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Bronchiectasis in Persons With Skin Lesions Resulting From Arsenic in Drinking Water
Abstract
Arsenic is a unique human carcinogen in that it causes lung cancer by exposure through ingestion (in drinking water) as well as through inhalation. Less is known about nonmalignant pulmonary disease after exposure to arsenic in drinking water.
We recruited 108 subjects with arsenic-caused skin lesions and 150 subjects without lesions from a population survey of over 7000 people in an arsenic-exposed region in West Bengal, India. Thirty-eight study participants who reported at least 2 years of chronic cough underwent high-resolution computed tomography (CT); these scans were read by investigators in India and the United States without knowledge of the presence or absence of skin lesions.
The mean (+/-standard deviation) bronchiectasis severity score was 3.4 (+/-3.6) in the 27 participants with skin lesions and 0.9 (+/-1.6) in the 11 participants without these lesions. In subjects who reported chronic cough, CT evidence of bronchiectasis was found in 18 (67%) participants with skin lesions and 3 (27%) subjects without skin lesions. Overall, subjects with arsenic-caused skin lesions had a 10-fold increased prevalence of bronchiectasis compared with subjects who did not have skin lesions (adjusted odds ratio=10; 95% confidence interval=2.7-37).
These results suggest that, in addition to being a cause of lung cancer, ingestion of high concentrations of arsenic in drinking water may be a cause of bronchiectasis.
... Multi-systemic involvement in this condition has been well established, including mucocutaneous, cardiovascular, neurological and hepatic disorders, along with malignant changes (1,3). Malignant (lung cancer) and non-malignant [bronchiectasis, diffuse interstitial lung disease (ILD), chronic obstructive lung disease] effects of chronic arsenic exposure on pulmonary system have been shown (4)(5)(6)(7)(8). In the small number of case series describing non-malignant pulmonary involvement, high-resolution computed tomography (HRCT) showed an increased number of bronchiectasis and pulmonary artery dilatation cases (4,5). ...
... Malignant (lung cancer) and non-malignant [bronchiectasis, diffuse interstitial lung disease (ILD), chronic obstructive lung disease] effects of chronic arsenic exposure on pulmonary system have been shown (4)(5)(6)(7)(8). In the small number of case series describing non-malignant pulmonary involvement, high-resolution computed tomography (HRCT) showed an increased number of bronchiectasis and pulmonary artery dilatation cases (4,5). However, there are not a large number of case series in the literature referring to arsenic exposure pulmonary involvement evaluated by HRCT. ...
... There are few studies where non-malignant effects of arsenic exposure on the pulmonary system were evaluated by HRCT (3,5,12). In a hospital-based study in Kolkata, West Bengal, nonmalignant lung diseases were evaluated by lung radiography. ...
Background:
The number of studies where non-malignant pulmonary diseases are evaluated after occupational arsenic exposure are very few.
Aims:
The aim of this study is to show the effects of occupational arsenic exposure on the lung by high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs).
Study design:
Retrospective cross-sectional study.
Methods:
In this study 256 workers who were suspected respiratory occupational arsenic exposure are included, having average age 32.9±7.8 years and working 3.5±2.7 years averagely. Hair and urinary arsenic levels are analysed. HRCT and PFTs are done.
Results:
In workers having occupational arsenic exposure HRCT showed 18.8% pulmonary involvement. In pulmonary involvement, pulmonary nodule with 64.5% was the most frequently seen lesion. The other findings of pulmonary involvement were 18.8% diffuse interstitial lung disease, 12.5% bronchiectasis, 27.1% bullae-emphysema. The mean age of patients having pulmonary involvement was higher and as well they were smoking more. The pulmonary involvement was 5.2 times more in patients having skin lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was significantly lower in patients of pulmonary involvement.
Conclusion:
Besides lung cancer, chronic occupational inhalation of arsenic exposure can cause non-malignant pulmonary findings as bronchiectasis, pulmonary nodule and diffuse interstitial lung diseases. Because of this, to detect the pulmonary involvement in the early stage, workers having occupational arsenic exposure should be followed by diffusion test and HRCT.
... Nine articles examined the implications from in utero/early life InAs exposure at different lifestages, including endpoints during infancy (Farzan et al., 2013(Farzan et al., , 2015Rahman et al., 2011;Raqib et al., 2009), childhood (Recio-Vega et al., 2014Smith et al., 2013), and adulthood (Dauphine et al., 2011;Smith et al., 2006Smith et al., , 2011. Thirteen publications stratified their results by sex (Parvez et al., 2013;Pesola et al., 2012;Dauphine et al., 2011;Smith et al., 1998Smith et al., , 2006Smith et al., , 2011Raqib et al., 2009;Mazumder et al., 2000Mazumder et al., , 2005von Ehrenstein et al., 2005;Milton et al., 2001;Tsai et al., 1999). One publication examined the relationship between arsenic metabolism and lung function (Recio-Vega et al., 2014). ...
... Articles examined symptoms individually or combined, and reported on anywhere from one to nineteen different symptom-related endpoints. Of the 18 publications on InAs and respiratory symptoms, 11 reported a statistically significant positive association between InAs and at least one respiratory symptom Bhattacharyya et al., 2014;Paul et al., 2013;Smith et al., 2013;Pesola et al., 2012;Parvez et al., 2010;Ghosh et al., 2007;Mazumder et al., 2000Mazumder et al., , 2005Guo et al., 2003;Milton et al., 2001). However seven did not find a significant association for any respiratory symptom assessed (Recio-Vega et al., 2014;Farzan et al., 2013Farzan et al., , 2015Amster et al., 2011;Dauphine et al., 2011;Nafees et al., 2011;von Ehrenstein et al., 2005). ...
... Cough. Fourteen publications examined the relationship between InAs and cough (Farzan et al., 2015;Bhattacharyya et al., 2014;Das et al., 2014;Recio-Vega et al., 2014;Smith et al., 2013;Amster et al., 2011;Dauphine et al., 2011;Nafees et al., 2011;Parvez et al., 2010;Mazumder et al., 2000Mazumder et al., , 2005von Ehrenstein et al., 2005;Guo et al., 2003;Milton et al., 2001). Publications commonly categorized cough by productive/non-productive and severity/frequency. ...
This systematic review synthesizes the diverse body of epidemiologic research accrued on inorganic arsenic exposure and respiratory health effects. Twenty-nine articles were identified that examined the relationship between inorganic arsenic exposure and respiratory outcomes (i.e. lung function, symptoms, acute respiratory infections, chronic non-malignant lung diseases, and non-malignant lung disease mortality). There was strong evidence of a general association between arsenic and non-malignant respiratory illness, including consistent evidence on lung function impairment, acute respiratory tract infections, respiratory symptoms, and non-malignant lung disease mortality. Overall, early life exposure (i.e. in utero and/or early-childhood) had a marked effect throughout the lifespan. This review also identified some research gaps, including limited evidence at lower levels of exposure (water arsenic <100μg/L), mixed evidence of sex differences, and some uncertainty on arsenic and any single non-malignant respiratory disease or pathological process. Common limitations, including potential publication bias; non-comparability of outcome measures across included articles; incomplete exposure histories; and limited confounder control attenuated the cumulative strength of the evidence as it relates to US populations. This systematic review provides a comprehensive assessment of the epidemiologic evidence and should be used to guide future research on arsenic's detrimental effects on respiratory health.
... Respiratory complications, including cough, chest sound, bronchitis, and asthma, were also observed [70]. Recent publications of arsenic-associated pulmonary effects support growing evidence indicating that long-term exposure increases risk of pulmonary tuberculosis [71] and pulmonary chronic infection and inflammation [72][73][74]. A population-based cohort study of 1552 infants born in Bangladesh [75] revealed dose-dependent increases in respiratory tract infection and diarrhea related to in utero arsenic exposure. ...
... A population-based cohort study of 1552 infants born in Bangladesh [75] revealed dose-dependent increases in respiratory tract infection and diarrhea related to in utero arsenic exposure. Respiratory tract infection might also be associated with arsenic-associated, adult non-malignant lung disease [71,72]. In southwestern Taiwan [76], individuals affected with Bowen's disease, a type of skin lesion typical of arsenic exposure, showed both cutaneous and systemic immune dysfunctions, probably due to the decreased expression of CD4 + cells, which are important factors for the recognition of antigens on the surface of a virusinfected cell. ...
... Sex-related differences in arsenic toxicity have been observed for skin [37] and respiratory manifestations [72], as women seem to be less sensitive, possibly due to sex hormone-related increased methylation capacity of arsenic in females compared to males. Differences in white blood cell (WBC) methylation by sex have also been observed in epidemiological studies [125]. ...
Increasing evidence suggests that inorganic arsenic, a major environmental pollutant, exerts immunosuppressive effects in epidemiological, in vitro, and animal models. The mechanisms, however, remain unclear, and little is known about variation in susceptibilities due to age and sex. We performed a review of the experimental and epidemiologic evidence on the association of arsenic exposure and immune diseases. The majority of the studies described arsenic as a potent immunosuppressive compound, though others have reported an increase in allergy and autoimmune diseases, suggesting that arsenic may also act as an immune system stimulator, depending on the dose or timing of exposure. Limited information, due to either the high concentrations of arsenic used in in vitro studies or the use of non-human data for predicting human risks, is available from experimental studies. Moreover, although there is emerging evidence that health effects of arsenic manifest differently between men and women, we found limited information on sex differences on the immunotoxic effects of arsenic. In conclusion, preliminary data show that chronic early-life exposure to arsenic might impair immune responses, potentially leading to increased risk of infections and inflammatory-like diseases during childhood and in adulthood. Further investigation to evaluate effects of arsenic exposure on the developing immune system of both sexes, particularly in human cells and using concentrations relevant to human exposure, should be a research priority.
... Arsenic has been associated with increased rates of pneumonia and with lung diseases such as bronchiectasis, tuberculosis, and COPD that are characterized by chronic or recurrent bacterial lung infection (D'Ippoliti et al. 2015;George et al. 2015;Mazumder et al. 2005;Smith et al. 2011). Given this, we hypothesized that arsenic may compromise pulmonary host defense and reasoned that a murine model of bacterial pneumonia might provide insight into the underlying mechanisms. ...
... In recent years, a growing number of epidemiologic reports have linked arsenic exposure via drinking water with a wide range of respiratory symptoms, signs, and diseases (D'Ippoliti et al. 2015;Mazumder et al. 2005;Steinmaus et al. 2016). In parallel, controlled exposure studies in rodents have suggested that the lung, perhaps due to its local arsenic metabolism and highly oxidizing microenvironment, may be uniquely susceptible to toxicity from orally ingested arsenic (Yamanaka et al. 1989). ...
Background:
Arsenic exposure via drinking water impacts millions of people worldwide. Although arsenic has been associated epidemiologically with increased lung infections, the identity of the lung cell types targeted by peroral arsenic and the associated immune mechanisms remain poorly defined.
Objectives:
We aimed to determine the impact of peroral arsenic on pulmonary antibacterial host defense.
Methods:
Female C57BL/6 mice were administered drinking water with 0, 250 ppb, or 25 ppm sodium arsenite for 5 wk and then challenged intratracheally with Klebsiella pneumoniae, Streptococcus pneumoniae, or lipopolysaccharide. Bacterial clearance and immune responses were profiled.
Results:
Arsenic had no effect on bacterial clearance in the lung or on the intrapulmonary innate immune response to bacteria or lipopolysaccharide, as assessed by neutrophil recruitment to, and cytokine induction in, the airspace. Alveolar macrophage TNFα production was unaltered. By contrast, arsenic-exposed mice had significantly reduced plasma TNFα in response to systemic lipopolysaccharide challenge, together suggesting that the local airway innate immune response may be relatively preserved from arsenic intoxication. Despite intact intrapulmonary bacterial clearance during pneumonia, arsenic-exposed mice suffered dramatically increased bacterial dissemination to the bloodstream. Mechanistically, this was linked to increased respiratory epithelial permeability, as revealed by intratracheal FITC-dextran tracking, serum Club Cell protein 16 measurement, and other approaches. Consistent with barrier disruption at the alveolar level, arsenic-exposed mice had evidence for alveolar epithelial type 1 cell injury.
