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Introduction: Hazardous exposures from the World Trade Center (WTC) terrorist attacks have been linked to increased incidence of adverse health conditions, often associated with increased mortality. We assessed mortality in a pooled cohort of WTC rescue/recovery workers over 15 years of follow-up., Materials and Methods: We analyzed mortality through 2016 in a pooled and deduplicated cohort of WTC rescue/recovery workers from three WTC-exposed cohorts (N = 60,631): the Fire Department of the City of New York (FDNY); the WTC Health Registry (WTCHR); and the General Responder Cohort (GRC). Standardized mortality ratios (SMRs) were estimated to assess mortality vs. the US and NY state populations. Multivariable Cox proportional hazards models were used to examine associations of WTC exposures (date of first arrival, working on the WTC debris pile) with mortality risk., Results: There were 1912 deaths over 697,943.33 person-years of follow-up. The SMR for all-cause mortality was significantly lower-than-expected, both when using US (SMR 0.43, 95% confidence interval [CI] 0.42-0.45) and NYS (SMR 0.51, 95% CI 0.49-0.53) as reference populations. SMRs were not elevated for any of the 28 major causes of death. Arriving at the WTC site on 9/11-9/17/2001 vs. 9/18/2001-6/30/2002 was associated with 30-50% higher risk of all-cause, heart disease and smoking-related mortality in non-FDNY/non-GRC members. Conversely, arriving on 9/11/2001 vs. 9/18/2001-6/30/2002 was associated with 40% lower all-cause and smoking-related mortality risk in FDNY members. Working on vs. off the WTC pile was associated with an increased risk of all-cause mortality in non-FDNY/non-GRC members (adjusted hazard ratio [aHR] 1.25, 95% CI 1.04-1.50), and cancer-specific mortality in GRC members (aHR 1.39, 95% CI 1.05-1.84), but lower mortality risks were found in FDNY members., Conclusions: We did not observe excess mortality among WTC rescue/recovery workers compared with general populations. However, significantly increased mortality risks among some sub-groups with high WTC exposure warrant further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: A refined job exposure matrix (JEM) based on incident types and severities and response characteristics was developed for firefighters to estimate quantities of smoke particles emitted during structural and non-structural fire incidents from 2010 to 2021., Methods: The cohort included a subset of 3237 Fire Department of the City of New York firefighters who responded to at least one incident between 2010 and 2021, prior to retirement. Fire incident data included dates, type, severity (alarm level) and location. Response data included dates worked, firehouse, position titles and shift lengths for each firefighter. The quantity of smoke particle mass generated during structural and non-structural fires adjusted by individual firefighter engagement was computed using the United States Environmental Protection Agency AP-42 emissions framework. Correlations between years of employment, fire responses and career total particle mass concentration by firefighter were examined. Linear regression models were fit and corresponding R 2 values were calculated., Results: Firefighters responded to a median of 424.7 (IQR=202.3-620.0) annual incidents/person; 17.6% were fire incidents (median=77.1; IQR=40.4-114.0). Structural fires were the most common type of fire incident (72.5% of annual incidents/person; median=55.9; IQR=29.6-85.5). Incident severity (alarm level) and firefighter engagement (position title) appeared to differentiate between high and low exposure regimes (R 2 =0.43). Incident severity explained most of the variability of particle exposures (R 2 =0.90)., Conclusions: Using the JEM, job-related smoke particle concentrations were estimated to vary by incident type, incident severity and firefighter engagement, highlighting the importance of using refined measures, so that future studies can more accurately evaluate associations between firefighting and health outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Individuals with very low immunoglobulin E (IgE) levels have a high risk of developing malignancy. Previous studies have revealed that World Trade Center (WTC) responders exposed to carcinogens have an elevated risk of some cancers., Objective: To evaluate the association between low-serum IgE levels and cancer development in WTC-exposed responders., Methods: IgE levels were measured in 1851 WTC responders after September 11, 2001. This is the first pilot study in humans comparing the odds of developing cancer in this high-risk population, between the "low-IgE" (IgE in the lowest third percentile) vs "non-low-IgE" participants., Results: A significantly higher proportion of hematologic malignancies was found in low-IgE (4/55, 7.3%) compared with non-low-IgE (26/1796, 1.5%, P < .01) responders. The proportion of solid tumors were similar in both groups (5.5% vs 11.4%, P > .05). After adjustment for relevant confounders (race, sex, age at blood draw, WTC arrival time, smoking status), the low-IgE participants had 7.81 times greater odds (95% confidence interval, 1.77-29.35) of developing hematologic cancer when compared with non-low-IgE participants. The hematologic cancers found in this cohort were leukemia (n = 1), multiple myeloma (n = 1), and lymphoma (n = 2). No statistical significance was found when estimating the odds ratio for solid tumors in relation to IgE levels., Conclusion: WTC responders with low serum IgE levels had the highest odds of developing hematologic malignancies. This hypothesis-generating study suggests that low serum IgE levels might be associated with the development of specific malignancies in at-risk individuals exposed to carcinogens. Larger, multicenter studies with adequate follow-up of individuals with different IgE levels are needed to better evaluate this relationship., (Copyright © 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

An elevated risk of myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS), was identified among Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed firefighters. Further investigation was needed to determine if these findings were reproducible in a more heterogeneous WTC-exposed rescue/recovery workers cohort, the Stony Brook University-General Responder Cohort GRC (SBU-GRC). MGUS risk was compared between the cohorts and to published general population estimates from Olmsted County, MN, USA. In this observational seroprevalence study, odds ratios (OR) and age-standardized risk ratios (RR) of MGUS (M-spike and light-chain-MGUS combined), M-spike, and light-chain-MGUS were estimated using logistic regression. Age-standardized prevalences were calculated for white males aged 50-79; RRs were estimated by comparing risk in the WTC-exposed cohort with the Olmsted County screened cohort. SBU-GRC had elevated odds of MGUS compared with FDNY (OR = 1.38; 95%CI = 1.00-1.89). The age-standardized prevalence of MGUS was 9.0/100 persons (95%CI = 7.5-10.6), over two-fold higher than the general population (RR = 2.08; 95%CI = 1.72-2.51); the age-standardized prevalence of light-chain-MGUS was 3.5-fold higher (RR = 3.54; 95%CI = 2.52-4.97). This study adds to mounting evidence supporting an association between WTC/environmental exposures and MGUS among rescue/recovery workers. Access to MGUS screenings for the entire WTC-exposed cohort could allow for treatment interventions that improve survival., (© 2022. The Author(s).)

We evaluated the incidence and risk factors for COVID-19 in a prospectively followed cohort of Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed workers, thus reducing the potential for selection bias, a limitation in published studies of hospitalized individuals. Participants were retired FDNY WTC-exposed rescue/recovery workers with ≥1 medical visit between 1 March 2020 and 1 August 2021. The cumulative incidence was calculated using self-reported COVID-19 diagnoses. Cox regression was performed to evaluate the association of WTC-exposure and COVID-19, adjusting for history of comorbidities, age, race, work assignment (emergency medical service providers vs. firefighter), and sex. The cumulative incidence of COVID-19 was 130 per 1000. The adjusted models showed the risk of infection was greater in those with highest WTC exposure versus less exposure (hazard ratio (HR) = 1.14 (95% CI 1.00-1.31)). Older age was associated with a lower risk of infection HR = 0.97 (95% CI 0.96-0.98). WTC-associated diseases (obstructive airways disease and interstitial lung disease) were not COVID-19 risk factors. This study is the first to show an association between WTC exposure and the risk of COVID-19. While participants are retired from FDNY work, the youngest individuals may still be in the workforce, explaining why younger age was a significant risk for COVID-19.

Twenty years after the September 11th, 2001 terrorist attacks, the association between exposures present at the World Trade Center (WTC) site and the risk of several specific types of cancer has been reported among rescue and recovery workers. The authors' objective was to conduct an updated review of these data. Most studies have found elevated rates of both prostate and thyroid cancers compared with rates in the general population, and some have reported statistically significant differences for the rates of all cancers as well. Studies including a larger combined cohort of WTC-exposed rescue and recovery workers from 3 main cohorts have since replicated findings for these cancers, with additional years of follow-up. Among this combined cohort, although a lower-than-expected standardized incidence ratio for all cancers was observed, WTC exposure was also related to an increased risk of cutaneous melanoma and tonsil cancer. Importantly, another study found that WTC-exposed rescue and recovery workers who are enrolled in the federally funded medical monitoring and treatment program experienced improved survival post-cancer diagnosis compared with New York state patients with cancer. On the basis of these combined cohort studies, the full effect of WTC exposure on cancer risk is becoming clearer. Consequently, the authors believe that surveillance of those with WTC exposure should be continued, and in-depth analysis of epidemiologic, molecular, and clinical aspects of specific cancers in these workers should be pursued., (© 2022 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)

