Showing papers by "Josep M. Antó published in 2017"
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease as discussed by the authors.
1,755 citations
Spanish National Research Council1, Autonomous University of Madrid2, University of Queensland3, Jimma University4, United Arab Emirates University5, University of Cartagena6, University of Qom7, Mekelle University8, University of Belgrade9, Stanford University10, University of São Paulo11, Debre Berhan University12, Bahir Dar University13, Haramaya University14, Debre markos University15, State University of New York System16, University System of Georgia17, Christian Medical College & Hospital18, University of Peradeniya19, Bielefeld University20, University of Newcastle21, Newcastle University22, Howard University23, University of Delhi24, University of Mazandaran25, Yokohama City University26, Juntendo University27, Albert Einstein College of Medicine28
TL;DR: The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.
1,601 citations
University of Montpellier1, French Institute of Health and Medical Research2, Swiss Institute of Allergy and Asthma Research3, Institute for Systems Biology4, Charité5, Paris Descartes University6, University Medical Center Groningen7, Medical University of Vienna8, Karolinska Institutet9, University of Toulouse10, University of Helsinki11, Ghent University12, Oslo University Hospital13, Pierre-and-Marie-Curie University14, Odense University Hospital15, Medical University of Łódź16, Biomax Informatics AG17, Utrecht University18, Bradford Royal Infirmary19, Karolinska University Hospital20, King's College London21, Ghent University Hospital22, University of Valencia23, University of Crete24, University of Bologna25, University of Paris26, Ludwig Maximilian University of Munich27, Helmholtz Centre for Environmental Research - UFZ28, Pompeu Fabra University29
TL;DR: The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms.
Abstract: Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non-IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.
146 citations
Karolinska Institutet1, Institute for Systems Biology2, University of Manitoba3, Stockholm County Council4, Laval University5, University of British Columbia6, Imperial College London7, University of Alberta8, University of Lyon9, Merck & Co.10, University of Southern California11, University of Montpellier12, Utrecht University13
TL;DR: The results indicated that gene‐environment interactions are important for asthma development and provided supportive evidence for interaction with air pollution for ADCY2, B4GALT5, and DLG2.
Abstract: Rationale: The evidence supporting an association between traffic-related air pollution exposure and incident childhood asthma is inconsistent and may depend on genetic factors.Objectives: To identify gene–environment interaction effects on childhood asthma using genome-wide single-nucleotide polymorphism (SNP) data and air pollution exposure. Identified loci were further analyzed at epigenetic and transcriptomic levels.Methods: We used land use regression models to estimate individual air pollution exposure (represented by outdoor NO2 levels) at the birth address and performed a genome-wide interaction study for doctors’ diagnoses of asthma up to 8 years in three European birth cohorts (n = 1,534) with look-up for interaction in two separate North American cohorts, CHS (Children’s Health Study) and CAPPS/SAGE (Canadian Asthma Primary Prevention Study/Study of Asthma, Genetics and Environment) (n = 1,602 and 186 subjects, respectively). We assessed expression quantitative trait locus effects in human lung...
104 citations
TL;DR: High residential surrounding greenness and higher proximity to green spaces were negatively associated with wheezing among children from the Euro-Siberian region, and higher residential surrounding greyness was found to increase the risk for bronchitis in this region.
Abstract: We assessed the effect of three different indices of urban built environment on allergic and respiratory conditions. This study involved 2472 children participating in the ongoing INMA birth cohort located in two bio-geographic regions (Euro-Siberian and Mediterranean) in Spain. Residential surrounding built environment was characterised as 1) residential surrounding greenness based on satellite-derived normalised difference vegetation index (NDVI), 2) residential proximity to green spaces and 3) residential surrounding greyness based on urban land use patterns. Information on wheezing, bronchitis, asthma and allergic rhinitis up to age 4 years was obtained from parent-completed questionnaires. Logistic regression and generalised estimating equation modelling were performed. Among children from the Euro-Siberian region, higher residential surrounding greenness and higher proximity to green spaces were negatively associated with wheezing. In the Mediterranean region, higher residential proximity to green spaces was associated with a reduced risk for bronchitis. A higher amount of residential surrounding greyness was found to increase the risk for bronchitis in this region. Associations between indices of urban residential greenness and greyness with respiratory diseases differ by region. The pathways underlying these associations require further exploration.
