Air Pollution and Autism Spectrum Disorder in Israel: A Negative Control Analysis.

BACKGROUND: Residual confounding is a major concern for causal inference in observational studies on air pollution-autism spectrum disorder (ASD) associations. This study is aimed at assessing confounding in these associations using negative control exposures. METHODS: This nested case-control study included all children diagnosed with ASD (detected through 31 December 2016) born during 2007-2012 in Israel and residing in the study area (N = 3,843), and matched controls of the same age (N = 38,430). We assigned individual house-level exposure estimates for each child. We estimated associations using logistic regression models, mutually adjusted for all relevant exposure periods (prepregnancy, pregnancy, and postnatal). We assessed residual confounding using postoutcome negative control exposure at age 28-36 months. RESULTS: In mutually adjusted models, we observed positive associations with ASD for postnatal exposures to NOx (odds ratio per interquartile range, 95% confidence interval: 1.19, 1.02-1.38) and NO2 (1.20, 1.00-1.43), and gestational exposure to PM2.5-10 (1.08, 1.01-1.15). The result for the negative control period was 1.04, 0.99-1.10 for PM2.5, suggesting some residual confounding, but no associations for PM2.5-10 (0.98, 0.81-1.18), NOx (1.02, 0.84-1.25), or NO2 (0.98, 0.81-1.18), suggesting no residual confounding. CONCLUSIONS: Our results further support a hypothesized causal link with ASD that is specific to postnatal exposures to traffic-related pollution.

Cancer and mortality in relation to traffic-related air pollution among coronary patients: Using an ensemble of exposure estimates to identify high-risk individuals.

BACKGROUND: Moderate correlations were previously observed between individual estimates of traffic-related air pollution (TRAP) produced by different exposure modeling approaches. This induces exposure misclassification for a substantial fraction of subjects. AIM: We used an ensemble of well-established modeling approaches to increase certainty of exposure classification and reevaluated the association with cancers previously linked to TRAP (lung, breast and prostate), other cancers, and all-cause mortality in a cohort of coronary patients. METHODS: Patients undergoing percutaneous coronary interventions in a major Israeli medical center from 2004 to 2014 (n = 10,627) were followed for cancer (through 2015) and mortality (through 2017) via national registries. Residential exposure to nitrogen oxides (NOx) -a proxy for TRAP- was estimated by optimized dispersion model (ODM) and land use regression (LUR) (rPearson = 0.50). Mutually exclusive groups of subjects classified as exposed by none of the methods (high-certainty low-exposed), ODM alone, LUR alone, or both methods (high-certainty high-exposed) were created. Associations were examined using Cox regression models. RESULTS: During follow-up, 741 incident cancer cases were diagnosed and 3051 deaths occurred. Using a ≥25 ppb cutoff, compared with high-certainty low exposed, the multivariable-adjusted hazard ratios (95% confidence intervals) for lung, breast and prostate cancer were 1.56 (1.13-2.15) in high-certainty exposed, 1.27 (0.86-1.86) in LUR-exposed alone, and 1.13 (0.77-1.65) in ODM-exposed alone. The association of the former category was strengthened using more extreme NOx cutoffs. A similar pattern, albeit less strong, was observed for mortality, whereas no association was shown for cancers not previously linked to TRAP. CONCLUSIONS: Use of an ensemble of TRAP exposure estimates may improve classification, resulting in a stronger association with outcomes.

Preexisting coronary heart disease and susceptibility to long-term effects of traffic-related air pollution: A matched cohort analysis.

BACKGROUND: Individuals with coronary heart disease are considered susceptible to traffic-related air pollution exposure. Yet, cohort-based evidence on whether preexisting coronary heart disease modifies the association of traffic-related air pollution with health outcomes is lacking. AIM: Using data of four Israeli cohorts, we compared associations of traffic-related air pollution with mortality and cancer between coronary heart disease patients and matched controls from the general population. METHODS: Subjects hospitalized with acute coronary syndrome from two patient cohorts (inception years: 1992-1993 and 2006-2014) were age- and sex-matched to coronary heart disease-free participants of two cycles of the Israeli National Health and Nutrition Surveys (inception years: 1999-2001 and 2005-2006). Ambient concentrations of nitrogen oxides at the residential place served as a proxy for traffic-related air pollution exposure across all cohorts, based on a high-resolution national land use regression model (50 m). Data on all-cause mortality (last update: 2018) and cancer incidence (last update: 2016) were retrieved from national registries. Cox-derived stratum-specific hazard ratios with 95% confidence intervals were calculated, adjusted for harmonized covariates across cohorts, including age, sex, ethnicity, neighborhood socioeconomic status, smoking, diabetes, hypertension, prior stroke and prior malignancy (the latter only in the mortality analysis). Effect-modification was examined by testing nitrogen oxides-by-coronary heart disease interaction term in the entire matched cohort. RESULTS: The cohort (mean (standard deviation) age 61.5 (14) years; 44% women) included 2393 matched pairs, among them 2040 were cancer-free at baseline. During a median (25th-75th percentiles) follow-up of 13 (10-19) and 11 (7-17) years, 1458 deaths and 536 new cancer cases were identified, respectively. In multivariable-adjusted models, a 10-parts per billion nitrogen oxides increment was positively associated with all-cause mortality among coronary heart disease patients (hazard ratio = 1.13, 95% confidence interval 1.05-1.22), but not among controls (hazard ratio = 1.00, 0.93-1.08) (pinteraction = 0.003). A similar pattern was seen for all-cancer incidence (hazard ratioCHD = 1.19 (1.03-1.37), hazard ratioCHD-Free = 0.93 (0.84-1.04) (pinteraction = 0.01)). Associations were robust to multiple sensitivity analyses. CONCLUSIONS: Coronary heart disease patients might be at increased risk for traffic-related air pollution-associated mortality and cancer, irrespective of their age and sex. Patients and clinicians should be more aware of the adverse health effects on coronary heart disease patients of chronic exposure to vehicle emissions.