Fatal Occupational Asthma in Cannabis Production - Massachusetts, 2022.

Multiple respiratory hazards have been identified in the cannabis cultivation and production industry, in which occupational asthma and work-related exacerbation of preexisting asthma have been reported. An employee working in a Massachusetts cannabis cultivation and processing facility experienced progressively worsening work-associated respiratory symptoms, which culminated in a fatal asthma attack in January 2022. This report represents findings of an Occupational Safety and Health Administration inspection, which included a worksite exposure assessment, coworker and next-of-kin interviews, medical record reviews, and collaboration with the Massachusetts Department of Public Health. Respiratory tract or skin symptoms were reported by four of 10 coworkers with similar job duties. Prevention is best achieved through a multifaceted approach, including controlling asthmagen exposures, such as cannabis dust, providing worker training, and conducting medical monitoring for occupational allergy. Evaluation of workers with new-onset or worsening asthma is essential, along with prompt diagnosis and medical management, which might include cessation of work and workers' compensation when relation to work exposures is identified. It is important to recognize that work in cannabis production is potentially causative.

Hospitalised heat-related acute kidney injury in indoor and outdoor workers in the USA.

OBJECTIVES: To characterise heat-related acute kidney injury (HR-AKI) among US workers in a range of industries. METHODS: Two data sources were analysed: archived case files of the Occupational Safety and Health Administration's (OSHA) Office of Occupational Medicine and Nursing from 2010 through 2020; and a Severe Injury Reports (SIR) database of work-related hospitalisations that employers reported to federal OSHA from 2015 to 2020. Confirmed, probable and possible cases of HR-AKI were ascertained by serum creatinine measurements and narrative incident descriptions. Industry-specific incidence rates of HR-AKI were computed. A capture-recapture analysis assessed under-reporting in SIR. RESULTS: There were 608 HR-AKI cases, including 22 confirmed cases and 586 probable or possible cases. HR-AKI occurred in indoor and outdoor industries including manufacturing, construction, mail and package delivery, and solid waste collection. Among confirmed cases, 95.2% were male, 50.0% had hypertension and 40.9% were newly hired workers. Incidence rates of AKI hospitalisations from 1.0 to 2.5 hours per 100 000 workers per year were observed in high-risk industries. Analysis of overlap between the data sources found that employers reported only 70.6% of eligible HR-AKI hospitalisations to OSHA, and only 41.2% of reports contained a consistent diagnosis. CONCLUSIONS: Workers were hospitalised with HR-AKI in diverse industries, including indoor facilities. Because of under-reporting and underascertainment, national surveillance databases underestimate the true burden of occupational HR-AKI. Clinicians should consider kidney risk from recurrent heat stress. Employers should provide interventions, such as comprehensive heat stress prevention programmes, that include acclimatisation protocols for new workers, to prevent HR-AKI.

Toxic environmental exposures and kidney health in children.

High-level exposures to a number of agents are known to have direct nephrotoxic effects in children. A growing body of literature supports the hypothesis that chronic, relatively low-level exposure to various nephrotoxicants may also increase the risk for chronic kidney disease (CKD) or accelerate its progression. In this review we highlight several environmental nephrotoxicants and their association with CKD in children and adolescents. We also discuss unique epidemiological challenges in the use of kidney biomarkers in environmental nephrotoxicology.

Challenges for environmental epidemiology research: are biomarker concentrations altered by kidney function or urine concentration adjustment?

Biomonitoring has become a standard approach for exposure assessment in occupational and environmental epidemiology. The use of biological effect markers to identify early adverse changes in target organs has also become widely adopted. However, the potential for kidney function to affect biomarker levels in the body and the optimal approach to adjustment of biomarker concentrations in spot urine samples for hydration status are two important but underappreciated challenges associated with biomarker use. Several unexpected findings, such as positive associations between urine nephrotoxicant levels and estimated glomerular filtration rate (eGFR), have been reported recently in research using biomarkers. These and other findings, discussed herein, suggest an impact of kidney glomerular filtration or tubule processing on biomarker levels. This is more commonly raised in the context of decreased kidney filtration, traditionally referred to as reverse causality; however, recent data suggest that populations with normal kidney filtration may be affected as well. Misclassification bias would result if biomarkers reflect kidney function as well as either exposures or early biological effect outcomes. Furthermore, urine biomarker associations with eGFR that differ markedly by approach used to adjust for urine concentration have been reported. Associations between urine measures commonly used for this adjustment, such as urine creatinine, and specific research outcomes could alter observed biomarker associations with outcomes. Research recommendations to address the potential impact of kidney function and hydration status adjustment on biomarkers are provided, including a range of approaches to study design, exposure and outcome assessment, and adjustment for urine concentration.

