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The impact of the COVID-19 pandemic on general practitioners’ (GP) care for patients with asthma and/or COPD is largely unknown. To describe the impact of the pandemic on asthma or COPD-related GP care, we analysed routinely recorded electronic health records data from Dutch general practices and out-of-hours (OOH) services. During the COVID-19 pandemic (2020), the contact rates for asthma and/or COPD were significantly lower in GP practices and OOH services compared with the pre-pandemic period (2019) (respectively, 15% lower and 28% lower). The proportion of telephone contacts increased significantly with 13%-point in GP practices and 12%-point at OOH services, while the proportion of face-to-face contacts decreased. Furthermore, the proportion of high urgent contacts with OOH services decreased by 8.5%-point. To conclude, the overall contact rates in GP practices and OOH services decreased, while more contacts were remote. Lower contact rates have, after a short follow-up, not resulted in more patients with exacerbations in OOH care. However, this might still be expected after a longer follow-up.

The increasing prevalence of reported annoyances in the indoor environment threatens public health. This study aimed to investigate the association between perceived annoyances from the home environment and respiratory infections among individuals with and without asthma or chronic obstructive pulmonary disease (COPD). A total of 16,688 individuals from the Danish Health and Morbidity Survey initiated in 2000 were grouped according to their patterns of perceived annoyances. Information on respiratory infections (all causes, bacterial, viral, and those leading to hospital admissions) was obtained from Danish registers up to 19 years after the survey. Poisson regression of incidence rates (IRs) was applied to estimate incidence rate ratios (IRRs). Annoyances significantly increased the IR for respiratory infections of all causes and bacterial respiratory infections in individuals without asthma or COPD, adjusted IRR 1.16 (95% CI: 1.01, 1.34) and 1.15 (95% CI: 1.02, 1.31), respectively. However, no difference was observed for viral respiratory infections nor hospital admissions. Individuals with asthma or COPD and a high level of annoyances had a non-significantly increased IR in all four analyses of respiratory infections. These findings provide support for perceived annoyances as an important risk factor for respiratory infections.

Over 20 years ago, the concept of asthma control was created and appropriate measurement tools were developed and validated. Loss of asthma control can lead to an exacerbation. Years ago, the term "clinically significant asthma exacerbation" was introduced to define when a loss of control is severe enough to declare it an asthma exacerbation. This term is also used by health insurances to determine when an exacerbation is eligible for reimbursement of biologics in clinical practice, however, it sometimes becomes apparent that a clear separation between loss of "asthma control" and an exacerbation is not always possible. In this review, we attempt to justify why exacerbations in early allergic asthma and adult eosinophilic asthma can differ significantly and why this is important in clinical practice as well as when dealing with health insurers.

Eczema and asthma are allergic diseases and two of the commonest chronic conditions in high-income countries. Their co-existence with other allergic conditions is common, but little research exists on wider multimorbidity with these conditions. We set out to identify and compare clusters of multimorbidity in people with eczema or asthma and people without. Using routinely-collected primary care data from the U.K. Clinical Research Practice Datalink GOLD, we identified adults ever having eczema (or asthma), and comparison groups never having eczema (or asthma). We derived clusters of multimorbidity from hierarchical cluster analysis of Jaccard distances between pairs of diagnostic categories estimated from mixed-effects logistic regressions. We analysed 434,422 individuals with eczema (58% female, median age 47 years) and 1,333,281 individuals without (55% female, 47 years), and 517,712 individuals with asthma (53% female, 44 years) and 1,601,210 individuals without (53% female, 45 years). Age at first morbidity, sex and having eczema/asthma affected the scope of multimorbidity, with women, older age and eczema/asthma being associated with larger morbidity clusters. Injuries, digestive, nervous system and mental health disorders were more commonly seen in eczema and asthma than control clusters. People with eczema and asthma of all ages and both sexes may experience greater multimorbidity than people without eczema and asthma, including conditions not previously recognised as contributing to their disease burden. This work highlights areas where there is a critical need for research addressing the burden and drivers of multimorbidity in order to inform strategies to reduce poor health outcomes.

Background: Asthma has a significant impact on people of all ages, particularly children. A lack of universally accepted case definition and confirmatory tests and a poor understanding of major risks interfere with a global response. We aimed to provide global estimates of asthma prevalence and cases in 2019 across four main epidemiological case definitions - current wheezing, ever wheezing, current asthma, and ever asthma. We further investigated major associated factors to determine regional and national distributions of prevalence and cases for current wheezing and ever asthma.Methods: We identified relevant population-based studies published between January 1, 1990, and December 31, 2019. Using a multilevel multivariable mixed-effects meta-regression model, we assessed the age- and sex-adjusted associations of asthma with study-level variables, including year, setting, region and socio-demographic index (SDI). Using a random-effects meta-analysis, we then identified risk factors for current wheezing and asthma. From a "risk factor-based model", which included current smoking, and biomass exposure for current wheezing, and rural setting, current smoking, biomass exposure, and SDI for ever asthma, we estimated case numbers and prevalence across regions and 201 countries and territories in 2019.Results: 220 population-based studies conducted in 88 countries were retained. In 2019, the global prevalence estimates of asthma in people aged 5-69 years by various definitions, namely current wheezing, ever wheezing, current asthma, and ever asthma were 11.5% (95% confidence interval (CI) = 9.1-14.3), 17.9% (95% CI = 14.2-22.3), 5.4% (95% CI = 3.2-9.0) and 9.8% (95% CI = 7.8-12.2), respectively. These translated to 754.6 million (95% CI = 599. 7-943.4), 1181.3 million (95% CI = 938.0-1,471.0), 357.4 million (95% CI = 213.0-590.8), 645.2 million (95% CI = 513.1-806.2) cases, respectively. The overall prevalence of current wheezing among people aged 5-69 years was the highest in the African Region at 13.2% (95% CI = 10.5-16.5), and the lowest in the Americas Region at 10.0% (95% CI = 8.0-12.5). For ever asthma, the estimated prevalence in those aged 5-69 years was also the highest in the African Region at 11.3% (95% CI = 9.0-14.1), but the lowest in South-East Asia Region (8.8, 95% CI = 7.0-11.0).Conclusions: Although varying approaches to case identification in different settings make epidemiological estimates of asthma very difficult, this analysis reaffirms asthma as a common global respiratory condition before the COVID-19 pandemic in 2019, with higher prevalence than previously reported in many world settings.

Background:Asthma and mental disorders frequently co-occur. Studies of their comorbidity have generally focused on associations related to a subset of mental disorders. Objective:To estimate bidirectional associations between asthma and 10 broad types of mental disorders. Methods:In a population-based cohort study, including all individuals born in Denmark between 1955 and 2011 (N = 5,053,471), we considered diagnoses of comorbid mental disorders among those with asthma, and vice versa, between 2000 and 2016. We used Cox regression models to calculate overall and time-dependent hazard ratios for mental disorder-asthma pairs and competing-risks survival analyses to estimate absolute risks. Results:Altogether, 376,756 individuals were identified as having an incident mental disorder and 364,063 incident asthma during follow-up. An increased risk was seen for all bidirectional mental disorder-asthma pairs. Following an asthma diagnosis, adjusted hazard ratios for different subsequent mental disorders ranged from 1.75 (95% CI, 1.64-1.87) for organic disorders to 2.75 (95% CI, 2.69-2.81) for personality disorders. Following a prior mental disorder diagnosis, hazard ratios for asthma ranged from 1.06 (95% CI, 1.00-1.12) for developmental disorders to 2.33 (95% CI, 2.28-2.39) for substance use disorders. Risks varied with time since prior disorder diagnosis but remained elevated. Cumulative incidence of (1) asthma after a mental disorder and (2) a mental disorder after asthma was higher in those with prior disorders than in matched reference groups. Conclusions:Our findings provide evidence of bidirectional associations between asthma and each of the mental disorder types, suggesting possible shared etiological factors or pathophysiologic processes.

Lactic acidosis is a common complication of status asthmaticus in adults. However, data is sparse in children. The aim of this study was to describe the prevalence and risk factors for lactic acidosis in children hospitalised for acute moderate or severe asthma. A total of 154 children 2–17 years of age were enrolled in a prospective observational study conducted in a tertiary hospital. All had capillary blood gas assessment 4 h after the first dose of salbutamol in hospital. The primary endpoint was the prevalence of lactic acidosis. Potential contributing factors such as age, sex, BMI, initial degree of asthma severity, type of salbutamol administration (nebuliser or inhaler), steroids, ipratropium bromide, and glucose-containing maintenance fluid represented secondary endpoints. All in all, 87% of patients had hyperlactatemia (lactate concentration > 2.2 mmol/l). Lactic acidosis (lactate concentration > 5 mmol/l and anion gap ≥ 16 mmol/l) was observed in 26%. In multivariate analysis, age more than 6 years (OR = 2.8, 95% CI 1.2–6.6), glycemia above 11 mmol/l (OR = 3.2 95% CI 1.4–7.4), and salbutamol administered by nebuliser (OR = 10, 95% CI 2.7–47) were identified as risk factors for lactic acidosis in children with moderate or severe asthma.Conclusion: Lactic acidosis is a frequent and early complication of acute moderate or severe asthma in children. What is Known:• Lactic acidosis during acute asthma is associated with b2-mimetics administration.• Salbutamol-related lactic acidosis is self-limited but important to recognise, as compensatory hyperventilation of lactic acidosis can be mistaken for respiratory worsening and lead to inappropriate supplemental bronchodilator administration.What is New:• Lactic acidosis is a frequent complication of acute asthma in the paediatric population.• Age older than 6 years, hyperglycaemia, and nebulised salbutamol are risk factors for lactic acidosis during asthma.

