LCxSFC Valve Technologies: Guidelines toward a Successful Online Modulation.

Online two-dimensional liquid chromatography can be used under various separation modes but is sometimes limited in terms of orthogonality, especially for the analysis of neutral compounds. The use of SFC in the second dimension offers a wide choice of mobile and stationary phases, suggesting retention properties complementary to those of the first dimension. Initial works on online LCxSFC coupling published in the literature highlighted the first difficulties of solvent compatibility or potential problems with bubbles created by CO2 in loops. The present work highlights the impact of the interface between the LC and SFC dimensions on the performance of the 2D separation. Six different configurations have been evaluated, differing by the addition of a makeup flow in the first dimension, a division, or a separation of flow paths in the second dimension. Their performances with empty loops eliminated the need for complex trapping columns, regardless of the LC mobile phase nature. Injection in partial fill mode was possible without any problems of CO2 bubble formation, solvent miscibility, pressure, or modulation repeatability in each of the studied configurations. Selected configurations even allowed for the use of a mobile phase split upstream of the valve, so that the online LCxSFC configuration could be as flexible as LCxLC instrumentation in terms of the first dimension flow rate or second dimension injected volume. The obtained results allowed for building guidelines presenting the best interfaces to set up depending on the nature of the mobile phases in both dimensions. Two applications on monomers of lignin and industrial polymers confirmed preliminary results on configuration testing and illustrated that online LCxSFC could now be easily implemented. Precision tests on retention time were conclusive and are promising for the future use of this technique in industrial routines.

Chemical exposome and children health: Identification of dose-response relationships from meta-analyses and epidemiological studies.

BACKGROUND: Health impact assessment studies quantifying the impact of the chemical exposome on children's health generally consider a small fraction of the exposome. Synthetizing available dose-response relationships is an essential step to fill this gap. We reviewed the literature for dose-response relationships relating the chemical exposome with children health. METHOD: We focused on 78 substance-outcome pairs for which the level of evidence had previously been classified as 'likely' or 'very likely'. We searched for dose-response relationships for these pairs from meta-analyses and, if none was available, from single epidemiological studies, from which we conducted meta-analyses whenever possible. RESULTS: We identified dose-response relationships for 50 of the 78 prioritized substance-outcome pairs (64%). Dose-response relationships stemmed from meta-analyses for 21 pairs, from de novo meta-analyses for 1 pair and single studies for 28 pairs. Dose-response relationships were available for tobacco (fetal and infant death, congenital heart defects, birth outcomes, orofacial clefts, respiratory health), lead (asthma, cognition, delayed puberty onset and iron deficiency anaemia), polychlorobiphenyls (PCBs) (cognition, respiratory infections and birth outcomes), bisphenol A (cognition), hexachlorobenzene (HCB) (respiratory health), Polybrominated diphenyl ethers (neurodevelopment), DDT (hypospadias, cryptorchidism, miscarriage), pesticides (neurodevelopment), methylmercury (cognition), PFAS (immune system, birth weight, behavior, miscarriage), arsenic (cognition, birth weight, death, respiratory health), cadmium (cognition, birth weight), manganese (behavior), sodium (blood pressure) and thallium (birth weight). For 28 of the 78 substance-outcome pairs (36%), no dose-response relationship was available from epidemiological studies in children. CONCLUSIONS: We identified dose-response relationships for 50 substance-outcome pairs, corresponding to 20 chemicals and 17 health outcomes. These can be used to perform more comprehensive quantitative health impact assessment of the exposome on child health. We also identified 28 substance-outcome pairs corresponding to 'likely' or 'very likely' effects for which research generating dose-response functions in children would be relevant.

Structural elucidation of complex polyesters polyols from bio-lubricant using off-line liquid chromatography x supercritical fluid chromatography coupled with Orbitrap mass spectrometry.

