Impact of long-term exposure to ambient ozone on lung function over a course of 20 years (The ECRHS study): a prospective cohort study in adults.

Background: While the adverse effects of short-term ambient ozone exposure on lung function are well-documented, the impact of long-term exposure remains poorly understood, especially in adults. Methods: We aimed to investigate the association between long-term ozone exposure and lung function decline. The 3014 participants were drawn from 17 centers across eight countries, all of which were from the European Community Respiratory Health Survey (ECRHS). Spirometry was conducted to measure pre-bronchodilation forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at approximately 35, 44, and 55 years of age. We assigned annual mean values of daily maximum running 8-h average ozone concentrations to individual residential addresses. Adjustments were made for PM2.5, NO2, and greenness. To capture the ozone-related change in spirometric parameters, our linear mixed effects regression models included an interaction term between long-term ozone exposure and age. Findings: Mean ambient ozone concentrations were approximately 65 µg/m³. A one interquartile range increase of 7 µg/m³ in ozone was associated with a faster decline in FEV1 of -2.08 mL/year (95% confidence interval: -2.79, -1.36) and in FVC of -2.86 mL/year (-3.73, -1.99) mL/year over the study period. Associations were robust after adjusting for PM2.5, NO2, and greenness. The associations were more pronounced in residents of northern Europe and individuals who were older at baseline. No consistent associations were detected with the FEV1/FVC ratio. Interpretation: Long-term exposure to elevated ambient ozone concentrations was associated with a faster decline of spirometric lung function among middle-aged European adults over a 20-year period. Funding: German Research Foundation.

Residential greenspace and lung function decline over 20 years in a prospective cohort: The ECRHS study.

BACKGROUND: The few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected. OBJECTIVE: We explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey. METHODS: Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990-1994), 44 (1999-2003), and 55 (2010-2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures. RESULTS: A 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (-1.25 mL/year [95% confidence interval: -2.18 to -0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent associations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. CONCLUSIONS: More residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detrimental association requires verification in future studies.

Long-term exposure to airborne metals and risk of cancer in the French cohort Gazel.

BACKGROUND: The specific compounds that make ambient fine particulate matter (PM2.5) carcinogen remain poorly identified. Some metals contribute to ambient PM2.5 and possibly to its adverse effects. But the challenge of assessing exposure to airborne metals limits epidemiological studies. OBJECTIVE: To analyze the relationships between several airborne metals and risk of cancer in a large population. METHODS: We estimated the individual exposure to 12 airborne metals of âˆ¼ 12,000 semi-urban and rural participants of the French population-based Gazel cohort using moss biomonitoring data from a 20-year national program. We used principal component analyses (PCA) to derive groups of metals, and focused on six single carcinogenic or toxic metals (arsenic, cadmium, chromium, lead, nickel, and vanadium). We used extended Cox models with attained age as time-scale and time-varying weighted average exposures, adjusted for individual and area-level covariables, to analyze the association between each exposure and all-site combined, bladder, lung, breast, and prostate cancer incidence. RESULTS: We identified 2,401 cases of all-site cancer between 2001 and 2015. Over the follow-up, median exposures varied from 0.22 (interquartile range (IQR): 0.18-0.28) to 8.68 (IQR: 6.62-11.79) µg.g-1 of dried moss for cadmium and lead, respectively. The PCA yielded three groups identified as "anthropogenic", "crustal", and "marine". Models yielded positive associations between most single and groups of metal and all-site cancer, with e.g. hazard ratios of 1.08 (95% CI: 1.03, 1.13) for cadmium or 1.06 (95% CI: 1.02,1.10) for lead, per interquartile range increase. These findings were consistent across supplementary analyses, albeit attenuated when accounting for total PM2.5. Regarding specific site cancers, we estimated positive associations mostly for bladder, and generally with large confidence intervals. CONCLUSION: Most single and groups of airborne metals, except vanadium, were associated with risk of cancer. These findings may help identify sources or components of PM2.5 that may be involved in its carcinogenicity.

