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Previous studies involving workers at brick kilns in the Kathmandu Valley of Nepal have investigated chronic exposure to hazardous levels of fine particulate matter (PM2.5) common in ambient and occupational environments. Such exposures are known to cause and/or exacerbate chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD) and asthma. However, there is a paucity of data regarding the status of systemic inflammation observed in exposed workers at brick manufacturing facilities within the country. In the current study, we sought to elucidate systemic inflammatory responses by quantifying the molecular cytokine/chemokine profiles in serum from the study participants. A sample of participants were screened from a kiln in Bhaktapur, Nepal (n = 32; 53% female; mean ± standard deviation: 28.42 ± 11.47 years old) and grouped according to job category. Blood was procured from participants on-site, allowed to clot at room temperature, and centrifuged to obtain total serum. A human cytokine antibody array was used to screen the inflammatory mediators in serum samples from each of the participants. For the current study, four job categories were evaluated with n = 8 for each. Comparisons were generated between a control group of administration workers vs. fire master workers, administration workers vs. green brick hand molders, and administration workers vs. top loaders. We discovered significantly increased concentrations of eotaxin-1, eotaxin-2, GCSF, GM-CSF, IFN-γ, IL-1α, IL-1ß, IL-6, IL-8, TGF-ß1, TNF-α, and TIMP-2 in serum samples from fire master workers vs. administration workers (p < 0.05). Each of these molecules was also significantly elevated in serum from green brick hand molders compared to administration workers (p < 0.05). Further, each molecule in the inflammatory screening with the exception of TIMP-2 was significantly elevated in serum from top loaders compared to administration workers (p < 0.05). With few exceptions, the fire master workers expressed significantly more systemic inflammatory molecular abundance when compared to all other job categories. These results reveal an association between pulmonary exposure to PM2.5 and systemic inflammatory responses likely mediated by cytokine/chemokine elaboration. The additional characterization of a broader array of inflammatory molecules may provide valuable insight into the susceptibility to lung diseases among this population.
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Exposure to respirable dust and crystalline silica (SiO2) has been linked to chronic obstructive pulmonary disease, silicosis, cancer, heart disease, and other respiratory diseases. Relatively few studies have measured respirable dust and SiO2 concentrations among workers at brick kilns in low- and middle-income countries. The purpose of this study was to measure personal breathing zone (PBZ) respirable dust and SiO2 concentrations among workers at one brick kiln in Bhaktapur, Nepal. A cross-sectional study was conducted among 49 workers in five job categories: administration, fire master, green (unfired) brick hand molder, green brick machine molder, and top loader. PBZ air samples were collected from each worker following Methods 0600 (respirable dust) and 7500 (respirable crystalline SiO2: cristobalite, quartz, tridymite) of the U.S. National Institute for Occupational Safety and Health. Eight-hour time-weighted average (TWA) respirable dust and quartz concentrations were also calculated. SiO2 percentage was measured in one bulk sample each of wet clay, the release agent used by green brick hand molders, and top coat soil at the brick kiln. The geometric mean (GM) sample and TWA respirable dust concentrations were 0.20 (95% confidence interval [CI]: 0.16, 0.27) and 0.12 (95% CI: 0.09, 0.16) mg/m3, respectively. GM sample and TWA quartz concentrations were 15.28 (95% CI: 11.11, 21.02) and 8.60 (95% CI: 5.99, 12.34) µg/m3, respectively. Job category was significantly associated with GM sample and TWA respirable dust and quartz concentrations (all p < 0.0001). Top loaders had the highest GM sample and TWA respirable dust concentrations of 1.49 and 0.99 mg/m3, respectively. Top loaders also had the highest GM sample and TWA quartz concentrations of 173.08 and 114.39 µg/m3, respectively. Quartz percentages in bulk samples were 16%-27%. Interventions including using wet methods to reduce dust generation, administrative controls, personal protective equipment, and education and training should be implemented to reduce brick kiln worker exposures to respirable dust and SiO2.