Is Early Prescribing of Opioid and Psychotropic Medications Associated With Delayed Return to Work and Increased Final Workers' Compensation Cost?

OBJECTIVE: To explore the association between the initial 60 days of prescriptions for psychotropic medications and final workers' compensation claim outcomes. METHODS: A cohort of 11,394 claimants involved in lost time injuries between 1999 and 2002 were followed through December 31, 2009. Logistic regressions and Cox Proportional Hazard Models were used in the analysis. RESULTS: The initial 60 days of prescriptions for psychotropic medications were significantly associated with a final claim cost at least $100,000. Odds ratios were 1.88 for short-acting opioids, 2.14 for hypnotics, antianxiety agents, or antidepressants, and 3.91 for long-acting opioids, respectively. Significant associations were also found between decreased time lost from work and decreased claim closures during the study period. CONCLUSIONS: Early prescription of opioids and other psychotropic drugs may be useful predictors of high claim costs and time lost from work.

The association of urine arsenic with prevalent and incident chronic kidney disease: evidence from the Strong Heart Study.

BACKGROUND: Few studies have evaluated associations between low to moderate arsenic levels and chronic kidney disease (CKD). The objective was to evaluate the associations of inorganic arsenic exposure with prevalent and incident CKD in American Indian adults. METHODS: We evaluated the associations of inorganic arsenic exposure with CKD in American Indians who participated in the Strong Heart Study in 3,851 adults ages 45-74 years in a cross-sectional analysis, and 3,119 adults with follow-up data in a prospective analysis. Inorganic arsenic, monomethylarsonate, and dimethylarsinate were measured in urine at baseline. CKD was defined as estimated glomerular filtration rate ≤ 60 ml/min/1.73 m, kidney transplant or dialysis. RESULTS: CKD prevalence was 10.3%. The median (IQR) concentration of inorganic plus methylated arsenic species (total arsenic) in urine was 9.7 (5.8, 15.7) µg/L. The adjusted odds ratio (OR; 95% confidence interval) of prevalent CKD for an interquartile range in total arsenic was 0.7 (0.6, 0.8), mostly due to an inverse association with inorganic arsenic (OR: 0.4 [0.3, 0.4]). Monomethylarsonate and dimethylarsinate were positively associated with prevalent CKD after adjustment for inorganic arsenic (OR: 3.8 and 1.8). The adjusted hazard ratio of incident CKD for an IQR in sum of inorganic and methylated arsenic was 1.2 (1.03, 1.41). The corresponding HRs for inorganic arsenic, monomethylarsonate, and dimethylarsinate were 1.0 (0.9, 1.2), 1.2 (1.00, 1.3), and 1.2 (1.0, 1.4). CONCLUSIONS: The inverse association of urine inorganic arsenic with prevalent CKD suggests that kidney disease affects excretion of inorganic arsenic. Arsenic species were positively associated with incident CKD. Studies with repeated measures are needed to further characterize the relation between arsenic and kidney disease development.

The association of the use of opioid and psychotropic medications with workers' compensation claim costs and lost work time.

OBJECTIVE: To study the relationship between the use of psychotropic and opioid medications with workers' compensation disability and costs. METHODS: The study population included lost time claimants injured between 1999 and 2002 followed to closing in December 31, 2009. RESULTS: Controlling for age, sex, marital status, attorney involvement, and spinal surgeries, multivariate logistic regression revealed that odds ratios (95% confidence interval) of claim costs ≥$100,000 compared with claimants who were never prescribed opioids were 4.3 for short-acting opioids only; 8.6 for any use of long-acting opioids; 2.8 for any use of hypnotics; 2.6 for any use of antipsychotics; 1.6 for any use of anti-anxiety agents; and 2.9 for any use of antidepressants. CONCLUSIONS: The use of psychotropic and opioid medications was associated with high workers' compensation costs and prolonged disability.