Long-term exposure to ambient air pollution and asthma symptom score in the CONSTANCES cohort.

BACKGROUND: The asthma symptom score allows to consider asthma as a continuum and to investigate its risk factors. One previous study has investigated the association between asthma score and air pollution and only for nitrogen dioxide (NO2). We aimed to study the associations between particulate matter with an aerodynamic diameter lower than 2.5 µm (PM2.5), black carbon (BC) and NO2 and the asthma symptom score in adults from CONSTANCES, a French population-based cohort. METHODS: Asthma symptom score (range: 0-5) was based on the number of five self-reported symptoms of asthma in the last 12 months. Annual individual exposure to PM2.5, BC and NO2 was estimated at participants' residential address using hybrid land-use regression models. Cross-sectional associations of each pollutant with asthma symptom score were estimated using negative binomial regressions adjusted for age, sex, smoking status and socioeconomic position. Associations with each symptom were estimated using logistic regression. The effect of BC independent of total PM2.5 was investigated with a residual model. RESULTS: Analyses were conducted on 135 165 participants (mean age: 47.2 years, 53.3% women, 19.0% smokers, 13.5% ever asthma). The ratio of mean score was 1.12 (95% CI 1.10 to 1.14), 1.14 (95% CI 1.12 to 1.16) and 1.12 (95% CI 1.10 to 1.14) per one IQR increase of PM2.5 (4.86 µg/m3), BC (0.88 10-5 m-1) and NO2 (17.3 µg/m3). Positive and significant associations were also found for each asthma symptom separately. BC effect persisted independently of total PM2.5. CONCLUSION: Exposure to each pollutant was associated with increased asthma symptom score in adults. This study highlights that BC could be one of the most harmful particulate matter components.

Association of urinary and ambient black carbon, and other ambient air pollutants with risk of prediabetes and metabolic syndrome in children and adolescents.

The effects of exposure to black carbon (BC) on various diseases remains unclear, one reason being potential exposure misclassification following modelling of ambient air pollution levels. Urinary BC particles may be a more precise measure to analyze the health effects of BC. We aimed to assess the risk of prediabetes and metabolic syndrome (MetS) in relation to urinary BC particles and ambient BC and to compare their associations in 5453 children from IDEFICS/I. Family cohort. We determined the amount of BC particles in urine using label-free white-light generation under femtosecond pulsed laser illumination. We assessed annual exposure to ambient air pollutants (BC, PM2.5 and NO2) at the place of residence using land use regression models for Europe, and we calculated the residential distance to major roads (≤250 m vs. more). We analyzed the cross-sectional relationships between urinary BC and air pollutants (BC, PM2.5 and NO2) and distance to roads, and the associations of all these variables to the risk of prediabetes and MetS, using logistic and linear regression models. Though we did not observe associations between urinary and ambient BC in overall analysis, we observed a positive association between urinary and ambient BC levels in boys and in children living ≤250 m to a major road compared to those living >250 m away from a major road. We observed a positive association between log-transformed urinary BC particles and MetS (ORper unit increase = 1.72, 95% CI = 1.21; 2.45). An association between ambient BC and MetS was only observed in children living closer to a major road. Our findings suggest that exposure to BC (ambient and biomarker) may contribute to the risk of MetS in children. By measuring the internal dose, the BC particles in urine may have additionally captured non-residential sources and reduced exposure misclassification. Larger studies, with longitudinal design including measurement of urinary BC at multiple time-points are warranted to confirm our findings.

Ambient air pollution exposure and depressive symptoms: Findings from the French CONSTANCES cohort.

