Occurrence of COVID-19 and serum per- and polyfluoroalkyl substances: A case-control study among workers with a wide range of exposures.

Per- and polyfluoroalkyl substances (PFAS) are a broad class of synthetic chemicals; some are present in most humans in developed countries. Some studies suggest that certain PFAS may have immunotoxic effects in humans, which could put individuals with high levels of exposure at increased risk for infectious diseases such as COVID-19. We conducted a case-control study to examine the association between COVID-19 diagnosis and PFAS serum concentrations among employees and retirees from two 3 M facilities, one of which historically generated perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS). Participants completed enrollment and follow-up study visits in the Spring of 2021. Participants were categorized as cases if they reported a COVID-19 diagnosis or became sick with at least one symptom of COVID-19 when someone else in their household was diagnosed, otherwise they were categorized as a control. COVID-19 diagnosis was modeled in relation to concentration of serum PFAS measured at enrollment after adjusting for covariates. The analytic sample comprised 573 individuals, 111 cases (19.4%) and 462 controls (80.6%). In adjusted models, the odds ratio of COVID-19 was 0.94 per interquartile range (14.3 ng/mL) increase in PFOS (95% confidence interval 0.85, 1.04). Results for PFOA, PFHxS, and perfluorononanoic acid (PFNA) were similar. Other PFAS present at lower concentrations were examined as categorical variables (above the limit of quantification [LOQ], yes vs. no [referent category]), and also showed no positive associations. In our study, which used individual-level data and included people with high occupational exposure, the serum concentrations of all PFAS examined were not associated with an increased odds ratio for COVID-19. At this point, the epidemiologic data supporting no association of COVID-19 occurrence with PFAS exposure are stronger than those suggesting a positive association.

An investigation of 3M Cordova, IL production worker's per- and polyfluoroalkyl substances biomonitoring results and mortality experience.

Per- and polyfluoroalkyl substances (PFAS) are a wide-ranging group of chemicals that have been used in a variety of polymer and surfactant applications. While 3M Cordova, Illinois was not one of 3M's primary manufacturing facilities for the legacy long-chain PFAS (PFOS, PFOA, PFHxS), it has been a major manufacturing site for short-chain PFAS (compounds that are or may degrade to PFBS or PFBA). The purpose of this research focused on: 1) an analysis of biomonitoring data of employees and retirees, and 2) an analysis of the cohort mortality of workers from 1970 to 2018. Employees had higher PFBS and PFBA serum concentrations than the retirees, while retirees had higher concentrations for PFOS, PFOA, and PFHxS. Compared to the 2017-2018 NHANES data, employees' PFOS and PFHxS concentrations in 2022 were two-fold higher, with PFOA levels comparable. These NHANES data did not include serum PFBS or PFBA. Cross-sectional trends of PFOS and PFOA levels from 1997 to 2022 showed PFOS declined from 151 ng/mL to 10.4 ng/mL. Similarly, PFOA decreased from 100 ng/mL to 1.5 ng/mL. A longitudinal analysis of 48 participants with measurements in both 2006 and 2022 showed concentrations decreased by 74% for PFOS and 90% for PFOA. In the mortality study, 1707 employees who worked 1 day or longer were followed for an average of 25.6 years and had 143 (8%) deaths. There were no significantly elevated risks for any specific cause of death, regardless of latency period (0 or 15 years). While no specific PFAS exposures were examined, worker mortality experience (1970-2018) was analyzed by major departments representing primary work areas. Employees and retirees at the Cordova facility continue to have elevated PFOS and PFHxS serum concentrations compared to the general population, however, their legacy PFAS concentrations have declined over time, consistent with the estimated serum elimination half-lives of these PFAS in humans assuming nominal ambient exposures. For PFBS and PFBA, the results indicated no long-term accumulation in the blood likely due to their short serum elimination half-lives. After nearly 50 years of follow-up, this Cordova workforce showed no increased risk of mortality from cancer or any other specific cause of death.