Arsenic and Chronic Kidney Disease: A Systematic Review.

In epidemiologic studies, high arsenic exposure has been associated with adverse kidney disease outcomes. We performed a systematic review of the epidemiologic evidence of the association between arsenic and various kidney disease outcomes. The search period was January 1966 through January 2014. Twenty-five papers (comprising 24 studies) meeting the search criteria were identified and included in this review. In most studies, arsenic exposure was assessed by measurement of urine concentrations or with an ecological indicator. There was a generally positive association between arsenic and albuminuria and proteinuria outcomes. There was mixed evidence of an association between arsenic exposure and chronic kidney disease (CKD), ß-2 microglobulin (ß2MG), and N-acetyl-ß-D-glucosaminidase (NAG) outcomes. There was evidence of a positive association between arsenic exposure and kidney disease mortality. Assessment of a small number of studies with three or more categories showed a clear dose-response association between arsenic and prevalent albuminuria and proteinuria, but not with CKD outcomes. Eight studies lacked adjustment for possible confounders, and two had small study populations. The evaluation of the causality of the association between arsenic exposure and kidney disease outcomes is limited by the small number of studies, lack of study quality, and limited prospective evidence. Because of the high prevalence of arsenic exposure worldwide, there is a need for additional well-designed epidemiologic and mechanistic studies of arsenic and kidney disease outcomes.

Association of arsenic and metals with concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D among adolescents in Torreón, Mexico.

BACKGROUND: Limited data suggest that lead (Pb), cadmium (Cd), and uranium (U) may disrupt vitamin D metabolism and inhibit production of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active vitamin D metabolite, from 25-hydroxyvitamin D [25(OH)D] in the kidney. OBJECTIVES: We evaluated the association between blood lead (BPb) and urine arsenic (As), Cd, molybdenum (Mo), thallium (Tl), and U with markers of vitamin D metabolism [25(OH)D and 1,25(OH)2D]. METHODS: We conducted a cross-sectional study of 512 adolescents in Torreón, a town in Mexico with a Pb smelter near residential areas. BPb was measured using atomic absorption spectrometry. Urine As, Cd, Mo, Tl, and U were measured using inductively coupled plasma mass spectrometry. Serum 25(OH)D and 1,25(OH)2D were measured using a chemiluminescent immunoassay and a radioimmunoassay, respectively. Multivariable linear models with vitamin D markers as the outcome were used to estimate associations of BPb and creatinine-corrected urine As and metal concentrations with serum vitamin D concentrations, controlling for age, sex, adiposity, smoking, socioeconomic status, and time outdoors. RESULTS: Serum 25(OH)D was positively associated with urine Mo and Tl [1.5 (95% CI: 0.4, 2.6) and 1.2 (95% CI: 0.3, 2.1) ng/mL higher with a doubling of exposure, respectively]. Serum 1,25(OH)2D was positively associated with urine As and U [3.4 (95% CI: 0.9, 5.9) and 2.2 (95% CI: 0.7, 3.7) pg/mL higher, respectively], with little change in associations after additional adjustment for serum 25(OH)D. Pb and Cd were not associated with 25(OH)D or 1,25(OH)2D concentrations. CONCLUSIONS: Overall, our findings did not support a negative effect of As or metal exposures on serum 1,25(OH)2D concentrations. Additional research is needed to confirm positive associations between serum 1,25(OH)2D and urine U and As concentrations and to clarify potential underlying mechanisms.

Impact of urine concentration adjustment method on associations between urine metals and estimated glomerular filtration rates (eGFR) in adolescents.

