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Background: From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer.Methods: We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls.Results: ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110, 110 to 800, and >800 μg/L were 1.00, 1.88 [95% confidence interval (CI), 0.96–3.71], and 5.24 (3.05–9.00; Ptrend < 0.001) for lung cancer, and 1.00, 2.94 (1.29–6.70), and 8.11 (4.31–15.25; Ptrend < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed.Conclusion: Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure.Impact: Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. Cancer Epidemiol Biomarkers Prev; 23(8); 1529–38. ©2014 AACR.

PDF - 115K, Table S1. Comparison of subjects included in this analysis to subjects excluded because they had high exposures both in early life and adulthood. Table S2. Comparison of residences of the Chile case control study controls at the time of ascertainment to the 2002 Chile census. Table S3. Cancer odds ratios in subjects exposed in utero and childhood using different age categories to define early-life exposure.

Objectives: to develop and implement a follow-up protocol for Biomonitoring California study participants with elevated levels of urinary arsenic, particularly inorganic forms. Methods: We selected 20 μg/L as the level of concern for urinary inorganic arsenic; samples with total arsenic ≥20 μg/L were speciated. Participants with elevated inorganic arsenic were notified of their level and invited to participate in a telephone survey to help determine possible exposure sources. We illustrate the protocol in four Biomonitoring California studies, which collected samples from 2010–2013 in locations across the state. Results: 48 participants in the four studies had elevated urinary inorganic arsenic levels. Consumption of rice and rice-based products was the most commonly identified potential source of inorganic arsenic exposure. Conclusions: Of 48 participants with elevated inorganic arsenic, 27 would have been missed if we had used the previously published threshold of 50 µg/L total arsenic to identify urine samples for speciation. This protocol fills a gap in the clinical literature by providing a more health-protective approach to identify individuals with elevated urinary inorganic arsenic and help determine potentially significant exposure sources.

Summary Background Non-Hodgkin lymphoma comprises a heterogeneous group of cancers with unresolved aetiology, although risk factors include environmental exposures to toxic chemicals. Although the ubiquitous pollutant benzene is an established leukemogen, its potential to cause non-Hodgkin lymphoma has been widely debated. We aimed to examine the potential link between benzene exposure and risk of non-Hodgkin lymphoma in humans by evaluating a wide array of cohort and case-control studies using electronic systematic review. Methods We did a comprehensive systematic review and meta-analysis of all qualified human epidemiological studies that assessed the relationship between benzene exposure and non-Hodgkin lymphoma. We queried the PubMed and Embase databases for relevant articles published before June 5, 2019, and applied the SysRev platform for study selection. All peer-reviewed human cohort and case-control studies that reported non-Hodgkin lymphoma risk estimates specifically for benzene exposure were eligible for inclusion. Studies that calculated relative risks (RRs) for industries or job types without identifying those specifically exposed to benzene, that combined non-Hodgkin lymphoma with other cancer types, or that reported many different solvent exposures together were excluded. From each study, two investigators independently extracted information on the study design, location, years, sample size, participation rates, age, sex, sources of cases and controls, diagnosis, histological verification, exposure assessment, results, adjustment, and statistical analysis, and subsequently assessed study quality. We calculated the meta-analysis relative risk (meta-RR) and CIs using the fixed effect and random effect models, as well as assessing publication bias. Findings Our search yielded 2481 articles. After screening and removal of duplicates, 20 case-control studies and eight cohort studies were included in our meta-analysis, which included a total of 9587 patients with non-Hodgkin lymphoma. We reported an increased meta-relative risk (meta-RR) of 33% in highly exposed groups, when data were available (meta-RR 1·33 [95% CI 1·13–1·57], n=28). The meta-RR rose to 1·51 (1·22–1·87, n=18) in the studies that provided results specifically for highly exposed individuals. In particular, we reported a doubling of this risk for diffuse large B-cell lymphoma, a major non-Hodgkin lymphoma subtype (1·67 [1·01–2·77]). We also detected increased risks for follicular lymphoma (1·47 [0·95–2·27]) and hairy cell leukaemia (1·77 [0·99–3·16]), though they were not statistically significant. Funnel plot, Egger's test (p=0·77) and Begg's test (p=0·98) did not show evidence of publication bias. We evaluated the major aspects of causal inference and found evidence to support all the Hill considerations for assigning causation. Interpretation Our findings suggest a causal link between benzene exposure and non-Hodgkin lymphoma, especially for diffuse large B-cell lymphoma. Funding National Institute of Environmental Health Sciences.

Background Arsenic (As) exposure through drinking water is a global public health concern. Epigenetic dysregulation including changes in DNA methylation (DNAm), may be involved in arsenic toxicity. Epigenome-wide association studies (EWAS) of arsenic exposure have been restricted to single populations and comparison across EWAS has been limited by methodological differences. Leveraging data from epidemiological studies conducted in Chile and Bangladesh, we use a harmonized data processing and analysis pipeline and meta-analysis to combine results from four EWAS. Methods DNAm was measured among adults in Chile with and without prenatal and early-life As exposure in PBMCs and buccal cells (N = 40, 850K array) and among men in Bangladesh with high and low As exposure in PBMCs (N = 32, 850K array; N = 48, 450K array). Linear models were used to identify differentially methylated positions (DMPs) and differentially variable positions (DVPs) adjusting for age, smoking, cell type, and sex in the Chile cohort. Probes common across EWAS were meta-analyzed using METAL, and differentially methylated and variable regions (DMRs and DVRs, respectively) were identified using comb-p. KEGG pathway analysis was used to understand biological functions of DMPs and DVPs. Results In a meta-analysis restricted to PBMCs, we identified one DMP and 23 DVPs associated with arsenic exposure; including buccal cells, we identified 3 DMPs and 19 DVPs (FDR LRRC27 was identified as a DMR and DVR. Arsenic-associated KEGG pathways included lysosome, autophagy, and mTOR signaling, AMPK signaling, and one carbon pool by folate. Conclusions Using a two-step process of (1) harmonized data processing and analysis and (2) meta-analysis, we leverage four DNAm datasets from two continents of individuals exposed to high levels of As prenatally and during adulthood to identify DMPs and DVPs associated with arsenic exposure. Our approach suggests that standardizing analytical pipelines can aid in identifying biological meaningful signals.

