Unsupervised identification of cardiometabolic profiles among adolescents: findings from the PARIS birth cohort study.

Metabolic syndrome (MetS) is known as a risk factor in cardiometabolic morbidity but there is no consensus on its definition for teenagers. We aimed to identify cardiometabolic health profiles and which parameters best discriminate them. K-means partitioning identified cardiometabolic profiles by sex using data on health measurements of 530 adolescents from the PARIS birth cohort. A discriminant analysis was performed. Cardiometabolic risk score and handgrip strength were also measured. Depending on definitions, MetS prevalence ranged from 0.2% to 1.3%. Two profiles were identified for the entire group and by sex: "healthy" and "at cardiometabolic risk." Weight and waist-to-height ratio or waist circumference explained more than 87% of the variance in the profile differentiation. The "at cardiometabolic risk" profiles included adolescents with overweight, a waist-to-height ratio over 0.5, and prehypertension. They had higher cardiometabolic risk scores and parents who were more likely to be overweight and have cardiometabolic diseases themselves. They also had higher birthweights, earlier adiposity-rebound and puberty ages, and lower relative handgrip strength.  Conclusion: The two profiles identified, based on cardiometabolic health, were associated with early indicators and handgrip strength. Results suggest that the waist-to-height ratio is a useful clinical tool for screening individuals at cardiometabolic risk and who therefore require clinical follow-up. What is Known: • Although there is a need for tools to assess cardiometabolic health during adolescence, there is no consensus on the definition of metabolic syndrome for this age group. What is Knew: • The findings suggest that waist-to-height ratio can serve as a simple and valuable clinical tool for screening individuals at cardiometabolic risk who may require clinical monitoring for early prevention of cardiovascular diseases.

Innovative graph analysis method to assess gene expression modulation after fine particles exposures of 3D human airway epithelia.

Environmental particles have dramatic consequences for health, especially for the most vulnerable people, such as asthmatics. To better understand the impact on gene expression modulation of fine particles (PM2.5-0.3) from different emission sources, a 3D-airway model, a human bronchial epithelium (MucilAir-HF™) reconstructed from primary cells from healthy (EpiH) or asthmatic (EpiA) donors, was used. Repeated air-liquid exposures were performed, and epithelia were sacrificed to extract RNAs and assess gene expression. Data were analyzed according to the emission sources, physiological status, and exposure doses using a recent model consisting in a graph analysis on pairwise expression ratio. The results were compared with those from the classical ΔΔCt method. The graph analysis method proved to have better statistical properties than the classical ΔΔCt method and demonstrated that repeated PM2.5-0.3 exposures induced a dose-dependent up-regulation of the metabolic gene (CYP1B1) and a down-regulation of the inflammation gene (CXCL10). These modulations were greater for "industrial" than for "urban traffic" fine particles, and the effects were found to be greater after exposure of EpiA than EpiH, thus emphasizing the importance of the epithelium's physiological status in sensitivity to particles. Our study is original in terms of the experimental conditions and the graphical statistical analysis model established. The results highlight the importance of particle chemistry on the modulation of cellular and molecular responses, which may vary according to the individual's vulnerability.

Changes in air quality in-taxis and in working conditions of taxi drivers pre- and post-lockdown, during the COVID-19 pandemic in the Paris area.

We evaluated the impact of the lockdown restriction measures in the Paris area on the variation of in-vehicle ultrafine particle (UFP) and black carbon (BC) concentrations between the pre- and post-lockdown period and professional drivers' working conditions and practices. The study was conducted with 33 taxi drivers. UFP and BC were measured inside their vehicles with DiSCmini® and microAeth® , respectively, on two typical working days pre- and post-lockdown. Job characteristics were self-reported. Our results showed that post-lockdown, both the number of clients and journey duration significantly decreased. Taxi drivers opened their windows significantly more and reduced the use of air recirculation. UFP decreased significantly by 32% and BC by 31% post-lockdown, with a weaker positive correlation compared to pre-lockdown. The reduction of in-vehicle UFP was due mainly to the reduction of traffic flow and ventilation settings, though the latter probably varied according to traffic conditions. The variation of in-vehicle BC also tended to be related to the decrease in traffic flow post-lockdown. We emphasize the role of traffic emissions on in-vehicle air pollution and that preventive measures such ventilation settings would help to minimize the exposure of professional drivers and passengers to air pollutants.