Positive associations between urine toxicant levels and measures of glomerular filtration rate (GFR) have been reported recently in a range of populations. The explanation for these associations, in a direction opposite that of traditional nephrotoxicity, is uncertain. Variation in associations by urine concentration adjustment approach has also been observed. Associations of urine cadmium, thallium and uranium in models of serum creatinine- and cystatin-C-based estimated GFR (eGFR) were examined using multiple linear regression in a cross-sectional study of adolescents residing near a lead smelter complex. Urine concentration adjustment approaches compared included urine creatinine, urine osmolality and no adjustment. Median age, blood lead and urine cadmium, thallium and uranium were 13.9 years, 4.0 µg/dL, 0.22, 0.27 and 0.04 g/g creatinine, respectively, in 512 adolescents. Urine cadmium and thallium were positively associated with serum creatinine-based eGFR only when urine creatinine was used to adjust for urine concentration (ß coefficient=3.1 mL/min/1.73 m(2); 95% confidence interval=1.4, 4.8 per each doubling of urine cadmium). Weaker positive associations, also only with urine creatinine adjustment, were observed between these metals and serum cystatin-C-based eGFR and between urine uranium and serum creatinine-based eGFR. Additional research using non-creatinine-based methods of adjustment for urine concentration is necessary.

Uranium associations with kidney outcomes vary by urine concentration adjustment method.

Uranium is a ubiquitous metal that is nephrotoxic at high doses. Few epidemiologic studies have examined the kidney filtration impact of chronic environmental exposure. In 684 lead workers environmentally exposed to uranium, multiple linear regression was used to examine associations of uranium measured in a 4-h urine collection with measured creatinine clearance, serum creatinine- and cystatin-C-based estimated glomerular filtration rates, and N-acetyl-ß-D-glucosaminidase (NAG). Three methods were utilized, in separate models, to adjust uranium levels for urine concentration--µg uranium/g creatinine; µg uranium/l and urine creatinine as separate covariates; and µg uranium/4 h. Median urine uranium levels were 0.07 µg/g creatinine and 0.02 µg/4 h and were highly correlated (rs=0.95). After adjustment, higher ln-urine uranium was associated with lower measured creatinine clearance and higher NAG in models that used urine creatinine to adjust for urine concentration but not in models that used total uranium excreted (µg/4 h). These results suggest that, in some instances, associations between urine toxicants and kidney outcomes may be statistical, due to the use of urine creatinine in both exposure and outcome metrics, rather than nephrotoxic. These findings support consideration of non-creatinine-based methods of adjustment for urine concentration in nephrotoxicant research.

Blood lead level and measured glomerular filtration rate in children with chronic kidney disease.

BACKGROUND: The role of environmental exposure to lead as a risk factor for chronic kidney disease (CKD) and its progression remains controversial, and most studies have been limited by a lack of direct glomerular filtration rate (GFR) measurement. OBJECTIVE: We evaluated the association between lead exposure and GFR in children with CKD. METHODS: In this cross-sectional study, we examined the association between blood lead levels (BLLs) and GFR measured by the plasma disappearance of iohexol among 391 participants in the Chronic Kidney Disease in Children (CKiD) prospective cohort study. RESULTS: Median BLL and GFR were 1.2 µg/dL and 44.4 mL/min per 1.73 m2, respectively. The average percent change in GFR for each 1-µg/dL increase in BLL was -2.1 (95% CI: -6.0, 1.8). In analyses stratified by CKD diagnosis, the association between BLL and GFR was stronger among children with glomerular disease underlying CKD; in this group, each 1-µg/dL increase in BLL was associated with a -12.1 (95% CI: -22.2, -1.9) percent change in GFR. In analyses stratified by anemia status, each 1-µg/dL increase in BLL among those with and without anemia was associated with a -0.3 (95% CI: -7.2, 6.6) and -4.6 (95% CI: -8.9, -0.3) percent change in GFR, respectively. CONCLUSIONS: There was no significant association between BLL and directly measured GFR in this relatively large cohort of children with CKD, although associations were observed in some subgroups. Longitudinal analyses are needed to examine the temporal relationship between lead and GFR decline, and to further examine the impact of underlying cause of CKD and anemia/hemoglobin status among patients with CKD.

Kidney function and tobacco smoke exposure in US adolescents.

