Club cell protein (CC16) in serum as an effect marker for small airway epithelial damage caused by diesel exhaust and blasting fumes in potash mining.

OBJECTIVE: The effect marker club cell protein (CC16) is secreted by the epithelium of the small respiratory tract into its lumen and passes into the blood. Increased amounts of CC16 in serum are observed during acute epithelial lung injury due to air pollutants. CC16 in serum was determined as part of this cross-sectional study in underground potash miners on acute and chronic health effects from exposures to diesel exhaust and blasting fumes. METHODS: Nitrogen oxides, carbon monoxide, and diesel particulate matter were measured in 672 workers at a German potash mining site on a person-by-person basis over an early shift or midday shift, together with CC16 serum concentrations before and after the respective shift. CC16 concentrations and CC16 shift-differences were evaluated with respect to personal exposure measurements and other quantitative variables by Spearman rank correlation coefficients. CC16 shift-differences were modeled using multiple linear regression. Above-ground workers as reference group were compared to the exposed underground workers. RESULTS: Serum concentrations of CC16 were influenced by personal characteristics such as age, smoking status, and renal function. Moreover, they showed a circadian rhythm. While no statistically significant effects of work-related exposure on CC16 concentrations were seen in never smokers, such effects were evident in current smokers. CONCLUSION: The small airways of current smokers appeared to be vulnerable to the combination of measured work-related exposures and individual exposure to smoking. Therefore, as health protection of smokers exposed to diesel exhaust and blasting fumes, smoking cessation is strongly recommended.

Underground salt and potash workers exposed to nitrogen oxides and diesel exhaust: assessment of specific effect biomarkers.

PURPOSE: Occupational exposure limits (OEL) for nitrogen oxides (NO, NO2) and diesel exhaust (EC-DPM) were reassessed by the German authorities in 2016/2017. We performed a clinical cross-sectional study among salt and potash underground workers exposed to these substances at relatively high levels to examine possible indicators of acute effects on workers' health. METHODS: We measured post- versus pre-shift differences in cardiovascular, inflammatory, immune, and respiratory effect biomarkers and assessed their associations with personal exposures measured during the same shift. We also compared post- versus pre-shift differences in biomarker levels between exposure groups defined based on work site and job type. RESULTS: None of the above-ground workers exceeded the OEL for NO2 and only 5% exceeded the OEL for EC-DPM exposure. Among underground workers, 33% of miners and 7% underground maintenance workers exceeded the OEL for NO2; the OEL for EC-DPM was exceeded by 56% of miners and 17% of maintenance workers. Some effect biomarkers (thrombocytes, neutrophils, MPO, TNF-α, IgE, FeNO) showed statistically significant differences between pre- versus post-shift measurements; however, there were no consistent associations between pre- and post-shift differences and exposure group or personal exposure measurements during the shift. CONCLUSIONS: We did not find evidence of associations between workplace exposure to NO, NO2 or EC-DPM and clinically relevant indicators of acute cardiovascular, inflammatory and immune, or respiratory effects among salt and potash underground workers in Germany.

Review of the Evidence from Epidemiology, Toxicology, and Lung Bioavailability on the Carcinogenicity of Inhaled Iron Oxide Particulates.

