanistic aspects on association with the prevalence of systemic allergic diseases have been reviewed by examining the birth cohort or in vitro analyses. A vision threatening form of ocular allergy, vernal keratoconjunctivitis, is prevalent in the African countries and Japan. Of the proposed associated factors, air pollution was shown to contribute not only to aggravating the symptoms but also to the increase in the incidence of its severe forms. Its mechanistic aspects are discussed in this review in the context of comorbid diseases.

Background A novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen–induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety. Methods This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen–allergic adults to receive placebo or cumulative doses of 70, 170 or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen–specific immunoglobulins were analysed before and after treatment. Results Conjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per-protocol set). Also, 39% of patients in the 170-μg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG4 levels increased to 1.6-fold (70 μg), 3.1-fold (170 μg) and 3.9-fold (370 μg) (mPP). Conclusion Three-week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.

Background Sensitization to both inhalant and food allergens has been shown to be risk factors for development of asthma and rhinoconjunctivitis (RC). However, few studies have addressed the role of transient or persistent IgE sensitization to specific allergens in early life for later development of allergic diseases. The aim of this study was to explore the association between transient and persistent sensitization in early life and the development of asthma and RC at 6 and 14 years. Methods The Danish Allergy Research Center (DARC) cohort is a prospective non-interventional birth cohort study comprising 562 children. For the purpose of this study, we examined a subgroup of the original cohort with specific IgE measured at, at least 3 of 4 follow-ups between 3 and 18 months of age (n = 366). Multiple logistic regression models were used to investigate the association between transient and persistent early-life sensitization to groups of and to individual allergens and asthma and RC at 6 and 14 years compared to a reference group with no sensitization. Results Both transient early-life sensitization and persistent early-life sensitization to cow's milk or hen's egg proteins were associated with asthma (aOR 3.99[1.41-11.32] and 5.95[1.78-19.92]) and RC (aOR 2.94[1.19-7.28] and 6.18[1.86-20.53]) at 14 years, this association being driven mainly by sensitization to hen's egg. Transient early-life sensitization to house dust mite (HDM) had increased risk of asthma (aOR 3.80[1.17-12.41]) at 14 years. Conclusions Early transient IgE sensitization and persistent IgE sensitization to hen's egg were associated with asthma and RC at 14 years. Furthermore, sensitization to HDM was associated with asthma at 14 years.

Allergic rhinitis is one of the most common human diseases that affect patients’ quality of of life. There has been a significant increase in incidence rates related to allergic rhinitis in the Russian Federation and the world. Second-generation antihistamines having high H1-receptor affinity constitute the main pharmacological group for the treatment of allergic rhinitis. The article presents an overview of Bilastin as a novel drug of the above group.

Allergic rhinitis is one of the most widespread human diseases. The article presents the modern classification of allergic rhinitis, the main approaches to treatment. The indications for carrying out hyposensitizing therapy for this disease have been determined, the effectiveness of nonspecific hyposensitizing therapy, conducted with the antihistamines of the second generation, which have a high affinity for H1 receptors. Also demonstrated the possibilities of the original drug bilastin (Nixar) – a representative of a group of antihistamines.

Background: Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global prevalence of symptoms of asthma in children. We undertook comprehensive analyses addressing risk factors for asthma symptoms in combination, at both the individual and the school level, to explore the potential role of reverse causation due to selective avoidance or confounding by indication. Objective: To explore the role of reverse causation in risk factors of asthma symptoms. Methods: We compared two sets of multilevel logistic regression analyses, using (a) individual level exposure data and (b) school level average exposure (ie prevalence), in two different age groups. In individual level analyses, reverse causation is a possible concern if individual level exposure statuses were changed as a result of asthma symptoms or diagnosis. School level analyses may suffer from ecologic confounding, but reverse causation is less of a concern because individual changes in exposure status as a result of asthma symptoms would only have a small effect on overall school exposure levels. Results: There were 131 924 children aged 6-7 years (2428 schools, 25 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (odds ratio = 2.06; 95% confidence interval 1.97-2.16), early life antibiotic use (1.65; 1.58-1.73) and open fire cooking (1.44; 1.26-1.65). In school level analyses, these risk factors again showed increased risks. There were 238 586 adolescents aged 13-14 years (2072 schools, 42 countries) with complete exposure, outcome and confounder data. The strongest associations in individual level analyses (fully adjusted) were for current paracetamol use (1.80; 1.75-1.86), cooking on an open fire (1.32; 1.22-1.43) and maternal tobacco use (1.23; 1.18-1.27). In school level analyses, these risk factors again showed increased risks. Conclusions & clinical relevance: These analyses strengthen the potentially causal interpretation of previously reported individual level findings, by providing evidence against reverse causation. We would like to acknowledge and thank the many funding bodies throughout the world that supported the individual ISAAC centres and collaborators and their meetings. In particular, we wish to thank the London School of Hygiene and Tropical Medicine, and the United Kingdom Medical Research Council for supporting the work involved in the current paper. We also wish to thank the Health Research Council of New Zealand, the Asthma and Respiratory Foundation of New Zealand, the Child Health Research Foundation, the Hawke's Bay Medical Research Foundation, the Waikato Medical Research Foundation, Glaxo Wellcome New Zealand, the NZ Lottery Board and Astra Zeneca New Zealand. Glaxo Wellcome International Medical Affairs supported the Regional Coordination and the ISAAC International Data Centre (IIDC). Without help from all of the above, ISAAC would not have given us all these results from so many countries. The research leading to these results has partially been supported by the United Kingdom Medical Research Council [grant number MR/N013638/1] and funding from the European Research Council under the European Union's Seventh Framework Programme [FP7/2007-2013/ERC grant agreement number 668954]. The Centre for Global NCDs is supported by the Wellcome Trust Institutional Strategic Support Fund [097834/Z/11/B].

Ragweed allergy is a major public health concern. Within Europe, ragweed is an introduced species and research has indicated that the amounts of ragweed pollen are likely to increase over Europe due to climate change, with corresponding increases in ragweed allergy. To address this threat, improving our understanding of predisposing factors for allergic sensitisation to ragweed and disease is necessary, specifically focusing upon factors that are potentially modifiable (i.e., environmental). In this study, a total of 4013 children aged 2–13 years were recruited across Croatia to undergo skin prick tests to determine sensitisation to ragweed and other aeroallergens. A parental questionnaire collected home environment, lifestyle, family and personal medical history, and socioeconomic information. Environmental variables were obtained using Geographical Information Systems and data from nearby pollen, weather, and air pollution stations. Logistic regression was performed (clustered on school) focusing on risk factors for allergic sensitisation and disease. Ragweed sensitisation was strongly associated with ragweed pollen at levels over 5000 grains m–3 year−1 and, above these levels, the risk of sensitisation was 12–16 times greater than in low pollen areas with about 400 grains m–3 year−1. Genetic factors were strongly associated with sensitisation but nearly all potentially modifiable factors were insignificant. This included measures of local land use and proximity to potential sources of ragweed pollen. Rural residence was protective (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55–0.98), but the factors underlying this association were unclear. Being sensitised to ragweed doubled (OR 2.17, 95% CI 1.59–2.96) the risk of rhinoconjunctivitis. No other potentially modifiable risk factors were associated with rhinoconjunctivitis. Ragweed sensitisation was strongly associated with ragweed pollen, and sensitisation was significantly associated with rhinoconjunctivitis. Apart from ragweed pollen levels, few other potentially modifiable factors were significantly associated with ragweed sensitisation. Hence, strategies to lower the risk of sensitisation should focus upon ragweed control.

