ACCOUNTING FOR THE ENDOGENEITY OF HEALTH AND ENVIRONMENTAL TOBACCO SMOKE EXPOSURE IN CHILDREN: AN APPLICATION TO CONTINUOUS LUNG FUNCTION

EPA Science Inventory

The goal of this study is to estimate an unbiased exposure effect of environmental tobacco smoke (ETS) exposure on children's continuous lung function. A majority of the evidence from health studies suggests that ETS exposure in early life contributes significantly to childhood ...

Effect of short-term stainless steel welding fume inhalation exposure on lung inflammation, injury, and defense responses in rats.

PubMed

Antonini, James M; Stone, Sam; Roberts, Jenny R; Chen, Bean; Schwegler-Berry, Diane; Afshari, Aliakbar A; Frazer, David G

2007-09-15

Many welders have experienced bronchitis, metal fume fever, lung function changes, and an increase in the incidence of lung infection. Questions remain regarding the possible mechanisms associated with the potential pulmonary effects of welding fume exposure. The objective was to assess the early effects of stainless steel (SS) welding fume inhalation on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to gas metal arc-SS welding fume at a concentration of 15 or 40 mg/m(3) x 3 h/day for 1, 3, or 10 days. The control group was exposed to filtered air. To assess lung defense responses, some animals were intratracheally inoculated with 5x10(4) Listeria monocytogenes 1 day after the last exposure. Welding particles were collected during exposure, and elemental composition and particle size were determined. At 1, 4, 6, 11, 14, and 30 days after the final exposure, parameters of lung injury (lactate dehydrogenase and albumin) and inflammation (PMN influx) were measured in the bronchoalveolar lavage fluid. In addition, particle-induced effects on pulmonary clearance of bacteria and macrophage function were assessed. SS particles were composed of Fe, Cr, Mn, and Ni. Particle size distribution analysis indicated the mass median aerodynamic diameter of the generated fume to be 0.255 microm. Parameters of lung injury were significantly elevated at all time points post-exposure compared to controls except for 30 days. Interestingly, no significant difference in lung PMNs was observed between the SS and control groups at 1, 4, and 6 days post-exposure. After 6 days post-exposure, a dramatic increase in lung PMNs was observed in the SS group compared to air controls. Lung bacteria clearance and macrophage function were reduced and immune and inflammatory cytokines were altered in the SS group. In summary, short-term exposure of rats to SS welding fume caused significant lung damage and suppressed lung defense responses to bacterial infection, but had a delayed effect on pulmonary inflammation. Additional chronic inhalation studies are needed to further examine the lung effects associated with SS welding fume exposure.

Effect of short-term stainless steel welding fume inhalation exposure on lung inflammation, injury, and defense responses in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Antonini, James M.; Stone, Sam; Roberts, Jenny R.

Many welders have experienced bronchitis, metal fume fever, lung function changes, and an increase in the incidence of lung infection. Questions remain regarding the possible mechanisms associated with the potential pulmonary effects of welding fume exposure. The objective was to assess the early effects of stainless steel (SS) welding fume inhalation on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to gas metal arc-SS welding fume at a concentration of 15 or 40 mg/m{sup 3} x 3 h/day for 1, 3, or 10 days. The control group was exposed to filtered air. To assess lung defense responses,more » some animals were intratracheally inoculated with 5 x 10{sup 4}Listeria monocytogenes 1 day after the last exposure. Welding particles were collected during exposure, and elemental composition and particle size were determined. At 1, 4, 6, 11, 14, and 30 days after the final exposure, parameters of lung injury (lactate dehydrogenase and albumin) and inflammation (PMN influx) were measured in the bronchoalveolar lavage fluid. In addition, particle-induced effects on pulmonary clearance of bacteria and macrophage function were assessed. SS particles were composed of Fe, Cr, Mn, and Ni. Particle size distribution analysis indicated the mass median aerodynamic diameter of the generated fume to be 0.255 {mu}m. Parameters of lung injury were significantly elevated at all time points post-exposure compared to controls except for 30 days. Interestingly, no significant difference in lung PMNs was observed between the SS and control groups at 1, 4, and 6 days post-exposure. After 6 days post-exposure, a dramatic increase in lung PMNs was observed in the SS group compared to air controls. Lung bacteria clearance and macrophage function were reduced and immune and inflammatory cytokines were altered in the SS group. In summary, short-term exposure of rats to SS welding fume caused significant lung damage and suppressed lung defense responses to bacterial infection, but had a delayed effect on pulmonary inflammation. Additional chronic inhalation studies are needed to further examine the lung effects associated with SS welding fume exposure.« less

Air Pollution and Lung Function in Minority Youth with Asthma in the GALA II (Genes-Environments and Admixture in Latino Americans) and SAGE II (Study of African Americans, Asthma, Genes, and Environments) Studies.

PubMed

Neophytou, Andreas M; White, Marquitta J; Oh, Sam S; Thakur, Neeta; Galanter, Joshua M; Nishimura, Katherine K; Pino-Yanes, Maria; Torgerson, Dara G; Gignoux, Christopher R; Eng, Celeste; Nguyen, Elizabeth A; Hu, Donglei; Mak, Angel C; Kumar, Rajesh; Seibold, Max A; Davis, Adam; Farber, Harold J; Meade, Kelley; Avila, Pedro C; Serebrisky, Denise; Lenoir, Michael A; Brigino-Buenaventura, Emerita; Rodriguez-Cintron, William; Bibbins-Domingo, Kirsten; Thyne, Shannon M; Williams, L Keoki; Sen, Saunak; Gilliland, Frank D; Gauderman, W James; Rodriguez-Santana, Jose R; Lurmann, Fred; Balmes, John R; Eisen, Ellen A; Burchard, Esteban G

2016-06-01

Adverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking. To assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry. The study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter ≤10 μm and ≤2.5 μm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry. A 5 μg/m(3) increase in average lifetime particulate matter less than or equal to 2.5 μm in diameter exposure was associated with a 7.7% decrease in FEV1 (95% confidence interval = -11.8 to -3.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function. Early-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.