Since the iron-age and throughout the industrial age, humans have been exposed to iron oxides. Here, we review the evidence from epidemiology, toxicology, and lung bioavailability as to whether iron oxides are likely to act as human lung carcinogens. Current evidence suggests that observed lung tumors in rats result from a generic particle overload effect and local inflammation that is rat-specific under the dosing conditions of intratracheal instillation. This mode of action therefore, is not relevant to human exposure. However, there are emerging differences seen in vitro, in cell uptake and cell bioavailability between "bulk" iron oxides and "nano" iron oxides. "Bulk" particulates, as defined here, are those where greater than 70% are >100 nm in diameter. Similarly, "nano" iron oxides are defined in this context as particulates where the majority, usually >95% for pure engineered forms of primary particulates (not agglomerates), fall in the range 1-100 nm in diameter. From the weight of scientific evidence, "bulk" iron oxides are not genotoxic/mutagenic. Recent evidence for "nano" iron oxide is conflicting regarding genotoxic potential, albeit genotoxicity was not observed in an in vivo acute oral dose study, and "nano" iron oxides are considered safe and are being investigated for biomedical uses; there is no specific in vivo genotoxicity study on "nano" iron oxides via inhalation. Some evidence is available that suggests, hypothetically due to the larger surface area of "nano" iron oxide particulates, that toxicity could be exerted via the generation of reactive oxygen species (ROS) in the cell. However, the potential for ROS generation as a basis for explaining rodent tumorigenicity is only apparent if free iron from intracellular "nano" scale iron oxide becomes bioavailable at significant levels inside the cell. This would not be expected from "bulk" iron oxide particulates. Furthermore, human epidemiological evidence from a number of studies suggests that iron oxide is not a human carcinogen, and therefore, based upon the complete weight of evidence, we conclude that "bulk" iron oxides are not human carcinogens.

Impact of diesel exhaust exposure on urinary 1-hydroxypyrene in underground salt and potash workers.

BACKGROUND: Diesel engine exhaust (DEE) and some of the polycyclic aromatic hydrocarbons (PAH) it contains are carcinogenic to humans (for example benzo(a)pyrene) and can cause lung cancer in workers. The objective of this study was to assess exposures to DEE and its component PAH and the potential associations between these two health hazards in a salt and potash mining population. METHODS: Between 2017 and 2019, 1003 underground workers (mining n = 801, maintenance n = 202) and 243 above-ground facility workers from two German mines participated. Personal exposure to DEE was assessed in air as elemental carbon for diesel particulate matter (EC-DPM), whereas exposure to PAH was assessed in pre- and post-shift urine samples in terms of 1-hydroxypyrene (1-OHP). Associations between EC-DPM and 1-OHP were studied using linear regression models. RESULTS: The highest EC-DPM exposures were measured in mining workers (median 0.06 mg/m³) followed by workers in the maintenance (0.03 mg/m3) and facility areas (<0.02 mg/m3). Exposures above the current German occupational threshold level of 0.05 mg/m3 were observed in 56%, 17%, and 5% of mining, maintenance and facility workers, respectively. 1-OHP increased statistically significantly across a work shift in underground workers but not in facility workers. Regression analyses revealed an increase of post-shift 1-OHP by almost 80% in mining and 40% in maintenance compared with facility workers. 1-OHP increased with increasing EC-DPM among underground workers. However, internal exposure of 1-OHP mainly remained at levels similar to those of the German general population in more than 90% of the urine samples. CONCLUSIONS: While exposures to DEE above the current German OEL for EC-DPM are quite common in the studied population of underground salt and potash miners (39.5% overall), urinary concentrations of 1-OHP did not reflect these findings.

Cross-sectional Study of Workers Employed at a Copper Smelter-Effects of Long-term Exposures to Copper on Lung Function and Chronic Inflammation.

OBJECTIVE: The aim of the study was to assess the effect of exposure to copper-containing dust on lung function and inflammatory endpoints among workers of a German copper plant, effects rarely studied before. METHODS: One hundred four copper-exposed smelter workers and 70 referent workers from the precious metal and lead facilities were included, with different metal exposures in both groups due to the different process materials. Body plethysmography, exhaled nitric oxide (FeNO) measurements, and blood sampling were conducted in all workers. Smoking status and the use of respiratory protective equipment were considered. In a subgroup of 40 nonsmoking volunteers (28 copper-exposed and 12 referents), sputum biomarkers were assessed. RESULTS: Median lung function values of both copper-exposed and the referent groups were within reference ranges of "healthy" individuals, and statistical differences between the groups were mostly not evident. Similarly, differences in blood and sputum biomarkers were too small to be biologically relevant. CONCLUSION: The results suggest the absence of the detectable effects of copper-containing dust exposure on lung function or chronic inflammation within the investigated cohort.

A Health Surveillance Study of Workers Employed at a Copper Smelter-Effects of Long-Term Exposure to Copper on Lung Function Using Spirometric Data.

