Serum per- and polyfluoroalkyl substance concentrations in four municipal US fire departments.

BACKGROUND: Firefighters have occupational and environmental exposures to per- and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants. METHODS: Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A-D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES. RESULTS: In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A-C, sum of branched perfluoromethylheptane sulfonate isomers (Sm-PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n-PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n-PFOA) was elevated in Departments B-D, and perfluorononanoate (PFNA) was elevated in Departments B-D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B-D. In female firefighters compared with NHANES, PFHxS and Sm-PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department. CONCLUSIONS: Serum PFHxS, Sm-PFOS, n-PFOS, n-PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.

Repeat measures of DNA methylation in an inception cohort of firefighters.

OBJECTIVES: Firefighters face exposures associated with adverse health outcomes including risk for multiple cancers. DNA methylation, one type of epigenetic regulation, provides a potential mechanism linking occupational hazards to adverse health outcomes. We hypothesised that DNA methylation profiles would change in firefighters after starting their service and that these patterns would be associated with occupational exposures (cumulative fire-hours and fire-runs). METHODS: We profiled DNA methylation with the Infinium MethylationEPIC in blood leucocytes at two time points in non-smoking new recruits: prior to live fire training and 20-37 months later. Linear mixed effects models adjusted for potential confounders were used to identify differentially methylated CpG sites over time using data from 50 individuals passing all quality control. RESULTS: We report 680 CpG sites with altered methylation (q value <0.05) including 60 with at least a 5% methylation difference at follow-up. Genes with differentially methylated CpG sites were enriched in biological pathways related to cancers, neurological function, cell signalling and transcription regulation. Next, linear mixed effects models were used to determine associations between occupational exposures with methylation at the 680 loci. Of these, more CpG sites were associated with fire-runs (108 for all and 78 for structure-fires only, q<0.05) than with fire-hours (27 for all fires and 1 for structure fires). These associations were independent of time since most recent fire, suggesting an impact of cumulative exposures. CONCLUSIONS: Overall, this study provides evidence that DNA methylation may be altered by fireground exposures, and the impact of this change on disease development should be evaluated.

Recovery Sleep versus Emotion Regulation in Predicting Fire Service Shift Workers Stress, Fatigue and Irritability.

Objective/Background: Fire service shift workers are at risk of developing mental health difficulties related to sleep loss and emotion dysregulation. We aimed to clarify the relationship between off-shift recovery sleep and emotion regulation on stress, fatigue and irritability. Participants: A total of 61 fire service shift workers (e.g. firefighter, captain, engineer, paramedic) on a "5/6" shift. Methods: Following five 24-hour shifts, participants reported on emotion regulation as well as daily sleep, stress, fatigue and irritability during six consecutive off-shift recovery days. Mediation analyses examined (1) emotion regulation as a predictor and sleep as a mediator of stress, fatigue and irritability outcomes; and (2) sleep as a predictor and emotion regulation as a mediator of stress, fatigue and irritability outcomes. Results: Greater self-reported total sleep time predicted lower recovery stress, fatigue, and irritability. Greater subjective sleep efficiency predicted lower recovery stress and fatigue, but not irritability. No significant relationships emerged for objective sleep or emotion regulation variables predicting stress, fatigue or irritability. There were no significant findings with either emotion regulation or sleep variables included as mediators. Conclusions: These findings suggest that stress management programs for fire service shift workers may be most effective when targeting sleep efficiency and quantity rather than emotion regulation strategies in the off-shift recovery period.

Establishing a proactive safety and health risk management system in the fire service.

BACKGROUND: Formalized risk management (RM) is an internationally accepted process for reducing hazards in the workplace, with defined steps including hazard scoping, risk assessment, and implementation of controls, all within an iterative process. While required for all industry in the European Union and widely used elsewhere, the United States maintains a compliance-based regulatory structure, rather than one based on systematic, risk-based methodologies. Firefighting is a hazardous profession, with high injury, illness, and fatality rates compared with other occupations, and implementation of RM programs has the potential to greatly improve firefighter safety and health; however, no descriptions of RM implementation are in the peer-reviewed literature for the North American fire service. METHODS: In this paper we describe the steps used to design and implement the RM process in a moderately-sized fire department, with particular focus on prioritizing and managing injury hazards during patient transport, fireground, and physical exercise procedures. Hazard scoping and formalized risk assessments are described, in addition to the identification of participatory-led injury control strategies. Process evaluation methods were conducted to primarily assess the feasibility of voluntarily instituting the RM approach within the fire service setting. RESULTS: The RM process was well accepted by the fire department and led to development of 45 hazard specific-interventions. Qualitative data documenting the implementation of the RM process revealed that participants emphasized the: value of the RM process, especially the participatory bottom-up approach; usefulness of the RM process for breaking down tasks to identify potential risks; and potential of RM for reducing firefighter injury. CONCLUSIONS: As implemented, this risk-based approach used to identify and manage occupational hazards and risks was successful and is deemed feasible for U.S. (and other) fire services. While several barriers and challenges do exist in the implementation of any intervention such as this, recommendations for adopting the process are provided. Additional work will be performed to determine the effectiveness of select controls strategies that were implemented; however participants throughout the organizational structure perceived the RM process to be of high utility while researchers also found the process improved the awareness and engagement in actively enhancing worker safety and health.