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Contaminantes Ocupacionales del Aire , Exposición Profesional , Humanos , Dióxido de Silicio/análisis , Exposición Profesional/análisis , Cuarzo/análisis , Polvo/análisis , Contaminantes Ocupacionales del Aire/análisis , Nepal , Estudios Transversales , Exposición por Inhalación/análisisRESUMEN
BACKGROUND: Job-exposure matrices (JEMs) are often used for exposure assessment in occupational exposure and epidemiology studies. However, general population JEMs are difficult to find and access for workers in the United States of America. OBJECTIVE: We aimed to use publicly available information to develop a JEM-like exposure assessment method to determine exposure to a wide range of occupational agents in a wide range of occupations for US general population studies. METHODS: We used information from the US Department of Labor's Occupational Information Network database (O*NET) for 19,636 job tasks and 974 civilian occupations. We used automated keyword searches to identify 1,804 job tasks that involved exposure to 50 occupational agents. We had 2 reviewers determine whether each identified job task actually involved exposure to the 50 occupational agents. We had a third reviewer, a certified industrial hygienist, assess any job task and exposure for which the first 2 reviewers disagreed. For each U.S. Census 2010 occupation code, we used this information to derive 3 exposure variables for each occupational agent: ever exposure, number of job tasks of exposure, and frequency of exposure. RESULTS: Our keyword searches identified a median of 10 (interquartile range [IQR]: 43.75) job tasks for each occupational agent, and the maximum was 308. We determined job tasks actually involved exposure to 45 occupational agents, including solvents, air pollution, pesticides, radiation, metals, etc. We derived the 3 exposure variables for these 45 occupational agents for 516 U.S. Census 2010 occupation codes. The median percentage for ever exposure to individual occupational agents was 1.16% (IQR: 1.74%), and the maximum was 11.43%. CONCLUSIONS: Our JEM-like exposure assessment method based on O*NET information can be used to determine exposure to a wide range of occupational agents in a wide range of occupations for the US general population.
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Exposición Profesional , Humanos , Estados Unidos , Exposición Profesional/análisis , Ocupaciones , Industrias , Metales , Servicios de InformaciónRESUMEN
Household and ambient air pollution remain public health problems in much of the world. Brick kiln employees in Nepal may be particularly at risk of high air pollution exposures and resulting health effects due to high levels of outdoor air pollution, substandard housing, and indoor biomass cooking. We conducted a cross-sectional study of indoor and outdoor air pollution concentrations at workers' homes at four fixed chimney Bull's trench brick kilns in Bhaktapur, Kathmandu Valley, Nepal. We measured air concentrations of carbon monoxide (CO), carbon dioxide (CO2), nitrogen dioxide (NO2), sulfur dioxide (SO2), and respirable crystalline silica (SiO2; cristobalite, quartz, tridymite) using established methods and conducted a survey about characteristics of homes or samples that may be associated with air pollution concentrations. Geometric mean concentrations of CO, CO2, and SiO2 (quartz) were 0.84 ppm, 1447.34 ppm, and 6.22 µg/m3, respectively, whereas concentrations of all other air pollutants measured below lower detection limits. Most characteristics of homes or samples were not associated with air pollution concentrations. We found a positive association between the variable how long lived in house and SiO2 (quartz) concentrations, which may reflect sustained take-home exposure to SiO2 (quartz) over time. Interventions should focus on administrative controls to reduce take-home exposure to SiO2 (quartz) in this population.
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Contaminantes Atmosféricos , Contaminación del Aire Interior , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Animales , Dióxido de Carbono , Monóxido de Carbono/análisis , Bovinos , Estudios Transversales , Monitoreo del Ambiente/métodos , Humanos , Masculino , Nepal , Dióxido de Nitrógeno/análisis , Cuarzo , Dióxido de Silicio , Dióxido de AzufreRESUMEN
Background: Coronavirus disease 2019 (COVID-19) began in 2019 with several unknown factors. The World Health Organization (WHO) subsequently developed COVID-19 occupational safety and health (OSH) guidelines to reduce occupational COVID-19 transmission. Many countries also developed their own COVID-19 OSH guidelines, but whether these guidelines included WHO's guidelines and whether including WHO's guidelines in countries' COVID-19 OSH guidelines reduced COVID-19 transmission is unknown. Objectives: The objectives of our study were to (1) compare the COVID-19 OSH guidelines of several countries to WHO's OSH guidelines, (2) estimate associations between characteristics of countries and their OSH guidelines and the number of WHO's OSH guidelines included in countries' OSH guidelines, and (3) estimate associations between WHO's OSH guidelines included in countries' OSH guidelines and COVID-19 risk, death risk, and case-fatality proportion. Methods: This study represents international, ecological research of 36 countries from all six world health regions. Countries' COVID-19 OSH guidelines were compared with WHO's OSH guidelines. Linear regression models adjusted for potential confounders were used to estimate associations of interest. Results: The median number of WHO's 15 COVID-19 OSH guidelines included in countries' COVID-19 OSH guidelines was eight. Countries' COVID-19 OSH guidelines focused on workers included significantly more of WHO's COVID-19 OSH guidelines than countries' COVID-19 OSH guidelines focused on general populations. Including "provide personal protective equipment for workers" and "create workplace policy for wearing personal protective equipment" in countries' COVID-19 OSH guidelines were significantly related to decreased COVID-19 risk, death risk, and/or case-fatality proportion. Conclusions: Countries' COVID-19 OSH guidelines should include WHO's guidelines, focus on workers, and include "provide personal protective equipment for workers" and "create workplace policy for wearing personal protective equipment."