OBJECTIVE: Significantly lower permissible occupational exposure limits for copper dust are being discussed in Europe and other jurisdictions. However, little data are published on exposures in occupational settings and copper-specific effects in humans. Hence, a health surveillance study was performed among workers employed at a copper smelter between 1972 and 2018. METHODS: Possible effects of long-term exposures to dust containing copper on lung function were assessed. Specifically, declines in forced expiratory volume in 1 second (FEV1) were compared between a copper-exposed and control group. Cumulative copper exposures were derived from historical airborne monitoring data. RESULTS: FEV1 declines among exposed and control never smokers were similar to a typical age-dependent decline of 29 mL/y. CONCLUSION: The study findings indicate that cumulative inhalable copper dust exposure averaging 4.61 mg/m3-years over an exposure duration of ∼22 years is not associated with adverse effects on lung function.

The impact of vascular leg disorders on physical activity in methadone-maintained adults.

Chronic venous disorders (CVD) and peripheral arterial disease (PAD) may affect diverse physical activity domains. How CVD and PAD and other relevant variables affect physical activity was examined in 569 opioid-addicted adults. Both CVD and PAD were significantly inversely related to daily walking, sports, and active living. Effects remained significant in the latent variable regression after controlling covariates. Overall activity was very low; most participants walked less than a half mile daily and rarely engaged in sports. Motivation for physical activity was the strongest predictor (ß = .55) of daily physical activity. Health-care professionals promoting physical activity for injection users should consider the vascular health of their legs and motivational variables in addition to general health.

Quantitative crystalline silica exposure assessment for a historical cohort epidemiologic study in the German porcelain industry.

A time-dependent quantitative exposure assessment of silica exposure among nearly 18,000 German porcelain workers was conducted. Results will be used to evaluate exposure-response disease risks. Over 8000 historical industrial hygiene (IH) measurements with original sampling and analysis protocols from 1954-2006 were obtained from the German Berufs- genossenschaft der keramischen-und Glas-Industrie (BGGK) and used to construct a job exposure matrix (JEM). Early measurements from different devices were converted to modern gravimetric equivalent values. Conversion factors were derived from parallel historical measurements and new side-by-side measurements using historical and modern devices in laboratory dust tunnels and active workplace locations. Exposure values were summarized and smoothed using LOESS regression; estimates for early years were derived using backward extrapolation techniques. Employee work histories were merged with JEM values to determine cumulative crystalline silica exposures for cohort members. Average silica concentrations were derived for six primary similar exposure groups (SEGs) for 1938-2006. Over 40% of the cohort accumulated <0.5 mg; just over one-third accumulated >1 mg/m(3)-years. Nearly 5000 workers had cumulative crystalline silica estimates >1.5 mg/m(3)-years. Similar numbers of men and women fell into each cumulative exposure category, except for 1113 women and 1567 men in the highest category. Over half of those hired before 1960 accumulated >3 mg/m(3)-years crystalline silica compared with 4.9% of those hired after 1960. Among those ever working in the materials preparation area, half accumulated >3 mg/m(3)-year compared with 12% of those never working in this area. Quantitative respirable silica exposures were estimated for each member of this cohort, including employment periods for which sampling used now obsolete technologies. Although individual cumulative exposure estimates ranged from background to about 40 mg/m(3)-years, many of these estimates reflect long-term exposures near modern exposure limit values, allowing direct evaluation of lung cancer and silicosis risks near these limits without extrapolation. This quantitative exposure assessment is the largest to date in the porcelain industry.

Impact of injection drug use on distribution and severity of chronic venous disorders.

We examined chronic venous disorders (CVD) in persons who injected illicit drugs. The study design was cross-sectional, comparative stratified by age, gender, ethnicity, as well as by three types of drug use (noninjection; arm or upper body injection only; and legs with or without upper body injection). Subjects completed demographic, health, and substances abuse questionnaires and were evaluated using the clinical component of the Clinical-Etiology-Anatomy-Pathophysiology Classification. Seven hundred and thirteen participants were evaluated. Those who injected in the legs +/- arms had significantly worse CVD. Thirty-nine percent of leg +/- arm injectors vs. 4.2% or noninjectors or arm only injectors had moderate to severe CVD. Persons who injected in the legs +/- arms were 9.14 times more likely to develop venous ulcers than those that injected in the arms and upper body only and 34.64 times more likely as those who never injected. CVD was associated with injecting in the groin, legs and feet as compared with other sites. The pattern of disorders associated with leg injection is consistent with the underlying pathology of chronic venous insufficiency.