BACKGROUND AND AIM: Few studies have reported the association between air pollution exposure with different dimensions of depression. We aimed to explore this association across different dimensions of depressive symptoms in a large population. METHODS: Data from the enrollment phase of the French CONSTANCES cohort (2012-2020) were analyzed cross-sectionally. Annual concentrations of particulate matter with a diameter < 2.5 µm (PM2.5), black carbon (BC), and nitrogen dioxide (NO2) from the land-use regression models were assigned to the residential addresses of participants. Total depressive symptoms and its four dimensions (depressed affect, disturbed interpersonal relations, low positive affect, somatic complaints) were measured using Centre of Epidemiologic Studies Depression questionnaire (CES-D). We reported results of negative binomial regression models (reported as Incidence Rate Ratio (IRR) and 95 % confidence interval (CI) for an interquartile range (IQR) increase in exposure), for each pollutant separately. Stratified analyses were performed by sex, income, family status, education, and neighborhood deprivation. RESULTS: The study included 123,754 participants (mean age, 46.50 ± 13.61 years; 52.4 % women). The mean concentration of PM2.5, BC and NO2 were 17.14 µg/m3 (IQR = 4.89), 1.82 10-5/m (IQR = 0.88) and 26.58 µg/m3 (IQR = 17.41) respectively. Exposures to PM2.5, BC and NO2 were significantly associated with a higher CES-D total (IRR = 1.022; 95 % CI = 1.002: 1.042, IRR = 1.027; 95 % CI = 1.013: 1.040, and IRR = 1.029; 95 % CI = 1.015: 1.042 respectively), and with depressed affect, and somatic complaints. For all pollutants, a higher estimate was observed for depressed affect. We found stronger adverse associations for men, lower-income participants, low and middle education groups, those living in highly deprived areas, and single participants. CONCLUSION: Our finding could assist the exploration of the etiological pathway of air pollution on depression and also considering primary prevention strategies in the areas with air pollution.

Exposure to greenspace and cancer incidence, prevalence, and mortality: A systematic review and meta-analyses.

We conducted a systematic review and meta-analysis of the available literature on the association between greenspace exposure and all-sites and site-specific cancer incidence, prevalence, and mortality in adults. We searched PubMed, Scopus, and Web of Science for original articles published, without language restriction until September 2021. We assessed the risk of bias in each study and the overall quality of evidence for exposure-outcome pairs that were reported in two or more studies. Out of the 18 included studies, cross-sectional studies were the most common study design (n = 8), and most of the studies were conducted in Europe (n = 8). In terms of risk of bias, the majority of cohorts (four out of six) and case-control studies (three out of four) were of good or very good quality, and cross-sectional studies were mostly (five out of eight) of poor quality. Outcomes (incidence, prevalence, mortality) on different cancer sites were reported: lung cancer (n = 9), prostate cancer (n = 4), breast cancer (n = 4), skin cancer (n = 3), colorectal cancer (n = 2), all-sites cancer (n = 2), brain cancer (n = 1), mouth and throat cancer (n = 1), and esophageal cancer (n = 1). The meta-analyses for the breast, lung, and prostate cancer incidence did not show statistically significant associations (for example for breast cancer: hazard ratio = 0.83; 95% confidence interval: 0.47-1.48). For skin cancer, the available evidence suggests that greenspace could be a potential risk factor. For the other cancers, the evidence was non-conclusive. The overall quality of evidence of all of the exposure-outcome pairs was very low. Given the wide confidence interval of the pooled estimates and very low quality of evidence, the findings should be interpreted with caution. Future large and longitudinal studies are needed to assess the potential association of greenspace exposure with cancers, considering types and quality of greenspace, evaluation of cancer sub-types, and adjustment for a sufficient set of covariates.

Influence of exposure assessment methods on associations between long-term exposure to outdoor fine particulate matter and risk of cancer in the French cohort Gazel.

