Since 2001, researchers have examined the human genome (G) mainly to discover causes of disease, despite evidence that G explains relatively little risk. We posit that unexplained disease risks are ...caused by the exposome (E; representing all exposures) and G × E interactions. Thus, etiologic research has been hampered by scientists' continuing reliance on low-tech methods to characterize E compared with high-tech omics for characterizing G.
Because exposures are inherently chemical in nature and arise from both endogenous and exogenous sources, blood specimens can be used to characterize exposomes. To explore the "blood exposome" and its connection to disease, we sought human blood concentrations of many chemicals, along with their sources, evidence of chronic-disease risks, and numbers of metabolic pathways.
From the literature we obtained human blood concentrations of 1,561 small molecules and metals derived from foods, drugs, pollutants, and endogenous processes. We mapped chemical similarities after weighting by blood concentrations, disease-risk citations, and numbers of human metabolic pathways.
Blood concentrations spanned 11 orders of magnitude and were indistinguishable for endogenous and food chemicals and drugs, whereas those of pollutants were 1,000 times lower. Chemical similarities mapped by disease risks were equally distributed by source categories, but those mapped by metabolic pathways were dominated by endogenous molecules and essential nutrients.
For studies of disease etiology, the complexity of human exposures motivates characterization of the blood exposome, which includes all biologically active chemicals. Because most small molecules in blood are not human metabolites, investigations of causal pathways should expand beyond the endogenous metabolome.
Background: Particulate matter (PM) in outdoor air pollution was recently designated a Group I carcinogen by the International Agency for Research on Cancer (IARC). This determination was based on ...the evidence regarding the relationship of PM2.5 and PM10 to lung cancer risk; however, the IARC evaluation did not include a quantitative summary of the evidence. Objective: Our goal was to provide a systematic review and quantitative summary of the evidence regarding the relationship between PM and lung cancer. Methods: We conducted meta-analyses of studies examining the relationship of exposure to PM2.5 and PM10 with lung cancer incidence and mortality. In total, 18 studies met our inclusion criteria and provided the information necessary to estimate the change in lung cancer risk per 10- mu g/m3 increase in exposure to PM. We used random-effects analyses to allow between-study variability to contribute to meta-estimates. Results: The meta-relative risk for lung cancer associated with PM2.5 was 1.09 (95% CI: 1.04, 1.14). The meta-relative risk of lung cancer associated with PM10 was similar, but less precise: 1.08 (95% CI: 1.00, 1.17). Estimates were robust to restriction to studies that considered potential confounders, as well as subanalyses by exposure assessment method. Analyses by smoking status showed that lung cancer risk associated with PM2.5 was greatest for former smokers 1.44 (95% CI: 1.04, 1.22), followed by never-smokers 1.18 (95% CI: 1.00, 1.39), and then current smokers 1.06 (95% CI: 0.97, 1.15). In addition, meta-estimates for adenocarcinoma associated with PM2.5 and PM10 were 1.40 (95% CI: 1.07, 1.83) and 1.29 (95% CI: 1.02, 1.63), respectively. Conclusion: The results of these analyses, and the decision of the IARC Working Group to classify PM and outdoor air pollution as carcinogenic (Group 1), further justify efforts to reduce exposures to air pollutants that can arise from many sources. Citation: Hamra GB, Guha N, Cohen A, Laden F, Raaschou-Nielsen O, Samet JM, Vineis P, Forastiere F, Saldiva P, Yorifuji T, Loomis D. 2014. Outdoor particulate matter exposure and lung cancer: a systematic review and meta-analysis. Environ Health Perspect 122:906-911; http://dx.doi.org/10.1289/ehp.1408092
The concept of “exposome” has been introduced to allow an empowerment of environmental research, by improving measurements of external stressors and of internal biological changes, the latter taking ...advantage of advancements in high-throughput technologies called “omics.” Here, I discuss the application of the exposome concept and techniques to the field of air pollution. I address some open issues in air pollution science, such as the effects of components in a mixture, low doses, biological pathways, and a meaningful interpretation of omic findings in the context of “hallmarks” of disease. The exposome may represent the next frontier for the regulation of low-dose environmental contaminants.