Arsenic contamination in drinking water is one of the major health issues worldwide. Over 140 million people from 50+ countries are exposed to drinking water containing arsenic at levels above “safe” levels of 10 μg/L. Several studies indicate that chronic arsenic exposure is associated with the development of carcinogenic changes in the lungs, bladder, liver, and skin and other potential health problems. In this project, we aim to characterize bladder cancer mutational signatures and somatic mutations in a cohort of bladder cancer patients known to have been highly exposed to arsenic in northern Chile by using whole-exome sequencing (WES). We analyzed WES data and identified somatic mutations and mutational signatures using Mutec2 and SigProfiler. Preliminary analyses from a small number of exposed patients identified two mutational signatures, previously described as having “unknown” etiology, that showed an association with arsenic exposure. We are currently validating these findings in additional samples and with functional studies. Alma Poceros-Coba Ph.D. Candidate is the recipient of the Conacyt-UC-MEXUS Doctoral Fellowship and is the recipient of the UCDCCC Travel Award. Citation Format: Alma A. Poceros-Coba, Ana Estrada-Florez, Ted Toal, Paul Lott, Macarena Garrido, Craig Steinmaus, Catterina Ferrecio R., Luis Carvajal-Carmona. Elucidating arsenic dependent carcinogenesis in humans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 229.

Objectives Abacavir's potential to cause cardiovascular disease (CVD) among people living with HIV (PLWH) is debated. We conduct a systematic review and meta-analyses to assess CVD risk from recent and cumulative abacavir exposure. Methods We searched Medline, Embase, Web of Science, abstracts from Conference on Retroviruses and Opportunistic Infections, and International AIDS Society/AIDS Conferences and bibliographies of review articles to identify research studies published through 2018 on CVD risk associated with abacavir exposure among PLWH. Studies assessing risk of CVD associated with recent (exposure within last 6 months) or cumulative abacavir exposure across all age-groups were eligible. Risks were quantified using fixed- and random-effects models. Results Of 378 unique citations, 68 full-text research articles and abstracts were reviewed. Seventeen studies assessed risk of CVD from recent or cumulative abacavir exposure. Summary relative risk (sRR) is increased for recent exposure ( n =16 studies, sRR=1.61; 95% confidence interval: 1.48–1.75), higher in antiretroviral-therapy-naive population ( n =5, 1.91; 1.48–2.46) and all studies reported RR>1. The sRR for recent exposure was similarly increased for the outcome of acute myocardial infarction, and for studies that adjusted for substance abuse, smoking, prior CVD, traditional CVD risk factors, and CD4 cell-count/HIV viral load. The sRR was increased for cumulative abacavir exposure (per year) ( n =4, 1.12; 1.05–1.20) but no increase was seen after adjusting for recent exposure ( n =5, 1.00; 0.93–1.08). Conclusions Our findings suggest an increased risk of CVD from recent abacavir exposure. The risk remained elevated after adjusting for potential confounders. Further investigations are needed to understand CVD risk from cumulative exposure.

While there is significant investigation and investment in brain and neurodegenerative disease research, current understanding of the etiologies of illnesses like Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and brain cancer remains limited. Environmental exposure to the pollutant formaldehyde, an emerging neurotoxin widely used in industry, is suspected to play a critical role in mediating these disorders, although findings are limited and inconsistent. Focusing on highly exposed groups, we performed a meta-analysis of human epidemiological studies of formaldehyde and neurodegenerative disease (N= 19) or brain tumors (N=12). To assess the biological plausibility of observed associations, we then conducted a bioinformatics analysis using WikiPathways and the Comparative Toxicogenomics Database and identified candidate genes and pathways that may be related to these interactions. We reported the meta-relative risk (meta-RR) of ALS following high exposures to formaldehyde was increased by 78% (meta-RR=1.78, 95% confidence interval, CI 1.20-2.65). Similarly, the meta-RR for brain cancer was increased by 71% (meta-RR=1.71; 95% CI 1.07-2.73) among highly exposed individuals. Multiple sensitivity analyses did not reveal sources of heterogeneity or bias. Our bioinformatics analysis revealed that the oxidative stress genes superoxide dismutase (SOD1, SOD2) and the pro-inflammatory marker tumor necrosis factor (TNF) were identified as the top relevant genes, and the folate metabolism, vitamin B12 metabolism, and the ALS pathways were highly affected by formaldehyde and related to the most brain diseases of interest. Further inquiry revealed the two metabolic pathways are also intimately tied with the formaldehyde cycle. Overall, our bioinformatics analysis supports the link of formaldehyde exposure to ALS or brain tumor reported from our meta-analysis. This new multifactorial approach enabled us to both interrogate the robustness of the epidemiological data and identify genes and pathways that may be involved in these interactions, ultimately lending strong evidence and potential biological plausibility for the association between formaldehyde exposure and brain disease.

PURPOSE OF REVIEW: Arsenic is associated with cancer, heart disease, diabetes, and other outcomes that are also related to obesity. These similar effects raise the possibility that arsenic plays a role in obesity causation. They also raise the possibility that obesity may be an important effect modifier of arsenic-caused disease. This review summarizes the complex relationship between arsenic and obesity, with an emphasis on current research from human studies. RECENT FINDINGS: Experimental studies provide some evidence that arsenic could play a role in obesity pathogenesis. To date, however, these associations have not been confirmed in human studies. In contrast, several epidemiologic studies have shown that the risks of arsenic-caused disease are markedly higher in obese individuals, highlighting obesity as an important susceptibility factor. SUMMARY: Arsenic exposure and obesity are prevalent and widespread. Research identifying vulnerable populations, including obese individuals, could lead to new interventions having broad public health effects.