BACKGROUND: Many studies investigated the relationship between outdoor fine particulate matter (PM2.5) and cancer. While they generally indicated positive associations, results have not been fully consistent, possibly because of the diversity of methods used to assess exposure. OBJECTIVES: To investigate how using different PM2.5 exposure assessment methods influences risk estimates in the large French general population-based Gazel cohort (20,625 participants at enrollment) with a 26-year follow-up with complete residential histories. METHODS: We focused on two cancer incidence outcomes: all-sites combined and lung. We used two distinct exposure assessment methods: a western European land use regression (LUR), and a chemistry-dispersion model (Gazel-Air) for France, each with a time series ≥20-years annual concentrations. Spearman correlation coefficient between the two estimates of PM2.5 was 0.71 across all person-years; the LUR tended to provide higher exposures. We used extended Cox models with attained age as time-scale and time-dependent cumulative exposures, adjusting for a set of confounders including sex and smoking, to derive hazard ratios (HRs) and their 95% confidence interval, implementing a 10-year lag between exposure and incidence/censoring. RESULTS: We obtained similar two-piece linear associations for all-sites cancer (3711 cases), with a first slope of HRs of 1.53 (1.24-1.88) and 1.43 (1.19-1.73) for one IQR increase of cumulative PM2.5 exposure for the LUR and the Gazel-Air models respectively, followed by a plateau at around 1.5 for both exposure assessments. For lung cancer (349 cases), the HRs from the two exposure models were less similar, with largely overlapping confidence limits. CONCLUSION: Our findings using long-term exposure estimates from two distinct exposure assessment methods corroborate the association between air pollution and cancer risk.

Assessing the impact of exposome on the course of chronic obstructive pulmonary disease and cystc fibrosis: The REMEDIA European Project Approach.

Because of the direct interaction of lungs with the environment, respiratory diseases are among the leading causes of environment-related deaths in the world. Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are two highly debilitating diseases that are of particular interest in the context of environmental studies; they both are characterized by a similar progressive loss of lung function with small bronchi alterations, and a high phenotypic variability of unknown origin, which prevents a good therapeutic efficacy. In the last years, there has been an evolution in the apprehension of the study of diseases going from a restricted "one exposure, one disease" approach to a broader concept with other associating factors, the exposome. The overall objective of the REMEDIA project is to extend the understanding of the contribution of the exposome to COPD and CF diseases. To achieve our aim, we will (1) exploit data from existing cohorts and population registries to create a unified global database gathering phenotype and exposome information; (2) develop a flexible individual sensor device combining environmental and biomarker toolkits; (3) use a versatile atmospheric simulation chamber to simulate the health effects of complex exposomes; (4) use machine learning supervised analyses and causal inference models to identify relevant risk factors; and (5) develop econometric and cost-effectiveness models to assess the costs, performance, and cost-effectiveness of a selection of prevention strategies. The results will be used to develop guidelines to better predict disease risks and constitute the elements of the REMEDIA toolbox. The multidisciplinary approach carried out by the REMEDIA European project should represent a major breakthrough in reducing the morbidity and mortality associated with COPD and CF diseases.

Long-term exposure to black carbon and mortality: A 28-year follow-up of the GAZEL cohort.

BACKGROUND: The current evidence on health effects of long-term exposure to outdoor airborne black carbon (BC) exposure remains scarce. OBJECTIVES: To examine the association between long-term exposure to BC and mortality in a large population-based French cohort, with 28 years of follow-up. METHODS: Data from the GAZEL cohort were collected between 1989 and 2017. Land use regression model with temporal extrapolation wa used to estimate yearly BC and PM2.5 exposure at the residential addresses from 1989 until censoring for 19,906 participants. Time-varying Cox models with attained age as time-scale was used to estimate the associations between BC and all-cause and cardiovascular mortality, after adjusting for individual and area-level covariates. To handle confounding by PM2.5, we used the residual of BC regressed on PM2.5 as an alternate exposure variable. For all-cause mortality, we also examined effect modification by sex, smoking status, BMI and fruit/vegetable intake. RESULTS: The median of 20-year moving average of BC exposure was 2.02 10-5/m in study population. We found significant associations between BC exposure and all-cause mortality (n = 2357) using both 20-year moving average of BC and residual of BC, with corresponding hazard ratios (HR) of 1.14 (95 %CI: 1.07-1.22) and 1.17 (95 %CI: 1.10-1.24) for an inter-quartile range (IQR) increase (0.86 10-5/m for BC and 0.57 10-5/m for residual of BC). We found a similar association between BC and cardiovascular mortality (n = 277) with a HR of 1.15 (95 %CI: 0.95-1.38). The dose-response relationship between BC and all-cause mortality was monotonic but nonlinear with a steeper slope at high BC levels. In addition, the effect of BC was higher among never-smokers and among those having fruit/vegetables less than twice a week. CONCLUSIONS: There was a positive association between long-term exposure to BC and increased mortality risk, reinforcing the emerging evidence that BC is a harmful component of PM2.5.