95 citations
French Institute of Health and Medical Research1, Buck Consultants2, Pierre-and-Marie-Curie University3, University of Montpellier4, Université catholique de Louvain5, Katholieke Universiteit Leuven6, Ghent University Hospital7, Pompeu Fabra University8, Charité9, Odense University Hospital10, Woolcock Institute of Medical Research11, Humanitas University12, Leiden University Medical Center13, Federal University of Bahia14, University of Porto15, Erasmus University Rotterdam16, University of Helsinki17, University of Paris18, University of Würzburg19, Medical University of Łódź20, Houston Advanced Research Center21, Vilnius University22, University of Barcelona23, Nova Southeastern University24, Karolinska Institutet25, Monash University26, National and Kapodistrian University of Athens27, University of Manchester28, University of Aberdeen29, University of Edinburgh30, Medical University of Warsaw31, University of Manitoba32, University of Coimbra33, Medical University of Graz34, University of Salerno35, University of Turku36, European Union of Medical Specialists37, Queen's University Belfast38
TL;DR: Data from a mobile phone app that collects data from daily visual analogue scales for overall allergic symptoms and the distribution of responses for the VAS supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.
Abstract: Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global 50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.
77 citations
Uppsala University1, Stockholm County Council2, Medical University of Vienna3, Imperial College London4, Karolinska University Hospital5, Karolinska Institutet6, University of Manchester7, Boston Children's Hospital8, Pompeu Fabra University9, French Institute of Health and Medical Research10, Versailles Saint-Quentin-en-Yvelines University11
TL;DR: IgE reactivity to a few allergen molecules early in life identifies children with a high risk of asthma and/or rhinitis at 16 years, and these findings will be of importance for developing preventive strategies for asthma and Rhinitis in children.
62 citations
TL;DR: The male predominance of rhinitis prevalence in childhood changed towards a female predominance in adolescence across the globe, except in Asia, where themale predominance remained beyond childhood.
Abstract: Background: A sex-related switch in the prevalence of asthma from childhood (male predominance) to adulthood (female predominance) has been described, but for allergic rhinitis this remains unclear. We aimed to examine sex- and age-group-specific differences in allergic rhinitis prevalence by systematically evaluating studies from across the globe. Methods: A systematic search of MEDLINE and Embase for population-based cross-sectional studies was performed regardless of the language of publication. The search was restricted to the present millennium (2000 to June 2014). Study quality was defined by the sampling method, response rate, sample size, and data collection method. To assess sex differences in the prevalence of self-or parent-reported symptoms of rhinitis, calculated pooled estimates of the male-female ratio (MFR) were obtained using random-effects model meta-analyses due to heterogeneity. A meta-regression analysis was also performed. Results: Out of 6,539 publications identified, 67 cross-sectional population-based studies (291,726 males and 301,781 females) were included in our meta-analysis. In children (<11 years of age) significantly more boys than girls had rhinitis symptoms (MFR 1.21, 95% CI 1.17-1.25), whereas in adolescents (11 to <18 years of age) males were significantly less often affected than females (MFR 0.90, 95% CI 0.85-0.95). No sex-specific prevalence difference was observed in adults (MFR 0.96, 95% CI 0.83-1.17). These findings were consistent in all continents except in Asia, where the male predominance remained beyond childhood. Conclusions: The male predominance of rhinitis prevalence in child-hood changed towards a female predominance in adolescence across the globe, except in Asia. Longitudinal studies are needed to confirm these cross-sectional data and examine possible determinants and underlying mechanisms. (C) 2017 S. Karger AG, Basel
61 citations
Brigham and Women's Hospital1, Pompeu Fabra University2, Lovelace Respiratory Research Institute3, University of Colorado Boulder4, University of Colorado Denver5, University of Florence6, University Medical Center Groningen7, University of Zurich8, Katholieke Universiteit Leuven9, AstraZeneca10, University of Nebraska Medical Center11, Northeastern University12, Johns Hopkins University School of Medicine13, Johns Hopkins University14, University of Barcelona15
TL;DR: In this article, the reproducibility of COPD clustering subtypes across studies was modest (median NMI range 0.17-0.43), for methods that excluded individuals that did not clearly belong to any cluster, agreement was better but still suboptimal.
Abstract: Background COPD is a heterogeneous disease, but there is little consensus on specific definitions for COPD subtypes. Unsupervised clustering offers the promise of ‘unbiased’ data-driven assessment of COPD heterogeneity. Multiple groups have identified COPD subtypes using cluster analysis, but there has been no systematic assessment of the reproducibility of these subtypes. Objective We performed clustering analyses across 10 cohorts in North America and Europe in order to assess the reproducibility of (1) correlation patterns of key COPD-related clinical characteristics and (2) clustering results. Methods We studied 17 146 individuals with COPD using identical methods and common COPD-related characteristics across cohorts (FEV 1 , FEV 1 /FVC, FVC, body mass index, Modified Medical Research Council score, asthma and cardiovascular comorbid disease). Correlation patterns between these clinical characteristics were assessed by principal components analysis (PCA). Cluster analysis was performed using k-medoids and hierarchical clustering, and concordance of clustering solutions was quantified with normalised mutual information (NMI), a metric that ranges from 0 to 1 with higher values indicating greater concordance. Results The reproducibility of COPD clustering subtypes across studies was modest (median NMI range 0.17–0.43). For methods that excluded individuals that did not clearly belong to any cluster, agreement was better but still suboptimal (median NMI range 0.32–0.60). Continuous representations of COPD clinical characteristics derived from PCA were much more consistent across studies. Conclusions Identical clustering analyses across multiple COPD cohorts showed modest reproducibility. COPD heterogeneity is better characterised by continuous disease traits coexisting in varying degrees within the same individual, rather than by mutually exclusive COPD subtypes.
60 citations
TL;DR: Investigation of the natural IgE and IgG responses toward a large panel of respiratory and food allergens in subjects exposed to different respiratory allergen loads found variability inallergen‐specific IgEand IgG frequencies depends on exposure, route of exposure, and overall immunogenicity of the allergenic.
Abstract: Background The nature of allergens and route and dose of exposure may affect the natural development of IgE and IgG responses. Objective We sought to investigate the natural IgE and IgG responses toward a large panel of respiratory and food allergens in subjects exposed to different respiratory allergen loads. Methods A cross-sectional analysis was conducted in 340 adults of the EGEA (Epidemiological study of the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy) (170 with and 170 without asthma) cohort. IgE and IgG responses to 47 inhalant and food allergen components were analyzed in sera using allergen microarray and compared between 5 French regions according to the route of allergen exposure (inhaled vs food allergens). Results Overall 48.8% of the population had allergen-specific IgE levels of 0.3 ISAC standardized units (ISU) or more to at least 1 of the 47 allergens with no significant differences across the regions. For ubiquitous respiratory allergens (ie, grass, olive/ash pollen, house dust mites), specific IgE did not show marked differences between regions and specific IgG (≥0.5 ISU) was present in most subjects everywhere. For regionally occurring pollen allergens (ragweed, birch, cypress), IgE sensitization was significantly associated with regional pollen exposure. For airborne allergens cross-reacting with food allergens, frequent IgG recognition was observed even in regions with low allergen prevalence (Bet v 1) or for allergens less frequently recognized by IgE (profilins). Conclusions The variability in allergen-specific IgE and IgG frequencies depends on exposure, route of exposure, and overall immunogenicity of the allergen. Allergen contact by the oral route might preferentially induce IgG responses.
60 citations
TL;DR: This study provides new insights into the dynamic epigenetic landscape of the first 8 years of life by identifying 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of p < 1.14 × 10−7.
Abstract: DNA methylation has been found to associate with disease, aging and environmental exposure, but it is unknown how genome, environment and disease influence DNA methylation dynamics in childhood. By analysing 538 paired DNA blood samples from children at birth and at 4–5 years old and 726 paired samples from children at 4 and 8 years old from four European birth cohorts using the Illumina Infinium Human Methylation 450 k chip, we have identified 14,150 consistent age-differential methylation sites (a-DMSs) at epigenome-wide significance of p < 1.14 × 10−7. Genes with an increase in age-differential methylation were enriched in pathways related to ‘development’, and were more often located in bivalent transcription start site (TSS) regions, which can silence or activate expression of developmental genes. Genes with a decrease in age-differential methylation were involved in cell signalling, and enriched on H3K27ac, which can predict developmental state. Maternal smoking tended to decrease methylation levels at the identified da-DMSs. We also found 101 a-DMSs (0.71%) that were regulated by genetic variants using cis-differential Methylation Quantitative Trait Locus (cis-dMeQTL) mapping. Moreover, a-DMS-associated genes during early development were significantly more likely to be linked with disease. Our study provides new insights into the dynamic epigenetic landscape of the first 8 years of life.
TL;DR: The prevalence of coexisting allergic rhinitis and asthma shows a clear male predominance in childhood and seems to switch to a female predominanceIn adolescents, although this switch was less pronounced for allergic Rhinitis only.
Abstract: Allergic rhinitis and asthma as single entities affect more boys than girls in childhood but more females in adulthood. However, it is unclear if this prevalence sex-shift also occurs in allergic rhinitis and concurrent asthma. Thus, our aim was to compare sex-specific differences in the prevalence of coexisting allergic rhinitis and asthma in childhood, adolescence and adulthood. Post-hoc analysis of systematic review with meta-analysis concerning sex-specific prevalence of allergic rhinitis. Using random-effects meta-analysis, we assessed male–female ratios for coexisting allergic rhinitis and asthma in children (0–10 years), adolescents (11–17) and adults (> 17). Electronic searches were performed using MEDLINE and EMBASE for the time period 2000–2014. We included population-based observational studies, reporting coexisting allergic rhinitis and asthma as outcome stratified by sex. We excluded non-original or non-population-based studies, studies with only male or female participants or selective patient collectives. From a total of 6539 citations, 10 studies with a total of 93,483 participants met the inclusion criteria. The male–female ratios (95% CI) for coexisting allergic rhinitis and asthma were 1.65 (1.52; 1.78) in children (N = 6 studies), 0.61 (0.51; 0.72) in adolescents (N = 2) and 1.03 (0.79; 1.35) in adults (N = 2). Male–female ratios for allergic rhinitis only were 1.25 (1.19; 1.32, N = 5) in children, 0.80 (0.71; 0.89, N = 2) in adolescents and 0.98 (0.74; 1.30, N = 2) in adults, respectively. The prevalence of coexisting allergic rhinitis and asthma shows a clear male predominance in childhood and seems to switch to a female predominance in adolescents. This switch was less pronounced for allergic rhinitis only.
French Institute of Health and Medical Research1, University of Basel2, Swiss Tropical and Public Health Institute3, Pompeu Fabra University4, University of Bristol5, University of Turin6, Utrecht University7, Ludwig Maximilian University of Munich8, National Institutes of Health9, Imperial College London10, University of Verona11, Umeå University12, University of Grenoble13
TL;DR: This study showed for the first time using homogenized measures of outcome and exposure across 16 cities the important heterogeneity regarding the association between SEP and NO2 in Western Europe.
French Institute of Health and Medical Research1, Transylvania University2, Pompeu Fabra University3, Charité4, Ghent University Hospital5, Pierre-and-Marie-Curie University6, University of Naples Federico II7, University of Montpellier8, Odense University Hospital9, University of Porto10, University of Helsinki11, Katholieke Universiteit Leuven12, University of Paris13, University of Würzburg14, Medical University of Łódź15, Oslo University Hospital16, University of Oslo17, University of Cologne18, University of Manchester19, National and Kapodistrian University of Athens20, Medical University of Warsaw21, University of Zurich22, Medical University of Graz23, University of Salerno24, European Union of Medical Specialists25, Vilnius University26, University of Turku27, Karolinska Institutet28, Boston Children's Hospital29, University of Edinburgh30
TL;DR: Compared Google Trends terms related to allergy and rhinitis in all European Union countries, Norway and Switzerland from 1 January 2011 to 20 December 2016, an awareness‐related spike of searches was identified and allergy seasonality can be compared across Europe.
Abstract: 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 1 January 2011 to 20 December 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).
Université catholique de Louvain1, Buck Consultants2, University of Porto3, University of Coimbra4, Federal University of Bahia5, Universidade Federal de Santa Catarina6, University of Naples Federico II7, University of Genoa8, University of Bari9, Pierre-and-Marie-Curie University10, Charité11, University of Cologne12, University of Edinburgh13, Pompeu Fabra University14, University of Barcelona15, Medical University of Łódź16, Medical University of Warsaw17, University of Graz18, Woolcock Institute of Medical Research19, Monash University20
TL;DR: This paper presents a meta-analyses of the immune systems of eight types of inflammatory bowel disease, conducted in the period of May 21 to 29, 2013 at the Mayo Clinic in Rochester, Minnesota.
Abstract: J Bousquet, MD , O VandenPlas, MD , M Bewick, MD , S Arnavielhe, PhD , A Bedbrook, BSc , R Murray, PhD , M van Eerd, MSc , J Fonseca, MD , M Morais-Almeida, MD , A Todo Bom, MD , AA Cruz, MD , F Sarquis Serpa, MD, 12 J da Silva, MD, 13 E Menditto, PhD, , G Passalacqua, MD , C Stellato , MD, 16 , MT Ventura, MD , D Caimmi, MD , P Demoly, MD , KC Bergmann, MD , T Keil, MD , L Klimek, MD , R Mösges, MD , S Shamai, MD, 22 T Zuberbier, MD , D Larenas-Linnemann, MD , M Rodriguez Gonzalez, MD, 24 MT Burguete Cabañas, MD, 25 D Ryan, MD , A Sheikh, MD , JM Anto, MD , J Mullol, MD , A Valero, MD 29 ML Kowalski, MD , P Kuna, MD , B Samolinski, MD , PV Tomazic, MD , S Bosnic-Anticevich, PhD , RE O'Hehir MD, , G De Vries, MSc , D Laune, PhD 5
Ghent University Hospital1, RMIT University2, Leiden University Medical Center3, University of Porto4, Medical University of Łódź5, Katholieke Universiteit Leuven6, University of Edinburgh7, Medical University of Warsaw8, Celal Bayar University9, Transylvania University10, Pierre-and-Marie-Curie University11, Pompeu Fabra University12, Charité13, Odense University Hospital14, Woolcock Institute of Medical Research15, Humanitas University16, Universidade Federal de Minas Gerais17, Eskişehir Osmangazi University18, Imperial College London19, Federal University of Bahia20, University of Montpellier21, Istanbul University22, Erasmus University Rotterdam23, University of Helsinki24, University of Paris25, University of Würzburg26, Karolinska Institutet27, Vilnius University28, University of Nantes29, University of Coimbra30, University of Cologne31, University of Barcelona32, Boston Children's Hospital33, Monash University34, University of Manchester35, National and Kapodistrian University of Athens36, University of Genoa37, University of Aberdeen38, University of Manitoba39, University of Salerno40, Medical University of Graz41, Université catholique de Louvain42, European Union of Medical Specialists43, University of Bari44, Queen's University Belfast45
TL;DR: MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitisand asthma multi-morbidity.
Abstract: A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.
TL;DR: The restrictive spirometric pattern is associated with deficits in the physical component of quality of life that are partly independent of the presence of respiratory symptoms, and is linked to worse health-related QoL.
Abstract: The restrictive spirometric pattern is associated with a substantial morbidity and mortality burden We sought to determine to what extent spirometric restriction is associated with impaired quality of life We used data from two large population-based European cohorts: 6698 European Community Respiratory Health Survey (ECRHS) and 6069 Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) adult participants The restrictive pattern was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥lower limit of normal (LLN) and FVC In both cohorts, the restrictive pattern was associated with heavy smoking, being underweight or obese and the coexistence of respiratory symptoms In univariate analyses, compared with the normal group, both the restrictive and obstructive pattern had significant Physical Component Summary deficits (−277 and −208, respectively, in ECRHS; −325 and −214, respectively, in SAPALDIA; all p-values The restrictive spirometric pattern is associated with deficits in the physical component of quality of life that are partly independent of the presence of respiratory symptoms
TL;DR: Asthma, eczema and rhinitis shared a larger number of associated proteins than expected by chance, and their associated proteins exhibited a significant degree of interconnectedness in the interaction network, suggesting that type 2 signaling pathways represent a relevant multimorbidity mechanism of allergic diseases.
Abstract: This work was supported by the Spanish Ministry of Science and Innovation (MICINN) grant BIO2011-22568, and by Mechanisms of the Development of ALLergy (MeDALL), a collaborative project done within the EU under the Health Cooperation Work Programme of the Seventh Framework programme (grant agreement number 261357).
TL;DR: An asthma outbreak of hospitalizations and deaths was noticed in Australia and in Kuwait and was clearly demonstrated using Google Trends (GT), a Web-based surveillance tool of interest in clinical practice.
Abstract: An asthma outbreak of hospitalizations and deaths was noticed in Australia (November 2016) and in Kuwait (December 2016) This outbreak was clearly demonstrated using Google Trends (GT), a Web-based surveillance tool of interest in clinical practice
TL;DR: This study was supported by the Swedish Asthma and Allergy Research Foundation, the Swedish Research Council, and the European Commission's Seventh Framework 29 Program MeDALL (Mechanisms for the Development of Allergy).
Abstract: This study was supported by the Swedish Asthma and Allergy Research Foundation; Stockholm County Council; the Swedish Research Council of Health, Working Life and Welfare; the Swedish Research Council; the Swedish Society of Medicine; the Swedish Heart-Lung Foundation; the Swedish Cancer and Allergy Foundation; the Konsul Th Berg's Foundation, the Magnus Bergvall Foundation, the Swedish Association for Allergology, the European Commission's Seventh Framework 29 Program MeDALL (Mechanisms for the Development of Allergy) under grant agreement no. 261357, and in part by grant no. F4605 of the Austrian Science Fund (FWF).
Karolinska Institutet1, University of Groningen2, University Medical Center Groningen3, Pompeu Fabra University4, University of Barcelona5, Boston Children's Hospital6, Swiss Tropical and Public Health Institute7, University of Basel8, Utrecht University9, French Institute of Health and Medical Research10
TL;DR: YKL‐40 levels, but not CHI3L1 SNPs or methylation levels, were associated with childhood asthma, and the effects of CHI 3L1 genetic variation on circulating YKL•40 levels are partly mediated by methylation profiles.
Abstract: Background Circulating levels of the chitinase-like protein YKL-40 are influenced by genetic variation in its encoding gene (chitinase 3–like 1 [CHI3L1] ) and are increased in patients with several diseases, including asthma. Epigenetic regulation of circulating YKL-40 early in life is unknown. Objective We sought to determine (1) whether methylation levels at CHI3L1 CpG sites mediate the association of CHI3L1 single nucleotide polymorphisms (SNPs) with YKL-40 levels in the blood and (2) whether these biomarkers ( CHI3L1 SNPs, methylation profiles, and YKL-40 levels) are associated with asthma in early childhood. Methods We used data from up to 2405 participants from the Spanish Infancia y Medio Ambiente; the Swedish Barn/Children, Allergy, Milieu, Stockholm, Epidemiological survey; and the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohorts. Associations between 68 CHI3L1 SNPs, methylation levels at 14 CHI3L1 CpG sites in whole-blood DNA, and circulating YKL-40 levels at 4 years of age were tested by using correlation analysis, multivariable regression, and mediation analysis. Each of these biomarkers was also tested for association with asthma at 4 years of age by using multivariable logistic regression. Results YKL-40 levels were significantly associated with 7 SNPs and with methylation at 5 CpG sites. Consistent associations between these 7 SNPs (particularly rs10399931 and rs4950928) and 5 CpG sites were observed. Alleles linked to lower YKL-40 levels were associated with higher methylation levels. Participants with high YKL-40 levels (defined as the highest YKL-40 tertile) had increased odds for asthma compared with subjects with low YKL-40 levels (meta-analyzed adjusted odds ratio, 1.90 [95% CI, 1.08-3.36]). In contrast, neither SNPs nor methylation levels at CpG sites in CHI3L1 were associated with asthma. Conclusions The effects of CHI3L1 genetic variation on circulating YKL-40 levels are partly mediated by methylation profiles. In our study YKL-40 levels, but not CHI3L1 SNPs or methylation levels, were associated with childhood asthma.
TL;DR: Being born large for gestational age is a marker of increased growth velocity in fetal life and a risk factor for childhood overweight and the role of overweight in the association between LGA and childhood asthma is unclear.
Abstract: BACKGROUND: Being born large for gestational age (LGA) is a marker of increased growth velocity in fetal life and a risk factor for childhood overweight. Both being born LGA and childhood overweight may influence the development of asthma, although the role of overweight in the association between LGA and childhood asthma is unclear. Importantly, recent studies have suggested that the association between overweight and asthma may be related to non-allergic pathways. If this also applies to the association between LGA and asthma, the association between being born LGA and asthma may be different for atopic and non-atopic children. OBJECTIVE: We investigated the association of being LGA with the prevalence of asthma at age 8 in atopic and non-atopic children and the role of overweight in this association. METHODS: Complete data on asthma, anthropometry and atopy at age of 8 years, and potential confounders were available for 1608 participants of the PIAMA birth cohort. Odds ratios for the association between LGA and asthma in atopic and non-atopic children were estimated by logistic regression analysis adjusting for potential confounders. Overweight was assessed as a potential modifier of the association between LGA and asthma. RESULTS: Being born LGA was not significantly associated with asthma at age of 8 in atopic and non-atopic children. However, overweight at age of 8 years modified the association between asthma at age of 8 and LGA. In non-atopic children, children who were born LGA and were overweight at age of 8 years had a significantly increased odds of asthma compared to non-LGA, non-overweight children (adj OR 7.04; 95% CI 2.2-24). CONCLUSIONS: We observed that non-atopic children born LGA, who were overweight by 8 years have an increased risk of asthma. If confirmed, these findings suggest that non-atopic children born LGA may be identified early in life as a high-risk group for asthma.
TL;DR: EASI shows that the relationships between E, A, S and I vary markedly within individuals (through life) and between individuals (at the same age) and helps to delineate some potentially relevant, but often overlooked concepts, such as disease progression, susceptibility to COPD and issues related to symptom perception.
Abstract: The natural history of chronic obstructive pulmonary disease (COPD) is still not well understood. Traditionally believed to be a self-inflicted disease by smoking, now we know that not all smokers develop COPD, that other inhaled pollutants different from cigarette smoke can also cause it, and that abnormal lung development can also lead to COPD in adulthood. Likewise, the inflammatory response that characterizes COPD varies significantly between patients, and not all of them perceive symptoms (mostly breathlessness) similarly. To investigate the variability and determinants of different "individual natural histories" of COPD, we developed a theoretical, multi-stage, computational model of COPD (EASI) that integrates dynamically and represents graphically the relationships between exposure (E) to inhaled particles and gases (smoking), the biological activity (inflammatory response) of the disease (A), the severity (S) of airflow limitation (FEV1) and the impact (I) of the disease (breathlessness) in different clinical scenarios. EASI shows that the relationships between E, A, S and I vary markedly within individuals (through life) and between individuals (at the same age). It also helps to delineate some potentially relevant, but often overlooked concepts, such as disease progression, susceptibility to COPD and issues related to symptom perception. In conclusion, EASI is an initial conceptual model to interpret the longitudinal and cross-sectional relationships between E, A, S and I in different clinical scenarios. Currently, it does not have any direct clinical application, thus it requires experimental validation and further mathematical development. However, it has the potential to open novel research and teaching alternatives.
TL;DR: Clinical and population studies, as well as those on genotypic associations or mechanisms, should consider the multimorbid polysensitized phenotype of allergic diseases to improve interpretation of the results and better understand allergic diseases.