Synthetic complex esters and polyol esters are incorporated as partially bio-based and biodegradable alternatives to petroleum base oils in lubricant formulations, to provide specific properties or performance and to help reducing their carbon footprint in certain cases. A sample can contain over 400 molecules of high chemical similarity including numerous isomers. To resolve such complexity, a separation technique with large peak capacity coupled to high-resolution mass spectrometry (HRMS) is essential. In this study, comprehensive off-line LCxSFC hyphenated with an Orbitrap analyzer was used for the structural elucidation of a synthetic bio-lubricant composed of a polyol reacted with fatty acids of varying length or with repetitive units of polyesters of ricinoleic acid. Retention in the LC first dimension was mostly due to the degree of oligomerization of ricinoleic acid within the polyester and to the chain length of the fatty acid. The SFC second dimension highlighted the esterification degree of the polyalcohol and the number and positions of fatty acids double bonds. The combination of both dimensions permitted the separation of isomers. The coupling of SFC with Orbitrap analyzer allowed an accurate assignment of molecular formulas. Finally, the fragmentation in the ionization source confirmed the attributed structures. By introducing a clear distribution of the chemical structures in the retention space, LCxSFC-HRMS provided a powerful analytical method for the comprehensive molecular characterization of the complex polyester polyols sample.

Personal exposure to particulate air pollution and vascular damage in peri-urban South India.

OBJECTIVE: Air pollution is a leading preventable risk factor for cardiovascular diseases. Previous studies mostly relied on concentrations at residence, which might not represent personal exposure. Personal air pollution exposure has a greater variability compared with levels of ambient air pollution, facilitating evaluation of exposure-response functions and vascular pathophysiology. We aimed to evaluate the association between predicted annual personal exposure to PM2.5 and black carbon (BC) and three vascular damage markers in peri-urban South India. METHODS: We analyzed the third wave of the APCAPS cohort (2010-2012), which recruited participants from 28 villages. We used predicted personal exposure to PM2.5 and BC derived from 610 participant-days of 24 h average gravimetric PM2.5 and BC measurements and predictors related to usual time-activity. Outcomes included carotid intima-media thickness (CIMT), carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx). We fit linear mixed models, adjusting for potential confounders and accounting for the clustered data structure. We evaluated nonlinear associations using generalized additive mixed models. RESULTS: Of the 3017 participants (mean age 38 years), 1453 (48%) were women. The average PM2.5 exposure was 51 µg/m3 (range 13-85) for men, and 61 µg/m3 (range 40-120) for women, while the average BC was 4 µg/m3 (range 3-7) for men and 8 µg/m3 (range 3-22) for women. A 10 µg/m3 increase of PM2.5 was positively associated with CIMT (0.026 mm, 95% CI 0.014, 0.037), cf-PWV (0.069 m/s, 95% CI 0.008, 0.131) and AIx (0.8%, 95% CI 0.3, 1.3) among men. The exposure-response function for PM2.5 and AIx among men showed non-linearity, particularly within the exposure range dominated by tobacco smoking and occupational exposures. Both PM2.5 and BC were positively associated with AIx among women (0.6%, 95% CI 0.2, 1.0, per 10 µg/m3 PM2.5; 0.5%, 95% CI 0.1, 0.8, per 2 µg/m3 BC). CONCLUSIONS: Personal exposure to particulate matter was associated with vascular damage in a peri-urban population in South India. Personal exposure to particulate matter appears to have gender-specific effects on the type of vascular damage, potentially reflecting differences in sources of personal exposure by gender.

Land-Use Change and Cardiometabolic Risk Factors in an Urbanizing Area of South India: A Population-Based Cohort Study.

BACKGROUND: Land-use changes in city fringes due to urbanization can lead to a reduction of greenspace that may reduce its associated health benefits. OBJECTIVES: We evaluated the association between changes in residential surrounding built-up land use and cardiometabolic risk factors in an urbanizing peri-urban area of south India and explored the mediating roles of air pollution, physical activity, and stress in these associations. METHODS: We analyzed data on 6,039 adults from the third follow-up of the Andhra Pradesh Children and Parent Study (APCAPS) cohort (2010-2012). We generated trajectories of change in residential surrounding built-up land use (buffer areas) from 1995-2009 (stable, slow increase, fast increase) using remote sensing data and image classification methods. We estimated associations between built-up land use trajectories and natural log-transformed blood pressure, waist circumference, triglycerides, fasting glucose, and non-high-density lipoprotein (non-HDL) cholesterol using linear mixed models. We accounted for multiple mediators and the multilevel structure of the data in mediation analyses. RESULTS: We observed positive associations between a fast increase in built-up land use within 300m of the home and all cardiometabolic risk factors. Compared with participants with stable trajectories, those with the largest increase in built-up land use had 1.5% (95% CI: 0.1, 2.9) higher systolic blood pressure, 2.4% (95% CI: 0.6, 4.3) higher diastolic blood pressure, 2.1% (95% CI: 0.5, 3.8) higher waist circumference, and 1.6% (95% CI: -0.6, 3.8) higher fasting glucose in fully adjusted models. Associations were positive, but not statistically significant, for triglycerides, fasting glucose, and non-HDL cholesterol. Physical activity and ambient particulate matter ≤2.5µm in aerodynamic diameter (PM2.5) partially mediated the estimated associations. Associations between fast build-up and all cardiometabolic risk factors except non-HDL cholesterol were stronger in women than men. DISCUSSION: Increases in built-up land use surrounding residences were consistently associated with higher levels of cardiometabolic risk factors. Our findings support the need for better integration of health considerations in urban planning in rapidly urbanizing settings. https://doi.org/10.1289/EHP5445.