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Radon (²²²Rn), a radioactive gas, is the second leading cause of lung cancer deaths in the U.S. Classroom radon concentrations in public schools in our target area had never been measured or had not been measured in many years. We had university students, primarily enrolled in environmental health courses, measure radon concentrations in 2289 classrooms in 66 of Utah's public schools and identify school characteristics associated with classroom radon concentrations. The geometric mean (GM) classroom radon concentration was 31.39 (95% confidence interval (CI): 27.16, 36.28) Bq/m3 (GM: 0.85; 95% CI: 0.72, 0.98 pCi/L). Thirty-seven (2%) classrooms in 13 (20%) schools had radon concentrations at or above the U.S. Environmental Protection Agency's (EPA) recommended action level of 148 Bq/m3 (4.0 pCi/L). Number of classrooms had a u-shaped association with classroom radon concentrations. The year the heating, ventilation, and air conditioning (HVAC) system was installed was inversely associated with having classroom radon concentrations at or above the EPA's recommended action level. Number of classrooms and number of students had u-shaped associations with having classroom radon concentrations at or above the EPA's recommended action level. Classroom radon concentrations decreased when schools' HVAC systems were on. Replacing HVAC systems and turning/keeping them on may be effective radon mitigation strategies to prevent radon-associated lung cancer, especially for small and large schools.
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Contaminantes Radiactivos del Aire , Contaminación del Aire Interior , Monitoreo de Radiación , Radón , Contaminantes Radiactivos del Aire/análisis , Contaminación del Aire Interior/análisis , Niño , Salud Ambiental , Arquitectura y Construcción de Instituciones de Salud , Humanos , Radón/análisis , Instituciones Académicas , Estudiantes , Universidades , UtahRESUMEN
Prior studies document a high prevalence of respiratory symptoms among brick workers in Nepal, which may be partially caused by non-occupational exposure to fine particulate matter (PM2.5) from cooking. In this study, we compared PM2.5 levels and 24 h trends in brick workers' homes that used wood or liquefied petroleum gas (LPG) cooking fuel. PM2.5 filter-based and real-time nephelometer data were collected for approximately 24 h in homes and outdoors. PM2.5 was significantly associated with fuel type and location (p < 0.0001). Pairwise comparisons found significant differences between gas, indoor (geometric mean (GM): 79.32 µg/m3), and wood, indoor (GM: 541.14 µg/m3; p = 0.0002), and between wood, indoor, and outdoor (GM: 48.38 µg/m3; p = 0.0006) but not between gas, indoor, and outdoor (p = 0.56). For wood fuel homes, exposure peaks coincided with mealtimes. For LPG fuel homes, indoor levels may be explained by infiltration of ambient air pollution. In both wood and LPG fuel homes, PM2.5 levels exceeded the 24 h limit (25.0 µg/m3) proposed by the World Health Organization. Our findings suggest that increasing the adoption of LPG cookstoves and decreasing ambient air pollution in the Kathmandu valley will significantly lower daily PM2.5 exposures of brick workers and their families.