Background and ObjectivesEpilepsy and depression share a bidirectional relationship; however, its magnitude and long-term temporal association remain to be elucidated. This study investigates the magnitude and long-term association between epilepsy and depression, comparing with the risks of the 2 disorders after another chronic medical illness (asthma).MethodsIn a nationwide register-based matched cohort study, we identified all individuals who received a first diagnosis of epilepsy, depression, and asthma from January 1, 1980, to December 31, 2016. We used a Cox regression model to estimate the risk of epilepsy after depression and vice versa and the risk of epilepsy or depression after asthma, compared with healthy references matched on age and sex, adjusting for medical comorbidity, substance abuse, and calendar time. Results were stratified by epilepsy subtype. We furthermore investigated the risk of admission with acute seizures for persons with epilepsy who became depressed.ResultsIn a population of 8,741,955 individuals, we identified 139,014 persons with epilepsy (54% males, median age at diagnosis 43 years [inter quartile range (IQR) 17–65 years]), 219,990 persons with depression (37% males, median age at diagnosis 43 years [IQR 29–60 years]), and 358,821 persons with asthma (49% males, median age at diagnosis 29 years [IQR 6–56 years]). The adjusted hazard ratio (aHR) of depression after epilepsy was 1.88 (95% CI 1.82–1.95), and the aHR of epilepsy after depression was 2.35 (95% CI 2.25–2.44). The aHR of depression after asthma was 1.63 (95% CI 1.59–1.67) and that of epilepsy after asthma, 1.48 (95% CI 1.44–1.53). The risk of depression was highest in the few years preceding and after an epilepsy diagnosis, and vice versa, but remained elevated during the entire follow-up period for both directions of the association. There was no evidence of a stronger association with depression for any epilepsy subtype. Receiving a diagnosis of depression subsequent to an epilepsy diagnosis was associated with a 1.20-fold (95% CI 1.07–1.36) increased HR of acute hospital admission with seizures.DiscussionWe identified a long-term bidirectional relationship between depression and epilepsy in a large-scale cohort study. Risk estimates were higher than those of epilepsy or depression after asthma.

Objectives To assess whether adolescents with asthma experience a lower mental well-being and lower general health than their peers without asthma.Study design Data from the Prevention and Incidence of Asthma and Mite Allergy study were used. At the ages of 11, 14, 17, and 20 years, 2651, 2522, 2094, and 2206 participants, respectively, completed questionnaires. Their parents completed questionnaires at the ages of 11 (n = 2660), 14 (n = 2338), and 17 years (n = 1872). Asthma was defined according to the Mechanisms of the Development of Allergy criteria. Mental well-being was measured using the Mental Health Index-5 and was reported by the adolescents. General health, measured on a 4-point Likert scale, was reported by the adolescents and their parents. We estimated associations of asthma with mental wellbeing and perceived general health using generalized estimating equations.Results At ages 11, 14, 17, and 20 years, 6.7%, 6.9%, 5.0%, and 6.6%, respectively, of the adolescents had asthma. Adolescents with asthma did not score differently on the Mental Health Index than their peers without asthma. Adolescents with asthma were less likely to experience good or excellent health than their peers without asthma (aOR, 0.37; 95% CI, 0.26-0.51 for intermittent asthma and 0.33; 95% CI, 0.25-0.41 for persistent asthma). These results remain similar across the different ages.Conclusions The mental well-being of adolescents with asthma is similar to that of their peers without asthma, although adolescents with asthma are less likely to perceive a good or excellent general health.

Objective: To evaluate the association between asthma prevalence and serum levels of vitamin D in Brazilian adolescents. Methods: This was a cross-sectional, school-based study involving adolescents between 12-17 years of age from four large Brazilian cities located at different latitudes (Fortaleza, Rio de Janeiro, Brasília, and Porto Alegre). Information on asthma diagnosis, lifestyle, and sociodemographic characteristics was collected by means of self-administered questionnaires. Serum concentrations of calcifediol were dichotomized as sufficient (≥ 20 ng/mL) or insufficient/deficient (< 20 ng/mL) levels. Bivariate analyses were carried out between vitamin D levels and prevalence of active asthma (AA), as well as other variables in study, using the chi-square test. Generalized linear models were configured to analyze potential confounding factors (p < 0.20). Results: Between 2013 and 2014, 1,053 adolescents were evaluated. The prevalences of AA and insufficient/deficient levels of calcifediol were 15.4% and 21%, respectively. There were no statistically significant associations between AA and hypovitaminosis D. The prevalences of AA and vitamin D insufficiency were, respectively, 2.34 (95% CI, 1,28-4.30) and 3.22 (95% CI, 1.75-5.95) times higher in Porto Alegre than in Rio de Janeiro, regardless of possible confounding factors. However, no significant associations were found between the prevalence of AA and vitamin-D-related variables in any of the cities. Conclusions: No association was found between AA and low levels of vitamin D in adolescents living at different latitudes in Brazil. RESUMO Objetivo: Avaliar a associação entre a prevalência de asma e níveis séricos de vitamina D em adolescentes brasileiros. Métodos: Estudo transversal de base escolar com adolescentes de 12 a 17 anos provenientes de quatro grandes cidades brasileiras em diferentes latitudes (Fortaleza, Rio de Janeiro, Brasília e Porto Alegre). Informações sobre o diagnóstico de asma, estilo de vida e características sociodemográficas foram coletadas por meio de questionários autoaplicáveis. As concentrações séricas de calcifediol foram dicotomizadas: suficientes (≥ 20 ng/mL) e insuficientes/deficientes (< 20 ng/mL). Foram realizadas análises bivariadas entre os níveis de vitamina D e a prevalência de asma ativa (AA), além de outras variáveis, por meio do teste do qui-quadrado. Modelos lineares generalizados foram configurados para analisar possíveis fatores de confusão (p < 0,20). Resultados: Entre 2013 e 2014, foram avaliados 1.053 adolescentes. A prevalência de AA e níveis insuficientes/deficientes de calcifediol foram de 15,4% e 21%, respectivamente. Não houve associações estatisticamente significativas entre AA e hipovitaminose D. As prevalências de AA e insuficiência de vitamina D foram, respectivamente, 2,34 (IC95%: 1,28-4,30) e 3,22 (IC95%: 1,75-5,95) vezes maiores em Porto Alegre que no Rio de Janeiro, independentemente de possíveis fatores de confusão. No entanto, não foram observadas associações significativas entre a prevalência de AA e variáveis relacionadas à vitamina D em nenhuma das cidades. Conclusões: Não se observou nenhuma associação entre AA e níveis baixos de vitamina D em adolescentes residentes em diferentes latitudes no Brasil.

