The World Trade Center Health Program: an introduction to best practices.

More than 20 years have elapsed since the September 11, 2001 (9/11) terrorist attacks on the World Trade Center (WTC), Pentagon and at Shanksville, PA. Many persons continue to suffer a variety of physical and mental health conditions following their exposures to a mixture of incompletely characterized toxicants and psychological stressors at the terrorist attack sites. Primary care and specialized clinicians should ask patients who may have been present at any of the 9/11 sites about their 9/11 exposures, especially patients with cancer, respiratory symptoms, chronic rhinosinusitis, gastroesophageal reflux disease, psychiatric symptoms, and substance use disorders. Clinicians, especially those in the NY metropolitan area, should know how to evaluate, diagnose, and treat patients with conditions that could be associated with exposure to the 9/11 attacks and its aftermath. As such, this issue of Archives contains a series of updates to clinical best practices relevant to medical conditions whose treatment is covered by the WTC Health Program. This first paper in the 14-part series describes the purpose of this series, defines the WTC Health Program and its beneficiaries, and explains how relevant Clinical Practice Guidelines were identified. This paper also reminds readers that because physical and mental health conditions are often intertwined, a coordinated approach to care usually works best and referral to health centers affiliated with the WTC Health Program may be necessary, since all such Centers offer multidisciplinary care.

Perceived Health Risks Among Firefighters; The New Jersey Firefighter Health Survey.

OBJECTIVE: There is a growing literature on the risk of chronic disease among firefighters, including cardiovascular disease (CVD) and cancer. However there is little information on firefighter's perception thereof. METHODS: Firefighters attending a union convention in New Jersey completed a survey with four domains: firefighting experience; perceived additional risk for chronic diseases (six-point Likert scale); cancer screening history; demographics, and risk behaviors. RESULTS: Among 167 enrolled firefighters, all were men and 86.6% active career. Median perceived risk ranged from high risk (colon, hematologic, breast, prostate, and testicular cancers) to very high risk (CVD, pulmonary diseases, all cancers, lung and oral cancer). CONCLUSIONS: NJ Firefighters attributed considerable additional risk to acquiring chronic disease as a result of their firefighting activities. Understanding firefighter perceptions of their own morbidity and mortality will help develop future firefighter preparatory programs.

Retrospective Assessment of Risk Factors for Head and Neck Cancer Among World Trade Center General Responders.

Objective: To assess the reliability of a questionnaire designed to reconstruct risk factors for head and neck cancer relative to the 9/11 World Trade Center (WTC) response and over the lifetime. Methods: As part of a nested case-control study, 200 WTC Health Program (WTCHP) General Responder Cohort (GRC) members completed a newly-developed study questionnaire via telephone (with a trained interviewer) or online (self-administered). We assessed agreement between measures of tobacco and alcohol use in our questionnaire results and data collected previously during WTCHP-GRC monitoring visits using Cohens Kappa (κ) and intraclass correlation coefficient (ICC) for categorical and continuous measures, respectively. We compared agreement by disease status, survey mode, and year of WTCHP enrollment. Results: We observed high agreement between measures of lifetime, pre-WTC, and post-WTC smoking prevalence (all κ > 0.85) and smoking duration (all ICC > 0.84). There was moderate agreement between measures of smoking frequency (ICC: 0.61-0.73). Agreement between measures of smoking frequency, but not duration, differed by disease status, and agreement between smoking measures was higher for participants who completed our survey by phone than by web. Among cases, there were no differences based on enrollment in the WTCHP before or after diagnosis. Conclusion: Agreement between measures was generally high, although potential reporting bias and a mode effect that should be considered when interpreting analyses of self-reported data in this population; however differential misclassification appears to be minimal. Our questionnaire may be useful for future studies examining similar behavioral risk factors among disaster-exposed populations.

Cancer in General Responders Participating in World Trade Center Health Programs, 2003-2013.