Conclusions:
Peroral arsenic has little effect on local airway immune responses to bacteria but compromises respiratory epithelial barrier integrity, increasing systemic translocation of inhaled pathogens and small molecules. https://doi.org/10.1289/EHP1878.
... The OR for bronchiectasis in the arsenic-exposed group was found to be 10.0 (95% CI: 2.7-37.0). The findings of previous studies suggest that high levels of arsenic ingestion in drinking water (above 400 μg/L) could potentially lead to the development of bronchiectasis (Mazumder et al. 2005). A meta-analysis of 9 previous studies found that arsenic exposure is associated with restrictive impairments, as evidenced by inverse associations between arsenic and both forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). ...
Individuals residing near petrochemical complexes have been found to have increasing the risk of respiratory distress and diseases. On visit 1 in 2016, all participants underwent urinary arsenic measurement and low-dose computed tomography (LDCT). The same participants had LDCT performed at visit 2 in 2018. Our study revealed that individuals with lung fibrotic changes had significantly higher levels of urinary arsenic compared to the non-lung fibrotic changes group. Moreover, we found that participants with urinary arsenic levels in the highest sextile (> 209.7 μg/g creatinine) had a significantly increased risk of lung fibrotic changes in both visit 1 (OR = 1.87; 95% CI= 1.16–3.02; P = 0.010) and visit 2 (OR = 1.74; 95% CI = 1.06–2.84; P = 0.028) compared to those in the lowest sextile (≤ 41.4 μg/g creatinine). We also observed a significantly increasing trend across urinary arsenic sextile in both visits (Ptrend = 0.015 in visit 1 and Ptrend = 0.026 in visit 2). Furthermore, participants with urinary arsenic levels in the highest sextile had a significantly increased risk of lung fibrotic positive to positive (OR = 2.18; 95% CI: 1.24, 3.82; P = 0.007) compared to the lowest sextile (reference category: lung fibrotic negative to negative). Our findings provide support for the hypothesis that arsenic exposure is significantly associated with an increased risk of lung fibrotic changes. It is advisable to reduce the levels of arsenic exposure for those residing near such petrochemical complexes.
... Arsenic exposure will cause inflammation, while long-term exposure to arsenic can cause chronic inflammation [30,31]. Ingested arsenic is associated with non-malignant pulmonary diseases such as bronchitis, asthma, and pneumonia [32][33][34]. Increased levels of serum Immunoglobin E and reduced lung function parameters have been reported in populations exposed to arsenic [5,35]. Several studies have also suggested that arsenic exposure in utero and in childhood is associated with an increased risk of respiratory effects [36][37][38]. ...
Arsenic is an environmental factor associated with epithelial–mesenchymal transition (EMT). Since macrophages play a crucial role in regulating EMT, we studied the effects of arsenic on macrophage polarization. We first determined the arsenic concentrations to be used by cell viability assays in conjunction with previous studies. In our results, arsenic treatment increased the alternatively activated (M2) macrophage markers, including arginase 1 (ARG-1) gene expression, chemokine (C-C motif) ligand 16 (CCL16), transforming growth factor-β1 (TGF-β1), and the cluster of differentiation 206 (CD206) surface marker. Arsenic-treated macrophages promoted A549 lung epithelial cell invasion and migration in a cell co-culture model and a 3D gel cell co-culture model, confirming that arsenic treatment promoted EMT in lung epithelial cells. We confirmed that arsenic induced autophagy/mitophagy by microtubule-associated protein 1 light-chain 3-II (LC3 II) and phosphor-Parkin (p-Parkin) protein markers. The autophagy inhibitor chloroquine (CQ) recovered the expression of the inducible nitric oxide synthase (iNOS) gene in arsenic-treated M1 macrophages, which represents a confirmation that arsenic indeed induced the repolarization of classically activated (M1) macrophage to M2 macrophages through the autophagy/mitophagy pathway. Next, we verified that arsenic increased M2 cell markers in mouse blood and lungs. This study suggests that mitophagy is involved in the arsenic-induced M1 macrophage switch to an M2-like phenotype.
... [4,[6][7][8][23][24][25] Further abnormal lung function tests characterized by obstructive and restrictive lung disease and Bronchiectesis diagnosed by high resolution CT were reported in hospital based and case control studies in West Bengal. [4,[25][26][27] Peripheral neuritis and defective hearing were observed in 2 cases each while dim vision was found in 7 cases of arsenicosis but in none of the arsenic exposed and unexposed control subjects. As specialized examination of eye and ear was not possible in the field survey, no definite comment could be made whether defective hearing and dim-vision found in our cases were caused by neurological deficit. ...
Background: Various clinical features are reported in arsenicosis cases in different case and cross sectional studies. The current study examines the specificity of these features in arsenicosis cases compared to arsenic exposed and unexposed controls. Methods: A stratified multi-stage design was adopted for selection of participants in two districts of West Bengal. The three cohorts consisted of 108 arsenicosis cases and 100 each of arsenic exposed and unexposed controls. Socio demographic characteristics and clinical features were recorded in field study. Water samples taken by the participants and their urine and hair samples were estimated for arsenic. Results: Mean peak arsenic level in drinking water was 259.53 ± 161.49 μg/L and 259.53 ± 161.49 μg/L (p>0.05) among arsenicosis cases and arsenic exposed controls respectively while it was below detection limit in unexposed controls. There was no difference in arsenic level in urine and hair among the former group. Significantly higher number of arsenicosis cases was found among poor farmers and agricultural laborers. There was no difference in BMI and smoking habit among the three cohorts. Chronic lung Disease was present in 40.74% of arsenicosis cases compared to 8% exposed (p0.001) and 5% unexposed (p<0.001) controls. Peripheral neuritis was observed only in two arsenicosis cases. Further, significant number of these cases had weakness and hypertension compared to controls. Conclusion: Poor people are predominantly affected due to arsenicosis in West Bengal. Skin lesions and chronic lung disease are the major causes of morbidity in these people.
... Acute Respiratory Infections is a leading cause of global burden for childhood health (Lanata et al., 2004). Arsenic contaminated drinking water caused lower respiratory infections among the infants (Rahman et al., 2011), respiratory infections (Raqib et al., 2009), pulmonary effects, asthma, wheezing as respiratory infections , non-malignant respiratory infections like Bronchiectasis (Mazumder et al., 2005). Arsenic exposure during pregnancy can cause mother's respiratory infections (breathing, wheezing and cough) (Farzan et al., 2013(Farzan et al., , 2016. ...
Bangladesh-the largest delta in the world, is one of the most climate change vulnerable country and children and older people are the most exposed groups to these negative effects. This research explores the effects of climate change variables have on child health by focusing on the prevalence and intensity of Acute Respiratory Infections and diarrhoea diseases for children under five. The data used for this research has been extracted from the Bangladesh Demographic and Health Survey (BDHS-2014) linked with the Climatic Research Unit (CRU). The study covers 7,886 households where there is at least one child under the age of five. Logistic regressions are used to analyze the effects of climatic variables have on child’s health while controlling for socioeconomic variables. The research reveals that climate variables have effects on diarrhea diseases and Acute Respiratory Infections for children under five even when socioeconomic factors are taken under consideration. Thus, we all should focus on climate change because it is an issue for all of us regardless of our social status. Incorporating climatic variables along with the existing health research model could reduce geographic implications. In addition, local narratives following health research model along with the generalized one incorporating climatic variables could be the best fit model to reduce these implications.
... Clinical manifestations occur differently in each heavy metal poisoning. Arsenic (As) targets the skin and pulmonary nervous system resulting in skin lesions and bronchiectasis (Mazumder et al., 2005). Cadmium causes damage to the kidney, reproductive system, and bone (Godt et al., 2006). ...
Hazardous metal pollution has raised a global concern to its increasing trend in response to industrial growth. As an emerging economy, Indonesia starts to receive a backlash of increasing anthropogenic activities resulting in higher emission of heavy metal pollutants. Heavy metals are non-biodegradable pollutants and toxic to humans and other living organisms. Herein, we have reviewed published investigations on the contamination of heavy metals (Pb, Cu, Hg, Ni, Cd, Zn and As) in aquatic and terrestrial animals, attributed to anthropogenic activities in Indonesia. Some reports found the contamination levels have surpassed the tolerable limits of international standards. Most of the research was conducted in the industrial area, indicating that the heavy metal released into the environment can reach the human body through the food chain. A report in a non-industrial area suspected the contamination to be originated from the chain of anthropogenic activities (fertiliser industry-agriculture-livestock industry).
... The liver is one of the main detoxification organs in the human body. In long-term chronic As poisoning, substantial amounts of organic As can be oxidized (III)As to (V)As by metabolizing the liver and reduced (V)As to (III)As or As methylation [21,22]. Dictyophora contains a variety of trace elements and nutrients. ...
Long-term arsenic (As) exposure can cause liver injury, hepatic cirrhosis, and cancer. Meanwhile, Dictyophora polysaccharides (DIP) have excellent antioxidation, anti-inflammation, and immune protection effects. There are currently few reports on the protection effects of DIP on As-induced hepatotoxicity and its pharmacological value. Therefore, this study was aimed at elucidating the protection of DIP on As-induced hepatotoxicity and exploring its preventive role in antifibrosis. In our study, the SD rat As poisoning model was established by the feeding method to explore the influence of As exposure on liver fibrosis. Then, DIP treatment was applied to the rats with As-induced liver fibrosis, and the changes of serum biochemical indexes and liver tissue pathology were observed. And the expression of fibrosis-related proteins TGF-β1, CTGF, and α-SMA levels was then determined to explore the DIP intervention function. The results demonstrated that through reduced pathological changes of hepatic and increased serum AST, ALT, TP, ALB, and A/G levels, DIP ameliorated liver fibrosis induced by As as reflected. And the administration of DIP decreased the concentration of HA, LN, PCIII, CIV, TBIL, and DBIL. In addition, the synthesis of TGF-β1 inhibited by DIP might regulate the expression of CTGF and decrease the proliferation of fibrinogen and fibroblasts, which reduced the synthesis of fibroblasts to transform into myofibroblasts. And a decrease of myofibroblasts downregulated the expression of α-SMA, which affected the synthesis and precipitation of ECM and alleviated the liver fibrosis caused by exposure to As. In conclusion, based on the pathological changes of liver tissue, serum biochemical indexes, and related protein expression, DIP can improve the As-induced liver fibrosis in rats and has strong medicinal value.
... Several studies in adults have suggested an increased risk of respiratory symptoms and diseases including impairment of lung function following chronic exposure to inorganic arsenic. [1][2][3][4][5][6] Long-term exposure to inorganic arsenic has been found to be associated with increased risk of respiratory symptoms such as chronic cough, dyspnea and breathlessness and the relationships were dose-dependent. [7][8][9][10] A cross-sectional study in Bangladesh found a greater risk of chronic bronchitis with added sounds in chest among people having arsenic-induced skin lesions compared with people without these lesions. ...
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.
... This arsenic is believed to result from arsenic-rich iron oxides in sediments being dissolved and released into the groundwater aquifer [2,3]. There is a growing body of literature linking arsenic exposure to adverse respiratory outcomes including reduced lung function [4][5][6], cough [7][8][9][10][11][12][13], and less conclusively lower respiratory tract infections [14], bronchitis [12,15,16], and pulmonary tuberculosis mortality [17]. However, most studies have been conducted in adult populations, and there have been no studies to date evaluating the association between arsenic and pneumonia in pediatric populations. ...