Long-term exposures to PM2.5, black carbon and NO2 and prevalence of current rhinitis in French adults: The Constances Cohort.

BACKGROUND: Rhinitis is one of the most common disease worldwide with a high and increasing prevalence. There is limited knowledge on the link between long-term exposure to air pollution and rhinitis. OBJECTIVES: We aim to study the associations between long-term exposure to air pollutants and self-reported current rhinitis among adults from Constances, a large French population-based cohort. METHODS: Current rhinitis was defined at inclusion from questionnaire by the presence of sneezing, runny or blocked nose in the last 12 months without a cold or the flu. Annual concentrations of nitrogen dioxide (NO2), particulate matter ≤ 2.5 µm (PM2.5) and black carbon (BC) were estimated at the participants' residential address by European land-use regression models. Cross-sectional associations between annual exposure to each air pollutant and current rhinitis were estimated using logistic models adjusted for age, sex, smoking, education level and French deprivation index. The health prevention centers were taken into account by marginal models with generalized estimating equations. Several supplementary analyses were performed. RESULTS: Analyses were performed on 127,108 participants (47 years old on average, 54% women, 19% current smokers). The prevalence of current rhinitis, allergic (AR) and non-allergic (NAR) rhinitis were 36%, 25% and 11% respectively. Adjusted ORs for current rhinitis were 1.13 (1.08, 1.17), 1.12 (1.07, 1.17), and 1.11 (1.06, 1.17) per one interquartile range increase of PM2.5 (4.85 µg/m3), BC (0.88 · 10-5 m-1) and NO2 (17.3 µg/m3) respectively. Significant and positive associations were also found for both AR and NAR. Results were similar in men and women, and in the different smoking strata, and were consistent with meta-analysis or after imputing missing covariates. DISCUSSION: An increase of modeled annual average residential exposure to PM2.5, BC, and NO2 was significantly associated with an increase of prevalence of current rhinitis in adults in the French general population. The results suggest that among air pollutants, BC may be of special interest.

Greenspace exposure and cancer incidence: A 27-year follow-up of the French GAZEL cohort.

BACKGROUND: Greenspace exposure has been suggested to be associated with a range of health outcomes. The available evidence on the association of this exposure with cancer is still very scarce and inconsistent. OBJECTIVES: We aimed to study the association between greenspace exposure and all-site and site-specific (prostate, breast, colorectal, bladder, lung, and malignant melanoma of skin) cancer incidence in the GAZEL cohort. METHODS: This study was based on over 27 years of follow-up (1989-2016) of 19,408 participants across France. We assessed the residential greenspace exposure within several buffers as well as residential proximity to green spaces (agricultural, urban, and forests) in each follow-up. We used time-dependent Cox models, controlling for time-varying personal and area-level variables, with different lags between exposure and outcome. Additional analysis was conducted according to the urban-rural residence of the participants' over follow-up. RESULTS: Over the 294,645 person-years of follow-up, we registered 4075 incident cases of cancer. We found an increase in the risk for all-sites cancer with an inter-quartile range increase of Normalized Difference in Vegetation Index across different buffers (hazard ratio (HR) of 1.08; 95% CI: 1.02, 1.14 for the 100 m buffer). We found a positive association of all-sites cancer with proximity to agricultural lands (HR: 1.03; 95% CI: 1.00, 1.05), and forests (HR:1.04; 95% CI: 1.00, 1.07), but not with urban green spaces. The cancer site-specific analyses suggested a protective role of greenspace for breast, lung, and colorectal cancers (e.g. breast cancer HR at 100 m buffer: 0.82; 95% CI: 0.69, 0.99). Non-significant associations were observed for prostate, bladder, and skin cancer. Stratified analyses based on urban, semi-urban, and rural classification did not suggest any differential pattern. CONCLUSION: We identified an increased risk of all-site cancer with increased greenspace and proximity to agricultural lands and forests; whereas potential protective role of greenspace for breast cancer.