BACKGROUND: Following the September 11, 2001, attacks on the World Trade Center (WTC), thousands of workers were exposed to an array of toxins known to cause adverse health effects, including cancer. This study evaluates cancer incidence in the WTC Health Program General Responder Cohort occurring within 12 years post exposure. METHODS: The study population consisted of 28 729 members of the General Responder Cohort enrolled from cohort inception, July 2002 to December 31, 2013. Standardized incidence ratios (SIRs) were calculated with cancer case inclusion and follow-up starting post September 11, 2001 (unrestricted) and, alternatively, to account for selection bias, with case inclusion and follow-up starting 6 months after enrollment in the WTC Health Program (restricted). Case ascertainment was based on linkage with six state cancer registries. Under the restricted criterion, hazard ratios were estimated using multivariable Cox proportional hazards models for all cancer sites combined and for prostate cancer. RESULTS: Restricted analyses identified 1072 cancers in 999 responders, with elevations in cancer incidence for all cancer sites combined (SIR = 1.09, 95% confidence interval [CI] = 1.02 to 1.16), prostate cancer (SIR = 1.25, 95% CI = 1.11 to 1.40), thyroid cancer (SIR = 2.19, 95% CI = 1.71 to 2.75), and leukemia (SIR = 1.41, 95% CI = 1.01 to 1.92). Cancer incidence was not associated with any WTC exposure index (composite or individual) for all cancer sites combined or for prostate cancer. CONCLUSION: Our analyses show statistically significant elevations in cancer incidence for all cancer sites combined and for prostate and thyroid cancers and leukemia. Multivariable analyses show no association with magnitude or type of exposure.

Risk factors for head and neck cancer in the World Trade Center Health Program General Responder Cohort: results from a nested case-control study.

OBJECTIVES: Head and neck cancers (HNCs) may be among the health consequences of involvement in the World Trade Center (WTC) response on and after 11 September 2001. We conducted a nested case-control study of WTC Health Program (WTCHP) general responders to examine the effects of WTC exposures and behavioural risk factors on HNC. METHODS: We enrolled 64 cases and 136 controls, matched on age, sex and race/ethnicity within risk sets. We assessed tobacco and alcohol use, sexual activity, and occupational exposures prior to, during and after WTC exposure until case diagnosis via questionnaire. We obtained WTC exposure information (duration (first to last day), total days and location of work) from the WTCHP General Responder Data Center. We assessed associations with HNC, and interaction among exposures, using conditional logistic regression. RESULTS: Responders in protective services versus other occupations had increased odds (OR: 2.51, 95% CI 1.09 to 5.82) of HNC. Among those in non-protective services occupations, arriving to the WTC effort on versus after 11 September 2001 was significantly associated with HNC (OR: 3.77, 95% CI 1.00 to 14.11). Duration of work was not significantly associated with HNC. Lifetime and post-WTC years of cigarette smoking and post-WTC number of sex partners were positively and significantly associated with HNC, while alcohol consumption was not. CONCLUSIONS: These findings suggest opportunities for HNC risk factor mitigation (eg, smoking cessation, human papillomavirus vaccination) and contribute to a risk factor profile which may assist WTCHP clinicians with identifying high-risk responders and improve detection and treatment outcomes in this population.

Sarcoid-Like Granulomatous Disease: Pathologic Case Series in World Trade Center Dust Exposed Rescue and Recovery Workers.

Sarcoid-like granulomatous diseases (SGD) have been previously identified in cohorts of World Trade Center (WTC) dust-exposed individuals. In the present studies, we analyzed lung and/or lymph node biopsies from patients referred to our clinic with suspected WTC dust-induced lung disease to evaluate potential pathophysiologic mechanisms. Histologic sections of lung and/or lymph node samples were analyzed for markers of injury, oxidative stress, inflammation, fibrosis, and epigenetic modifications. Out of seven patients examined, we diagnosed four with SGD and two with pulmonary fibrosis; one was diagnosed later with SGD at another medical facility. Patients with SGD were predominantly white, obese men, who were less than 50 years old and never smoked. Cytochrome b5, cytokeratin 17, heme oxygenase-1, lipocalin-2, inducible nitric oxide synthase, cyclooxygenase 2, tumor necrosis factor α, ADP-ribosylation factor-like GTPase 11, mannose receptor-1, galectin-3, transforming growth factor ß, histone-3 and methylated histone-3 were identified in lung and lymph nodes at varying levels in all samples examined. Three of the biopsy samples with granulomas displayed peri-granulomatous fibrosis. These findings are important and suggest the potential of WTC dust-induced fibrotic sarcoid. It is likely that patient demographics and/or genetic factors influence the response to WTC dust injury and that these contribute to different pathological outcomes.