... In mice, exposure of low to moderate concentrations of arsenic in drinking water (10-100 mg/L) led to a decrease in immune gene expression and aberration in inflammatory protein expression (10,36), resulting in susceptibility to airway inflammation (11). Both arsenic (37,38) and tuberculosis (22) are known to be associated with increased risk of developing bronchiectasis, suggesting some potential common pathophysiology for the long-term impact of arsenic and tuberculosis on lung disease. In both tuberculosis-associated lung injury and arsenic-induced effects on airway physiology, matrix metalloproteinases (MMPs), degradation enzymes, are likely central; MMPs can promote different stages of lung remodeling during tuberculosis, including promoting alveolar destruction (39) and, in arsenic-exposed individuals, MMP-9 impairs repair mechanisms in human lung epithelial cells (40). ...
Rationale:
Permanent lung function impairment after active tuberculosis infection is relatively common. It remains unclear which spirometric pattern is most prevalent after tuberculosis.
Objective:
Our objective was to elucidate the impact of active tuberculosis survival on lung health in the Strong Heart Study, a population of American Indians historically highly impacted by tuberculosis. As arsenic exposure has also been related to lung function in the Strong Heart Study, we also assessed the joint effect between arsenic exposure and past active tuberculosis.
Methods:
The Strong Heart Study is an ongoing population-based, prospective study of cardiovascular disease and its risk factors in American Indian adults. This study uses tuberculosis data and spirometry data from the Visit 2 examination (1993-1995). Prior active tuberculosis was ascertained by a review of medical records. FVC, FEV1, and FEV1/FVC were measured by spirometry. An additional analysis was conducted to evaluate the potential association between active tuberculosis and arsenic exposure.
Results:
A history of active tuberculosis was associated with reduced percent predicted FVC and FEV1, an increased odds of airflow obstruction (odds ratio 1.45, 95% CI 1.08, 1.95), and spirometric restrictive pattern (odds ratio 1.73, 95% CI 1.24, 2.40). These associations persisted after adjustment for diabetes and other risk factors, including smoking. We also observed the presence of cough, phlegm, and exertional dyspnea after a history of active tuberculosis. In the additional analysis, increasing urinary arsenic concentrations were associated with decreasing lung function in those with a history of active tuberculosis, but a reduced odds of active tuberculosis was found with elevated arsenic.
Conclusions:
Our findings support existing knowledge that a history of active tuberculosis is a risk factor for long-term respiratory impairment. Arsenic exposure, although inversely associated with prior active tuberculosis, was associated with a further decrease in lung function among those with a prior active tuberculosis history. The possible interaction between arsenic and tuberculosis, as well as the reduced odds of tuberculosis associated with arsenic exposure, warrants further investigation, as many populations at risk of developing active tuberculosis are also exposed to arsenic-contaminated water.
... Likewise, epidemiologic investigations suggest that inflammatory changes in the lung (indicative of cytotoxicity), such as bronchitis (Mazumder 2007) and bronchiectasis (Mazumder et al. 2005;Mazumder 2007) are increased in response to exposure to high levels of inorganic arsenic in the drinking water, but this has not been investigated to the same extent as the skin arseniasis changes . For the urinary bladder, there are no noninvasive techniques that can evaluate the precursor changes in the bladder, so this cannot be directly investigated in the human urothelium. ...
The biologic effects of inorganic arsenic predominantly involve reaction of the trivalent forms with sulfhydryl groups in critical proteins in target cells, potentially leading to various toxicologic events including cancer. This mode of action is a threshold process, requiring sufficient concentrations of trivalent arsenic to disrupt normal cellular function. Nevertheless, cancer risk assessments for inorganic arsenic have traditionally utilized various dose-response models that extrapolate risks from high doses assuming low-dose linearity without a threshold. We present here an approach for a cancer risk assessment for inorganic arsenic in drinking water that involves considerations of this threshold process. Extensive investigations in mode of action analysis, in vitro studies (>0.1 µM), and in animal studies (>2 mg/L in drinking water or 2 mg/kg of diet), collectively indicate a threshold basis for inorganic arsenic-related cancers. These studies support a threshold for the effects of arsenic in humans of 50–100 µg/L in drinking water (about 65 µg/L). We then evaluate the epidemiology of cancers of the urinary bladder, lung, and skin and non-cancer skin changes for consistency with this calculated value, focusing on studies involving low-level exposures to inorganic arsenic primarily in drinking water (approximately <150 µg/L). Based on the relevant epidemiological studies with individual-level data, a threshold level for inorganic arsenic in the drinking water for these cancers is estimated to be around 100 µg/L, with strong evidence that it is between 50 and 150 µg/L, consistent with the value calculated based on mechanistic, in vitro and in vivo investigations. This evaluation provides an alternative mode of action-based approach for assessing health-protective levels for oral arsenic exposure based on the collective in vitro, in vivo, and human evidence rather than the use of a linear low-dose extrapolation based on default assumptions and theories.
... In a hospital-based study of 29 cases of chronic arsenic toxicity with nonmalignant lung disease in West Bengal, a diagnosis of interstitial lung disease, based on clinical evaluation, chest x-ray, and in limited cases HRCT scans, was made in nine cases [27]. In this study, COPD was the most commonly diagnosed lung disease whereas in a larger populationbased study, bronchiectasis was the most commonly diagnosed lung disease on CT scans [28]. ...
Purpose of Review
The incidence of pulmonary fibrosis is increasing worldwide and may, in part, be due to occupational and environmental exposures. Secondary fibrotic interstitial lung diseases may be mistaken for idiopathic pulmonary fibrosis with important implications for both disease management and prognosis. The purposes of this review are to shed light on possible underlying causes of interstitial pulmonary fibrosis and to encourage dialogue on the importance of acquiring a thorough patient history of occupational and environmental exposures.
Recent Findings
A recent appreciation for various occupational and environmental metals inducing both antigen-specific immune reactions in the lung and nonspecific “innate” immune system responses has emerged and with it a growing awareness of the potential hazards to the lung caused by low-level metal exposures. Advancements in the contrast and quality of high-resolution CT scans and identification of histopathological patterns of interstitial pulmonary fibrosis have improved clinical diagnostics. Moreover, recent findings indicate specific hotspots of pulmonary fibrosis within the USA. Increased prevalence of lung disease in these areas appears to be linked to occupational/environmental metal exposure and ethnic susceptibility/vulnerability.
Summary
A systematic overview of possible occupational and environmental metals causing interstitial pulmonary fibrosis and a detailed evaluation of vulnerable/susceptible populations may facilitate a broader understanding of potential underlying causes and highlight risks of disease predisposition.
... These mechanisms have also been linked to arsenic exposure [36][37][38]. Cystic fibrosis and arsenic have both shown to be associated with bronchiectasis, a rare lung disease [6,39], suggesting that arsenic may act through similar mechanisms. Cystic fibrosis is an autosomal recessive genetic lung disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. ...
Purpose of review:
Hundreds of millions of people worldwide are exposed to arsenic via contaminated water. The goal of this study was to identify whether arsenic-associated lung function deficits resemble obstructive- or restrictive-like lung disease, in order to help illuminate a mechanistic pathway and identify at-risk populations.
Recent findings:
We recently published a qualitative systematic review outlining the body of research on arsenic and non-malignant respiratory outcomes. Evidence from several populations, at different life stages, and at different levels of exposure showed consistent associations of arsenic exposure with chronic lung disease mortality, respiratory symptoms, and lower lung function levels. The published review, however, only conducted a broad qualitative description of the published studies without considering specific spirometry patterns, without conducting a meta-analysis, and without evaluating the dose-response relationship. We searched PubMed and Embase for studies on environmental arsenic exposure and lung function. We performed a meta-analysis using inverse-variance-weighted random effects models to summarize adjusted effect estimates for arsenic and forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio. Across nine studies, median water arsenic levels ranged from 23 to 860 μg/L. The pooled estimated mean difference (MD) comparing the highest category of arsenic exposure (ranging from > 11 to > 800 μg/L) versus the lowest (ranging from < 10 to < 100 μg/L) for each study for FEV1 was - 42 mL (95% confidence interval (CI) - 70, - 16) and for FVC was - 50 mL (95% CI - 63, - 37). Three studies reported effect estimates for FEV1/FVC, for which there was no evidence of an association; the pooled estimated MD was 0.01 (95% CI - 0.005, 0.024). This review supports that arsenic is associated with restrictive impairments based on inverse associations between arsenic and FEV1 and FVC, but not with FEV1/FVC. Future studies should confirm whether low-level arsenic exposure is a restrictive lung disease risk factor in order to identify at-risk populations in the USA.
... Genotoxic effects of sodium arsenite through the generation of reactive oxygen species were reported with the formation of micronuclei in the polychromatic erythrocytes in the bone marrow cells of Wistar rats (Balakumar et al, 2010). Portal tract fibrosis was reported in the liver of arsenic-exposed group (Mazumder et al, 2005). The urinary system is a more sensitive target for DMA than for MMA (Cohen et al, 2001). ...
... Genotoxic effects of sodium arsenite through the generation of reactive oxygen species were reported with the formation of micronuclei in the polychromatic erythrocytes in the bone marrow cells of Wistar rats (Balakumar et al, 2010). Portal tract fibrosis was reported in the liver of arsenic-exposed group (Mazumder et al, 2005). The urinary system is a more sensitive target for DMA than for MMA (Cohen et al, 2001). ...
... The authors found that high arsenic exposure was associated with a high prevalence of respiratory conditions such as asthma, bronchitis, cough, and chest sounds. Others have documented arsenic-related exacerbation of non-malignant lung disease and bronchiectasis severity [67]. All of these studies point to mechanisms of pulmonary toxicity by arsenic, with the potential to lead to immune-mediated disease and infection susceptibility later in life. ...
Purpose of review:
Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life.
Recent findings:
The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.
... Other than respiratory problems, reduced pulmonary function was also reported to be associated with the consumption of arsenical drinking water. In another study, 29 cases of chronic arsenic toxicity in a hospital survey for non-malignant lung diseases in Kolkata west Bengal 35 . In this study Interstitial lung disease was diagnosed in 31%, obstructive lung disease in 58.6% and bronchiectasis in 10% of participant cases. ...
... The study further concluded that chronic exposure to arsenic-contaminated water could cause respiratory effects (Mazumder et al. 1998). Mazumder et al. (2005) conducted a study on the severity of chronic non-malignant bronchiectasis among the population of the arsenic-exposed region of West Bengal. Among the study's total population of 38 people (27 having arsenical skin lesions, and 11 having no skin lesions) they found a bronchiectasis severity score of 3.4 (±3.6) for the exposed population having skin lesions, compared to 0.9 (±1.6) in the population having no skin lesions. ...
During a 28-year field survey in India (1988–2016), groundwater arsenic contamination and its health effects were registered in the states of West Bengal, Jharkhand, Bihar and Uttar Pradesh in the Ganga River flood plain, and the states of Assam and Manipur in the flood plain of Brahamaputra and Imphal rivers. Groundwater of Rajnandgaon village in Chhattisgarh state, which is not in a flood plain, is also arsenic contaminated. More than 170,000 tubewell water samples from the affected states were analyzed and half of the samples had arsenic >10 μg/L (maximum concentration 3,700 μg/L). Chronic exposure to arsenic through drinking water causes various health problems, like dermal, neurological, reproductive and pregnancy effects, cardiovascular effects, diabetes mellitus, diseases of the respiratory and gastrointestinal systems, and cancers, typically involving the skin, lungs, liver, bladder, etc. About 4.5% of the 8,000 children from arsenic-affected villages of affected states were registered with mild to moderate arsenical skin lesions. In the preliminary survey, more than 10,000 patients were registered with different types of arsenic-related signs and symptoms, out of more than 100,000 people screened from affected states. Elevated levels of arsenic were also found in biological samples (urine, hair, nails) of the people living in affected states. The study reveals that the population who had severe arsenical skin lesions may suffer from multiple Bowens/cancers in the long term. Some unusual symptoms, such as burning sensation, skin itching and watering of eyes in the presence of sun light, were also noticed in arsenicosis patients.