Lung Function in Rural Guatemalan Women Before and After a Chimney Stove Intervention to Reduce Wood Smoke Exposure: Results From the Randomized Exposure Study of Pollution Indoors and Respiratory Effects and Chronic Respiratory Effects of Early Childhood Exposure to Respirable Particulate Matter Study.

PubMed

Guarnieri, Michael; Diaz, Esperanza; Pope, Daniel; Eisen, Ellen A; Mann, Jennifer; Smith, Kirk R; Smith-Sivertsen, Tone; Bruce, Nigel G; Balmes, John R

2015-11-01

COPD is the third most frequent cause of death globally, with much of this burden attributable to household biomass smoke exposure in developing countries. As biomass smoke exposure is also associated with cardiovascular disease, lower respiratory infection, lung cancer, and cataracts, it presents an important target for public health intervention. Lung function in Guatemalan women exposed to wood smoke from open fires was measured throughout the Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) stove intervention trial and continued during the Chronic Respiratory Effects of Early Childhood Exposure to Respirable Particulate Matter (CRECER) cohort study. In RESPIRE, early stove households received a chimney woodstove at the beginning of the 18-month trial, and delayed stove households received a stove at trial completion. Personal exposure to wood smoke was assessed with exhaled breath carbon monoxide (CO) and personal CO tubes. Change in lung function between intervention groups and as a function of wood smoke exposure was assessed using random effects models. Of 306 women participating in both studies, acceptable spirometry was collected in 129 early stove and 136 delayed stove households (n = 265), with a mean follow-up of 5.6 years. Despite reduced wood smoke exposures in early stove households, there were no significant differences in any of the measured spirometric variables during the study period (FEV1, FVC, FEV1/FVC ratio, and annual change) after adjustment for confounding. In these young Guatemalan women, there was no association between lung function and early randomization to a chimney stove or personal wood smoke exposure. Future stove intervention trials should incorporate cleaner stoves, longer follow-up, or potentially susceptible groups to identify meaningful differences in lung function.

[Oxidative stress, lung function and exposure to air pollutants in Mexican schoolchildren with and without asthma].

PubMed

Romero-Calderón, Ana Teresa; Moreno-Macías, Hortensia; Manrique-Moreno, Joel David Francisco; Riojas-Rodríguez, Horacio; Torres-Ramos, Yessica Dorín; Montoya-Estrada, Araceli; Hicks-Gómez, Juan José; Linares-Segovia, Benigno; Cárdenas, Beatriz; Bárcenas, Claudia; Barraza-Villarreal, Albino

2017-01-01

To assess the association between the air pollutants exposure on markers of oxidative stress and lung function in schoolchildren with and without asthma from Salamanca and Leon Guanajuato, Mexico. We realized determinations of oxidative stress biomarkers and lung function tests in 314 schoolchildren. Information of air pollutants (O3, SO2, CO, PM2.5 and PM10) were obtained from monitoring stations and multiple linear regression models were run to assess the association. An increase of 0.09 pmol in conjugated dienes was observed by exposure to PM10 lag 1 in asthmatics from Salamanca (p<0.05). The exposure to O3 during the same day increased the concentration of Lipohydroperoxides in 4.38 nmol in asthmatics of Salamanca, as well as in 2.31 nmol by exposure to PM10 lag 2 (p<0.05). The forced vital capacity decreased by 138 and 203 ml in children without asthma, respectively, due to exposure to carbon monoxide (p<0.05). Exposure to air pollutants increase oxidative stress and decreased lung function in schoolchildren, with and without asthma.

Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function

PubMed Central

Larcombe, Alexander N.; Foong, Rachel E.; Boylen, Catherine E.; Zosky, Graeme R.

2012-01-01

Please cite this paper as: Larcombe et al. (2012) Acute diesel exhaust particle exposure increases viral titre and inflammation associated with existing influenza infection, but does not exacerbate deficits in lung function. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12012. Background  Exposure to diesel exhaust particles (DEP) is thought to exacerbate many pre‐existing respiratory diseases, including asthma, bronchitis and chronic obstructive pulmonary disease, however, there is a paucity of data on whether DEP exacerbates illness due to respiratory viral infection. Objectives  To assess the physiological consequences of an acute DEP exposure during the peak of influenza‐induced illness. Methods  We exposed adult female BALB/c mice to 100 μg DEP (or control) 3·75 days after infection with 104·5 plaque forming units of influenza A/Mem71 (or control). Six hours, 24 hours and 7 days after DEP exposure we measured thoracic gas volume and lung function at functional residual capacity. Bronchoalveolar lavage fluid was taken for analyses of cellular inflammation and cytokines, and whole lungs were taken for measurement of viral titre. Results  Influenza infection resulted in significantly increased inflammation, cytokine influx and impairment to lung function. DEP exposure alone resulted in less inflammation and cytokine influx, and no impairment to lung function. Mice infected with influenza and exposed to DEP had higher viral titres and neutrophilia compared with infected mice, yet they did not have more impaired lung mechanics than mice infected with influenza alone. Conclusions  A single dose of DEP is not sufficient to physiologically exacerbate pre‐existing respiratory disease caused by influenza infection in mice. PMID:22994877