Association between lung function of school age children and short-term exposure to air pollution and pollen: the PARIS cohort.

BACKGROUND: Daily levels of ambient air pollution and pollen may affect lung function but have rarely been studied together. We investigated short-term exposure to pollen and air pollution in relation to lung function in school-age children from a French population-based birth cohort. METHODS: This study included 1063 children from the PARIS (Pollution and Asthma Risk: an Infant Study) cohort whose lung function and FeNO measurements were performed at age 8 years old. Exposure data were collected up to 4 days before testing. We estimated daily total pollen concentration, daily allergenic risk indices for nine pollen taxa, as well as daily concentrations of three air pollutants (particulate matter less than 10 µm (PM10), nitrogen dioxide (NO2), ozone (O3)). Children with similar pollen and air pollution exposure were grouped using multidimensional longitudinal cluster analysis. Associations between clusters of pollen and air pollution exposure and respiratory indices (FEV1, FVC, FeNO) were studied using multivariable linear and logistic regression models adjusted for potential confounders. RESULTS: Four clusters of exposure were identified: no pollen and low air pollution (Cluster 1), grass pollen (Cluster 2), PM10 (Cluster 3) and birch/plane-tree pollen with high total pollen count (Cluster 4). Compared with children in Cluster 1, children in Cluster 2 had significantly lower FEV1 and FVC levels, and children from Cluster 3 had higher FeNO levels. For FEV1 and FVC, the associations appeared stronger in children with current asthma. Additional analysis suggested a joint effect of grass pollen and air pollution on lung function. CONCLUSION: Daily ambient chemical and biological air quality could adversely influence lung function in children.

Infant feeding clusters are associated with respiratory health and allergy at school age in the PARIS birth cohort.

BACKGROUND: As infant feeding may influence allergy development, we aimed to identify groups of infants based on feeding practices and to examine their associations with respiratory health/allergy at 8 years in the PARIS birth cohort. METHODS: Data on breastfeeding, consumption of infant formula (regular, pre-/probiotics, partially hydrolysed with hypoallergenic label [pHF-HA], extensively hydrolysed [eHF], soya) and solid food introduction were collected using repeated questionnaires at 1, 3, 6, 9 and 12 months. Infants with similar feeding practices over the first year of life were grouped using multidimensional longitudinal cluster analysis. Respiratory/allergic morbidity was studied at 8 years as symptoms, doctor's diagnoses (asthma, hay fever, eczema, food allergy), and measurement of lung function, FeNO and specific IgE. Associations between feeding-related clusters and respiratory/allergic morbidity were investigated using multivariable logistic and linear regression models adjusted for potential confounders including early respiratory/allergic outcomes and parental history of allergy. RESULTS: Five clusters were identified among 3446 infants: Cluster 1 (45%) mainly fed with regular formula, Cluster 2 (27%) exclusively breastfed during the first 3 months, and three other clusters consuming different types of formula (pre-/probiotics for Cluster 3 [17%], pHF-HA for Cluster 4 [7%], eHF/soya for Cluster 5 [4%]). Compared to Cluster 1, children from Cluster 2 tended to have a lower risk of asthma and children from Cluster 4 had a significant lower lung function (FEV1 , FVC), higher FeNO and higher risk of sensitization at 8 years. CONCLUSION: Early pHF-HA use was negatively associated with objective measures of respiratory/allergic morbidity at school age, while children breastfed for at least 3 months seem protected against asthma at 8 years old.

Mediterranean diet and lung function, sensitization, and asthma at school age: The PARIS cohort.