Aim: A double-blind placebo-controlled study was conducted according to EMA guidelines, to evaluate safety, tolerability and short-term treatment effects of three updosing regimens of Dermatophagoides pteronyssinus subcutaneous allergen immunotherapy. Patients & methods: Forty-eight patients were randomized to groups: A (six weekly doses), B (eight weekly doses) or C (eight doses, two clustered doses over 3 weeks). Results: The most frequent adverse events were local reactions. No serious adverse events were found. Severe systemic reactions were reported more frequently in Group C. Decreased cutaneous responses and increased specific IgGs were shown in all active groups, even within the short-term. Conclusion: Dermatophagoides pteronyssinus subcutaneous allergen immunotherapy in depot presentation exhibited good safety and tolerability. Group A seemed to show the best profile for further clinical development.

Allergic rhinitis is one of most widespread human diseases associated with severe limitations in physical, psychological, and social aspects of life, which is the reason for the decline in quality of life. The drugs of first choice in patients with symptoms of seasonal and perennial allergic rhinitis of intermittent as well as of persistent courses are antihistamines of 2nd generation with high affinity to H1-receptors. The article is about a new representative of the above group of drugs, the original drug Niksar® (bilastine).

Aim: To evaluate tolerability and efficacy of Parietaria judaica subcutaneous immunotherapy on patients with allergic rhinoconjunctivitis. Patients & methods: 51 patients were assigned to build-up scheme (six increasing doses) of P. judaica depot native extract, plus three maintenance monthly administrations. Results: Out of 470 administered doses, only 3.8% elicited systemic reactions (1.5% nonspecific and 2.3% grade I). Concerning the exploratory efficacy parameters: cutaneous reactivity at the final visit versus baseline was significantly decreased; specific titers of IgG and IgG4 increased significantly and patients showed a significant decrease in the rhinitis symptoms score. Conclusion:P. judaica subcutaneous immunotherapy (Allergovac((R)) depot ROXALL Medicina Espana S.A., Zamudio, Spain) with an abbreviated up-dosing scheme showed an adequate safety and tolerability profile and induced preliminary efficacy changes.

ObjectiveTo determine the prevalence of symptoms of asthma, rhinitis, and atopic eczema in adolescents (AD; 13‐14 years) living in seven Brazilian cities, by applying the standardized written questionnaire (WQ) of the International Study of Asthma and Allergies in Childhood (ISAAC), and to evaluate the time trend nine years after the last assessment of ISAAC phase 3 (ISP3).MethodsThe ISAAC‐WQ was answered by 20,099 AD from the Northern, Northeastern, Southeastern, and Southern Brazilian regions. Values obtained were compared to those observed in ISP3 using nonparametric (chi‐squared or Fisher) tests, and the ratio of annual increment/decrement was established for each of the centers, according to the symptom assessed.ResultsConsidering the national data and comparing to values of ISP3, there was a decrease in the mean prevalence of active asthma (18.5% vs. 17.5%) and an increase in the frequency of severe asthma (4.5% vs. 4.7%) and physician‐diagnosed asthma (14.3% vs. 17.6%). An increase in prevalence of rhinitis, rhinoconjunctivitis, and atopic eczema was also observed.ConclusionsThe prevalence of asthma, rhinitis, and atopic eczema in Brazil was variable; higher prevalence values, especially of asthma and eczema, were observed in regions located closer to the Equator.ResumoObjetivoDeterminar a prevalência de sintomas relacionados à asma, à rinite e ao eczema atópico em adolescentes (13‐14 anos, AD) residentes em sete cidades brasileiras com o questionário escrito (QE) padronizado do International Study of Asthma and Allergies in Childhood (Isaac) e verificar a tendência temporal passados nove anos da última avaliação do Isaac fase 3 (ISF3).MétodosO QE Isaac foi respondido por 20.099 AD (13‐14 anos) moradores em centros das regiões Norte, Nordeste, Sudeste e Sul. Os índices obtidos foram comparados aos do ISF3 com o teste não paramétrico (qui‐quadrado ou Fisher) e foi estabelecida a taxa de incremento/decremento anual para cada um dos centros segundo o sintoma avaliado.ResultadosEm relação ao ISF3, considerando‐se os dados nacionais, houve queda da prevalência média de asma ativa (18,5% vs. 17,5%) com elevação da frequência de asma grave (4,5% vs. 4,7%) e de asma diagnosticada por médico (14,3% vs. 17,6%). Aumento da prevalência de rinite e rinoconjuntivite e de eczema flexural também ocorreram.ConclusõesA prevalência de asma, rinite e eczema atópico no Brasil foi variável. Valores mais altos, sobretudo de asma e eczema, foram observados nos centros localizados mais próximos ao Equador.

