Isabelle Momas

MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine

To cite this article: Bousquet J, Anto J, Auffray C, Akdis M, Cambon‐Thomsen A, Keil T, Haahtela T, Lambrecht BN, Postma DS, Sunyer J, Valenta R, Akdis CA, Annesi‐Maesano I, Arno A, Bachert C, Ballester F, Basagana X, Baumgartner U, Bindslev‐Jensen C, Brunekreef B, Carlsen KH, Chatzi L, Crameri R, Eveno E, Forastiere F, Garcia‐Aymerich J, Guerra S, Hammad H, Heinrich J, Hirsch D, Jacquemin B, Kauffmann F, Kerkhof M, Kogevinas M, Koppelman GH, Kowalski ML, Lau S, Lodrup‐Carlsen KC, Lopez‐Botet M, Lotvall J, Lupinek C, Maier D, Makela MJ, Martinez FD, Mestres J, Momas I, Nawijn MC, Neubauer A, Oddie S, Palkonen S, Pin I, Pison C, Rancé F, Reitamo S, Rial‐Sebbag E, Salapatas M, Siroux V, Smagghe D, Torrent M, Toskala E, van Cauwenberge P, van Oosterhout AJM, Varraso R, von Hertzen L, Wickman M, Wijmenga C, Worm M, Wright J, Zuberbier T. MeDALL (Mechanisms of the Development of ALLergy): an integrated approach from phenotypes to systems medicine. Allergy 2011; 66: 596–604.

Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research

BACKGROUND During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.

Risk factors and characteristics of respiratory and allergic phenotypes in early childhood

BACKGROUND Unsupervised approaches can be used to analyze complex respiratory and allergic disorders. OBJECTIVE We investigated the respiratory and allergic phenotypes of children followed in the Pollution and Asthma Risk: An Infant Study (PARIS) birth cohort. METHODS Information on respiratory and allergic disorders, medical visits, and medications was collected during medical examinations of children at 18 months of age; biomarker data were also collected (total and allergen-specific IgE levels and eosinophilia). Phenotypes were determined by using latent class analysis. Associated risk factors were determined based on answers to questionnaires about environmental exposures. RESULTS Apart from a reference group, which had a low prevalence of respiratory symptoms or allergies (n=1271 [69.4%]), 3 phenotypes were identified. On the basis of clinical signs of severity and use of health care resources, we identified a mild phenotype (n=306 [16.7%]) characterized by occasional mild wheeze and 2 severe phenotypes separated by atopic status. The atopic severe phenotype (n=59 [3.2%]) included 49 (83%) children with wheezing and was characterized by a high prevalence of atopy (61% with allergenic sensitization) and atopic dermatitis (78%). In contrast, atopy was rare among children with the nonatopic severe phenotype (n=195 [11%]); this group included 88% of the children with recurrent wheezing. Risk factors for respiratory disease included parental history of asthma, male sex, siblings, day care attendance, exposure to tobacco smoke or molds, indoor renovations, and being overweight, although these factors did not have similar affects on risk for all phenotypes. CONCLUSION Atopy should be taken into account when assessing the risk of severe exacerbations (that require hospital-based care) in wheezing infants; precautions should be taken against respiratory irritants and molds and to prevent children from becoming overweight.

An in vitro model to evaluate the inflammatory response after gaseous formaldehyde exposure of lung epithelial cells.

Asthma is a public health problem worldwide, and indoor air pollution considered to be a potential etiology. New tools need to be developed to study the effects of air pollutants in vitro and modelize inhalation exposure. This study was thus set up to design an in vitro model, using a direct exposure device to study the cellular effects of air pollutants at environmental doses on lung epithelial cells, and apply this to gaseous formaldehyde (FA). A549 cells were exposed using the direct exposure device (air/liquid interface) to FA without, after and before TNFalpha (1 ng/mL) sensitization. 24h after exposure, cellular viability (XTT) and inflammation (IL-6, IL-8 and MCP-1) were assessed. No effects on cellular viability were observed for concentrations < or =50 microg/m(3). After TNFalpha sensitization, FA-exposure induced a significant increase in IL-8 (p<0.001), which could lead to the initiation or pathogenesis of non-specific respiratory inflammation. The results of this study demonstrate the feasibility and sensitivity of the exposure system for testing inflammatory cellular effects of indoor gaseous compounds at environmental doses directly on human respiratory cells.

Effects of Air Pollution on Adults with Chronic Obstructive Pulmonary Disease

Abstract Few studies have been conducted on the effects of air pollution on patients with chronic obstructive pulmonary disease (COPD). During a 14-mo period, 39 Parisian adults with severe COPD were monitored by their physicians. Daily levels of 4 air pollutants were provided by an urban air-quality network. Exacerbation of COPD was associated only with ozone (O3) (odds ratio [OR] = 1.44 for a 10-μg/m3 increase in O3; 95% confidence interval [Cl] = 1.14, 1.82), with a lag of 2-3 days. The effect of O3 was greater in patients whose carbon dioxide pressure (PaCO2) was higher than 43 mm Hg (OR = 1.83; 95% Cl = 1.36, 2.47) vs. those with a lower PaCO2 (OR = 1.26; 95% Cl = 0.90, 1.77). The effect of O3 was unchanged, regardless of the maintenance medications used. The only air pollutant to which patients with severe COPD were particularly sensitive was O3.