Supplemental Digital Content is available in the text., Background: We previously reported chronic respiratory effects in children who were then 7–17 years of age in Matlab, Bangladesh. One group of children had been exposed to high concentrations of arsenic in drinking water in utero and early childhood (average 436 µg/L), and the other group of children were never known to have been exposed to >10 µg/L. The exposed children, both males and females, had marked increases in chronic respiratory symptoms. Methods: The current study involves a further follow-up of these children now 14–26 years of age with 463 located and agreeing to participate. They were interviewed for respiratory symptoms and lung function was measured. Data were collected on smoking, body mass index (BMI), and number of rooms in the house as a measure of socioeconomic status. Results: Respiratory effects were still present in males but not females. In the high exposure group (>400 µg/L in early life) the odds ratio (OR) among male participants for dry cough in the last 12 months was 2.36 (95% confidence interval [CI] = 1.21, 4.63, P = 0.006) and for asthma OR = 2.51 (95% CI = 1.19, 5.29, P = 0.008). Forced vital capacity (FVC) was reduced in males in the early life high-exposure group compared with those never exposed (−95ml, P = 0.04), but not in female participants. Conclusions: By the age range 14–26, there was little remaining evidence of chronic respiratory effects in females but pronounced effects persisted in males. Mechanisms for the marked male female differences warrant further investigation along with further follow-up to see if respiratory effects continue in males.

BACKGROUND: The prevalence of type 2 diabetes (T2D) has more than doubled since 1980. Poor nutrition, sedentary lifestyle, and obesity are among the primary risk factors. While an estimated 70% of cases are attributed to excess adiposity, there is an increased interest in understanding the contribution of environmental agents to diabetes causation and severity. Arsenic is one of these environmental chemicals, with multiple epidemiology studies supporting its association with T2D. Despite extensive research, the molecular mechanism by which arsenic exerts its diabetogenic effects remains unclear. OBJECTIVES: We conducted a literature search focused on arsenite exposure in vivo and in vitro, using relevant end points to elucidate potential mechanisms of oral arsenic exposure and diabetes development. METHODS: We explored experimental results for potential mechanisms and elucidated the distinct effects that occur at high vs. low exposure. We also performed network analyses relying on publicly available data, which supported our key findings. RESULTS: While several mechanisms may be involved, our findings support that arsenite has effects on whole-body glucose homeostasis, insulin-stimulated glucose uptake, glucose-stimulated insulin secretion, hepatic glucose metabolism, and both adipose and pancreatic beta-cell dysfunction. DISCUSSION: This review applies state-of-the-science approaches to identify the current knowledge gaps in our understanding of arsenite on diabetes development.

Background Sit-stand workstations are proposed solutions to reduce sedentary time at work. Numerous companies are using them to mitigate health concerns such as musculoskeletal discomfort. Objective To review the literature on sit-stand workstations and low back discomfort. Method We conducted a meta-analysis on literature published before 17 November 2016 that addressed the relationship between sit-stand workstations and musculoskeletal discomfort, focusing on the low back. Results Twelve articles were identified and eight that presented results in means (SD) were included. Among a pain-free population, the standardised mean difference was -0.230 for low back discomfort with use of sit-stand workstations. When applying the SMD to studies using the 10-point pain scale, the effect estimates ranged between -0.30 and -0.51. Conclusion sit-stand workstations may reduce low back pain among workers. Further research is needed to help quantify dosage parameters and other health outcomes. Practitioner Summary: In a sedentary population, changing posture may reduce the chance of developing low back pain. The literature lacks studies on specific populations such as those who have pre-existing low back pain and also does not adequately address the dosage of sit-stand time required to help reduce pain.

Background Region II in northern Chile (population 442 570) experienced a sudden major increase in arsenic water concentrations in 1958 in the main city of Antofagasta, followed by a major reduction in exposure when an arsenic removal plant was installed in 1970. It provides a unique opportunity to study latency effects of exposure to arsenic, and this is the first study with mortality data up to 40 years after exposure reduction. Methods We previously identified high mortality rates in Region II up to the year 2000. Here we present rate ratios (RRs) for Region II compared with all the rest of Chile from 2001 to 2010, and with unexposed Region V (population 1 539 852) for all years from 1950 to 2010. All statistical tests were one-sided. Results From 2001 to 2010, comparing Region II with the rest of Chile, lung and bladder mortality were still greatly elevated (RR = 3.38, 95% confidence interval [CI] = 3.19 to 3.58, P < .001 for lung cancer in men; RR = 2.41, 95% CI = 2.20 to 2.64, P < .001 for lung cancer in women; RR = 4.79, 95% CI = 4.20 to 5.46, P < .001 for bladder cancer in men; RR = 6.43, 95% CI = 5.49 to 7.54, P < .001 for bladder cancer in women). Kidney cancer mortality was also elevated (RR = 1.75, 95% CI = 1.49 to 2.05, P < .001 for men; RR = 2.09, 95% CI = 1.69 to 2.57, P < .001 for women). Earlier short latency acute myocardial infarction mortality increases had subsided. Conclusions Lung, bladder, and kidney cancer mortality due to arsenic exposure have very long latencies, with increased risks manifesting 40 years after exposure reduction. Our findings suggest that arsenic in drinking water may involve one of the longest cancer latencies for a human carcinogen.