Purpose: The Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) cohort was established to (1) investigate how exposures before conception and in previous generations influence health and disease, particularly allergies and respiratory health, (2) identify susceptible time windows and (3) explore underlying mechanisms. The ultimate aim is to facilitate efficient intervention strategies targeting multiple generations. Participants: RHINESSA includes study participants of multiple generations from ten study centres in Norway (1), Denmark (1), Sweden (3), Iceland (1), Estonia (1), Spain (2) and Australia (1). The RHINESSA core cohort, adult offspring generation 3 (G3), was first investigated in 2014-17 in a questionnaire study (N=8818, age 18-53 years) and a clinical study (subsample, n=1405). Their G2 parents participated in the population-based cohorts, European Community Respiratory Heath Survey and Respiratory Health In Northern Europe, followed since the early 1990s when they were 20-44 years old, at 8-10 years intervals. Study protocols are harmonised across generations. Findings to date Collected data include spirometry, skin prick tests, exhaled nitric oxide, anthropometrics, bioimpedance, blood pressure; questionnaire/interview data on respiratory/ general/reproductive health, indoor/outdoor environment, smoking, occupation, general characteristics and lifestyle; biobanked blood, urine, gingival fluid, skin swabs; measured specific and total IgE, DNA methylation, sex hormones and oral microbiome. Research results: suggest that parental environment years before conception, in particular, father’s exposures such as smoking and overweight, may be of key importance for asthma and lung function, and that there is an important susceptibility window in male prepuberty. Statistical analyses developed to approach causal inference suggest that these associations may be causal. DNA methylation studies suggest a mechanism for transfer of father’s exposures to offspring health and disease through impact on offspring DNA methylation. Future plans: Follow-up is planned at 5–8 years intervals, first in 2021-2023. Linkage with health registries contributes to follow-up of the cohort., Coordination of the RHINESSA study has received funding from the Research Council of Norway (Grants No. 274767, 214123, 228174, 230 827 and 273838), ERC StG project BRuSH #804199, the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 633 212 (the ALEC Study WP2), the Bergen Medical Research Foundation, and the Western Norwegian Regional Health Authorities (Grants No. 912011, 911 892 and 911631). Study centres have further received local funding from the following: Bergen: the above grants for study establishment and co- ordination, and, in addition, World University Network (REF and Sustainability grants), Norwegian Labour Inspection, the Norwegian Asthma and Allergy Association and Trond Mohn Foundation (Grant ID BFS2017TMT02). Albacete and Huelva: Sociedad Española de Patología Respiratoria (SEPAR) Fondo de Investigación Sanitaria (FIS PS09). Gøteborg, Umeå and Uppsala: the Swedish Heart and Lung Foundation, the Swedish Asthma and Allergy Association. Reykjavik: Iceland University. Melbourne: Australian National Health and Medical Research Council (NHMRC) Project Grant ID1128450. Tartu: the Estonian Research Council (Grant No. PUT562). Århus: The Danish Wood Foundation (Grant No. 444508795), the Danish Working Environment Authority (Grant No. 20150067134), Aarhus University (PhD scholarship).The RHINE study received funding by Norwegian Research Council, Norwegian Asthma and Allergy Association, Danish Lung Association, Swedish Heart and Lung Foundation, Vårdal Foundation for Health CareHealthcare Science and Allergy Research, Swedish Asthma and Allergy Association, Icelandic Research Council, and Estonian Science Foundation. The RHINE IV ongoing study has received funding from the Research Council of Norway project Life- GAP grant No. 300 765.Co- ordination of the ECRHS study has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 633 212 (the ALEC study), the Medical Research Council (ECRHS III) and the European Commission FP5 and FP7 (ECRHS I and II). The ECRHS IV ongoing study in the ten RHINESSA study centres has received funding from the European Union’s Horizon 2020 research and innovation programme projects EPHOR under grant agreement No. 874 703 and European Research Council (ERC) project BRuSH under grant agreement No. 804199, and from the Research Council of Norway grant No. 273 838. Funding agencies for ECRHS I, II and III are reported in online supplement.Coordination of the RHINESSA study has received funding from the Research Council of Norway (Grants No. 274767, 214123, 228174, 230 827 and 273838), ERC StG project BRuSH #804199, the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 633 212 (the ALEC Study WP2), the Bergen Medical Research Foundation, and the Western Norwegian Regional Health Authorities (Grants No. 912011, 911 892 and 911631). Study centres have further received local funding from the following: Bergen: the above grants for study establishment and co-ordination, and, in addition, World University Network (REF and Sustainability grants), Norwegian Labour Inspection, the Norwegian Asthma and Allergy Association and Trond Mohn Foundation (Grant ID BFS2017TMT02). Albacete and Huelva: Sociedad Española de Patología Respiratoria (SEPAR) Fondo de Investigación Sanitaria (FIS PS09). Gøteborg, Umeå and Uppsala: the Swedish Heart and Lung Foundation, the Swedish Asthma and Allergy Association. Reykjavik: Iceland University. Melbourne: Australian National Health and Medical Research Council (NHMRC) Project Grant ID1128450. Tartu: the Estonian Research Council (Grant No. PUT562). Århus: The Danish Wood Foundation (Grant No. 444508795), the Danish Working Environment Authority (Grant No. 20150067134), Aarhus University (PhD scholarship).The RHINE study received funding by Norwegian Research Council, Norwegian Asthma and Allergy Association, Danish Lung Association, Swedish Heart and Lung Foundation, Vårdal Foundation for Health CareHealthcare Science and Allergy Research, Swedish Asthma and Allergy Association, Icelandic Research Council, and Estonian Science Foundation. The RHINE IV ongoing study has received funding from the Research Council of Norway project Life-GAP grant No. 300 765.Co-ordination of the ECRHS study has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 633 212 (the ALEC study), the Medical Research Council (ECRHS III) and the European Commission FP5 and FP7 (ECRHS I and II). The ECRHS IV ongoing study in the ten RHINESSA study centres has received funding from the European Union’s Horizon 2020 research and innovation programme projects EPHOR under grant agreement No. 874 703 and European Research Council (ERC) project BRuSH under grant agreement No. 804199, and from the Research Council of Norway grant No. 273 838. Funding agencies for ECRHS I, II and III are reported in online supplement.

Objective: To provide an update on trends in asthma mortality in Brazil for two age groups: 0-4 years and 5-34 years. Methods: Data on mortality from asthma, as defined in the International Classification of Diseases, were obtained for the 1980-2014 period from the Mortality Database maintained by the Information Technology Department of the Brazilian Unified Health Care System. To analyze time trends in standardized asthma mortality rates, we conducted an ecological time-series study, using regression models for the 0- to 4-year and 5- to 34-year age groups. Results: There was a linear trend toward a decrease in asthma mortality in both age groups, whereas there was a third-order polynomial fit in the general population. Conclusions: Although asthma mortality showed a consistent, linear decrease in individuals ≤ 34 years of age, the rate of decline was greater in the 0- to 4-year age group. The 5- to 34-year group also showed a linear decline in mortality, and the rate of that decline increased after the year 2004, when treatment with inhaled corticosteroids became more widely available. The linear decrease in asthma mortality found in both age groups contrasts with the nonlinear trend observed in the general population of Brazil. The introduction of inhaled corticosteroid use through public policies to control asthma coincided with a significant decrease in asthma mortality rates in both subsets of individuals over 5 years of age. The causes of this decline in asthma-related mortality in younger age groups continue to constitute a matter of debate. RESUMO Objetivo: Apresentar uma atualização das tendências da mortalidade da asma no Brasil em duas faixas etárias: 0-4 anos e 5-34 anos Métodos: Dados relativos ao período de 1980 a 2014 referentes à mortalidade da asma, conforme se definiu na Classificação Internacional de Doenças, foram extraídos Sistema de Informação sobre Mortalidade do Departamento de Tecnologia da Informação do Sistema Único de Saúde. Para analisar as tendências temporais das taxas padronizadas de mortalidade da asma, realizou-se um estudo ecológico de séries temporais com modelos de regressão para as faixas etárias de 0 a 4 anos e 5 a 34 anos Resultados: Houve uma tendência linear de redução da mortalidade da asma em ambas as faixas etárias e uma tendência polinomial de terceira ordem na população geral Conclusões: Embora a mortalidade da asma tenha apresentado redução linear consistente em indivíduos com idade ≤ 34 anos, a taxa de declínio foi maior na faixa etária de 0 a 4 anos. A faixa etária de 5 a 34 anos também apresentou redução linear da mortalidade, e essa redução tornou-se mais pronunciada após o ano de 2004, quando o tratamento com corticosteroides inalatórios tornou-se mais amplamente disponível. A redução linear da mortalidade da asma em ambas as faixas etárias contrasta com a tendência não linear observada na população geral do Brasil. A introdução do uso de corticosteroides inalatórios por meio de políticas públicas de controle da asma coincidiu com uma diminuição significativa das taxas de mortalidade da asma em ambos os subgrupos de indivíduos com mais de 5 anos de idade. As causas dessa redução da mortalidade da asma em faixas etárias mais jovens ainda são objeto de debate.

Background Comorbidity patterns of childhood infections, atopic diseases, and adverse childhood experiences (ACE) are related to immune system programming conditions. The aim of this study was to make a step beyond the hygiene hypothesis and to comprehensively classify these patterns with latent class analysis (LCA). A second aim was to characterize the classes by associations with immunological, clinical, and sociodemographic variables. Methods LCA was applied to data from the CoLaus|PsyCoLaus study (N = 4874, age range 35–82 years) separately for men and women. It was based on survey information on chickenpox, measles, mumps, rubella, herpes simplex, pertussis, scarlet fever, hay fever, asthma, eczema, urticaria, drug allergy, interparental violence, parental maltreatment, and trauma in early childhood. Subsequently, we examined how immune-mediated classes were reflected in leukocyte counts, inflammatory markers (IL-1β, IL-6, TNF-α, hsCRP), chronic inflammatory diseases, and mental disorders, and how they differed across social classes and birth cohorts. Results LCA results with five classes were selected for further analysis. Latent classes were similar in both sexes and were labeled according to their associations as neutral, resilient, atopic, mixed (comprising infectious and atopic diseases), and ACE class. They came across with specific differences in biomarker levels. Mental disorders typically displayed increased lifetime prevalence rates in the atopic, the mixed, and the ACE classes, and decreased rates in the resilient class. The same patterns were apparent in chronic inflammatory diseases, except that the ACE class was relevant specifically in women but not in men. Conclusions This is the first study to systematically determine immune-mediated classes that evolve early in life. They display characteristic associations with biomarker levels and somatic and psychiatric diseases occurring later in life. Moreover, they show different distributions across social classes and allow to better understand the mechanisms beyond the changes in the prevalence of chronic somatic and psychiatric diseases.