Contribution of Long-Term Exposure to Outdoor Black Carbon to the Carcinogenicity of Air Pollution: Evidence regarding Risk of Cancer in the Gazel Cohort.

BACKGROUND: Black carbon (BC), a component of fine particulate matter [particles with an aerodynamic diameter ≤2.5 µm (PM2.5)], may contribute to carcinogenic effects of air pollution. Until recently however, there has been little evidence to evaluate this hypothesis. OBJECTIVE: This study aimed to estimate the associations between long-term exposure to BC and risk of cancer. This study was conducted within the French Gazel cohort of 20,625 subjects. METHODS: We assessed exposure to BC by linking subjects' histories of residential addresses to a map of European black carbon levels in 2010 with back- and forward-extrapolation between 1989 and 2015. We used extended Cox models, with attained age as time-scale and time-varying cumulative exposure to BC, adjusted for relevant sociodemographic and lifestyle variables. To consider latency between exposure and cancer diagnosis, we implemented a 10-y lag, and as a sensitivity analysis, a lag of 2 y. To isolate the effect of BC from that of total PM2.5, we regressed BC on PM2.5 and used the residuals as the exposure variable. RESULTS: During the 26-y follow-up period, there were 3,711 incident cancer cases (all sites combined) and 349 incident lung cancers. Median baseline exposure in 1989 was 2.65 10-5/m [interquartile range (IQR): 2.23-3.33], which generally slightly decreased over time. Using 10 y as a lag-time in our models, the adjusted hazard ratio per each IQR increase of the natural log-transformed cumulative BC was 1.17 (95% confidence interval: 1.06, 1.29) for all-sites cancer combined and 1.31 (0.93, 1.83) for lung cancer. Associations with BC residuals were also positive for both outcomes. Using 2 y as a lag-time, the results were similar. DISCUSSION: Our findings for a cohort of French adults suggest that BC may partly explain the association between PM2.5 and lung cancer. Additional studies are needed to confirm our results and further disentangle the effects of BC, total PM2.5, and other constituents. https://doi.org/10.1289/EHP8719.

Air pollution exposure and bladder, kidney and urinary tract cancer risk: A systematic review.

BACKGROUND: Exposure to outdoor air pollution has been linked to lung cancer, and suspicion arose regarding bladder, kidney, and urinary tract cancer (urological cancers). However, most of evidence comes from occupational studies; therefore, little is known about the effect of exposure to air pollution on the risk of urological cancers in the general population. METHOD: We systematically searched Medline, Scopus, and Web of Science for articles investigating the associations between long-term exposure to air pollution and the risk of urological cancer (incidence or mortality). We included articles using a specific air pollutant (PM10, PM2.5, …) or proxies (traffic, proximity index …). We assessed each study's quality with the Newcastle-Ottawa scale and rated the quality of the body of evidence for each pollutant-outcome with the GRADE approach. The different study methodologies regarding exposure or outcome prevented us to perform a meta-analysis. RESULTS: twenty articles (four case-control, nine cohort, and seven ecologic) met our inclusion criteria and were included in this review: eighteen reported bladder, six kidney, and two urinary tract. Modeling air pollutants was the most common exposure assessment method. Most of the included studies reported positive associations between air pollution and urological cancer risk. However, only a few reached statistical significance (e.g. for bladder cancer mortality, adjusted odds-ratio of 1.13 (1.03-1.23) for an increase of 4.4 µg.m-3 of PM2.5). Most studies inadequately addressed confounding, and cohort studies had an insufficient follow-up. DISCUSSION: Overall, studies suggested positive (even though mostly non-significant) associations between air pollution exposure and bladder cancer mortality and kidney cancer incidence. We need more studies with better confounding control and longer follow-ups.