The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to aerosolized dust, gases and potential carcinogens. Clonal hematopoiesis (CH) is defined as the acquisition of somatic mutations in blood cells and is associated with smoking and exposure to genotoxic stimuli. Here we show that deep targeted sequencing of blood samples identified a significantly higher proportion of WTC-exposed first responders with CH (10%; 48 out of 481) when compared with non-WTC-exposed firefighters (6.7%; 17 out of 255; odds ratio, 3.14; 95% confidence interval, 1.64-6.03; P = 0.0006) after controlling for age, sex and race/ethnicity. The frequency of somatic mutations in WTC-exposed first responders showed an age-related increase and predominantly affected DNMT3A, TET2 and other CH-associated genes. Exposure of lymphoblastoid cells to WTC particulate matter led to dysregulation of DNA replication at common fragile sites in vitro. Moreover, mice treated with WTC particulate matter developed an increased burden of mutations in hematopoietic stem and progenitor cell compartments. In summary, the high burden of CH in WTC-exposed first responders provides a rationale for enhanced screening and preventative efforts in this population., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Statistically significantly increased cancer incidence has been reported from 3 cohorts of World Trade Center (WTC) disaster rescue and recovery workers. We pooled data across these cohorts to address ongoing public concerns regarding cancer risk 14 years after WTC exposure., Methods: From a combined deduplicated cohort of 69 102 WTC rescue and recovery workers, a sample of 57 402 workers enrolled before 2009 and followed through 2015 was studied. Invasive cancers diagnosed in 2002-2015 were identified from 13 state cancer registries. Standardized incidence ratios (SIRs) were used to assess cancer incidence. Adjusted hazard ratios (aHRs) were estimated from Cox regression to examine associations between WTC exposures and cancer risk., Results: Of the 3611 incident cancers identified, 3236 were reported as first-time primary (FP) cancers, with an accumulated 649 724 and 624 620 person-years of follow-up, respectively. Incidence for combined FP cancers was below expectation (SIR = 0.96, 95% confidence interval [CI] = 0.93 to 0.99). Statistically significantly elevated SIRs were observed for melanoma-skin (SIR = 1.43, 95% CI = 1.24 to 1.64), prostate (SIR = 1.19, 95% CI = 1.11 to 1.26), thyroid (SIR = 1.81, 95% CI = 1.57 to 2.09), and tonsil (SIR = 1.40, 95% CI = 1.00 to 1.91) cancer. Those arriving on September 11 had statistically significantly higher aHRs than those arriving after September 17, 2001, for prostate (aHR = 1.61, 95% CI = 1.33 to 1.95) and thyroid (aHR = 1.77, 95% CI = 1.11 to 2.81) cancers, with a statistically significant exposure-response trend for both., Conclusions: In the largest cohort of 9/11 rescue and recovery workers ever studied, overall cancer incidence was lower than expected, and intensity of WTC exposure was associated with increased risk for specific cancer sites, demonstrating the value of long-term follow-up studies after environmental disasters., (© The Author(s) 2022. Published by Oxford University Press.)

On 11 September 2001 the World Trade Center (WTC) in New York was attacked by terrorists, causing the collapse of multiple buildings including the iconic 110-story 'Twin Towers'. Thousands of people died that day from the collapse of the buildings, fires, falling from the buildings, falling debris, or other related accidents. Survivors of the attacks, those who worked in search and rescue during and after the buildings collapsed, and those working in recovery and clean-up operations were exposed to severe psychological stressors. Concurrently, these 'WTC-affected' individuals breathed and ingested a mixture of organic and particulate neurotoxins and pro-inflammogens generated as a result of the attack and building collapse. Twenty years later, researchers have documented neurocognitive and motor dysfunctions that resemble the typical features of neurodegenerative disease in some WTC responders at midlife. Cortical atrophy, which usually manifests later in life, has also been observed in this population. Evidence indicates that neurocognitive symptoms and corresponding brain atrophy are associated with both physical exposures at the WTC and chronic post-traumatic stress disorder, including regularly re-experiencing traumatic memories of the events while awake or during sleep. Despite these findings, little is understood about the long-term effects of these physical and mental exposures on the brain health of WTC-affected individuals, and the potential for neurocognitive disorders. Here, we review the existing evidence concerning neurological outcomes in WTC-affected individuals, with the aim of contextualizing this research for policymakers, researchers and clinicians and educating WTC-affected individuals and their friends and families. We conclude by providing a rationale and recommendations for monitoring the neurological health of WTC-affected individuals., (© 2021. Springer Nature Limited.)

After the terrorist attacks on September 11, 2001 (9/11), many rescue/recovery workers developed respiratory symptoms and pulmonary diseases due to their extensive World Trade Center (WTC) dust cloud exposure. Nearly all Fire Department of the City of New York (FDNY) workers were present within 48 h of 9/11 and for the next several months. Since the FDNY had a well-established occupational health service for its firefighters and Emergency Medical Services workers prior to 9/11, the FDNY was able to immediately start a rigorous monitoring and treatment program for its WTC-exposed workers. As a result, respiratory symptoms and diseases were identified soon after 9/11. This focused review summarizes the WTC-related respiratory diseases that developed in the FDNY cohort after 9/11, including WTC cough syndrome, obstructive airways disease, accelerated lung function decline, airway hyperreactivity, sarcoidosis, and obstructive sleep apnea. Additionally, an extensive array of biomarkers has been identified as associated with WTC-related respiratory disease. Future research efforts will not only focus on further phenotyping/treating WTC-related respiratory disease but also on additional diseases associated with WTC exposure, especially those that take decades to develop, such as cardiovascular disease, cancer, and interstitial lung disease., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rationale: Metabolic syndrome (MetSyn) increases the risk of World Trade Center (WTC) lung injury (LI). However, the temporal relationship of MetSyn, exposure intensity, and lung dysfunction is not well understood. Objective: To model the association of longitudinal MetSyn characteristics with WTC lung disease to define modifiable risk. Methods: Firefighters, for whom consent was obtained ( N  = 5,738), were active duty on September 11, 2001 (9/11). WTC-LI ( n  = 1,475; FEV 1 % predicted 1 % predicted ⩾LLN at all exams) was the primary outcome, and FVC% predicted 1 /FVC <0.70 were secondary outcomes. We assessed 1 ) the effect of concurrent MetSyn on longitudinal lung function by linear mixed models, 2 ) the temporal effect of MetSyn and exposure by Weibull proportional hazards, 3 ) the effects of MetSyn's rate of change by two-stage models, and 4 ) the nonlinear joint effect of longitudinal MetSyn components by a partially linear single-index model (PLSI). Measurements and Main Results: WTC-LI cases were more often ever-smokers, arrived in the morning (9/11), and had MetSyn. Body mass index ⩾30 kg/m 2 and high-density lipoprotein <40 mg/dl were most contributory to concurrent loss of FEV 1 % predicted and FVC% predicted while conserving FEV 1 /FVC. Body mass index ⩾30 kg/m 2 and dyslipidemia significantly predicted WTC-LI, FVC% predicted

Rescue/recovery workers who responded to the World Trade Center (WTC) attacks were exposed to known/suspected carcinogens. Studies have identified a trend toward an elevated risk of cutaneous melanoma in this population; however, few found significant increases. Furthermore, temporal aspects of the association have not been investigated. A total of 44,540 non-Hispanic White workers from the WTC Combined Rescue/Recovery Cohort were studied between March 12, 2002 and December 31, 2015. Cancer data were obtained through linkages with 13 state registries. Poisson regression was used to estimate hazard ratios and 95% confidence intervals using the New York State population as the reference; change points in hazard ratios were estimated using profile likelihood. We observed 247 incident cases of melanoma. No increase in incidence was detected during 2002-2004. From 2005 to 2015, the hazard ratio was 1.34 (95% confidence interval = 1.18-1.52). A dose‒response relationship was observed by arrival time at the WTC site. Risk was elevated just over 3 years after the attacks . Whereas WTC-related exposures to UVR or other agents might have contributed to this result, exposures other than those at the WTC site, enhanced medical surveillance, and lack of a control group with a similar proportion of rescue/recovery workers cannot be discounted. Our results support continued study of this population for melanoma., (© 2021 The Authors.)