Antibody response to COVID-19 vaccines among workers with a wide range of exposure to per- and polyfluoroalkyl substances.

Per- and polyfluoroalkyl substances (PFAS) are a broad class of synthetic chemicals; some are present in most humans in developed countries. Several studies have shown associations between certain PFAS, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), and reduced antibody concentration after vaccination against diseases such as Tetanus. Recent studies have reported associations between COVID-19 occurrence and exposure to certain types of PFAS. However, studies of antibody concentration after COVID-19 vaccination in relation to PFAS serum concentrations have not been reported. We examined COVID-19 antibody responses to vaccines and PFAS serum concentrations among employees and retirees from two 3M facilities, one of which historically manufactured PFOS, PFOA, and perfluorohexane sulfonic acid (PFHxS). Participants completed enrollment and follow-up study visits in the Spring of 2021, when vaccines were widely available. In total 415 participants with 757 observations were included in repeated measures analyses. Log-transformed concentrations of anti-spike IgG and neutralizing antibodies were modeled in relation to concentration of PFAS at enrollment after adjusting for antigenic stimulus group (9 groups determined by COVID-19 history and number and type of vaccination) and other variables. The fully adjusted IgG concentration was 3.45 percent lower (95% CI -7.03, 0.26) per 14.5 ng/mL (interquartile range) increase in PFOS; results for neutralizing antibody and PFOS were similar. For PFOA, PFHxS, and perfluorononanoic acid (PFNA), the results were comparable to those for PFOS, though of smaller magnitude. In our study data, the fully adjusted coefficients relating concentration of vaccine-induced antibodies to COVID-19 and interquartile range difference in serum concentration of PFOS, PFOA, PFHxS, and PFNA were inverse but small with confidence intervals that included zero. Our analysis showed that the coefficient for the four PFAS examined in detail was considerably affected by adjustment for antigenic stimulus group.

A Pathology Review of the Lower Gastrointestinal Tract in Relation to Ulcerative Colitis in Rats and Cynomolgus Macaques Treated With Ammonium Perfluorooctanoate.

Among many short-term, subchronic, and chronic toxicology studies with ammonium perfluorooctanoate (PFOA), the gastrointestinal tract has not been identified as a target organ for PFOA-related toxicity in laboratory animals where the corresponding serum PFOA concentrations typically approach several orders of magnitude higher than the general human population. These lack of gastrointestinal tract-related findings were in direct contrast to an epidemiological observation where a positive trend was observed for ulcerative colitis, an idiopathic chronic inflammatory condition of the gut, in a Mid-Ohio River community whose drinking water contained higher levels of PFOA. This study was conducted to perform a histological reevaluation of large intestine sections in laboratory animals from 2 long-term toxicological studies: one was with Sprague Dawley rats that received ammonium PFOA in their diet for 2 years and the other one was with cynomolgus macaques that received daily capsules of ammonium PFOA for 6 months. In both studies, there was a lack of histological evidence of treatment-related inflammatory lesions that was suggestive of the occurrence of ulcerative colitis in these laboratory animals even under the most rigorous treatment schedules. These findings do not offer support for the biological plausibility of the epidemiological associations reported.

Bladder cancer screening in aluminum smelter workers.

OBJECTIVE: To present results of a bladder cancer screening program conducted in 18 aluminum smelters in the United States from January 2000 to December 2010. METHODS: Data were collected on a cohort of workers with a history of working in coal tar pitch volatile exposed areas including urine analysis for conventional cytology and ImmunoCyt/uCyt+ assay. RESULTS: ImmunoCyt/uCyt+ and cytology in combination showed a sensitivity of 62.30%, a specificity of 92.60%, a negative predictive value of 99.90%, and a positive predictive value of 2.96%. Fourteen cases of bladder cancer were detected, and the standardized incidence ratio of bladder cancer was 1.18 (95% confidence interval, 0.65 to 1.99). Individuals who tested positive on either test who were later determined to be cancer free had undergone expensive and invasive tests. CONCLUSIONS: Evidence to support continued surveillance of this cohort has not been demonstrated.