Association between ambient and household air pollution with carotid intima-media thickness in peri-urban South India: CHAI-Project.

BACKGROUND: Evidence linking ambient air pollution with atherosclerosis is lacking from low- and middle-income countries. Additionally, evidence regarding the association between household air pollution and atherosclerosis is limited. We evaluated the association between ambient fine particulate matter [particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5)] and biomass fuel use on carotid intima-media thickness (CIMT), a surrogate of atherosclerosis, in India. METHODS: We analysed the third follow-up of the Andhra Pradesh Children and Parent Study cohort (2010-2012), which recruited participants from 28 peri-urban villages. Our primary outcome was mean CIMT, measured using a standardized protocol. We estimated annual average PM2.5 outdoors at residence using land-use regression. Biomass cooking fuel was self-reported. We fitted a within-between linear-mixed model adjusting for potential confounders. RESULTS: Among 3278 participants (48% women, mean age 38 years), mean PM2.5 was 32.7 [range 24.4-38.2] µg/m3, and 60% used biomass. After confounder adjustment, we observed positive associations between within-village variation in PM2.5 and CIMT in all participants [1.79%, 95% confidence interval (CI), -0.31 to 3.90 per 1 µg/m3 of PM2.5] and in men (2.98%, 95% CI, 0.23-5.72, per 1 µg/m3 of PM2.5). Use of biomass cooking fuel was associated with CIMT in all participants (1.60%, 95% CI, -0.46 to 3.65), especially in women with an unvented stove (6.14%, 95% CI, 1.40-10.89). The point-estimate for the PM2.5 association was larger in sub-groups with higher cardiometabolic risk profile. CONCLUSIONS: Ambient and household air pollution were positively associated with CIMT in a peri-urban population of India, although with limited precision for some estimates. We observed differences in the association between ambient and household air pollution and CIMT by gender.

Personal exposure to particulate matter in peri-urban India: predictors and association with ambient concentration at residence.

Scalable exposure assessment approaches that capture personal exposure to particles for purposes of epidemiology are currently limited, but valuable, particularly in low-/middle-income countries where sources of personal exposure are often distinct from those of ambient concentrations. We measured 2 × 24-h integrated personal exposure to PM2.5 and black carbon in two seasons in 402 participants living in peri-urban South India. Means (sd) of PM2.5 personal exposure were 55.1(82.8) µg/m3 for men and 58.5(58.8) µg/m3 for women; corresponding figures for black carbon were 4.6(7.0) µg/m3 and 6.1(9.6) µg/m3. Most variability in personal exposure was within participant (intra-class correlation ~20%). Personal exposure measurements were not correlated (Rspearman < 0.2) with annual ambient concentration at residence modeled by land-use regression; no subgroup with moderate or good agreement could be identified (weighted kappa ≤ 0.3 in all subgroups). We developed models to predict personal exposure in men and women separately, based on time-invariant characteristics collected at baseline (individual, household, and general time-activity) using forward stepwise model building with mixed models. Models for women included cooking activities and household socio-economic position, while models for men included smoking and occupation. Models performed moderately in terms of between-participant variance explained (38-53%) and correlations between predictions and measurements (Rspearman: 0.30-0.50). More detailed, time-varying time-activity data did not substantially improve the performance of the models. Our results demonstrate the feasibility of predicting personal exposure in support of epidemiological studies investigating long-term particulate matter exposure in settings characterized by solid fuel use and high occupational exposure to particles.

Does the oxidative stress play a role in the associations between outdoor air pollution and persistent asthma in adults? Findings from the EGEA study.

