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Wise SK, Lin SY, Toskala E, 2018, International consensus statement on allergy and rhinology: allergic rhinitis-executive summary, INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY, Vol: 8, Pages: 85-107, ISSN: 2042-6976
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- Citations: 187
Belgrave D, Cassidy R, Custovic A, et al., 2018, Predictive Modelling Strategies to Understand Heterogeneous Manifestations of Asthma in Early Life, 16th IEEE International Conference on Machine Learning and Applications (ICMLA), Publisher: IEEE, Pages: 68-75
Wheezing is common among children and ~50% of those under 6 years of age are thought to experience at least one episode of wheeze. However, due to the heterogeneity of symptoms there are difficulties in treating and diagnosing these children. `Phenotype specific therapy' is one possible avenue of treatment, whereby we use significant pathology and physiology to identify and treat pre-schoolers with wheeze. By performing feature selection algorithms and predictive modelling techniques, this study will attempt to determine if it is possible to robustly distinguish patient diagnostic categories among pre-school children. Univariate feature analysis identified more objective variables and recursive feature elimination a larger number of subjective variables as important in distinguishing between patient categories. Predicative modelling saw a drop in performance when subjective variables were removed from analysis, indicating that these variables are important in distinguishing wheeze classes. We achieved 90%+ performance in AUC, sensitivity, specificity, and accuracy, and 80%+ in kappa statistic, in distinguishing ill from healthy patients. Developed in a synergistic statistical - machine learning approach, our methodologies propose also a novel ROC Cross Evaluation method for model post-processing and evaluation. Our predictive modelling's stability was assessed in computationally intensive Monte Carlo simulations.
Demenais F, Margaritte-Jeannin P, Barnes KC, et al., 2017, Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks, Nature Genetics, Vol: 50, Pages: 42-53, ISSN: 1061-4036
We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.
Tang HHF, Teo SM, Belgrave DCM, et al., 2017, Non-parametric mixture models identify trajectories of childhood immune development relevant to asthma and allergy, Publisher: bioRxiv
Events in early life contribute to subsequent risk of asthma; however, the causes and trajectories of childhood wheeze are heterogeneous and do not always result in asthma. Similarly, not all atopic individuals develop wheeze, and vice versa. The reasons for these differences are unclear. Using unsupervised model-based cluster analysis, we identified latent clusters within a prospective birth cohort with deep immunological and respiratory phenotyping. We characterised each cluster in terms of immunological profile and disease risk, and replicated our results in external cohorts from the UK and USA. We discovered three distinct trajectories, one of which is a high-risk "atopic" cluster with increased propensity for allergic diseases throughout childhood. Atopy contributes varyingly to later wheeze depending on cluster membership. Our findings demonstrate the utility of unsupervised analysis in elucidating heterogeneity in asthma pathogenesis and provide a foundation for improving management and prevention of childhood asthma.
Wickman M, Lupinek C, Andersson N, et al., 2017, Detection of IgE Reactivity to a Handful of Allergen Molecules in Early Childhood Predicts Respiratory Allergy in Adolescence., EBioMedicine, Vol: 26, Pages: 91-99, ISSN: 2352-3964
BACKGROUND: Sensitization in early childhood may precede respiratory allergy in adolescence. METHODS: IgE reactivity against 132 allergen molecules was evaluated using the MeDALL microarray in sera obtained from a random sample of 786 children at the age of 4, 8 and 16years in a population based birth cohort (BAMSE). Symptoms were analyzed by questionnaire at ages 4, 8 and 16years. Clinically and independent relevant allergen molecules accounting for ≥90% of IgE reactivities in sensitized individuals and at all time-points were identified as risk molecules and used to predict respiratory allergy. The data was replicated in the Manchester Asthma and Allergy Study (MAAS) birth cohort by studying IgE reactivity with the use of a commercial IgE microarray. Sera were obtained from children at the ages of 3, 5, 8 and 11years (N=248) and the outcome was studied at 11years. FINDINGS: In the BAMSE cohort 4 risk molecules could be identified, i.e.: Ara h 1 (peanut), Bet v 1 (birch), Fel d 1 (cat), Phl p 1 (grass). For MAAS the corresponding number of molecules was 5: Der p 1 (dust mite), Der f 2 (dust mite), Phl p 1 (grass), Phl p 5 (grass), Fel d 1 (cat). In BAMSE, early IgE reactivity to ≥3 of 4 allergen molecules at four years predicted incident and persistent asthma and/or rhinitis at 16years (87% and 95%, respectively). The corresponding proportions in the MAAS cohort at 16years were 100% and 100%, respectively, for IgE reactivity to ≥3 of 5 risk molecules. INTERPRETATIONS: IgE reactivity to a few allergen molecules early in life identifies children with a high risk of asthma and/or rhinitis at 16years. These findings will be of importance for developing preventive strategies for asthma and rhinitis in children.