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Contaminantes Atmosféricos , Contaminación del Aire Interior/efectos adversos , Culinaria/instrumentación , Material Particulado/análisis , Petróleo/efectos adversos , Madera , Contaminación del Aire Interior/análisis , Monitoreo del Ambiente/métodos , Incendios , Humanos , Nepal , Madera/químicaRESUMEN
Brick workers and their families in Nepal generally live in poorly ventilated on-site housing at the brick kiln, and may be at higher risk for non-occupational exposure to fine particulate matter air pollution and subsequent respiratory diseases due to indoor and outdoor sources. This study characterized non-occupational exposure to PM2.5 by comparing overall concentrations and specific chemical components of PM2.5 inside and outside of brick workers' on-site housing. For all samples, the geometric mean PM2.5 concentration was 184.65 µg/m3 (95% confidence interval: 134.70, 253.12 µg/m3). PM2.5 concentrations differed by kiln number (p = 0.009). Kiln number was significantly associated with 16 of 29 (55%) air pollutant, temperature, or relative humidity variables. There was not a significant interaction between kiln number and location of sample for PM2.5 (p = 0.16), but there was for relative humidity (p = 0.02) and temperature (p = 0.01). Results were qualitatively similar when we repeated analyses using indoor samples only. There was no difference in the chemical makeup of indoor and outdoor PM2.5 in this study, suggesting that outdoor PM2.5 air pollution easily infiltrates into on-site brick worker housing. Outdoor and indoor PM2.5 concentrations found in this study far exceed recommended levels. These findings warrant future interventions targeted to this vulnerable population.
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Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Incendios , Vivienda , Exposición Profesional , Tamaño de la Partícula , Lugar de Trabajo , Contaminación del Aire/análisis , Monitoreo del Ambiente/métodos , Femenino , Humanos , Masculino , Nepal , Material Particulado/análisisRESUMEN
Recent work suggests that evaporative coolers increase the level and diversity of bioaerosols, but this association remains understudied in low-income homes. We conducted a cross-sectional study of metropolitan, low-income homes in Utah with evaporative coolers (n = 20) and central air conditioners (n = 28). Dust samples (N = 147) were collected from four locations in each home and analyzed for dust-mite allergens Der p1 and Der f1, endotoxins, and ß-(1 â 3)-d-glucans. In all sample locations combined, Der p1 or Der f1 was significantly higher in evaporative cooler versus central air conditioning homes (OR = 2.29, 95% CI = 1.05-4.98). Endotoxin concentration was significantly higher in evaporative cooler versus central air conditioning homes in furniture (geometric mean (GM) = 8.05 vs 2.85 EU/mg, P < .01) and all samples combined (GM = 3.60 vs 1.29 EU/mg, P = .03). ß-(1 â 3)-d-glucan concentration and surface loads were significantly higher in evaporative cooler versus central air conditioning homes in all four sample locations and all samples combined (P < .01). Our study suggests that low-income, evaporative cooled homes have higher levels of immunologically important bioaerosols than central air-conditioned homes in dry climates, warranting studies on health implications and other exposed populations.
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Aire Acondicionado/métodos , Polvo/análisis , Endotoxinas/análisis , Pyroglyphidae , beta-Glucanos/análisis , Contaminación del Aire Interior/análisis , Animales , Clima , Estudios Transversales , Vivienda , Humanos , Pobreza , Proteoglicanos , Utah , VolatilizaciónRESUMEN
BACKGROUND: Commercial use of carbon nanotubes and nanofibers (CNT/F) in composites and electronics is increasing; however, little is known about health effects among workers. We conducted a cross-sectional study among 108 workers at 12 U.S. CNT/F facilities. We evaluated chest symptoms or respiratory allergies since starting work with CNT/F, lung function, resting blood pressure (BP), resting heart rate (RHR), and complete blood count (CBC) components. METHODS: We conducted multi-day, full-shift sampling to measure background-corrected elemental carbon (EC) and CNT/F structure count concentrations, and collected induced sputum to measure CNT/F in the respiratory tract. We measured (nonspecific) fine and ultrafine particulate matter mass and count concentrations. Concurrently, we conducted physical examinations, BP measurement, and spirometry, and collected whole blood. We evaluated associations between exposures and health measures, adjusting for confounders related to lifestyle and other occupational exposures. RESULTS: CNT/F air concentrations were generally low, while 18% of participants had evidence of CNT/F in sputum. Respiratory allergy development was positively associated with inhalable EC (p=0.040) and number of years worked with CNT/F (p=0.008). No exposures were associated with spirometry-based metrics or pulmonary symptoms, nor were CNT/F-specific metrics related to BP or most CBC components. Systolic BP was positively associated with fine particulate matter (p-values: 0.015-0.054). RHR was positively associated with EC, at both the respirable (p=0.0074) and inhalable (p=0.0026) size fractions. Hematocrit was positively associated with the log of CNT/F structure counts (p=0.043). CONCLUSIONS: Most health measures were not associated with CNT/F. The positive associations between CNT/F exposure and respiratory allergies, RHR, and hematocrit counts may not be causal and require examination in other studies.