Residential air pollution does not modify the positive association between physical activity and lung function in current smokers in the ECRHS study.

BACKGROUND: Very few studies have examined whether a long-term beneficial effect of physical activity on lung function can be influenced by living in polluted urban areas. OBJECTIVE: We assessed whether annual average residential concentrations of nitrogen dioxide (NO2) and particulate matter with aerodynamic diameters < 2.5 µm (PM2.5) and <10 µm (PM10) modify the effect of physical activity on lung function among never- (N = 2801) and current (N = 1719) smokers in the multi-center European Community Respiratory Health Survey. METHODS: Associations between repeated assessments (at 27-57 and 39-67 years) of being physically active (physical activity: ≥2 times and ≥1 h per week) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were evaluated using adjusted mixed linear regression models. Models were conducted separately for never- and current smokers and stratified by residential long-term NO2, PM2.5 mass and PM10 mass concentrations (≤75th percentile (low/medium) versus >75th percentile (high)). RESULTS: Among current smokers, physical activity and lung function were positively associated regardless of air pollution levels. Among never-smokers, physical activity was associated with lung function in areas with low/medium NO2, PM2.5 mass and PM10 mass concentrations (e.g. mean difference in FVC between active and non-active subjects was 43.0 mL (13.6, 72.5), 49.5 mL (20.1, 78.8) and 49.7 mL (18.6, 80.7), respectively), but these associations were attenuated in high air pollution areas. Only the interaction term of physical activity and PM10 mass for FEV1 among never-smokers was significant (p-value = 0.03). CONCLUSIONS: Physical activity has beneficial effects on adult lung function in current smokers, irrespective of residential air pollution levels in Western Europe. Trends among never-smokers living in high air pollution areas are less clear.

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.

[Historical Review of Kaposi sarcoma in pre-HAART era: evolution with different chemotherapy schedules and remission with ganciclovir use]. / Revisión histórica del sarcoma de Kaposi en la era pre-TARAA (terapia antirretroviral altamente activa): evolución con diferentes esquemas de quimioterapia y remisión con el uso de ganciclovir.

Ganciclovir has shown in vitro anti-human herpesvirus-8 activity, Kaposi sarcoma agent. We analyzed all Kaposi sarcoma patients from 1985 to 1996 pre-HAART era and identified Kaposi sarcoma/AIDS patients who achieved complete remission prior to HAART use. RESULTS: We saw 155 Kaposi sarcoma patients up to 1996, 150 with enough information, only 12 received ganciclovir, eight of them for ≥ 21 days; four died within 16 weeks of ganciclovir administration. We identified four male patients with extensive Kaposi sarcoma with complete remission achieved after ganciclovir for CMV end-organ disease. Complete remission was achieved (9, 5, 10 and 5 months) after ganciclovir, which persisted even after antiretroviral therapy failure. All received two nucleosides and indinavir was later added with irregular compliance. The CD4 counts when ganciclovir was started: 11 (4%), 60 (5%), 127 (14%), and 38 (3%) and when they achieved complete remission: 37 (4%), 109 (9%), 313 (13%) and 136 (9%), respectively. Two patients died with no Kaposi sarcoma relapse three years later, with wasting syndrome and other pulmonary-embolism seven years later. One was lost to follow-up in complete remission in the year 2000, the other was alive in 2014 with 27% 820 CD4 cells/ml. The use of ganciclovir was statistically significantly associated with Kaposi sarcoma remission p = 0.001. CONCLUSIONS: Ganciclovir use was associated to complete remission of Kaposi sarcoma in the pre-HAART era.

Susceptibility Factors Relevant for the Association Between Long-Term Air Pollution Exposure and Incident Asthma.