OBJETIVO: Determinar a prevalência de sintomas relacionados à asma, à rinite e ao eczema atópico em adolescentes (13-14 anos, AD) residentes em sete cidades brasileiras com o questionário escrito (QE) padronizado do International Study of Asthma and Allergies in Childhood (Isaac) e verificar a tendência temporal passados nove anos da última avaliação do Isaac fase 3 (ISF3). MÉTODOS: O QE Isaac foi respondido por 20.099 AD (13-14 anos) moradores em centros das regiões Norte, Nordeste, Sudeste e Sul. Os índices obtidos foram comparados aos do ISF3 com o teste não paramétrico (qui-quadrado ou Fisher) e foi estabelecida a taxa de incremento/decremento anual para cada um dos centros segundo o sintoma avaliado. RESULTADOS: Em relação ao ISF3, considerando-se os dados nacionais, houve queda da prevalência média de asma ativa (18,5% vs. 17,5%) com elevação da frequência de asma grave (4,5% vs. 4,7%) e de asma diagnosticada por médico (14,3% vs. 17,6%). Aumento da prevalência de rinite e rinoconjuntivite e de eczema flexural também ocorreram. CONCLUSÕES: A prevalência de asma, rinite e eczema atópico no Brasil foi variável. Valores mais altos, sobretudo de asma e eczema, foram observados nos centros localizados mais próximos ao Equador. OBJECTIVE: To determine the prevalence of symptoms of asthma, rhinitis, and atopic eczema in adolescents (AD; 13-14 years) living in seven Brazilian cities, by applying the standardized written questionnaire (WQ) of the International Study of Asthma and Allergies in Childhood (ISAAC), and to evaluate the time trend nine years after the last assessment of ISAAC phase 3 (ISP3). METHODS: The ISAAC-WQ was answered by 20,099 AD from the Northern, Northeastern, Southeastern, and Southern Brazilian regions. Values obtained were compared to those observed in ISP3 using nonparametric (chi-squared or Fisher) tests, and the ratio of annual increment/decrement was established for each of the centers, according to the symptom assessed. RESULTS: Considering the national data and comparing to values of ISP3, there was a decrease in the mean prevalence of active asthma (18.5% vs. 17.5%) and an increase in the frequency of severe asthma (4.5% vs. 4.7%) and physician-diagnosed asthma (14.3% vs. 17.6%). An increase in prevalence of rhinitis, rhinoconjunctivitis, and atopic eczema was also observed. CONCLUSIONS: The prevalence of asthma, rhinitis, and atopic eczema in Brazil was variable; higher prevalence values, especially of asthma and eczema, were observed in regions located closer to the Equator. Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Department of Pediatrics Universidade Federal do Paraná Universidade Federal de Pernambuco Department of Pediatrics Universidade Estadual do Pará Universidade Federal de Alagoas Department of Pediatrics Universidade Federal de Sergipe Department of Pediatrics Universidade Federal de Minas Gerais Department of Pediatrics Universidade de Santiago UNIFESP, EPM, Department of Pediatrics SciELO

Background and Aim The burden of childhood asthma and its risk factors is an important but neglected public health challenge in Latin America. We investigated the association between allergic symptoms and dietary intake in children from this region. Methods As part of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase III, questionnaire collected dietary intake was investigated in relation to risk of parental/child reported current wheeze (primary outcome) and rhino-conjunctivitis and eczema. Per-country adjusted logistic regressions were performed, and combined effect sizes were calculated with meta-analyses. Results 143,967 children from 11 countries had complete data. In children aged 6–7 years, current wheeze was negatively associated with higher fruit intake (adjusted odds ratio [aOR] 0.65; 95% CI 0.74, 0.97). Current rhino-conjunctivitis and eczema were statistically negatively associated with fruit intake (aOR 0.72; 95% CI 0.64, 0.82; and OR 0.64, 95% CI 0.56, 0.74, respectively). Vegetable intake was negatively associated with risk of symptoms in younger children, but these associations were attenuated in the 13–14 years old group. Fastfood/burger intake was positively associated with all three outcomes in the older children. Conclusion A higher intake of fruits and vegetables was associated with a lower prevalence of allergic symptoms in Latin American children. Conversely, intake of fastfood was positively associated with a higher prevalence of wheeze in adolescents. Improved dietary habits in children might help reduce the epidemic of allergic symptoms in Latin America. Food interventions in asthmatic children are needed to evaluate the possible public health impact of a better diet on respiratory health. Electronic supplementary material The online version of this article (doi:10.1007/s00408-017-0044-z) contains supplementary material, which is available to authorized users.

Allergic rhinitis is one of the most common chronic diseases in childhood. The International Study of Asthma and Allergies in Childhood reported an average prevalence rhinitis of 8.5% among 6-7-year-old children, and 14.6% for 13-14 year-old children1. The burden of allergic rhinitis to individual patients and the society is often underestimated, and there is a general lack of data on the risk factors and phenotypes of rhinitis in childhood and adolescence2.

Background: BM32 is a grass pollen allergy vaccine based on recombinant fusion proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4 major grass pollen allergens and the hepatitis B preS protein. Objective: We sought to study the safety and clinical efficacy of immunotherapy (allergen immunotherapy) with BM32 in patients with grass pollen-induced rhinitis and controlled asthma. Methods: A double-blind, placebo-controlled, multicenter allergen immunotherapy field study was conducted for 2 grass pollen seasons. After a baseline season, subjects (n = 181) were randomized and received 3 preseasonal injections of either placebo (n = 58) or a low dose (80 mu g, n = 60) or high dose (160 mu g, n = 63) of BM32 in year 1, respectively, followed by a booster injection in autumn. In the second year, all actively treated subjects received 3 preseasonal injections of the BM32 low dose, and placebo-treated subjects continued with placebo. Clinical efficacy was assessed by using combined symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of Life Questionnaires, and asthma symptom scores. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology. Allergen-specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP ISAC. Results: Although statistical significance regarding the primary end point was not reached, BM32-treated subjects, when compared with placebo-treated subjects, showed an improvement regarding symptom medication, visual analog scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom scores in both treatment years. This was accompanied by an induction of allergen-specific IgG without induction of allergen-specific IgE and a reduction in the seasonally induced increase in allergen-specific IgE levels in year 2. In the first year, more grade 2 reactions were observed in the active (n = 6) versus placebo (n = 1) groups, whereas there was almost no difference in the second year. Conclusions: Injections of BM32 induced allergen-specific IgG, improved clinical symptoms of seasonal grass pollen allergy, and were well tolerated.

Whether exposure to outdoor air pollution increases the prevalence of rhinoconjunctivitis in children is unclear. Using data from Phase Three of the International Study of Asthma and Allergies in childhood (ISAAC), we investigated associations of rhinoconjunctivitis prevalence in adolescents with model-based estimates of ozone, and satellite-based estimates of fine (diameter

Importance Sublingual immunotherapy and subcutaneous immunotherapy are effective in seasonal allergic rhinitis. Three years of continuous treatment with subcutaneous immunotherapy and sublingual immunotherapy has been shown to improve symptoms for at least 2 years following discontinuation of treatment. Objective To assess whether 2 years of treatment with grass pollen sublingual immunotherapy, compared with placebo, provides improved nasal response to allergen challenge at 3-year follow-up. Design, Setting, and Participants A randomized double-blind, placebo-controlled, 3–parallel-group study performed in a single academic center, Imperial College London, of adult patients with moderate to severe seasonal allergic rhinitis (interfering with usual daily activities or sleep). First enrollment was March 2011, last follow-up was February 2015. Interventions Thirty-six participants received 2 years of sublingual immunotherapy (daily tablets containing 15 µg of major allergen Phleum p 5 and monthly placebo injections), 36 received subcutaneous immunotherapy (monthly injections containing 20 µg of Phleum p 5 and daily placebo tablets) and 34 received matched double-placebo. Nasal allergen challenge was performed before treatment, at 1 and 2 years of treatment, and at 3 years (1 year after treatment discontinuation). Main Outcomes and Measures Total nasal symptom scores (TNSS; range; 0 [best] to 12 [worst]) were recorded between 0 and 10 hours after challenge. The minimum clinically important difference for change in TNSS within an individual is 1.08. The primary outcome was TNSS comparing sublingual immunotherapy vs placebo at year 3. Subcutaneous immunotherapy was included as a positive control. The study was not powered to compare sublingual immunotherapy with subcutaneous immunotherapy. Results Among 106 randomized participants (mean age, 33.5 years; 34 women [32.1%]), 92 completed the study at 3 years. In the intent-to-treat population, mean TNSS score for the sublingual immunotherapy group was 6.36 (95% CI, 5.76 to 6.96) at pretreatment and 4.73 (95% CI, 3.97 to 5.48) at 3 years, and for the placebo group, the score was 6.06 (95% CI, 5.23 to 6.88) at pretreatment and 4.81 (95% CI, 3.97 to 5.65) at 3 years. The between-group difference (adjusted for baseline) was −0.18 (95% CI, −1.25 to 0.90; [P = .75]). Conclusions and Relevance Among patients with moderate to severe seasonal allergic rhinitis, 2 years of sublingual grass pollen immunotherapy was not significantly different from placebo in improving the nasal response to allergen challenge at 3-year follow-up. Trial Registration clinicaltrials.gov Identifier: NCT01335139; EudraCT Number: 2010-023536-16