The Effect of Wood Aerosols and Bioaerosols on the Respiratory Systems of Wood Manufacturing Industry Workers in Golestan Province

PubMed Central

Badirdast, Phateme; Salehpour, Soussan; Ghadjari, Ali; Khodakarim, Soheila; Panahi, Davod; Fadaei, Moslem; Rahimi, Abolfazl

2017-01-01

Background: Occupational exposure to dust leads to acute and chronic respiratory diseases, occupational asthma, and depressed lung function. In the light of a lack of comprehensive studies on the exposure of Iranian workers to wood dusts, the objective of this study was to monitor the occupational exposure to wood dust and bioaerosol, and their correlation with the lung function parameters in chipboard manufacturing industry workers. Materials and Methods: A cross-sectional study was conducted on chipboard workers in Golestan Province; a total of 150 men (100 exposed cases and 50 controls) were assessed. Workers were monitored for inhalable wood dust and lung function parameters, i.e., FVC, FEV1, FEV1/FVC, and FEF25–75%. The workers’ exposure to bioaerosols was measured using a bacterial sampler; a total of 68 area samples were collected. The analysis was performed using the Mann-Whitney, Kruskal-Wallis, and regression statistical tests. Results: The geometric mean value and geometric standard deviation of inhalable wood dust for the exposed and control groups were 19 ± 2.00 mg/m3 and 0.008 ± 0.001 mg/m3, respectively. A statistically significant correlation was observed between the lung parameters and cumulative exposure to inhalable wood dust, whereas a statistically significant correlation was not observed between the lung parameters and bioaerosol exposure. However, the exposure of Iranian workers to bioaerosols was higher, compared to their foreign coworkers. Conclusion: Considering the high level of exposure among workers in this study along with their lung function results, long-term exposure to wood dust may be detrimental to the workers’ health and steps to limit their exposure should be considered seriously. PMID:28638425

Imaging Phenotype of Occupational Endotoxin-Related Lung Function Decline.

PubMed

Lai, Peggy S; Hang, Jing-Qing; Zhang, Feng-Ying; Sun, J; Zheng, Bu-Yong; Su, Li; Washko, George R; Christiani, David C

2016-09-01

Although occupational exposures contribute to a significant proportion of obstructive lung disease, the phenotype of obstructive lung disease associated with work-related organic dust exposure independent of smoking remains poorly defined. We identified the relative contributions of smoking and occupational endotoxin exposure to parenchymal and airway remodeling as defined by quantitative computed tomography (CT). The Shanghai Textile Worker Study is a longitudinal study of endotoxin-exposed cotton workers and endotoxin-unexposed silk workers that was initiated in 1981. Spirometry, occupational endotoxin exposure, and smoking habits were assessed at 5-year intervals. High-resolution computed tomography (CT) was performed in 464 retired workers in 2011, along with quantitative lung densitometric and airway analysis. Significant differences in all CT measures were noted across exposure groups. Occupational endotoxin exposure was associated with a decrease (-1.3%) in percent emphysema (LAAI-950), a 3.3-Hounsfield unit increase in 15th percentile density, an 18.1-g increase in lung mass, and a 2.3% increase in wall area percent. Current but not former smoking was associated with a similar CT phenotype. Changes in LAAI-950 were highly correlated with 15th percentile density (correlation -1.0). Lung mass was the only measure associated with forced expiratory volume in 1 sec (FEV1) decline, with each 10-g increase in lung mass associated with an additional loss (-6.1 mL) of FEV1 (p = 0.001) between 1981 and 2011. There are many similarities between the effects of occupational endotoxin exposure and those of tobacco smoke exposure on lung parenchyma and airway remodeling. The effects of occupational endotoxin exposure appear to persist even after the cessation of exposure. LAAI-950 may not be a reliable indicator of emphysema in subjects without spirometric impairment. Lung mass is a CT-based biomarker of accelerated lung function decline. Lai PS, Hang J, Zhang F, Sun J, Zheng BY, Su L, Washko GR, Christiani DC. 2016. Imaging phenotype of occupational endotoxin-related lung function decline. Environ Health Perspect 124:1436-1442; http://dx.doi.org/10.1289/EHP195.

Pre- and postnatal exposure of mice to concentrated urban PM2.5 decreases the number of alveoli and leads to altered lung function at an early stage of life.

PubMed

de Barros Mendes Lopes, Thais; Groth, Espen E; Veras, Mariana; Furuya, Tatiane K; de Souza Xavier Costa, Natalia; Ribeiro Júnior, Gabriel; Lopes, Fernanda Degobbi; de Almeida, Francine M; Cardoso, Wellington V; Saldiva, Paulo Hilario Nascimento; Chammas, Roger; Mauad, Thais

2018-06-04

Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM 2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM 2.5 (from São Paulo, Brazil; target dose 600 μg/m 3 for 1 h daily). Exposure was started on embryonic day 5.5 (E5.5, time of placental implantation). Lung tissue of fetuses and offspring was submitted to stereological and transcriptomic analyses at E14.5 (pseudoglandular stage of lung development), E18.5 (saccular stage) and P40 (postnatal day 40, alveolarized lung). Additionally, lung function and cellularity of bronchoalveolar lavage (BAL) fluid were studied in offspring animals at P40. Compared to control animals that were exposed to filtered air throughout gestation and postnatal life, PM-exposed mice exhibited higher lung elastance and a lower alveolar number at P40 whilst the total lung volume and cellularity of BAL fluid were not affected. Glandular and saccular structures of fetal lungs were not altered upon gestational exposure; transcriptomic signatures, however, showed changes related to DNA damage and its regulation, inflammation and regulation of cell proliferation. A differential expression was validated at E14.5 for the candidates Sox8, Angptl4 and Gas1. Our data substantiate the in utero biomolecular effect of gestational exposure to air pollution and provide first-time stereological evidence that pre- and early life-postnatal exposure compromise lung development, leading to a reduced number of alveoli and an impairment of lung function in the adult mouse. Copyright © 2018 Elsevier Ltd. All rights reserved.