BACKGROUND AND OBJECTIVE: Active smoking and secondhand smoke (SHS) are known risk factors for kidney disease in adults. We evaluated the association between exposure to active smoking or SHS and kidney function in US adolescents. METHODS: This is a cross-sectional study in 7516 adolescents aged 12-17 who participated in NHANES 1999-2010 and had serum creatinine and cotinine measures. Active smoking was defined as self-reported smoking or serum cotinine concentrations >10 ng/mL. SHS was defined as nonactive smokers who self-reported living with ≥1 smokers or serum cotinine concentrations ≥ 0.05 ng/mL. Kidney function was determined by using the chronic kidney disease in children estimated glomerular filtration rate (eGFR) equation. RESULTS: Median (interquartile range) eGFR and serum cotinine concentrations were 96.8 (85.4-109.0) mL/minute per 1.73 m(2) and 0.07 (0.03-0.59) ng/mL, respectively. After multivariable adjustment, eGFR decreased 1.1 mL/minute per 1.73 m(2) (95% confidence interval [CI]: -1.8 to -0.3) per interquartile range increase in serum cotinine concentrations. The mean (95%CI) difference in eGFR for serum cotinine tertiles 1, 2, and 3 among children exposed to SHS compared to unexposed were -0.4 (-1.9 to 1.2), -0.9 (-2.7 to 0.9), and -2.2 (-4.0 to -0.4) mL/minute per 1.73 m(2), respectively (P = .03). The corresponding values among tertiles of active smokers compared to unexposed were 0.2 (-2.2 to 2.6), -1.9 (-3.8 to 0.0), and -2.6 (-4.6 to -0.6) mL/minute per 1.73 m(2) (P = .01). CONCLUSIONS: Tobacco smoke exposure was associated with decreased eGFR in US adolescents, supporting the possibility that tobacco smoke effects on kidney function begin in childhood.

Urine arsenic and prevalent albuminuria: evidence from a population-based study.

BACKGROUND: Long-term arsenic exposure is a major global health problem. However, few epidemiologic studies have evaluated the association of arsenic with kidney measures. Our objective was to evaluate the cross-sectional association between inorganic arsenic exposure and albuminuria in American Indian adults from rural areas of Arizona, Oklahoma, and North and South Dakota. STUDY DESIGN: Cross-sectional. SETTING & PARTIPANTS: Strong Heart Study locations in Arizona, Oklahoma, and North and South Dakota. 3,821 American Indian men and women aged 45-74 years with urine arsenic and albumin measurements. PREDICTOR: Urine arsenic. OUTCOMES: Urine albumin-creatinine ratio and albuminuria status. MEASUREMENTS: Arsenic exposure was estimated by measuring total urine arsenic and urine arsenic species using inductively coupled plasma mass spectrometry (ICPMS) and high-performance liquid chromatography-ICPMS, respectively. Urine albumin was measured by automated nephelometric immunochemistry. RESULTS: The prevalence of albuminuria (albumin-creatinine ratio ≥30 mg/g) was 30%. Median value for the sum of inorganic and methylated arsenic species was 9.7 (IQR, 5.8-15.6) µg per gram of creatinine. Multivariable-adjusted prevalence ratios of albuminuria (albumin-creatinine ratio ≥30 mg/g) comparing the 3 highest to lowest quartiles of the sum of inorganic and methylated arsenic species were 1.16 (95% CI, 1.00-1.34), 1.24 (95% CI, 1.07-1.43), and 1.55 (95% CI, 1.35-1.78), respectively (P for trend <0.001). The association between urine arsenic and albuminuria was observed across all participant subgroups evaluated and was evident for both micro- and macroalbuminuria. LIMITATIONS: The cross-sectional design cannot rule out reverse causation. CONCLUSIONS: Increasing urine arsenic concentrations were cross-sectionally associated with increased albuminuria in a rural US population with a high burden of diabetes and obesity. Prospective epidemiologic and mechanistic evidence is needed to understand the role of arsenic as a kidney disease risk factor.

Associations of multiple metals with kidney outcomes in lead workers.