Objective: To compare cancer incidence in Fire Department of the City of New York (FDNY) firefighters who worked at the World Trade Center (WTC) site to incidence in a population of non-WTC-exposed firefighters, the Career Firefighter Health Study (CFHS) cohort, and to compare rates from each firefighter cohort to rates in demographically similar US males., Methods: FDNY (N=10 786) and CFHS (N=8813) cohorts included male firefighters who were active on 11 September 2001 (9/11) and were followed until death or 31 December 2016. Cases were identified from 15 state cancer registries. Poisson regression models assessed cancers in each group (FDNY and CFHS) versus US males, and associations between group and cancer rates; these models estimated standardised incidence ratios (SIRs) and adjusted relative rates (RRs), respectively. Secondary analyses assessed surveillance bias and smoking history., Results: We identified 915 cancer cases in 841 FDNY firefighters and 1002 cases in 909 CFHS firefighters. FDNY had: higher rates for all cancers (RR=1.13; 95% CI 1.02 to 1.25), prostate (RR=1.39; 95% CI 1.19 to 1.63) and thyroid cancer (RR=2.53; 95% CI 1.37 to 4.70); younger median ages at diagnosis (55.6 vs 59.4; p<0.001, all cancers); and more cases with localised disease when compared with CFHS. Compared with US males, both firefighter cohorts had elevated SIRs for prostate cancer and melanoma. Control for surveillance bias in FDNY reduced most differences., Conclusions: Excess cancers occurred in WTC-exposed firefighters relative to each comparison group, which may partially be explained by heightened surveillance. Two decades post-9/11, clearer understanding of WTC-related risk requires extended follow-up and modelling studies (laboratory or animal based) to identify workplace exposures in all firefighters., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A recent study of World Trade Center (WTC)-exposed firefighters and emergency medical service workers demonstrated that elevated thyroid cancer incidence may be attributable to frequent medical testing, resulting in the identification of asymptomatic tumors. We expand on that study by comparing the incidence of thyroid cancer among three groups: WTC-exposed rescue/recovery workers enrolled in a New York State (NYS) WTC-medical monitoring and treatment program (MMTP); WTC-exposed rescue/recovery workers not enrolled in an MMTP (non-MMTP); and the NYS population., Methods: Person-time began on 9/12/2001 or at enrollment in a WTC cohort and ended at death or on 12/31/2015. Cancer data were obtained through linkages with 13 state cancer registries. We used Poisson regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for MMTP and non-MMTP participants. NYS rates were used as the reference. To estimate potential changes over time in WTC-associated risk, change points in RRs were estimated using profile likelihood., Results: The thyroid cancer incidence rate among MMTP participants was more than twice that of NYS population rates (RR = 2.31; 95% CI = 2.00-2.68). Non-MMTP participants had a risk similar to NYS (RR = 0.96; 95% CI = 0.72-1.28). We observed no change points in the follow-up period., Conclusion: Our findings support the hypothesis that no-cost screening (a benefit provided by WTC-MMTPs) is associated with elevated identification of thyroid cancer. Given the high survival rate for thyroid cancer, it is important to weigh the costs and benefits of treatment, as many of these cancers were asymptomatic and may have been detected incidentally., (© 2021 Wiley Periodicals LLC.)

Background: World Trade Center (WTC)-exposed responders may be eligible to receive no-cost medical monitoring and treatment for certified conditions, including cancer. The survival of responders with cancer has not previously been investigated., Methods: This study compared the estimated relative survival of WTC-exposed responders who developed cancer while enrolled in two WTC medical monitoring and treatment programs in New York City (WTC-MMTP responders) and WTC-exposed responders not enrolled (WTC-non-MMTP responders) to non-responders from New York State (NYS-non-responders), all restricted to the 11-southernmost NYS counties, where most responders resided. Parametric survival models estimated cancer-specific and all-cause mortality. Follow-up ended at death or on December 31, 2016., Results: From January 1, 2005 to December 31, 2016, there were 2,037 cancer cases and 303 deaths (248 cancer-related deaths) among WTC-MMTP responders, 564 cancer cases, and 143 deaths (106 cancer-related deaths) among WTC-non-MMTP responders, and 574,075 cancer cases and 224,040 deaths (158,645 cancer-related deaths) among the NYS-non-responder population. Comparing WTC-MMTP responders with NYS-non-responders, the cancer-specific mortality hazard ratio (HR) was 0.72 (95% confidence interval [CI] = 0.64-0.82), and all-cause mortality HR was 0.64 (95% CI = 0.58-0.72). The cancer-specific HR was 0.94 (95% CI = 0.78-1.14), and all-cause mortality HR was 0.93 (95% CI = 0.79-1.10) comparing WTC-non-MMTP responders to the NYS-non-responder population., Conclusions: WTC-MMTP responders had lower mortality compared with NYS-non-responders, after controlling for demographic factors and temporal trends. There may be survival benefits from no-out-of-pocket-cost medical care which could have important implications for healthcare policy, however, other occupational and socioeconomic factors could have contributed to some of the observed survival advantage., (© 2021 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals LLC.)

Background: Accelerated-FEV 1 -decline, defined as rate of decline in FEV 1  > 64 ml/year, is a risk factor for asthma and chronic obstructive pulmonary disease in World Trade Center (WTC)-exposed firefighters. Accelerated-FEV 1 -decline in this cohort is associated with elevated blood eosinophil concentrations, a mediator of Th-2 response. We hypothesized that an association exists between Th-2 biomarkers and FEV 1 decline rate in those with accelerated-FEV 1 -decline., Methods: Serum was drawn from Fire Department of the City of New York (FDNY) firefighters 1-6 months (early) (N = 816) and 12-13 years (late) (N = 983) after 9/11/2001. Th-2 biomarkers IL-4, IL-13, and IL-5 were assayed by multiplex Luminex. Individual FEV 1 decline rates were calculated using spirometric measurements taken: (1) between 9/11/2001 and 9/10/2020 for the early biomarker group and (2) between late measurement date and 9/10/2020 for the late biomarker group. Associations of early and late Th-2 biomarkers with subsequent FEV 1 decline rates were analyzed using multivariable linear regression controlling for demographics, smoking status, and other potential confounders., Results: In WTC-exposed firefighters with accelerated-FEV 1 -decline, IL-4, IL-13, and IL-5 measured 1-6 months post-9/11/2001 were associated with greater FEV 1 decline ml/year between 9/11/2001 and 9/10/2020 (-2.9 ± 1.4 ml/year per IL-4 doubling; -8.4 ± 1.2 ml/year per IL-13 doubling; -7.9 ± 1.3 ml/year per IL-5 doubling). Among late measured Th-2 biomarkers, only IL-4 was associated with subsequent FEV 1 decline rate (-4.0 ± 1.6 ml/year per IL-4 doubling)., Conclusions: In WTC-exposed firefighters with accelerated-FEV 1 -decline, elevated serum IL-4 measured both 1-6 months and 12-13 years after 9/11 is associated with greater FEV 1 decline/year. Drugs targeting the IL-4 pathway may improve lung function in this high-risk subgroup., (© 2021 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals LLC.)

Background: Firefighting has been associated with posttraumatic stress disorder (PTSD) and other mental health conditions. We previously found that among Fire Department of the City of New York (FDNY) responders to the World Trade Center (WTC) disaster, higher-intensity WTC-exposure predicted PTSD symptoms, depressive symptoms, and subjective cognitive concerns. The present study aims to compare these symptoms in the FDNY WTC-exposed cohort versus a comparison cohort of non-FDNY, non-WTC-exposed firefighters., Methods: The study population included WTC-exposed male firefighters from FDNY (N = 8466) and non-WTC-exposed male firefighters from Chicago (N = 1195), Philadelphia (N = 770), and San Francisco (N = 650) fire departments who were employed on 9/11/2001 and completed a health questionnaire between 3/1/2018 and 12/31/2020. Current PTSD symptoms, depressive symptoms, and subjective cognitive concerns were assessed via validated screening instruments. Multivariable linear regression analyses stratified by fire department estimated the impact of covariates on each outcome., Results: Adjusted mean PTSD symptom scores ranged from 23.5 ± 0.6 in Chicago firefighters to 25.8 ± 0.2 in FDNY, and adjusted mean depressive symptom scores ranged from 7.3 ± 0.5 in Chicago to 9.4 ± 0.6 in Philadelphia. WTC-exposure was associated with fewer subjective cognitive concerns (β = -0.69 ± 0.05, p < .001) after controlling for covariates. Across cohorts, older age was associated with more cognitive concerns, but fewer PTSD and depressive symptoms., Conclusions: WTC-exposed firefighters had fewer cognitive concerns compared with non-WTC-exposed firefighters. We were unable to estimate associations between WTC exposure and PTSD symptoms or depressive symptoms due to variability between non-WTC-exposed cohorts. Longitudinal follow-up is needed to assess PTSD, depressive, and cognitive symptom trajectories in firefighter populations as they age., (© 2021 Wiley Periodicals LLC.)

Background: Greater than average loss of one-second forced expiratory volume (FEV 1 ) is a risk factor for asthma, chronic obstructive pulmonary disease (COPD), and asthma/COPD overlap syndrome in World Trade Center (WTC)-exposed firefighters. Inhaled corticosteroids and long-acting beta agonists (ICS/LABA) are used to treat obstructive airways disease but their impact on FEV 1 -trajectory in this population is unknown., Methods: The study population included WTC-exposed male firefighters who were treated with ICS/LABA for 2 years or longer (with initiation before 2015), had at least two FEV 1 measurements before ICS/LABA initiation and two FEV 1 measurements posttreatment between September 11, 2001 and September 10, 2019. Linear mixed-effects models were used to estimate FEV 1 -slope pre- and post-treatment., Results: During follow-up, 1023 WTC-exposed firefighters were treated with ICS/LABA for 2 years or longer. When comparing intervals 6 years before and 6 years after treatment, participants had an 18.7 ml/year (95% confidence interval [CI]: 11.3-26.1) improvement in FEV 1 -slope after adjustment for baseline FEV 1 , race, height, WTC exposure, weight change, blood eosinophil concentration, and smoking status. After stratification by median date of ICS/LABA initiation (January 14, 2010), earlier ICS/LABA-initiators had a 32.5 ml/year (95% CI: 19.5-45.5) improvement in slope but later ICS/LABA-initiators had a nonsignificant FEV 1 -slope improvement (7.9 ml/year, 95% CI: -0.5 to 17.2)., Conclusions: WTC-exposed firefighters treated with ICS/LABA had improved FEV 1 slope after initiation, particularly among those who started earlier. Treatment was, however, not associated with FEV 1 -slope improvement if started after the median initiation date (1/14/2010), likely because onset of disease began before treatment initiation. Research on alternative treatments is needed for patients with greater than average FEV 1 -decline who have not responded to ICS/LABA., (© 2021 The Authors. American Journal of Industrial Medicine published by Wiley Periodicals LLC.)