Exposure to neonatal cigarette smoke causes durable lung changes but does not potentiate cigarette smoke–induced chronic obstructive pulmonary disease in adult mice

PubMed Central

McGrath-Morrow, Sharon; Malhotra, Deepti; Lauer, Thomas; Collaco, J. Michael; Mitzner, Wayne; Neptune, Enid; Wise, Robert; Biswal, Shyam

2016-01-01

The impact of early childhood cigarette smoke (CS) exposure on CS-induced chronic obstructive pulmonary disease (COPD) is unknown. This study was performed to evaluate the individual and combined effects of neonatal and adult CS exposure on lung structure, function, and gene expression in adult mice. To model a childhood CS exposure, neonatal C57/B6 mice were exposed to 14 days of CS (Neo CS). At 10 weeks of age, Neo CS and control mice were exposed to 4 months of CS. Pulmonary function tests, bronchoalveolar lavage, and lung morphometry were measured and gene expression profiling was performed on lung tissue. Mean chord lengths and lung volumes were increased in neonatal and/or adult CS-exposed mice. Differences in immune, cornified envelope protein, muscle, and erythrocyte genes were found in CS-exposed lung. Neonatal CS exposure caused durable structural and functional changes in the adult lung but did not potentiate CS-induced COPD changes. Cornified envelope protein gene expression was decreased in all CS-exposed mice, whereas myosin and erythrocyte gene expression was increased in mice exposed to both neonatal and adult CS, suggesting an adaptive response. Additional studies may be warranted to determine the utility of these genes as biomarkers of respiratory outcomes. PMID:21649527

Work-related symptoms and dose-response relationships for personal exposures and pulmonary function among woodworkers.

PubMed

Mandryk, J; Alwis, K U; Hocking, A D

1999-05-01

Four sawmills, a wood chipping mill, and five joineries in New South Wales, Australia, were studied for the effects of personal exposure to wood dust, endotoxins. (1-->3)-beta-D-glucans, Gram-negative bacteria, and fungi on lung function among woodworkers. Personal inhalable and respirable dust sampling was carried out. The lung function tests of workers were conducted before and after a workshift. The mean percentage cross-shift decrease in lung function was markedly high for woodworkers compared with the controls. Dose-response relationships among personal exposures and percentage cross-shift decrease in lung function and percentage predicted lung function were more pronounced among joinery workers compared with sawmill and chip mill workers. Woodworkers had markedly high prevalence of regular cough, phlegm, and chronic bronchitis compared with controls. Significant associations were found between percentage cross-shift decrease in FVC and regular phlegm and blocked nose among sawmill and chip mill workers. Both joinery workers and sawmill and chip mill workers showed significant relationships between percentage predicted lung function (FVC, FEV1, FEV1/FVC, FEF25-75%) and respiratory symptoms. Wood dust and biohazards associated with wood dust are potential health hazards and should be controlled.

Increased lung function decline in blue-collar workers exposed to welding fumes.

PubMed

Thaon, Isabelle; Demange, Valérie; Herin, Fabrice; Touranchet, Annie; Paris, Christophe

2012-07-01

There is no consensus at the present time about the effect of welding on lung function decline. This study compared lung function decline between blue-collar workers exposed and not exposed to welding fumes in a French longitudinal cohort of 21,238 subjects aged 37 to 52 years at inclusion. Medical data, occupation, sector of activity, and spirometry were recorded twice by occupational physicians in 1990 and 1995. A job-exposure matrix was used to identify 503 male blue-collar workers exposed to welding fumes and 709 control subjects and to define the weekly duration of exposure to welding fumes. Baseline lung function parameters were higher in workers exposed to welding fumes than in control subjects. After a 5-year follow-up, welding-fume exposure was associated with a nonsignificant decline in FVC (P = .06) and FEV(1) (P = .07) after adjustment for age, pack-years, BMI, and baseline value of the parameter. A significant accelerated decline in FEV(1) (P = .046) was also observed in never smokers exposed to welding fumes. An “exposure-response” relationship was observed between FEV(1) decline and weekly duration of exposure to welding fumes in nonsmokers but not in smokers. Blue-collar workers exposed to welding fumes showed accelerated decline in lung function, which, in nonsmokers, was related to weekly duration of exposure.

Diesel exhaust modulates ozone-induced lung function decrements in healthy human volunteers

PubMed Central

2014-01-01

The potential effects of combinations of dilute whole diesel exhaust (DE) and ozone (O3), each a common component of ambient airborne pollutant mixtures, on lung function were examined. Healthy young human volunteers were exposed for 2 hr to pollutants while exercising (~50 L/min) intermittently on two consecutive days. Day 1 exposures were either to filtered air, DE (300 μg/m3), O3 (0.300 ppm), or the combination of both pollutants. On Day 2 all exposures were to O3 (0.300 ppm), and Day 3 served as a followup observation day. Lung function was assessed by spirometry just prior to, immediately after, and up to 4 hr post-exposure on each exposure day. Functional pulmonary responses to the pollutants were also characterized based on stratification by glutathione S-transferase mu 1 (GSTM1) genotype. On Day 1, exposure to air or DE did not change FEV1 or FVC in the subject population (n = 15). The co-exposure to O3 and DE decreased FEV1 (17.6%) to a greater extent than O3 alone (9.9%). To test for synergistic exposure effects, i.e., in a greater than additive fashion, FEV1 changes post individual O3 and DE exposures were summed together and compared to the combined DE and O3 exposure; the p value was 0.057. On Day 2, subjects who received DE exposure on Day 1 had a larger FEV1 decrement (14.7%) immediately after the O3 exposure than the individuals’ matched response following a Day 1 air exposure (10.9%). GSTM1 genotype did not affect the magnitude of lung function changes in a significant fashion. These data suggest that altered respiratory responses to the combination of O3 and DE exposure can be observed showing a greater than additive manner. In addition, O3-induced lung function decrements are greater with a prior exposure to DE compared to a prior exposure to filtered air. Based on the joint occurrence of these pollutants in the ambient environment, the potential exists for interactions in more than an additive fashion affecting lung physiological processes. PMID:25178924

Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma.

PubMed

Bunyavanich, S; Boyce, J A; Raby, B A; Weiss, S T

2012-02-01

Distinct receptors likely exist for leukotriene (LT)E(4), a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE(4)-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. Nineteen single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n = 1266). Using family based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. Five SNPs in P2RY12 were associated with multiple lung function measures (P-values 0.006–0.025). Haplotypes in P2RY12 were also associated with lung function (P-values 0.0055–0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P-values 0.0028–0.040). The P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment.

Five-year lung function observations and associations with a smoking ban among healthy miners at high altitude (4000 m).

PubMed

Vinnikov, Denis; Blanc, Paul D; Brimkulov, Nurlan; Redding-Jones, Rupert

2013-12-01

To assess the annual lung function decline associated with the reduction of secondhand smoke exposure in a high-altitude industrial workforce. We performed pulmonary function tests annually among 109 high-altitude gold-mine workers over 5 years of follow-up. The first 3 years included greater likelihood of exposure to secondhand smoke exposure before the initiation of extensive smoking restrictions that came into force in the last 2 years of observation. In repeated measures modeling, taking into account the time elapsed in relation to the smoking ban, there was a 115 ± 9 (standard error) mL per annum decline in lung function before the ban, but a 178 ± 20 (standard error) mL per annum increase afterward (P < 0.001, both slopes). Institution of a workplace smoking ban at high altitude may be beneficial in terms of lung function decline.

A long term study of pulmonary function among US refractory ceramic fibre workers

PubMed Central

LeMasters, Grace K; Hilbert, Timothy J; Levin, Linda S; Rice, Carol H; Borton, Eric K; Lockey, James E

2010-01-01

Background Cross-sectional studies have shown declines in lung function among refractory ceramic fibre (RCF) workers with increasing fibre exposure. This study followed current and former workers (n=1396) for up to 17 years and collected 5243 pulmonary function tests. Methods Cumulative fibre exposure and production years were categorised into exposure levels at five manufacturing locations. Conventional longitudinal models did not adequately partition age-related changes from other time-dependent variables. Therefore, a restricted cubic spline model was developed to account for the non-linear decline with age. Results Cumulative fibre >60 fibre-months/cc showed a significant loss in lung function at the first test. When results were examined longitudinally, cumulative exposure was confounded with age as workers with the highest cumulative exposure were generally older. A longitudinal model adjusted by age groups was implemented to control for this confounding. No consistent longitudinal loss in lung function was observed with RCF exposure. Smoking, initial weight and weight increase were significant factors. Conclusion No consistent decline was observed longitudinally with exposure to RCF, although cross-sectional and longitudinal findings were discordant. Confounding and accelerated lung function declines with ageing and the correlation of multiple time-dependent variables should be considered in order to minimise error and maximise precision. An innovative statistical methodology for these types of data is described. PMID:20798015

Violence exposure, a chronic psychosocial stressor, and childhood lung function

PubMed Central

Suglia, Shakira Franco; Ryan, Louise; Laden, Francine; Dockery, Douglas; Wright, Rosalind J

2011-01-01

Background Chronic psychosocial stressors, including violence, have been linked to neuropsychological and behavioral development in children as well as physiologic alterations that may lead to broader health effects. Methods We examined the relationship between violence and childhood lung function in a prospective birth cohort of 313 urban children 6 and 7 years of age. Mothers reported on their child’s lifetime exposure to community violence (ETV) and interparental conflict in the home [Conflict Tactics Scale (CTS)] within one year of the lung function assessment. Results In linear regression analyses, adjusting for maternal education, child’s age, race, birthweight, tobacco smoke exposure, and medical history, girls in the highest CTS verbal aggression tertile had a 5.5% (95% CI: −9.6, −1.5) decrease in percent predicted FEV1 and a 5.4% (95% CI: −9.7, −1.1) decrease in FVC compared to girls in the lowest tertile. The CTS verbal aggression subscale was associated with lung function among boys in the same direction, albeit this was not statistically significant. Boys in the highest ETV tertile had a 3.4% (95% CI: −8.0, 1.1) lower FEV1 and 5.3% lower (95% CI: −10.2, −0.4) FVC compared to boys in the lowest tertile. The ETV score was not a significant predictor of girl’s lung function. Conclusions Interparental conflict, specifically verbal aggression, and exposure to community violence were associated with decreased childhood lung function independent of socioeconomic status, tobacco smoke exposure, birthweight and respiratory illness history. Gender differences were noted based on the type of violence exposure which may warrant further exploration. PMID:18158365

Elemental composition of particulate matter and the association with lung function.