Two- and live/real time three-dimensional transthoracic echocardiographic assessment of infective endocarditis of a valved pulmonary conduit.

We describe the use of a nonstandard left infraclavicular approach in making the diagnosis of an infected valved conduit with two-dimensional transthoracic echocardiography. The patient was an adult with tetralogy of Fallot and pulmonary atresia who had undergone multiple surgical repair procedures. The initial diagnosis of infective endocarditis was made by transesophageal echocardiography. Both techniques demonstrated a single, large vegetation in the conduit. Live/real time three-dimensional transthoracic echocardiography, on the other hand, provided further information by demonstrating several additional vegetations in the conduit and more comprehensively assessed their size by enabling measurement of their azimuthal dimensions and volumes. The patient was treated with antibiotics with complete resolution of the vegetations.

Comparison of three commercially available softwares for measuring left ventricular perfusion and function by gated SPECT myocardial perfusion imaging.

BACKGROUND: The three softwares, Quantitative Perfusion SPECT (QPS), Emory Cardiac Toolbox, and 4 Dimension-Myocardial SPECT (4DM) are widely used with myocardial perfusion imaging (MPI) to determine perfusion defect size (PDS) and left ventricular (LV) function. There are limited data on the degree of agreement between these methods in quantifying the LV perfusion pattern and function. METHODS AND RESULTS: In 120 consecutive patients who had abnormal regadenoson SPECT MPI with a visually derived summed stress score ≥4, the correlation between the softwares for measurements of PDS, reversible, and fixed defects was poor to fair (Spearman's ρ = 0.18-0.72). Overall, estimation of defect size was smaller by QPS and larger by 4DM. There was discordance among the softwares in 62% of the cases in defining PDS as small/moderate/large. The correlation between the softwares was better for measuring LVEF, volumes and mass (ρ = 0.84-0.97), and discrepant results for defining normal/mild-moderate/severe LV systolic dysfunction were prevalent in 28% of the patients. CONCLUSION: There are significant differences between the softwares in measuring PDS as well as LV function, and more importantly in defining small, moderate, or large ischemic burden. These results suggest the necessity of using the same software when assessing interval changes by serial imaging.

Comparison of Serum Per- and Polyfluoroalkyl Substances Concentrations in Incumbent and Recruit Firefighters and Longitudinal Assessment in Recruits.

OBJECTIVE: Firefighters are occupationally exposed to per- and polyfluoroalkyl substances (PFAS). This study objective was to compare serum PFAS concentrations in incumbent and recruit firefighters and evaluate temporal trends among recruits. METHODS: Serum PFAS concentrations were measured in 99 incumbent and 55 recruit firefighters at enrollment in 2015-2016, with follow-up 20 to 37 months later for recruits. Linear and logistic regression and linear mixed-effects models were used for analyses. Fireground exposure impact on PFAS concentrations was investigated using adjusted linear and logistic regression models. RESULTS: Incumbents had lower n-PFOA and PFNA than recruits and most PFAS significantly decreased over time among male recruits. No significant links were found between cumulative fireground exposures and PFAS concentrations. CONCLUSIONS: Serum PFAS concentrations were not increased in incumbent firefighters compared with recruits and were not associated with cumulative fireground exposures.

Firefighting, per- and polyfluoroalkyl substances, and DNA methylation of genes associated with prostate cancer risk.