Inter-individual differences in arsenic metabolism have been linked to arsenic-related disease risks. Arsenic (+3) methyltransferase (AS3MT) is the primary enzyme involved in arsenic metabolism, and we previously demonstrated in vitro that N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) also methylates the toxic inorganic arsenic (iAs) metabolite, monomethylarsonous acid (MMA), to the less toxic dimethylarsonic acid (DMA). Here, we evaluated whether AS3MT and N6AMT1 gene polymorphisms alter arsenic methylation and impact iAs-related cancer risks. We assessed AS3MT and N6AMT1 polymorphisms and urinary arsenic metabolites (%iAs, %MMA, %DMA) in 722 subjects from an arsenic-cancer case-control study in a uniquely exposed area in northern Chile. Polymorphisms were genotyped using a custom designed multiplex, ligation-dependent probe amplification (MLPA) assay for 6 AS3MT SNPs and 14 tag SNPs in the N6AMT1 gene. We found several AS3MT polymorphisms associated with both urinary arsenic metabolite profiles and cancer risk. For example, compared to wildtypes, individuals carrying minor alleles in AS3MT rs3740393 had lower %MMA (mean difference = −1.9%, 95% CI: −3.3, −0.4), higher %DMA (mean difference = 4.0%, 95% CI: 1.5, 6.5), and lower odds ratios for bladder (OR = 0.3; 95% CI: 0.1–0.6) and lung cancer (OR = 0.6; 95% CI: 0.2–1.1). Evidence of interaction was also observed for both lung and bladder cancer between these polymorphisms and elevated historical arsenic exposures. Clear associations were not seen for N6AMT1. These results are the first to demonstrate a direct association between AS3MT polymorphisms and arsenic-related internal cancer risk. This research could help identify subpopulations that are particularly vulnerable to arsenic-related disease. Environ. Mol. Mutagen., 2017. © 2017 Wiley Periodicals, Inc.

Objective Evaluate whether arsenic-related diabetes risks differ between people of low and high socioeconomic status (SES). Methods We used data collected between October 2007-December 2010 from a population-based cancer case-control study (N = 1301) in Northern Chile, an area with high arsenic water concentrations (>800 µg/L) and comprehensive records of past exposure. Information on lifetime exposure and potential confounders were obtained using structured interviews, questionnaires, and residential histories. Type 2 diabetes was defined as physician-diagnosed diabetes or oral hypoglycemic medication use. SES was measured using a 14-point scale based on ownership of household appliances, cars, internet access, or use of domestic help. Logistic regression was used to assess the relationship between arsenic and diabetes within strata of SES. Results Among those with low SES, the odds ratio (OR) for diabetes comparing individuals in the highest to lowest tertile of lifetime average arsenic exposure was 2.12 (95% confidence interval (CI) 1.29–3.49, p = 0.004). However, those in the high SES group were not at increased risk (OR = 1.12 [95% CI = 0.72–1.73]). Conclusions Our findings provide evidence that risks of arsenic-related diabetes may be higher in Chile in people with low versus high SES.

Arsenic in drinking water is known to cause cancer and noncancer diseases, but little is known about its association with age at exposure. Here, we investigated age at arsenic exposure and mortality in Antofagasta, Chile, 30-40 years after a distinct period of very high water arsenic concentrations (1958-1970). We calculated standardized mortality ratios (SMRs) comparing Antofagasta with the rest of Chile for 2001-2010 by sex and age at potential first exposure. A remarkable relationship with age at first exposure was found for bronchiectasis, with increased risk in adults 30-40 years after exposure being confined to those who were in utero (SMR = 11.7, 95% confidence interval (CI): 4.3, 25.4) or aged 1-10 years (SMR = 5.4, 95% CI: 1.1, 15.8) during the high-exposure period. Increased SMRs for lung, bladder, and laryngeal cancer were evident for exposures starting at all ages, but the highest SMRs were for exposures beginning at birth (for bladder cancer, SMR = 16.0 (95% CI: 10.3, 23.8); for laryngeal cancer, SMR = 6.8 (95% CI: 2.2, 15.8); for lung cancer, SMR = 3.8 (95% CI: 2.9, 4.9)). These findings suggest that interventions targeting early-life arsenic exposure could have major impacts in reducing long-term mortality due to arsenic 30-40 years after exposure ends.

Perchlorate exposure occurs from ingestion of natural or man-made perchlorate in food or water. Perchlorate is used in a variety of industrial products including missile fuel, fireworks, and fertilizers, and industrial contamination of drinking water supplies has occurred in a number of areas. Perchlorate blocks iodide uptake into the thyroid and decreases the production of thyroid hormone, a critical hormone for metabolism, neurodevelopment, and other physiologic functions. Occupational and clinical dosing studies have not identified clear adverse effects, but may be limited by small sample sizes, short study durations, and the inclusion of mostly healthy adults. Expanding evidence suggests that young children, pregnant women, fetuses, and people co-exposed to similarly acting agents may be especially susceptible to perchlorate. Given the ubiquitous nature of perchlorate exposure, and the importance of thyroid hormone for brain development, studying the impact of perchlorate on human health could have far-reaching public health implications.

In previous articles in the American Journal of Epidemiology (Am J Epidemiol. 2013;177(5):431–442) and American Journal of Public Health (Am J Public Health. 2013;103(10):1895–1901), Masters et al. reported age-specific hazard ratios for the contrasts in mortality rates between obesity categories. They corrected the observed hazard ratios for selection bias caused by what they postulated was the nonrepresentativeness of the participants in the National Health Interview Study that increased with age, obesity, and ill health. However, it is possible that their regression approach to remove the alleged bias has not produced, and in general cannot produce, sensible hazard ratio estimates. First, one must consider how many nonparticipants there might have been in each category of obesity and of age at entry and how much higher the mortality rates would have to be in nonparticipants than in participants in these same categories. What plausible set of numerical values would convert the (“biased”) decreasing-with-age hazard ratios seen in the data into the (“unbiased”) increasing-with-age ratios that they computed? Can these values be encapsulated in (and can sensible values be recovered from) 1 additional internal variable in a regression model? Second, one must examine the age pattern of the hazard ratios that have been adjusted for selection. Without the correction, the hazard ratios are attenuated with increasing age. With it, the hazard ratios at older ages are considerably higher, but those at younger ages are well below 1. Third, one must test whether the regression approach suggested by Masters et al. would correct the nonrepresentativeness that increased with age and ill health that I introduced into real and hypothetical data sets. I found that the approach did not recover the hazard ratio patterns present in the unselected data sets: The corrections overshot the target at older ages and undershot it at lower ages.

Background: Evidence suggests that prolonged exposure to arsenic through drinking water increases the risk of hypertension in adults. However, few studies have evaluated the impact of early life ar...