BACKGROUND: Evidences that oxidative stress plays a role in the associations between outdoor air pollution and asthma are growing. We aimed to study the role of plasma fluorescent oxidation products levels (FlOPs; an oxidative stress-related biomarker), as potential mediators, in the associations between outdoor air pollution and persistent asthma. METHODS: Analyses were conducted in 204 adult asthmatics followed up in the French case-control and family study on asthma (EGEA; the Epidemiological study of the Genetic and Environmental factors of Asthma). Persistent asthma was defined as having current asthma at EGEA2 (baseline, 2003-2007) and EGEA3 (follow-up, 2011-2013). Exposures to nitrogen dioxide, nitrogen oxides, road traffic, particulate matter with a diameter ≤ 10 µm (PM10) and ≤ 2.5 µm were estimated by ESCAPE models (2009-2010), and ozone (O3) by IFEN models (2004). We used a mediation analysis to assess the mediated effect by FlOPs levels and the interaction between FlOPs levels and air pollution. RESULTS: FlOPs levels increased with PM10 and O3 (adjusted ß = 0.04 (95%CI 0.001-0.08), aß = 0.04 (95%CI 0.009-0.07) per 10 µg/m3, respectively), and the risk of persistent asthma increased with FlOPs levels (aOR = 1.81 (95%CI 1.08-3.02)). The risk of persistent asthma decreased with exposures to NO2, NOx and PM2.5 (aOR ranging from 0.62 to 0.94), and increased with exposures to PM10, O3, O3-summer and road traffic, the greater effect being observed for O3 (aOR = 1.78, 95% CI 0.73-4.37, per 10 µg/m3). Using mediation analysis, we observed a positive total effect (aOR = 2.16, 95%CI 0.70-11.9), a positive direct effect of O3 on persistent asthma (OR = 1.68, 95%CI 0.57-7.25), and a positive indirect effect mediated by FIOPs levels (aOR = 1.28 (95%CI 1.01-2.29)) accounting for 41% of the total effect. CONCLUSIONS: Our results add insights on the role of oxidative stress in the association between air pollution and persistent asthma.

Low socioeconomic position and neighborhood deprivation are associated with uncontrolled asthma in elderly.

BACKGROUND: While uncontrolled asthma in adults is frequent in Europe, the impact of socioeconomic position (SEP) was little investigated. We aimed to investigate the respective association of individual- and area-level SEP with uncontrolled asthma among French elderly women. METHODS: Analyses were conducted in the Asthma-E3N study, among participants with current asthma (i.e., asthma attacks, treatment, or symptoms in previous year). Asthma control was evaluated using Asthma Control Test (uncontrolled: score ≤19); SEP was defined at both individual- and area-level, using educational level (low, medium, high), the French Deprivation index (tertiles defined at national level), and by merging them in a combined-SEP index. Associations between SEP and asthma control were estimated for 2258 women by logistic regression adjusted for age. Analyses were stratified by asthma controller medication use estimated through a drug reimbursement database. RESULTS: Women were 70 years on average and 24% had uncontrolled asthma. A low educational level (11%) was associated with an increased risk of uncontrolled asthma [odds ratio (95% confidence interval) = 1.9 (1.4,2.6)], especially among women not using controller medication [3.1 (1.9,5.1)]. Using the combined-SEP index, the highest risk of uncontrolled asthma was observed among women with the most disadvantaged socioeconomic profile (low educational level and low-SEP neighborhood) [2.5 (1.5,4.2)]. CONCLUSIONS: Women with low SEP had more often uncontrolled asthma, which might be partly explained by inadequate asthma treatment. To achieve the best management of asthma for elderly patients, a specific attention should be given not only to disadvantaged population and neighborhoods, but also to disadvantaged populations in affluent neighborhoods.

Lack of association between particulate air pollution and blood glucose levels and diabetic status in peri-urban India.