In this review, we identified 15 studies in children and 10 studies in adults that assessed the association between long-term exposure to air pollution and incident asthma and that conducted stratified analyses to explore potential susceptibility factors. Overall, adult never-/former smokers seem to be at higher risk of incident asthma due to air pollution. Children without atopy and children from low socioeconomic status families also seem to be at higher risk of incident asthma due to air pollution. While interaction between air pollution and genes involved in the response to oxidative stress pathways have been explored, results are somewhat inconsistent and in need of replication. To evaluate interactions, large sample sizes are necessary, and much more research, including data pooling from existing studies, is needed to further explore susceptibility factors for asthma incidence due to long-term air pollution exposure.

Ambient air pollution and adult asthma incidence in six European cohorts (ESCAPE).

BACKGROUND: Short-term exposure to air pollution has adverse effects among patients with asthma, but whether long-term exposure to air pollution is a cause of adult-onset asthma is unclear. OBJECTIVE: We aimed to investigate the association between air pollution and adult onset asthma. METHODS: Asthma incidence was prospectively assessed in six European cohorts. Exposures studied were annual average concentrations at home addresses for nitrogen oxides assessed for 23,704 participants (including 1,257 incident cases) and particulate matter (PM) assessed for 17,909 participants through ESCAPE land-use regression models and traffic exposure indicators. Meta-analyses of cohort-specific logistic regression on asthma incidence were performed. Models were adjusted for age, sex, overweight, education, and smoking and included city/area within each cohort as a random effect. RESULTS: In this longitudinal analysis, asthma incidence was positively, but not significantly, associated with all exposure metrics, except for PMcoarse. Positive associations of borderline significance were observed for nitrogen dioxide [adjusted odds ratio (OR) = 1.10; 95% CI: 0.99, 1.21 per 10 µg/m3; p = 0.10] and nitrogen oxides (adjusted OR = 1.04; 95% CI: 0.99, 1.08 per 20 µg/m3; p = 0.08). Nonsignificant positive associations were estimated for PM10 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 10 µg/m3), PM2.5 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 5 µg/m3), PM2.5absorbance (adjusted OR = 1.06; 95% CI: 0.95, 1.19 per 10-5/m), traffic load (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 4 million vehicles × meters/day on major roads in a 100-m buffer), and traffic intensity (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 5,000 vehicles/day on the nearest road). A nonsignificant negative association was estimated for PMcoarse (adjusted OR = 0.98; 95% CI: 0.87, 1.14 per 5 µg/m3). CONCLUSIONS: Results suggest a deleterious effect of ambient air pollution on asthma incidence in adults. Further research with improved personal-level exposure assessment (vs. residential exposure assessment only) and phenotypic characterization is needed.

The risks of acute exposure to black carbon in Southern Europe: results from the MED-PARTICLES project.

OBJECTIVES: While several studies have reported associations of daily exposures to PM2.5 (particles less than 2.5 µm) with mortality, few studies have examined the impact of its constituents such as black carbon (BC), which is also a significant contributor to global climate change. METHODS: We assessed the association between daily concentrations of BC and total, cardiovascular and respiratory mortality in two southern Mediterranean cities. Daily averages of BC were collected for 2 years in Barcelona, Spain and Athens, Greece. We used case-crossover analysis and examined single and cumulative lags up to 3 days. RESULTS: We observed associations between BC and all mortality measures. For a 3-day moving average, cardiovascular mortality increased by 4.5% (95% CI 0.7 to 8.5) and 2.0% (95% CI 0 to 4.0) for an interquartile change in BC in Athens and Barcelona, respectively. Considerably higher effects for respiratory mortality and for those above age 65 were observed. In addition, BC exhibited much greater toxicity per microgram than generic PM2.5. CONCLUSIONS: Our findings suggest that BC, derived in western industrialised nations primarily from diesel engines and biomass burning, poses a significant burden to public health, particularly in European cities with high-traffic density.