PubMed

Eeftens, Marloes; Hoek, Gerard; Gruzieva, Olena; Mölter, Anna; Agius, Raymond; Beelen, Rob; Brunekreef, Bert; Custovic, Adnan; Cyrys, Josef; Fuertes, Elaine; Heinrich, Joachim; Hoffmann, Barbara; de Hoogh, Kees; Jedynska, Aleksandra; Keuken, Menno; Klümper, Claudia; Kooter, Ingeborg; Krämer, Ursula; Korek, Michal; Koppelman, Gerard H; Kuhlbusch, Thomas A J; Simpson, Angela; Smit, Henriëtte A; Tsai, Ming-Yi; Wang, Meng; Wolf, Kathrin; Pershagen, Göran; Gehring, Ulrike

2014-09-01

Negative effects of long-term exposure to particulate matter (PM) on lung function have been shown repeatedly. Spatial differences in the composition and toxicity of PM may explain differences in observed effect sizes between studies. We conducted a multicenter study in 5 European birth cohorts-BAMSE (Sweden), GINIplus and LISAplus (Germany), MAAS (United Kingdom), and PIAMA (The Netherlands)-for which lung function measurements were available for study subjects at the age of 6 or 8 years. Individual annual average residential exposure to copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM smaller than 2.5 μm (PM2.5) and smaller than 10 μm (PM10) was estimated using land-use regression models. Associations between air pollution and lung function were analyzed by linear regression within cohorts, adjusting for potential confounders, and then combined by random effects meta-analysis. We observed small reductions in forced expiratory volume in the first second, forced vital capacity, and peak expiratory flow related to exposure to most elemental pollutants, with the most substantial negative associations found for nickel and sulfur. PM10 nickel and PM10 sulfur were associated with decreases in forced expiratory volume in the first second of 1.6% (95% confidence interval = 0.4% to 2.7%) and 2.3% (-0.1% to 4.6%) per increase in exposure of 2 and 200 ng/m, respectively. Associations remained after adjusting for PM mass. However, associations with these elements were not evident in all cohorts, and heterogeneity of associations with exposure to various components was larger than for exposure to PM mass. Although we detected small adverse effects on lung function associated with annual average levels of some of the evaluated elements (particularly nickel and sulfur), lower lung function was more consistently associated with increased PM mass.

Occupational Lung Disease Risk and Exposure to Butter-Flavoring Chemicals After Implementation of Controls at a Microwave Popcorn Plant

PubMed Central

Kanwal, Richard; Kullman, Greg; Fedan, Kathleen B.; Kreiss, Kathleen

2011-01-01

Objectives After an outbreak of severe lung disease among workers exposed to butter-flavoring chemicals at a microwave popcorn plant, we determined whether or not lung disease risk declined after implementation of exposure controls. Methods National Institute for Occupational Safety and Health staff performed eight serial cross-sectional medical and industrial hygiene surveys at the plant from November 2000 through August 2003. Medical surveys included standardized questionnaires and spirometry testing. Industrial hygiene surveys measured levels of production-related air contaminants, including butter-flavoring chemicals such as diacetyl. All diacetyl concentrations above detectable limits were corrected for the effects of absolute humidity and days to sample extraction. Results Ventilation and isolation of the production process resulted in one to three orders of magnitude reductions in diacetyl air concentrations in different areas of the plant. Workers with past high exposures had stable chest symptoms over time; nasal, eye, and skin irritation symptoms declined. New workers had lower symptom prevalences and higher lung function than workers with past high exposures, and they did not worsen over time. In workers who had at least three spirometry tests, those with past high exposures were more likely to experience rapid declines in lung function than new workers. Conclusions Implemented controls lowered exposures to butter-flavoring chemicals and decreased lung disease risk for much of the plant workforce. Some workers with continuing potential for intermittent, short-term peak and measurable time-weighted exposures remain at risk and should use respiratory protection and have regularly scheduled spirometry to detect rapid lung function declines that may be work-related. Close follow-up of such workers is likely to yield additional information on risks due to peak and time-weighted exposure levels. PMID:21800743

Occupational lung disease risk and exposure to butter-flavoring chemicals after implementation of controls at a microwave popcorn plant.

PubMed

Kanwal, Richard; Kullman, Greg; Fedan, Kathleen B; Kreiss, Kathleen

2011-01-01

After an outbreak of severe lung disease among workers exposed to butter-flavoring chemicals at a microwave popcorn plant, we determined whether or not lung disease risk declined after implementation of exposure controls. National Institute for Occupational Safety and Health staff performed eight serial cross-sectional medical and industrial hygiene surveys at the plant from November 2000 through August 2003. Medical surveys included standardized questionnaires and spirometry testing. Industrial hygiene surveys measured levels of production-related air contaminants, including butter-flavoring chemicals such as diacetyl. All diacetyl concentrations above detectable limits were corrected for the effects of absolute humidity and days to sample extraction. Ventilation and isolation of the production process resulted in one to three orders of magnitude reductions in diacetyl air concentrations in different areas of the plant. Workers with past high exposures had stable chest symptoms over time; nasal, eye, and skin irritation symptoms declined. New workers had lower symptom prevalences and higher lung function than workers with past high exposures, and they did not worsen over time. In workers who had at least three spirometry tests, those with past high exposures were more likely to experience rapid declines in lung function than new workers. Implemented controls lowered exposures to butter-flavoring chemicals and decreased lung disease risk for much of the plant workforce. Some workers with continuing potential for intermittent, short-term peak and measurable time-weighted exposures remain at risk and should use respiratory protection and have regularly scheduled spirometry to detect rapid lung function declines that may be work-related. Close follow-up of such workers is likely to yield additional information on risks due to peak and time-weighted exposure levels.