BACKGROUND: The Mediterranean diet (MD) has known health benefits, but its specific impact on allergy development is unclear. As part of the PARIS birth cohort follow-up, we aimed to investigate the adherence of 8-year-old children to the MD and its association with allergic/respiratory morbidity at school age. METHODS: Diet was assessed using a food frequency questionnaire completed by the parents. Adherence to the MD was assessed based on two scores: the KIDMED index and the Mediterranean Diet Score (MDS). Current allergic diseases (asthma, rhinitis, eczema), lung function indices (FEV1 and FVC), FeNO and specific IgE levels were determined during a health check-up at 8 years. Associations between levels of adherence to the MD and respiratory/allergic morbidity were studied using multivariable logistic and linear regression models adjusted for potential confounders. RESULTS: A total of 975 children were included in the present study, 35.6% with low adherence to the MD, 55.7% with moderate adherence and 8.7% with high adherence according to the KIDMED index. High family socioeconomic status, any breastfeeding at 6 months and consumption of organic food were associated with higher adherence to the MD. Compared with low adherence, high adherence was associated with lower risk of asthma and sensitization at 8 years, as well as higher FEV1 and FVC. CONCLUSION: This study suggests a protective effect of high adherence to the MD on allergic and respiratory morbidity at school age. These results need to be confirmed by further longitudinal analyses. A healthy diet may prevent allergic and respiratory morbidity in school-aged children.

Early postnatal exposure to traffic-related air pollution and asthma in adolescents: vulnerability factors in the PARIS birth cohort.

BACKGROUND: Associations between early traffic-related air pollution (TRAP) exposure and respiratory and allergic morbidity in adolescents are inconsistent. However, sub-groups might be more vulnerable to the health effects of this exposure. OBJECTIVES: We investigated associations between early exposure to TRAP and respiratory and allergic morbidity at age 13 years in the PARIS birth cohort, and potential modifying effects of sex, parental allergy, stressful family event and lower respiratory tract infections (LRTI). METHODS: This study deals with data from 732 children of the PARIS birth cohort followed up using repeated questionnaires until 13 years of age. Prenatal TRAP exposure was assessed by measuring daily concentrations of nitrogen dioxide at the nearest station to mother's home. Early postnatal TRAP exposure was calculated for each child during the first year of life by a nitrogen oxides (NOx) air dispersion model taking into account both residence and daycare. Associations between TRAP exposures and asthma, rhinitis and related symptoms were assessed using multivariable logistic regression models adjusted for potential confounding factors. Effect modification was explored by testing multiplicative interactions. RESULTS: An increase in interquartile range (17.0 µg/m3) of early postnatal NOx exposure was positively related to current asthma (adjusted odds ratio aOR = 1.21; 95% confidence interval CI: 1.02, 1.43), severe wheeze (aOR = 1.23; 95% CI: 1.02, 1.47) and persistent asthma at 13 years old (aOR = 1.26; 95% CI: 1.03, 1.55) and tended to be associated with asthma ever. Parental history of allergy, asthma, early stressful family event and LRTI modified these associations with TRAP exposure. No relationship with rhinitis was found. Prenatal TRAP exposure did not show any association with respiratory and allergic morbidity. DISCUSSION: This study is one of the first to show several modifiers of the association between early postnatal TRAP exposure and asthma at adolescence. Not all adolescents seem equally affected by early postnatal TRAP exposure: those presenting parental history of allergy, especially asthma, those with early stressful family event or LRTI appear to be more vulnerable.

Influence of the environmental relative humidity on the inflammatory response of skin model after exposure to various environmental pollutants.