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Contaminantes Ocupacionales del Aire/toxicidad , Sistema Cardiovascular/efectos de los fármacos , Leucocitos/efectos de los fármacos , Nanofibras/toxicidad , Nanotubos de Carbono/toxicidad , Exposición Profesional/análisis , Sistema Respiratorio/efectos de los fármacos , Adulto , Anciano , Contaminantes Ocupacionales del Aire/análisis , Contaminantes Ocupacionales del Aire/farmacocinética , Biomarcadores/sangre , Recuento de Células Sanguíneas , Estudios Transversales , Femenino , Humanos , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Nanofibras/análisis , Nanotubos de Carbono/análisis , Pruebas de Función Respiratoria , Esputo/química , Encuestas y CuestionariosRESUMEN
BACKGROUND: Carbon nanotubes and nanofibers (CNT/F) are increasingly used for diverse applications. Although animal studies suggest CNT/F exposure may cause deleterious health effects, human epidemiological studies have typically been small, confined to single workplaces, and limited in exposure assessment. OBJECTIVES: We conducted an industrywide cross-sectional epidemiological study of 108 workers from 12 U.S. sites to evaluate associations between occupational CNT/F exposure and sputum and blood biomarkers of early effect. METHODS: We assessed CNT/F exposure via personal breathing zone, filter-based air sampling to measure background-corrected elemental carbon (EC) (a CNT/F marker) mass and microscopy-based CNT/F structure count concentrations. We measured 36 sputum and 37 blood biomarkers. We used factor analyses with varimax rotation to derive factors among sputum and blood biomarkers separately. We used linear, Tobit, and unconditional logistic regression models to adjust for potential confounders and evaluate associations between CNT/F exposure and individual biomarkers and derived factors. RESULTS: We derived three sputum and nine blood biomarker factors that explained 78% and 67%, respectively, of the variation. After adjusting for potential confounders, inhalable EC and total inhalable CNT/F structures were associated with the most sputum and blood biomarkers, respectively. Biomarkers associated with at least three CNT/F metrics were 72â¯kDa type IV collagenase/matrix metalloproteinase-2 (MMP-2), interleukin-18, glutathione peroxidase (GPx), myeloperoxidase, and superoxide dismutase (SOD) in sputum and MMP-2, matrix metalloproteinase-9, metalloproteinase inhibitor 1/tissue inhibitor of metalloproteinases 1, 8-hydroxy-2'-deoxyguanosine, GPx, SOD, endothelin-1, fibrinogen, intercellular adhesion molecule 1, vascular cell adhesion protein 1, and von Willebrand factor in blood, although directions of associations were not always as expected. CONCLUSIONS: Inhalable rather than respirable CNT/F was more consistently associated with fibrosis, inflammation, oxidative stress, and cardiovascular biomarkers.
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Biomarcadores/análisis , Nanofibras/toxicidad , Nanotubos de Carbono/toxicidad , Exposición Profesional/análisis , Exposición Profesional/estadística & datos numéricos , Esputo/química , Biomarcadores/sangre , Estudios Transversales , Humanos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Recent animal studies have suggested the potential for wide-ranging health effects resulting from exposure to carbon nanotubes and nanofibers (CNT/F). To date, no studies in the US have directly examined the relationship between occupational exposure and potential human health effects. OBJECTIVES: Our goal was to measure CNT/F exposures among US workers with representative job types, from non-exposed to highly exposed, for an epidemiologic study relating exposure to early biologic effects. METHODS: 108 participants were enrolled from 12 facilities across the US. Personal, full-shift exposures were assessed based on the mass of elemental carbon (EC) at the respirable and inhalable aerosol particle size fractions, along with quantitatively characterizing CNT/F and estimating particle size via transmission electron microscopy (TEM). Additionally, sputum and dermal samples were collected and analyzed to determine internal exposures and exposures to the hands/wrists. RESULTS: The mean exposure to EC was 1.00⯵g/m3 at the respirable size fraction and 6.22⯵g/m3 at the inhalable fraction. Analysis by TEM found a mean exposure of 0.1275 CNT/F structures/cm3, generally to agglomerated materials between 2 and 10⯵m. Internal exposures to CNT/F via sputum analysis were confirmed in 18% of participants while â¼70% had positive dermal exposures. CONCLUSIONS: We demonstrated the occurrence of a broad range of exposures to CNT/F within 12 facilities across the US. Analysis of collected sputum indicated internal exposures are currently occurring within the workplace. This is an important first step in determining if exposures in the workforce have any acute or lasting health effects.