Background: Studies of World Trade Center (WTC)-exposed rescue/recovery workers report the increased occurrence of health conditions after work at the WTC disaster site. However, the extent to which these associations are due to WTC exposure is unclear, in part due to the lack of suitable comparison groups. Accordingly, we identified a previously assembled National Institute for Occupational Safety and Health (NIOSH) cohort of career firefighters from three US cities (n = 29,992). Here, we document the challenges in establishing this non-WTC-exposed firefighter cohort for the goal of tracking and comparing cancer and chronic health conditions in WTC-exposed and non-WTC-exposed firefighters., Methods: Follow-up process included institutional review board applications, data use agreements, state cancer registry linkages and vital status determination for the NIOSH firefighter cohort. After completion of these steps, we undertook outreach to the three original city fire departments and union officials, before contact tracing and direct recruitment of 14,566 living firefighters to complete a confidential health survey. We staggered recruitment efforts by the city, using letters, postcards, emails, videos, and telephone outreach. Participants who completed the survey received $10., Results: A total of 4962 of 14,566 alive firefighters responded to the baseline survey (34.1% response rate). Respondents were older and more likely to be non-Hispanic white than nonrespondents., Conclusions: We provide an overview of the process for the first survey to collect information on physical and mental health conditions among US firefighters. The data collected will have an important impact on studies of WTC rescue/recovery work, firefighting, and related health conditions., (© 2021 Wiley Periodicals LLC.)

Background: Lung cancer is a leading cause of cancer incidence and death in the United States. Risk factor-based guidelines and risk model-based strategies are used to identify patients who could benefit from low-dose chest CT (LDCT) screening. Few studies compare guidelines or models within the same cohort. We evaluate lung cancer screening performance of two risk factor-based guidelines (US Preventive Services Task Force 2014 recommendations [USPSTF-2014] and National Comprehensive Cancer Network Group 2 [NCCN-2]) and two risk model-based strategies, Prostate Lung Colorectal and Ovarian Cancer Screening (PLCOm2012) and the Bach model) in the same occupational cohort., Research Question: Which risk factor-based guideline or model-based strategy is most accurate in detecting lung cancers in a highly exposed occupational cohort?, Study Design and Methods: Fire Department of City of New York (FDNY) rescue/recovery workers exposed to the September 11, 2001 attacks underwent LDCT lung cancer screening based on smoking history and age. The USPSTF-2014, NCCN-2, PLCOm2012 model, and Bach model were retrospectively applied to determine how many lung cancers were diagnosed using each approach., Results: Among the study population (N = 3,953), 930 underwent a baseline scan that met at least one risk factor or model-based LDCT screening strategy; 73% received annual follow-up scans. Among the 3,953, 63 lung cancers were diagnosed, of which 50 were detected by at least one LDCT screening strategy. The NCCN-2 guideline was the most sensitive (79.4%; 50/63). When compared with NCCN-2, stricter age and smoking criteria reduced sensitivity of the other guidelines/models (USPSTF-2014 [44%], PLCOm2012 [51%], and Bach[46%]). The 13 missed lung cancers were mainly attributable to smoking less and quitting longer than guideline/model eligibility criteria. False-positive rates were similar across all four guidelines/models., Interpretation: In this cohort, our findings support expanding eligibility for LDCT lung cancer screening by lowering smoking history from ≥30 to ≥20 pack-years and age from 55 years to 50 years old. Additional studies are needed to determine its generalizability to other occupational/environmental exposed cohorts., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Purpose: The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens. High incidence of multiple myeloma and precursor conditions has been reported among first responders to the WTC disaster. To expand on our prior screening studies, and to characterize the genomic impact of the exposure to known and potential carcinogens in the WTC debris, we were motivated to perform whole-genome sequencing (WGS) of WTC first responders and recovery workers who developed a plasma cell disorder after the attack., Experimental Design: We performed WGS of nine CD138-positive bone marrow mononuclear samples from patients who were diagnosed with plasma cell disorders after the WTC disaster., Results: No significant differences were observed in comparing the post-WTC driver and mutational signature landscapes with 110 previously published WGSs from 56 patients with multiple myeloma and the CoMMpass WGS cohort ( n = 752). Leveraging constant activity of the single-base substitution mutational signatures 1 and 5 over time, we estimated that tumor-initiating chromosomal gains were windowed to both pre- and post-WTC exposure., Conclusions: Although limitations in sample size preclude any definitive conclusions, our findings suggest that the observed increased incidence of plasma cell neoplasms in this population is due to complex and heterogeneous effects of the WTC exposure that may have initiated or contributed to progression of malignancy., (©2021 American Association for Cancer Research.)

Objective: To determine if oxygen saturation (out-of-hospital SpO2), measured by New York City (NYC) 9-1-1 Emergency Medical Services (EMS), was an independent predictor of coronavirus disease 2019 (COVID-19) in-hospital mortality and length of stay, after controlling for the competing risk of death. If so, out-of-hospital SpO2 could be useful for initial triage., Methods: A population-based longitudinal study of adult patients transported by EMS to emergency departments (ED) between March 5 and April 30, 2020 (the NYC COVID-19 peak period). Inclusion required EMS prehospital SpO2 measurement while breathing room air, transport to emergency department, and a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction test. Multivariable logistic regression modeled mortality as a function of prehospital SpO2, controlling for covariates (age, sex, race/ethnicity, and comorbidities). A competing risk model also was performed to estimate the absolute risks of out-of-hospital SpO2 on the cumulative incidence of being discharged from the hospital alive., Results: In 1673 patients, out-of-hospital SpO2 and age were independent predictors of in-hospital mortality and length of stay, after controlling for the competing risk of death. Among patients ≥66 years old, the probability of death was 26% with an out-of-hospital SpO2 >90% versus 54% with an out-of-hospital SpO2 ≤90%. Among patients <66 years old, the probability of death was 11.5% with an out-of-hospital SpO2 >90% versus 31% with an out-of-hospital SpO2 ≤ 90%. An out-of-hospital SpO2 level ≤90% was associated with over 50% decreased likelihood of being discharged alive, regardless of age., Conclusions: Out-of-hospital SpO2 and age predicted in-hospital mortality and length of stay: An out-of-hospital SpO2 ≤90% strongly supports a triage decision for immediate hospital admission. For out-of-hospital SpO2 >90%, the decision to admit depends on multiple factors, including age, resource availability (outpatient vs inpatient), and the potential impact of new treatments., Competing Interests: The authors have no conflicts of interest to report., (© 2021 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

Three cohorts including the Fire Department of the City of New York (FDNY), the World Trade Center Health Registry (WTCHR), and the General Responder Cohort (GRC), each funded by the World Trade Center Health Program have reported associations between WTC-exposures and cancer. Results have generally been consistent with effect estimates for excess incidence for all cancers ranging from 6 to 14% above background rates. Pooling would increase sample size and de-duplicate cases between the cohorts. However, pooling required time consuming steps: obtaining Institutional Review Board (IRB) approvals and legal agreements from entities involved; establishing an honest broker for managing the data; de-duplicating the pooled cohort files; applying to State Cancer Registries (SCRs) for matched cancer cases; and finalizing analysis data files. Obtaining SCR data use agreements ranged from 6.5 to 114.5 weeks with six states requiring >20 weeks. Records from FDNY ( n = 16,221), WTCHR ( n = 29,372), and GRC ( n = 33,427) were combined de-duplicated resulting in 69,102 unique individuals. Overall, 7894 cancer tumors were matched to the pooled cohort, increasing the number cancers by as much as 58% compared to previous analyses. Pooling resulted in a coherent resource for future research for studies on rare cancers and mortality, with more representative of occupations and WTC- exposure.

Objectives: In New York City, a multi-disciplinary Mass Casualty Consultation team is proposed to support prioritization of patients for coordinated inter-facility transfer after a large-scale mass casualty event. This study examines factors that influence consultation team prioritization decisions., Methods: As part of a multi-hospital functional exercise, 2 teams prioritized the same set of 69 patient profiles. Prioritization decisions were compared between teams. Agreement between teams was assessed based on patient profile demographics and injury severity. An investigator interviewed team leaders to determine reasons for discordant transfer decisions., Results: The 2 teams differed significantly in the total number of transfers recommended (49 vs 36; P = 0.003). However, there was substantial agreement when recommending transfer to burn centers, with 85.5% agreement and inter-rater reliability of 0.67 (confidence interval: 0.49-0.85). There was better agreement for patients with a higher acuity of injuries. Based on interviews, the most common reason for discordance was insider knowledge of the local community hospital and its capabilities., Conclusions: A multi-disciplinary Mass Casualty Consultation team was able to rapidly prioritize patients for coordinated secondary transfer using limited clinical information. Training for consultation teams should emphasize guidelines for transfer based on existing services at sending and receiving hospitals, as knowledge of local community hospital capabilities influence physician decision-making.