The skin is an essential barrier, protecting the body against the environment and its numerous pollutants. Several environmental pollutants are known to affect the skin, inducing premature aging through mechanisms including oxidative stress, inflammation, and impairment of skin functions. Even climate conditions can impact the skin. Therefore, using a Reconstructed Human Epidermis (RHE), we tested the effect of two samples of fine particulate matters (PM0.3-2.5 - one metals-rich sample and the other organic compounds-rich), two Volatile Organic Compounds mixtures (VOCs - from a solvent-based paint and a water-based paint) and Tobacco Smoke (TS). All pollutants affected cellular functionality, but to a lesser extent for the water-based paint VOC. This effect was enhanced when RHE were preconditioned for 2 h by a semi-dry airflow (45% relative humidity) before pollutants application, compared to preconditioning by a humid airflow (90% relative humidity). In the absence of preconditioning, IL-1α, IL-6, IL-8, and RANTES were almost systematically induced by pollutants. When RHE were preconditioned by a semi-dry or humid airflow before being subjected to pollutants, the increase of IL-1α, IL-8, and RANTES falls into two groups. Similarly to RHE not treated with pollutants, RHE treated with VOCs after preconditioning by a semi-dry airflow showed increased IL-1α, IL-8, and RANTES release. On the contrary, RHE treated with PM or TS after preconditioning by a semi-dry airflow show a lower increase in IL-1α, IL-8, and RANTES compared to preconditioning by a humid airflow. The effect of real environmental relative humidity conditions of the air, combined with acute exposure to various environmental pollutants, seemed to relate mainly to structural changes of the skin, determining the outcome of the inflammatory response depending on the physicochemical characteristics of pollutants.

Determinants of ultrafine particles, black carbon, nitrogen dioxide, and carbon monoxide concentrations inside vehicles in the Paris area: PUF-TAXI study.

This study presents real-time concentrations of traffic-related air pollutants during 499 trips conducted by 50 Parisian taxi drivers from PUF-TAXI project. Ultrafine particles (UFP), black carbon (BC), and nitrogen dioxide (NO2 )/carbon monoxide (CO) were measured inside vehicles by Diffusion Size Classifier Miniature® , microAeth® , and Gas-Pro® , respectively, for nine hours. Vehicle/trip data characteristics were collected by questionnaires and on ambient conditions by monitoring stations. The associations between pollutant levels and their potential determinants were analyzed using generalized estimating equation model. Determinants of in-vehicle pollutants levels were identified: (1) ambient factors (meteorology and ambient pollution)-affecting BC, NO2, and CO; (2) vehicle characteristics-affecting all pollutants; and (3) trip-related driving habits-affecting UFP, BC, and CO. We highlight that commuters can, therefore, avoid high in-vehicle air pollutant concentrations mainly by (1) closing windows and activating air-conditioning under air recirculation mode in congested traffic; (2) smooth driving; and (3) maintaining cabin air filters.

Cross-sectional study of in-vehicle exposure to ultrafine particles and black carbon inside Lebanese taxicabs.

Taxi drivers' exposure to traffic-related air pollutants inside their vehicles has been reported in different countries but not yet in Lebanon. Thus, we conducted a cross-sectional study on 20 Lebanese taxi drivers to (1) assess their exposure to ultrafine particles (UFP) and black carbon (BC) inside their vehicles and (2) identify determinants of this exposure. UFP and BC were measured using Diffusion Size Classifier Miniature® and microAeth® Model AE51, respectively, for 5 hours. Data on characteristics of vehicles and trips were collected by face-to-face interviews. Associations between pollutant levels and their determinants were analyzed by multiple linear regression. The mean of UFP count (35.2 ± 17.6 x 103 particles cm-3 ) and BC (5.2 ± 1.9 µg m-3 ) concentrations in-taxis was higher in the morning measurements compared with those in the afternoon measurements. UFP count increased in-taxis by 60% for every 10 minutes spent in blocked traffic and by 84% starting from two trips with smokers compared to trips without smokers. Conversely, UFP count decreased by 30% for every 10 minutes under both air-conditioning and air recirculation mode with windows closed. BC was not affected by any of these factors. Our findings suggest easy ways to reduce UFP exposure inside vehicles for all commuters.