Severe Obstructive Sleep Apnea Is Associated with Alterations in the Nasal Microbiome and an Increase in Inflammation.

RATIONALE: Obstructive sleep apnea (OSA) is associated with recurrent obstruction, subepithelial edema, and airway inflammation. The resultant inflammation may influence or be influenced by the nasal microbiome. OBJECTIVES: To evaluate whether the composition of the nasal microbiota is associated with obstructive sleep apnea and inflammatory biomarkers. METHODS: Two large cohorts were used: 1) a discovery cohort of 472 subjects from the WTCSNORE (Seated, Supine and Post-Decongestion Nasal Resistance in World Trade Center Rescue and Recovery Workers) cohort, and 2) a validation cohort of 93 subjects rom the Zaragoza Sleep cohort. Sleep apnea was diagnosed using home sleep tests. Nasal lavages were obtained from cohort subjects to measure: 1) microbiome composition (based on 16S rRNA gene sequencing), and 2) biomarkers for inflammation (inflammatory cells, IL-8, and IL-6). Longitudinal 3-month samples were obtained in the validation cohort, including after continuous positive airway pressure treatment when indicated. MEASUREMENTS AND MAIN RESULTS: In both cohorts, we identified that: 1) severity of OSA correlated with differences in microbiome diversity and composition; 2) the nasal microbiome of subjects with severe OSA were enriched with Streptococcus, Prevotella, and Veillonella; and 3) the nasal microbiome differences were associated with inflammatory biomarkers. Network analysis identified clusters of cooccurring microbes that defined communities. Several common oral commensals (e.g., Streptococcus, Rothia, Veillonella, and Fusobacterium) correlated with apnea-hypopnea index. Three months of treatment with continuous positive airway pressure did not change the composition of the nasal microbiota. CONCLUSIONS: We demonstrate that the presence of an altered microbiome in severe OSA is associated with inflammatory markers. Further experimental approaches to explore causal links are needed.

Excess HPV-related head and neck cancer in the world trade center health program general responder cohort.

The World Trade Center (WTC) attacks exposed rescue and recovery workers to a complex mix of toxicants, including carcinogens. our study compared site-specific cancer incidence of head and neck cancers (HNC) from 2003 through 2012 among 33,809 consented WTC General Responder Cohort (GRC) members to the New Jersey State Cancer Registry, using standardized incidence ratios (SIRs). HNC grouped using SEER ICD-O-3 codes into HPV-related (oropharyngeal) and non-related (other oral-nasal; laryngeal) tumors based on anatomical site. For the 73 GRC members identified with HNC, proportional hazard regression assessed the relationship between WTC exposure and other socio-demographic characteristics. An overall excess of HNC was not observed (SIR = 1.00, 95% CI: 0.78, 1.25) but excess cancer was seen in the latest observation period (2009-2012: SIR = 1.4; 95% CI: 1.01, 1.89). A similar temporal pattern was seen for HPV-related oropharyngeal cancer and laryngeal cancer, but not for non-HPV-related sites (oral-nasal cancer). HNC was significantly associated with increasing age (8% per year, 95% CI: 5%, 12%), non-Hispanic white ethnic group-ethnicity (hazard ratio (HR) = 3.51, 95 CI: 1.49, 8.27); there was a borderline association with the 9/11 occupation of military/protective services vs. others (HR = 1.83 95% CI: 0.99, 3.38; p = 0.0504). Caution is needed in interpreting these results given the small number of cases, potential for surveillance bias, and long latency for most cancers. Our findings highlight the need to examine the potentially carcinogenic effects of WTC exposure in the context of other strong risk factors, and the need for continued medical monitoring of WTC responders.

Cancer epidemiology update, following the 2011 IARC evaluation of radiofrequency electromagnetic fields (Monograph 102).

Epidemiology studies (case-control, cohort, time trend and case studies) published since the International Agency for Research on Cancer (IARC) 2011 categorization of radiofrequency radiation (RFR) from mobile phones and other wireless devices as a possible human carcinogen (Group 2B) are reviewed and summarized. Glioma is an important human cancer found to be associated with RFR in 9 case-control studies conducted in Sweden and France, as well as in some other countries. Increasing glioma incidence trends have been reported in the UK and other countries. Non-malignant endpoints linked include acoustic neuroma (vestibular Schwannoma) and meningioma. Because they allow more detailed consideration of exposure, case-control studies can be superior to cohort studies or other methods in evaluating potential risks for brain cancer. When considered with recent animal experimental evidence, the recent epidemiological studies strengthen and support the conclusion that RFR should be categorized as carcinogenic to humans (IARC Group 1). Opportunistic epidemiological studies are proposed that can be carried out through cross-sectional analyses of high, medium, and low mobile phone users with respect to hearing, vision, memory, reaction time, and other indicators that can easily be assessed through standardized computer-based tests. As exposure data are not uniformly available, billing records should be used whenever available to corroborate reported exposures.

Head and Neck Cancer in World Trade Center Responders: A Case Series.

OBJECTIVE: The aim of this study was to report on cases of head and neck cancer (HNC) among World Trade Center (WTC) responders participating in the WTC Health Program and seen at Rutgers WTC Center of Clinical Excellence. METHODS: Medical records were abstracted by two clinical reviewers and discrepancies resolved. Cases were defined as WTC responders diagnosed with HNC between December 9, 2005, and December 31, 2016. RESULTS: Sixteen HNC patients met the case definition, most (13) arrived at the WTC location on 9/11 or within the following 2 days, and half worked in law enforcement during the 9/1 response. CONCLUSION: An association between HNC and WTC exposure is biologically plausible and should be further investigated. Research to enumerate the risk factor profile for these cancers may contribute to understanding mechanisms by which WTC exposure can contribute to carcinogenesis and to prevention and early detection strategies.

Prostate cancer characteristics in the World Trade Center cohort, 2002-2013.

An increased incidence of prostate cancer was reported in three cohorts of World Trade Center (WTC) respondents. It is uncertain whether this increase is because of WTC-related exposures or enhanced surveillance. Prostate cancer cases (2002-2013) were obtained from the WTC Health Program. Age, race, and Gleason score distribution were compared with New York State Cancer Registry cases from the same time period. Multivariate models were adjusted for age and race. Analyses of clinical characteristics of prostate cancer cases within the cohort were also carried out, adjusting for age, race, and WTC exposure categories. WTC respondents had a prostate cancer age-standardized rate ratio of 1.65 [95% confidence interval (CI): 1.37-1.93] compared with New York State; age-specific ratios were highest for ages 30-49 (2.28; 95% CI: 1.51-3.43), 70-74 (2.05; 95% CI: 1.03-4.10), and 80-84 years (5.65; 95% CI: 1.41-22.58). High WTC exposure was associated with advanced clinical stage (5.58; 95% CI: 1.05-29.76; Ptrend=0.03). WTC respondents continue to have a higher prostate cancer rate compared with New York State as a whole. Respondents with a higher WTC exposure level may have had more advanced clinical stage of prostate cancer.

Mortality among World Trade Center rescue and recovery workers, 2002-2011.

BACKGROUND: Rescue and recovery workers responding to the 2001 collapse of the World Trade Center (WTC) sustained exposures to toxic chemicals and have elevated rates of multiple morbidities. METHODS: Using data from the World Trade Center Health Program and the National Death Index for 2002-2011, we examined standardized mortality ratios (SMR) and proportional cancer mortality ratios (PCMR) with indirect standardization for age, sex, race, and calendar year to the U.S. general population, as well as associations between WTC-related environmental exposures and all-cause mortality. RESULTS: We identified 330 deaths among 28,918 responders (SMR 0.43, 95%CI 0.39-0.48). No cause-specific SMRs were meaningfully elevated. PCMRs were elevated for neoplasms of lymphatic and hematopoietic tissue (PCMR 1.76, 95%CI 1.06-2.75). Mortality hazard ratios showed no linear trend with exposure. CONCLUSIONS: Consistent with a healthy worker effect, all-cause mortality among responders was not elevated. There was no clear association between intensity and duration of exposure and mortality. Surveillance is needed to monitor the proportionally higher cancer mortality attributed to lymphatic/hematopoietic neoplasms.

Posttraumatic stress symptoms and smoking among World Trade Center disaster responders: A longitudinal investigation.