Prostate cancer is the leading incident cancer among men in the United States. Firefighters are diagnosed with this disease at a rate 1.21 times higher than the average population. This increased risk may result from occupational exposures to many toxicants, including per- and polyfluoroalkyl substances (PFAS). This study assessed the association between firefighting as an occupation in general or PFAS serum levels, with DNA methylation. Only genomic regions previously linked to prostate cancer risk were selected for analysis: GSTP1, Alu repetitive elements, and the 8q24 chromosomal region. There were 444 male firefighters included in this study, with some analyses being conducted on fewer participants due to missingness. Statistical models were used to test associations between exposures and DNA methylation at CpG sites in the selected genomic regions. Exposure variables included proxies of cumulative firefighting exposures (incumbent versus academy status and years of firefighting experience) and biomarkers of PFAS exposures (serum concentrations of 9 PFAS). Proxies of cumulative exposures were associated with DNA methylation at 15 CpG sites and one region located within FAM83A (q-value <0.1). SbPFOA was associated with 19 CpG sites (q < 0.1), but due to low detection rates, this PFAS was modeled as detected versus not detected in serum. Overall, there is evidence that firefighting experience is associated with differential DNA methylation in prostate cancer risk loci, but this study did not find evidence that these differences are due to PFAS exposures specifically.

Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach.

Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occupational firefighting. 200 urine samples from 100 firefighters collected at baseline and two to four hours post-fire were analyzed using untargeted liquid-chromatography and high-resolution mass spectrometry. Changes in metabolite abundance after a fire were estimated with fixed effects linear regression, with false discovery rate (FDR) adjustment. Partial least squares discriminant analysis (PLS-DA) was also used, and variable important projection (VIP) scores were extracted. Systemic changes were evaluated using pathway enrichment for highly discriminating metabolites. Metabolome-wide-association-study (MWAS) identified 268 metabolites associated with firefighting activity at FDR q < 0.05. Of these, 20 were annotated with high confidence, including the amino acids taurine, proline, and betaine; the indoles kynurenic acid and indole-3-acetic acid; the known uremic toxins trimethylamine n-oxide and hippuric acid; and the hormone 7a-hydroxytestosterone. Partial least squares discriminant analysis (PLS-DA) additionally implicated choline, cortisol, and other hormones. Significant pathways included metabolism of urea cycle/amino group, alanine and aspartate, aspartate and asparagine, vitamin b3 (nicotinate and nicotinamide), and arginine and proline. Firefighters show a broad metabolic response to fires, including altered excretion of indole compounds and uremic toxins. Implicated pathways and features, particularly uremic toxins, may be important regulators of firefighter's increased risk for urinary tract cancers.

Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters.

Epigenetic changes may be biomarkers of health. Epigenetic age acceleration (EAA), the discrepancy between epigenetic age measured via epigenetic clocks and chronological age, is associated with morbidity and mortality. However, the intersection of epigenetic clocks with microRNAs (miRNAs) and corresponding miRNA-based health implications have not been evaluated. We analyzed DNA methylation and miRNA profiles from blood sampled among 332 individuals enrolled across 2 U.S.-based firefighter occupational studies (2015-2018 and 2018-2020). We considered 7 measures of EAA in leukocytes (PhenoAge, GrimAge, Horvath, skin-blood, and Hannum epigenetic clocks, and extrinsic and intrinsic epigenetic age acceleration). We identified miRNAs associated with EAA using individual linear regression models, adjusted for sex, race/ethnicity, chronological age, and cell type estimates, and investigated downstream effects of associated miRNAs with miRNA enrichment analyses and genomic annotations. On average, participants were 38 years old, 88% male, and 75% non-Hispanic white. We identified 183 of 798 miRNAs associated with EAA (FDR q < 0.05); 126 with PhenoAge, 59 with GrimAge, 1 with Horvath, and 1 with the skin-blood clock. Among miRNAs associated with Horvath and GrimAge, there were 61 significantly enriched disease annotations including age-related metabolic and cardiovascular conditions and several cancers. Enriched pathways included those related to proteins and protein modification. We identified miRNAs associated with EAA of multiple epigenetic clocks. PhenoAge had more associations with individual miRNAs, but GrimAge and Horvath had greater implications for miRNA-associated pathways. Understanding the relationship between these epigenetic markers could contribute to our understanding of the molecular underpinnings of aging and aging-related diseases.

Occupational Years of Service and Leukocyte Epigenetic Aging: Relationships in United States Firefighters.

OBJECTIVE: The aim of the study is to examine associations between years of firefighting service and eight chronological age-adjusted measures of blood leukocyte epigenetic age acceleration: Horvath, Hannum, SkinBloodClock, Intrinsic, Extrinsic, PhenoAge, GrimAge, and DNAm telomere length. METHODS: The study used a repeated measures analysis of data from 379 incumbent firefighters from eight career departments and 100 recruit firefighters from two of the departments, across the United States. RESULTS: Incumbent firefighters had on average greater epigenetic age acceleration compared with recruit firefighters, potentially due to the cumulative effect of occupational exposures. However, among incumbent firefighters, additional years of service were associated with epigenetic age deceleration, particularly for GrimAge, a strong predictor of mortality. CONCLUSIONS: Long-term studies with more specific occupational exposure classification are needed to better understand the relationship between years of service and aging biomarkers.