Integrating Clinical and Epidemiologic Data on Allergic Diseases Across Birth Cohorts: A Harmonization Study in the Mechanisms of the Development of Allergy Project.

The numbers of international collaborations among birth cohort studies designed to better understand asthma and allergies have increased in the last several years. However, differences in definitions and methods preclude direct pooling of original data on individual participants. As part of the Mechanisms of the Development of Allergy (MeDALL) Project, we harmonized data from 14 birth cohort studies (each with 3-20 follow-up periods) carried out in 9 European countries during 1990-1998 or 2003-2009. The harmonization process followed 6 steps: 1) organization of the harmonization panel; 2) identification of variables relevant to MeDALL objectives (candidate variables); 3) proposal of a definition for each candidate variable (reference definition); 4) assessment of the compatibility of each cohort variable with its reference definition (inferential equivalence) and classification of this inferential equivalence as complete, partial, or impossible; 5) convocation of a workshop to agree on the reference definitions and classifications of inferential equivalence; and 6) preparation and delivery of data through a knowledge management portal. We agreed on 137 reference definitions. The inferential equivalence of 3,551 cohort variables to their corresponding reference definitions was classified as complete, partial, and impossible for 70%, 15%, and 15% of the variables, respectively. A harmonized database was delivered to MeDALL investigators. In asthma and allergy birth cohorts, the harmonization of data for pooled analyses is feasible, and high inferential comparability may be achieved. The MeDALL harmonization approach can be used in other collaborative projects.

Unsupervised trajectories of respiratory/allergic symptoms throughout childhood in the PARIS cohort.

BACKGROUND: Natural course and co-occurrence of asthma, eczema, and allergic rhinitis through childhood are still not fully documented. We aim to identify and characterize profiles based on the time course, severity, and apparent triggers of respiratory/allergy symptoms in school-aged children. METHODS: Data on occurrence, severity, and triggers of asthma, rhinitis, and dermatitis symptoms were collected annually during the follow-up of the PARIS birth cohort. Children with similar symptom trajectories until 8-9 years were grouped into profiles using multidimensional (all symptoms considered simultaneously) cluster analysis. Associations between profiles and different health outcomes were analyzed using logistic or linear regression models. RESULTS: Six distinct symptomatic profiles were identified. A profile was defined by persistent dermatitis symptoms, associated with sensitization to food and aeroallergens. Two profiles were characterized by wheezing: one with early transient wheezing and the other with persistent wheezing related to doctor-diagnosed asthma, airway obstruction, and perennial aeroallergen sensitization. Three profiles were characterized by rhinitis symptoms: one non-allergic and two allergic, either with persistent rhinitis symptoms related to allergic multimorbidity and sensitization to perennial aeroallergens, or with late-onset symptoms, related to both pollen and perennial aeroallergens sensitization as well as low lung function. CONCLUSION: This study brings further insights into the developmental profiles of respiratory/allergic outcomes from birth to school age. The identified profiles clearly differed regarding objective features such as diagnosed morbidity, sensitization, or lung function measurements, thus highlighting their biologic and clinical relevance. Allergic rhinitis profiles deserve particular attention, since they were likely to be involved in multimorbidity patterns.

Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes.

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.

Early polysensitization is associated with allergic multimorbidity in PARIS birth cohort infants.