BACKGROUND: Limited evidence exists on the effect of particulate air pollution on blood glucose levels. We evaluated the associations of residential and personal levels of fine particulate matter (PM2.5) and black carbon (BC) with blood glucose and diabetic status among residents of 28 peri-urban villages in South India. METHODS: We used cross-sectional data from 5065 adults (≥18 years, 54% men) included in the Andhra Pradesh Children and Parents Study. Fasting plasma glucose was measured once in 2010-2012 and prevalent prediabetes and diabetes were defined following the American Diabetes Association criteria. We estimated annual ambient PM2.5 and BC levels at residence using land-use regression models and annual personal exposure to PM2.5 and BC using prediction models based on direct measurements from a subsample of 402 participants. We used linear and logistic nested mixed-effect models to assess the association between exposure metrics and health outcomes. For personal exposures, we stratified analyses by sex. RESULTS: Mean (SD) residential PM2.5 and BC were 32.9 (2.6) µg/m3 and 2.5 (2.6) µg/m3, respectively; personal exposures to PM2.5 and BC were 54.5 (11.5) µg/m3 and 5.8 (2.5) µg/m3, respectively. Average (SD) fasting blood glucose was 5.3 (1.3) mmol/l, 16% of participants had prediabetes, and 5.5% had diabetes. Residential PM2.5 and BC were not associated with higher blood glucose levels. Personal PM2.5 (20 µg/m3 increase) and BC (1 µg/m3 increase) were negatively associated with blood glucose levels in women (PM2.5: -1.93, 95%CI: -3.12, -0.73; BC: -0.63, 95%CI: -0.90, -0.37). In men, associations were negative for personal PM2.5 (-1.99, 95%CI: -3.56, -0.39) and positive for personal BC (0.49, 95%CI: -0.44, 1.43). We observed no evidence of associations between any exposure and prevalence of prediabetes/diabetes. CONCLUSIONS: Our results do not provide evidence that residential exposures to PM2.5 or BC are associated with blood glucose or prevalence of prediabetes/diabetes in this population. Associations with personal exposure may have been affected by unmeasured confounding, highlighting a challenge in using personal exposure estimates in air pollution epidemiology. These associations should be further examined in longitudinal studies.

Ambient Particulate Air Pollution and Blood Pressure in Peri-urban India.

BACKGROUND: Evidence linking long-term exposure to particulate air pollution to blood pressure (BP) in high-income countries may not be transportable to low- and middle-income countries. We examined cross-sectional associations between ambient fine particulate matter (PM2.5) and black carbon (BC) with BP (systolic [SBP] and diastolic [DBP]) and prevalent hypertension in adults from 28 peri-urban villages near Hyderabad, India. METHODS: We studied 5531 participants from the Andhra Pradesh Children and Parents Study (18-84 years, 54% men). We measured BP (2010-2012) in the right arm and defined hypertension as SBP ≥130 mmHg and/or DBP ≥80 mmHg. We used land-use regression models to estimate annual average PM2.5 and BC at participant's residence. We applied linear and logistic nested mixed-effect models stratified by sex and adjusted by cooking fuel type to estimate associations between within-village PM2.5 or BC and health. RESULTS: Mean (SD) PM2.5 was 33 µg/m (2.7) and BC was 2.5 µg/m (0.23). In women, a 1 µg/m increase in PM2.5 was associated with 1.4 mmHg higher SBP (95% confidence interval [CI]: 0.12, 2.7), 0.87 mmHg higher DBP (95% CI: -0.18, 1.9), and 4% higher odds of hypertension (95% CI: 0%, 9%). In men, associations with SBP (0.52 mmHg; 95% CI: -0.82, 1.8), DBP (0.41 mmHg; 95% CI: -0.69, 1.5), and hypertension (2% higher odds; 95% CI: -2%, 6%) were weaker. No associations were observed with BC. CONCLUSION: We observed a positive association between ambient PM2.5 and BP and hypertension in women. Longitudinal studies in this region are needed to corroborate our findings.

Risk of asthma onset after natural and surgical menopause: Results from the French E3N cohort.

BACKGROUND: The gender switch in asthma incidence around puberty has been put forward to suggest a role of sex hormones in asthma. However, there are limited and inconsistent findings on change in asthma incidence with menopause. We aimed to investigate the associations between menopause and asthma incidence, and interactions with overweight/obesity. METHODS: Asthma incidence was assessed in 67,872 women free of asthma at baseline (aged 41-68 years) and regularly followed up as a part of the French E3N cohort. Adjusted hazard ratios (aHR) were derived from Cox models considering age as the time-scale, menopausal status as a time-varying covariate and taking into account menopausal treatment. RESULTS: During 843,243 person-years of follow-up, 1205 new-onset asthma cases were identified. Compared with pre-menopause, surgical menopause was associated with an increased risk of asthma onset (aHR = 1.33 [95%CI 1.01-1.75]) but no association was observed for natural menopause (aHR = 1.05 [0.84-1.32]). In women with natural menopause, a further analysis separating the transition through menopause and the later post-menopausal period did not show any change in asthma incidence with menopause in the total sample or in normal-weight women alone. However, in overweight/obese women, peri-menopausal and post-menopausal women had an increased risk of developing asthma compared with pre-menopausal women of the same age (aHR = 1.91 [1.00-3.66] and aHR = 2.08 [1.07-4.06] respectively). CONCLUSION: Surgical menopause was associated with an increased risk of asthma onset. For natural menopause, no change in asthma incidence was observed in normal-weight women. However, overweight/obese women had an increased risk of developing asthma after natural menopause.