OBJECTIVES: Environmental exposure to multiple metals is common. A number of metals cause nephrotoxicity with acute and/or chronic exposure. However, few epidemiologic studies have examined the impact of metal coexposure on kidney function. Therefore, the authors evaluated associations of antimony and thallium with kidney outcomes and assessed the impact of cadmium exposure on those associations in lead workers. METHODS: Multiple linear regression was used to examine associations between ln-urine thallium, antimony and cadmium levels with serum creatinine- and cystatin-C-based glomerular filtration measures and ln-urine N-acetyl-ß-D-glucosaminidase (NAG). RESULTS: In 684 participants, median urine thallium and antimony were 0.39 and 0.36 µg/g creatinine, respectively. After adjustment for lead dose, urine creatinine and kidney risk factors, higher ln-urine thallium was associated with higher serum creatinine- and cystatin-C-based estimates of glomerular filtration rate; associations remained significant after adjustment for antimony and cadmium (regression coefficient for serum creatinine-based estimates of glomerular filtration rate =5.2 ml/min/1.73 m2; 95% CI =2.4 to 8.0). Antimony associations with kidney outcomes were attenuated by thallium and cadmium adjustment; thallium and antimony associations with NAG were attenuated by cadmium. CONCLUSIONS: Urine thallium levels were significantly associated with both serum creatinine- and cystatin-C-based glomerular filtration measures in a direction opposite that expected with nephrotoxicity. Given similarities to associations recently observed with cadmium, these results suggest that interpretation of urine metal values, at exposure levels currently present in the environment, may be more complex than previously appreciated. These results also support multiple metal analysis approaches to decrease the potential for inaccurate risk conclusions.

Secondhand tobacco smoke: a source of lead exposure in US children and adolescents.

OBJECTIVES: We evaluated the relationship between secondhand tobacco smoke (SHS) exposure and blood lead levels in US children and adolescents. METHODS: We analyzed data from 6830 participants aged 3-19 years in the National Health and Nutrition Examination Survey (1999-2004) who were not active smokers and for whom SHS exposure information and blood lead measurements were available. RESULTS: After multivariable adjustment, participants in the highest quartile of serum cotinine (≥ 0.44 µg/L) had 28% (95% confidence interval = 21%, 36%) higher blood lead levels than had those in the lowest quartile (< 0.03 µg/L). Similarly, blood lead levels were 14% and 24% higher in children who lived with 1 or with 2 or more smokers, respectively, than they were in children living with no smokers. Among participants for whom lead dust information was available, the associations between SHS and blood lead levels were similar before and after adjustment for lead dust concentrations. CONCLUSIONS: SHS may contribute to increased blood lead levels in US children. Lead dust does not appear to mediate this association, suggesting inhalation as a major pathway of exposure. Eliminating SHS exposure could reduce lead exposure in children.

Blood cadmium and estimated glomerular filtration rate in Korean adults.

BACKGROUND: Cadmium is a nephrotoxicant at high exposure levels. Few studies have evaluated the role of cadmium in kidney function at low-exposure levels. OBJECTIVE: We evaluated the association of blood cadmium with estimated glomerular filtration rate (eGFR) in the Korean adult population. METHODS: We evaluated 1,909 adults ≥ 20 years of age who participated in the 2005 Korean National Health and Nutrition Examination Survey and had blood cadmium determinations. eGFR was calculated using the Modification of Diet in Renal Disease equation. RESULTS: Blood cadmium geometric means were 1.57 µg/L for men and 1.49 µg/L for women. The difference in eGFR levels that compared participants in the highest versus lowest cadmium tertiles, after multivariable adjustment, was -1.85 [95% confidence interval (CI): -3.55, -0.16] mL/min per 1.73 m2 in women and 0.67 (-1.16, 2.50) mL/min per 1.73 m2 in men. Among men, the association between blood cadmium and eGFR was modified by blood lead levels (p-value for interaction = 0.048). The fully adjusted differences in eGFR levels for a 2-fold increase in blood cadmium levels were -1.14 (-3.35, 1.07) and 1.84 (0.54, 3.14) mL/min per 1.73 m2 in men with blood lead levels below and above the median (2.75 µg/dL), respectively. CONCLUSION: Elevated blood cadmium levels were associated with lower eGFR in women, which supports the role of cadmium as a risk factor for chronic kidney disease. In men, there was no overall association, although elevated blood cadmium levels were associated with higher eGFR levels in men with high blood lead levels and nonstatistically associated with lower eGFR levels in men with low blood lead levels.