INTRODUCTION: The use of antibiotics prenatally, during pregnancy, or neonatally may have adverse effects on the neonatal gut microbiome, and adversely affect the development of the infant immune system, leading to childhood atopy, asthma, allergy and obesity. Areas covered: Vaginal eubiosis and dysbiosis from molecular-based, cultivation-independent techniques, and how this affects the neonatal gut microbiome and early development of the immune system, the association between maternal antibiotics and the beneficial role of vitamin D in the development of atopy, asthma, allergy and obesity, efforts to reduce the use of antibiotics in pregnancy and therapeutic interventions such as vaginal 'seeding', probiotics, breastfeeding and neonatal dietary supplementation. Expert opinion: Currently available research gives insufficient attention to confounding variables. There remains uncertainty as to whether it is relevant that the mother suffered from the same condition as the purported infant outcome variable, for which she may have received antibiotics. In most studies, there is a lack of control for the number of antibiotic courses administered, the timing of use, the use of broad spectrum or narrow range antibiotics, the indication for antibiotics, the dose-dependent nature of the effect, the class of antibiotics used, or a varying degree of risk.

Background Studies have shown that airway obstruction and increased bronchial reactivity are present in early life in children developing asthma, which challenges the dogma that airway inflammation leads to low lung function. Further studies are needed to explore whether low lung function and bronchial hyperreactivity are inherent traits increasing the risk of developing airway inflammation and asthmatic symptoms in order to establish timely primary preventive initiatives. Methods and findings We investigated 367 (89%) of the 411 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort born to mothers with asthma, who were assessed by spirometry and bronchial reactivity to methacholine from age 1 month, plethysmography and bronchial reversibility from age 3 years, cold dry air hyperventilation from age 4 years, and exercise challenge at age 7 years. The COPSAC pediatricians diagnosed and treated asthma based on symptom load, response to inhaled corticosteroid, and relapse after treatment withdrawal according to a standardized algorithm. Repeated measures mixed models were applied to analyze lung function trajectories in children with asthma ever or never at age 1 month to 13 years. The number of children ever versus never developing asthma in their first 13 years of life was 97 (27%) versus 270 (73%), respectively. Median age at diagnosis was 2.0 years (IQR 1.2–5.7), and median remission age was 6.2 years (IQR 4.2–7.8). Children with versus without asthma had reduced lung function (z-score difference, forced expiratory volume, −0.31 [95% CI −0.47; −0.15], p < 0.001), increased airway resistance (z-score difference, specific airway resistance, +0.40 [95% CI +0.24; +0.56], p < 0.001), increased bronchial reversibility (difference in change in forced expiratory volume in the first second [ΔFEV1], +3% [95% CI +2%; +4%], p < 0.001), increased reactivity to methacholine (z-score difference for provocative dose, −0.40 [95% CI −0.58; −0.22], p < 0.001), decreased forced expiratory volume at cold dry air challenge (ΔFEV1, −4% [95% CI −7%; −1%], p < 0.01), and decreased forced expiratory volume after exercise (ΔFEV1, −4% [95% CI −7%; −1%], p = 0.02). Both airway obstruction and bronchial hyperreactivity were present before symptom debut, independent of disease duration, and did not improve with symptom remission. The generalizability of these findings may be limited by the high-risk nature of the cohort (all mothers had a diagnosis of asthma), the modest study size, and limited ethnic variation. Conclusions Children with asthma at some point at age 1 month to 13 years had airway obstruction and bronchial hyperreactivity before symptom debut, which did not worsen with increased asthma symptom duration or attenuate with remission. This suggests that airway obstruction and bronchial hyperreactivity are stable traits of childhood asthma since neonatal life, implying that symptomatic disease may in part be a consequence of these traits but not their cause., Hans Bisgaard and colleagues analyze cohort data for evidence as to whether symptomatic asthma is the cause or consequence of early-life airway obstruction and bronchial hyperreactivity., Author summary Why was this study done? It is believed that asthma develops from inflammation in the lungs that leads to loss of lung function, but low lung function may be an inherent trait in children at risk of asthma instead of a consequence of inflammation. It is important to explore whether low lung function is an inherent trait that increases the risk of developing airway inflammation and asthma in order to establish primary preventive initiatives for low lung function. What did the researchers do and find? Ninety-seven children who developed asthma and 270 children without asthma from the Danish COPSAC2000 birth cohort born to mothers with asthma were studied extensively with longitudinal lung function measurements from age 1 month to 13 years. Lung function was measured by spirometry from age 1 month and plethysmography from age 3 years, including assessments of bronchial reversibility to inhaled β2-agonist from age 3 years. Bronchial reactivity was assessed by methacholine challenge from age 1 month, cold dry air hyperventilation from age 4 years, and exercise challenge at age 7 years. Children developing asthma had reduced lung function from age 1 month throughout childhood compared to the children without asthma. The lung function deficit was present before the children developed asthma, did not progress with symptoms, and remained even if symptoms ceased. What do these findings mean? Low lung function appears to begin in early childhood in a group of children who will develop asthma. The lung function trait is established prior to development of airway inflammation and asthma, and does not worsen with increased duration of asthma symptoms. As airway obstruction and increased bronchial reactivity manifest as early as 1 month of age, it is possible that preventive measures undertaken during pregnancy will be most effective.

Objectives This study was designed to examine the association between loss-of-function mutations in the filaggrin gene (FLG) and atopic dermatitis (AD) and asthma in adult twins. Methods A previously well-characterized cohort of 575 adult twins were genotyped for the loss-of-function mutations in FLG (R501X, 2282del4 and R2447X) most common among northern Europeans. Subjects were examined for symptoms of atopic diseases as well as for lung function, airway responsiveness, and atopy. Results In the whole population of twins, the risk for AD was significantly increased in individuals with FLG mutations in comparison with wild-type carriers (34.3% vs. 21.8%) after adjustment for possible confounders (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.07–3.41; P = 0.028). A significant association was also observed for persistent AD (OR 2.10, 95% CI 1.02–4.36; P = 0.046). There were no significant differences in risk for asthma by FLG mutation status in individuals with and without AD, respectively (P-value for interaction, 0.595). In 11 dizygotic twin pairs discordant for FLG mutation status, risk for AD was higher in the twin carrying the FLG mutation (five of 11 [45.5%] twins had developed AD) than in the non-carrier co-twin (two of 11 [18.2%] twins had developed AD) (OR 2.50, 95% CI 0.45–13.85; P = 0.293). FLG status did not explain a significant proportion of the variation in AD (P = 0.328) or asthma (P = 0.321). Conclusions Filaggrin gene mutations are risk factors for the presence and persistence of AD and explain the discordance of AD within dizygotic twin pairs.

Objective : To present the Programa Infantil de Prevenção de Asma (PIPA, Program for the Prevention of Childhood Asthma) and the characteristics of the patients followed in this program. Methods : Implemented in the city of Uruguaiana, Brazil, PIPA has as its target population children and adolescents (< 18 years of age) with asthma or suspected asthma. Patients either enroll in PIPA spontaneously or are referred by pediatricians or primary care physicians. In this retrospective study, we use a standardized protocol to assess PIPA patients. Results : By the end of the study period, 646 patients were being followed. Of those, 298 (46.1%) were ≤ 3 years of age. In this group of patients, recurrent wheezing was identified in 60.7%, and the first episode of wheezing occurred in the first six months of life in 86.0%. Severe wheezing was identified in 29.5% and 45.4% in the children ≤ 3 and > 3 years of age, respectively. Physician-diagnosed asthma was reported in 26.5% and 82.2%, respectively. In the sample as a whole, the prevalence of passive smoking was high (> 36%), occurring during pregnancy in > 15%; > 40% of the patients had been born by cesarean section; and 30% had a mother who had had < 8 years of schooling. Conclusions : A prevention program for children with asthma is an effective strategy for controlling the disease. Knowledge of local epidemiological and environmental characteristics is essential to reducing the prevalence of the severe forms of asthma, to improving the use of health resources, and to preventing pulmonary changes that could lead to COPD in adulthood.

BACKGROUND: There is increasing interest in the possible link between maternal hypothyroidism in the perinatal period and childhood asthma risk. We explored this in the present study while accounting for the timing of hypothyroidism diagnosis. Further, we evaluated whether the risk was moderated by thyroid hormone treatment during pregnancy.METHODS: We conducted a population-based cohort study using Danish national registers. All liveborn singletons in Denmark from 1998 to 2007 were identified. Maternal hypothyroidism and asthma in the children were defined by data from the Patient Register and Prescription Registry. We estimated incidence rate ratios (IRRs) of asthma among children born to hypothyroid mothers versus children born to mothers with no recorded thyroid dysfunction using Poisson regression models.RESULTS: Of 595,669 children, 3,524 children were born to mothers with hypothyroidism diagnosed before delivery and 4,664 diagnosed after delivery. Overall 48,990 children received treatment for asthma. The IRRs of asthma was 1.16 (95% confidence interval (CI): 1.03-1.30) and 1.12 (95% CI: 1.02-1.24) for children born to mothers with hypothyroidism diagnosed before and after delivery, compared to children born to mothers with no thyroid dysfunction. The highest risk was observed among children born to mothers with hypothyroidism diagnosed before delivery who did not receive thyroid hormone treatment during pregnancy (IRR=1.37, 95% CI: 1.04-1.80).CONCLUSION: Our findings suggest that maternal hypothyroidism, especially when it is untreated, increases childhood asthma risk. Early detection and appropriate treatment of hypothyroidism in pregnant women may be an area for possible prevention of childhood asthma. This article is protected by copyright. All rights reserved.