When, Where, and What? Characterizing Personal PM2.5 Exposure in Periurban India by Integrating GPS, Wearable Camera, and Ambient and Personal Monitoring Data.

Evidence identifying factors that influence personal exposure to air pollutants in low- and middle-income countries is scarce. Our objective was to identify the relative contribution of the time of the day ( when?), location ( where?), and individuals' activities ( what?) to PM2.5 personal exposure in periurban South India. We conducted a panel study in which 50 participants were monitored in up to six 24-h sessions ( n = 227). We integrated data from multiple sources: continuous personal and ambient PM2.5 concentrations; questionnaire, GPS, and wearable camera data; and modeled long-term exposure at residence. Mean 24-h personal exposure was 43.8 µg/m3 (SD 24.6) for men and 39.7 µg/m3 (SD 12.0) for women. Temporal patterns in exposure varied between women (peak exposure in the morning) and men (more exposed throughout the rest of the day). Most exposure occurred at home, 67% for men and 89% for women, which was proportional to the time spent in this location. Ambient daily PM2.5 was an important predictor of 24-h personal exposure for both genders. Among men, activities predictive of higher hourly average exposure included presence near food preparation, in the kitchen, in the vicinity of smoking, or in industry. For women, predictors of exposure were largely related to cooking.

Wearable camera-derived microenvironments in relation to personal exposure to PM2.5.

Data regarding which microenvironments drive exposure to air pollution in low and middle income countries are scarce. Our objective was to identify sources of time-resolved personal PM2.5 exposure in peri-urban India using wearable camera-derived microenvironmental information. We conducted a panel study with up to 6 repeated non-consecutive 24 h measurements on 45 participants (186 participant-days). Camera images were manually annotated to derive visual concepts indicative of microenvironments and activities. Men had slightly higher daily mean PM2.5 exposure (43 µg/m3) compared to women (39 µg/m3). Cameras helped identify that men also had higher exposures when near a biomass cooking unit (mean (sd) µg/m3: 119 (383) for men vs 83 (196) for women) and presence in the kitchen (133 (311) for men vs 48 (94) for women). Visual concepts associated in regression analysis with higher 5-minute PM2.5 for both sexes included: smoking (+93% (95% confidence interval: 63%, 129%) in men, +29% (95% CI: 2%, 63%) in women), biomass cooking unit (+57% (95% CI: 28%, 93%) in men, +69% (95% CI: 48%, 93%) in women), visible flame or smoke (+90% (95% CI: 48%, 144%) in men, +39% (95% CI: 6%, 83%) in women), and presence in the kitchen (+49% (95% CI: 27%, 75%) in men, +14% (95% CI: 7%, 20%) in women). Our results indicate wearable cameras can provide objective, high time-resolution microenvironmental data useful for identifying peak exposures and providing insights not evident using standard self-reported time-activity.

Outdoor air pollution, exhaled 8-isoprostane and current asthma in adults: the EGEA study.

Associations between outdoor air pollution and asthma in adults are still scarce, and the underlying biological mechanisms are poorly understood. Our aim was to study the associations between 1) long-term exposure to outdoor air pollution and current asthma, 2) exhaled 8-isoprostane (8-iso; a biomarker related to oxidative stress) and current asthma, and 3) outdoor air pollution and exhaled 8-iso.Cross-sectional analyses were conducted in 608 adults (39% with current asthma) from the first follow-up of the French case-control and family study on asthma (EGEA; the Epidemiological study of the Genetic and Environmental factors of Asthma). Data on nitrogen dioxide, nitrogen oxides, particulate matter with a diameter ≤10 and ≤2.5 µm (PM10 and PM2.5), road traffic, and ozone (O3) were from ESCAPE (European Study of Cohorts for Air Pollution Effects) and IFEN (French Institute for the Environment) assessments. Models took account of city and familial dependence.The risk of current asthma increased with traffic intensity (adjusted (a)OR 1.09 (95% CI 1.00-1.18) per 5000 vehicles per day), with O3 exposure (aOR 2.04 (95% CI 1.27-3.29) per 10 µg·m-3) and with exhaled 8-iso concentration (aOR 1.50 (95% CI 1.06-2.12) per 1 pg·mL-1). Among participants without asthma, exhaled 8-iso concentration increased with PM2.5 exposure (adjusted (a)ß 0.23 (95% CI 0.005-0.46) per 5 µg·m-3), and decreased with O3 and O3-summer exposures (aß -0.20 (95% CI -0.39- -0.01) and aß -0.52 (95% CI -0.77- -0.26) per 10 µg·m-3, respectively).Our results add new insights into a potential role of oxidative stress in the associations between outdoor air pollution and asthma in adults.