Custovic A, Ihuoma H, Belgrave DC, et al., 2017, Cat ownership, cat allergen exposure, and trajectories of sensitization and asthma throughout childhood, Journal of Allergy and Clinical Immunology, Vol: 141, Pages: 820-822.e7, ISSN: 0091-6749
Bousquet J, Onorato GL, Bachert C, et al., 2017, CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: a SUNFRAIL report, Clinical and Translational Allergy, Vol: 7, ISSN: 2045-7022
A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIASentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a GoodPractice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real lifedata in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and PromotingHealthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of GoodPractices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in communitydwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items ofJA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from12 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.
Deliu M, Yavuz TS, Sperrin M, et al., 2017, Features of asthma which provide meaningful insights for understanding the disease heterogeneity., Clinical and Experimental Allergy, Vol: 48, Pages: 39-47, ISSN: 0954-7894
BACKGROUND: Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. OBJECTIVE: To develop a framework for the discovery of stable and clinically meaningful asthma subtypes. METHODS: We performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process. RESULTS: Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as: "Difficult asthma" (n = 132); "Early-onset mild atopic" (n = 210); "Early-onset mild non-atopic: (n = 153); "Late-onset" (n = 105); and "Exacerbation-prone asthma" (n = 13). Multinomial regression demonstrated that lung function was significantly diminished among children with "Difficult asthma"; blood eosinophilia was a significant feature of "Difficult," "Early-onset mild atopic," and "Late-onset asthma." Children with moderate-to-severe asthma were present in each cluster. CONCLUSIONS AND CLINICAL RELEVANCE: An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key de
Pavord ID, Beasley R, Agusti A, et al., 2017, After asthma: redefining airways diseases., Lancet, Vol: 391, Pages: 350-400, ISSN: 0140-6736
Hellings PW, Fokkens WJ, Bachert C, et al., 2017, Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis - A EUFOREA-ARIA-EPOS-AIRWAYS ICP statement, Allergy, Vol: 72, Pages: 1297-1305, ISSN: 0105-4538
Precision medicine (PM) is increasingly recognized as the way forward for optimizing patient care. Introduced in the field of oncology, it is now considered of major interest in other medical domains like allergy and chronic airway diseases, which face an urgent need to improve the level of disease control, enhance patient satisfaction and increase effectiveness of preventive interventions. The combination of personalized care, prediction of treatment success, prevention of disease and patient participation in the elaboration of the treatment plan is expected to substantially improve the therapeutic approach for individuals suffering from chronic disabling conditions. Given the emerging data on the impact of patient stratification on treatment outcomes, European and American regulatory bodies support the principles of PM and its potential advantage over current treatment strategies. The aim of the current document was to propose a consensus on the position and gradual implementation of the principles of PM within existing adult treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS). At the time of diagnosis, prediction of success of the initiated treatment and patient participation in the decision of the treatment plan can be implemented. The second‐level approach ideally involves strategies to prevent progression of disease, in addition to prediction of success of therapy, and patient participation in the long‐term therapeutic strategy. Endotype‐driven treatment is part of a personalized approach and should be positioned at the tertiary level of care, given the efforts needed for its implementation and the high cost of molecular diagnosis and biological treatment.