Background - Cross‐sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether this inequality changes after puberty. We examined the sex‐specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty onset in longitudinal cohort data. Methods - In six European population‐based birth cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, concurrent asthma and rhinitis), puberty status and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero‐allergens. With generalized estimating equations, we analysed the effects of sex, age, puberty (yes/no) and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta‐analysis. Findings - We included data from 19 013 participants from birth to age 14‐20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs males 0.79 (95%‐confidence interval 0.73‐0.86) and 0.86 (0.79‐0.94), respectively (sex‐puberty interaction P = .089). Similarly, for current asthma only, females were less often affected than boys both before and after puberty onset: 0.71, 0.63‐0.81 and 0.81, 0.64‐1.02, respectively (sex‐puberty interaction P = .327). The prevalence of allergic multimorbidity showed the strongest sex effect before puberty onset (female‐male‐OR 0.55, 0.46‐0.64) and a considerable shift towards a sex‐balanced prevalence after puberty onset (0.89, 0.74‐1.04); sex‐puberty interaction: P < .001. Interpretation - The male predominance in prevalence before puberty and the “sex‐shift” towards females after puberty onset were strongest in multimorbid patients who had asthma and rhinitis concurrently. European Union under the Health Cooperation Work Programme of the 7th Framework Programme. Grant Number: 261357

International audience; The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults.

There are increasing numbers of emergency medical paediatric admissions. Our hypothesis was that characteristics of children and details of their emergency admissions are also changing over time. Details of emergency admissions in Scotland 2000–2013 were analysed. There were 574,403 emergency admissions, median age 2.3 years. The age distribution, proportion of boys and socioeconomic status of children admitted were essentially unchanged. Emergency admissions rose by 49% from 36/1000 children per annum to 54/1000 between 2000 and 2013. Emergency admissions that were discharged on the same day rose by 186% from 8.6/1000 to 24.6/1000. The mean duration of emergency admission fell from 1.7 to 1.0 days. The odds for an emergency admission with upper respiratory infection, “viral infection”, tonsillitis, bronchiolitis and lower respiratory tract infection all rose. In contrast the odds for an emergency admission with asthma and gastroenteritis fell. Conclusions: The demographics of children with emergency admissions have not changed substantially but characteristics of admissions have changed considerably, in particular admissions which are short stay and due to respiratory infection are much more common. The fall in the absolute number of children with some acute medical diagnoses suggests that the rise in admissions is not necessarily inexorable. What is Known: • Emergency admission prevalence is rising in many countries across Europe. What is New: • Our paper is the first to comprehensively analyse emergency medical paediatric admissions by exploring how characteristics of admissions and the children admitted have changed over time for a whole population. • The “take home message” is that whilst characteristics of emergency admissions have changed (e.g. number, duration of stay, readmissions, diagnoses), the characteristics of the children have not changed. Electronic supplementary material The online version of this article (10.1007/s00431-017-3064-z) contains supplementary material, which is available to authorized users.

Background: Observational studies have shown that body mass index (BMI) is positively associated with asthma. However, observational data are prone to confounding and reverse causation. In Mendelian randomization, genetic variants are used as unconfounded markers of exposures to examine causal effects. We examined the causal effect of BMI on asthma, hay fever, allergic sensitization, serum total immunoglobulin E (IgE), forced expiratory volume in one-second (FEV1) and forced vital capacity (FVC). Methods: We included 490 497 participants in the observational and 162 124 participants in the genetic analyses. A genetic risk score (GRS) was created using 26 BMI-associated single nucleotide polymorphisms (SNPs). Results were pooled in meta-analyses and expressed as odds ratios (ORs) or β-estimates with 95% confidence interval (CI). Results: The GRS was significantly associated with asthma (OR=1.009; 95% CI: 1.004, 1.013), but not with hay fever (OR= 0.998; 95% CI: 0.994, 1.002) or allergic sensitization (OR=0.999; 95% CI: 0.986, 1.012) per BMI-increasing allele. The GRS was significantly associated with decrease in FEV1: β=−0.0012 (95% CI: −0.0019, −0.0006) and FVC: β=−0.0022 (95% CI: −0.0031, −0.0014) per BMI-increasing allele. Effect sizes estimated by instrumental variable analyses were OR=1.07 (95% CI: 1.03, 1.10) for asthma, a 9 ml decrease in FEV1 (95% CI: 2.0-15 mL decrease) and a 16 ml decrease in FVC (95% CI: 7.0-24 mL decrease) per 1 kg/m 2 higher BMI. Conclusions: The results support the conclusion that increasing BMI is causally related to higher prevalence of asthma and decreased lung function, but not with hay fever or biomarkers of allergy.

Google Trends (GT) searches trends of specific queries in Google and reflects the real-life epidemiology of allergic rhinitis. We compared Google Trends terms related to allergy and rhinitis in all European Union countries, Norway and Switzerland from January 1, 2011 to December 20, 2016. The aim was to assess whether the same terms could be used to report the seasonal variations of allergic diseases. Using the Google Trend 5-year graph, an annual and clear seasonality of queries was found in all countries apart from Cyprus, Estonia, Latvia, Lithuania and Malta. Different terms were found to demonstrate seasonality depending on the country - namely: "hay fever"; "allergy"; and "pollen" - showing cultural differences. A single set of terms cannot be used across all European countries, but allergy seasonality can be compared across Europe providing the above three terms are used. Using longitudinal data in different countries and multiple terms, we identified an awareness-related spike of searches (December 2016). This article is protected by copyright. All rights reserved.

Severe respiratory syncytial virus (RSV) infection during infancy is associated with ongoing respiratory morbidity. In a large birth cohort of 2210 healthy preterm infants born at 32-35 weeks of gestation, we aimed to determine the role of atopy in the link between RSV hospitalization and current wheeze at age 6. We defined current wheeze as parent-reported wheeze or the use of respiratory medication in the past 12 months. Based on a positive family history of atopic disease, we distinguished between children with and without atopic predisposition. Six-year follow-up data was obtained in 997/1559 (64%) children of which 102 (10.2%) children had been hospitalized with RSV during infancy. Current wheeze was present in 184/997 (18.6%) children. RSV hospitalization was an independent risk factor for current wheeze in children without atopic predisposition (aOR 4.05 [95% CI 1.22-12.52]) but not in children with this atopic background (aOR 1.50 [95% CI 0.81-2.71]).Conclusion: This is the largest published birth cohort demonstrating that in late preterm infants, atopic predisposition defines the relationship between RSV hospitalization and current wheeze. Future RSV prevention trials aiming to prevent ongoing respiratory symptoms should be analyzed separately for atopic status. What is Known: • RSV infection is responsible for a significant burden of disease in young children worldwide. • Severe RSV infection in early life is associated with asthmatic symptoms later in life. What is New: • This is the largest published birth cohort reporting about the role of atopic predisposition in the link between severe RSV infection and current wheeze at school age. • We show that RSV hospitalization in infancy is an independent risk factor for current wheeze in late preterm children without atopic predisposition at age 6. This was not seen in children with atopic predisposition.

OBJECTIVE: To describe the prevalences of asthma and rhinitis in adolescents (13-14 years of age) in the city of Fortaleza, Brazil, in 2010, comparing the results with those obtained in a prevalence survey conducted in 2006-2007. METHODS: This was a cross-sectional study involving probabilistic samples of 3,015 and 3,020 adolescents in surveys conducted in 2006-2007 and 2010, respectively. The International Study of Asthma and Allergies in Childhood protocol was used on both occasions. RESULTS: Comparing the two periods, there were no significant differences regarding cumulative wheezing, active asthma, four or more wheezing attacks within the last year, sleep disturbed by wheezing more than one night per week, and speech-limiting wheezing. The prevalences of exercise-induced wheezing, dry cough at night, and physician-diagnosed asthma were significantly higher in 2010 than in the 2006-2007 period (p < 0.01 for all). The prevalence of physician-diagnosed rhinitis was significantly lower in 2010 (p = 0.01), whereas there were no significant differences between the two periods regarding cumulative rhinitis, current rhinitis, and rhinoconjunctivitis. In both periods, dry cough at night, current rhinitis, and rhinoconjunctivitis were significantly more prevalent in females than in males (p < 0.01 for all). Also in both periods, active asthma, current rhinitis, and rhinoconjunctivitis were more prevalent in private school students than in public school students (p < 0.01 for all). CONCLUSIONS: Our data show that the prevalences of asthma and rhinitis symptoms remain high among 13- and 14-year-olds in Fortaleza, predominantly among females and private school students.