The purpose of this review is to evaluate progress in molecular epidemiology over the past 24 years in cancer etiology and
prevention to draw lessons for future research incorporating the new ...generation of biomarkers. Molecular epidemiology was
introduced in the study of cancer in the early 1980s, with the expectation that it would help overcome some major limitations
of epidemiology and facilitate cancer prevention. The expectation was that biomarkers would improve exposure assessment, document
early changes preceding disease, and identify subgroups in the population with greater susceptibility to cancer, thereby increasing
the ability of epidemiologic studies to identify causes and elucidate mechanisms in carcinogenesis. The first generation of
biomarkers has indeed contributed to our understanding of risk and susceptibility related largely to genotoxic carcinogens.
Consequently, interventions and policy changes have been mounted to reduce risk from several important environmental carcinogens.
Several new and promising biomarkers are now becoming available for epidemiologic studies, thanks to the development of high-throughput
technologies and theoretical advances in biology. These include toxicogenomics, alterations in gene methylation and gene expression,
proteomics, and metabonomics, which allow large-scale studies, including discovery-oriented as well as hypothesis-testing
investigations. However, most of these newer biomarkers have not been adequately validated, and their role in the causal paradigm
is not clear. There is a need for their systematic validation using principles and criteria established over the past several
decades in molecular cancer epidemiology. (Cancer Epidemiol Biomarkers Prev 2007;16(10):1954–65)
Longitudinal evidence linking urban greenspace to reduced rates of all-cause and cause-specific mortality has mostly been established using greenness measures of limited specificity such as ...vegetation indices. Evidence on specific green space types, including private residential gardens is less well established.
We examined associations of greenspace with all-cause, non-injury, cardiovascular disease (CVD) and respiratory disease deaths in UK Biobank – a national prospective cohort of adults with linked Office for National Statistics mortality records. We included private residential gardens and other greenspace types, e.g., public parks, sport facilities, using categories from Ordnance Survey MasterMap™ Greenspace. We used Cox proportional hazards models, adjusted for individual and area-level covariates, and stratified analyses by sex, household income, and area-level deprivation. In sensitivity analyses, we further adjusted for air pollution, road-traffic noise, indirect tobacco smoke exposure, and physical activity, and restricted analyses to non-movers.
In 232,926 participants, we observed 13,586 all-cause, 13,159 non-injury, 2,796 cardiovascular (CVD), and 968 respiratory disease deaths. Private residential garden cover showed inverse associations with all-cause, non-injury, CVD, and chronic respiratory disease mortality, after adjustment for covariates and other types of greenspace, with hazard ratios and 95 % confidence intervals of 0.94 (0.91, 0.97), 0.95 (0.92, 0.97), 0.92 (0.86, 0.98) and 0.87 (0.78, 0.98), respectively, per interquartile range (IQR) increase in private residential garden cover (IQR = 21.6 % increase within 100 m buffer). Other greenspace types showed weaker inverse associations with CVD and chronic respiratory disease mortality than private residential gardens. Sex, household income, and area level deprivation modified associations. Findings were robust to sensitivity analyses.
Our finding that private residential gardens substantially contributed to inverse associations of total greenspace with premature mortality has implications for public health and urban planning. Inequities in access, ownership, views and use of private residential gardens, and potential health inequities, should be addressed.