Background: Allergic rhinitis (AR) and asthma are both inflammatory diseases and are often associated. Relationships between fractional exhaled nitric oxide (FeNO) and asthma, atopy, and quality of life have been shown.Aims: This study aimed to determine whether FeNO in children with AR (n=158) or combined AR and asthma (n=93) was associated with clinical symptoms, house dust mite (HDM)-specific IgE, and rhinitis-specific quality of life, both cross-sectionally and longitudinally.Methods: Children with AR aged 6-18 years (n=251) in primary care were assessed for FeNO, nasal symptom scores, asthma symptom scores, quality of life, and HDM-specific IgE at baseline and 2 years later.Results: We found similarly elevated FeNO in children with only AR and in those with combined AR and asthma. No correlations were found between FeNO and nasal or asthma symptoms and rhinitis-related quality of life. Longitudinal correlations were strongest for HDM-specific IgE (r=0.91, pConclusions: FeNO was similar in a selected group of children with AR with and without asthma in primary care and was unrelated to symptoms or quality of life in both groups. FeNO is unlikely to be a useful biomarker of the clinical severity of upper or lower airway disease in primary care. (C) 2013 Primary Care Respiratory Society UK. All rights reserved. CMA de Bot etal. Prim Care Respir J 2013; 22(1): 44-50 http://dx.doi.org/10.4104/pcrj.2013.00009

Background Three years of treatment with either sublingual or subcutaneous allergen immunotherapy has been shown to be effective and to induce long-term tolerance. The Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy (GRASS) trial demonstrated that 2 years of treatment through either route was effective in suppressing the response to nasal allergen challenge, although it was insufficient for inhibition 1 year after discontinuation. Objective We sought to examine in the GRASS trial the time course of immunologic changes during 2 years of sublingual and subcutaneous immunotherapy and for 1 year after treatment discontinuation. Methods We performed multimodal immunomonitoring to assess allergen-specific CD4 T-cell properties in parallel with analysis of local mucosal cytokine responses induced by nasal allergen exposure and humoral immune responses that included IgE-dependent basophil activation and measurement of serum inhibitory activity for allergen-IgE binding to B cells (IgE-facilitated allergen binding). Results All 3 of these distinct arms of the immune response displayed significant and coordinate alterations during 2 years of allergen desensitization, followed by reversal at 3 years, reflecting a lack of a durable immunologic effect. Although frequencies of antigen-specific T H 2 cells in peripheral blood determined by using HLA class II tetramer analysis most closely paralleled clinical outcomes, IgE antibody–dependent functional assays remained inhibited in part 1 year after discontinuation. Conclusion Two years of allergen immunotherapy were effective but insufficient for long-term tolerance. Allergen-specific T H 2 cells most closely paralleled the transient clinical outcome, and it is likely that recurrence of the T-cell drivers of allergic immunity abrogated the potential for durable tolerance. On the other hand, the persistence of IgE blocking antibody 1 year after discontinuation might be an early indicator of a protolerogenic mechanism.

Resumo: Objectivos â Determinar a prevalência da associação de sintomas de rinoconjuntivite e asma em adolescentes, analisar se os sintomas de asma são mais intensos e frequentes entre os adolescentes com sintomas de rinoconjuntivite alérgica e avaliar se os adolescentes reconhecem os sintomas de rinoconjuntivite.Métodos â Realizou-se um estudo do tipo corte transversal com dois componentes: um estudo de prevalência e um estudo entre casos (sintomas de rinoconjuntivite), com um grupo de comparação (ausência de sintomas de rinoconjuntivite) a partir de informações dos questionários aplicados na fase 3 do ISAAC, no ano de 2002, na cidade do Recife.Resultados â A prevalência da associação de sintomas de rinoconjuntivite e de provável asma foi de 5,1% (48/940; IC 95%: 3,8 %-6,6%), apenas de asma de 10,9% (103/940; IC 95%: 9,1%-13,1%) e de rinoconjuntivite isolada foi de 9,7% (91/940; IC 95%: 7,9%-13%). Entre os adolescentes com sintomas de rinite, 81,3% (39/48) tinham provável asma persistente, 31,8% (48/151) dos com sintomas de asma referiam também sintomas de rinoconjuntivite. Não reconheciam os sintomas de rinoconjuntivite 65,1% (86/132) dos adolescentes que apresentavam esses sintomas.Conclusão â A associação de sintomas de rinoconjuntivite e asma é frequente e está associada à maior gravidade dos sintomas de asma. O facto de os adolescentes não reconhecerem os sintomas de rinoconjuntivite reflecte o subdiagnóstico, que pode resultar na desvalorização dos sintomas e, consequentemente, no tratamento inadequado.Rev Port Pneumol 2009; XV (4): 613-628 Abstract: Aim â Our study aimed to determine the rate of association of rhinoconjunctivitis and asthma symptoms in adolescents to analyse whether asthma symptoms are more severe and frequent in asthmatics with concomitant allergic rhinitis and assess if adolescents are aware of having rhinoconjunctivitis.Methods â A cross-sectional study, with two components: a study in prevalence and an inter-case study (rhinitis symptoms) with a comparison group (no rhinitis symptoms), based on information from questionnaires applied in phase 3 of ISAAC in Recife in 2002.Results â Associated rhinoconjunctivitis and probable asthma symptoms were observed in 5.1% of adolescents (48/940; CI 95%: 3.8 %-6.6%), probable asthma alone in 10.9% (103/940; CI 95%: 9.1%-13.1%) and rhinoconjunctivitis alone in 9.7% (91/940; CI 95%: 7.9%-13%). Among the rhinitisbearing adolescents, almost 81.3% (39/48) had persistent probable asthma and 31.8% (48/151) of asthmatic patients rhinoconjunctivitis. 65.1% (86/132) of adolescents with diagnosed rhinitis were unaware of rhinitis symptoms.Conclusions â The association of rhinoconjunctivitis and asthma symptoms is frequent and associated to more severe asthma symptoms. Adolescentsâ unawareness of rhinitis symptoms reflects the underdiagnosis that can result in downplaying the symptoms, and the consequent undertreatment.Rev Port Pneumol 2009; XV (4): 613-628 Palavras-chave: Asma, rinite, adolescentes, prevalência, Key-words: Prevalence, rhinoconjunctivitis, asthma, adolescents