Risk factors for #COVID19 infection and severe disease (hospitalisation or death) in NYC first responders: greater pre-pandemic rate of FEV 1 decline is associated with severe COVID-19, as is emergency medical service work versus firefighting https://bit.ly/3nZPuZY., Competing Interests: Conflict of interest: M.D. Weiden has nothing to disclose. Conflict of interest: R. Zeig-Owens reports grants from NIOSH outside the submitted work. Conflict of interest: A. Singh has nothing to disclose. Conflict of interest: T. Schwartz has nothing to disclose. Conflict of interest: Y. Liu has nothing to disclose. Conflict of interest: B. Vaeth has nothing to disclose. Conflict of interest: A. Nolan has nothing to disclose. Conflict of interest: K.L. Cleven has nothing to disclose. Conflict of interest: K. Hurwitz has nothing to disclose. Conflict of interest: S. Beecher has nothing to disclose. Conflict of interest: D.J. Prezant has nothing to disclose., (Copyright ©ERS 2021.)

Background: Diet is a modifier of metabolic syndrome which in turn is associated with World Trade Center obstructive airways disease (WTC-OAD). We have designed this study to (1) assess the dietary phenotype (food types, physical activity, and dietary habits) of the Fire Department of New York (FDNY) WTC-Health Program (WTC-HP) cohort and (2) quantify the association of dietary quality and its advanced glycation end product (AGE) content with the development of WTC-OAD., Methods: WTC-OAD, defined as developing WTC-Lung Injury (WTC-LI; FEV 1  < LLN) and/or airway hyperreactivity (AHR; positive methacholine and/or positive bronchodilator response). Rapid Eating and Activity Assessment for Participants-Short Version (REAP-S) deployed on 3/1/2018 in the WTC-HP annual monitoring assessment. Clinical and REAP-S data of consented subjects was extracted (7/17/2019). Diet quality [low-(15-19), moderate-(20-29), and high-(30-39)] and AGE content per REAP-S questionnaire were assessed for association with WTC-OAD. Regression models adjusted for smoking, hyperglycemia, hypertension, age on 9/11, WTC-exposure, BMI, and job description., Results: N = 9508 completed the annual questionnaire, while N = 4015 completed REAP-S and had spirometry. WTC-OAD developed in N = 921, while N = 3094 never developed WTC-OAD. Low- and moderate-dietary quality, eating more (processed meats, fried foods, sugary drinks), fewer (vegetables, whole-grains),and having a diet abundant in AGEs were significantly associated with WTC-OAD. Smoking was not a significant risk factor of WTC-OAD., Conclusions: REAP-S was successfully implemented in the FDNY WTC-HP monitoring questionnaire and produced valuable dietary phenotyping. Our observational study has identified low dietary quality and AGE abundant dietary habits as risk factors for pulmonary disease in the context of WTC-exposure. Dietary phenotyping, not only focuses our metabolomic/biomarker profiling but also further informs future dietary interventions that may positively impact particulate matter associated lung disease.

The factors that predict treatment of lung injury in occupational cohorts are poorly defined. We aimed to identify patient characteristics associated with initiation of treatment with inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) >2 years among World Trade Center (WTC)-exposed firefighters. The study population included 8530 WTC-exposed firefighters. Multivariable logistic regression assessed the association of patient characteristics with ICS/LABA treatment for >2 years over two-year intervals from 11 September 2001-10 September 2017. Cox proportional hazards models measured the association of high probability of ICS/LABA initiation with actual ICS/LABA initiation in subsequent intervals. Between 11 September 2001-1 July 2018, 1629/8530 (19.1%) firefighters initiated ICS/LABA treatment for >2 years. Forced Expiratory Volume in 1 s (FEV 1 ), wheeze, and dyspnea were consistently and independently associated with ICS/LABA treatment. High-intensity WTC exposure was associated with ICS/LABA between 11 September 2001-10 September 2003. The 10th percentile of risk for ICS/LABA between 11 September 2005-10 Septmeber 2007 was associated with a 3.32-fold increased hazard of actual ICS/LABA initiation in the subsequent 4 years. In firefighters with WTC exposure, FEV 1 , wheeze, and dyspnea were independently associated with prolonged ICS/LABA treatment. A high risk for treatment was identifiable from routine monitoring exam results years before treatment initiation.

Objectives: To describe the impact of the COVID-19 pandemic on New York City's (NYC) 9-1-1 emergency medical services (EMS) system and assess the efficacy of pandemic planning to meet increased demands., Methods: Longitudinal analysis of NYC 9-1-1 EMS system call volumes, call-types, and response times during the COVID-19 peak-period (March 16-April 15, 2020) and post-surge period (April 16-May 31, 2020) compared with the same 2019 periods., Results: EMS system received 30,469 more calls from March 16-April 15, 2020 compared with March 16-April 15, 2019 (161,815 vs 127,962; P  < 0.001). On March 30, 2020, call volume increased 60% compared with the same 2019 date. The majority were for respiratory (relative risk [RR] = 2.50; 95% confidence interval [CI] = 2.44-2.56) and cardiovascular (RR = 1.85; 95% CI = 1.82-1.89) call-types. The proportion of high-acuity, life-threatening call-types increased compared with 2019 (42.3% vs 36.4%). Planned interventions to prioritize high-acuity calls resulted in the average response time increasing by 3 minutes compared with an 11-minute increase for low low-acuity calls. Post-surge, EMS system received fewer calls compared with 2019 (154,310 vs 193,786; P  < 0.001)., Conclusions: COVID-19-associated NYC 9-1-1 EMS volume surge was primarily due to respiratory and cardiovascular call-types. As the pandemic stabilized, call volume declined to below pre-pandemic levels. Our results highlight the importance of EMS system-wide pandemic crisis planning., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of the American College of Emergency Physicians.)

Importance: Risk factors for out-of-hospital death due to novel coronavirus disease 2019 (COVID-19) are poorly defined. From March 1 to April 25, 2020, New York City, New York (NYC), reported 17 118 COVID-19-related deaths. On April 6, 2020, out-of-hospital cardiac arrests peaked at 305 cases, nearly a 10-fold increase from the prior year., Objective: To describe the characteristics (race/ethnicity, comorbidities, and emergency medical services [EMS] response) associated with outpatient cardiac arrests and death during the COVID-19 pandemic in NYC., Design, Setting, and Participants: This population-based, cross-sectional study compared patients with out-of-hospital cardiac arrest receiving resuscitation by the NYC 911 EMS system from March 1 to April 25, 2020, compared with March 1 to April 25, 2019. The NYC 911 EMS system serves more than 8.4 million people., Exposures: The COVID-19 pandemic., Main Outcomes and Measures: Characteristics associated with out-of-hospital arrests and the outcomes of out-of-hospital cardiac arrests., Results: A total of 5325 patients were included in the main analysis (2935 men [56.2%]; mean [SD] age, 71 [18] years), 3989 in the COVID-19 period and 1336 in the comparison period. The incidence of nontraumatic out-of-hospital cardiac arrests in those who underwent EMS resuscitation in 2020 was 3 times the incidence in 2019 (47.5/100 000 vs 15.9/100 000). Patients with out-of-hospital cardiac arrest during 2020 were older (mean [SD] age, 72 [18] vs 68 [19] years), less likely to be white (611 of 2992 [20.4%] vs 382 of 1161 [32.9%]), and more likely to have hypertension (2134 of 3989 [53.5%] vs 611 of 1336 [45.7%]), diabetes (1424 of 3989 [35.7%] vs 348 of 1336 [26.0%]), and physical limitations (2259 of 3989 [56.6%] vs 634 of 1336 [47.5%]). Compared with 2019, the odds of asystole increased in the COVID-19 period (odds ratio [OR], 3.50; 95% CI, 2.53-4.84; P < .001), as did the odds of pulseless electrical activity (OR, 1.99; 95% CI, 1.31-3.02; P = .001). Compared with 2019, the COVID-19 period had substantial reductions in return of spontaneous circulation (ROSC) (727 of 3989 patients [18.2%] vs 463 of 1336 patients [34.7%], P < .001) and sustained ROSC (423 of 3989 patients [10.6%] vs 337 of 1336 patients [25.2%], P < .001), with fatality rates exceeding 90%. These associations remained statistically significant after adjustment for potential confounders (OR for ROSC, 0.59 [95% CI, 0.50-0.70; P < .001]; OR for sustained ROSC, 0.53 [95% CI, 0.43-0.64; P < .001])., Conclusions and Relevance: In this population-based, cross-sectional study, out-of-hospital cardiac arrests and deaths during the COVID-19 pandemic significantly increased compared with the same period the previous year and were associated with older age, nonwhite race/ethnicity, hypertension, diabetes, physical limitations, and nonshockable presenting rhythms. Identifying patients with the greatest risk for out-of-hospital cardiac arrest and death during the COVID-19 pandemic should allow for early, targeted interventions in the outpatient setting that could lead to reductions in out-of-hospital deaths.