Background/Aim: The city of Antofagasta, the major city in northern Chile, had a specific period (1958-1970) with very high arsenic water concentrations of around 870 ug/L. We previously reported i...

Background: Long term exposure to arsenic through drinking water has been reported to increase the risk of chronic kidney diseases in adults. However, information on the impact of early life arseni...

Background Colonization with Staphylococcus aureus is a well-defined risk factor for disease in hospitals, which can range from minor skin infections to severe, systemic diseases. However, the generalizability of this finding has not been thoroughly investigated outside of the hospital environment. We aimed to assess the role of S. aureus colonization as a risk factor for disease in the community. Methods We performed a meta-analysis of observational studies and searched PubMed for articles published between December 1979 and May 23, 2016. We included cohort, cross-sectional, and case-control studies that reported quantitative estimates of both S. aureus colonization and disease statuses of all study subjects. We excluded studies on recently hospitalized subjects, long-term care facilities, surgery patients, dialysis patients, hospital staff, S. aureus outbreaks, and livestock-associated infections. Our meta-analysis was performed using random-effects analysis to obtain pooled odds ratios (ORs) to compare the odds of S. aureus disease with respect to S. aureus colonization status. Results We identified 3477 citations, of which 12 articles on 6998 subjects met the eligibility criteria. Overall, subjects colonized with S. aureus were more likely to progress to disease than those who were non-colonized: (OR 1.87, 95% CI 1.21–2.88, n = 7 studies). We observed a larger effect with methicillin-resistant S. aureus colonization (7.06, 4.60–10.84, n = 7 studies). However, the methicillin-sensitive S. aureus colonization was not associated with greater odds of disease (1.20, 0.69–2.06, n = 4 studies). Heterogeneity was present across studies in all of the subgroups: S. aureus (I2 = 95.0%, χ2 = 120.3, p

Background The prevalence of type 2 diabetes (T2D) has nearly doubled since 1980. Elevated body mass index (BMI) is the leading risk factor for T2D, mediated by inflammation and oxidative stress. Arsenic shares similar pathogenic processes, and may contribute to hyperglycemia and β-cell dysfunction. Objectives We assessed a unique situation of individuals living in Northern Chile with data on lifetime arsenic exposure to evaluate the relationship between arsenic and T2D, and investigate possible interactions with BMI. Methods We analyzed data collected from October 2007-December 2010 from an arsenic-cancer case-control study. Information on self-reported weight, height, smoking, diet, and other factors were obtained. Diabetes was defined by self-reported physician-diagnoses or use of hypoglycemic medication. A total of 1053 individuals, 234 diabetics and 819 without known diabetes were included. Results The T2D odds ratio (OR) for cumulative arsenic exposures of 610–5279 and ≥ 5280 μg/L-years occurring 40 years or more before interview were 0.97 (95% CI: 0.66–1.43) and 1.53 (95% CI: 1.05–2.23), respectively. Arsenic-associated T2D ORs were greater in subjects with increased BMIs. For example, the ORs for past cumulative exposures ≥ 5280 μg/L-years was 1.45 (95% CI: 0.74–2.84) in participants with BMIs Conclusions These findings identify increased odds of T2D with arsenic exposure, which are significantly increased in individuals with excess BMI.

Elevated body mass index (BMI) is a risk factor for cardiovascular disease, diabetes, cancer, and other diseases. Inflammation or oxidative stress induced by high BMI may explain some of these effects. Millions of people drink arsenic-contaminated water worldwide, and ingested arsenic has also been associated with inflammation, oxidative stress, and cancer.To assess the unique situation of people living in northern Chile exposed to high arsenic concentrations in drinking water and investigate interactions between arsenic and BMI, and associations with lung and bladder cancer risks.Information on self-reported body mass index (BMI) at various life stages, smoking, diet, and lifetime arsenic exposure was collected from 532 cancer cases and 634 population-based controls.In subjects with BMIs90th percentile in early adulthood (27.7 and 28.6 kg/m(2) in males and females, respectively), odds ratios (OR) for lung and bladder cancer combined for arsenic concentrations of100, 100-800 and800 µg/L were 1.00, 1.64 (95% CI, 1.19-2.27), and 3.12 (2.30-4.22). In subjects with BMIs ≥90th percentile in early adulthood, the corresponding ORs were higher: 1.00, 1.84 (0.75-4.52), and 9.37 (2.88-30.53), respectively (synergy index=4.05, 95% CI, 1.27-12.88). Arsenic-related cancer ORs20 were seen in those with elevated BMIs in both early adulthood and in later life. Adjustments for smoking, diet, and other factors had little impact.These findings provide novel preliminary evidence supporting the notion that environmentally-related cancer risks may be markedly increased in people with elevated BMIs, especially in those with an elevated BMI in early-life.

Perchlorate (ClO4−) is a ubiquitous environmental contaminant with high human exposure potential; it has both natural and man-made sources in the environment. Natural perchlorate forms in the atmosphere from where it deposits onto the surface of Earth, whereas synthetic perchlorate is manufactured as an oxidant for industrial, aerospace, and military applications. Perchlorate exposure can potentially cause adverse health effects in humans by interfering with the production of thyroid hormones through competitively blocking iodide uptake. To control and reduce perchlorate exposure, the contributions of different sources of perchlorate exposure need to be quantified. Thus, we demonstrate a novel approach for determining the contribution of different perchlorate exposure sources by quantifying stable and radioactive chlorine isotopes of perchlorate extracted from composite urine samples from two distinct populations: one in Atlanta, USA and one in Taltal, Chile (Atacama region). Urinary perchlorate from the Atlanta region resembles indigenous natural perchlorate from the southwestern USA [δ37Cl = +4.1 ± 1.0 ‰; 36Cl/Cl = 1811 (± 136) × 10−15], and urinary perchlorate from the Taltal, Chile region is similar to natural perchlorate in nitrate salt deposits from the Atacama Desert of northern Chile [δ37Cl = −11.0 ± 1.0 ‰; 36Cl/Cl = 254 (± 40) × 10−15]. Neither urinary perchlorate resembled the isotopic pattern found in synthetic perchlorate. These results indicate that natural perchlorate of regional provenance is the dominant exposure source for the two sample populations, and that chlorine isotope ratios provide a robust tool for elucidating perchlorate exposure pathways.