... Importantly, CAT are mainly known to result in skin lesions and various systemic manifestations like chronic lung diseases (chronic bronchitis, chronic obstructive pulmonary disease and bronchiectasis), liver diseases (non-cirrhotic portal fibrosis) and other diseases like peripheral vascular disease, polyneuropathy, hypertension and ischeamic heart disease, oedema, diabetes mellitus, weakness and even anaemia [10,11]. Among all, dermal effects following the exposure to arsenic are hallmarks of arsenic poisoning [12,13]. Chronic arsenic exposure leads to the development of skin lesions, including hyperkeratosis and hyperpigmentation [14]. ...
Background
Visceral leishmaniasis (VL), with the squeal of Post-kala-azar dermal leishmaniasis (PKDL), is a global threat for health. Studies have shown sodium stibogluconate (SSG) resistance in VL patients with chronic arsenic exposure. Here, we assessed the association between arsenic exposure and risk of developing PKDL in treated VL patients.
Methods
In this retrospective study, PKDL patients (n = 139), earlier treated with SSG or any other drug during VL, were selected from the study cohort. Trained physicians, unaware of arsenic exposure, interviewed them and collected relevant data in a questionnaire format. All probable water sources were identified around the patient’s house and water was collected for evaluation of arsenic concentration. A GIS-based village-level digital database of PKDL cases and arsenic concentration in groundwater was developed and individual point location of PKDL cases were overlaid on an integrated GIS map. We used multivariate logistic regression analysis to assess odds ratios (ORs) for association between arsenic exposure and PKDL development.
Results
Out of the 429 water samples tested, 403 had arsenic content of over 10 μg/L, with highest level of 432 μg/L among the seven study villages. Multivariate adjusted ORs for risk of PKDL development in comparison of arsenic concentrations of 10.1–200 μg/L and 200.1–432.0 μg/L were 1.85 (1.13–3.03) and 2.31 (1.39–3.8) respectively. Interestingly, similar results were found for daily dose of arsenic and total arsenic concentration in urine sample of the individual. The multivariate-adjusted OR for comparison of high baseline arsenic exposure to low baseline arsenic exposure of the individuals in the study cohort was 1.66 (95% CI 1.02–2.7; p = 0.04).
Conclusion
Our findings indicate the need to consider environmental factors, like long time arsenic exposure, as an additional influence on treated VL patients towards risk of PKDL development in Bihar.
... Arsenic problems occur in groundwater because of a combination of its high toxicity at relatively low concentrations (in the g -1 range) and its mobility in water in the pH ranges of many groundwaters and over a wide range of redox conditions . Elevated levels of arsenic are cause of concern because it is associated with a number of adverse health outcomes, including several types of cancer, vascular diseases, dermatological ailments, diabetes, respiratory diseases, cognitive decline, and infant mortality (Mazumder et al., 2005;Rahman et al., 2006;Yang et al., 2003). Groundwater arsenic concentrations correlate with fluorine, consequently to excessive amounts of one element there is a high concentration of the other, leading to an accumulation of health risk (Pérez and Fernández, 2004;Boglione, et al., 2009). ...
... Gastrointestinal symptoms such as nausea, vomiting, diarrhea, abdominal pain, and hematemesis are observed in short-term high-dose and long-term low-dose exposure (Jomova et al., 2011). Elevated liver enzymes with portal fibrosis, cirrhosis, and bronchiectasis can be observed (Liu et al., 2002;Mazumder et al., 2005;Rahman et al., 2009). The most typical neurologic manifestation is symmetrical peripheral sensory and motor neuropathy, which may last for years and is only partially reversible (Fincher and Koerker, 1987;Mathew et al., 2010). ...
Arsenic-contaminated drinking water presents a serious health hazard in certain geographic locations around the world. Chromated copper arsenate, a pesticide and preservative that was used to pressure treat residential lumber in the United States beginning in the 1940s and was banned by the Environmental Protection Agency in 2003, poses a potential source of arsenic exposure and toxicity. In this study, we review the clinical manifestations of arsenic intoxication with the focus on dermatologic manifestations. Dermatologists should be aware that although chromated copper arsenate-treated wood for residential use was banned in 2003, the exposure risk remains. Long-term follow up is necessary to detect arsenic induced cutaneous and visceral malignancy in patients with history of arsenic exposure.
... Cytokines such as TNF-α [83] Cardiovascular markers such as VCAM-1 [84] Diarrhoea and bacterial infection sequelae such as myocarditis and diabetes [85] Lower respiratory tract infections and diarrhoea [86] Bronchiectasis and obstructive lung diseases [87, 88] Cardiovascular diseases [89][90][91]Impaired lung function [92][93][94]Anaemia [95] Cognitive decline [96] All cause [97] Infectious diseases [97] Cancer [97, 98] Cardiovascular [98][99][100][101]Cerebrovascular disease, diabetes and kidney diseases [102] Overcrowding Acute lower respiratory illness [103] Bacterial carriage [104] Pneumonia [105, 106] Acute rheumatic fever [107] Meningococcal disease [108] Skin infections [109] Acute hospitalisation rates [110] Childhood mortality [111, 112] Note: CRp, C-reactive protein; COpd, chronic obstructive pulmonary disease; TNF, tumour necrosis factor; vCAM-1, vascular cell adhesion molecule 1. Table 1). PM specifically from mineral dusts has also been associated with adverse health outcomes such as silicosis and fibrosis [50, 51, 56]. ...
Objective: A considerable health disparity exists between Aboriginal and non-Aboriginal Australians, including a higher incidence and severity of cardiovascular and respiratory diseases.The burden of these diseases appears to be greatest in communities located in the remote regions of Australia. Unique environmental challenges in these regions may be a contributing factor; however these are yet to be adequately investigated. We aimed to develop a case to improve our understanding of environmental risk factors in remote Aboriginal communities. Methods: We comprehensively reviewed the literature regarding physical environmental challenges that are likely to be highly prevalent in remote Aboriginal communities, and have been linked
with adverse health. We focused on exposure to inhaled geogenic (earth-derived) dust and biomass smoke, bacterial and heavy metal contamination of drinking water and overcrowding. Results: These environmental factors are anecdotally high in remote Aboriginal communities and have been linked, mostly epidemiologically, to cardiovascular, respiratory and other infectious diseases. These challenges are an under-recognised
problem and are likely to have a significant impact on Aboriginal community health; increased research focus in this area would be of great benefit. Implications: It is crucial to identify and quantify these physical environmental factors, and to determine the mechanisms through which they impact on health, particularly as these factors are modifiable and may be suppressed using relatively simple, cost effective changes in community infrastructure. Protection against these exposures is likely to reduce their cumulative negative effects on individuals across the life course and result in significantly improved health in remote Aboriginal Australian communities.
... This arsenic is believed to result from arsenic-rich iron oxides in sediments being dissolved and released into the groundwater aquifer [2,3]. There is a growing body of literature linking arsenic exposure to adverse respiratory outcomes including reduced lung function [4][5][6], cough [7][8][9][10][11][12][13], and less conclusively lower respiratory tract infections [14], bronchitis [12,15,16], and pulmonary tuberculosis mortality [17]. However, most studies have been conducted in adult populations, and there have been no studies to date evaluating the association between arsenic and pneumonia in pediatric populations. ...
Background:
Pneumonia is the leading cause of death for children under 5 years of age globally, making research on modifiable risk factors for childhood pneumonia important for reducing this disease burden. Millions of children globally are exposed to elevated levels of arsenic in drinking water. However, there is limited data on the association between arsenic exposure and respiratory infections, particularly among pediatric populations.
Methods:
This case control study of 153 pneumonia cases and 296 controls 28 days to 59 months of age in rural Bangladesh is the first to assess whether arsenic exposure is a risk factor for pneumonia in a pediatric population. Cases had physician diagnosed World Health Organization defined severe or very severe pneumonia. Urine collected during hospitalization (hospital admission time point) and 30 days later (convalescent time point) from cases and a single specimen from community controls was tested for urinary arsenic by graphite furnace atomic absorption.
Results:
The odds for pneumonia was nearly double for children with urinary arsenic concentrations higher than the first quartile (≥6 μg/L) at the hospital admission time point (Odd Ratio (OR):1.88 (95 % Confidence Interval (CI): 1.01, 3.53)), after adjustment for urinary creatinine, weight for height, breastfeeding, paternal education, age, and number of people in the household. This was consistent with findings at the convalescent time point where the adjusted OR for children with urinary arsenic concentrations greater than the first quartile (≥6 μg/L) was 2.32 (95 % CI: 1.33, 4.02).
Conclusion:
We observed a nearly two times higher odds of pneumonia for children with creatinine adjusted urinary arsenic concentrations greater than the first quartile (≥6 μg/L) at the hospital admission time point. This novel finding suggests that low to moderate arsenic exposure may be a risk factor for pneumonia in children under 5 years of age.
Arsenic exposure is associated with airway inflammation and decreased lung function tests. Whether arsenic exposure associated with lung interstitial changes remains unknown. We conducted this population-based study in southern Taiwan during 2016 and 2018. Our study recruited individuals aged over 20 years, residing in the vicinity of a petrochemical complex and with no history of cigarette smoking. In both the 2016 and 2018 cross-sectional studies, we conducted chest low-dose computed tomography (LDCT) scans, as well as urinary arsenic and blood biochemistry analyses. Lung interstitial changes included lung fibrotic changes that were defined as the presence of curvilinear or linear densities, fine lines, or plate opacity in specific lobes; additionally, other interstitial changes were defined as the presence of ground-glass opacity (GGO) or bronchiectasis on the LDCT images. In both cross-sectional studies conducted in 2016 and 2018, participants with lung fibrotic changes exhibited a statistically significant increase in the mean urinary arsenic concentrations compared to those without fibrotic changes (geometric mean = 100.1 vs. 82.8 μg/g creatinine, p < 0.001 for cross-sectional study 2016, and geometric mean = 105.6 vs. 71.0 μg/g creatinine, p < 0.001 for cross-sectional study 2018). After controlling for age, gender, body mass index, platelet counts, hypertension, aspartate aminotransferase, cholesterol, HbA1c, and educational levels, we observed a significant positive association between a unit increase in log urinary arsenic concentrations and the risk of lung fibrotic changes in both cross-sectional study 2016 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.04-1.90, p = 0.028) and cross-sectional study 2018 (OR = 3.03, 95% CI = 1.38-6.63, p = 0.006). Our study did not find a significant association between arsenic exposure and bronchiectasis or GGO. It is imperative for the government to take significant measures to reduce arsenic exposure levels among individuals living near petrochemical complexes.
Ingested inorganic arsenic (iAs) is a human carcinogen that is also linked to other adverse health effects, such as respiratory outcomes. Yet, among populations consuming low-arsenic drinking water, the impact of iAs exposure on childhood respiratory health is still uncertain. For a Spanish child study cohort (INfancia y Medio Ambiente—INMA), low-arsenic drinking water is usually available and ingestion of iAs from food is considered the major source of exposure. Here, we explored the association between iAs exposure and children’s respiratory outcomes assessed at 4 and 7 years of age ( n = 400). The summation of 4-year-old children’s urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) was used as a biomarker of iAs exposure (∑As) (median of 4.92 μg/L). Children’s occurrence of asthma, eczema, sneeze, wheeze, and medication for asthma and wheeze at each assessment time point (i.e., 4- and 7-year) was assessed with maternal interviewer-led questionnaires. Crude and adjusted Poisson regression models using Generalized Estimating Equation (GEE) were performed to account for the association between natural logarithm transformed (ln) urinary ∑As in μg/L at 4 years and repeated assessments of respiratory symptoms at 4 and 7 years of age. The covariates included in the models were child sex, maternal smoking status, maternal level of education, sub-cohort, and children’s consumption of vegetables, fruits, and fish/seafood. The GEE—splines function using Poisson regression showed an increased trend of the overall expected counts of respiratory symptoms with high urinary ∑As. The adjusted expected counts (95% confidence intervals) at ln-transformed urinary ∑As 1.57 (average concentration) and 4.00 (99 th percentile concentration) were 0.63 (0.36, 1.10) and 1.33 (0.61, 2.89), respectively. These exploratory findings suggest that even relatively low-iAs exposure levels, relevant to the Spanish and other populations, may relate to an increased number of respiratory symptoms during childhood.