Assessment of indoor environment in Paris child day care centers

BACKGROUND Children are sensitive to indoor environmental pollution. Up until now there has been a lack of data on air quality in child day care centers. OBJECTIVES The aim of this study is to document the indoor environment quality of Paris child day care centers by repeated measurements, and to compare pollutant levels in child day care centers with levels in Paris dwellings. METHODS We selected 28 child day care centers frequented by a random sample of babies who participated in the PARIS birth cohort environmental investigation, and visited the child day care centers for one week twice in one year. Biological contaminants assessed were fungi, endotoxin, dust mite allergens, and chemical pollutants: aldehydes, volatile organic compounds and nitrogen dioxide (NO2). Relative humidity, temperature, and carbon dioxide levels were measured simultaneously. A standardized questionnaire was used to gather information about the buildings and their inhabitants. RESULTS Airborne endotoxin levels in child day care centers were higher than those found in Paris dwellings. Dust mite allergens in child day care centers were below the threshold level for sensitization in the majority of samples, and in common with dwelling samples. Penicillium and Cladosporium were the most commonly identified genera fungi. The child day care center indoor/outdoor ratio for most chemical pollutants was above unity except for NO2, the levels for NO2 being significantly higher than those measured in homes. CONCLUSION Chemical and biological contamination in child day care centers appears to be low, apart from endotoxin and NO2. Failure to take child exposure in child day care centers into account could result in an overestimation of childrens exposure to other pollutants.

Relative importance of risk factors in bladder carcinogenesis: some new results about Mediterranean habits.

In the Mediterranean region of France where bladder cancer mortality and incidence are high, a case-control study with 219 male incident cases and 794 randomized, male population-controls was carried out in 1987–89 to investigate bladder cancer risk factors and more specifically, regional factors. A stepwise logistic regression was applied to the data. This investigation confirms the role of tobacco and of certain occupational exposures in bladder carcinogenesis. There was a significant dose-response relationship with lifelong coffee drinking and alcohol consumption; however the risk estimates were only significantly elevated for the heaviest drinkers. The intake of saccharin was not associated with risk of bladder cancer. Infrequent consumption of carrots, spinach, and marrows conferred an increased risk, suggesting a protective effect of vitamin A. Finally, this investigation results in some new hypotheses. The study of residences and birthplaces has revealed a lower risk for those who have lived in a non-Mediterranean area and a higher risk for those born in a Mediterranean area. These features might be explained by some Mediterranean dietary habits, such as a high consumption of spices (odds ratio =3.64, 95 percent confidence interval=2.21–5.98).

Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

MeDALL (Mechanisms of the Development of ALLergy; EU FP7‐CP‐IP; Project No: 261357; 2010–2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large‐scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy‐related diseases. To complement the population‐based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Contribution of indoor and outdoor environments to PM2.5 personal exposure of children—VESTA study

Several studies among adult populations showed that an array of outdoor and indoor sources of particles emissions contributed to personal exposures to atmospheric particles, with tobacco smoke playing a prominent role (J. Expo. Anal. Environ. Epidemiol. 6 (1996) 57, Environ. Int. 24 (1998) 405, Arch. Environ. Health 54 (1999) 95). The Vesta study was carried out to assess the role of exposure to traffic emissions in the development of childhood asthma. In this paper, we present data on 68 children aged 8-14 years, living in the metropolitan areas of Paris (n = 30), Grenoble (n = 15) and Toulouse (n = 23), France, who continuously carried, over 48 h, a rucksack that contained an active PM2.5 sampler. Data about home indoor sources were collected by questionnaires. In parallel, daily concentrations of PM10 in ambient air were monitored by local air quality networks. The contribution of indoor and outdoor factors to personal exposures was assessed using multiple linear regression models. Average personal exposure across all children was 23.7 microg/m3 (S.D. = 19.0 microg/m3), with local means ranging from 18.2 to 29.4 microg/m3. The final model explains 36% of the total between-subjects variance, with environmental tobacco smoke contributing for more than a third to this variability; presence of pets at home, proximity of the home to urban traffic emissions, and concomitant PM10 ambient air concentrations were the other main determinants of personal exposure.

Paving the way of systems biology and precision medicine in allergic diseases

MeDALL (Mechanisms of the Development of ALLergy; EU FP7‐CP‐IP; Project No: 261357; 2010–2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large‐scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy‐related diseases. To complement the population‐based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.