Occupational injury risk by sex in a manufacturing cohort.

OBJECTIVES: This study expands previous research comparing injury risk for women and men in a cohort of 24,000 US aluminium manufacturing workers in 15 facilities from 2001 to 2010. METHODS: We compared injury rates (all injury, first aid, medical treatment, restricted work and lost work time) by sex and by job and sex. Using a mixed effect modelling approach, we calculated ORs and 95% CIs adjusting for age, job tenure, ethnicity and year as fixed effects and person, job and plant as random effects. Additionally, we modelled the data stratified by plant type to examine potential differences in injury risk between smelter (generally recognised as more hazardous) and fabrication production environments. RESULTS: Risk of injury was higher for women in four out of the five injury outcomes: all injuries combined (OR: 1.58, CI 1.48 to 1.67), injuries requiring first aid (OR: 1.61, CI 1.54 to 1.70), injuries requiring medical treatment (OR: 1.18, CI 1.03 to 1.36) and injuries requiring restricted work (OR: 1.65, CI 1.46 to 1.87). No difference in the risk of lost time injury by sex was found in this cohort. Analyses stratified by plant type showed similarly elevated injury risk for women, although the risk estimates were higher in smelters than fabrication plants. CONCLUSIONS: To our knowledge, this is the largest single-firm study examining injury risk by sex with sufficient data to appropriately adjust for job. We show a consistently higher injury risk for women compared with men in the smelting and fabrication environments.

Diffuse parenchymal diseases associated with aluminum use and primary aluminum production.

Aluminum use and primary aluminum production results in the generation of various particles, fumes, gases, and airborne materials with the potential for inducing a wide range of lung pathology. Nevertheless, the presence of diffuse parenchymal or interstitial lung disease related to these processes remains controversial. The relatively uncommon occurrence of interstitial lung diseases in aluminum-exposed workers--despite the extensive industrial use of aluminum--the potential for concurrent exposure to other fibrogenic fibers, and the previous use of inhaled aluminum powder for the prevention of silicosis without apparent adverse respiratory effects are some of the reasons for this continuing controversy. Specific aluminum-induced parenchymal diseases described in the literature, including existing evidence of interstitial lung diseases, associated with primary aluminum production are reviewed.

Effect of systematic ergonomic hazard identification and control implementation on musculoskeletal disorder and injury risk.

OBJECTIVES: This study aimed to examine the effect of an ergonomic hazard control (HC) initiative, undertaken as part of a company ergonomics standard, on worker injury risk. METHODS: Using the company's ergonomic hazards database to identify jobs with and without ergonomic HC implementation and linking to individual job and injury histories, injury risk among person-jobs with HC implementation (the HC group) was compared to those without HC (NoHC group) using random coefficient models. Further analysis of the HC group was conducted to determine the effect of additional ergonomic hazards controlled on injury risk. RESULTS: Among 123 jobs at 17 plant locations, 347 ergonomic hazards were quantitatively identified during the study period. HC were implemented for 204 quantified ergonomic hazards in 84 jobs, impacting 10 385 persons (12 967 person-jobs). No HC were implemented for quantified ergonomic hazards in the remaining 39 jobs affecting 4155 persons (5046 person-jobs). Adjusting for age, sex, plant origin, and year to control for any temporal trend in injury risk, the relative risk (RR) for musculoskeletal disorder (MSD) was 0.85 and the RR for any injury or MSD was 0.92 in the HC compared to NoHC group. Among the HC group, each ergonomic hazard controlled was associated with risk reduction for MSD and acute injury outcomes (RR 0.93). CONCLUSION: Systematic ergonomic HC through participatory ergonomics, as part of a mandatory company ergonomics standard, is associated with MSD and injury risk reduction among workers in jobs with HC implemented.