Arsenic is a known carcinogen and is naturally available in earth’s crust. Inorganic arsenic is an environmental pollutant with immunosuppressive properties. Human papillomavirus (HPV) is considered one of the most common sexually transmitted diseases in the United States. HPV is linked to several types of cancers in males, including oral, anal, and penile cancer. However, limited information is available on the effect of arsenic on HPV in males. The purpose of this study was to examine the association of urinary arsenic species (speciated and total) and the prevalence of HPV infection in the male population. HPV prevalence in males was analyzed using the 2013–2014 and 2015–2016 National Health and Nutrition Examination Survey (NHANES) dataset. Logistic regression analysis was used to examine associations of seven types of urinary arsenic species (arsenous acid, arsenic acid, arsenobetaine, arsenocholine, dimethylarsinic acid (DMA), monomethylarsonic acid (MMA), total arsenic acid) with HPV risk for male participants aged 18–59 years (N = 1516). Demographic characteristics were included in the logistic regression model for each arsenic variable. All statistical analyses were conducted by using the software R (version 4.2.0). Increasing DMA was positively associated with the prevalence of low-risk HPV (odds ratio (OR): 1.075, 95% confidence interval (CI): 1.025, 1.128) in addition to the sum of total toxic arsenic species (TUA1) including arsenous acid, arsenic acid, DMA, and MMA (OR: 1.068, 95% CI: 1.022, 1.116). High-risk HPV strains were found to be positively associated with arsenic acid (OR: 1.806, 95% CI: 1.134, 2.876) and total arsenic minus the sum of the two organic arsenic species arsenobetaine and arsenocholine (TUA2) at quartile 3 (Q3) level (OR: 1.523, 95% CI: 1.102, 2.103). The logistic regression models also showed that race and marital status were significant factors related to high-risk HPV. Our study reported that DMA and TUA1 are associated with low-risk HPV and arsenic acid is associated with high-risk HPV infections in males. Future research is required to confirm or refute this finding.
This study investigates the direct climate-related variable have on children's health in Bangladesh, focusing on two diseases with a high prevalence and relatively high child mortality in this country: diarrheal diseases and Acute Respiratory Infections (ARIs). It is well established in the literature that SES variables affect children's health. The research shows, controlling for SES, climate conditions have effects on diarrhoea diseases and Acute Respiratory Infections for children under five. The data used for this study has been extracted from the Bangladesh Demographic and Health Survey (BDHS-2014) linked with precipitation and temperature data linked through the household GPS information, a dataset that 7,886 households where there is at least one child under the age of five. Logistic regressions are used to analyze the effects climatic variables have on children's health while controlling for socioeconomic variables. As climate change will only intensify the environmental issues, SES doesn't seem to offer protection when confronted with climate change.
Arsenic (As), a toxic metalloid, primarily originates from both natural and anthropogenic activities. Reports suggested that millions of people globally exposed to high levels of naturally occurring As compounds via inhalation and ingestion. There is evidence that As is a well-known lung carcinogen. However, there has been relatively little evidence suggesting its non-malignant lung effects. This review comprehensively summarises current experimental and clinical studies implicating the association of As exposure and the development of several non-malignant lung diseases. Experimental studies provided evidence that As exposure induces redox imbalance, apoptosis, inflammatory response, epithelial-to-mesenchymal transition (EMT), and affected normal lung development through alteration of the components of intracellular signaling cascades. In addition, we also discuss the sources and possible mechanisms of As influx and efflux in the lung. Finally, current experimental studies on treatment strategies using phytochemicals and our perspective on future research with As are also discussed.
Arsenic in the environment occurs in both organic and inorganic compounds in their trivalent or pentavalent state. Certain fish and crustaceans contain very high levels of organic arsenic, often as arsenobetaine. In most other foodstuffs, levels of arsenic are low and the form is not known. The total daily intake of arsenic in the general population is reported to be approximately a few tenths of a milligram but varies to a great extent depending on the amount of fish consumed.
Both organic arsenic in seafood and inorganic arsenic in water, beverages, and drugs have been shown to be readily absorbed (70%–90%) by the gastrointestinal tract. Some reports also indicate a fairly high degree of absorption after the inhalation of arsenic.
Absorbed arsenic, irrespective of the form, is widely distributed in the body. After exposure to inorganic arsenic, clearance of arsenic from the skin, upper gastrointestinal tract, epididymis, thyroid, and skeleton is slower than from other organs. The highest levels of arsenic in humans are normally found in the hair, nails, and skin. The main route of excretion is through the kidneys. After ingestion of arsenite or arsenate, approximately 35% of the dose is excreted within 2 days. From animal experiments, it seems that insoluble inorganic arsenic inhaled through the airway is deposited and retained in lung tissue for a relatively long time. Animal data indicate arsenobetaine accumulation in cartilage, testes, epididymis, and muscle. Of ingested arsenobetaine, 50%–80% is excreted in the urine within 2 days.
Biotransformation of inorganic arsenic has been shown to occur in both animals and humans. Methylated compounds, such as methylarsonic acid and dimethylarsinic acid, have been detected in the urine after ingestion or inhalation of inorganic arsenic. Reduction of arsenate and oxidation of arsenite in vivo has been demonstrated in experimental animals. Recently, a human arsenic methyltransferase has been identified.
Medications, contaminated food, beverages, and drinking water have given rise to a number of episodes of arsenic poisoning.
Inorganic arsenic-induced skin lesions such as dermatoses, which may include eruption, pigmentation, or leukodermal hyperkeratosis, may ultimately lead to the development of skin cancer and Bowen disease. Effects on the nervous system (e.g., peripheral nervous disturbance), as well as on the heart and circulatory system (e.g., abnormal electrocardiograms, peripheral vascular disturbances with gangrene of the extremities, ischemic heart disease, cerebral infarction, and erectile dysfunction), have also been reported after chronic exposure to inorganic arsenic. Hematological changes after inorganic arsenic exposure are characterized by anemia and leukopenia. Chronic oral ingestion of inorganic arsenic in drinking water has also been reported to cause internal cancers (of the lung, bladder, kidney, and liver), diabetes, hypertension, cataract, pterygium, and developmental retardation.
Arsenic poisoning among industrial workers is characterized by perforation of the nasal septum, skin changes, and peripheral neuritis. There is substantial epidemiological evidence of an excessive risk of lung cancer among workers exposed to arsenic.
Arsine gas is a powerful hemolytic poison encountered under some industrial conditions. Arsine poisoning is characterized by nausea, vomiting, headache, shortness of breath, and hemoglobinuria.
Exposure to environmental toxicants such as Arsenic (As) can result in As-induced alterations in immune regulators. Consequently, people who are more prone to viral infections like influenza A or B, H1N1, SARS CoV (Severe Acute Respiratory Syndrome Coronavirus), and SARS CoV2 may develop susceptibility to immune responses in their lungs because our previous reports delineated the ability of QIAPI 1®, a melanin precursor, to dissociate water molecules with simultaneous therapeutic efficacy against central nervous system (CNS) diseases, retinopathy, and As-induced renal toxicity. Given the commonalities of lung pathology of SARS CoV and As-induced toxicity, the aim of this study is to decipher the efficacy of QIAPI 1® against pentavalent As-induced lung toxicity by examining the pulmonary pathology. Hematoxylin & Eosin (H&E) staining was used for ascertaining the lung pathology in Wistar rat models. Animals were divided into 3 groups: control group, group treated with pentavalent As, and a group treated with pentavalent As and QIAPI 1®. There were no significant changes in lung histopathology in the control group as indicated by intact morphology. As-treated group revealed damage to the histoarchitecture with pulmonary edema, interstitial fibrosis, diffuse alveolar damage, Bronchiolitis obliterans organizing pneumonia (BOOP)-lesions, formation of hyaline membrane, multinucleated giant pneumocytes, atypical pneumocytes, inflammatory cell infiltration, and interstitial edema. The group treated with As and QIAPI 1® significantly associated with mitigated histological signs of lung inflammation induced by Arsenic. Therefore, QIAPI 1® can be recommended as antagonistic to As-induced lung toxicity. In conclusion, this model could be preferred as a hypothetical model to examine the efficacy of QIAPI 1® in SARS CoV2-induced pulmonary damage. Future studies are warranted to delineate the efficacy of QIAPI 1® against SARS CoV and SARS CoV2 lung pathology.
Rice accumulates arsenic, an established lung toxicant. Little is known about the association of rice consumption with arsenic-related health effects, particularly interstitial lung disease. The Multi-Ethnic Study of Atherosclerosis enrolled 6,814 White, Black, Hispanic and Chinese adults from six U.S. cities, between 2000-2002. We included 2,250 participants with spirometry, 2,557 with full-lung computed tomography scans, and 5,710 with cardiac computed tomography. Rice consumption and 310 participants with urinary arsenic were assessed at baseline. Spirometry and full-lung computed tomography-derived total lung capacity, high attenuation areas (HAA) and interstitial lung abnormalities, were measured at examination 5. HAA was measured in 1-3 visits from cardiac computed tomography scans. 12% reported eating ≥1 servings of rice/day. Comparing ≥1 servings/day versus <1 serving/week, the mean difference (95% CI) for forced vital capacity was -102 (-198, -7) mL and for forced expiratory volume in 1 second was -90 (-170, -11) mL after adjustment for demographics, anthropometrics, dietary factors, and smoking. The cross-sectional adjusted percent difference (95% CI) for total lung capacity was -1.33 (-4.29, 1.72) and for cardiac-based HAA was 3.66 (1.22, 6.15) %. Sensitivity analyses with urinary arsenic were consistent with rice findings. Daily rice consumption was associated with lower lung function and higher cardiac-based HAA.
Abstract Chronic exposure to environmental heavy metals is a worldwide health concern. It is acknowledged to be an important cause of lower respiratory tract damage in children. However, the molecular mechanisms underlying the heavy metal-induced cellular stress/toxicity are not completely understood. Small non-coding RNAs (sncRNAs), such as microRNAs (miRNA) and more recently identified tRNA-derived RNA fragments (tRFs), are critical to the posttranscriptional control of genes. We used deep sequencing to investigate whether cellular sncRNA profiles are changed by environmental heavy metals. We found that the treatment of arsenite, an important groundwater heavy metal, leads to abundant production of tRFs, that are ~30 nucleotides (nts) long and most of which correspond to the 5′-end of mature tRNAs. It is unlikely for these tRFs to be random degradation by-products, as the type of induced tRFs is heavy metal-dependent. Three most inducible tRFs and their roles in arsenite-induced cellular responses were then investigated. We identified that p65, an important transcription factor belonging to NF-κB family and also a key factor controlling inflammatory gene expression, is a regulated target of a tRF derived from 5′-end of mature tRNA encoding AlaCGC (tRF5-AlaCGC). tRF5-AlaCGC activates p65, subsequently leading to enhanced secretion of IL-8 in arsenite response. In this study, we also identified that endonuclease Dicer and angiogenin temporally control the induction of tRF5-AlaCGC, providing an insight into the control of tRF biogenesis and subsequently the prevention of cellular damage.
This paper reviews how active research in West Bengal has unmasked the endemic arsenism that has detrimental effects on the health of millions of people and their offspring. It documents how the pathways of exposure to this toxin/poison have been greatly expanded through intensive application of groundwater in agriculture in the region within the Green Revolution framework. A goal of this paper is to compare and contrast the similarities and differences in arsenic occurrence in West Bengal with those of other parts of the world and assess the unique socio-cultural factors that determine the risks of exposure to arsenic in local groundwater. Successful intervention options are also critically reviewed with emphasis on integrative strategies that ensure safe water to the population, proper nutrition, and effective ways to reduce the transfer of arsenic from soil to crops. While no universal model may be suited for the vast areas of the world affected with by natural contamination of groundwater with arsenic, we have emphasized community-specific sustainable options that can be adapted. Disseminating scientifically correct information among the population coupled with increased community level participation and education are recognized as necessary adjuncts for an engineering intervention to be successful and sustainable.