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Contaminantes Ocupacionales del Aire/análisis , Industrias , Exposición por Inhalación/análisis , Nanofibras , Nanotubos de Carbono , Exposición Profesional/análisis , Tamaño de la Partícula , Contaminantes Ocupacionales del Aire/efectos adversos , Carbono/efectos adversos , Estudios Transversales , Monitoreo del Ambiente , Humanos , Exposición por Inhalación/efectos adversos , Microscopía Electrónica de Transmisión , Nanofibras/efectos adversos , Nanofibras/análisis , Nanotubos de Carbono/efectos adversos , Nanotubos de Carbono/análisis , Enfermedades Profesionales/etiología , Exposición Profesional/efectos adversos , Ocupaciones , Enfermedades Respiratorias/etiología , Enfermedades de la Piel/etiología , Esputo , Estados Unidos , Trabajo , Lugar de TrabajoRESUMEN
Background: Histoplasmosis is a fungal infection associated with exposure to bat guano. An outbreak of an unknown severe febrile illness occurred among tunnel workers in the Dominican Republic, and resulted in several deaths. We conducted an investigation to confirm etiology and recommend control measures. Methods: A case was defined as fever and ≥2 symptoms consistent with histoplasmosis in a tunnel worker, July-September 2015. We interviewed workers and family members, reviewed medical records, tested serum and urine for Histoplasma antigen/antibody, and conducted a cohort study to identify risk factors for histoplasmosis and severe infection (intensive care). Results: A crew of 36 male workers removed large amounts of bat guano from tunnels without respiratory protection for a median of 24 days per worker (range, 1-25 days). Median age was 32 years (range, 18-62 years); none were immunocompromised. Thirty (83%) workers had illness that met the case definition, of whom 28 (93%) were hospitalized, 9 (30%) required intensive care, 6 (20%) required intubation, and 3 (10%) died. The median time from symptom onset to antifungal treatment was 6 days (range, 1-11 days). Twenty-two of 34 (65%) workers had laboratory evidence of infection. Conclusions: Severe illnesses and death likely resulted from exposure to large inocula of Histoplasma capsulatum spores in an enclosed space, lack of respiratory protection, and delay in recognition and treatment. Clinician education about histoplasmosis, improved laboratory capacity to diagnose fungal infections, and occupational health guidance to protect workers against endemic fungi are recommended in the Dominican Republic.
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Brotes de Enfermedades , Histoplasmosis/epidemiología , Histoplasmosis/etiología , Exposición Profesional , Adolescente , Adulto , Animales , Antifúngicos/uso terapéutico , Estudios de Cohortes , República Dominicana , Histoplasmosis/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Dispositivos de Protección Respiratoria , Adulto JovenRESUMEN
Blood lead and bone turnover may be associated with the risk of amyotrophic lateral sclerosis (ALS). We aimed to assess whether these factors were also associated with time from ALS diagnosis to death through a survival analysis of 145 ALS patients enrolled during 2007 in the National Registry of Veterans with ALS. Associations of survival time with blood lead and plasma biomarkers of bone resorption (C-terminal telopeptides of type I collagen (CTX)) and bone formation (procollagen type I amino-terminal peptide (PINP)) were estimated using Cox models adjusted for age at diagnosis, diagnostic certainty, diagnostic delay, site of onset, and score on the Revised ALS Functional Rating Scale. Hazard ratios were calculated for each doubling of biomarker concentration. Blood lead, plasma CTX, and plasma PINP were mutually adjusted for one another. Increased lead (hazard ratio (HR) = 1.38; 95% confidence interval (CI): 1.03, 1.84) and CTX (HR = 2.03; 95% CI: 1.42, 2.89) were both associated with shorter survival, whereas higher PINP was associated with longer survival (HR = 0.59; 95% CI: 0.42, 0.83), after ALS diagnosis. No interactions were observed between lead or bone turnover and other prognostic indicators. Lead toxicity and bone metabolism may be involved in ALS pathophysiology.