Development of land-use regression models for fine particles and black carbon in peri-urban South India.

Land-use regression (LUR) has been used to model local spatial variability of particulate matter in cities of high-income countries. Performance of LUR models is unknown in less urbanized areas of low-/middle-income countries (LMICs) experiencing complex sources of ambient air pollution and which typically have limited land use data. To address these concerns, we developed LUR models using satellite imagery (e.g., vegetation, urbanicity) and manually-collected data from a comprehensive built-environment survey (e.g., roads, industries, non-residential places) for a peri-urban area outside Hyderabad, India. As part of the CHAI (Cardiovascular Health effects of Air pollution in Telangana, India) project, concentrations of fine particulate matter (PM2.5) and black carbon were measured over two seasons at 23 sites. Annual mean (sd) was 34.1 (3.2) µg/m3 for PM2.5 and 2.7 (0.5) µg/m3 for black carbon. The LUR model for annual black carbon explained 78% of total variance and included both local-scale (energy supply places) and regional-scale (roads) predictors. Explained variance was 58% for annual PM2.5 and the included predictors were only regional (urbanicity, vegetation). During leave-one-out cross-validation and cross-holdout validation, only the black carbon model showed consistent performance. The LUR model for black carbon explained a substantial proportion of the spatial variability that could not be captured by simpler interpolation technique (ordinary kriging). This is the first study to develop a LUR model for ambient concentrations of PM2.5 and black carbon in a non-urban area of LMICs, supporting the applicability of the LUR approach in such settings. Our results provide insights on the added value of manually-collected built-environment data to improve the performance of LUR models in settings with limited data availability. For both pollutants, LUR models predicted substantial within-village variability, an important feature for future epidemiological studies.

Multimorbidity medications and poor asthma prognosis.

Multimedication related to multimorbidity is common in the elderly with asthma. We aimed at comprehensively characterising medications used by elderly women and assessing how multimedication impacts on asthma prognosis.We performed network-based analyses on drug administrative databases to visualise the prevalence of drug classes and their interconnections among 17 458 elderly women from the Asthma-E3N study, including 4328 women with asthma. Asthma groups sharing similar medication profiles were identified by a clustering method relying on all medications and were studied in association with adverse asthma events (uncontrolled asthma, attacks/exacerbations and poor asthma-related quality of life).The network-based analysis showed more multimedication in women with asthma than in those without asthma. The clustering method identified three multimedication profiles in asthma: "Few multimorbidity-related medications" (43.5%), "Predominantly allergic multimorbidity-related medications" (32.8%) and "Predominantly metabolic multimorbidity-related medications" (23.7%). Compared with women belonging to the "Few multimorbidity-related medications" profile, women belonging to the two other profiles had an increased risk of uncontrolled asthma and asthma attacks/exacerbations, and had lower asthma-related quality of life.The integrative data-driven approach on drug administrative databases identified specific multimorbidity-related medication profiles that were associated with poor asthma prognosis. These findings support the importance of multimorbidity in the unmet needs in asthma management.

Asthma Medication Ratio Phenotypes in Elderly Women.