Arsenic is a Class I carcinogen causing cancer of the skin, lungs, bladder, liver, kidney, and probably prostate and ovary. Exposure can be by ingestion of contaminated drinking water or food, or by inhalation of fumes from burning coal. Arsenic does not induce point mutations like a classic DNA-damaging mutagen. The carcinogenic mechanism is unclear, but evidence exists supporting DNA repair inhibition, stem cell expansion, reactive oxygen generation, aneuploidy, and epigenetic dysregulation. The lack of UV signature mutation spectra in arsenic-induced skin cancers argues against DNA repair inhibition as a mechanism. Recent studies on epigenetic dysregulation point toward differential gene expression consistent with a role in arsenic carcinogenesis. Limited animal models for arsenic carcinogenesis and limited studies conducted in human cancers caused by arsenic exposure limit the ability to elucidate mechanisms. Research focused on tumors from people suffering from arsenicosis is needed for a clearer understanding of molecular events underlying arsenic-induced carcinogenesis.
Arsenic removal from contaminated water has become a global concern, and the development of arsenic removal processes from potable water is still a major challenge. Several chemical based arsenic removal technologies are available, which are chiefly based on the combination of the processes like oxidation, coagulation, filtration, ion exchange, and adsorption. However, any technology selected for the purpose should comply standard set by WHO for drinking water with a capacity to remove arsenic below 10 ppb. Further, technology related issues like sludge disposal, operation and maintenance, etc. are very important for considering any implementation for supply of arsenic-free potable water. It is undoubtedly a challenging task to develop appropriate, efficient, and cost-effective and user friendly technology to serve the arsenic-free water to the humanity of diverse economic and ecologic locations facing dreadful situations with arsenic.
Arsenic is a widespread element in the environment and it is highly toxic to human health. It is a Group A human carcinogen. Chronic arsenic exposure causes various dreaded ailments including cancer in skin, lung, and bladder, as well as in other organs. Arsenic induces epigenetic alterations and aberrant DNA methylation, causing inherent damage to cells. Addressing the issue at molecular level, researchers are interested to understand the distribution, metabolism, and potential modes of actions of inorganic arsenic (iAs). Paradoxically, apart from poisoning, arsenic has long been in medicinal use for treatment of various diseases like asthma, syphilis, trypanosomiasis, lichen planus, verruca plenum, tropical eosinophilia, and psoriasis. It is also a potentially important chemotherapeutic agent against acute promyelocytic leukemia and can help in activating the cytotoxic effects of DNA damaging chemotherapeutics. To extend precise therapeutic strategies against arsenic, integrated study on environmental monitoring, health surveillance, exposure data, individual risk characterization, and human biomarkers are required which will be able to provide mechanistic insight into the pathogenesis of disease processes.
While exposure to arsenic can occur through a number of routes, including ingestion in water, foods, and soil, early work focused on the ability of arsenic to increase the risk of lung cancer through inhalation, especially in occupational settings. This chapter focuses on the role of arsenic in airway remodeling and how that relationship might lead to both carcinogenic and noncarcinogenic lung diseases. It outlines lung cancer and noncancer adverse health outcomes following arsenic exposures that have been reported in human populations and/or animal studies. Those adverse outcomes suggest that the extracellular matrix (ECM) and aberrant cell motility and wound repair are targets of arsenic, leading to the chronic lung disease phenotypes seen in populations exposed to high levels of arsenic. Aberrant wound repair and signaling mechanisms involved in cellular migration, as well as changes in airway epithelial barrier structure and function, have been demonstrated following arsenic exposure as well.
Exposure to arsenic has been associated with increased risk of reduced lung function in adults, but the adverse impacts in early life are unclear. We aim to examine whether prenatal and childhood arsenic exposure is associated with reduced lung function and increased airway inflammation in school-aged children. Children born in the MINIMat cohort in rural Bangladesh were evaluated at 9years of age (n=540). Arsenic exposure was assessed in urine (U-As) that was collected from mothers during early pregnancy and their children aged 4.5 and 9years. In the 9-year-old children, lung function was assessed using spirometry and airway inflammation was assessed by the NIOX MINO system. C-reactive protein (CRP) and Clara cell secretory protein (CC16) concentrations were measured in plasma by immunoassays. The U-As concentrations in 9-year-old children were lower (median 53μg/l) compared to their mothers (median 76μg/l). Maternal U-As (log2 transformed) was inversely associated with forced vital capacity (FVC) and forced expiratory volume at 1s (FEV1) (β=-12; 95% CI: -22, -1.5; p=0.031 and β=-12; 95% CI: -22, -1.9; p=0.023, respectively) in all children, and the associations were stronger in boys and among children with adequate height and weight, as well as among those whose mothers had higher percentages of methylarsonic acid (MMA) and lower percentages of dimethylarsinic acid (DMA). U-As (log2 transformed) at 4.5 and 9years was positively associated with fractional exhaled nitric oxide (FENO) concentrations in boys (β=0.89; 95% CI: 0.13, 1.66; p=0.022 and β=0.88; 95% CI: 0.16, 1.61; p=0.017, respectively) but not in girls. Increased CC16 concentrations were associated with higher lung function indices. In conclusion, our findings suggest that prenatal arsenic exposure is related to impaired lung function, while childhood exposure may increase airway inflammation, particularly in boys.
Long-term arsenic exposure results in atherosclerosis and cancers, along with aberrant immune responses. Animal-based and epidemiological studies indicate that arsenic exposure increases susceptibility to viral and bacterial infections. This study aimed to assess whether arsenic exposure is associated with the development of fungal infection, which is substantially attributed to as a cause of aberrant immunity. Based on two well-established cohorts from two basins in southwestern (SW; high arsenic area) and northeastern (NE; low arsenic area) Taiwan (n = 297 and 2738, respectively), the arsenic exposure in well water was estimated using HPLC-ICP-MS. Fungal infections were defined via clinical and mycological assessments (PCR of fungal 18S rRNA) of nail samples. Individuals in SW cohort with cumulative arsenic exposure > 10,000 μg/L ∗ years had a higher risk of developing fungal infections (OR = 1.57, 95% CI = 1.08–1.92) after adjusting for diabetes and occupation. In NE cohort, female sex, alcohol consumption, and chronic kidney diseases were associated with toenail infections. In contrast, fingernail infections (OR = 1.33, 95% CI = 1.05–1.68) were highly associated with arsenic exposure in a dose-dependent manner. We are the first to report palmar and plantar hyperkeratosis upon low arsenic exposure in 3.9% and 6.7% individuals, respectively. This is the first large-scale study showing arsenic exposure is associated with fungal infections in a dose-dependent manner.
In 2012, China revised its Criminal Procedure Law (2012 CPL). One of the major changes is its official approval of the use of victim-offender reconciliation, or ‘criminal reconciliation’ in certain public prosecution cases. This change, on the one hand, echoes the Confucian doctrine that favours harmonious inter-personal relationships and mediation, while, on the other hand, it deviates from the direction of legal reforms dating from the 1970s through the late 1990s. Questions have emerged concerning not only the cause of this change in legal norms but also the proper position of criminal reconciliation in the current criminal justice system in China. The answers to these questions largely rely on understanding the role of traditional informal dispute resolution as well as its interaction with legal norms. Criminal reconciliation in ancient China functioned as a means to centralise imperial power by decentralizing decentralising its administration. Abolishing or enabling such a mechanism in law is merely a small part of the government’s strategy to react to political or social crises and to maintain social stability. However, its actual effect depends on the vitality of Confucianism, which in turn relies on the economic foundation and corresponding structure of society.
It has become increasingly clear that the individual genetic background influences susceptibility to metal toxicity. Genetic variation in genes that regulate metal toxicokinetics and toxicodynamics influence the degree of metal accumulation and retention in the body, as well as toxic effects. Moreover, factors that regulate gene expression, so-called epigenetic factors, have been identified as targets for metal toxicity. This chapter addresses what is currently known about such gene-environment interactions. The picture that emerges for most metals is that the genetic influence is probably not attributed to a single gene for each metal; rather it is polygenic, with some genes having a stronger effect than others. The presence of variants of the human leukocyte antigen system and the risk of beryllium-related pulmonary disease was one of the first and maybe the strongest example of a gene-environment interaction. There are also clear gene-environment interactions for arsenic and lead. Evidence is rapidly growing for epigenetic effects of metals, e.g. for arsenic, cadmium, and lead, which may explain the association between metal exposure early in life and toxic effects later in life, as well as metal carcinogenicity.
Chronic arsenic toxicity is associated with various clinical manifestations known as arsenicosis. Pigmentation and keratosis are the specific skin lesion characteristics of chronic arsenic toxicity. Arsenicosis is also associated with various systemic manifestations over and above skin lesions, important ones being chronic lung disease such as chronic bronchitis, chronic obstructive pulmonary disease, and bronchiectasis, liver disease such as non-cirrhotic portal fibrosis, polyneuropathy and cerebrovascular disease, peripheral vascular disease, hypertension and ischemic heart disease, diabetes mellitus, non-pitting edema of the limbs, weakness and anemia, congestion of eyes, pterygium and cataract, and erectile dysfunction. Cancer of skin, lung, and urinary bladder are important cancers associated with chronic arsenic toxicity. Treatment of arsenicosis is unsatisfactory and is mostly symptomatic. Stoppage of drinking of arsenic-contaminated water is the mainstay of the management of arsenicosis as specific chelation therapy has limited value. Early skin cancer, detectable by regular active surveillance, is curable.
Arsenic contamination in ground water and its toxic effect on human health is a recent public health problem in Bangladesh. So far 44 districts were found affected with arsenic contamination in ground water. Among these 44 districts, arsenicosis cases were identified in 26 districts. A total of 1625 cases were detected from 133 villages in 157 thanas of these districts. The majority (90%) of the cases were detected in the rural areas. It is estimated that about 35 million people in Bangladesh are at risk of arsenic toxicity. All the three stages of manifestations of chronic arsenicosis were observed in Bangladesh. But majority of patients were found in initial and second stage. Among the arsenicosis patients the common manifestations were melanosis, keratosis, hyperkeratosis and depigmentation (Leukomelanosis). So far there is no specific treatment of such chronic arsenic toxicity in human health. Mild cases have shown to be improved by withdrawing further intake of arsenic contaminated water. Symptoms are improved by taking protein rich diet and vitamin A, E & C at initial and second stages of toxicity. Recently chelating agent Penicillamine has been used in selected cases for the treatment of arsenicosis. People of the affected and high-risk areas are advised to use arsenic safe water to prevent health hazards. Indexing words: Arsenic contamination, Arsenicosis, Ground water
Chronic ,Arsenic Poisoning ,and Respiratory Effects in Bangladesh: Abul Hasnat MILTON, et al.Arsenic Cell, NGO Forum for Drinking Water Supply & Sanitation, Bangladesh—A large population in Bangladesh ,have ,been ,exposed ,to naturally occurring inorganic arsenic through their drinking water. A prevalence comparison,study of respiratory disorders among,subjects with and without arsenic,exposure ,through ,drinking ,water ,was conducted in Bangladesh. Characteristic skin lesions, keratoses and pigmentation alteration, and the water arsenic level confirmed the arsenic exposure. Three villages were ,selected ,from ,health awareness campaign,programs. Participants in these courtyard meetings who had suspected skin lesions. i.e., keratosis, hyperpigmentation and hypopigmentation, were examined,by a,well-trained medical officer to confirm the diagnosis. Unexposed,subjects were randomly selected from another village, where tubewells were not contaminated,with arsenic. We interviewed and examined,218 individuals irrespective of age and sex from these villages. The arsenic level in their drinking water was measured,and the mean arsenic level was 614 µg/l(ranging from 136 µg/lto 1,000 µg/l). Information regarding respiratory system signs and symptoms,was also collected. There were few smokers, and analyses were therefore confined to nonsmokers. The overall crude prevalence (or risk)
1 We compared the prevalence of signs and symptoms of chronic arsenic poisoning in two rural populations.
2 The arsenic concentration in the drinking water of the exposed population was 0.41 mg/l, and 0.007 mg/l in the control population.