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Esclerosis Amiotrófica Lateral/etiología , Remodelación Ósea , Colágeno Tipo I/sangre , Plomo/sangre , Salud de los Veteranos/estadística & datos numéricos , Adulto , Distribución por Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/sangre , Esclerosis Amiotrófica Lateral/mortalidad , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptidos/sangre , Modelos de Riesgos Proporcionales , Sistema de Registros , Medición de Riesgo , Distribución por Sexo , Análisis de Supervivencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Military veterans may have higher rates of amyotrophic lateral sclerosis (ALS) mortality than non-veterans. Few studies, with sparse exposure information and mixed results, have studied relationships between military-related factors and ALS survival. We evaluated associations between military-related factors and ALS survival among U.S. military veteran cases. METHODS: We followed 616 medical record-confirmed cases from enrollment (2005-2010) in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study until death or July 25, 2013, whichever came first. We ascertained vital status information from several sources within the Department of Veterans Affairs. We obtained information regarding military service, deployments, and 39 related exposures via standardized telephone interviews. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals. We adjusted for potential confounding and missing covariate data biases via inverse probability weights. We also used inverse probability weights to adjust for potential selection bias among a case group that included a disproportionate number of long-term survivors at enrollment. RESULTS: We observed 446 deaths during 24,267 person-months of follow-up (median follow-up: 28 months). Survival was shorter for cases who served before 1950, were deployed to World War II, or mixed and applied burning agents, with HRs between 1.58 and 2.57. Longer survival was associated with exposure to: paint, solvents, or petrochemical substances; local food not provided by the Armed Forces; or burning agents or Agent Orange in the field with HRs between 0.56 and 0.73. CONCLUSIONS: Although most military-related factors were not associated with survival, associations we observed with shorter survival are potentially important because of the large number of military veterans.
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Esclerosis Amiotrófica Lateral/epidemiología , Personal Militar , Sobrevivientes/estadística & datos numéricos , Veteranos , Ácido 2,4,5-Triclorofenoxiacético/toxicidad , Ácido 2,4-Diclorofenoxiacético/toxicidad , Adulto , Anciano , Agente Naranja , Esclerosis Amiotrófica Lateral/etiología , Esclerosis Amiotrófica Lateral/mortalidad , Conflictos Armados/historia , Sustancias para la Guerra Química/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Masculino , Registros Médicos/estadística & datos numéricos , Persona de Mediana Edad , Dibenzodioxinas Policloradas/toxicidad , Modelos de Riesgos Proporcionales , Estados Unidos/epidemiologíaRESUMEN
Amyotrophic lateral sclerosis (ALS) and Parkinson's disease, both progressive neurodegenerative diseases, affect >1 million Americans (1,2). Consistently reported risk factors for ALS include increasing age, male sex, and cigarette smoking (1); risk factors for Parkinson's disease include increasing age, male sex, and pesticide exposure, whereas cigarette smoking and caffeine consumption are inversely associated (2). Relative to cancer or respiratory diseases, the role of occupation in neurologic diseases is much less studied and less well understood (3). CDC evaluated associations between usual occupation and ALS and Parkinson's disease mortality using data from CDC's National Institute for Occupational Safety and Health (NIOSH) National Occupational Mortality Surveillance (NOMS), a population-based surveillance system that includes approximately 12.1 million deaths from 30 U.S. states.* Associations were estimated using proportionate mortality ratios (PMRs), standardizing indirectly by age, sex, race, and calendar year to the standard population of all NOMS deaths with occupation information. Occupations associated with higher socioeconomic status (SES) had elevated ALS and Parkinson's disease mortality. The shifts in the U.S. workforce toward older ages and higher SES occupations highlight the importance of understanding this finding, which will require studies with designs that provide evidence for causality, detailed exposure assessment, and adjustment for additional potential confounders.
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Esclerosis Amiotrófica Lateral/mortalidad , Disparidades en el Estado de Salud , Ocupaciones/estadística & datos numéricos , Enfermedad de Parkinson/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clase Social , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Prospective cohort studies are important tools for identifying causes of disease. However, these studies are susceptible to attrition. When information collected after enrollment is through interview or exam, attrition leads to missing information for nonrespondents. The Agricultural Health Study enrolled 52,394 farmers in 1993-1997 and collected additional information during subsequent interviews. Forty-six percent of enrolled farmers responded to the 2005-2010 interview; 7% of farmers died prior to the interview. We examined whether response was related to attributes measured at enrollment. To characterize potential bias from attrition, we evaluated differences in associations between smoking and incidence of 3 cancer types between the enrolled cohort and the subcohort of 2005-2010 respondents, using cancer registry information. In the subcohort we evaluated the ability of inverse probability weighting (IPW) to reduce bias. Response was related to age, state, race/ethnicity, education, marital status, smoking, and alcohol consumption. When exposure and outcome were associated and case response was differential by exposure, some bias was observed; IPW conditional on exposure and covariates failed to correct estimates. When response was nondifferential, subcohort and full-cohort estimates were similar, making IPW unnecessary. This example provides a demonstration of investigating the influence of attrition in cohort studies using information that has been self-reported after enrollment.