Venous ulcers: A reappraisal analyzing the effects of neuropathy, muscle involvement, and range of motion upon gait and calf muscle function.

Chronic venous insufficiency is a complex disease that can result in severe sequelae including venous ulceration. Though the exact progression from chronic venous insufficiency to venous ulcer remains unclear, the high cost and burden of this disease on patients and society is quite clear. Sustained ambulatory venous pressures or venous hypertension plays an integral role in the development of venous ulceration and involves the failure of the calf muscle pump system. Standard of care involves compression therapy to assist the calf muscle pump. However, several cofactors may contribute to or exacerbate this disease and understanding their impact may provide insight into new treatment modalities. Nerve involvement, which may result in neuropathic pain and muscle dysfunction, alterations in mobility and a decrease in range of motion may lead to gait alterations all affecting calf muscle pump function. In this paper, we analyze these cofactors and discuss possible treatment options to target them. Physicians treating this disease should be aware of the numerous factors involved in its development. Exploring new treatment options may 1 day lessen the burden and suffering caused by venous insufficiency.

From professional silos to interprofessional education: campuswide focus on quality of care.

OBJECTIVES: The Institute of Medicine called for the integration of interprofessional education (IPE) into health professions curricula, in order to improve health care quality. In response, we developed, implemented, and evaluated a campus wide IPE program, shifting from traditional educational silos to greater collaboration. METHODS: Students (155) and faculty (30) from 6 academic programs (nursing, medicine, public health, allied health, dentistry, and pharmacy) engaged with a university hospital partner to deliver this program. The content addressed principles of IPE, teamwork development and 2 common quality care problems: hospital-acquired infections and communication errors. Pre-/post-surveys, the Readiness for Interprofessional Learning Scale, and the Interprofessional Education Perception Scale, were used for descriptive assessment of student learning. RESULTS: Students demonstrated increased understanding of health care quality and interprofessional teamwork principles and reported positive attitudes toward shared learning. While responses to the Readiness for Interprofessional Learning Scale grew more positive after the program, scores on the Interprofessional Education Perception Scale were more homogeneous. Both students and faculty highly evaluated the experience. CONCLUSION: This program was a first step in preparing individuals for collaborative learning, fostering awareness and enthusiasm for IPE among students and faculty, and demonstrating the feasibility of overcoming common barriers to IPE such as schedule coordination and faculty buy-in.

Peripheral arterial disease among substance abusers in drug treatment.

OBJECTIVE: Examine the occurrence of and risk factors for peripheral arterial disease (PAD) in a sample in drug treatment. DESIGN: Cross-sectional/stratified design. SETTING: Ten methadone treatment centers in a large Midwestern metropolitan area in the United States. PARTICIPANTS: Six hundred forty participants (290 men [45.3%]; mean [SD] age, 46.54 years [8.85 years]) were included in the study. Sixty-one percent were African American, and 93.5% had a history of smoking cigarettes. MAIN OUTCOME MEASURES: PAD was defined as an ankle brachial index of less than 0.90 in at least 1 leg. Measures included demographic, health, and illicit drug use history questionnaires; the Walking Impairment Questionnaire; and body mass index. The Positive Attitude Toward Physical Activities/Exertion Questionnaire was added 9 months into the study; this decreased the sample size of the logistic regression for the predictors of PAD to 498. MAIN RESULTS: PAD was identified in 16.7% of the sample; the mean ankle brachial index value for persons with PAD was 0.84 (SD, 0.05). Multiple logistic regression analysis found that sex (women) (odds ratio [OR], 2.10), history of ever smoking cigarettes (OR, 5.16), years of smoking cigarettes (OR, 1.60 per 10 years' smoking), and having a positive attitude toward physical activities/exertion (OR, 0.63) made significant contributions to the predictors for PAD after controlling other background and risk variables. CONCLUSION: PAD is prevalent in persons undergoing drug treatment and is best accounted for by cigarette smoking, sex differences, and physical inactivity. PAD in drug abusers should be evaluated, and the current findings merit further investigation.

Reliability and clinical validity of a technique to assess lifetime illicit injection drug use.

A lifetime injection drug history is necessary to examine the impact of injection drug use on a physical health problem but it may cover time periods for which information and/or data reported may not be reliable. A test-retest study design was used to examine a technique of questioning persons about lifetime illicit injection drug use history (the Lifetime Injection History Questionnaire), including its reliability and relation to chronic venous disorders as an assessment of validity. Study participants included 104 persons (60 men, 44 women, M age = 49.3 years) provided services at a methadone maintenance treatment center located in a large industrial city in the Midwest. Kappa values for "ever injected" drugs ranged from 1.00 for heroin to .50 for nonprescription methadone (median = .75). High interclass correlations were found for youngest and oldest ages of injecting, years not injecting, and total injecting years (.90 to .98). Interclass correlation values for years injecting in the upper body and lower body were .79 and .70, respectively. Interrater reliability for the clinical portion of the venous disease assessment tool (the Clinical-Etiology-Anatomy-Pathophysiology - CEAP - classification) was high: .97, right leg; .94, left leg. Controlling for age, gender, comorbidities, and body mass index, a classification of injection drug use based on the Lifetime Injection History scales accounted for 32% of the variance in the clinical CEAP scores. This is the first study to examine years of injection drug use that takes periods not injecting drugs into consideration. Focused substance abuse questioning (eg, drug, route, years of use) may help clinicians evaluate health problems related to drug use.

The standing heel-rise test: relation to chronic venous disorders and balance, gait, and walk time in injection drug users.

Injection drug use can impair mobility. When mobility is impaired in combination with other potential pathologic changes to the veins, muscles, and joints of the lower legs, chronic venous disorders can develop. The heel-rise test, an assessment of eccentric-concentric muscle action of calf muscle function with regard to plantar flexion, can be used to measure ankle mobility. To examine the test-retest reliability and construct validity of the heel-rise test in relation to chronic venous disorders in persons with a history of injection drug use (N = 104), a test-retest study (M = 45.9+/-12.9 days from first to second test) was conducted. Participants were assessed for chronic venous disorders of the legs and walk time; they also completed the heel-rise and Tinetti Balance and Gait tests. Test-retest reliability was found to be good for full heel rise of right and left legs (ICC = .66 and .67, respectively). Heel-rise performance was positively correlated with balance (r = .38 to .47) and gait (r = .38 to .45) and negatively related to walk time (r = -.30 to -.35) (P <0.01). Participants who injected in the groin, legs, or feet performed fewer heel rises than those who injected in the arms and upper body only or those who did not inject drugs. Chronic venous disorders accounted for 7% to 17% of the variance in heel rise. The heel-rise test as a measure of calf muscle function is supported by these results, implicating the role of mobility restriction in the etiology of venous disease. Although more research is needed regarding its performance, the heel-rise test may be a low-cost, noninvasive screening or assessment tool in a variety of outpatient settings.

Injection drug use: an understudied cause of venous disease.

Injection drug use has devastating effects on the veins, skin, muscles, and joints of the lower extremities, thus increasing the risk of chronic venous disease (CVD). We examined the following risk factors for CVD in persons who injected drugs: health and drug use history, ankle mobility, pain, and skin and wound assessment. Because of deep venous thrombosis and injury and immobility to the calf muscle pump from injected drugs, CVD occurs at a young age. Decreased ankle joint movement, decreased walking, and increased pain are associated with worsening CVD clinical classification. Associated venous ulcers tend to be multiple and large by the time wound care is sought. Cellulitis and abscesses may also be present. Injection drug users serve as a model for the multifactorial nature of CVD including vein damage, diminished ankle range of motion, and decreased calf muscle strength. Persons who inject drugs need to have their lower extremities assessed for CVD on a routine basis.

Lung cancer mortality in the German chromate industry, 1958 to 1998.

OBJECTIVES: We conducted a mortality study of two German chromate production facilities and evaluated possible dose-response relationships between hexavalent chromium exposure and lung cancer. METHODS: Mortality was followed-up through 1998 and limited to those employed since each plant converted to a no-lime production process. More than 12,000 urinalysis results of chromium levels were available, as was smoking information. RESULTS: All-cause mortality indicated a healthy worker effect (standardized mortality ratio [SMR] = 0.80, 95% confidence interval [CI] = 0.67-0.96); however, lung cancers appeared to be increased (SMR = 1.48, 95% CI = 0.93-2.25). No clear dose-response was found in stratified analyses by duration of employment and time since hire. On the basis of urinary chromium data, lung cancer risk was elevated only in the highest exposure group (SMR = 2.09, 95% CI = 1.08-3.65). CONCLUSIONS: These data suggest a possible threshold effect of occupational hexavalent chromium exposure on lung cancer.

Low-level hexavalent chromium exposure and rate of mortality among US chromate production employees.

OBJECTIVE: Although numerous studies have reported an elevated lung cancer risk among chromium chemical production employees, few studies have focused on employees hired after major process changes and enhanced industrial hygiene controls were implemented. METHODS: This study examines the mortality experience of two post-change cohorts of chromate production employees constituting the current US chromium chemical industry. RESULTS: Mortality among chromium chemical workers generally was lower than expected on the basis of national and state-specific referent populations. Lung cancer mortality was 16% lower than expected, with only three lung cancer deaths (3.59 expected). CONCLUSION: The absence of an elevated lung cancer risk may be a favorable reflection of the post-change environment. However, longer follow-up allowing an appropriate latency for the entire cohort will be needed to confirm this conclusion.

Aerobic exercise training fails to lower hypertriglyceridemia levels in persons with advanced HIV-1 infection.

The purpose of this study was to determine whether blood lipid and lipoprotein concentrations varied in 5 men with advanced HIV-1 infection after 12 months of aerobic exercise training. Prior to exercise, the mean baseline cholesterol and high-density lipoprotein cholesterol (HDL-C) serum concentration were each lower, and mean baseline triglyceride concentration was higher compared to a healthy population norm. Consistent exercise training for 12 months failed to significantly (p > .05) alter cholesterol or HDL-C. Triglyceride concentration was significantly (p < .05) elevated above baseline (63 mg/dL) regardless of exercise compliance. The results suggest that long-term exercise training cannot correct lipid profile abnormality, particularly hypertriglyceridemia, common to individuals with advanced HIV-1 infection.

Double-blinded, placebo-controlled trial of midodrine for exercise performance enhancement in tetraplegia: a pilot study.

BACKGROUND/OBJECTIVE: Spinal cord injury (SCI) impairs cardiovascular autonomic responses to exercise and, depending on the level of injury, may result in hypotension and pathologic fatigue with exertion. Other clinical populations with sympathetic regulatory dysfunction, but without skeletal muscle paralysis, exhibit similar signs and symptoms. Their ability to engage in physical activity improves with elevation of blood pressure through pharmacologic treatment: Midodrine, an oral alpha-sympathomimetic agent, has been shown to be safe and efficacious for this purpose. Use of this medication in individuals with SCI merits investigation. METHODS: Double-blind, placebo-controlled, randomized, crossover, within-subjects protocol. Four participants with chronic, motor-complete injuries from C6 to C8 underwent 4 peak exercise tests (PXT) using a wheelchair ergometer, following administration of midodrine, 5 mg, 10 mg, and placebo, in random order. Heart rate, blood pressure, oxygen consumption (VO2), and perceived exertion were measured. RESULTS: Treatment with midodrine, 10 mg, was associated with elevated systolic blood pressure during peak exercise in 3 participants. Two participants showed a concurrent decrease in perceived exertion and increase in VO2. No adverse effects of midodrine were evident. CONCLUSION: Midodrine enhances exercise performance in some individuals with SCI, similar to other clinical populations with cardiovascular autonomic dysfunction.