Long-term ambient air pollution and lung function impairment in Chinese children from a high air pollution range area: The Seven Northeastern Cities (SNEC) study

NASA Astrophysics Data System (ADS)

Zeng, Xiao-Wen; Vivian, Elaina; Mohammed, Kahee A.; Jakhar, Shailja; Vaughn, Michael; Huang, Jin; Zelicoff, Alan; Xaverius, Pamela; Bai, Zhipeng; Lin, Shao; Hao, Yuan-Tao; Paul, Gunther; Morawska, Lidia; Wang, Si-Quan; Qian, Zhengmin; Dong, Guang-Hui

2016-08-01

Epidemiological studies have reported inconsistent and inconclusive associations between long-term exposure to ambient air pollution and lung function in children from Europe and America, where air pollution levels were typically low. The aim of the present study is to examine the relationship between air pollutants and lung function in children selected from heavily industrialized and polluted cities in northeastern China. During 2012, 6740 boys and girls aged 7-14 years were recruited in 24 districts of seven northeastern cities. Portable electronic spirometers were used to measure lung function. Four-year average concentrations of particulate matter with an aerodynamic diameter ≤10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) were measured at monitoring stations in the 24 districts. Two-staged regression models were used in the data analysis, controlling for covariates. Overall, for all subjects, the increased odds of lung function impairment associated with exposure to air pollutants, ranged from 5% (adjusted odds ratio [aOR] = 1.05; 95% confidence interval [CI] = 1.01, 1.10) for FVC < 85% predicted per 46.3 μg/m3 for O3 to 81% (aOR = 1.81; 95%CI = 1.44, 2.28) for FEV1 < 85% predicted per 30.6 μg/m3 for PM10. The linear regression models consistently showed a negative relationship between all air pollutants and lung function measures across subjects. There were significant interaction terms indicating gender differences for lung function impairment and pulmonary function from exposure to some pollutants (P < 0.10). In conclusion, long term exposure to high concentrations of ambient air pollution is associated with decreased pulmonary function and lung function impairment, and females appear to be more susceptible than males.

Role of epithelial-mesenchymal transition (EMT) and fibroblast function in cerium oxide nanoparticles-induced lung fibrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Jane

The emission of cerium oxide nanoparticles (CeO{sub 2}) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO{sub 2} induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO{sub 2}-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO{sub 2} (0.15 to 7 mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure. The results show that at 28 days after CeO{sub 2} (3.5 mg/kg)more » exposure, lung fibrosis was evidenced by increased soluble collagen in bronchoalveolar lavage fluid, elevated hydroxyproline content in lung tissues, and enhanced sirius red staining for collagen in the lung tissue. Lung fibroblasts and alveolar type II (ATII) cells isolated from CeO{sub 2}-exposed rats at 28 days post-exposure demonstrated decreasing proliferation rate when compare to the controls. CeO{sub 2} exposure was cytotoxic and altered cell function as demonstrated by fibroblast apoptosis and aggregation, and ATII cell hypertrophy and hyperplasia with increased surfactant. The presence of stress fibers, expressed as α-smooth muscle actin (SMA), in CeO{sub 2}-exposed fibroblasts and ATII cells was significantly increased compared to the control. Immunohistofluorescence analysis demonstrated co-localization of TGF-β or α-SMA with prosurfactant protein C (SPC)-stained ATII cells. These results demonstrate that CeO{sub 2} exposure affects fibroblast function and induces EMT in ATII cells that play a role in lung fibrosis. These findings suggest potential adverse health effects in response to CeO{sub 2} nanoparticle exposure. - Highlights: • CeO{sub 2} exposure induced lung fibrosis. • CeO{sub 2} were detected in lung tissue, alveolar type II (ATII) cells and fibroblasts. • CeO{sub 2} caused ATII cell hypertrophy and hyperplasia and altered fibroblast function. • Increased α-SMA in CeO{sub 2}-exposed lung fibroblasts indicating myofibroblast formation. • CeO{sub 2} induced EMT in ATII cells demonstrated as increased α-SMA expression.« less

Longitudinal analysis of respiratory outcomes among bauxite exposed workers in Western Australia.

PubMed

Dennekamp, Martine; de Klerk, Nicholas Hubert; Reid, Alison; Abramson, Michael John; Cui, Jisheng; Del Monaco, Anthony; Fritschi, Lin; Benke, Geza Paul; Sim, Malcolm Ross; Musk, Arthur William

2015-08-01

Occupational exposure to bauxite is common in the aluminium industry but little is known about the associated health effects. This study investigates respiratory health in relation to respirable bauxite dust exposure longitudinally over a 13 year period. An inception cohort study recruited 91 male bauxite miners and 363 male alumina refinery workers. Annual measurements of respiratory symptoms and lung function were made. Cumulative exposure to bauxite was derived from job histories and air monitoring data. Mixed-effects modeling was used. No associations were found between cumulative bauxite exposure and respiratory symptoms or lung function. However, when analysis was restricted to the first three rounds, FEV1 was significantly lower in all exposure groups than in those unexposed but with no significant trend. Increasing exposure to bauxite dust in the aluminum industry was not associated with respiratory symptoms or consistent decrements in lung function. © 2015 Wiley Periodicals, Inc.

Air pollution during pregnancy and lung development in the child.