Further validation that claims data are a useful tool for epidemiologic research on hypertension.

BACKGROUND: The practice of using medical service claims in epidemiologic research on hypertension is becoming increasingly common, and several published studies have attempted to validate the diagnostic data contained therein. However, very few of those studies have had the benefit of using actual measured blood pressure as the gold standard. The goal of this study is to assess the validity of claims data in identifying hypertension cases and thereby clarify the benefits and limitations of using those data in studies of chronic disease etiology. METHODS: Disease status was assigned to 19,150 employees at a U.S. manufacturing company where regular physical examinations are performed. We compared the presence of hypertension in the occupational medical charts against diagnoses obtained from administrative claims data. RESULTS: After adjusting for potential confounders, those with measured blood pressure indicating stage 1 hypertension were 3.69 times more likely to have a claim than normotensives (95% CI: 3.12, 4.38) and those indicating stage 2 hypertension were 7.70 times more likely to have a claim than normotensives (95% CI: 6.36, 9.35). Comparing measured blood pressure values identified in the medical charts to the algorithms for diagnosis of hypertension from the claims data yielded sensitivity values of 43-61% and specificity values of 86-94%. CONCLUSIONS: The medical service claims data were found to be highly specific, while sensitivity values varied by claims algorithm suggesting the possibility of under-ascertainment. Our analysis further demonstrates that such under-ascertainment is strongly skewed toward those cases that would be considered clinically borderline or mild.

Recognizing occupational illnesses and injuries.

Given the burden of occupational illnesses and injuries in the United States, family physicians should understand the role workplace exposures may play in patients' chief concerns. Incorporating employment screening questions into patients' intake questionnaires is an efficient means of identifying potential occupational causes of symptoms. Recommended questions include what kind of job patients have; whether their symptoms are worse at work; whether they are or have been exposed to dust, fumes, chemicals, radiation, or loud noise; and whether they think their health problems may be related to their work. These questions are especially important when the diagnosis or etiology is in doubt. Depending on patients' responses to the screening questions, a more detailed occupational history may be appropriate. It can be useful to ask about routine tasks performed during a typical work shift, as well as anything out of the ordinary (e.g., a change in routine, an injury or accident). The occupational history should include information about alcohol and tobacco use, second or part-time jobs, military service, hobbies, and home environment. Patients with suspected occupational illnesses or injuries may benefit from referral to an occupational medicine specialist for a more detailed assessment and follow-up.

Reproductive outcomes among male and female workers at an aluminum smelter.

OBJECTIVES: Several adverse pregnancy outcomes were reported among female laboratory workers in a North American aluminum smelter. To determine whether these outcomes were associated with any occupational exposure at the plant, a cross-sectional survey was undertaken. METHODS: Rates of miscarriage, premature singleton birth, and major congenital anomaly occurring during employment were compared with a reference group comprised of all pregnancies that occurred before employment. RESULTS: Among female workers, the excess of congenital anomalies among female laboratory workers that defined the initial cluster was observed, but no specific pattern was found. CONCLUSIONS: On the basis of these analyses, the increase in congenital anomalies could not be attributed to occupational exposures at the smelter nor could potential exposure likely explain the diverse anomalies described.

Sex differences in injury patterns among workers in heavy manufacturing.

The objective of the study was to determine if female workers in a heavy manufacturing environment have a higher risk of injury compared with males when performing the same job and to evaluate sex differences in type or severity of injury. By use of human resources and incident surveillance data for the hourly population at 6 US aluminum smelters, injuries that occurred from January 1, 1996, through December 21, 2005, were analyzed. Multivariate logistic regression, adjusted for job, tenure, and age category, was used to calculate odds ratios and 95% confidence intervals for female versus male injury risk for all injuries, recordable injuries, and lost work time injuries. The analysis was repeated for acute injuries and musculoskeletal disorder-related injuries separately. Female workers in this industry have a greater risk for sustaining all forms of injury after adjustment for age, tenure, and standardized job category (odds ratio = 1.365, 95% confidence interval: 1.290, 1.445). This excess risk for female workers persisted when injuries were dichotomized into acute injuries (odds ratio = 1.2) and musculoskeletal disorder-related injuries (odds ratio = 1.1). This study provides evidence of a sex disparity in occupational injury with female workers at higher risk compared with their male counterparts in a heavy manufacturing environment.