3 The arsenic was present mainly (70%) in its pentavalent form.
4 The objective was to quantitate health effects and risks derived from chronic ingestion of arsenic in contaminated water.
5 In the exposed population, 21.6% of the sample, showed at least one of the cutaneous signs of chronic arsenic poisoning against 2.2% in the control town.
6 Non-specific symptoms were more prevalent in the exposed population and they occurred more frequently in those individuals with skin signs.
7 The relative risk of suffering a particular manifestation of poisoning, ranged from 1.9 to 36 times higher in the exposed population.
8 We estimated the risks above mentioned, which were derived from exposure to minute quantities of arsenic in a known proportion of its oxidation states during a life time period.
A cross-sectional survey was conducted between April 1995 and March 1996 to investigate arsenic-associated skin lesions of keratosis and hyperpigmentation in West Bengal, India, and to determine their relationship to arsenic water levels.
In all, 7683 participants were examined and interviewed, and the arsenic levels in their drinking water measured.
Although water concentrations ranged up to 3400 microg/l of arsenic, over 80% of participants were consuming water containing <500 microg/l. The age-adjusted prevalence of keratosis was strongly related to water arsenic levels, rising from zero in the lowest exposure level (<50 microg/l) to 8.3 per 100 for females drinking water containing >800 microg/l, and increasing from 0.2 per 100 in the lowest exposure category to 10.7 per 100 for males in the highest exposure level (> or =800 microg/l). However, 12 cases with keratosis (2 females and 10 males) were drinking water containing <100 microg/l of arsenic. Findings were similar for hyperpigmentation, with strong dose-response relationships. Among those with hyperpigmentation, 29 cases were exposed to drinking water containing <100 microg/l. Calculation by dose per body weight showed that men had roughly two to three times the prevalence of both keratosis and hyperpigmentation compared to women apparently ingesting the same dose of arsenic from drinking water. Subjects who were below 80% of the standard body weight for their age and sex had a 1.6 fold increase in the prevalence of keratoses, suggesting that malnutrition may play a small role in increasing susceptibility.
The surprising finding of cases who had arsenic-associated skin lesions with apparently low exposure to arsenic in drinking water needs to be confirmed in studies with more detailed exposure assessment. Further research is also needed concerning susceptibility factors which might be present in the exposed population.
In a multicenter study, we evaluated the relationships between the extent and severity of bronchiectasis on CT and clinical symptoms, spirometric abnormality, and sputum characteristics.
The study population included 261 patients with symptomatic, physiologically significant bronchiectasis, who were enrolled in another study evaluating the clinical efficacy of deoxyribonudease in treatment of bronchiectasis. Patients with cystic fibrosis, allergic bronchopulmonary aspergillosis, and fungal or mycobacterial infection were excluded. In addition to high-resolution CT scanning, all patients underwent clinical evaluation, spirometry, and sputum culture. CT features scored by consensus of two observers included the extent of bronchiectasis, type of bronchiectasis (cylindric, varicose, or cystic), extent of mucoid impaction, and degree of bronchial wall thickening.
Scores for the severity and extent of bronchiectasis correlated with the forced expiratory volume in 1 sec (FEV1) (r = -.362, p < .0001) and with the forced vital capacity (FVC) (r = -.362, p < .0001). Scores for bronchial wall thickening correlated with the FEV1 (r = -.367, p < .0001) and FVC (r = -.239, p < .001). Patients with cystic bronchiectasis were significantly more likely to grow Pseudomonas from their sputa and to have purulent sputa than were patients with cylindric or varicose bronchiectasis. Patients with cystic bronchiectasis had significantly lower FEV1 and FVC values than did patients with cylindric or varicose bronchiectasis.
In this patient population, we found weak but significant correlations between the degree of morphologic abnormality on CT and the extent of physiologic impairment. Cystic bronchiectasis was associated with sputum purulence and with the growth of Pseudomonas. CT classification of the type of bronchiectasis may be useful as an index of severity of disease.
We assessed the levels of arsenic in drilled wells in Finland and studied the association of arsenic exposure with the risk of bladder and kidney cancers. The study persons were selected from a register-based cohort of all Finns who had lived at an address outside the municipal drinking-water system during 1967-1980 (n = 144,627). The final study population consisted of 61 bladder cancer cases and 49 kidney cancer cases diagnosed between 1981 and 1995, as well as an age- and sex-balanced random sample of 275 subjects (reference cohort). Water samples were obtained from the wells used by the study population at least during 1967-1980. The total arsenic concentrations in the wells of the reference cohort were low (median = 0.1 microg/L; maximum = 64 microg/L), and 1% exceeded 10 microg/L. Arsenic exposure was estimated as arsenic concentration in the well, daily dose, and cumulative dose of arsenic. None of the exposure indicators was statistically significantly associated with the risk of kidney cancer. Bladder cancer tended to be associated with arsenic concentration and daily dose during the third to ninth years prior to the cancer diagnosis; the risk ratios for arsenic concentration categories 0.1-0.5 and [Greater/equal to] 0.5 microg/L relative to the category with < 0.1 microg/L were 1.53 [95% confidence interval (CI), 0.75-3.09] and 2.44 (CI, 1.11-5.37), respectively. In spite of very low exposure levels, we found some evidence of an association between arsenic and bladder cancer risk. More studies are needed to confirm the possible association between arsenic and bladder cancer risk at such low exposure levels.
Nine districts in West Bengal, India, and 42 districts in Bangladesh have arsenic levels in groundwater above the World Health Organization maximum permissible limit of 50 microg/L. The area and population of the 42 districts in Bangladesh and the 9 districts in West Bengal are 92,106 km(2) and 79.9 million and 38,865 km(2) and 42.7 million, respectively. In our preliminary study, we have identified 985 arsenic-affected villages in 69 police stations/blocks of nine arsenic-affected districts in West Bengal. In Bangladesh, we have identified 492 affected villages in 141 police stations/blocks of 42 affected districts. To date, we have collected 10,991 water samples from 42 arsenic-affected districts in Bangladesh for analysis, 58,166 water samples from nine arsenic-affected districts in West Bengal. Of the water samples that we analyzed, 59 and 34%, respectively, contained arsenic levels above 50 microg/L. Thousands of hair, nail, and urine samples from people living in arsenic-affected villages have been analyzed to date; Bangladesh and West Bengal, 93 and 77% samples, on an average, contained arsenic above the normal/toxic level. We surveyed 27 of 42 districts in Bangladesh for arsenic patients; we identified patients with arsenical skin lesions in 25 districts. In West Bengal, we identified patients with lesions in seven of nine districts. We examined people from the affected villages at random for arsenical dermatologic features (11,180 and 29,035 from Bangladesh and West Bengal, respectively); 24.47 and 15.02% of those examined, respectively, had skin lesions. After 10 years of study in West Bengal and 5 in Bangladesh, we feel that we have seen only the tip of iceberg.
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A large population in West Bengal, India has been exposed to naturally occurring inorganic arsenic through their drinking water. A cross-sectional survey involving 7683 participants of all ages was conducted in an arsenic-affected region between April 1995 and March 1996. The main focus of the study was skin keratoses and pigmentation alterations, two characteristic signs of ingested inorganic arsenic. Strong exposure-response gradients were found for these skin lesions. The study also collected limited information concerning respiratory system signs and symptoms, which we report here because increasing evidence suggests that arsenic ingestion also causes pulmonary effects.
Participants were clinically examined and interviewed, and the arsenic content in their current primary drinking water source was measured. There were few smokers and analyses were confined to non-smokers (N = 6864 participants).
Among both males and females, the prevalence of cough, shortness of breath, and chest sounds (crepitations and/or rhonchi) in the lungs rose with increasing arsenic concentrations in drinking water. These respiratory effects were most pronounced in individuals with high arsenic water concentrations who also had skin lesions. Prevalence odds ratio (POR) estimates were markedly increased for participants with arsenic-induced skin lesions who also had high levels of arsenic in their current drinking water source (> or = 500 microg/l) compared with individuals who had normal skin and were exposed to low levels of arsenic (<50 microg/l). In participants with skin lesions, the age-adjusted POR estimates for cough were 7.8 for females (95% CI : 3.1-19.5) and 5.0 for males (95% CI : 2.6-9.9); for chest sounds POR for females was 9.6 (95% CI : 4.0-22.9) and for males 6.9 (95% CI : 3.1-15.0). The POR for shortness of breath in females was 23.2 (95% CI : 5.8-92.8) and in males 3.7 (95% CI : 1.3-10.6).
These results add to evidence that long-term ingestion of inorganic arsenic can cause respiratory effects.
Background There have been 13 randomised controlled trials of prophylactic amiodarone in patients with recent myocardial infarction (MI) or congestive heart failure (CHF). None of these was powered to detect a mortality reduction of about 20%. We undertook a meta-analysis, based on data from individual patients, to provide a more sensitive and accurate assessment of the benefits and risks of prophylactic amiodarone. Methods Individual data from the studies were abstracted according to a predefined protocol. The summary odds ratios were calculated according to standard methods. Findings There were eight post-MI and five CHF trials; nine trials were double-blind and placebo-controlled, and four compared amiodarone with usual care. 6553 patients were randomly assigned treatment, of which 78% were in post-MI trials and 22% in CHF trials. 89% had had previous MI. The mean left-ventricular ejection fraction was 31%, and median frequency of ventricular premature depolarisation 18 per h. Total mortality was reduced by 13% (odds ratio 0.87 [95% CI 0.78-0.99], p=0.030) based on classic fixed-effects meta-analysis and by 15% (0.85 [0.71-1.02], p=0.081) with the more conservative random-effects approach. Arrhythmic/sudden death was reduced by 29% (0.71 [0.59-0.85], p=0.0003). There was no effect on nonarrhythmic deaths (1.02 [0.87-1.19], p=0.84). There was no difference in treatment effect between post-Mi and CHF studies. The risk of arrhythmic/sudden death in control-group patients was higher in CHF than in post-MI studies (10.7 vs 4.1%), and the best single predictor of risk of arrhythmic/sudden death among all patients was symptomatic CHF. The excess (amiodarone minus control) risk of pulmonary toxicity was 1% per year. Interpretation Prophylactic amiodarone reduces the rate of arrhythmic/sudden death in high-risk patients with recent MI or CHF and this effect results in an overall reduction of 13% in total mortality.
This is a second report of epidemiological and clinical investigation, related to the arsenic health problem, unique in the world, occurring in the city of Antofagasta, Chile. The arsenic problem originates in the chronic contamination of water supply in the city during 12 years. This phenomena, investigated clinically and epidemiologically and first reported in 1971, prompted the installation of a water treatment plant. This report aims to evaluate the working efficiency of the plant. The study was carried out through the examination of arsenic content in hair and nail clipping samples of the inhabitants of Antofagasta and the determination of this element in cultivated vegetables and carbonated beverages. Also a clinical study in school children, looking for cutaneous lesions attributed to arsenicism, was made. Results are encouraging. They reveal that contamination persists but in significantly lower levels.
The antecedent of chronic arsenic poisoning was found in 5 cases at the time of autopsy. In all of them a peculiar vascular lesion was found, consisting of intimal thickening in the small and medium sized arteries. The most frequently involved organs were the heart, gastrointestinal tract, liver, skin and pancreas. In 2 cases, there was myocardial infarction; in a third case, an 'acute abdomen' was described. The vascular lesion is considered to be characteristic and easily recognized. The great majority of lesions found at autopsy were considered to be secondary to the vascular damage; others, although related to arsenic poisoning, were dependent on different pathogenetic mechanisms.