Fire Department of New York (FDNY) rescue and recovery workers exposed to World Trade Center (WTC) particulates suffered loss of forced expiratory volume in 1 s (FEV 1 ). Metabolic Syndrome increased the risk of developing WTC-lung injury (WTC-LI) . We aim to attenuate the deleterious effects of WTC exposure through a dietary intervention targeting these clinically relevant disease modifiers. We hypothesize that a calorie-restricted Mediterranean dietary intervention will improve metabolic risk, subclinical indicators of cardiopulmonary disease, quality of life, and lung function in firefighters with WTC-LI. To assess our hypothesis, we developed the Food Intake REstriction for Health OUtcome Support and Education (FIREHOUSE), a randomized controlled clinical trial (RCT). Male firefighters with WTC-LI and a BMI > 27 kg/m 2 will be included. We will randomize subjects (1:1) to either: (1) Low Calorie Mediterranean (LoCalMed)-an integrative multifactorial, technology-supported approach focused on behavioral modification, nutritional education that will include a self-monitored diet with feedback, physical activity recommendations, and social cognitive theory-based group counseling sessions; or (2) Usual Care. Outcomes include reduction in body mass index (BMI) (primary), improvement in FEV 1 , fractional exhaled nitric oxide, pulse wave velocity, lipid profiles, targeted metabolic/clinical biomarkers, and quality of life measures (secondary). By implementing a technology-supported LoCalMed diet our FIREHOUSE RCT may help further the treatment of WTC associated pulmonary disease.

The World Trade Center (WTC) attacks on 9/11/2001 have consistently been associated with elevated rates of physical and mental health morbidities, while evidence about mortality has been limited. We examined mortality between 9/12/2001 and 12/31/2017 among 15,431 WTC-exposed Fire Department of the City of New York (FDNY) firefighters and emergency medical service providers (EMS), specifically assessing associations between intensity of WTC-exposure and mortality risk. Standardized mortality ratios (SMR) and 95% confidence intervals (CI) compared FDNY cohort mortality with the US general population using life table analysis. Deaths were identified via linkage to the National Death Index. Cox proportional hazards regression models were used to identify associations between intensity of WTC-exposure and mortality, accounting for age, sex, race/ethnicity, smoking history, and other relevant confounders. We identified 546 deaths and a lower than expected all-cause mortality rate (SMR = 0.34; 95% CI, 0.31–0.37). No cause-specific SMRs were meaningfully elevated. Mortality hazard ratios showed no association or linear trend with level of WTC-exposure. Our results provide evidence of the healthy worker effect, despite exposure to the World Trade Center. More follow-up time may be needed to assess the full impact of WTC-exposure on mortality in this occupational population.

We observed that World Trade Center (WTC) exposure, post-traumatic stress disorder (PTSD) symptoms and depressive symptoms were associated with subjective cognitive concerns in Fire Department of the City of New York (FDNY) rescue/recovery workers. This follow-up study examined whether PTSD symptoms and/or depressive symptoms mediate the observed association between WTC exposure and subjective cognitive concerns. We included WTC-exposed FDNY workers who completed the Cognitive Function Instrument (CFI), measuring self-perceived cognitive decline ( N = 9516). PTSD symptoms and depressive symptoms were assessed using the PCL-S and CES-D, respectively. Multivariable linear regression estimated the association between WTC exposure and CFI score, adjusting for confounders. Mediation analyses followed the methods of Vanderweele (2014). Participants' average age at CFI assessment was 56.6 ± 7.6 years. Higher-intensity WTC exposure was associated with worse CFI score, an effect that was entirely mediated by PTSD symptoms (%mediated: 110.9%; 95%CI: 83.1-138.9). When substituting depressive symptoms for PTSD symptoms, the WTC exposure-CFI association was largely mediated (%mediated: 82.1%; 95%CI: 60.6-103.7). Our findings that PTSD symptoms and depressive symptoms mediate the association between WTC exposure and subjective cognitive concerns indicate that in the absence of these symptoms, WTC exposure in rescue/recovery workers would not be associated with subjective cognition. Interventions targeting PTSD and depression may have additional value in mitigating cognitive decline in WTC-exposed populations.

Importance: Elevated incidence rates of thyroid cancer among World Trade Center (WTC)-exposed individuals may be associated with the identification of asymptomatic cancers during medical surveillance., Objective: To examine the association between WTC exposure and thyroid cancer among Fire Department of the City of New York (hereafter, Fire Department) rescue/recovery workers as well as the association with medical surveillance., Design, Setting, and Participants: This closed-cohort study classified the method of detection (asymptomatic and symptomatic) of thyroid cancers in 14 987 men monitored through the Fire Department-WTC Health Program diagnosed from September 12, 2001, to December 31, 2018. Age-, sex-, and histologic-specific Fire Department incidence rates were calculated and compared with demographically similar men in Olmsted County, Minnesota, from the Rochester Epidemiology Project using age-standardized rates, relative rates (RRs), and 95% CIs. The secondary analysis was restricted to papillary carcinomas., Exposures: World Trade Center exposure was defined as rescue/recovery work at the WTC site from September 11, 2001, to July 25, 2002., Main Outcomes and Measures: The outcomes evaluated comprised (1) number of incident thyroid cancers and their detection method categorizations in the Fire Department and Rochester Epidemiology Project cohorts; (2) Fire Department, Rochester Epidemiology Project, and Surveillance, Epidemiology, and End Results-21 age-standardized incidence rates of thyroid cancer; and (3) RRs comparing Fire Department and Rochester Epidemiology Project overall and by detection method categorization., Results: Seventy-two post-9/11 Fire Department cases of thyroid cancer were identified. Among the 65 cases (90.3%) with a categorized detection method, 53 cases (81.5%) were asymptomatic and 12 cases (18.5%) were symptomatic. Median (interquartile range) age at diagnosis was 50.2 (44.0-58.6) vs 46.6 (43.9-52.9) years for asymptomatic vs symptomatic cases. Associated primarily with asymptomatic cancers, the overall age-standardized incidence of Fire Department thyroid cancers (24.7; 95% CI, 17.4-52.3) was significantly higher than the Rochester Epidemiology Project (10.4; 95% CI, 8.5-12.7) and Surveillance, Epidemiology, and End Results-21 (9.1; 95% CI, 9.0-9.1) per 100 000 person-years. Furthermore, the RR of thyroid cancer among symptomatic men in Fire Department cases was not significantly different from that of men in the Rochester Epidemiology Project (0.8; 95% CI, 0.4-1.5); however, the rate of asymptomatic cancers was more than 3-fold that of the Rochester Epidemiology Project rate (RR, 3.1; 95% CI, 2.1-4.7)., Conclusions and Relevance: Excess asymptomatic thyroid cancer in Fire Department WTC-exposed rescue/recovery workers is apparently attributable to the identification of occult lesions during medical surveillance. Among WTC-exposed cohorts and the general population, these findings appear to have important implications for how thyroid cancer incidence rates are interpreted and how diagnoses should be managed.

Objective: In occupational hearing conservation programmes, age adjustments may be used to subtract expected age effects. Adjustments used in the U.S. came from a small dataset and overlooked important demographic factors, ages, and stimulus frequencies. The present study derived a set of population-based age adjustment tables and validated them using a database of exposed workers. Design: Cross-sectional population-based study and retrospective longitudinal cohort study for validation. Study sample: Data from the U.S. National Health and Nutrition Examination Survey (unweighted n  = 9937) were used to produce these tables. Male firefighters and emergency medical service workers (76,195 audiograms) were used for validation. Results: Cross-sectional trends implied less change with age than assumed in current U.S. regulations. Different trends were observed among people identifying with non-Hispanic Black race/ethnicity. Four age adjustment tables (age range: 18-85) were developed (women or men; non-Hispanic Black or other race/ethnicity). Validation outcomes showed that the population-based tables matched median longitudinal changes in hearing sensitivity well. Conclusions: These population-based tables provide a suitable replacement for those implemented in current U.S. regulations. These tables address a broader range of worker ages, account for differences in hearing sensitivity across race/ethnicity categories, and have been validated for men using longitudinal data.

Objective: To determine if World Trade Center (WTC) exposure is associated with hearing loss., Methods: Logistic regression to evaluate the immediate impact of WTC exposure and parametric survival analysis to assess longitudinal outcomes., Results: Those arriving on the morning of September 11, 2001 had elevated odds of low-frequency (odds ratio [OR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.47) and high-frequency (OR: 1.16; 95% CI: 1.02 to 1.31) hearing loss at their first post-September 11, 2001 examination. Longitudinally, participants arriving before September 13, 2001 and spending more than or equal to 6 months at the WTC-site had greater risk of hearing loss in the low frequencies (risk ratio [RR]: 1.31; 95% CI: 1.05 to 1.60) and high frequencies (RR: 1.37; 95% CI: 1.22 to 1.54). By 2016, 3194 (37%) had abnormal hearing sensitivity in either ear and 1751 (20%) in both ears., Conclusions: More heavily WTC-exposed workers were at increased risk of hearing loss, and group differences persisted for at least 15 years. Those with abnormal hearing sensitivity may benefit from interventions such as hearing aids and other rehabilitation.