Bousquet J, Agache I, Aliberti MR, et al., 2017, Transfer of innovation on allergic rhinitis and asthma multimorbidity in the elderly (MACVIA-ARIA) - Reference Site Twinning (EIP on AHA), Allergy, Vol: 73, Pages: 77-92, ISSN: 0105-4538
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 while ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study is 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 understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will: (i) assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) study phenotypic characteristics and treatment over a period of one year of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) 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. This article is protected by copyright. All rights reserved.
Murray C, Foden P, Lowe L, et al., 2017, Diagnosis of asthma in symptomatic children based on measures of lung function: an analysis of data from a population-based birth cohort study., Lancet Child & Adolescent Health, Vol: 1, Pages: 114-123, ISSN: 2352-4642
BACKGROUND: Concerns have been expressed about asthma overdiagnosis. The UK National Institute of Health and Care Excellence (NICE) proposed a new diagnostic algorithm applying four lung function measures sequentially (ratio of forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] <70%, bronchodilator reversibility ≥12%, fractional exhaled nitric oxide [FeNO] ≥35 parts per billion, and peak expiratory flow variability >20%). We aimed to assess the diagnostic value of three of the tests individually, and then test the proposed algorithm in symptomatic children. METHODS: We used follow-up data at age 13-16 years from the Manchester Asthma and Allergy Study, a prospective, population-based, birth cohort study. We initially present results for the whole population, then by subgroup of disease. To simulate the situation in primary care, we included participants reporting symptoms of wheeze, cough, or breathlessness in the previous 12 months and who were not on regular inhaled corticosteroids. We used an epidemiological definition of current asthma, defined as all three of physician-diagnosed asthma, current wheeze, and current use of asthma treatment, reported by parents in a validated questionnaire. We assigned children with negative answers to all three questions as non-asthmatic controls. We also measured spirometry, bronchodilator reversibility, and FeNO at follow-up; data for peak expiratory flow variability were not available. We calculated the proportion of participants with a current positive lung function test at each step of the algorithm, and recorded the number of participants that met our definition of asthma. FINDINGS: Of 1184 children born into the cohort, 772 attended follow-up at age 13-16 years between July 22, 2011, and Nov 11, 2014. Among 630 children who completed spirometry, FEV1:FVC was less than 70% in ten (2%) children, of whom only two (20%) had current asthma. Bronchodilator reversibility was positive in 54 (9%) of 6
Custovic A, 2017, Allergic Rhinitis, 16 International Congress of Pediatric Pulmonology, Publisher: WILEY, Pages: S38-S39, ISSN: 8755-6863
Allergic rhinitis is one of the most common chronic diseases in childhood. The International Study of Asthma and Allergies in Childhood reported an average prevalence rhinitis of 8.5% among 6-7-year-old children, and 14.6% for 13-14 year-old children1. The burden of allergic rhinitis to individual patients and the society is often underestimated, and there is a general lack of data on the risk factors and phenotypes of rhinitis in childhood and adolescence2.
Custovic A, Turner P, 2017, Food Allergy, 16 International Congress of Pediatric Pulmonology, Publisher: WILEY, Pages: S19-S20, ISSN: 8755-6863
Around 4,500 hospital admissions in the UK per annum are attributed to food allergy, of which one third are due to severe, anaphylactic reactions. Peanut is one of the most potent allergenic foods, causing IgE-mediated reactions in at least 2% of UK school-age children1. In young children, the most common food allergy is that to cow's milk, affecting up to 1 in 30 infants2.Allergic reactions to foods are unpredictable, and accidental exposures can result in severe allergic reactions, and in rare instances fatal reactions. Due to the potential for life-threatening allergic reactions (anaphylaxis) and the restrictions needed to mitigate this risk, food allergy has a major impact on the quality of life, since for both patients and their families the pressures of avoidance of implicated foods and the fear of a reaction due to accidental exposure significantly impair the quality of life.