Background: Drinking water from natural sources in coastal Bangladesh has become contaminated by varying degrees of salinity due to saltwater intrusion from rising sea levels, cyclone and storm ...surges, and upstream withdrawal of freshwater. Objective: Our objective was to estimate salt intake from drinking water sources and examine environmental factors that may explain a seasonal excess of hypertension in pregnancy. Methods: Water salinity data (1998-2000) for Dacope, in rural coastal Bangladesh, were obtained from the Centre for Environment and Geographic Information System in Bangladesh. Information on drinking water sources, 24-hr urine samples, and blood pressure was obtained from 343 pregnant Dacope women during the dry season (October 2009 through March 2010). The hospitalbased prevalence of hypertension in pregnancy was determined for 969 pregnant women (July 2008 through March 2010). Results: Average estimated sodium intakes from drinking water ranged from 5 to 16 g/day in the dry season, compared with 0.6-1.2 g/day in the rainy season. Average daily sodium excretion in urine was 3.4 g/day (range, 0.4— 7.7 g/day). Women who drank shallow tube-well water were more likely to have urine sodium > 100 mmol/day than women who drank rainwater odds ratio (OR) = 2.05; 95% confidence interval (CI), 1.11-3.80. The annual hospital prevalence of hypertension in pregnancy was higher in the dry season (OR = 12.2%; 95% CI, 9.5—14.8) than in the rainy season (OR = 5.1%; 95% CI, 2.91-7.26). Conclusions: The estimated salt intake from drinking water in this population exceeded recommended limits. The problem of saline intrusion into drinking water has multiple causes and is likely to be exacerbated by climate change—induced sea-level rise.
Chronic inflammation has been proposed as having a prominent role in the construction of social inequalities in health. Disentangling the effects of early life and adulthood social disadvantage on ...inflammation is key in elucidating biological mechanisms underlying socioeconomic disparities. Here we explore the relationship between socioeconomic position (SEP) across the life course and inflammation (as measured by CRP levels) in up to 23,008 participants from six European cohort studies from three countries conducted between 1958 and 2013. We find a consistent inverse association between SEP and CRP across cohorts, where participants with a less advantaged SEP have higher levels of inflammation. Educational attainment is most strongly related to inflammation, after adjusting for health behaviours, body mass index and later-in-life SEP. These findings suggest socioeconomic disadvantage in young adulthood is independently associated with later life inflammation calling for further studies of the pathways operating through educational processes.
Long Covid: where we stand and challenges ahead Mantovani, Alberto; Morrone, Maria Concetta; Patrono, Carlo ...
Cell death and differentiation,
10/2022, Volume:
29, Issue:
10
Journal Article
Peer reviewed
Open access
Abstract
Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially as Long Covid, has been defined as a constellation of signs and symptoms which persist for weeks ...or months after the initial SARS-CoV-2 infection. PASC affects a wide range of diverse organs and systems, with manifestations involving lungs, brain, the cardiovascular system and other organs such as kidney and the neuromuscular system. The pathogenesis of PASC is complex and multifactorial. Evidence suggests that seeding and persistence of SARS-CoV-2 in different organs, reactivation, and response to unrelated viruses such as EBV, autoimmunity, and uncontrolled inflammation are major drivers of PASC. The relative importance of pathogenetic pathways may differ in different tissue and organ contexts. Evidence suggests that vaccination, in addition to protecting against disease, reduces PASC after breakthrough infection although its actual impact remains to be defined. PASC represents a formidable challenge for health care systems and dissecting pathogenetic mechanisms may pave the way to targeted preventive and therapeutic approaches.
Summary Molecular data are now widely used in epidemiological studies to investigate the transmission, distribution, biology, and diversity of pathogens. Our objective was to establish ...recommendations to support good scientific reporting of molecular epidemiological studies to encourage authors to consider specific threats to valid inference. The statement Strengthening the Reporting of Molecular Epidemiology for Infectious Diseases (STROME-ID) builds upon the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative. The STROME-ID statement was developed by a working group of epidemiologists, statisticians, bioinformaticians, virologists, and microbiologists with expertise in control of infection and communicable diseases. The statement focuses on issues relating to the reporting of epidemiological studies of infectious diseases using molecular data that were not addressed by STROBE. STROME-ID addresses terminology, measures of genetic diversity within pathogen populations, laboratory methods, sample collection, use of molecular markers, molecular clocks, timeframe, multiple-strain infections, non-independence of infectious-disease data, missing data, ascertainment bias, consistency between molecular and epidemiological data, and ethical considerations with respect to infectious-disease research. In total, 20 items were added to the 22 item STROBE checklist. When used, the STROME-ID recommendations should advance the quality and transparency of scientific reporting, with clear benefits for evidence reviews and health-policy decision making.
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