© 2014 © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Arsenic concentrations greater than 100 μg/L in drinking water are a known cause of cancer, but the risks associated with lower concentrations are less well understood. The unusual geology and good information on past exposure found in northern Chile are key advantages for investigating the potential long-term effects of arsenic. We performed a case-control study of lung cancer from 2007 to 2010 in areas of northern Chile that had a wide range of arsenic concentrations in drinking water. Previously, we reported evidence of elevated cancer risks at arsenic concentrations greater than 100 μg/L. In the present study, we restricted analyses to the 92 cases and 288 population-based controls who were exposed to concentrations less than 100 μg/L. After adjustment for age, sex, and smoking behavior, these exposures from 40 or more years ago resulted in odds ratios for lung cancer of 1.00, 1.43 (90% confidence interval: 0.82, 2.52), and 2.01 (90% confidence interval: 1.14, 3.52) for increasing tertiles of arsenic exposure, respectively (P for trend = 0.02). Mean arsenic water concentrations in these tertiles were 6.5, 23.0, and 58.6 μg/L. For subjects younger than 65 years of age, the corresponding odds ratios were 1.00, 1.62 (90% confidence interval: 0.67, 3.90), and 3.41 (90% confidence interval: 1.51, 7.70). Adjustments for occupation, fruit and vegetable intake, and socioeconomic status had little impact on the results. These findings provide new evidence that arsenic water concentrations less than 100 μg/L are associated with higher risks of lung cancer.

Background Elevated body mass index (BMI) and arsenic are both associated with cancer and with non-malignant lung disease. Using a unique exposure situation in Northern Chile with data on lifetime arsenic exposure, we previously identified the first evidence of an interaction between arsenic and BMI for the development of lung cancer. Objectives We examined whether there was an interaction between arsenic and BMI for the development of non-malignant lung disease. Methods Data on lifetime arsenic exposure, respiratory symptoms, spirometry, BMI, and smoking were collected from 751 participants from cities in Northern Chile with varying levels of arsenic water concentrations. Spirometry values and respiratory symptoms were compared across subjects in different categories of arsenic exposure and BMI. Results Adults with both a BMI above the 90th percentile (>33.9 kg/m 2 ) and arsenic water concentrations ≥11 µg/L exhibited high odds ratios (ORs) for cough (OR = 10.7, 95% confidence interval (CI): 3.03, 50.1), shortness of breath (OR = 14.2, 95% CI: 4.79, 52.4), wheeze (OR = 14.4, 95% CI: 4.80, 53.7), and the combined presence of any respiratory symptom (OR = 9.82, 95% CI: 4.22, 24.5). In subjects with lower BMIs, respiratory symptom ORs for arsenic water concentrations ≥11 µg/L were markedly lower. In never-smokers, reductions in forced vital capacity associated with arsenic increased as BMI increased. Analysis of the FEV 1 /FVC ratio in never-smokers significantly increased as BMI and arsenic concentrations increased. Similar trends were not observed for FEV 1 alone or in ever-smokers. Conclusions This study provides preliminary evidence that BMI may increase the risk for arsenic-related non-malignant respiratory disease.

BackgroundAt high medicinal doses perchlorate is known to decrease the production of thyroid hormone, a critical factor for fetal development. In a large and uniquely exposed cohort of pregnant women, we recently identified associations between environmental perchlorate exposures and decreased maternal thyroid hormone during pregnancy. Here, we investigate whether perchlorate might be associated with birthweight or preterm birth in the offspring of these women.MethodsMaternal urinary perchlorate, serum thyroid hormone concentrations, birthweight, gestational age, and urinary nitrate, thiocyanate, and iodide were collected in 1957 mother-infant pairs from San Diego County during 2000-2003, a period when the county's water supply was contaminated with perchlorate. Associations between perchlorate exposure and birth outcomes were examined using linear and logistic regression analyses adjusted for maternal age, weight, race/ethnicity, and other factors.ResultsPerchlorate was not associated with birth outcomes in the overall population. However, in analyses confined to male infants, log10 maternal perchlorate concentrations were associated with increasing birthweight (β=143.1gm, p=0.01), especially among preterm births (β=829.1g, p

Inter-individual differences in arsenic metabolism have been linked to arsenic-related disease risks. Arsenic (+3) methyltransferase (AS3MT) is the primary enzyme involved in arsenic metabolism, and we previously demonstrated in vitro that N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) also methylates the toxic inorganic arsenic (iAs) metabolite, monomethylarsonous acid (MMA), to the less toxic dimethylarsonic acid (DMA). Here, we evaluated whether AS3MT and N6AMT1 gene polymorphisms alter arsenic methylation and impact iAs-related cancer risks. We assessed AS3MT and N6AMT1 polymorphisms and urinary arsenic metabolites (%iAs, %MMA, %DMA) in 722 subjects from an arsenic-cancer case-control study in a uniquely exposed area in northern Chile. Polymorphisms were genotyped using a custom designed multiplex, ligation-dependent probe amplification (MLPA) assay for 6 AS3MT SNPs and 14 tag SNPs in the N6AMT1 gene. We found several AS3MT polymorphisms associated with both urinary arsenic metabolite profiles and cancer risk. For example, compared to wildtypes, individuals carrying minor alleles in AS3MT rs3740393 had lower %MMA (mean difference = -1.9%, 95% CI: -3.3, -0.4), higher %DMA (mean difference = 4.0%, 95% CI: 1.5, 6.5), and lower odds ratios for bladder (OR = 0.3; 95% CI: 0.1-0.6) and lung cancer (OR = 0.6; 95% CI: 0.2-1.1). Evidence of interaction was also observed for both lung and bladder cancer between these polymorphisms and elevated historical arsenic exposures. Clear associations were not seen for N6AMT1. These results are the first to demonstrate a direct association between AS3MT polymorphisms and arsenic-related internal cancer risk. This research could help identify subpopulations that are particularly vulnerable to arsenic-related disease. Environ. Mol. Mutagen. 58:411-422, 2017. © 2017 Wiley Periodicals, Inc.