BACKGROUND: With population aging, further asthma research is needed in the elderly. OBJECTIVE: We assessed the relevance of the controller-to-total asthma medication ratio and its fluctuations over time to identify participants with a subsequent risk of poor asthma-related outcomes among well-characterized elderly women. METHODS: We studied 4,328 women with ever asthma (69.6 ± 6.1 years) from the Asthma-E3N study (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale), which combined drug claims data since 2004 with prospective individual characteristics. The levels of the yearly controller-to-total asthma medication ratio from 2004 to 2011 were included in latent class analysis to identify groups of women characterized by specific long-term fluctuations of the ratio. Multiple regression models estimated the subsequent risk of uncontrolled asthma, asthma attacks, asthma exacerbations, and poor asthma-related quality of life associated with the level and the fluctuations of the ratio. RESULTS: A short-term (12 months) ratio below 0.5 was associated with a higher risk of subsequent uncontrolled asthma, asthma attacks, asthma exacerbations (odds ratio [95% confidence interval (CI)] = 2.13 [1.41; 3.23], 1.51 [1.01; 2.26], and 2.18 [1.37; 3.44], respectively), and a lower total asthma quality of life questionnaire score (ß [95% CI] = -0.49 [-0.68; -0.29]). The analysis of the long-term fluctuations of the ratio identified 5 profiles ("Never regular treatment," 53.2%; "Persistent high ratio," 21.8%; "Increasing ratio," 4.4%; "Initiating treatment," 8.8%; "Treatment discontinuation," 11.8%). The subsequent risk of poor asthma-related outcomes was significantly higher in profiles characterized by no or interrupted asthma maintenance therapy over time, compared with the "Persistent high ratio" group. CONCLUSIONS: The level and the long-term fluctuations of the controller-to-total asthma medication ratio predict poor asthma-related outcomes in elderly women.

Ability of ecological deprivation indices to measure social inequalities in a French cohort.

BACKGROUND: Despite the increasing interest in place effect to explain health inequalities, there is currently no consensus on which kind of area-based socioeconomic measures researchers should use to assess neighborhood socioeconomic position (SEP). The study aimed to evaluate the reliability of different area-based deprivation indices (DIs) in capturing socioeconomic residential conditions of French elderly women cohort. METHODS: We assessed area-based SEP using 3 DIs: Townsend Index, French European Deprivation Index (FEDI) and French Deprivation index (FDep), among women from E3N (Etude épidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale). DIs were derived from the 2009 French census at IRIS level (smallest geographical units in France). Educational level was used to evaluate individual-SEP. To evaluate external validity of the 3 DIs, associations between two well-established socially patterned outcomes among French elderly women (smoking and overweight) and SEP, were compared. Odd ratios were computed with generalized estimating equations to control for clustering effects from participants within the same IRIS. RESULTS: The analysis was performed among 63,888 women (aged 64, 47% ever smokers and 30% overweight). Substantial agreement was observed between the two French DIs (Kappa coefficient = 0.61) and between Townsend and FEDI (0.74) and fair agreement between Townsend and FDep (0.21). As expected among French elderly women, those with lower educational level were significantly less prone to be ever smoker (Low vs. High; OR [95% CI] = 0.43 [0.40-0.46]) and more prone to being overweight (1.89 [1.77-2.01]) than women higher educated. FDep showed expected associations at area-level for both smoking (most deprived vs. least deprived quintile; 0.77 [0.73-0.81]) and overweight (1.52 [1.44-1.62]). For FEDI opposite associations with smoking (1.13 [1.07-1.19]) and expected association with overweight (1.20 [1.13-1.28]) were observed. Townsend showed opposite associations to those expected for both smoking and overweight (1.51 [1.43-1.59]; 0.93 [0.88-0.99], respectively). CONCLUSION: FDep seemed reliable to capture socioeconomic residential conditions of the E3N women, more educated in average than general French population. Results varied strongly according to the DI with unexpected results for some of them, which suggested the importance to test external validity before studying social disparities in health in specific populations.

Predictors of Daily Mobility of Adults in Peri-Urban South India.

Daily mobility, an important aspect of environmental exposures and health behavior, has mainly been investigated in high-income countries. We aimed to identify the main dimensions of mobility and investigate their individual, contextual, and external predictors among men and women living in a peri-urban area of South India. We used 192 global positioning system (GPS)-recorded mobility tracks from 47 participants (24 women, 23 men) from the Cardiovascular Health effects of Air pollution in Telangana, India (CHAI) project (mean: 4.1 days/person). The mean age was 44 (standard deviation: 14) years. Half of the population was illiterate and 55% was in unskilled manual employment, mostly agriculture-related. Sex was the largest determinant of mobility. During daytime, time spent at home averaged 13.4 (3.7) h for women and 9.4 (4.2) h for men. Women's activity spaces were smaller and more circular than men's. A principal component analysis identified three main mobility dimensions related to the size of the activity space, the mobility in/around the residence, and mobility inside the village, explaining 86% (women) and 61% (men) of the total variability in mobility. Age, socioeconomic status, and urbanicity were associated with all three dimensions. Our results have multiple potential applications for improved assessment of environmental exposures and their effects on health.