Longitudinal evaluation of whole blood miRNA expression in firefighters.

BACKGROUND: Dysregulated microRNA (miRNA) expression could provide a mechanism linking firefighter exposure to increased cancer risk. OBJECTIVE: To determine if changes in longitudinal miRNA expression in firefighters are associated with occupational exposures. METHODS: Whole blood MiRNA was evaluated in 52 new recruits prior to live-fire training and 20-37 months later. Linear mixed effects models adjusted for age, ethnicity, BMI, and batch effects were used to determine associations separately for all fires and structure fires only between employment duration, cumulative fire-hours and fire-runs, and time since most recent fire with (1) nine a priori and (2) the full array of 799 miRNAs. RESULTS: For multivariable models including all fires, two a priori miRNAs were associated with employment duration and four with time since most recent fire. For multivariable models restricted to structure fires, three a priori miRNAs were associated with employment duration and one with fire-runs. Additional miRNAs from the full array were associated with employment duration for all fires and/or structure fires. In general, tumor suppressive miRNAs decreased and oncogenic miRNAs increased with exposure. SIGNIFICANCE: Changes in miRNAs may serve as biomarkers of exposure effects and a mechanism for increased cancer risk in firefighters.

Differential DNA Methylation by Hispanic Ethnicity Among Firefighters in the United States.

Firefighters are exposed to a variety of environmental hazards and are at increased risk for multiple cancers. There is evidence that risks differ by ethnicity, yet the biological or environmental differences underlying these differences are not known. DNA methylation is one type of epigenetic regulation that is altered in cancers. In this pilot study, we profiled DNA methylation with the Infinium MethylationEPIC in blood leukocytes from 31 Hispanic white and 163 non-Hispanic white firefighters. We compared DNA methylation (1) at 12 xenobiotic metabolizing genes and (2) at all loci on the array (>740 000), adjusting for confounders. Five of the xenobiotic metabolizing genes were differentially methylated at a raw P-value <.05 when comparing the 2 ethnic groups, yet were not statistically significant at a 5% false discovery rate (q-value <.05). In the epigenome-wide analysis, 76 loci exhibited DNA methylation differences at q < .05. Among these, 3 CpG sites in the promoter region of the biotransformation gene SULT1C2 had lower methylation in Hispanic compared to non-Hispanic firefighters. Other differentially methylated loci included genes that have been implicated in carcinogenesis in published studies (FOXK2, GYLTL1B, ZBTB16, ARHGEF10, and more). In this pilot study, we report differential DNA methylation between Hispanic and non-Hispanic firefighters in xenobiotic metabolism genes and other genes with functions related to cancer. Epigenetic susceptibility by ethnicity merits further study as this may alter risk for cancers linked to toxic exposures.

Evaluation of fireground exposures using urinary PAH metabolites.

BACKGROUND: Firefighters have increased cancer incidence and mortality rates compared to the general population, and are exposed to multiple products of combustion including known and suspected carcinogens. OBJECTIVE: The study objective was to quantify fire response exposures by role and self-reported exposure risks. METHODS: Urinary hydroxylated metabolites of polycyclic aromatic hydrocarbons (PAH-OHs) were measured at baseline and 2-4 h after structural fires and post-fire surveys were collected. RESULTS: Baseline urine samples were collected from 242 firefighters. Of these, 141 responded to at least one of 15 structural fires and provided a post-fire urine. Compared with baseline measurements, the mean fold change of post-fire urinary PAH-OHs increased similarly across roles, including captains (2.05 (95% CI 1.59-2.65)), engineers (2.10 (95% CI 1.47-3.05)), firefighters (2.83 (95% CI 2.14-3.71)), and paramedics (1.84 (95% CI 1.33-2.60)). Interior responses, smoke odor on skin, and lack of recent laundering or changing of hoods were significantly associated with increased post-fire urinary PAH-OHs. SIGNIFICANCE: Ambient smoke from the fire represents an exposure hazard for all individuals on the fireground; engineers and paramedics in particular may not be aware of the extent of their exposure. Post-fire surveys identified specific risks associated with increased exposure.

Per- and polyfluoroalkyl substances, epigenetic age and DNA methylation: a cross-sectional study of firefighters.

Background: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. Methods: With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Results: Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. Conclusion: PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

Assessment of the toxicity of firefighter exposures using the PAH CALUX bioassay.