Belgrave DCM, Granell R, Simpson A, et al., 2017, Latent profile analysis to identify heterogeneous subgroups of lung function for personalised and targeted early intervention, International Conference of the American-Thoracic-Society (ATS), Publisher: American Thoracic Society, ISSN: 1073-449X
Gold DR, Adamkiewicz G, Arshad SH, et al., 2017, NIAID, NIEHS, NHLBI, and MCAN Workshop Report: The indoor environment and childhood asthma-implications for home environmental intervention in asthma prevention and management., Journal of Allergy and Clinical Immunology, Vol: 140, Pages: 933-949, ISSN: 1097-6825
Environmental exposures have been recognized as critical in the initiation and exacerbation of asthma, one of the most common chronic childhood diseases. The National Institute of Allergy and Infectious Diseases; National Institute of Environmental Health Sciences; National Heart, Lung, and Blood Institute; and Merck Childhood Asthma Network sponsored a joint workshop to discuss the current state of science with respect to the indoor environment and its effects on the development and morbidity of childhood asthma. The workshop included US and international experts with backgrounds in allergy/allergens, immunology, asthma, environmental health, environmental exposures and pollutants, epidemiology, public health, and bioinformatics. Workshop participants provided new insights into the biologic properties of indoor exposures, indoor exposure assessment, and exposure reduction techniques. This informed a primary focus of the workshop: to critically review trials and research relevant to the prevention or control of asthma through environmental intervention. The participants identified important limitations and gaps in scientific methodologies and knowledge and proposed and prioritized areas for future research. The group reviewed socioeconomic and structural challenges to changing environmental exposure and offered recommendations for creative study design to overcome these challenges in trials to improve asthma management. The recommendations of this workshop can serve as guidance for future research in the study of the indoor environment and on environmental interventions as they pertain to the prevention and management of asthma and airway allergies.
Bush A, Custovic A, 2017, Formula one: best is no formula, EUROPEAN RESPIRATORY JOURNAL, Vol: 49, ISSN: 0903-1936
Sanchez-Borges M, Fernandez-Caldas E, Thomas WR, et al., 2017, International consensus (ICON) on: clinical consequences of mite hypersensitivity, a global problem, World Allergy Organization Journal, Vol: 10, ISSN: 1939-4551
Since mite allergens are the most relevant inducers of allergic diseases worldwide, resulting in significant morbidity and increased burden on health services, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), formed by the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), the European Academy of Allergy and Clinical Immunology (EAACI), and the World Allergy Organization (WAO), has proposed to issue an International Consensus (ICON) on the clinical consequences of mite hypersensitivity. The objectives of this document are to highlight aspects of mite biology that are clinically relevant, to update the current knowledge on mite allergens, routes of sensitization, the genetics of IgE responses to mites, the epidemiologic aspects of mite hypersensitivity, the clinical pictures induced by mites, the diagnosis, specific immunotherapeutic approaches, and prevention.