BACKGROUND: Profiles of allergic sensitization are poorly documented in infancy. Relations between early sensitization and allergic morbidity need to be clarified. METHODS: This study dealt with children involved in the Pollution and Asthma Risk: an Infant Study (PARIS), a population-based prospective birth cohort. Allergic sensitization to twelve food and four inhalant allergens was assessed at 18 months and defined by a specific immunoglobulin E (IgE) level ≥0.35 kUA /l. Health data were collected by standardized questionnaires at 2 and 6 years. Early allergic profiles were identified by an unsupervised cluster analysis based on health data at 2 years and IgE measurements. Profiles were compared with regard to allergic morbidity and multimorbidity at 6 years. RESULTS: Sensitization to any allergen concerned 13.6% of infants. By cluster analysis, 1525 infants were grouped into three profiles: 89.2% not or rarely sensitized (only 3.7% of sensitized), 9.2% mainly sensitized to one or few allergens (45.2% of monosensitized and 45.9% of paucisensitized) and 1.6% all polysensitized. The prevalence of doctor-diagnosed asthma, rhinitis, eczema, food allergy and multimorbidity at 2 years increased from profile one to profile three (p-trend <0.001). At 6 years, symptoms of current asthma, rhinitis, eczema and multimorbidity were significantly more frequent in the last two profiles. CONCLUSIONS: This study highlights, as early as 18 months of age, three profiles of increasing severity with regard to allergic sensitization and diseases. These profiles also differ in terms of allergic morbidity at 6 years. Early sensitization can predict allergic multimorbidity in childhood, and in the case of early polysensitization, multimorbidity is more frequent as soon as infancy.

Forced expiratory flows' contribution to lung function interpretation in schoolchildren.

Forced expiratory flow (FEF) at low lung volumes are supposed to be better at detecting lung-function impairment in asthmatic children than a forced volume. The aim of this study was to examine whether FEF results could modify the interpretation of baseline and post-bronchodilator spirometry in asthmatic schoolchildren in whom forced expiratory volumes are within the normal range. Spirometry, with post-bronchodilator vital capacity within 10% of that of baseline in healthy and asthmatic children, was recorded prospectively. We defined abnormal baseline values expressed as z-scores <-1.645, forced expiratory volume in 1 s (FEV1) reversibility as a baseline increase >12%, FEF reversibility as an increase larger than the 2.5th percentile of post-bronchodilator changes in healthy children. Among 66 healthy and 50 asthmatic schoolchildren, only two (1.7%) children with normal vital capacity and no airways obstruction had abnormal baseline forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%). After bronchodilation, among the 45 asthmatic children without FEV1 reversibility, 5 (11.1%) had an FEF25-75% increase that exceeded the reference interval. Isolated abnormal baseline values or significant post-bronchodilator changes in FEF are rare situations in asthmatic schoolchildren with good spirometry quality.

Systematic Review on the Definition of Allergic Diseases in Children: The MeDALL Study.

BACKGROUND: During the last decades, a large number of phenotypes and disease classifications of allergic diseases have been proposed. Despite the heterogeneity across studies, no systematic review has been conducted on phenotype classification and the criteria that define allergic diseases. We aimed to identify clinically expressed, population-based phenotypes of allergic diseases and their interrelationships, to explore disease heterogeneity and to evaluate the measurements employed in disease diagnosis. METHODS: We conducted a search of MEDLINE up to December 2012, to identify relevant original studies published in the English language that examine at least one objective of this systematic review in subjects aged 0-18 years. The screening of titles and abstracts and the extraction of data were conducted independently by two reviewers. RESULTS: From a total of 13,767 citations, 197 studies met the criteria for inclusion, with 54% being cohort studies. Allergic diseases were studied as a single entity in 55% (109/197) of the studies or in the context of multimorbidity in 45%. Asthma accounted for 81.7% of the studies examining single diseases. Overall, up to 33 different phenotypes of allergic disease were reported. Transient early, late-onset and persistent wheeze were the most frequently reported phenotypes. Most studies (78%) used questionnaires. The skin-prick test was the preferred measurement of sensitization (64%). Spirometry and bronchial hyperresponsiveness were assessed in one third of the studies, peak flow rate in 8.6% and disease severity in 35%. CONCLUSIONS: Studies reporting phenotypes of allergic diseases in children are highly heterogeneous and often lack objective phenotypical measures. A concerted effort to standardize methods and terminology is necessary.

Birth cohorts in asthma and allergic diseases: report of a NIAID/NHLBI/MeDALL joint workshop.