BACKGROUND: Risk factors for the development of myelodysplastic syndromes (MDS) include age, exposure to ionising radiation, and cytotoxic drug treatment. Recently, asthma also has been suggested as a risk factor for MDS.METHODS: We undertook this nationwide population-based cohort study on patients with a first-time hospital-based asthma diagnosis during 2002-2013 and followed them for the development of MDS/chronic myelomonocytic leukaemia (CMML).RESULTS: We identified 75 995 patients with incident asthma and no previous MDS/CMML diagnosis. Seventy-eight patients subsequently developed MDS and nine patients developed CMML during 402 892 person-years. The cumulative risks of developing MDS/CMML among asthma patients were 0.02% (95% CI: 0.01-0.04%) and 0.07% (95% CI: 0.05-0.09%) during the first year and the first five years of follow-up, respectively. The standardised incidence ratio of MDS/CMML among asthma patients overall was 1.6 (95% CI: 1.3-2.0) with little variation across subgroups.CONCLUSIONS: Asthma may be a risk factor for the development of MDS/CMML.

Objective: To determine the prevalence of smoking experimentation among adolescents with asthma or allergic rhinitis. Methods: This was a cross-sectional study involving adolescent students (13-14 years of age) in the city of Belo Horizonte, Brazil. The participants completed the Centers for Disease Control and Prevention and International Study of Asthma and Allergies in Childhood questionnaires, both of which have been validated for use in Brazil. We calculated the prevalence of smoking experimentation in the sample as a whole, among the students with asthma symptoms, and among the students with allergic rhinitis symptoms, as well as in subgroups according to gender and age at smoking experimentation. Results: The sample comprised 3,325 adolescent students. No statistically significant differences were found regarding gender or age. In the sample as a whole, the prevalence of smoking experimentation was 9.6%. The mean age for smoking experimentation for the first time was 11.1 years of age (range, 5-14 years). Among the adolescents with asthma symptoms and among those with allergic rhinitis symptoms, the prevalence of self-reported smoking experimentation was 13.5% and 10.6%, respectively. Conclusions: The proportion of adolescents with symptoms of asthma or allergic rhinitis who reported smoking experimentation is a cause for concern, because there is strong evidence that active smoking is a risk factor for the occurrence and increased severity of allergic diseases.

BACKGROUND: The prevalence of sensitization and allergic disease has increased significantly worldwide. The aim of the "Aalst Allergy Study" was to document prevalences of sensitization and allergic symptoms, and to evaluate the effect of personal and environmental influences on these prevalences in an unbiased Belgian pediatric population. METHODS: A cross-sectional study was performed in an unbiased population of 2021 Belgian schoolchildren (3.4-14.8 years). Skin prick testing with the most common aeroallergens was performed. Allergic symptoms as well as potential risk factors for sensitization and allergic disease were documented by a parental questionnaire. RESULTS: The prevalence of sensitization to the most common aeroallergens and the prevalence of allergic diseases (eczema, asthma and rhinoconjunctivitis) were in line with the data in the literature. The association of current allergic symptoms with sensitization was only significant in the children aged > or =6 years. Age, gender, body mass index, bedroom environment and exposure to pets were the factors significantly associated with sensitization and allergic symptoms. CONCLUSIONS: Our study corroborates the reported prevalences of sensitization and allergic diseases. Moreover the study illustrates the complexity of the search for factors involved in the process of sensitization and allergic disease. The impact of different potential causative factors is not only influenced by mutual interactions of these factors, but also by the existence of distinct subtypes of disease.

The goal of asthma management is to achieve disease control. Poorly controlled asthma is associated with an increased number of days lost from school, exacerbations and days in hospital. Furthermore, children with uncontrolled asthma have more frequent contacts with the health-care system. Recent studies have added new information about the effects of poorly controlled asthma on a range of important, but less studied outcomes, including risk of obesity, daily physical activity, cardiovascular fitness, stress, concentration and focused attention, learning disabilities and risk of depression. From these studies it seems that poor asthma control may have a greater impact on the child than previously thought. This may have important long-term consequences for the child such as an increased risk of life-style associated diseases and poorer school performance. The level of control seems to be the most important determinant of these adverse effects and improvement in asthma control is associated with improvements in many of the outcomes. However, the improvement has to be maintained for a very long time (> 1 year).Accurate assessment of the level of asthma control is difficult. Various tools and scores have been developed. They are all based on various questionnaires, but their validation has been difficult because we have no golden standard to compare with. It seems as if the tests are most valuable when they suggest that the disease is poorly controlled because a large proportion of children in whom the tests suggest good asthma control may still have poorly controlled asthma when various objective outcomes are included in the assessment. A main reason for that seems to be that none of the tests accurately detects the child's adaptation in lifestyle. If you do not exercise you have fewer symptoms. © 2015 .

Background and objective: Hospitalization for respiratory syncytial virus (RSV) infection and asthma share common determinants, and meta-analyses indicate that children delivered by caesarean section (CS) are at increased risk of asthma. We aimed to investigate whether birth by CS is associated with an increased risk of hospitalization for RSV illness. Methods: This was a population-based national register-based cohort study, conducted between January, 1997 and June, 2003, which included all children born in Denmark and all hospitalizations for RSV disease in them from 0 to 23 months of age. We used Cox regression with adjustment for prematurity, asphyxia, birthweight, multiple births, single parenthood, maternal smoking during pregnancy, older siblings and asthma diagnoses up to 2 weeks before hospitalization for RSV infection, to compare the effects of acute or elective CS versus vaginal delivery, on subsequent hospitalization for RSV disease. A test for homogeneity was used to assess for effect over time. Results: 399,175 children with 10,758 hospitalizations for RSV illness were included; 31,715 were born by acute CS and 30,965 by elective CS. Adjusted hazard ratios for hospitalization for RSV infection in children born by acute CS and by elective CS were 1.09 (1.01-1.17) and 1.27 (1.19-1.36), respectively. The effect of elective CS remained unchanged throughout the first 2 years of life (P = 0.53), whereas the effect of acute CS was only present in the second year of life (P = 0.001). Conclusion: Delivery by caesarian section is associated with an increased risk of hospitalization for RSV infection. This effect continues at least throughout the first 2 years of life.

INTRODUCTION: The development of atopic diseases early in life suggests an important role of perinatal risk factors.OBJECTIVES: To study whether early life exposures modify the genetic influence on atopic diseases in a twin population.METHODS: Questionnaire data on atopic diseases from 850 monozygotic and 2,279 like-sex dizygotic twin pairs, 3-9 years of age, from the Danish Twin Registry were cross-linked with data on prematurity, Caesarean section, maternal age at birth, parental cohabitation, season of birth, and maternal smoking during pregnancy, from the Danish National Birth Registry. Significant predictors of atopic diseases were identified with logistic regression and subsequently tested for genetic effect modification using variance components analysis.RESULTS: After multivariable adjustment, prematurity (gestational age below 32 weeks) (OR=1.93, CI=1.45-2.56); Caesarean section (OR=1.25, CI=1.05-1.49); and maternal smoking during pregnancy (OR=1.70, CI=1.42-2.04) significantly influenced the risk of asthma, whereas none of the factors were significantly associated with atopic dermatitis and hay fever. Variance components analysis stratified by exposure status showed no significant change in the heritability of asthma according to the identified risk factors.CONCLUSION: In this population-based study of children there was no evidence of genetic effect modification of atopic diseases by several identified early life risk factors. The causal relationship between these risk factors and atopic diseases may therefore be mediated via mechanisms different from gene-environment interaction. The development of atopic diseases early in life suggests an important role of perinatal risk factors.

Summary OBJECTIVE: The prevalence of ragweed allergy is increasing worldwide. Ragweed distribution and abundance is spreading in Europe in a wide area ranging from the Rhone valley in France to Hungary and Ukraine, where the rate of the prevalence can peak at as high as 12%. Lowgrade ragweed colonisation was seen in Geneva and Ticino, less than two decades ago. There were fears that allergies to ragweed would increase Switzerland. The intent of this study was to assess the rate of prevalence of sensitisation and allergy to ragweed in the population living in the first rural Swiss setting where ragweed had been identified in 1996, and to evaluate indirectly the efficacy of elimination and containment strategies. MATERIAL AND METHODS: In 2009, 35 adults in a rural village in the Canton of Geneva were recruited. Data were collected by means of questionnaires and skin-prick tests were done on each participant. The study was approved by the local Ethics Committee. RESULTS: Based on questionnaires, 48.6% had rhinitis (95% confidence interval [CI] 32.9–64.4; n = 17/35) and 17.1% asthma (95% CI 8.1–32.6; n = 6/35). Atopy was diagnosed in 26.4% (95% CI 12.9–44.4) of the sample (n = 9/34). Ragweed sensitisation was found in 2.9% (95% CI 0.7–19.7; n = 1/34), mugwort sensitisation in 2.9% (95% CI 0.1–14.9; n = 1/35), alder sensitisation in 17.1% (95% CI 6.6–33.6; n = 6/35), ash sensitisation in 12.5% (95% CI 3.5–29.0; n = 4/32) and grass sensitisation in 22.9% (95% CI 10.4–40.1; n = 8/35). Ragweed (95% CI 0.1–14.9; n = 1/34) and mugwort allergies (95% CI 0.1–14.9; n = 1/35) were both found in 2.9% of the population. CONCLUSION: This study showed a surprisingly low incidence of ragweed sensitisation and allergy, of 2.9% and 2.9%, respectively, 20 years after the first ragweed detection in Geneva. The feared rise in ragweed allergy seems not to have happened in Switzerland, compared with other ragweed colonised countries. These results strongly support early field strategies against ragweed.

