The evidence of the effects of air pollution on cognitive function in adults is scare. Furthermore, most of the previous studies did not have individual measures of air pollution, using aggregated data, did not have a comprehensive set of confounding variables, did not have standardized cognitive tests but used registry-based diagnosis of disease, only contained one measurement of cognitive function, only included older adults and had small sample size. In summary, the study of the effects of air pollution on cognition still has many questions to answer and presents several methodological challenges, but we will overcome most of them in this project. Our project aims to evaluate the association between air pollution exposure and cognitive function in a large cohort of adults living all over France. Our overarching hypothesis is that air pollution, even at low levels of exposure, is a potential determinant for cognitive outcomes in adults. A secondary objective is to assess if exposure to heavy metals (HM) from air pollution, and which ones, are associated with cognitive outcomes in adults. Our project is based on the CONSTANCES cohort which is a large population-based cohort launched in late 2012, aiming to include 200,000 participants. The cohort is designed as a randomly selected sample of French adults aged 18-69 years at inception, living in different regions throughout France. At inclusion, the selected subjects are invited to fill a questionnaire and to attend a comprehensive health examination. The follow-up includes an annual questionnaire, a health examination every 5 years and the linkage to health national databases (“SNIIRAM” and the national mortality database). A large range of data is collected on social and demographic characteristics, socioeconomic status, life events, behaviours, and occupational factors; the health data cover a wide spectrum. A unique feature of CONSTANCES is the inclusion of a comprehensive set of cognitive tests exploring global cognitive performances, attention and executive functioning, verbal fluency, memory, and psychomotor speed starting as young as 45 years, earlier in life than most of the available population-based cohorts studying cognitive impairment or decline. Air pollution exposure will be assessed individually at the home address using three complementary maps of exposure. First, for classic pollutants, we will use a dispersion models that gives annual concentrations of PM10, PM2.5, NO2, SO2, C6H6 and O3 and a Europe-wide LUR model that gives annual concentrations of NO2, PM10 and PM2.5. Then we will assess exposure to atmospheric heavy metals using the data from the BRAMM network, a moss-biomonitoring database over France. Four trans-disciplinary partners are involved in the project, including researchers with a strong background in environmental epidemiology, in cohorts management, in cognition and in ecology and bio-monitoring. In conclusion, we will assess air pollution effects on cognitive function in a large cohort of adults in whom we performed cognitive tests from the age of 45, an earlier age than of the majority of other cohorts, allowing to identify accelerated decline in cognitive functions in early stages. Furthermore we will have three different fine scale models of air pollution exposure, all covering all the French territory, allowing for exposure assessment at individual level at the residential address. Two models will give exposure for classic pollutants and one very novel as it uses mosses that will allow assessing exposure to atmospheric HM. Our project will contribute to the knowledge of cognition impairment and its environmental determinants. Such knowledge can benefit public health and the society in general, by providing facts to policy makers to handle air pollution and trying to reduce population exposure to the air pollutants highlighted by our proposal.

Asthma is a common chronic respiratory disease, which can cause lifelong respiratory morbidity. It is widely accepted that asthma has origins early in life. Microbial and chemical exposures are two important risk factors for asthma in young children, but current knowledge remains insufficient to develop efficient prevention strategies. The recent development of high-throughput sequencing approaches to characterize both the environmental and the human microbiome has strengthened evidence for the role of microbial communities in asthma pathogenesis. This emerging field is seen as a major opportunity to provide new insight into the pathways linking early-life environment to disease development. However, major questions remain regarding (1) the exact role of specific airway microbiota profiles, and their evolution, in asthma development; (2) the impact of modifiable risk factors in the early-life environment on airway microbiota; and (3) whether airway microbiota mediates and/or modulates the environment-asthma association. The need for large, prospective studies with repeated assessment of airway microbiota in early life has been emphasized. Our proposal is centered on young children attending daycares, an environment where many of them spend a high amount of time, and which is thought to impact asthma risk. The central goal of the CRESMINA project is to study the relationships between daycare environment, nasal microbiota, and respiratory health in young children attending daycare centers, with 3 specific aims: (1) to determine the association of environmental exposures in daycare with baseline and longitudinal nasal microbiota profiles, for the following daycare-related exposures: number and characteristics of occupants, environmental microbiota (settled dust), indoor air chemical exposures and cleaning/disinfection practices; (2) to determine the association of baseline and longitudinal nasal microbiota profiles with respiratory health (primary outcome: longitudinal wheezing phenotypes from infancy to age 4 years); (3) to examine the mediating and/or modulating role of nasal microbiota in the association between environmental exposures in daycare and respiratory health. These questions will be examined in the CRESPI study (Respiratory health of Children in daycare), a cohort of 2000 children attending daycare in Paris region, which will be initiated in January 2019 in the context of an ANSES-funded project (CRESPINET), and will include detailed characterization of chemical exposures in daycare centers. The CRESMINA proposal builds on the subset of infants (age <1 year at baseline, n~800) enrolled in the CRESPI cohort. We plan to: characterize the children’s nasal microbiota based on two nasal swab collections, in infancy and at age 24 months; improve characterization of daycare environment by measuring environmental microbiota in settled dust; and improve characterization of respiratory health outcomes by extending follow-up until age 4 years. Composition of both nasal and environment microbiota will be characterized by 16S rRNA gene sequencing, using methods recommended by the NIH Human Microbiome Projects. Statistical analyses of Aims 1 to 3 will include characterization of baseline/longitudinal microbiota profiles and longitudinal wheezing profiles through clustering approaches, multinomial logistic regression models with adjustment for a large set of potential confounders, and use of recent methods (marginal structural models) for mediation analysis based on causal inference approaches. In summary, the CRESMINA project will identify specific nasal microbiota profiles differentially associated with early-life determinants of asthma and with poor respiratory outcomes; and disentangle their potential mediating / modulating roles. This knowledge could be key to the development of targeted strategies to modulate risk of developing asthma in children.

Since 2010, massive and repeated invasions of sargassum seaweed have taken place on coasts of Caribbean countries. Stranding of brown algae represents not only an environmental and economic disaster but also a real threat to human health due to the production of toxic gaseous and organic compounds that are not yet completely all identified. Among them acute toxicity of hydrogen sulfide H2S and ammonia NH3 is well-known. In contrast, there has been no comprehensive assessment regarding potential human health hazards associated with chronic exposure to H2S. This lack of knowledge is critical because residents of hitten coasts have repeated and prolonged exposure to low concentrations of potentially toxic gases. Our clinical study performed at CHU Martinique in 2018 found that the most frequent clinical signs of chronic exposure were conjunctival and upper airway irritation, difficult breathing or shortness of breath, skin rashes and headaches. As preliminary results pointed to the respiratory system, we propose to better characterize human health consequences of gaseous emanation produced by decomposing sargassum and their association with ambient H2S and NH3 levels. Lung consequences will be assessed via spirometry and body plethysmography testing. Biomarkers of lung inflammation and oxidative stress will be measured in the exhaled air and breath condensate. Signaling pathways involved in lung toxicity will be further characterized in a mouse model. Genotoxicity and effects of prenatal exposition in mice on lung development and postnatal lung dysfunction will also be studied. Lastly, we will investigate relationships between air quality perceptions, health concerns, and social consequences based on an anthropological approach via individual observations. ). Overall, our efforts will concentrate to characterize and eventually control noxious lung impacts of sargassum thread through integrated approaches using up-to-date technologies and clinical studies.