Population-based birth cohorts on asthma and allergies increasingly provide new insights into the development and natural history of the diseases. More than 130 birth cohorts focusing on asthma and allergy have been initiated in the last 30 years. A National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; Mechanisms of the Development of Allergy (MeDALL; Framework Programme 7 of the European Commission) joint workshop was held in Bethesda, Maryland, on September 11-12, 2012, with 3 objectives: (1) documenting the knowledge that asthma/allergy birth cohorts have provided, (2) identifying the knowledge gaps and inconsistencies, and (3) developing strategies for moving forward, including potential new study designs and the harmonization of existing asthma birth cohort data. The meeting was organized around the presentations of 5 distinct workgroups: (1) clinical phenotypes, (2) risk factors, (3) immune development of asthma and allergy, (4) pulmonary development, and (5) harmonization of existing birth cohorts. This article presents the workgroup reports and provides Web links (AsthmaBirthCohorts.niaid.nih.gov or www.medall-fp7.eu), where the reader will find tables describing the characteristics of the birth cohorts included in this report, the type of data collected at differing ages, and a selected bibliography provided by the participating birth cohorts.

Childhood allergic asthma is not a single phenotype.

OBJECTIVE: IgE-mediated allergic asthma phenotype appears to be heterogeneous. We set out to define distinct allergic phenotypes by unsupervised cluster analysis. STUDY DESIGN: A total of 18 variables were analyzed: sex and age, eczema and food allergy, asthma duration, asthma severity and control, severe exacerbations, total IgE level, allergic sensitization, fractional exhaled nitric oxide, and functional parameters. Clusters obtained were cross-tabulated with environmental parameters. RESULTS: Four clusters were identified in 125 children (average age 8.9 years): (1) 57 children constituted the "House dust mite Sensitization and Mild Asthma" cluster, 98% of these were monosensitized and had mild asthma (74%); (2) 12 children had "Pollen Sensitization with Severe Exacerbations," 92 % with severe exacerbations and pollen sensitization; (3) 20 children had "Multiple Allergies and Severe Asthma," with 95% having moderate to severe asthma, and a significantly decreased forced expiratory flow rate at 25%-75% of forced vital capacity, 100% had eczema and higher values of IgE (1123 kU/L) and fractional exhaled nitric oxide (67 ppb) (this cluster was associated with molds at home [P = .004]); and (4) 36 children had "Multiple Allergic Sensitizations and Mild Asthma," 97% of these with multiple sensitizations and 100% mild asthma. CONCLUSIONS: The identification of 2 novel severe allergic asthma phenotypes "Pollen Sensitization with Severe Exacerbations"and "Multiple Allergies and Severe Asthma" could lead to specific targeted treatment.

The development of the MeDALL Core Questionnaires for a harmonized follow-up assessment of eleven European birth cohorts on asthma and allergies.

BACKGROUND: Numerous birth cohorts have been initiated in the world over the past 30 years using heterogeneous methods to assess the incidence, course and risk factors of asthma and allergies. The aim of the present work is to provide the stepwise proceedings of the development and current version of the harmonized MeDALL-Core Questionnaire (MeDALL-CQ) used prospectively in 11 European birth cohorts. METHODS: The harmonization of questions was accomplished in 4 steps: (i) collection of variables from 14 birth cohorts, (ii) consensus on questionnaire items, (iii) translation and back-translation of the harmonized English MeDALL-CQ into 8 other languages and (iv) implementation of the harmonized follow-up. RESULTS: Three harmonized MeDALL-CQs (2 for parents of children aged 4-9 and 14-18, 1 for adolescents aged 14-18) were developed and used for a harmonized follow-up assessment of 11 European birth cohorts on asthma and allergies with over 13,000 children. CONCLUSIONS: The harmonized MeDALL follow-up produced more comparable data across different cohorts and countries in Europe and will offer the possibility to verify results of former cohort analyses. Thus, MeDALL can become the starting point to stringently plan, conduct and support future common asthma and allergy research initiatives in Europe.