PURPOSE: The current longitudinal study examined posttraumatic stress disorder (PTSD) symptom severity in relation to smoking abstinence and reduction over time among responders to the World Trade Center (WTC) disaster. METHOD: Participants were 763 police and 1881 non-traditional (e.g., construction workers) WTC responders who reported being smokers at an initial examination obtained between July 2002 and July 2011 at the WTC Health Program (WTC-HP). WTC responders were reassessed, on average, 2.5 years later. RESULTS: For police WTC responders, higher levels of WTC-related PTSD symptoms at the initial visit were associated with a decreased likelihood of smoking abstinence (OR=0.98, p=.002) and with decreased smoking reduction (ß=-.06, p=.012) at the follow-up visit. WTC-related PTSD symptom severity was not related to likelihood of smoking abstinence or change in number of cigarettes smoked among non-traditional responders. Post hoc analyses suggested that for police, hyperarousal PTSD symptoms were predictive of decreased abstinence likelihood at the follow-up visit (OR=0.56, p=.006). DISCUSSION: The present findings suggest that PTSD symptoms may be differentially related to smoking behavior among police and non-traditional WTC responders in a naturalistic, longitudinal investigation. Future work may benefit from exploring further which aspects of PTSD (as compared to each other and to common variance) explain smoking maintenance.

Cancer incidence in world trade center rescue and recovery workers, 2001-2008.

BACKGROUND: World Trade Center (WTC) rescue and recovery workers were exposed to a complex mix of pollutants and carcinogens. OBJECTIVE: The purpose of this investigation was to evaluate cancer incidence in responders during the first 7 years after 11 September 2001. METHODS: Cancers among 20,984 consented participants in the WTC Health Program were identified through linkage to state tumor registries in New York, New Jersey, Connecticut, and Pennsylvania. Standardized incidence ratios (SIRs) were calculated to compare cancers diagnosed in responders to predicted numbers for the general population. Multivariate regression models were used to estimate associations with degree of exposure. RESULTS: A total of 575 cancers were diagnosed in 552 individuals. Increases above registry-based expectations were noted for all cancer sites combined (SIR = 1.15; 95% CI: 1.06, 1.25), thyroid cancer (SIR = 2.39; 95% CI: 1.70, 3.27), prostate cancer (SIR = 1.21; 95% CI: 1.01, 1.44), combined hematopoietic and lymphoid cancers (SIR = 1.36; 95% CI: 1.07, 1.71), and soft tissue cancers (SIR = 2.26; 95% CI: 1.13, 4.05). When restricted to 302 cancers diagnosed ≥ 6 months after enrollment, the SIR for all cancers decreased to 1.06 (95% CI: 0.94, 1.18), but thyroid and prostate cancer diagnoses remained greater than expected. All cancers combined were increased in very highly exposed responders and among those exposed to significant amounts of dust, compared with responders who reported lower levels of exposure. CONCLUSION: Estimates should be interpreted with caution given the short follow-up and long latency period for most cancers, the intensive medical surveillance of this cohort, and the small numbers of cancers at specific sites. However, our findings highlight the need for continued follow-up and surveillance of WTC responders.

"Sarcoid like" granulomatous pulmonary disease in World Trade Center disaster responders.

BACKGROUND: More than 20,000 responders have been examined through the World Trade Center (WTC) Medical Monitoring and Treatment Program since September 11, 2001. Studies on WTC firefighters have shown elevated rates of sarcoidosis. The main objective of this study was to report the incidence of "sarcoid like" granulomatous pulmonary disease in other WTC responders. METHODS: Cases of sarcoid like granulomatous pulmonary disease were identified by: patient self-report, physician report and ICD-9 codes. Each case was evaluated by three pulmonologists using the ACCESS criteria and only "definite" cases are reported. RESULTS: Thirty-eight patients were classified as "definite" cases. Six-year incidence was 192/100,000. The peak annual incidence of 54 per 100,000 person-years occurred between 9/11/2003 and 9/11/2004. Incidence in black responders was nearly double that of white responders. Low FVC was the most common spirometric abnormality. CONCLUSIONS: Sarcoid like granulomatous pulmonary disease is present among the WTC responders. While the incidence is lower than that reported among firefighters, it is higher than expected.

Quality of spirometry performed by 13,599 participants in the World Trade Center Worker and Volunteer Medical Screening Program.