Background A growing number of studies have identified an association between exposure to inorganic arsenic and hypertension. However, results have not been consistent across studies. Additional studies are warranted, given the global prevalence of both arsenic exposure and morbidity attributable to hypertension. Methods We analyzed data collected from October 2007-December 2010 for a population-based cancer case-control study in northern Chile. Data included lifetime individual arsenic exposure estimates and information on potential confounders for a total of 1266 subjects. Those self-reporting either a physician diagnosis of hypertension or use of an anti-hypertensive medication were classified as having hypertension (n=612). The association between hypertension and drinking water arsenic exposure was analyzed using logistic regression models. Results Compared to those in the lowest category for lifetime highest 5-year average arsenic exposure ( 623 μg/L) exposure categories had adjusted hypertension ORs of 1.49 (95% CI: 1.09, 2.05) and 1.65 (95% CI: 1.18, 2.32), respectively. Similar results were observed in analyses of lifetime cumulative exposures and analyses restricted to exposures from the distant past. Conclusions We identified evidence of increased odds of hypertension with exposure to arsenic in drinking water among study participants. Our findings add to the growing body of research supporting this association, which could have important public health implications.

Objectives Chromium VI (hexavalent chromium, Cr(VI)) is an established cause of lung cancer, but its association with gastrointestinal cancer is less clear. The goal of this study was to examine whether the current human epidemiological research on occupationally inhaled Cr(VI) supports the hypothesis that Cr(VI) is associated with human stomach cancer. Methods Following a thorough literature search and review of individual studies, we used meta-analysis to summarise the current epidemiological literature on inhaled Cr(VI) and stomach cancer, explore major sources of heterogeneity, and assess other elements of causal inference. Results We identified 56 cohort and case–control studies and 74 individual relative risk (RR) estimates on stomach cancer and Cr(VI) exposure or work in an occupation associated with high Cr(VI) exposure including chromium production, chrome plating, leather work and work with Portland cement. The summary RR for all studies combined was 1.27 (95% CI 1.18 to 1.38). In analyses limited to only those studies identifying increased risks of lung cancer, the summary RR for stomach cancer was higher (RR=1.41, 95% CI 1.18 to 1.69). Conclusions Overall, these results suggest that Cr(VI) is a stomach carcinogen in humans, which is consistent with the tumour results reported in rodent studies.

Background: From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer. Methods: We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls. Results: ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110, 110 to 800, and >800 μg/L were 1.00, 1.88 [95% confidence interval (CI), 0.96–3.71], and 5.24 (3.05–9.00; Ptrend < 0.001) for lung cancer, and 1.00, 2.94 (1.29–6.70), and 8.11 (4.31–15.25; Ptrend < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed. Conclusion: Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. Impact: Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. Cancer Epidemiol Biomarkers Prev; 23(8); 1529–38. ©2014 AACR.

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g.

Millions of people are exposed to arsenic in drinking water, which at high concentrations is known to cause lung cancer in humans. At lower concentrations, the risks are unknown. We enrolled 196 lung cancer cases and 359 controls matched on age and gender from western Nevada and Kings County, California in 2002-2005. After adjusting for age, sex, education, smoking and occupational exposures, odds ratios for arsenic concentrations ≥85 µg/L (median = 110 µg/L, mean = 173 µg/L, maximum = 1,460 µg/L) more than 40 years before enrollment were 1.39 (95% CI = 0.55-3.53) in all subjects and 1.61 (95% CI = 0.59-4.38) in smokers. Although odds ratios were greater than 1.0, these increases may have been due to chance given the small number of subjects exposed more than 40 years before enrollment. This study, designed before research in Chile suggested arsenic-related cancer latencies of 40 years or more, illustrates the enormous sample sizes needed to identify arsenic-related health effects in low-exposure countries with mobile populations like the U.S. Nonetheless, our findings suggest that concentrations near 100 µg/L are not associated with markedly high relative risks.

Background Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited. Methods This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7–17 years. Children with in utero and early life arsenic exposure were compared with children exposed to less than 10 µg/l in utero and throughout childhood. Because most children drank the same water as their mother had drunk during pregnancy, we could not assess only in utero or only childhood exposure. Results Children exposed in utero to more than 500 µg/l of arsenic were more than eight times more likely to report wheezing when not having a cold [odds ratio (OR) = 8.41, 95% confidence interval (CI): 1.66–42.6, P < 0.01] and more than three times more likely to report shortness of breath when walking on level ground (OR = 3.86, 95% CI: 1.09–13.7, P = 0.02) and when walking fast or climbing (OR = 3.19, 95% CI: 1.22–8.32, P < 0.01]. However, there was little evidence of reduced lung function in either exposure category. Conclusions Children with high in utero and early life arsenic exposure had marked increases in several chronic respiratory symptoms, which could be due to in utero exposure or to early life exposure, or to both. Our findings suggest that arsenic in water has early pulmonary effects and that respiratory symptoms are a better marker of early life arsenic toxicity than changes in lung function measured by spirometry.

Exposure to arsenic (As) in drinking water is a major health concern. More than 100 million individuals are exposed to levels over the current World Health Organization standard of 10 µg/L worldwide. Arsenic is one of the few agents established as a human carcinogen prior to understanding its mechanism of carcinogenicity. OMIC technologies have enabled researchers to utilize agnostic approaches to explore new, unknown mechanisms through which As causes disease in exposed human populations. In this article, we present recent studies in which OMIC technologies have been used to explore differences in human biological samples to identify markers of exposure, disease susceptibility, and effect in As-exposed and/or diseased tissues.

Perchlorate, thiocyanate, and low iodine intake can all decrease iodide intake into the thyroid gland. This can reduce thyroid hormone production since iodide is a key component of thyroid hormone. Previous research has suggested that each of these factors alone may decrease thyroid hormone levels, but effect sizes are small. We hypothesized that people who have all three factors at the same time have substantially lower thyroid hormone levels than people who do not, and the effect of this combined exposure is substantially larger than the effects seen in analyses focused on only one factor at a time. Using data from the 2007-2008 National Health and Nutrition Examination Survey, subjects were categorized into exposure groups based on their urinary perchlorate, iodine, and thiocyanate concentrations, and mean serum thyroxine concentrations were compared between groups. Subjects with high perchlorate (n=1939) had thyroxine concentrations that were 5.0% lower (mean difference=0.40 μg/dl, 95% confidence interval=0.14-0.65) than subjects with low perchlorate (n=2084). The individual effects of iodine and thiocyanate were even smaller. Subjects with high perchlorate, high thiocyanate, and low iodine combined (n=62) had thyroxine concentrations 12.9% lower (mean difference=1.07 μg/dl, 95% confidence interval=0.55-1.59) than subjects with low perchlorate, low thiocyanate, and adequate iodine (n=376). Potential confounders had little impact on results. Overall, these results suggest that concomitant exposure to perchlorate, thiocyanate, and low iodine markedly reduces thyroxine production. This highlights the potential importance of examining the combined effects of multiple agents when evaluating the toxicity of thyroid-disrupting agents.

Following reports of high cytotoxicity and mutagenicity of monomethyl arsonous acid (MMA(III)) and early reports of urinary MMA(III) in arsenic-exposed individuals, MMA(III) has often been included in population studies. Use of urinary MMA(III) as an indicator of exposure and/or health risk is challenged by inconsistent results from field studies and stability studies, which indicate potential artifacts. We measured urinary arsenic species in children chronically exposed to arsenic in drinking water, using collection, storage, and analysis methods shown to conserve MMA(III). MMA(III) was easily oxidized in sample storage and processing, but recoveries of 80% or better in spiked urine samples were achieved. Attempts to preserve the distribution of MMA between trivalent and pentavalent forms using complexing agents were unsuccessful and MMA(III) spiked into treated urine samples actually showed lower stability than in untreated samples. In 643 urine samples from a highly exposed population from the Matlab district in Bangladesh stored for 3-6 months at ≤-70 °C, MMA(III) was detected in 41 samples, with an estimated median value of 0.3 μg/l, and levels of MMA(III) above 1 μg/l in only two samples. The low urinary concentrations in highly exposed individuals and known difficulties in preserving sample oxidation state indicate that urinary MMA(III) is not suitable for use as an epidemiological biomarker.

Woolf-King, S., Steinmaus, C. M., Reingold, A. L. & Hahn, J. A. (2013). An update on alcohol use and risk of HIV infection in sub-Saharan Africa: Meta-analysis and future research directions. International Journal of Alcohol and Drug Research, 2(1) , 99-110. doi: 10.7895/ijadr.v2i1.45 ( http://dx.doi.org/10.7895/ijadr.v2i1.45 ) Aims: Sub-Saharan Africa is disproportionately affected by HIV/AIDS, and growing evidence suggests that alcohol consumption is a co-occurring problem in the region. We conducted a meta-analysis on studies of alcohol use and HIV infection in sub-Saharan Africa in order to assess associations, evaluate heterogeneity in the literature, identify susceptible subgroups, and suggest avenues for future research. Design: We performed a systematic review, including published review articles and electronic database searches, and identified 35 studies on alcohol use and HIV. Setting and participants: All of the studies included in the meta-analysis occurred with adults in sub-Saharan Africa. Measurements: Pooled odds ratio ( OR ) estimates were calculated using both the fixed inverse variance weighting method and the random effects method when evidence of heterogeneity was present. Findings: The pooled OR estimate for all studies was 1.61 (95% CI: 1.44–1.80). The association between alcohol use and prevalence or incident HIV infection was particularly large among samples who reported problem drinking ( OR = 2.17, 95% CI: 1.64–2.87) and drinking in sexual contexts ( OR = 1.79, 95% CI: 1.55–2.06). Some evidence of publication bias was present; however, the OR remained statistically significant in small and large studies and with population-based and high-risk samples. Conclusions: These results suggest that alcohol consumption, particularly at high levels and in sexual contexts, is associated with an increased risk of HIV infection. An increased focus on methods that allow for more sensitive tests of the event-level association between alcohol consumption and risk of HIV infection may provide a better understanding of the causal mechanisms underlying this relationship.

We used meta-analysis to measure the effect of high-altitude climate therapy (HACT) on lung function outcomes in asthma, and systematically searched PubMed, Embase and www.elibrary.ru for publications appearing from 1970 to mid-2015. We included studies carried out with children or adults with an exposure of up to 12 weeks at an altitude of ≥1500 m above sea level. Changes in forced expiratory volume in 1 s (FEV1), FEV1/vital capacity ratio or peak expiratory flow rate as the HACT intervention outcomes were analysed. We included data for 907 participants (age range 4–58 years) from 21 studies, altogether including 28 substrata based on asthma type or severity. Only three of 21 included studies had high quality, whereas 93% of substudies reported lung function improvement with an overall pooled standardised mean difference (SMD) of 0.53 (95% CI 0.43–0.62). The measured effect of HACT was greater in adults (SMD 0.75, 95% CI 0.63–0.88, n=14) than in children (SMD 0.24, 95% CI 0.09–0.38, n=14). Studies at altitude >2000 m above sea level yielded the same effect as those at lower altitude. Based on a cut-point of a 0.50 change in SMD to define a meaningful clinical difference, HACT appears to have efficacy as an intervention. This extent of benefit appears to be limited to adults with asthma., High-altitude alpine therapy may be an effective intervention to improve lung function in patients with asthma http://ow.ly/u3i23008vU5

Introduction Regulatory agencies are evaluating the need for new standards on arsenic, and some have suggested that prospective studies should be given priority in this process. Methods We compared...

Background Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤ 10 μg/L. Results Compared to adults never exposed > 10 μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 mL decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 mL). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed.