Andrew C. Todd

The World Trade Center Disaster and the Health of Workers: Five-Year Assessment of a Unique Medical Screening Program

Background Approximately 40,000 rescue and recovery workers were exposed to caustic dust and toxic pollutants following the 11 September 2001 attacks on the World Trade Center (WTC). These workers included traditional first responders, such as firefighters and police, and a diverse population of construction, utility, and public sector workers. Methods To characterize WTC-related health effects, the WTC Worker and Volunteer Medical Screening Program was established. This multicenter clinical program provides free standardized examinations to responders. Examinations include medical, mental health, and exposure assessment questionnaires; physical examinations; spirometry; and chest X rays. Results Of 9,442 responders examined between July 2002 and April 2004, 69% reported new or worsened respiratory symptoms while performing WTC work. Symptoms persisted to the time of examination in 59% of these workers. Among those who had been asymptomatic before September 11, 61% developed respiratory symptoms while performing WTC work. Twenty-eight percent had abnormal spirometry; forced vital capacity (FVC) was low in 21%; and obstruction was present in 5%. Among nonsmokers, 27% had abnormal spirometry compared with 13% in the general U.S. population. Prevalence of low FVC among nonsmokers was 5-fold greater than in the U.S. population (20% vs. 4%). Respiratory symptoms and spirometry abnormalities were significantly associated with early arrival at the site. Conclusion WTC responders had exposure-related increases in respiratory symptoms and pulmonary function test abnormalities that persisted up to 2.5 years after the attacks. Long-term medical monitoring is required to track persistence of these abnormalities and identify late effects, including possible malignancies. Lessons learned should guide future responses to civil disasters.

Past adult lead exposure is associated with longitudinal decline in cognitive function

Objective: To determine whether adults with past exposure to neurotoxicants have progressive declines in cognitive function years after exposure has ceased, and whether tibia lead is a predictor of the magnitude of change. Methods: A total of 535 former organolead manufacturing workers with a mean age of 55.6 years, a mean duration of 16 years since last occupational lead exposure, and low blood lead levels at the first study visit and 118 controls were evaluated with neurobehavioral tests two to four times over 4 years. “Peak” tibia lead levels, estimated from current levels measured by X-ray fluorescence, were used to predict changes in cognitive function over time. Results: In former lead workers, peak tibia lead ranged from −2.2 to 98.7 μg Pb/g bone mineral. Compared to controls, former lead workers performed worse over time for three tests of visuo-constructive ability and verbal memory and learning (p < 0.05). In former lead workers, peak tibia lead predicted declines for six tests of verbal memory and learning, visual memory, executive ability, and manual dexterity (p < 0.05 for four tests and < 0.10 for two additional tests). On average, for these six tests, an increase of 15.7 μg/g of peak tibia lead was equivalent in its effects on annual test decline to 5 more years of age at baseline. Conclusions: These are the first data to suggest that cognitive function can progressively decline due to past occupational exposures to a neurotoxicant.

Persistence of multiple illnesses in World Trade Center rescue and recovery workers: a cohort study.

BACKGROUND More than 50,000 people participated in the rescue and recovery work that followed the Sept 11, 2001 (9/11) attacks on the World Trade Center (WTC). Multiple health problems in these workers were reported in the early years after the disaster. We report incidence and prevalence rates of physical and mental health disorders during the 9 years since the attacks, examine their associations with occupational exposures, and quantify physical and mental health comorbidities. METHODS In this longitudinal study of a large cohort of WTC rescue and recovery workers, we gathered data from 27,449 participants in the WTC Screening, Monitoring, and Treatment Program. The study population included police officers, firefighters, construction workers, and municipal workers. We used the Kaplan-Meier procedure to estimate cumulative and annual incidence of physical disorders (asthma, sinusitis, and gastro-oesophageal reflux disease), mental health disorders (depression, post-traumatic stress disorder [PTSD], and panic disorder), and spirometric abnormalities. Incidence rates were assessed also by level of exposure (days worked at the WTC site and exposure to the dust cloud). FINDINGS 9-year cumulative incidence of asthma was 27·6% (number at risk: 7027), sinusitis 42·3% (5870), and gastro-oesophageal reflux disease 39·3% (5650). In police officers, cumulative incidence of depression was 7·0% (number at risk: 3648), PTSD 9·3% (3761), and panic disorder 8·4% (3780). In other rescue and recovery workers, cumulative incidence of depression was 27·5% (number at risk: 4200), PTSD 31·9% (4342), and panic disorder 21·2% (4953). 9-year cumulative incidence for spirometric abnormalities was 41·8% (number at risk: 5769); three-quarters of these abnormalities were low forced vital capacity. Incidence of most disorders was highest in workers with greatest WTC exposure. Extensive comorbidity was reported within and between physical and mental health disorders. INTERPRETATION 9 years after the 9/11 WTC attacks, rescue and recovery workers continue to have a substantial burden of physical and mental health problems. These findings emphasise the need for continued monitoring and treatment of the WTC rescue and recovery population. FUNDING Centers for Disease Control and Prevention and National Institute for Occupational Safety and Health.