Summary Background The optimal dose of grass pollen tablets for sublingual immunotherapy (SLIT) in allergic rhinoconjunctivitis patients was previously established in a multinational, randomized, double-blind, placebo-controlled study in 628 adults. Patients were randomized to receive once-daily 5-grass pollen sublingual tablets of 100 IR (index of reactivity), 300 IR or 500 IR, or placebo starting 4 months before the pollen season. Objective The aim of this complementary analysis was to determine whether 300 IR 5-grass pollen SLIT-tablets is effective in different subtypes of patients who are allergic to grass pollen. Methods Different subgroups could be identified regarding comorbidities (with or without asthma during the grass-pollen season), sensitization (mono/polysensitization) and symptom severity. An additional exploratory analysis was performed within four subgroups based on pre-treatment assessment: Group 1=high specific IgE; Group 2=high symptom scores; Group 3=high skin sensitivity; Group 4=any of Group 1, 2 or 3. Results Asthma and sensitization status were not significant covariates as the average Rhinoconjunctivitis Total Symptom Score (RTSS) was identical for patients with and without grass-pollen asthma, as well as for mono- and polysensitized patients. Across the four subgroups, average RTSSs (± SD) for the optimal dosage (300 IR) were 3.91 ± 3.16, 3.83 ± 3.14, 2.55 ± 2.13 and 3.61 ± 2.97, for subgroups 1, 2, 3 and 4, respectively. ancova showed that in Group 1 average RTSS did not differ significantly with different doses of SLIT. In Groups 2, 3 and 4, doses of 300 IR and 500 IR were significantly more effective than 100 IR and placebo (P0.035). All doses of SLIT administered in this study can be considered safe in the patients investigated. Conclusions The risk-benefit ratio validates the use of 300 IR tablets in clinical practice in all of these patient subgroups, regardless of severity profile, sensitization status and presence of asthma.

Aim: To evaluate the efficacy of Dermatophagoides pteronyssinus (DPT) subcutaneous immunotherapy in allergic rhinoconjunctivitis patients. Patients & methods: This 17-week double-blind study randomized 136 patients (95 evaluable) to five dose groups of DPT depot extract (0.0625–0.75 skin prick test [SPT] units) or placebo, administered in a six updosing schedule. Results: A dose–response was observed for clinical efficacy (allergen concentration needed to induce a positive nasal provocation test response from baseline to final visit) and safety (adverse reactions). Local and systemic reactions occurred with 14.8 and 6.4% of administered doses, respectively; a single anaphylactic reaction occurred in each of Groups 3, 4 and 5 (0.3% of doses). Conclusion: The risk–benefit profile appeared most favorable with a DPT dose of 0.125 SPT units.

Summary Background Allergic rhinoconjunctivitis is a global health problem. Around 14 million people in Spain, France, Italy, and Austria suffer from grass pollen induced allergic rhinitis. Standard care only provides symptoms relief, while allergen specific immunotherapy (SIT) treats the underlying cause of the disease. Grazax ® from ALK-Abello is a new, tablet-based, effective route of SIT for home treatment. The objective was to assess the cost-effectiveness of Grazax ® in four Southern European countries. Methods A prospective pharmacoeconomic analyses was carried out alongside a multinational, clinical trial measuring the efficacy of Grazax ® . Pooled data on resource use and health outcomes were collected. A societal perspective was adopted, and the analysis had a nine-year time horizon. The primary outcome measure was quality adjusted life years (QALYs). Results Grazax ® was superior to standard care for all efficacy endpoints, including QALYs gained, and resulted in significantly less use of rescue medication and fewer hours missed from work. Grazax ® was cost-effective for all countries for an annual price in the range of €1500–€1900. The result was improved by inclusion of future costs of asthma and exclusion of Spanish trial centers which experienced an exceptionally low pollen season. Conclusion The analysis illustrates that allergen SIT with Grazax ® for grass pollen induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe.

In contrast to many countries, a decrease in childhood wheeze prevalence was previously reported for the Netherlands. In repeated cross-sectional surveys in 2001, 2005 and 2010, we investigated whether this trend continued, and additionally examined prevalence trends of eczema, asthma and rhinoconjunctivitis among 8- to 11-year-old schoolchildren eligible for a routine physical examination. Overall, similar to 90% participated (mean age: 8.8 years in 2001 and 10.5 years in 2005 and 2010). Eczema, wheeze and asthma prevalence did not change significantly between 2001 and 2010, but rhinoconjunctivitis prevalence increased from 8.4% in 2001 to 12.3% in both 2005 and 2010 (P-trend

Background Allergic rhinitis (AR) is an increasing and common condition affecting many people globally, especially children. The aim of the study was to investigate the association between the frequency of truck traffic and allergic rhinitis symptoms, rhinoconjunctivitis and hayfever among 13 to 14 year old school children in Ekurhuleni Metropolitan Municipality, Gauteng Province, South Africa. Methods In a cross-sectional study design, 3764 children from 16 randomly selected high schools were eligible to participate, 3468 completed the International Study of Asthma and Allergies in Childhood (ISAAC) Phase I questionnaire of which 3424 were suitable for analysis; the overall response rate was 92 %. Data were analysed using multilevel logistic regression analysis. Results The prevalence of self-reported rhinitis ever, current rhinitis rhinoconjunctivitis and hayfever was 52, 40, 21 and 37 % respectively. Rhinitis ever, current rhinitis and current rhinoconjunctivitis were significantly associated with the frequency of trucks passing near residences almost all day on weekdays, (OR 1.46 95 % CI: 1.16 − 1.84), (OR 1.60 95 % CI: 1.24–2.02) and (OR 1.42 95 % CI: 1.09–1.84) respectively. No association was observed between truck traffic and hay fever in the multiple analyses. Conclusion The study shows a high prevalence of allergic rhinitis symptoms amongst children. The results support the hypothesis that traffic related pollution plays a role in the prevalence of allergic rhinitis symptoms in children residing in the area.

The clinical studies on the effectiveness of homeopathy in respiratory allergy (18 randomized trials and 9 observational studies) are described. The literature of common immunologic disorders including also upper respiratory tract infections (URTI) and otorhinolaryngology (reported in part 1), is evaluated and discussed. Most of initial evidence-based research was addressed to the question of whether homeopathic high dilutions are placebos or possess specific effects, but this question has been often equivocal and is still a matter of debate. The evidence demonstrates that in some conditions homeopathy shows significant promise, e.g.Galphimia glauca(low dilutions/potencies) in allergic oculorhinitis, classical individualized homeopathy in otitis and possibly in asthma and allergic complaints, and a few low-potency homeopathic complexes in sinusitis and rhinoconjunctivitis. A general weakness of evidence derives from lack of independent confirmation of reported trials and from presence of conflicting results, as in case of homeopathic immunotherapy and of classical homeopathy for URTI. The suitable methods to evaluate homeopathy effectiveness, without altering the setting of cure, are also analyzed.

Background: Food allergy is an abnormal immunological response following exposure (usually ingestion) to a food. Elimination of the allergen is the principle treatment for food allergy, including allergy to fruit. Accidental ingestion of allergenic foods can result in severe anaphylactic reactions. Allergen-specific immunotherapy (SIT) is a specific treatment, when the avoidance of allergenic foods is problematic. Recently, studies have been conducted on different types of immunotherapy for the treatment of food allergy, including oral (OIT) and sublingual immunotherapy (SLIT). Objectives: To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with food allergy to fruits, when compared with placebo or an elimination strategy. Search methods: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and AMED were searched for published results along with trial registries and the Journal of Negative Results in BioMedicine for grey literature. The date of the most recent search was July 2015. Selection criteria: Randomised controlled trials (RCTs) comparing OIT or SLIT with placebo or an elimination diet were included. Participants were children or adults diagnosed with food allergy who presented immediate fruit reactions. Data collection and analysis: We used standard methodological procedures expected by the Cochrane Collaboration. We assessed treatment effect through risk ratios (RRs) for dichotomous outcomes. Main results: We identified two RCTs (N=89) eligible for inclusion. These RCTs addressed oral or sublingual immunotherapy, both in adults, with an allergy to apple or peach respectively. Both studies enrolled a small number of participants and used different methods to provide these differing types of immunotherapy. Both studies were judged to be at high risk of bias in at least one domain. Overall, the quality of evidence was judged to be very low due to the small number of studies and participants and possible bias. The studies were clinically heterogeneous and hence we did not pool the results. A study comparing SLIT with placebo for allergy to peach did not detect a significant difference between the number of patients desensitised at six months following a double-blind placebo-controlled food challenge (RR 1.16, 95% confidence interval (CI) 0.49 to 2.74). The second study, comparing OIT versus no treatment for apple allergy, found an effect on desensitisation in favour of the intervention using an oral provocation test at eight months, but results were imprecise (RR 17.50, 95% CI 1.13 to 270.19). Neither study reported data on evidence of immunologic tolerance. In both studies, the incidence of mild and moderate adverse events was higher in the intervention groups than in the controls. In the study comparing SLIT with placebo, patients in the intervention group experienced significantly more local adverse reactions than participants in the control group (RR 3.21, 95% CI 1.51 to 6.82), though there was not a significant difference in the number of participants experiencing systemic adverse reactions (RR 0.81, 95% CI 0.22 to 3.02). In the study of OIT, two of the 25 participants in the intervention group reported relevant side effects, whereas no participants in the control group reported relevant side effects. Authors' conclusions: There is insufficient evidence for using OIT or SLIT to treat allergy to fruit, specifically related to peach and apple. Mild or moderate adverse reactions were reported more frequently in people receiving OIT or SLIT. However, these reactions could be treated successfully with medications. © 2015 The Cochrane Collaboration.

The study investigated the association between community proximity to mine dumps, and current wheeze, rhinoconjunctivitis, and asthma among adolescents. This study was conducted during May–November 2012 around five mine dumps in South Africa. Communities in close proximity to mine dumps had an increased likelihood of current wheeze OR 1.38 (95 % CI: 1.10–1.71), rhinoconjunctivitis OR 1.54 (95 % CI: 1.29–1.82), and a protective association with asthma OR 0.29 (95 % CI: 0.23–0.35). Factors associated with health outcomes included other indoor and outdoor pollution sources. Wheeze and rhinoconjunctivitis appear to be a public health problem in these communities. The findings of this study serve as a base for further detailed epidemiological studies for communities in close proximity to the mine dumps e.g. a planned birth cohort study.

Summary Aim To adapt the Asthma Quality of Life Questionnaire (AQLQ(S)), the Asthma Control Questionnaire (ACQ) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)) for a personal digital assistant (Palm TX) and to examine the validity of the electronic versions by comparing them with the original paper versions. Methods 84 adults with asthma and 32 with rhinitis were randomised to complete either the paper or the electronic version first. After 2h, they completed the other version. Results 68 asthma and 27 rhinitis patients provided analysable data. For the AQLQ(S) and RQLQ(S) differences between paper and electronic were significant. Concordance between paper and electronic, evaluated using an intraclass correlation coefficient were: AQLQ=0.92, ACQ=0.90 and RQLQ=0.85. Concordance for the individual domains of the AQLQ and RQLQ ranged from 0.52 to 0.94. These levels of concordance did not reach the a priori defined requirement for validity. Conclusions The significant bias between paper and electronic versions and only modest concordance provides evidence that patients may respond differently to questionnaires in different formats and show that different formats must not be used interchangeably.

The last few decades have seen a marked increase in the global prevalence of allergic diseases particularly among children. Among the factors attributed to this rise has been reduced exposure to pathogens during childhood leading to insufficient maturation of the regulatory arm of developing immune systems. Over the years, a number of epidemiological studies have observed an inverse relationship between parasitic worm (helminth) infections and allergies. The purpose of this review is to highlight insights from population studies conducted among children published between 2008 and 2013 that explore the complex dynamics between helminth infections and allergies. These insights include the effect of anthelmintic treatment on allergic responses, an elucidation of immune mechanisms and an examination of helminth-induced immunoglobulin E cross-reactivity. A better understanding of the relationship between helminths and allergies is imperative as research directions move toward harnessing the therapeutic potential of helminths and their products in the treatment of allergic disorders.

Background Longitudinal prospective population-based birth cohort studies of the natural history of sensitization and allergic diseases from childhood to adulthood are few. The aim of the present prospective study was to investigate the natural course of sensitization and allergic diseases in a random population-based sample of 276 children from a 1-year birth cohort of unselected Danish children followed from birth to 26 years of age. Methods Questionnaire-based interviews, physical examination, skin prick tests, specific IgE testing, and from 10 years also spirometry, were carried out at 1.5, 5, 10, 15 and 26 years of age. Predefined diagnostic criteria were used. Results Follow-up rates were high, 193 (70%) attended the 26-year follow-up. The prevalence of current eczema was stable during childhood; 13% (1.5 yrs.), 9.2% (5 yrs.), 10.8% (10 yrs.), and 9.8% (15 yrs.), and 5.7% at 26 yrs. From birth to 26 years the cumulative prevalence of eczema, food allergy, asthma, and rhinoconjunctivitis was 23.5%, 13.8%, 17%, and 27.9% respectively. More than half of the participants had one or more allergic disease in the period between birth and 26 years of age. The rates of sensitization (S-IgE = 0.35 kU/l) were 8%, 23%, 26%, 32%, and 31% at 1.5, 5, 10, 15, and 26 years of age, respectively. Sensitization to food allergens was most prevalent in early infancy, whereas sensitization to inhalant allergens dominated later on. Conclusion The results support the concept of the allergic march. Allergic diseases are not only occurring in childhood but persist into adulthood.