The present study aimed to investigate the prevalence of atopic dermatitis in primary schoolchildren in Denizli, Turkey, and to determine the possible risk factors for atopic dermatitis in home environment. A self-administered questionnaire was handled to the parents of 2,100 children aged 7 to 15 years, from three randomized primary schools and 1,644 (78.9%) completed and returned the questionnaire. The questionnaire included the United Kingdom Working Party diagnostic criteria and asked about conditions that could affect the course of atopic dermatitis. The prevalence of atopic dermatitis and coexisting factors that may affect the course of the disease were evaluated in 1,644 children (825 girls and 819 boys). The prevalence of atopic dermatitis was detected as 4.9%. Passive smoking, heating systems either in the house or in the child's bedroom, and the number of people living in the house had no significant effect (p > 0.005). The difference in prevalence of atopic dermatitis between developed and developing countries is striking. The determination of the factors that have an influence in this issue will probably enable us to change the course and frequency of atopic dermatitis. © 2008 The Authors.

OBJECTIVE: To evaluate the impact of asthma on activities of daily living and on health status in patients with controlled, partially controlled, or uncontrolled asthma in Brazil. METHODS: We used data related to 400 patients in four Brazilian cities (São Paulo, Rio de Janeiro, Salvador, and Curitiba), obtained in a survey conducted throughout Latin America in 2011. All study subjects were > 12 years of age and completed a standardized questionnaire in face-to-face interviews. The questions addressed asthma control, hospitalizations, emergency room visits, and school/work absenteeism, as well as the impact of asthma on the quality of life, sleep, and leisure. The level of asthma control was determined in accordance with the Global Initiative for Asthma criteria. RESULTS: Among the 400 respondents, asthma was controlled in 37 (9.3%), partially controlled in 226 (56.5%), and uncontrolled in 137 (34.2%). The numbers of patients with uncontrolled or partially controlled asthma who visited the emergency room, who were hospitalized, and who missed school/work were higher than were those of patients with controlled asthma (p = 0.001, p = 0.05, and p = 0.01, respectively). Among those with uncontrolled asthma, the impact of the disease on activities of daily living, sleep, social activities, and normal physical exertion was greater than it was among those with controlled or partially controlled asthma (p < 0.001). CONCLUSIONS: In Brazil, asthma treatment should be monitored more closely in order to increase treatment adherence and, consequently, the level of asthma control, which can improve patient quality of life and minimize the negative impact of the disease. OBJETIVO: Avaliar o impacto da asma nas atividades da vida diária e na saúde em pacientes com asma controlada, parcialmente controlada ou não controlada no Brasil. MÉTODOS: Foram utilizados dados de 400 pacientes de quatro cidades brasileiras (São Paulo, Rio de Janeiro, Curitiba e Salvador) obtidos em um inquérito realizado em países da América Latina em 2011. Todos os indivíduos do estudo tinham idade > 12 anos e responderam a um questionário padronizado por meio de entrevista presencial. As questões abordavam o controle da asma, número de hospitalizações, de consultas de urgência, absenteísmo na escola/trabalho e impacto da asma na qualidade de vida, sono e lazer. O nível de controle da asma foi verificado segundo os critérios da Global Initiative for Asthma. RESULTADOS: Entre 400 entrevistados, a asma estava controlada em 37 (9,3%); parcialmente controlada, em 226 (56,5%); e não controlada, em 137 (34,2%). O número de pacientes com asma não controlada ou parcialmente controlada que apresentaram hospitalizações, visitas ao pronto-socorro e faltas na escola/trabalho foi maior do que o daqueles com asma controlada (p = 0,001, p = 0,05 e p = 0,01, respectivamente). Os participantes com asma não controlada apresentaram um maior impacto da doença em atividades da vida diária, sono, atividades sociais e esforço físico normal do que aqueles com asma parcialmente controlada ou controlada (p < 0,001). CONCLUSÕES: Medidas terapêuticas devem ser mais intensamente adotadas em nosso país para melhorar o controle da asma e estimular a aderência ao tratamento. Isso, seguramente, proporcionará uma melhor qualidade de vida aos pacientes e uma redução do impacto negativo da doença.

Chlamydia pneumoniae: possible association with asthma in children

International audience; BACKGROUND: Chronic respiratory diseases (CRD) are greatly underestimated. The aim of this study was to assess the burden associated with reported CRD and chronic obstructive pulmonary disease, as defined on the basis of various standardized criteria, by estimating their point prevalence in a sample of individuals attending the Primary Health Care (PHC) level and Emergency Room (ER) Departments in Cape Verde (CV) archipelago. The second aim of the study was to identify factors related to airways obstruction and reported CRD in this population. METHODS: A cross-sectional study was carried out in CV during 2 weeks. Outpatients aged more than 20 years seeking care at PHC level and ER answered a standardized questionnaire and were subjected to spirometry, independently of their complaint. Two criteria for airways obstruction were taken into account: forced expiratory volume (FEV(1))

Although it is generally agreed that sensitization is an important risk factor for allergic diseases, the extent to which sensitization accounts for allergic symptoms in children is controversial. As part of the Aalst Allergy Study, this cross-sectional study investigated the prevalence of allergic symptoms and their association with sensitization in an unselected population of Flemish children aged 3.4-14.8 yr. Skin prick testing with the most common aeroallergens was performed and allergic symptoms were documented by a parental questionnaire. In the children older than 6 yr, a significant association of current wheezing, current dyspnea, airway hyperreactivity, rhinoconjunctivitis, and current eczema with sensitization was found, while in the pre-school children these associations were less pronounced. The association with sensitization was strongest for rhinoconjunctivitis and current respiratory symptoms - the association was less striking for children with current eczema. The impact of a positive family history of allergy on the association with sensitization was more important for eczema than for the other analyzed allergic symptoms. Persistent and late-onset wheezers were significantly more likely than non-wheezers and transient early wheezers to be associated with sensitization and a personal history of rhinoconjunctivitis. Late-onset wheezing was associated with a positive family history of allergy, while transient early wheezing was associated with day-care attendance. An association with eczema was found for all three childhood wheezing phenotypes. The association of allergic symptoms with sensitization is significant in the older but less pronounced in pre-school children and is more pronounced for current allergic symptoms. Diagnosis and disease definition of allergy symptoms remains difficult at pre-school age. The influence of a positive family history of allergy on the association of the respective allergic symptoms with sensitization was most important for eczema. Our data confirm the atopic characteristics of the different wheeze phenotypes.

BACKGROUND: Ambrosia artemisiifolia (short name = Ambrosia common ragweed) pollen is a potent allergen and has recently been found in Switzerland, spreading from the southwest of the country. The aim of this study is to describe Ambrosia sensitisation rates in the population-based SAPALDIA cohort (Swiss Study on Air Pollution And Lung Diseases In Adults) and to test whether an increase in these rates could be observed. METHODS: Among the 6345 participants from 8 areas who provided blood samples in 1991 and 2002, 5823 had valid results for specific IgE against common inhalant allergens tested with Phadiatop. In 2002 Ambrosia sensitisation was measured and positive tests were analysed for Artemisia vulgaris (mugwort). Blood samples taken in 1991 in Ticino and Geneva were also tested for Ambrosia. RESULTS: Sensitisation rate (Phadiatop) did not increase significantly between the two surveys and sensitisation was found in 30% of the participants. A proportion of 7.9% showed specific IgE to Ambrosia pollen. The sensitisation rate in Lugano and Geneva had not changed substantially since 1991. Among those sensitised to Ambrosia 82% also showed specific IgE against Artemisia, suggesting a high rate of cross-reactivity. Only 1.3% were sensitized to Ambrosia alone. The incidence of asthma or hay fever in participants with specific IgE to Ambrosia pollen was not higher than in the general study population. CONCLUSION: Currently Ambrosia pollen does not appear to be an important cause of inhalant allergies in Switzerland. Sensitisation rates are low and have not increased since 1991. Due to cross-reactivity Ambrosia sensitisation may be a consequence of primary sensitisation to Artemisia. Elimination of Ambrosia plants is nevertheless mandatory to avoid a future increase.