Past adult lead exposure is linked to neurodegeneration measured by brain MRI

Objective: To determine whether cumulative lead dose in former organolead workers was associated with MRI measures of white matter lesions (WML) and global and structure-specific brain volumes. Methods: MRIs, tibia lead, and other measures were obtained from 532 former organolead workers with a mean age of 56 years and a mean of 18 years since last occupational exposure to lead. Cumulative lead dose was measured by tibia lead, obtained by X-ray fluorescence, and expressed as μg lead per gram of bone mineral (μg Pb/g). WML were evaluated using the Cardiovascular Health Study grading scale. A total of 21 global and specific brain regions were evaluated. Results: A total of 36% of individuals had WML grade of 1 to 7 (0 to 9 scale). Increasing peak tibia lead was associated with increasing WML grade (p = 0.004). The adjusted OR for a 1 μg Pb/g increase in tibia lead was 1.042 (95% CI = 1.021, 1.063) for a CHS grade of 5+ (≥5 vs <5). In linear regression, the coefficient for tibia lead was negative for associations with all structures. Higher tibia lead was significantly related to smaller total brain volume, frontal and total gray matter volume, and parietal white matter volume. Of nine smaller specific regions of interest, higher tibia lead was associated with smaller volumes for the cingulate gyrus and insula. Conclusions: These data suggest that cumulative lead dose is associated with persistent brain lesions, and may explain previous findings of a progressive decline in cognitive function.

In vivo measurements of lead in bone in long-term exposed lead smelter workers.

In-vivo measurements of lead concentrations in calcaneus (mainly trabecular bone) and tibia (mainly cortical bone) were performed by x-ray fluorescence (XRF) in 70 active and 30 retired lead smelter workers who had long-term exposure to lead. Comparison was made with 31 active and 10 retired truck assembly workers who had no known occupational exposure to lead. After physical examination, all participants provided blood and urine samples and answered a computerized questionnaire. Since 1950, blood lead has been determined repeatedly in lead workers at the smelter, which made it possible to calculate a time-integrated blood lead index for each worker. Lead concentrations in blood, urine, calcaneus, and tibia in active and retired lead workers were significantly higher than in the corresponding control groups (p < .001). The highest bone lead concentrations were found among retired lead workers (p < .001), which was the result of considerably higher lead exposure during 1940 to 1960. Lead concentrations in calcaneus in active lead workers were significantly higher than in tibia when expressed in ug of lead per gram of bone mineral, which suggests a quicker absorption over time in this mainly trabecular bone. The estimated biological half-times were 16 y in calcaneus (95% confidence interval [95% CI] = 11-29 y) and 27 y in tibia (95% CI = 16-98 y). A strong positive correlation was found between lead concentrations in calcaneus and tibia for all lead workers (r = 0.54; p < .001). A strong positive correlation was also found between the bone lead concentrations and the cumulative blood lead index. Blood lead, at the time of study, correlated well with bone lead concentrations in retired--but not in active--workers, reflecting the importance of the endogenous (skeletal) lead exposure. The findings in this study indicate that bone lead measurements by XRF can give a good index of long-term lead exposure. Tibia measurements offer a higher precision than calcaneus measurements. The method is of particular interest in epidemiologic studies of adverse health effects caused by long-term lead exposure.

The longitudinal association of lead with blood pressure.

Background. Several investigators have reported an association of blood lead or bone lead with increased blood pressure and hypertension, but questions remain concerning whether these effects are acute or chronic in nature. Methods. In this longitudinal study, we evaluated the relation of lead, measured in blood and tibia, to changes in blood pressure between 1994 and 1998. We studied 496 current and former employees of a chemical-manufacturing facility in the eastern United States who had previous occupational exposure to inorganic and organic lead. Cohort members who provided three or four blood pressure measurements during the study were included. Results. Mean age at baseline was 55.8 years with a mean of 18 years since last occupational exposure to lead. Blood lead at baseline averaged 4.6 &mgr;g/dL (standard deviation [SD] = 2.6) or 0.22 &mgr;mole/Liter (SD = 0.13). Tibia lead at year three averaged 14.7-&mgr;g/gm (SD = 9.4) bone mineral. Change in systolic blood pressure during the study was associated with lead dose, with an average annual increase of 0.64 mmHg (standard error [SE] = 0.25), 0.73 mmHg (SE = 0.26), and 0.61 mmHg (SE = 0.27) for every standard deviation increase in blood lead at baseline, tibia lead at year three, or peak past tibia lead, respectively. Conclusions. The results support an etiologic role for lead in the elevation of systolic blood pressure among adult males and are consistent with both acute and chronic modes of action.

Neurobehavioral function and tibial and chelatable lead levels in 543 former organolead workers

Objective: To evaluate the associations between tibial lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and neurobehavioral function in former organolead manufacturing workers with past exposure to organic and inorganic lead. Methods: Data were collected from 543 subjects with a mean age of 58 years and an average of 17.8 years since last lead exposure. Years since last exposure to lead was used to estimate tibial lead levels in the year of last occupational lead exposure, termed “peak tibial lead.” Current tibial lead levels, measured by x-ray fluorescence, were extrapolated back using a clearance half-time of lead in tibia of 27 years, assuming first-order clearance from tibia. Results: Peak tibial lead levels ranged from −2.2 to 105.9 μg Pb/g bone mineral, and DMSA-chelatable lead levels were between 1.2 and 136 μg. After adjustment for confounding variables, peak tibial lead was a significant negative predictor of performance on the Wechsler Adult Intelligence Scale–Revised vocabulary subtest (p = 0.02), serial digit learning test (p = 0.04), Rey Auditory-Verbal Learning Test (immediate recall and recognition, p = 0.03 for each), Trail Making Test B (p = 0.03), finger tapping (dominant hand [p = 0.02] and nondominant hand [p < 0.01]), Purdue pegboard (dominant hand, nondominant hand, both hands, and assembly, p < 0.01 for each), and Stroop Test (p < 0.01). Moreover, with one exception, average neurobehavioral test scores were poorer at higher peak tibial lead levels. DMSA-chelatable lead was only significantly associated with choice reaction time (p = 0.01). Conclusion: Peak tibial lead was consistently associated with poorer neurobehavioral test scores, particularly in the domains of manual dexterity, executive ability, verbal intelligence, and verbal memory.

Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes.

A cross-sectional study was performed to evaluate the influence of polymorphisms in the [delta]-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by (109)Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral administration of 10 mg/kg DMSA. The primary goals of the analysis were to examine blood lead, tibia lead, and DMSA-chelatable lead levels by ALAD and VDR genotypes, controlling for covariates; and to evaluate whether ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 microg/dL), tibia lead (-7-338 microg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2,103 microg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the Bb genotype, and 0.5% (n = 4) had the BB genotype. Although the ALAD and VDR genes are located on different chromosomes, lead workers homozygous for the ALAD(1) allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD(2) allele had higher blood lead levels (on average, 2.9 microg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p < 0.05) higher blood lead levels (on average, 4.2 microg/dL), chelatable lead levels (on average, 37.3 microg), and tibia lead levels (on average, 6.4 microg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.

Environmental lead exposure and cognitive function in community-dwelling older adults

Objective: To determine if long-term exposure to high levels of lead in the environment is associated with decrements in cognitive ability in older Americans. Methods: We completed a cross-sectional analysis using multiple linear regression to evaluate associations of recent (in blood) and cumulative (in tibia) lead dose with cognitive function in 991 sociodemographically diverse, community-dwelling adults, aged 50 to 70 years, randomly selected from 65 contiguous neighborhoods in Baltimore, MD. Tibia lead was measured with 109Cd induced K-shell X-ray fluorescence. Seven summary measures of cognitive function were created based on standard tests in these domains: language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction. Results: The mean (SD) blood lead level was 3.5 (2.2) μg/dL and tibia lead level was 18.7 (11.2) μg/g. Higher tibia lead levels were consistently associated with worse cognitive function in all seven domains after adjusting for age, sex, APOE-ε4, and testing technician (six domains p ≤ 0.01, one domain p ≤ 0.05). Blood lead was not associated with any cognitive domain. Associations with tibia lead were attenuated after adjustment for years of education, wealth, and race/ethnicity. Conclusions: Independent of recent lead dose, retained cumulative dose resulting from previous environmental exposures may have persistent effects on cognitive function. A portion of age-related decrements in cognitive function in this population may be associated with earlier lead exposure.

Residential proximity to electricity transmission and distribution equipment and risk of childhood leukemia, childhood lymphoma, and childhood nervous system tumors: systematic review, evaluation, and meta-analysis

In 1979, Wertheimer and Leeper reported an increased risk of cancer mortality among children living near ‘electrical wiring configurations’, suggestive of high current flow. Since then, numerous, often inconclusively small, investigations with conflicting results have studied the possible asociation between exposure to electric and magnetic fields (EMF) and health effects. The high prevalence of exposure to EMF has drawn attention to the issue of carcinogenesis. We report here the results of a meta-analysis of 13 epidemiologic studies of residential proximity to electricity transmission and distribution equipment and risk of childhood leukemia, lymphoma, and nervous system tumors. The combined relative risks for leukemia, lymphoma, and nervous system tumors are 1.49 (95 percent confidence interval [CI]=1.11–2.00); 1.58 (CI=0.91–2.76); and 1.89 (CI=1.34–2.67) respectively. The reports of the primary studies were evaluated for epidemiologic quality and adequacy of exposure assessment. We found no statistically significant relation between combined relative risk estimates and 15 indicators of epidemiologic quality. Assessment of EMF exposure in the primary studies was found to be imperfect and imprecise. Additional high quality epidemiologic research, incorporating comprehensive assessments of EMF exposure collected concurrently with surrogate measures of exposure, is needed to confirm these results.