Background In recent years, the prevalence of asthma, rhinoconjunctivitis and eczema symptoms in childhood has considerably increased in developing countries including Bolivia, possibly due to changes in lifestyle, environmental and domestic factors. This study aimed to assess the association between environmental factors and asthma, rhinoconjuctivitis and eczema symptoms in school-aged children from Oropeza Province in Chuquisaca, Bolivia. Methods A cross-sectional study was performed in 2340 children attending the fifth grade in 36 randomly selected elementary schools in Oropeza province. The prevalence of symptoms was determined using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Environmental factors were assessed by the ISAAC environmental questionnaire including questions related to exposure to pets, farm animals, indoor and outdoor pollution, presence of disease vectors at home and precarious household conditions. Generalized linear mixed-effects models were adjusted for age, sex and place of living. Results Thirty seven percent of children reported that at least one of their parents smoked at home. Wood or coal was used as cooking fuel in 19% of the homes and 29% reported intense truck traffic on the street where they lived. With respect to hygiene conditions, 86% reported exposure to dogs, 59% exposure to cats and 36% regular contact to farm animals. More than one precarious household condition was reported by 8% of children. In the adjusted model exposure to dog (adjusted OR 1.4; CI 95% 1.0-1.9), cat (1.2; 1.0-1.5), farm animals (1.5; 1.2-1.8); intense truck traffic (1.3; 1.0-1.6), parents smoking at home (1.2; 1.0-1.5), presence of disease vectors at home (fourth quartile vs. first quartile: 1.6; 1.2-2.3) and two or more precarious household conditions (1.5; 1.0-2.2) were significantly associated with rhinoconjunctivitis symptoms. The associations were similar for asthma and eczema symptoms; however it did not reach the level of statistical significance for all items. Conclusion Our results support previous findings reported for poor communities especially in Latin America, showing that lower hygiene conditions did not have protective effect against asthma and rhinoconjunctivitis and eczema symptoms.

Introduction An association between pollen count (Poaceae) and symptoms is well known, but to a lesser degree the importance of priming and lag effects. Also, threshold levels for changes in symptom severity need to be validated. The present study aims to investigate the relationship between pollen counts, symptoms and health related quality of life (HRQL), and to validate thresholds levels, useful in public pollen warnings. Material and methods Children aged 7–18 with grass pollen allergy filled out a symptom diary during the pollen season for nose, eyes and lung symptoms, as well as a HRQL questionnaire every week. Pollen counts were monitored using a volumetric spore trap. Results 89 (91%) of the included 98 children completed the study. There was a clear association between pollen count, symptom severity and HRQL during the whole pollen season, but no difference in this respect between early and late pollen season. There was a lag effect of 1–3 days after pollen exposure except for lung symptoms. We found only two threshold levels, at 30 and 80 pollen grains/m3 for the total symptom score, not three as is used today. The nose and eyes reacted to low doses, but for the lung symptoms, symptom strength did hardly change until 50 pollen grains/m3. Conclusion Grass pollen has an effect on symptoms and HRQL, lasting up to 5 days after exposure. Symptoms from the lungs appear to have higher threshold levels than the eyes and the nose. Overall symptom severity does not appear to change during the course of season. Threshold levels need to be revised. We suggest a traffic light model for public pollen warnings directed to children, where green signifies “no problem”, yellow signifies “can be problems, especially if you are highly sensitive” and red signifies “alert – take action”.

Background Oral allergy syndrome (OAS) triggered by fruit and vegetables often occurs in patients with pollen-induced rhinoconjunctivitis because of cross-reactive epitopes in pollen and associated foods. This open observational study examined the effect of pollen-specific sublingual immunotherapy ([SLIT] B. U. Pangramin or SLITone involving birch/alder/hazel, grasses/rye, and/or mugwort) on OAS triggered by several foods in patients treated in standard practice. Very few studies have examined SLIT use in this situation. Methods Patients (n = 102) had pollen-induced rhinoconjunctivitis and OAS and were followed for up to 12 months. Baseline OAS (triggers, symptoms, and symptom severity) was assessed by questionnaire and patient history. Change in OAS was assessed using oral challenge test with 1 or 2 dominant food triggers (and compared with the sum score calculated from the OAS questionnaire at baseline) and clinician ratings of change. Pollen-induced rhinoconjunctivitis symptoms and medication use were also measured. Results In the oral challenge test, 77.0% of patients were considered responders (decrease in sum score of ≥ 50%; no difference in patients receiving B. U. Pangramin or SLITone). At baseline, investigators rated OAS severity as at least moderate in 94.9% of patients compared with 36.9% after 12 months of treatment. After 12 months, OAS was rated as much or very much improved in 72.9% of patients. Sublingual immunotherapy significantly reduced rhinoconjunctivitis symptoms and medication use. Only 10% of patients experienced adverse drug reactions. Conclusion This study supplements the sparse literature on this topic and suggests that pollen-specific SLIT can reduce OAS triggered by pollen-associated foods in patients with pollen-induced rhinoconjunctivitis.

Asthma and rhinitis epidemiology has wide variations around the world. The aim of this review was verify the prevalence of asthma and rhinitis in South America and report differences from other regions of the world. We reviewed studies with International Study of Asthma and Allergies in Childhood (ISAAC) methodology in South America, Phases I and III. In South America the ISAAC Phase I ranked four countries among top ten in prevalence of asthma and three countries among top ten in prevalence of rhinoconjunctivitis. ISAAC Phase III showed little changes in asthma and rhinitis prevalence in South American countries. The prevalence increases of asthma and rhinitis in South American centers indicate that the burden of both is continuing to rise, but the differences in prevalence are lessening. Revisión por pares

Objective Allergic rhinitis is one of the most frequent chronic diseases among children. The objective of the study was to assess the prevalence of rhinoconjunctivitis and determine clinical, social and environmental associated factors, among school children aged 6–7 years and adolescents aged 13–14 years in Bogota, Colombia. Methods We used ISAAC (International Study of Asthma and Allergies in Childhood) phase III study methodology and questionnaire for design and data collection, and we did a secondary analysis of these data. The sample consisted of 3830 registers from adolescents between 13 and 14 years old and 3256 registers from children between 6 and 7 years. Results The prevalence of rhinoconjunctivitis symptoms in the last year was 17.2% (95% CI, 15.9–18.5) in children vs. 24.9% (95% CI, 23.6–26.3) in adolescents. In both groups there was a female predominance in children (17.8% vs. 16.5%), and in the teenagers group (28.0% vs. 21.4%), though the differences were not statistically significant. The factors associated with rhinoconjunctivitis in the group of 6–7 years where: asthma [OR 3.9; (95% CI, 2.8–5.4)], atopic dermatitis [OR 2.3; (95% CI, 1.7–3.1)], use of acetaminophen in the last year [OR 2.6; (95% CI, 1.4–4.9)], use of antibiotics in the first year of live [OR 1.7; (95% CI, 1.3–2.3)], higher maternal education [OR 1.5; (95% CI, 1.0–2.3)] and cesarean delivery [OR 1.6; (95% CI, 1.2–2.1)]. Among the 13–14 year age-group, factors associated with rhinoconjunctivitis included: asthma [OR 2.6; (95% CI, 2.0–3.4)], atopic dermatitis [OR 1.8; (95% CI, 1.4–2.3)], use of acetaminophen in the last year [OR 1.8; (95% CI, 1.4–2.4)], consumption of fast-food three times or more per week [OR 1.5; (95% CI, 1.2–2.0), ever smoked [OR 1.4; (95% CI, 1.2–1.7)] and meat consumption was protective factor [OR 0.7; (95% CI, 0.5–0.9)]. Conclusion In both studied groups, the estimated prevalence of rhinoconjunctivitis symptoms was relatively high. Future in-depth research is needed to assess the complex interactions between allergic rhinoconjunctivitis symptoms and social and environmental factors.

Background The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials. Objective To investigate sustained efficacy and disease modification in a 5-year double-blind, placebo-controlled trial, including 2 years of blinded follow-up after completion of a 3-year period of treatment, with the SQ-standardized grass allergy immunotherapy tablet, Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU, ∗ ∗SQ-T (standardized quality tablet units) and BAU (biological activity units) are quantitative measures of biological activity; ie, the potency of allergen extracts/vaccines. One grass AIT contains 75,000 SQ-T of timothy (Phleum pratense) grass pollen extract (measure of total biological potency using ALK in-house reference), equivalent to 2,800 BAU (measure of total biological potency, defined by the FDA). ALK, Denmark) or placebo. Methods A randomized, double-blind, placebo-controlled, multinational, phase III trial included adults with a history of moderate-to-severe grass pollen–induced allergic rhinoconjunctivitis, with or without asthma, inadequately controlled by symptomatic medications. Two hundred thirty-eight participants completed the trial. End points included rhinoconjunctivitis symptom and medication scores, combined scores, asthma symptom and medication scores, quality of life, days with severe symptoms, immunologic end points, and safety parameters. Results The mean rhinoconjunctivitis daily symptom score was reduced by 25% to 36% ( P ≤ .004) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial. The rhinoconjunctivitis DMS was reduced by 20% to 45% ( P ≤ .022 for seasons 1-4; P = .114 for season 5), and the weighted rhinoconjunctivitis combined score was reduced by 27% to 41% ( P ≤ .003) in favor of active treatment. The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group, with relative differences of 49% to 63% ( P ≤ .0001). Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response. No safety issues were identified. Conclusion The results confirm disease modification by SQ-standardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis.

Background The aim of this study was to clarify whether some environmental and genetic factors (food allergy, older siblings, early day-care attendance and parents' allergy history) are related to the development of allergic symptoms (wheezing in the previous 12 months [WP], eczema symptoms in the previous 12 months [EP], and rhinoconjunctivitis symptoms in the previous 12 months [RP]) in Japanese children. Methods: Using the modified version of the International Study on Asthma and Allergies in Childhood (ISSAC) questionnaire, we studied the prevalence of WP, EP and RP among six-year-old children attending 72 primary schools throughout Himeji City, Japan, during the two years from 2005 to 2006. Results Food allergy and parents' history of allergy showed a significant relationship with the prevalence of WP, EP and RP. Day-care attendance in the first two years of life and presence of older siblings showed a significant inverse relationship with the prevalence of RP. However, neither day-care attendance nor presence of older siblings was related to the development of W and ER. Conclusions Among Japanese children, food allergy and parents' history of allergy are risk factors for WP, ES or RS. However, early day-care attendance and presence of older siblings might be protective factors against RS. Infections in early life may affect the prevalence of rhinoconjunctivitis in six-year-old children.

Background: Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale randomized, double-blind, placebo-controlled trial.Objective: We sought to investigate sustained efficacy I year after a 3-year period of daily treatment with the SQ-standardized grass allergy immunotherapy tablet Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU; ALK-Abello, Horsholm, Denmark).Methods: A randomized, double-blind, placebo-controlled, phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. The analysis set comprised 257 subjects at the follow-up. Efficacy end points were rhinoconjunctivitis symptom and medication scores, quality of life, and percentages of symptom and medication free days. Immunologic end points included grass pollen-specific serum IgG4 and IgE-blocking factor. Safety was assessed based on adverse events.Results: Significant improvements in efficacy were consistently shown during 3 years' treatment. One year after treatment, the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores (26%, P Conclusion: Three years of treatment with the SQ-standardized grass allergy immunotherapy tablet resulted in consistent clinical improvement and accompanying immunologic changes that were sustained I year after treatment, which is indicative of disease modification and associated long-term benefits. (J Allergy Clin Immunol 2010;125:131-38.)

Immunotherapy is the only treatment for allergy that has the potential to alter the natural course of the disease. Sublingual immunotherapy (SLIT) for grass pollen-induced rhino-conjunctivitis has been developed to make immunotherapy available to a broader group of allergic patients. In the largest clinical programme ever conducted with allergen-specific immunotherapy, over 1,700 adults and 260 children have been exposed to Grazax(®). Grazax is formulated as an oral lyophilisate (tablet) for sublingual administration, containing 75,000 SQ-T standardized allergen extract of grass pollen from Phleum pratense. Grazax is indicated for treatment of grass pollen-induced rhinitis and conjunctivitis in adult patients with clinically relevant symptoms and diagnosed with a positive skin prick test and/or specific IgE test to grass pollen. In phase I trials doses from 2,500 to 1,000,000 SQ-T were tested. All doses were well tolerated and 75,000 SQ-T, with approximately 15 mug major allergen protein, was chosen as the optimal dose. Three phase III trials are ongoing, one being a long-term trial. Results from GT-08 trial first and second treatment years showed a reduction of 30% and 36%, respectively, in daily rhino-conjunctivitis symptom scores and a reduction of 38% and 46% of daily rhino-conjunctivitis medication scores compared with placebo over the entire grass pollen season. Subjects treated with Grazax also had an increased number of well days and improved quality of life, and more subjects experienced excellent rhino-conjunctivitis control. The most common adverse events related to Grazax are local reactions, such as pruritus, edema mouth, ear pruritus, throat irritation, and sneezing. We conclude that Grazax is efficacious and safe for treatment of rhino-conjunctivitis due to grass pollen allergy.