Firefighters can be exposed to a complex set of contaminants while at a fire scene. Identifying new ways to monitor and assess exposure, particularly relating to toxicity is essential to determine the effectiveness of intervention techniques to reduce exposure. This study investigated the use of the polycyclic aromatic hydrocarbon (PAH) CALUX® bioassay for the assessment of exposure and associated toxicity firefighters might encounter. This was done through analysis of extracts of dermal wipes and urine samples collected from firefighters before and after a controlled fire. An increased bioassay response was observed from post-fire neck and calf samples, indicating a greater concentration of PAH-like compounds on the skin. The use of a baby wipe to clean the face and neck during rehab resulted in the attenuation of the observed bioassay response from the neck post-fire. Though a correlation was observed between the bioassay response and hydroxylated PAH concentrations found in the urine, the increased bioassay response from the post-fire urine samples was likely due to unknown compounds other than the hydroxylated PAHs tested. Our results suggest that this bioassay provides a useful measure of firefighter exposure, particularly relating to the potential toxicity of contaminants.

Evaluation of Interventions to Reduce Firefighter Exposures.

OBJECTIVE: Evaluate the effectiveness of firefighter exposure reduction interventions. METHODS: Fireground interventions included use of self-contained breathing apparatus by engineers, entry team wash down, contaminated equipment isolation, and personnel showering and washing of gear upon return to station. Urinary polycyclic aromatic hydrocarbon metabolites (PAH-OHs) were measured after structural fire responses before and after intervention implementation. Separately, infrared sauna use following live-fire training was compared to standard postfire care in a randomized trial. RESULTS: The fireground interventions significantly reduced mean total urinary postfire PAH-OHs in engineers (-40.4%, 95%CI -63.9%, -2.3%) and firefighters (-36.2%, 95%CI -56.7%, -6.0%) but not captains (-11.3% 95%CI -39.4%, 29.9%). Sauna treatment non-significantly reduced total mean PAH-OHs by -43.5% (95%CI -68.8%, 2.2%). CONCLUSIONS: The selected fireground interventions reduced urinary PAH-OHs in engineers and firefighters. Further evaluation of infrared sauna treatment is needed.

MicroRNA Changes in Firefighters.

OBJECTIVES: Firefighters have elevated cancer incidence and mortality rates. MicroRNAs play prominent roles in carcinogenesis, but have not been previously evaluated in firefighters. METHODS: Blood from 52 incumbent and 45 new recruit nonsmoking firefighters was analyzed for microRNA expression, and the results adjusted for age, obesity, ethnicity, and multiple comparisons. RESULTS: Nine microRNAs were identified with at least a 1.5-fold significant difference between groups. All six microRNAs with decreased expression in incumbent firefighters have been reported to have tumor suppressor activity or are associated with cancer survival, and two of the three microRNAs with increased expression in incumbent firefighters have activities consistent with cancer promotion, with the remaining microRNA associated with neurological disease. CONCLUSION: Incumbent firefighters showed differential microRNA expression compared with new recruits, providing potential mechanisms for increased cancer risk in firefighters.

Implementing risk management to reduce injuries in the U.S. Fire Service.

INTRODUCTION: Risk management, a proactive process to identify and mitigate potential injury risks and implement control strategies, was used to reduce the risk of occupational injury in a fire department. The objective of this research was to study the implementation of the risk management process for future replication. A second objective was to document changes in fire personnel's knowledge, attitudes, and behaviors related to the selected control strategies that were implemented as part of the risk management process. METHOD: A number of control strategies identified through the risk management process were implemented over a 2-year period beginning in January 2011. Approximately 450 fire personnel completed each of the three cross-sectional surveys that were administered throughout the implementation periods. Fire personnel were asked about their awareness, knowledge, and use of the control strategies. RESULTS: Fire personnel were generally aware of the control strategies that were implemented. Visual reminders (e.g., signage) were noted as effective by fire personnel who noticed them. Barriers to use of specific control strategies such as new procedures on the fireground or new lifting equipment for patient transfer included lack of knowledge of the new protocols, lack of awareness/access to/availability of the new equipment, and limited training on its use. Implementation challenges were noted, which limited self-reported adherence to the control strategies. CONCLUSIONS: Fire personnel generally recognized the potential for various control strategies to manage risk and improve their health and safety; however, implementation challenges limited the effectiveness of certain control strategies. The study findings support the importance of effective implementation to achieve the desired impacts of control strategies for improving health and safety. PRACTICAL APPLICATIONS: Employees must be aware of, have knowledge about, and receive training in safety and health interventions in order to adopt desired behaviors.