Serum IgA ≤70 mg/dL (low IgA) is associated with exacerbations of chronic obstructive pulmonary disease. The association of low IgA with longitudinal lung function is poorly defined. This study included 917 World Trade Center (WTC)-exposed firefighters with longitudinal spirometry measured between September 2001 and September 2018 and IgA measured between October 2001 and March 2002. Low IgA, compared with IgA >70 mg/dL, was associated with lower forced expiratory volume in 1 s (FEV 1 ) % predicted in the year following 11 September 2001 (94.1% vs 98.6%, p<0.001), increased risk of FEV 1 /FVC <0.70 (HR 3.8, 95% CI 1.6 to 8.8) and increased antibiotic treatment (22.5/100 vs 11.6/100 person-years, p=0.002). Following WTC exposure, early IgA ≤70 mg/dL was associated with worse lung function and increased antibiotic treatment., Competing Interests: Competing interests: BP, RZ-O, AS, CBH, YL, TS, DG, MPW, DJP and MDW report grants and/or contracts from the National Institute of Occupational Safety and Health, during the conduct of the study and outside the submitted work. LL reports grants from AstraZeneca and Chiesi (both awards), and expert consultation for Boehringer Ingelheim GmbH and Novartis outside the submitted work., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Published studies examining the association between World Trade Center (WTC) exposure on and after September 11, 2001, and longer-term cardiovascular disease (CVD) outcomes have reported mixed findings., Objective: To assess whether WTC exposure was associated with elevated CVD risk in Fire Department of the City of New York (FDNY) firefighters., Design, Settings, and Participants: In this cohort study, the association between WTC exposure and the risk of CVD was assessed between September 11, 2001, and December 31, 2017, in FDNY male firefighters. Multivariable Cox regression analyses were used to estimate CVD risk in association with 2 measures of WTC exposure: arrival time to the WTC site and duration of work at the WTC site. Data analyses were conducted from May 1, 2018, to March 8, 2019., Main Outcomes and Measures: The primary CVD outcome included myocardial infarction, stroke, unstable angina, coronary artery surgery or angioplasty, or CVD death. The secondary outcome (all CVD) included all primary outcome events or any of the following: transient ischemic attack; stable angina, defined as either use of angina medication or cardiac catheterization without intervention; cardiomyopathy; and other CVD (aortic aneurysm, peripheral arterial vascular intervention, and carotid artery surgery)., Results: There were 489 primary outcome events among 9796 male firefighters (mean [SD] age on September 11, 2001, was 40.3 [7.4] years and 7210 individuals [73.6%] were never smokers). Age-adjusted incident rates of CVD were higher for firefighters with greater WTC exposure. The multivariable adjusted hazard ratio (HR) for the primary CVD outcome was 1.44 (95% CI, 1.09-1.90) for the earliest arrival group compared with those who arrived later. Similarly, those who worked at the WTC site for 6 or more months vs those who worked less time at the site were more likely to have a CVD event (HR, 1.30; 95% CI, 1.05-1.60). Well-established CVD risk factors, including hypertension (HR, 1.41; 95% CI, 1.10-1.80), hypercholesterolemia (HR, 1.56; 95% CI, 1.28-1.91), diabetes (HR, 1.99; 95% CI, 1.33-2.98), and smoking (current: HR, 2.13; 95% CI, 1.68-2.70; former: HR, 1.55; 95% CI, 1.23-1.95), were significantly associated with CVD in the multivariable models. Analyses with the all-CVD outcome were similar., Conclusions and Relevance: The findings of the study suggest a significant association between greater WTC exposure and long-term CVD risk. The findings appear to reinforce the importance of long-term monitoring of the health of survivors of disasters.

Background: Metabolic syndrome (MetSyn) predicted future development of World Trade Center lung injury (WTC-LI) in a subgroup of firefighters who never smoked and were male. An intracohort validation of MetSyn as a predictor of WTC-LI is examined in the cohort exposed to the World Trade Center (WTC) that has been followed longitudinally for 16 years., Methods: Results of pulmonary function tests (n = 98,221) in workers exposed to the WTC (n = 9,566) were evaluated. A baseline cohort of firefighters who had normal FEV 1 before 9/11 and who had had serum drawn before site closure on July 24, 2002 (n = 7,487) was investigated. Case subjects with WTC-LI (n = 1,208) were identified if they had at least two measured instances of FEV 1 less than the lower limit of normal (LLN). Cox proportional hazards modeled early MetSyn biomarker ability to predict development of FEV 1 less than the LLN., Results: Case subjects were more likely to smoke, be highly exposed, and have MetSyn. There was a significant exposure dose response; the individuals most highly exposed had a 30.1% increased risk of developing WTC-LI, having MetSyn increased risk of developing WTC-LI by 55.7%, and smoking increased risk by 15.2%. There was significant interaction between smoking and exposure., Conclusions: We validated the usefulness of MetSyn to predict future WTC-LI in a larger population of individuals who were exposed. MetSyn defined by dyslipidemia, insulin resistance, and cardiovascular disease suggests that systemic inflammation can contribute to future lung function loss., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Therapeutic hypothermia, the standard for post-resuscitation care of out-of-hospital sudden cardiac arrest (SCA), is an area that the most recent resuscitation guidelines note "has not been studied adequately." We conducted a two-phase study examining the role of intra-arrest hypothermia for out-of-hospital SCA, first standardizing the resuscitation and transport of patients to resuscitation centers where post-resuscitation hypothermia was required and then initiating hypothermia during out-of-hospital resuscitation efforts. The primary end points were return of spontaneous circulation (ROSC), sustained ROSC, survival to hospital admission, and survival to discharge. Comparing the cohort of standard hospital-initiated hypothermia (Phase I) with the prehospital-initiated hypothermia via large-volume ice-cold saline (LVICS) infusion (Phase II), no difference was noted for any end point: ROSC (56.4% vs. 53.4%, p  = 0.51; 95% confidence interval [CI]: -5.7 to 11.4), sustained ROSC (46.9% vs. 42.8%, p  = 0.38; 95% CI: -4.7 to 12.4), hospital admission (44.7% vs. 37.7%, p  = 0.13; 95% CI: -1.9 to 15.4), hospital discharge among those surviving to admission (40.0% vs. 28.0%, p  = 0.08; 95% CI: -1.5 to 27.8), or neurological outcome among those surviving to discharge (76.0% vs. 71.4%, p  = 0.73; 95% CI: -26.9 to 38.7). Patients presenting in ventricular fibrillation were more likely to survive to hospital discharge in both phases, although a trend toward worsened early outcomes (ROSC, sustained ROSC, and survival to admission) with intra-arrest hypothermia was noted in this subgroup. Multivariable regression analyses failed to demonstrate any survival benefit associated with the intra-arrest initiation of hypothermia via LVICS. Our study, the largest study of intra-arrest initiation of hypothermia published to date, failed to demonstrate any effect on survival for out-of-hospital SCA patients, confirming findings of previously published smaller studies. We therefore do not recommend the use of intra-arrest cooling via LVICS infusion as part of routine out-of-hospital SCA resuscitative efforts.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. It may develop in response to an exposure or inflammatory trigger in the background of a genetically primed abnormal immune response. Thus, genetic studies are potentially important to our understanding of the pathogenesis of sarcoidosis. We developed a case-control study which explored the genetic variations between firefighters in the Fire Department of the City of New York (FDNY) with World Trade Center (WTC)-related sarcoidosis and those with WTC exposure, but without sarcoidosis. The loci of fifty-one candidate genes related to granuloma formation, inflammation, immune response, and/or sarcoidosis were sequenced at high density in enhancer/promoter, exonic, and 5' untranslated regions. Seventeen allele variants of human leukocyte antigen (HLA) and non-HLA genes were found to be associated with sarcoidosis, and all were within chromosomes 1 and 6. Our results also suggest an association between extrathoracic involvement and allele variants of HLA and non-HLA genes found not only on chromosomes 1 and 6, but also on chromosomes 16 and 17. We found similarities between genetic variants with WTC-related sarcoidosis and those reported previously in sporadic sarcoidosis cases within the general population. In addition, we identified several allele variants never previously reported in association with sarcoidosis. If confirmed in larger studies with known environmental exposures, these novel findings may provide insight into the gene-environment interactions key to the development of sarcoidosis.

Peripheral neuropathy can result from numerous conditions including metabolic disorders, inflammatory disease, or exposure to environmental or biological toxins. We analyzed questionnaire data from 9239 Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed firefighters and emergency medical service workers (EMS) to evaluate the association between work at the WTC site and subsequent peripheral neuropathy symptoms using the validated Diabetic Neuropathy Symptom (DNS) score. We grouped the population into an "Indicated" group with conditions known to be associated with paresthesia ( N = 2059) and a "Non-Indicated" group without conditions known to be associated ( N = 7180). The level of WTC exposure was categorized by time of arrival to the WTC. Overall, 25% of workers aged 40 and older reported peripheral neuropathy symptoms: 30.6% in the Indicated and 23.8% in the Non-Indicated groups, respectively. Multivariable logistic models performed on the Non-Indicated group, and on the Non-Indicated in comparison with non-WTC exposed National Health and Nutrition Examination Survey (NHANES), found that the highest level of WTC-exposure was significantly associated with DNS positive outcomes, after controlling for potential confounders. In conclusion, this study suggests that symptoms of peripheral neuropathy and paresthesias are common and are associated with WTC-exposure intensity.

Fire Department of the City of New York (FDNY) firefighters experienced intense dust exposure working at the World Trade Center (WTC) site on and after 11/9/2001 (9/11). We hypothesized that high-intensity WTC exposure caused abnormalities found on chest computed tomography (CT). Between 11/9/2001-10/9/2018, 4277 firefighters underwent a clinically-indicated chest CT. Spirometric measurements and symptoms were recorded during routine medical examinations. High-intensity exposure, defined as initial arrival at the WTC on the morning of 9/11, increased the risk of bronchial wall thickening, emphysema, and air trapping. Early post-9/11 symptoms of wheeze and shortness of breath were associated with bronchial wall thickening, emphysema, and air trapping. The risk of accelerated forced expiratory volume at one second (FEV 1 ) decline (>64 mL/year decline) increased with bronchial wall thickening and emphysema, but decreased with air trapping. The risk of airflow obstruction also increased with bronchial wall thickening and emphysema but decreased with air trapping. In a previously healthy occupational cohort, high-intensity WTC exposure increased the risk for CT abnormalities. Bronchial wall thickening and emphysema were associated with respiratory symptoms, accelerated FEV 1 decline, and airflow obstruction. Air trapping was associated with respiratory symptoms, although lung function was preserved. Physiologic differences between CT abnormalities suggest that distinct types of airway injury may result from a common exposure.

Airway hyperreactivity (AHR) related to environmental exposure is a significant public health risk worldwide. Similarly, metabolic syndrome (MetSyn), a risk factor for obstructive airway disease (OAD) and systemic inflammation, is a significant contributor to global adverse health. This prospective cohort study followed N = 7486 World Trade Center (WTC)-exposed male firefighters from 11 September 2001 (9/11) until 1 August 2017 and investigated N = 539 with newly developed AHR for clinical biomarkers of MetSyn and compared them to the non-AHR group. Male firefighters with normal lung function and no AHR pre-9/11 who had blood drawn from 9 September 2001-24 July 2002 were assessed. World Trade Center-Airway Hyperreactivity (WTC-AHR) was defined as either a positive bronchodilator response (BDR) or methacholine challenge test (MCT). The electronic medical record (EMR) was queried for their MetSyn characteristics (lipid profile, body mass index (BMI), glucose), and routine clinical biomarkers (such as complete blood counts). We modeled the association of MetSyn characteristics at the first post-9/11 exam with AHR. Those with AHR were significantly more likely to be older, have higher BMIs, have high intensity exposure, and have MetSyn. Smoking history was not associated with WTC-AHR. Those present on the morning of 9/11 had 224% increased risk of developing AHR, and those who arrived in the afternoon of 9/11 had a 75.9% increased risk. Having ≥3 MetSyn parameters increased the risk of WTC-AHR by 65.4%. Co-existing MetSyn and high WTC exposure are predictive of future AHR and suggest that systemic inflammation may be a contributor.

Background: The goal of this study was to estimate the impact of exposure to the World Trade Center (WTC) site on annual and persistent rates of otalgia and hearing impairment among Fire Department of the City of New York (FDNY) Firefighters and Emergency Medical Service Workers (EMS)., Methods: Responders completed routine physical health questionnaires at monitoring visits. We used logistic and marginal logistic regression models to explore the association between otalgia and hearing impairment and WTC arrival time., Results: The highest-exposed group had greater odds of persistent ear symptoms (OR 1.33, 95%CI 1.11-1.59) compared with the least-exposed; the odds of persistent hearing problems between the groups were not significantly different. We found consistent WTC-exposure gradients when the average population odds of these outcomes were assessed each year., Conclusions: Our findings demonstrate that the odds of long-term ear symptoms were significantly associated with the intensity of WTC exposure., (© 2018 Wiley Periodicals, Inc.)

Objectives: Chronic rhinosinusitis (CRS) has high socioeconomic burden but underexplored risk factors. The collapse of the World Trade Center (WTC) towers on 11 September 2001 (9/11) caused dust and smoke exposure, leading to paranasal sinus inflammation and CRS. We aim to determine which job tasks are risk factors for CRS in WTC-exposed Fire Department of the City of New York (FDNY) firefighters and emergency medical services (EMS) workers., Methods: This cohort study included a 16-year follow-up of 11 926 WTC-exposed FDNY rescue/recovery workers with data on demographics, WTC exposure, job tasks and first post-9/11 complete blood counts. Using multivariable Cox regression, we assessed the associations of WTC exposure, work assignment (firefighter/EMS), digging and rescue tasks at the WTC site and blood eosinophil counts with subsequent CRS, adjusting for potential confounders., Results: The rate of CRS was higher in firefighters than EMS (1.80/100 person-years vs 0.70/100 person-years; p<0.001). The combination of digging and rescue work was a risk factor for CRS (HR 1.54, 95% CI 1.23 to 1.94, p<0.001) independent of work assignment and WTC exposure., Conclusions: Compared with EMS, firefighters were more likely to engage in a combination of digging and rescue work, which was a risk factor for CRS. Chronic irritant exposures associated with digging and rescue work may account for higher post-9/11 CRS rates among firefighters., Competing Interests: Competing interests: All authors received support from grants and/or contracts from the National Institute of Occupational Safety and Health and/or NIH/NHLBI., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Previously healthy firefighters with World Trade Center (WTC) dust exposure developed airway disease. Risk factors for irritant-associated asthma/COPD overlap are poorly defined., Methods: This study included 2,137 WTC-exposed firefighters who underwent a clinically indicated bronchodilator pulmonary function test (BD-PFT) between 9/11/2001 and 9/10/2017. A post-BD FEV 1 increase of > 12% and 200 mL from baseline defined asthma, and a post-BD FEV 1 /FVC ratio < 0.7 identified COPD cases. Participants who met both criteria had asthma/COPD overlap. Eosinophil levels were measured on screening blood tests performed shortly after 9/11/2001 and prior to BD-PFT; a subgroup of participants also had serum IgE and 21 cytokines measured (n = 215). Marginal Cox regression models for multiple events assessed the associations of eosinophil levels or serum biomarkers with subsequent diagnosis, with age, race, smoking, WTC exposure, first post-9/11 FEV 1 /FVC ratio, and BMI included as covariates., Results: BD-PFT diagnosed asthma/COPD overlap in 99 subjects (4.6%), isolated-asthma in 202 (9.5%), and isolated-COPD in 215 (10.1%). Eosinophil concentration ≥ 300 cells/μL was associated with increased risk of asthma/COPD overlap (hazard ratio [HR], 1.85; 95% CI, 1.16-2.95) but not with isolated-asthma or isolated-COPD. Serum IL-4 also predicted asthma/COPD overlap (HR, 1.51 per doubling of cytokine concentration; 95% CI, 1.17-1.95). Greater IL-21 concentration was associated with both isolated-asthma and isolated-COPD (HRs of 1.73 [95% CI, 1.27-2.35] and 2.06 [95% CI, 1.31-3.23], respectively)., Conclusions: In WTC-exposed firefighters, elevated blood eosinophil and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific T-helper cell type 2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: The goals of this study were to assess the impact of work at the World Trade Center (WTC) site in relation to new, post-9/11/2001 (9/11) antibody to hepatitis C Virus (anti-HCV); and, evaluate secular trends in WTC-exposed male Fire Department of New York City (FDNY) Firefighters and Emergency Medical Services (EMS) responders., Methods: FDNY monitors responder health through physical exams and routine blood work. We used descriptive statistics to compare trans-9/11 and post-9/11 incidence and to assess trends in prevalence from 2000 to 2012., Results: Trans-9/11 incidence of new anti-HCV was 0.42 per 100 persons compared with post-9/11 incidence of 0.34 (P = 0.68). Overall seroprevalence was 1.3%; rates declined from 1.79 per 100 to 0.49 per 100 over time (P < 0.0001)., Conclusions: Work at the WTC was not associated with new infection. Biennial seroprevalence in responders declined over time, supporting the FDNY decision to discontinue routine annual testing in this cohort., (© 2018 Wiley Periodicals, Inc.)

Importance: The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood., Objective: To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS., Design, Setting, and Participants: Case series of multiple myeloma in firefighters diagnosed between September 11, 2001, and July 1, 2017, together with a seroprevalence study of MGUS in serum samples collected from Fire Department of the City of New York (FDNY) firefighters between December 2013 and October 2015. Participants included all WTC-exposed FDNY white, male firefighters with a confirmed physician diagnosis of multiple myeloma (n = 16) and WTC-exposed FDNY white male firefighters older than 50 years with available serum samples (n = 781)., Exposures: WTC exposure defined as rescue and/or recovery work at the WTC site between September 11, 2001, and July 25, 2002., Main Outcomes and Measures: Multiple myeloma case information, and age-adjusted and age-specific prevalence rates for overall MGUS (ie, MGUS and light-chain MGUS), MGUS, and light-chain MGUS., Results: Sixteen WTC-exposed white male firefighters received a diagnosis of multiple myeloma after September 11, 2001; median age at diagnosis was 57 years (interquartile range, 50-68 years). Serum/urine monoclonal protein isotype/free light-chain data were available for 14 cases; 7 (50%) had light-chain multiple myeloma. In a subset of 7 patients, myeloma cells were assessed for CD20 expression; 5 (71%) were CD20 positive. In the screening study, we assayed peripheral blood from 781 WTC-exposed firefighters. The age-standardized prevalence rate of MGUS and light-chain MGUS combined was 7.63 per 100 persons (95% CI, 5.45-9.81), 1.8-fold higher than rates from the Olmsted County, Minnesota, white male reference population (relative rate, 1.76; 95% CI, 1.34-2.29). The age-standardized prevalence rate of light-chain MGUS was more than 3-fold higher than in the same reference population (relative rate, 3.13; 95% CI, 1.99-4.93)., Conclusions and Relevance: Environmental exposure to the WTC disaster site is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype.