Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

Can Habitual Exercise Help Reduce Serum Concentrations of Lipophilic Chemical Mixtures?Association between Physical Activity and Persistent Organic Pollutants

Background@#Low-dose persistent organic pollutants (POPs), especially organochlorine pesticides (OCPs), have emerged as a new risk factor of many chronic diseases. As serum concentrations of POPs in humans are mainly determined by both their release from adipose tissue to circulation and their elimination from circulation, management of these internal pathways may be important in controlling the serum concentrations of POPs. As habitual physical activity can increase the elimination of POPs from circulation, we evaluated whether chronic physical activity is related to low serum POP concentrations. @*Methods@#A cross-sectional study of 1,850 healthy adults (age ≥20 years) without cardio-metabolic diseases who participated in the U.S. National Health and Nutrition Examination Survey 1999 to 2004 was conducted. Information on moderate or vigorous leisure-time physical activity was obtained based on questionnaires. Serum concentrations of OCPs and polychlorinated biphenyls were investigated as typical POPs. @*Results@#Serum concentrations of OCPs among physically active subjects were significantly lower than those among physically inactive subjects (312.8 ng/g lipid vs. 538.0 ng/g lipid, P<0.001). This difference was maintained after adjustment for potential confounders. When analyses were restricted to physically active subjects, there were small decreases in the serum concentrations of OCPs with increasing duration of physical activity, showing a curvilinear relationship over the whole range of physical activity (Pquadratic <0.001). In analyses stratified by age, sex, body mass index, and smoking status, a strong inverse association was similarly observed among all subgroups. @*Conclusion@#Physical activity may assist in decreasing serum concentrations of lipophilic chemical mixtures such as OCPs.

Associations between Cigarette Smoking and Total Mortality Differ Depending on Serum Concentrations of Persistent Organic Pollutants among the Elderly

There are substantial variations of relative risks (RR) in smoking-related mortality by country and time. We hypothesized the RRs in smoking-related mortality might differ depending on serum concentrations of persistent organic pollutants (POPs). We evaluated the associations of cigarette smoking with total mortality in 610 elderly (aged > or = 70 yr) (702 elderly for organochlorine pesticides [OCPs]) after stratification by serum concentration of POPs, in the National Health and Nutrition Examination Survey (NHANES) 1999-2004 followed through 2006. Summary measures of POPs subclasses showed significant or marginally significant interaction with cigarette smoking on the risk of total mortality. P values for interaction were 0.069 for polychlorinated dibenzo-p-dioxins (PCDDs), 0.008 for polychlorinated biphenyls (PCBs), and 0.024 for OCPs. The effect of smoking on total mortality showed different patterns according to the serum concentration of some POPs. Former or current smokers had 1.4 to 2.9 times higher mortality rates compared with never smokers among participants with higher serum concentrations of POPs (2nd or 3rd tertiles). However, when the level of PCBs or OCPs were low (1st tertile), there were little positive associations between smoking and mortality. Our study suggests that the background exposure to several POPs may be related to variability in smoking-related total mortality.

Associations between Cigarette Smoking and Total Mortality Differ Depending on Serum Concentrations of Persistent Organic Pollutants among the Elderly

There are substantial variations of relative risks (RR) in smoking-related mortality by country and time. We hypothesized the RRs in smoking-related mortality might differ depending on serum concentrations of persistent organic pollutants (POPs). We evaluated the associations of cigarette smoking with total mortality in 610 elderly (aged > or = 70 yr) (702 elderly for organochlorine pesticides [OCPs]) after stratification by serum concentration of POPs, in the National Health and Nutrition Examination Survey (NHANES) 1999-2004 followed through 2006. Summary measures of POPs subclasses showed significant or marginally significant interaction with cigarette smoking on the risk of total mortality. P values for interaction were 0.069 for polychlorinated dibenzo-p-dioxins (PCDDs), 0.008 for polychlorinated biphenyls (PCBs), and 0.024 for OCPs. The effect of smoking on total mortality showed different patterns according to the serum concentration of some POPs. Former or current smokers had 1.4 to 2.9 times higher mortality rates compared with never smokers among participants with higher serum concentrations of POPs (2nd or 3rd tertiles). However, when the level of PCBs or OCPs were low (1st tertile), there were little positive associations between smoking and mortality. Our study suggests that the background exposure to several POPs may be related to variability in smoking-related total mortality.

Interaction Between Persistent Organic Pollutants and C-reactive Protein in Estimating Insulin Resistance Among Non-diabetic Adults / 예방의학회지

OBJECTIVES: Chronic inflammation is now thought to play a key pathogenetic role in the associations of obesity with insulin resistance and diabetes. Based on our recent findings on persistent organic pollutants (POPs) including the lack of an association between obesity and either insulin resistance or diabetes prevalence among subjects with very low concentrations of POPs, we hypothesized that POP concentrations may be associated with inflammation and modify the associations between inflammation and insulin resistance in non-diabetic subjects. METHODS: Cross-sectional associations among serum POPs, C-reactive protein (CRP), and homeostasis model assessment of insulin resistance (HOMA-IR) were investigated in 748 non-diabetic participants aged > or =20 years. Nineteen types of POPs in 5 subclasses were selected because the POPs were detectable in > or =60% of the participants. RESULTS: Among the five subclasses of POPs, only organochlorine (OC) pesticides showed positive associations with CRP concentrations, while polychlorinated biphenyls (PCBs) showed inverse associations with CRP concentrations. There were statistically significant interactions between CRP and OC pesticides and between CRP and PCBs, in estimating HOMA-IR (P for interaction <0.01 and <0.01, respectively). CRP was not associated with HOMA-IR among subjects with low concentrations of OC pesticides or PCBs, while CRP was strongly associated with HOMA-IR among subjects with high concentrations of these POPs. CONCLUSIONS: In the current study, OC pesticides were associated with increased levels of CRP, a marker of inflammation, and both OC pesticides and PCBs may also modify the associations between CRP and insulin resistance.

Relationship Between Serum Concentrations of Organochlorine Pesticides and Metabolic Syndrome Among Non-Diabetic Adults / 예방의학회지

OBJECTIVES: This study was performed to investigate if organochlorine pesticides (OCPs) were associated with metabolic syndrome and insulin resistance among non-diabetes. METHODS: Among subjects who participated in a community-based health survey, 50 non-diabetic subjects with metabolic syndrome and 50 normal controls were selected. Insulin resistance was measured by the homeostasis model assessment (HOMA-IR). Eight OCPs were selected. RESULTS: After adjusting for confounders except for body mass index (BMI), beta-hexachlorocyclohexane (beta-HCH) and heptachlor epoxide were positively associated with metabolic syndrome. Odds ratios across tertiles of beta-HCH and heptachlor epoxide were 1.0, 3.2 and 4.4, and 1.0, 4.0 and 6.0, respectively (p for trend = 0.01 and or =100 mg/dL)) were separately analyzed, all components were positively, but not significantly, associated with heptachlor epoxide. As the serum concentration of heptachlor epoxide increased, HOMA-IR increased significantly in subjects with metabolic syndrome even after adjusting for BMI (p value <0.05 and <0.01). CONCLUSIONS: Despite the small sample size, this study suggests that the background exposure to some OCPs may be associated with metabolic syndrome.