OBJECTIVE: To determine the ability of spirometry technicians in the World Trade Center Worker and Volunteer Medical Screening Program to meet American Thoracic Society spirometry quality goals. METHODS: Spirometry technicians were trained centrally and performed spirometry sessions at 6 sites in the greater New York City area. We reviewed and graded the spirometry results for quality every month. RESULTS: About 80% (range 70-88%) of the spirometry sessions met the American Thoracic Society spirometry goals. In general, the spirometry technicians with the most experience were more successful in meeting the quality goals. Participant characteristics explained very little of the quality variability. CONCLUSIONS: The overall spirometry quality in this multicenter program was very good. Efforts to improve spirometry quality should focus on the performance of individual spirometry technicians.

Multiple myeloma in World Trade Center responders: a case series.

OBJECTIVES: We report on cases of multiple myeloma (MM) observed in World Trade Center (WTC) responders registered in the WTC Medical Program. METHODS: Possible cases of MM diagnosed between September 11, 2001, and September 10, 2007, in responders were confirmed if they met the World Health Organization and Mayo Clinic diagnostic criteria. RESULTS: Among 28,252 responders of known sex and age, eight cases of MM were observed (6.8 expected). Four of these cases were observed in responders younger than 45 years at the time of diagnosis (1.2 expected). A slight deficit of MM cases was observed in responders older than 45 years (4 observed, 5.6 expected). CONCLUSION: In this case series, we observe an unusual number of MM cases in WTC responders under 45 years. This finding underscores the importance of maintaining surveillance for cancer and other emerging diseases in this highly exposed population.

Longitudinal assessment of spirometry in the World Trade Center medical monitoring program.

BACKGROUND: Multiple studies have demonstrated an initial high prevalence of spirometric abnormalities following World Trade Center (WTC) disaster exposure. We assessed prevalence of spirometric abnormalities and changes in spirometry between baseline and first follow-up evaluation in participants in the WTC Worker and Volunteer Medical Monitoring Program. We also determined the predictors of spirometric change between the two examinations. METHODS: Prebronchodilator and postbronchodilator spirometry, demographics, occupational history, smoking status, and respiratory symptoms and exposure onset were obtained at both examinations (about 3 years apart). RESULTS: At the second examination, 24.1% of individuals had abnormal spirometry findings. The predominant defect was a low FVC without obstruction (16.1%). Between examinations, the majority of individuals did not have a greater-than-expected decline in lung function. The mean declines in prebronchodilator FEV(1) and FVC were 13 mL/yr and 2 mL/yr, respectively (postbronchodilator results were similar and not reported). Significant predictors of greater average decline between examinations were lack of bronchodilator responsiveness at examination 1 and weight gain [corrected]. CONCLUSIONS: Elevated rates of spirometric abnormalities were present at both examinations, with reduced FVC most common. Although the majority had a normal decline in lung function, lack of bronchodilator response at examination 1 and weight gain were significantly associated with greater-than-normal lung function declines [corrected]. Due to the presence of spirometric abnormalities > 5 years after the disaster in many exposed individuals, longer-term monitoring of WTC responders is essential.

WTC medical monitoring and treatment program: comprehensive health care response in aftermath of disaster.

The attack on the World Trade Center (WTC) on September 11th, 2001 exposed thousands of individuals to an unprecedented mix of chemicals, combustion products and micronized building materials. Clinicians at the Mount Sinai Irving Selikoff Center for Occupational and Environmental Medicine, in partnership with affected stakeholder organizations, developed a medical screening program to evaluate the health status of workers and volunteers who spent time at the WTC site and thus sustained exposure in the aftermath of September 11th. Standardized questionnaires were adapted for use in this unique population and all clinicians underwent training to ensure comparability. The WTC Worker and Volunteer Medical Screening Program (MSP) received federal funding in April 2002 and examinations began in July 2002. The MSP and the follow up medical monitoring program has successfully recruited nearly 22,000 responders, and serves as a model for the rapid development of a medical screening program to assess the health of populations exposed to environmental hazards as a result of natural and man-made disasters. The MSP constitutes a successful screening program for WTC responders. We discuss the challenges that confronted the program; the absence of a prior model for the rapid development of a program to evaluate results from mixed chemical exposures; little documentation of the size of the exposed population or of who might have been exposed; and uncertainty about both the nature and potential severity of immediate and long-term health effects.