Investigations on the arsenic contamination of human environment in the northern provinces of Tarapaca, Antofagasta, and Coquimbo, as well as clinical studies on endemic chronic arsenic poisoning, were made. In Tarapaca Province, the total number of exposed nitrate workers since 1890 was about 30,000. But in Antofagasta and Coquimbo Provinces (1970), the number of exposed persons was 265,000 and 142,000 respectively. In Antofagasta Province, some population groups have been exposed to dietary arsenic for periods up to 41 years. The safety standard of arsenic in drinking water in the Federal Republic of Germany and in the U.S.A. is 0.05 ppm. The Hojalar, Toconce, Loa and Siloli Rivers exhibited a mean of 0.992, 0.940, 0.337 and 0.104 ppm, respectively. Soil samples from Antofagasta Commune exhibited a mean of 4.374 ppm. The mean arsenic levels found in fresh vegetables were partly high: lettuce 0.062, cauliflower 0.070, celery 0.104, and radish 0.100 mg/100 g. In other food items: fresh cow's milk 0.083 ppm, fresh human milk 0.216, vanilla ice cream 0.156, orange juice 0.120, pineapple juice 0.390, spaghetti 0.014 mg/100, and canned mackerel 0.025 mg/100g. The mean levels (ppm) in soft drinks and beer were high in Pepsi Cola (0.265), Ginger-ale (0.275), Bilz (0.275), Fanta (0.250), Coca Cola (0.204), Seltz water (0.291), Pilsner beer (0.553), Escudo (0.388), and Malta (0.484). Almost all the signs and symptoms of chronic arsenic poisoning observed in children at Antofagasta Commune in the 1968-69 period markedly decreased their prevalence in 1972, because of the decrease in the arsenic level of drinking water. The weighted mean arsenic concentration in drinking water at Antofagasta Commune for 1955-1970 (up to 30th April) was 0.5980 ppm. The corresponding level (weighted mean) from 1st June, 1970 to 30th March, 1972 was 0.815 ppm. In May 1970, a Water Filtration Plant went into operation at Salar del Carmen, near Antofagasta. A similar Filtration Plant in July 1978 started operating at Cerro Topater, near Calama. Based on mean age (years) and mean value of arsenic dose (mg/kg body weight/day), a weighted non linear regression model was developed. The non linear regression equation was C = 0.0303 exp (- 0.0257 t) + 0.0720 exp (- 0.2636 t), where C is arsenic concentration expressed as mean dose and t is time expressed as mean age.
An investigation on the relationship between dietary arsenic exposure and cardiovascular diseases was made. In Antofagasta Commune, northern Chile, since 1955 arsenic has polluted public drinking water. This environmental contamination is of geological origin. The concentration of arsenic in drinking water for the 1955-1970 period was 0.5980 ppm (weighted mean). In the period June 1970-March 1972, the concentration decreased to 0.0815 ppm (weighted mean), due to a Water Filtration Plant which started operating in May 1970. Greater Santiago showed 0.00 ppm of arsenic in drinking water. Amongst 10 autopsied patients (age range: 1 year 7 months to 18 years) with chronic arsenical dermatosis from Antofagasta Commune, 9 showed marked fibrous intimal thickening of the arterial wall and/or restricted lumen of the left coronary artery, 2 of these 9 also exhibiting myocardial infarction. Of the 10 patients, 7 developed cardiomegaly, which was related to chronic exposure to dietary arsenic. Two series of patients with myocardial infarction under 40 years of age, one from Antofagasta Commune (exposed to arsenic), the other from Greater Santiago (not exposed to arsenic) were compared. The Yates' corrected chi 2 value (1 d.f.) being 11.7776. The difference was statistically highly significant (P approximately equal to 0.0006018). Furthermore, in Antofagasta Commune, the number of cases (< 40 yr) which had myocardial infarction with chronic arsenical dermatosis were compared with the cases (< 40 yr) which showed myocardial infarction without chronic arsenical dermatosis. The Yates' corrected chi 2 value (1 d.f.) was 13.0395. A highly significant difference was detected (P approximately equal to 0.0003044). Children (0-15 yr)from the two cities were also compared.(ABSTRACT TRUNCATED AT 250 WORDS)
Inorganic arsenic (In-As) is known to be a human carcinogen, causing lung cancer by inhalation and skin cancer by ingestion. Ecologic studies in Taiwan have found a dose-response relation between ingestion of In-As from drinking water and bladder cancer, but questions have been raised concerning the validity and generalizability of the findings. Several areas of Argentina have had high exposures to arsenic from naturally contaminated drinking water, particularly the eastern region of the province of Córdoba. In this study, we investigated bladder cancer mortality for the years 1986-1991 in Córdoba's 26 counties, using rates for all of Argentina as the standard for comparison. Bladder cancer standardized mortality ratios (SMRs) were consistently higher in counties with documented arsenic exposure. We grouped counties into low-, medium-, and high-exposure categories; the corresponding SMRs [with 95% confidence intervals (CI)] were 0.80 (95% CI = 0.66-0.96), 1.42 (95% CI = 1.14-1.74), and 2.14 (95% CI = 1.78-2.53) for men, and 1.21 (95% CI = 0.85-1.64), 1.58 (95% CI = 1.01-2.35), and 1.82 (95% CI = 1.19-2.64) for women. The clear trends found in a population with different genetic composition and a high-protein diet support the findings in Taiwan.
Studies in Taiwan and Argentina suggest that ingestion of inorganic arsenic from drinking water results in increased risks of internal cancers, particularly bladder and lung cancer. The authors investigated cancer mortality in a population of around 400,000 people in a region of Northern Chile (Region II) exposed to high arsenic levels in drinking water in past years. Arsenic concentrations from 1950 to the present were obtained. Population-weighted average arsenic levels reached 570 microg/liter between 1955 to 1969, and decreased to less than 100 microg/liter by 1980. Standardized mortality ratios (SMRs) were calculated for the years 1989 to 1993. Increased mortality was found for bladder, lung, kidney, and skin cancer. Bladder cancer mortality was markedly elevated (men, SMR = 6.0 (95% confidence interval (CI) 4.8-7.4); women, SMR = 8.2 (95% CI 6.3-10.5)) as was lung cancer mortality (men, SMR = 3.8 (95% CI 3.5-4.1); women, SMR = 3.1 (95% CI 2.7-3.7)). Smoking survey data and mortality rates from chronic obstructive pulmonary disease provided evidence that smoking did not contribute to the increased mortality from these cancers. The findings provide additional evidence that ingestion of inorganic arsenic in drinking water is indeed a cause of bladder and lung cancer. It was estimated that arsenic might account for 7% of all deaths among those aged 30 years and over. If so, the impact of arsenic on the population mortality in Region II of Chile is greater than that reported anywhere to date from environmental exposure to a carcinogen in a major population.
Blackfoot disease was prevalent in a limited area on the southwest coast of Taiwan, where artesian well water containing arsenic (median = 0.78 ppm arsenic) had been used for many years. Previous studies of arsenic exposure in the blackfoot disease endemic area have been focused on malignant tumors. We, therefore, conducted this study to analyze mortality of all death causes in blackfoot disease endemic areas and to determine other neglected cancers or noncancer diseases related to artesian well water containing high levels of arsenic. We calculated standardized mortality ratios for cancer and noncancer diseases, by sex, during the period from 1971 to 1994 and compared them to the local reference group (i.e, Chiayi-Tainan County) and the national reference group (i.e., Taiwan population). The results revealed marked standardized mortality ratio differences for the 2 reference groups. Greater mortality was found for males and females with bladder, kidney, skin, lung, nasal-cavity, bone, liver, larynx, colon, and stomach cancers, as well as lymphoma than in the local reference population. With respect to noncancer diseases, we found greater mortality for males and females who had vascular disease, ischemic heart disease, diabetes mellitus, and bronchitis than in the local reference group. Mortalities for other diseases--including rectal cancer, cerebrovascular disease, and other diseases--were higher among cases than the local reference group. Our results indicated that the hazardous effect of arsenic is systemic. Diseases related to arsenic exposure included those reported previously by other investigators, as well as diseases reported in the present study.
Arsenic in drinking water causes a widespread concern in Bangladesh, where a major proportion of tube wells is contaminated. Arsenic ingestion causes skin lesions, which is considered as definite exposure. A prevalence comparison study of respiratory effects among subjects with and without arsenic exposure through drinking water was conducted in Bangladesh. Exposed participants were recruited through health awareness campaign programs. Unexposed participants were randomly selected, where tubewells were not contaminated with arsenic. A total of 169 individuals participated (44 exposed individuals exhibiting skin lesions; 125 unexposed individuals). The arsenic concentrations ranged from 136 to 1000 micro g l(-1). The information regarding respiratory system signs and symptoms were also collected and the analyses were confined to nonsmokers. The crude prevalence ratio for chronic bronchitis and chronic cough amounted to 2.1 (95% CI 0.7-6.1). The prevalence ratios for chronic bronchitis increased with increasing exposure, i.e., 1.0, 1.6, 2.7 and 2.6 using unexposed as the reference. The prevalence ratios for chronic cough were 1.0, 1.6, 2.7 and 2.6 for the exposure categories, using the same unexposed as the reference. The dose-response trend was the same (P < 0.1) for both conditions. These results add to evidence that long-term ingestion of arsenic exposure can cause respiratory effects.
Over 6 million people live in areas of West Bengal, India, where groundwater sources are contaminated with naturally occurring arsenic. The key objective of this nested case-control study was to characterize the dose-response relation between low arsenic concentrations in drinking water and arsenic-induced skin keratoses and hyperpigmentation.
We selected cases (persons with arsenic-induced skin lesions) and age- and sex-matched controls from participants in a 1995-1996 cross-sectional survey in West Bengal. We used a detailed assessment of arsenic exposure that covered at least 20 years. Participants were reexamined between 1998 and 2000. Consensus agreement by four physicians reviewing the skin lesion photographs confirmed the diagnosis in 87% of cases clinically diagnosed in the field.
The average peak arsenic concentration in drinking water was 325 microg/liter for cases and 180 microg/liter for controls. The average latency for skin lesions was 23 years from first exposure. We found strong dose-response gradients with both peak and average arsenic water concentrations.
The lowest peak arsenic ingested by a confirmed case was 115 microg/liter. Confirmation of case diagnosis and intensive longitudinal exposure assessment provide the basis for a detailed dose-response evaluation of arsenic-caused skin lesions.
Chronic arsenic toxicity due to drinking arsenic-contaminated water has been one of the worst environmental health hazards affecting eight districts of West Bengal since the early eighties. Detailed clinical examination and investigation of 248 such patients revealed protean clinical manifestations of such toxicity. Over and above hyperpigmentation and keratosis, weakness, anaemia, burning sensation of eyes, solid swelling of legs, liver fibrosis, chronic lung disease, gangrene of toes, neuropathy, and skin cancer are some of the other manifestations. A cross-sectional survey involving 7683 participants of all ages was conducted in an arsenic-affected region between April 1995 and March 1996. Out of a population of 7683 surveyed, 3467 and 4216 people consumed water containing As below and above 0.05 mg/L, respectively. Except pain abdomen the prevalence of all other clinical manifestations tested (e.g., pigmentation, keratosis, hepatomegaly, weakness, nausea, lung disease and neuropathy) were found to be significantly higher in As exposed people (water As > 0.05 mg/L) compared to control population (water As level < 0.05 mg/L). The prevalence of pigmentation and keratosis, hepatomegaly, chronic respiratory disease and weakness rose significantly with increasing arsenic concentrations in drinking water. The respiratory effects were most pronounced in individuals with high arsenic water concentrations who also had skin lesion. Therapy with chelating agent DMSA was not found to be superior to placebo effect. However, therapy with DMPS caused significant improvement of clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90 +/- 2.84 to 3.27 +/- 1.73; p < 0.0001. Efficacy of specific chelation therapy for patients suffering from chronic As toxicity has further need to be fully substantiated. However, supportive treatment could help in reducing many symptoms of the patients. Treatment in hospital with good nutritious diet has been found to reduce symptom score in a subset of placebo treated patients in West Bengal during the course of DMSA and DMPS trial. People should be advised to stop drinking As contaminated water or exposure to As from any other source. The various clinical manifestations should be treated symptomatically.