Turner PJ, custovic A, Shamji MH, 2017, Basophils, high-affinity IgE receptors and CCL2 in human anaphylaxis, Journal of Allergy and Clinical Immunology, Vol: 140, Pages: 750-758.e15, ISSN: 1097-6825
Background: The role of basophils in anaphylaxis is unclear.Objective: Toinvestigatewhetherbasophils havean important rolein human anaphylaxis.Methods:In an emergency department study, we recruited 31 patientswith acute anaphylaxis,predominantly to hymenopteravenom. Wemeasuredexpression ofbasophilactivation markers(CD63, CD203c), the absolute number of circulating basophils, whole-bloodFcεRI, CPA3and HDCgene expression, and serum markers(CCL2, CCL5,CCL11, IL-3,TSLP)at threetime points(during the anaphylactic episode, and inconvalescent samples7and 30 days later). We recruited 134 hymenoptera-allergic and76healthy controlsfor comparison. Wetheninvestigated whether the changes observed during venom-related anaphylaxis also occur during allergic reactions to food in 22 peanut-allergic individuals undergoing double-blind placebo-controlled food challenge to peanut(DBPCFC).Results:The number of circulating basophils was significantly lower during anaphylaxis(median 3.5 cells/μl) than7and 30 days later(17.5 and 24.7 cells/μl, P<0.0001), and compared to venom-allergicand healthy controls (21and23.4 cells/μl,P<0.0001). FcεRIexpressionduring anaphylaxiswasalso significantly lower than in convalescent samples (P≤0.002) and venom-allergiccontrols(P<0.0001).CCL2 (but not other serum markers) wassignificantlyhigherduring anaphylaxis(median 658 pg/ml) than in convalescent samples (314and 311 pg/ml, 7 and 30days,P<0.001). Peanut-induced allergic reactions resulted in a significant decrease in circulating basophilscompared to pre-challenge samples(P=0.016), a decrease in FcεRI expression (P=0.007), and anincrease inCCL2(P=0.003).Conclusions: Our findings implyan important and specific role forbasophils in the pathophysiology of human anaphylaxis.
Murray CS, Foden P, Sumner H, et al., 2017, Preventing Severe Asthma Exacerbations in Children: A Randomised Trial of Mite Impermeable Bedcovers., American Journal of Respiratory and Critical Care Medicine, Vol: 196, Pages: 150-158, ISSN: 1535-4970
RATIONALE: Allergen exposure in sensitised asthmatics interacts with viruses in increasing the risk of asthma exacerbation. OBJECTIVES: To evaluate the use of house dust mite impermeable bedding on severe asthma exacerbations in children. METHODS: We randomized mite-sensitised asthmatic children (3-17 years), following an emergency hospital attendance with an asthma exacerbation, to receive mite-impermeable (Active) or control (Placebo) bed encasings. MEASUREMENTS AND MAIN RESULTS: Over a 12-month intervention period the occurrence of severe asthma exacerbations were investigated. Of 434 asthmatic children who consented, 286 (mean age 7.7 years, 65.8% male) were mite sensitised and 284 were randomised (146 Active; 138 Placebo). At 12 months, significantly fewer children in the Active group had attended hospital with an exacerbation compared to the Placebo group (36/123 [29.3%] versus 49/118 [41.5%], p=0.047). In the multivariable analysis, the risk of emergency hospital attendance was 45% lower in the Active group (Hazard Ratio 0.55[95%CI, 0.36-0.85], p=0.006) compared with the Placebo group. The annual rate of emergency hospital attendance with exacerbations was 27% lower in the Active compared with the Placebo group, but this did not reach significance (Estimated marginal mean [95% CI]: Active 0.38[0.26-0.56] vs Placebo 0.52[0.35-0.76], p=0.18). No difference between the groups in the risk of prednisolone use for exacerbation was found (Hazard Ratio 0.82[0.58-1.17], p=0.28). CONCLUSIONS: Mite-impermeable encasings are effective in reducing the number of mite sensitised asthmatic children attending hospital with asthma exacerbations, but not the number requiring oral prednisolone. This simple measure may reduce the health care burden of asthma exacerbations in children.
Bousquet J, Farrell J, Crooks G, et al., 2017, Erratum to: Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5), CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 7, ISSN: 2045-7022
Kreiner E, Waage J, Standl M, et al., 2017, Shared genetic variants suggest common pathways in allergy and autoimmune diseases., Journal of Allergy and Clinical Immunology, Vol: 140, Pages: 771-781, ISSN: 1097-6825
BACKGROUND: The relationship between allergy and autoimmune disorders is complex and poorly understood. OBJECTIVE: We sought to investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. METHODS: We meta-analyzed 2 genome-wide association studies on self-reported allergy and sensitization comprising a total of 62,330 subjects. These results were used to calculate enrichment for single nucleotide polymorphisms (SNPs) previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites and characterized commonalities in variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DNase-hypersensitive site data. Finally, we compared the allergy data with those of all known diseases. RESULTS: Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (P = 1.4e-17) encompassing 29 loci at a false discovery rate of less than 0.05. Such enrichment seemed to be a general characteristic for autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in patients with autoimmune diseases but not those with other diseases. CONCLUSION: We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared disease mechanisms. Further studies of these shared genetic mechanisms might help in understanding the complex relationship between these diseases, including the parallel increase in disease prevalence.
Custovic A, 2017, Epidemiology of Allergic Diseases, Middleton's Allergy Essentials: First Edition, Pages: 51-72, ISBN: 9780323375795
The prevalence rates of asthma, IgE-mediated sensitization and allergic diseases vary throughout the world, and are highest in the English speaking nations and in the developed countries. There has been 2-3-fold increase in asthma prevalence in the latter part of the 20th century. More recent evidence suggests that the increase is asthma may have flattened off, and that in some age groups asthma rates may be decreasing in the areas of high prevalence. However, in many parts of the world asthma prevalence continues to increase, and the global differences may be getting smaller. The timeframe in which sharp increase in the prevalence of asthma and allergies has occurred is too short for the change to be attributable to genetic factors alone. The answer therefore must lie in the influences of environmental exposures and associated lifestyle, both of which have undergone rapid and profound changes. Numerous environmental changes have occurred in parallel, including changes in patterns of early-life microbial exposure, family size and childcare arrangements, diet and exercise, housing design, and environmental exposure to a number of pollutants. The increase in the prevalence of asthma and allergic diseases is likely a consequence of environmental factors increasing the risk in genetically susceptible individuals through gene-environment interactions. Thus, when identifying environmental protective and susceptibility factors which are amenable to intervention, genetic predisposition of the individual will have to be taken into account to enable the development of genotype-specific strategies for prevention. One of the challenges facing epidemiology in 21st century is how best to utilize vast amount of available data, how to integrate different scales of data and different levels of directness of measurement of variables of interest to inform the design of personalized prevention strategies and targeted treatments.
Bousquet J, Bewick M, Cano A, et al., 2017, Building bridges for innovation in ageing: Synergies between action groups of the EIP on AHA, Journal of Nutrition, Health and Aging, Vol: 21, Pages: 92-104, ISSN: 1279-7707
The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups’ new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
Bousquet J, Hellings PW, Agache I, et al., 2016, ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle, Clinical and Translational Allergy, Vol: 6, ISSN: 2045-7022
The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma and rhinitis and (3) to develop guidelines with all stakeholders that could be used globally for all countries and populations. ARIA—disseminated and implemented in over 70 countries globally—is now focusing on the implementation of emerging technologies for individualized and predictive medicine. MASK [MACVIA (Contre les Maladies Chroniques pour un Vieillissement Actif)-ARIA Sentinel NetworK] uses mobile technology to develop care pathways for the management of rhinitis and asthma by a multi-disciplinary group and by patients themselves. An app (Android and iOS) is available in 20 countries and 15 languages. It uses a visual analogue scale to assess symptom control and work productivity as well as a clinical decision support system. It is associated with an inter-operable tablet for physicians and other health care professionals. The scaling up strategy uses the recommendations of the European Innovation Partnership on Active and Healthy Ageing. The aim of the novel ARIA approach is to provide an active and healthy life to rhinitis sufferers, whatever their age, sex or socio-economic status, in order to reduce health and social inequalities incurred by the disease.