Background: Changing occurrence rates of asthma, allergic rhinitis and atopic dermatitis are of public health concern and require surveillance. Changes in prevalence rates of these atopic diseases were monitored during 10 years and their trend with time was determined taking into account the influence of personal and environmental risk factors. Methods: Four cross-sectional surveys in 5–7-year old children were performed in seven different communities in Switzerland between 1992 and 2001. Prevalence of respiratory and allergic symptoms and of affecting risk factors including parental environmental concern were assessed using a standardized parental questionnaire. Results: A total of 988 (74.1%), 1778 (79.0%), 1406 (82.6%) and 1274 (78.9%) children participated, respectively, in the 1992, 1995, 1998 and 2001 surveys. Prevalence rates of asthma and hay fever symptoms remained quite stable over time (wheeze/past year: 8.8%, 7.8%, 6.4% and 7.4%, sneezing attack during pollen season: 5.0%, 5.6%, 5.4% and 4.6%). Rates of reported atopic dermatitis symptoms (specific skin rash/past year: 4.6%, 6.5%,7.4% and 7.6%) showed an increase over time, but those of diagnosis of eczema did not show a clear pattern (18.4%, 15.7%, 14.0% and 15.2%). Stratified analysis by parental environmental concern and by parental atopy showed similar trends. Rates of atopic dermatitis symptoms showed significant increase in girls but stayed stable in boys. Conclusion: Results of these four consecutive surveys suggest that the increase in prevalence of asthma and hay fever in 5–7-year old children living in Switzerland may have ceased. However, symptoms of atopic dermatitis may still be on the rise, especially among girls.

BackgroundFew longitudinal data exist on the incidence of asthma in young adults and on the overall mortality risk due to asthma. A 7-year follow-up prospective study was performed to assess the incidence of asthma and mortality from all causes in a cohort of young adults.MethodsThe life status of a cohort of 6031 subjects, aged 20–44 years, who replied to a respiratory screening questionnaire between 1991 and 1992, was ascertained in 1999. A new questionnaire investigating the history of asthma was subsequently sent to the 5236 subjects who were still alive and residents in the areas of the study. 3880 subjects (74%) replied to the second questionnaire.ResultsThe incidence of adult-onset asthma was 15.3/10,000/year (95%CI:11.2–20.8). The presence of asthma-like symptoms (IRR:4.17; 95%CI:2.20–7.87) and allergic rhinitis (IRR:3.30; 95%CI:1.71–6.36) at baseline were independent predictors of the onset of asthma, which was more frequent in women (IRR:2.32; 95%CI:1.16–4.67) and increased in the younger generations.The subjects who reported asthma attacks or nocturnal asthma symptoms at baseline had an excess mortality risk from all causes (SMR = 2.05; 95%CI:1.06–3.58) in the subsequent seven years. The excess mortality was mainly due to causes not related to respiratory diseases.ConclusionAsthma occurrence is a relevant public health problem even in young adults. The likelihood of developing adult onset asthma is significantly higher in people suffering from allergic rhinitis, in women and in more recent generations. The presence of asthma attacks and nocturnal symptoms seems to be associated with a potential excess risk of all causes mortality.

In order to analyse trends in the bronchiolitis hospitalisations in the Netherlands from 1991 to 1999 for children aged 0-4 years, the national number of bronchiolitis hospitalisations were compared with those of asthma and pneumonia hospitalisations of the same age group. The number of bronchiolitis hospitalisations significantly increased, whereas the number of asthma and pneumonia hospitalisations remained unchanged.

In order to analyse trends in the bronchiolitis hospitalisations in the Netherlands from 1991 to 1999 for children aged 0-4 years, the national number of bronchiolitis hospitalisations were compared with those of asthma and pneumonia hospitalisations of the same age group. The number of bronchiolitis hospitalisations significantly increased, whereas the number of asthma and pneumonia hospitalisations remained unchanged.

In order to analyse trends in the bronchiolitis hospitalisations in the Netherlands from 1991 to 1999 for children aged 0-4 years, the national number of bronchiolitis hospitalisations were compared with those of asthma and pneumonia hospitalisations of the same age group. The number of bronchiolitis hospitalisations significantly increased, whereas the number of asthma and pneumonia hospitalisations remained unchanged.

Seventy four asthmatic children aged 7 to 11 years were examined along with controls matched by age and sex. Clinical and laboratory investigations preceded a 28-day follow-up where data about morning and evening peak expiratory flow rate (PEF), symptoms and treatment were recorded. The coefficient of variation of PEF was found to be an objective measurement of asthma severity that has statistically significant correlation with both symptoms (r s= .36) and treatment (r s= .60). Moreover, it separates mild and severe asthmatics, as confirmed by statistically significant differences (p= .008 or less) in symptoms, treatment, skin allergy and airways response to exercise. Skin allergy and airways responsiveness to exercise were found to be predictors of both disease and severity. By means of logistic regression analysis it was possible to establish the probabilities for both asthma and severe asthma when children presenting and not presenting these characteristics are compared. One single positive skin test represent a probability of 88% for the development of asthma and a probability of 70% for severe disease. A PEF reduction of 10% after an exercise test implies a probability of 73% for disease and a probability of 64% for severe disease. Increases in these variables imply geometrically increased risks and their presence together have a multiplicative effect in the final risk.

Objective Recently, self-reported asthma was combined with reported age of onset to investigate the disease's natural history. To assess the validity of reported results, we investigated the reliability of the method. Study Design and Settings The European Community Respiratory Health Survey was a longitudinal study with interviews in 1991/93 and in 2000/02. Lifelong asthma and age of asthma onset were assessed through self-administered questionnaires. Responses of 10,933 participants in the follow-up were combined to separate true from false incident cases. The repeatability of questions was assessed and the bias in cumulative incidence (CI) estimation was quantified. Results Age at onset had excellent reliability (mean difference between the two interviews = −0.20, weighted κ = 0.88) allowing the differentiation of false and true incident cases. Given this information, lifelong asthma question's reliability was very high (agreement = 0.96, κ = 0.83). Misclassified subjects had respiratory conditions similar to the asthmatics. Baseline asthma was underreported and, if ignoring the onset age, the CI was severely overestimated (observed 5.82%, actual 3.02%). Conclusion Questionnaire-based longitudinal studies make more reliable estimates possible when all the retrospective information is used: the reported age of onset plays a key role and should be accounted for when investigating the natural history of diseases.

Objective: To present official longitudinal data on the impact of asthma in Brazil between 2008 and 2013. Methods: This was a descriptive study of data collected between 2008 and 2013 from an official Brazilian national database, including data on asthma-related number of hospitalizations, mortality, and hospitalization costs. A geographical subanalysis was also performed. Results: In 2013, 2,047 people died from asthma in Brazil (5 deaths/day), with more than 120,000 asthma-related hospitalizations. During the whole study period, the absolute number of asthma-related deaths and of hospitalizations decreased by 10% and 36%, respectively. However, the in-hospital mortality rate increased by approximately 25% in that period. The geographic subanalysis showed that the northern/northeastern and southeastern regions had the highest asthma-related hospitalization and in-hospital mortality rates, respectively. An analysis of the states representative of the regions of Brazil revealed discrepancies between the numbers of asthma-related hospitalizations and asthma-related in-hospital mortality rates. During the study period, the cost of asthma-related hospitalizations to the public health care system was US$ 170 million. Conclusions: Although the numbers of asthma-related deaths and hospital admissions in Brazil have been decreasing since 2009, the absolute numbers are still high, resulting in elevated direct and indirect costs for the society. This shows the relevance of the burden of asthma in middle-income countries. RESUMO Objetivo: Apresentar dados longitudinais oficiais sobre o impacto da asma no Brasil entre 2008 e 2013. Métodos: Estudo descritivo de dados extraídos de um banco de dados do governo brasileiro entre 2008 e 2013, no qual foram analisados as hospitalizações e óbitos por asma, bem como o custo das hospitalizações. Foi também realizada uma subanálise geográfica. Resultados: Em 2013, 2.047 pessoas morreram de asma no Brasil (5 óbitos/dia), com mais de 120.000 hospitalizações por asma. Durante o período de estudo, o número absoluto de óbitos e hospitalizações por asma diminuiu 10% e 36%, respectivamente. No entanto, a taxa de mortalidade hospitalar aumentou aproximadamente 25%. A subanálise geográfica mostrou que as regiões Norte/Nordeste e Sudeste apresentaram as maiores taxas de hospitalização e mortalidade hospitalar por asma, respectivamente. A análise dos estados representativos de cada região mostrou discrepâncias entre as hospitalizações por asma e as taxas de mortalidade hospitalar por asma. Durante o período de estudo, as hospitalizações por asma custaram US$ 170 milhões ao sistema público de saúde. Conclusões: Embora os óbitos e hospitalizações por asma no Brasil estejam diminuindo desde 2009, os números absolutos ainda são altos, com elevados custos diretos e indiretos para a sociedade, o que mostra a relevância do impacto da asma em países de renda média.