Asunto(s)
Enfermedades de los Trabajadores Agrícolas/epidemiología , Sesgo , Diseño de Investigaciones Epidemiológicas , Agricultores/estadística & datos numéricos , Perdida de Seguimiento , Neoplasias/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de los Trabajadores Agrícolas/etiología , Enfermedades de los Trabajadores Agrícolas/prevención & control , Causas de Muerte , Femenino , Estudios de Seguimiento , Humanos , Entrevistas como Asunto , Iowa/epidemiología , Masculino , Persona de Mediana Edad , North Carolina , Oportunidad Relativa , Estudios Prospectivos , Fumar/epidemiologíaRESUMEN
Amyotrophic lateral sclerosis (ALS) may be associated with low body mass index (BMI) at the time of diagnosis. However, the role of premorbid BMI in the development of ALS and survival after diagnosis remains unclear. In 2005-2010, we interviewed 467 patients with ALS from the US National Registry of Veterans with ALS and 975 frequency-matched veteran controls. In this sample, we evaluated the association of BMI and BMI change at different ages with ALS risk using unconditional logistic models and with survival after ALS diagnosis using Cox proportional hazards models. After adjustment for confounders, compared with a moderate increase in BMI between ages 25 and 40 years, stable or decreasing BMI was positively associated with ALS risk (odds ratio (OR) = 1.61, 95% confidence interval (CI): 1.20, 2.16). A 1-unit increase in BMI at age 40 years (OR = 0.95, 95% CI: 0.91, 0.98) but not at age 25 years (OR = 0.99, 95% CI: 0.95, 1.03) was inversely associated with ALS. These associations were similar for bulbar and spinal ALS but stronger for those with a delay of less than 1 year between symptom onset and diagnosis. We found no association between prediagnosis BMI and survival. A decreasing BMI from early to middle age and a low BMI in middle age may be positively associated with ALS risk.
Asunto(s)
Esclerosis Amiotrófica Lateral/metabolismo , Índice de Masa Corporal , Salud de los Veteranos/estadística & datos numéricos , Adulto , Esclerosis Amiotrófica Lateral/mortalidad , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Sistema de Registros , Distribución por Sexo , Análisis de Supervivencia , Estados Unidos/epidemiología , Pérdida de PesoRESUMEN
Some trace metals may increase risk of amyotrophic lateral sclerosis (ALS), whereas others may be beneficial. Our goal was to examine associations of ALS with blood levels of selenium (Se), zinc (Zn), copper (Cu), and manganese (Mn). We conducted a case-control study of 163 neurologist confirmed patients from the National Registry of Veterans with ALS and 229 frequency-matched veteran controls. We measured metal levels in blood using inductively coupled plasma mass spectrometry and estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between ALS and a doubling of metal levels using unconditional logistic regression, adjusting for age, gender, and race/ethnicity. ALS was inversely associated with both Se (OR=0.4, 95% CI: 0.2-0.8) and Zn (OR=0.4, 95% CI: 0.2-0.8). Inverse associations with Se were stronger in patients with bulbar compared to spinal onset, worse function, longer diagnostic delay, and longer collection delay; inverse associations with Zn were stronger for those with worse function and longer collection delay. In contrast, ALS was positively associated with Cu (OR=3.4, 95% CI: 1.5-7.9). For Mn, no linear trend was evident (OR=0.9, 95% CI: 0.6-1.3, Ptrend=0.51). Associations of Se, Zn, Cu, and Mn with ALS were independent of one another. Adjustment for lead levels attenuated the positive association of ALS with Cu but did not change associations with Se, Zn, or Mn. In conclusion, Se and Zn were inversely associated with ALS, particularly among those with worse function, suggesting that supplementation with these metals may benefit such patients, while Cu was positively associated with ALS. Deficiencies of Se and Zn and excess Cu may have a role in ALS etiology.