Impairment and disability evaluation: the role of the family physician.

Physicians are frequently involved in the assessment of impairment and disability as the treating physician, in consultation, or as an independent medical examiner. The key elements of this assessment include a comprehensive clinical evaluation and appropriate standardized testing to establish the diagnosis, characterize the severity of impairment, and communicate the patient's abilities, restrictions, and need for accommodation. In some cases, a functional capacity evaluation performed by a physical or occupational therapist or a neuropsychological evaluation performed by a neuropsychologist may be required to further clarify the functional capacity of the patient. The results of the impairment evaluation should be communicated in clear, simple terms to nonmedical professionals representing the benefits systems. These individuals make the final determination on the extent of disability and eligibility for benefits and compensation under that particular benefits system.

Beryllium sensitization in aluminum smelter workers.

OBJECTIVE: To determine whether beryllium-related disease exists among aluminum smelter workers. METHODS: A total of 1278 employees from four aluminum smelters determined to have significant beryllium exposure based on 5 years of sampling were invited to participate in medical surveillance that included a respiratory symptoms questionnaire, spirometry, and blood beryllium lymphocyte proliferation test. RESULTS: Of these, 734 employees participated in the program. Beryllium exposure from 965 personal samples ranged from 0.002 to 13.00 microg/m time-weighted average, with a median of 0.05 microg/m, geometric mean of 0.05 microg/m, and arithmetic mean of 0.22 microg/m. Only two employees had confirmed beryllium sensitization (0.27%). CONCLUSION: There is evidence of beryllium sensitization among aluminum smelter workers. When compared with beryllium-exposed workers in other industries, aluminum smelter workers had lower rates of sensitization. The low beryllium sensitization rate observed may be related to work practices and the properties of the beryllium found in this work environment.

Incidence of asthma among aluminum workers.

Exposures to respiratory irritants encountered in aluminum smelters in Europe, Australia, and New Zealand have been suggested as the cause of "potroom asthma." However, there remains disagreement in North America regarding the existence of this entity. This study was designed to assess whether asthma occurs excessively among potroom workers and if so, delineate dose-response relationships for possible causal risk factors. The asthma incidence ratio between potroom and nonpotroom workers after adjusting for smoking was 1.40. Although bivariate analyses showed a relationship between asthma incidence and exposure to total fluoride, gaseous fluoride, particulate fluoride, sulfur dioxide, and smoking, only the effects of gaseous fluoride (relative risk [RR] = 5.1) and smoking (RR = 7.7) remained significant in a multivariate model. Potroom asthma appears to occur at the studied U.S. aluminum smelters at doses within regulatory guidelines.

Pulmonary impairment and disability.

Respiratory disorders, including occupational and environmental lung diseases, are prevalent. Physicians are frequently called upon to determine impairment and aid in the assessment of disability caused by these conditions, either as the treating physician or as an independent medical examiner. In this article we reviewed the role of physicians in determining the presence and severity of pulmonary disorders. A comprehensive clinical assessment and appropriate standardized tests, to objectively characterize the severity of impairment, are the key elements of the evaluation. This assessment may also include the physician's opinion regarding causative factors. Finally, disability determination is made by nonclinicians, through administrative means, based on the degree of impairment and a review of circumstances specific to the individual. Knowledge of these components of disability evaluation will help physicians to better serve their patients and supply appropriate data to the adjudicating system.