DeVries A, Wlasiuk G, Miller SJ, et al., 2016, Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers, Journal of Allergy and Clinical Immunology, Vol: 140, Pages: 534-542, ISSN: 1097-6825
BackgroundThe timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception.ObjectiveWe sought to assess whether the trajectory to asthma begins already at birth and whether epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception.MethodsWe used the Methylated CpG Island Recovery Assay chip to survey DNA methylation in cord blood mononuclear cells from 36 children (18 nonasthmatic and 18 asthmatic subjects by age 9 years) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n = 60) and in 2 replication cohorts (the Manchester Asthma and Allergy Study [n = 30] and the Childhood Origins of Asthma Study [n = 28]) was analyzed by using bisulfite sequencing or Illumina 450K arrays. Cord blood mononuclear cell–derived IL-1β levels were measured by means of ELISA.ResultsNeonatal immune cells harbored 589 differentially methylated regions that distinguished IIS children who did and did not have asthma by age 9 years. In all 3 cohorts methylation in SMAD3, the most connected node within the network of asthma-associated, differentially methylated regions, was selectively increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk. Moreover, SMAD3 methylation in IIS neonates with maternal asthma was strongly and positively associated with neonatal production of IL-1β, an innate inflammatory mediator.ConclusionsThe trajectory to childhood asthma begins at birth and involves epigenetic modifications in immunoregulatory and proinflammatory pathways. Maternal asthma influences epigenetic mechanisms that contribute to the inception of this trajectory.
Bousquet J, Bewick M, Cano A, et al., 2016, Erratum to: Building bridges for innovation in ageing: Synergies between action groups of the EIP on AHA, Journal of Nutrition, Health and Aging, Vol: 2016, Pages: 1-1, ISSN: 1279-7707
The authors would like to change and use the correct name of M. Khaitov which is M. Kaitov on this manuscript. The authors have incorrectly used her other name during the finalization of this research. With this, the authors hereby publish the correct author names as presented above.
Calderon MA, Demoly P, Casale T, et al., 2016, Allergy immunotherapy across the life cycle to promote active and healthy ageing: from research to policies, Clinical and Translational Allergy, Vol: 6, ISSN: 2045-7022
Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.
Belgrave D, Henderson J, Simpson A, et al., 2016, Disaggregating asthma: big Investigation vs. big data, Journal of Allergy and Clinical Immunology, Vol: 139, Pages: 400-407, ISSN: 1097-6825
We are facing a major challenge in bridging the gap between identifying subtypes of asthma, to understanding causal mechanisms, and translating this knowledge into personalized prevention and management strategies. In recent years, "big data" has been sold as a panacea for generating hypotheses and driving new frontiers of healthcare; the idea that the data must and will speak for themselves is fast becoming a new dogma. One of the dangers of ready accessibility of healthcare data and computational tools for data analysis is that the process of data mining may become uncoupled from the scientific process of clinical interpretation, understanding the provenance of the data and external validation. Although advances in computational methods can be valuable for using unexpected structure in data to generate hypotheses, there remains a need for testing hypotheses and interpreting results with scientific rigor. We argue for combining data-driven and hypothesis-driven methods in a careful synergy, and the importance of carefully characterized birth and patient cohorts with genetic, phenotypic, biological and molecular data in this process cannot be overemphasized. The main challenge on the road ahead is to harness 'bigger' healthcare data in ways that produce meaningful clinical interpretation and to translate this into better diagnoses and properly personalized prevention and treatment plans. There is a pressing need for cross-disciplinary research with an integrative approach to data science, whereby basic scientists, clinicians, data analysts and epidemiologists work together to understand the heterogeneity of asthma.
Deliu M, Belgrave D, Sperrin M, et al., 2016, Asthma phenotypes in childhood, Expert Review of Clinical Immunology, Vol: 13, Pages: 705-713, ISSN: 1744-8409
INTRODUCTION: Asthma is no longer thought of as a single disease, but rather a collection of varying symptoms expressing different disease patterns. One of the ongoing challenges is understanding the underlying pathophysiological mechanisms that may be responsible for the varying responses to treatment. Areas Covered: This review provides an overview of our current understanding of the asthma phenotype concept in childhood and describes key findings from both conventional and data-driven methods. Expert Commentary: With the vast amounts of data generated from cohorts, there is hope that we can elucidate distinct pathophysiological mechanisms, or endotypes. In return, this would lead to better patient stratification and disease management, thereby providing true personalised medicine.
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