Abstract: To the Editor: We read with great interest 3 consecutive articles recently published in the Journal. Allergic diseases are complex and represent multiple phenotypes that have not been well characterized until recently. Mechanisms of the Development of Allergy (MeDALL) has pooled 14 European birth cohorts with omics and IgE measurements using a refined microarray technique. An important message from MeDALL was the identification of the multimorbid polysensitized phenotype of allergic diseases. Although polysensitization and multimorbidity were known, they had never been associated in a single phenotype. In MeDALL, using hypothesis and data-driven methods, this novel phenotype was shown to be associated with some important features of allergic diseases including longitudinal trajectories with a low probability of remission of IgE sensitization and clinical allergy, elevated levels of total and specific IgE, high levels of blood eosinophils, and a high rate of family history. However, the links between this phenotype and the severity of allergic diseases were not fully understood. The 3 recent studies published in the journal bring new knowledge to the understanding of severe asthma in a well-defined population. The studies were based on the same population and were analyzed using 3 different methodologies including a cluster analysis. Interestingly, they all found that rhinitis and polysensitization were associated with severe or uncontrolled asthma. In addition, the cluster approach showed that the severe asthma phenotype was associated with both severe rhinitis and polysensitization. As in MeDALL, it was found that phenotype characterization is complex and that more than a single phenotype is associated with severe disease in sensitized and nonsensitized individuals. We think that the authors have confirmed the previously described multimorbid polysensitized phenotype that is now associated with the severity of asthma and rhinitis or peanut allergy. The results of the short follow-up of the studies and those generated by MeDALL provide novel insight and generate hypotheses in the implication of this severe phenotype on the prediction of the severity of allergic disease. The additional impact of polysensitization in asthma and rhinitis multimorbidity suggests the importance to better characterize subjects with allergic diseases and sensitization to specific allergens both for clinical practice and for mechanistic studies. Clinical and population studies, as well as those on genotypic associations or mechanisms, should consider the multimorbid polysensitized phenotype to improve interpretation of the results and better understand allergic diseases. Jean Bousquet, MD Josep M. Anto, MD Jocelyne Just, MD Thomas Keil, MD Val erie Siroux, PhD Magnus Wickman, MD From MACVIA-France, Contre les MAladies Chroniques pour un VIeillissement Actif en France, European Innovation Partnership on Active and Healthy Ageing Reference Site, Montpellier, France; ISGLoBAL, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; the Allergology Department, Centre de l’Asthme et des Allergies, Hôpital d’Enfants Armand-Trousseau (APHP), Paris, France; the Institute of Social Medicine, Epidemiology and Health Economics, Charit e Universit€atsmedizin Berlin, Berlin, Germany; INSERM, Universit e Grenoble Alpes, Montpellier, France; and Sachs’ Children and Youth Hospital, S€odersjukhuset, Stockholm, Sweden. E-mail: jean.bousquet@orange.fr. Disclosure of potential conflict of interest: J. Bousquet reports personal fees from Almirall, Meda, Merck, MSD, Novartis, Sanofi-Aventis, Takeda, Teva, and Uriach. J. Just reports grants and personal fees from Novartis, ALK Abello, Stallergenes-Green, Astra Zeneca, and Thermofischer. T. Keil reports personal fees from the European Union for FP7-project MeDALL. V. Siroux reports personal fees from TEVA, AstraZeneca, and Novartis. The rest of the authors declare that they have no relevant conflicts of interest.
TL;DR: The strength of the association between PA quantity and mortality is comparable across GOLD stages and across intensity levels.
Abstract: Rationale: Physical activity (PA) has been associated with mortality in patients with COPD. We aimed to investigate 1) this association across the disease severity and 2) whether the previously reported protective effect of PA is due to its quantity and/or intensity. Methods: We pooled data about PA (Sensewear armband), clincial characteristics and mortality from patients with COPD tested in Belgium (n=179), Spain (n= 173), Germany (n=168), United Kingdom (n=101) and Brazil (n=137) for these analyses. The quantity (daily step count) and intensity (mean METs during periods of at least 1.5 METs) of PA were included as exposures. Analyses (Cox proportional hazard regression) were adjusted for age, gender, severity of airflow limitation and BMI. Results: 758 patients (74% male, 67±8 years, FEV 1 56±22 % pred , BMI 27±5 kg.m −2 , 5881±4007 steps/day, mean PA intensity 3.18±0.52 METs) were included and 149 (20%) died during the 4-year follow up. Being more active was related to lower mortality risk (Hazard ratio, 95%CI 0.85 [0.79 to 0.91] per 1000 steps more, p<0.001). The association between PA quantity and mortality was similar across GOLD stages (interaction effect p=0.39, Figure 1A) and across intensity levels (interaction effect p=0.67, Figure 1B).
Conclusion: The strength of the association between PA quantity and mortality is comparable across GOLD stages and across intensity levels.