PubMed

Korten, Insa; Ramsey, Kathryn; Latzin, Philipp

2017-01-01

Air pollution exposure has increased extensively in recent years and there is considerable evidence that exposure to particulate matter can lead to adverse respiratory outcomes. The health impacts of exposure to air pollution during the prenatal period is especially concerning as it can impair organogenesis and organ development, which can lead to long-term complications. Exposure to air pollution during pregnancy affects respiratory health in different ways. Lung development might be impaired by air pollution indirectly by causing lower birth weight, premature birth or disturbed development of the immune system. Exposure to air pollution during pregnancy has also been linked to decreased lung function in infancy and childhood, increased respiratory symptoms, and the development of childhood asthma. In addition, impaired lung development contributes to infant mortality. The mechanisms of how prenatal air pollution affects the lungs are not fully understood, but likely involve interplay of environmental and epigenetic effects. The current epidemiological evidence on the effect of air pollution during pregnancy on lung function and children's respiratory health is summarized in this review. While evidence for the adverse effects of prenatal air pollution on lung development and health continue to mount, rigorous actions must be taken to reduce air pollution exposure and thus long-term respiratory morbidity and mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alcohol and Airways Function in Health and Disease

PubMed Central

Sisson, Joseph H.

2007-01-01

The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The impact of alcohol on lung airway functions is dependent on the concentration, duration and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation and probably attenuates the airway inflammation and injury observed in asthma and COPD. Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management and likely worsens outcomes including lung function and mortality in COPD patients. Non-alcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase type 2 (ALDH2). The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation and the interaction with other airway exposure agents, such as cigarette smoke, represent opportunities for future investigation. PMID:17764883

Alcohol and airways function in health and disease.

PubMed

Sisson, Joseph H

2007-08-01

The volatility of alcohol promotes the movement of alcohol from the bronchial circulation across the airway epithelium and into the conducting airways of the lung. The exposure of the airways through this route likely accounts for many of the biologic effects of alcohol on lung airway functions. The effect of alcohol on lung airway functions is dependent on the concentration, duration, and route of exposure. Brief exposure to mild concentrations of alcohol may enhance mucociliary clearance, stimulates bronchodilation, and probably attenuates the airway inflammation and injury observed in asthma and chronic obstructive pulmonary disease (COPD). Prolonged and heavy exposure to alcohol impairs mucociliary clearance, may complicate asthma management, and likely worsens outcomes including lung function and mortality in COPD patients. Nonalcohol congeners and alcohol metabolites act as triggers for airway disease exacerbations especially in atopic asthmatics and in Asian populations who have a reduced capacity to metabolize alcohol. Research focused on the mechanisms of alcohol-mediated changes in airway functions has identified specific mechanisms that mediate alcohol effects within the lung airways. These include prominent roles for the second messengers calcium and nitric oxide, regulatory kinases including PKG and PKA, alcohol- and acetaldehyde-metabolizing enzymes such as aldehyde dehydrogenase 2. The role alcohol may play in the pathobiology of airway mucus, bronchial blood flow, airway smooth muscle regulation, and the interaction with other airway exposure agents, such as cigarette smoke, represents opportunities for future investigation.

Short-Term Exposure to Air Pollution and Lung Function in the Framingham Heart Study

PubMed Central

Ljungman, Petter L.; Wilker, Elissa H.; Gold, Diane R.; Schwartz, Joel D.; Koutrakis, Petros; Washko, George R.; O’Connor, George T.; Mittleman, Murray A.

2013-01-01

Rationale: Short-term exposure to ambient air pollution has been associated with lower lung function. Few studies have examined whether these associations are detectable at relatively low levels of pollution within current U.S. Environmental Protection Agency (EPA) standards. Objectives: To examine exposure to ambient air pollutants within EPA standards and lung function in a large cohort study. Methods: We included 3,262 participants of the Framingham Offspring and Third Generation cohorts living within 40 km of the Harvard Supersite monitor in Boston, Massachusetts (5,358 examinations, 1995–2011) who were not current smokers, with previous-day pollutant levels in compliance with EPA standards. We compared lung function (FEV1 and FVC) after previous-day exposure to particulate matter less than 2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in the “moderate” range of the EPA Air Quality Index to exposure in the “good” range. We also examined linear relationships between moving averages of pollutant concentrations 1, 2, 3, 5, and 7 days before spirometry and lung function. Measurements and Main Results: Exposure to pollutant concentrations in the “moderate” range of the EPA Air Quality Index was associated with a 20.1-ml lower FEV1 for PM2.5 (95% confidence interval [CI], −33.4, −6.9), a 30.6-ml lower FEV1 for NO2 (95% CI, −60.9, −0.2), and a 55.7-ml lower FEV1 for O3 (95% CI, −100.7, −10.8) compared with the “good” range. The 1- and 2-day moving averages of PM2.5, NO2, and O3 before testing were negatively associated with FEV1 and FVC. Conclusions: Short-term exposure to PM2.5, NO2, and O3 within current EPA standards was associated with lower lung function in this cohort of adults. PMID:24200465

The mammalian respiratory system and critical windows of exposure for children's health.

PubMed Central

Pinkerton, K E; Joad, J P

2000-01-01

The respiratory system is a complex organ system composed of multiple cell types involved in a variety of functions. The development of the respiratory system occurs from embryogenesis to adult life, passing through several distinct stages of maturation and growth. We review embryonic, fetal, and postnatal phases of lung development. We also discuss branching morphogenesis and cellular differentiation of the respiratory system, as well as the postnatal development of xenobiotic metabolizing systems within the lungs. Exposure of the respiratory system to a wide range of chemicals and environmental toxicants during perinatal life has the potential to significantly affect the maturation, growth, and function of this organ system. Although the potential targets for exposure to toxic factors are currently not known, they are likely to affect critical molecular signals expressed during distinct stages of lung development. The effects of exposure to environmental tobacco smoke during critical windows of perinatal growth are provided as an example leading to altered cellular and physiological function of the lungs. An understanding of critical windows of exposure of the respiratory system on children's health requires consideration that lung development is a multistep process and cannot be based on studies in adults. Images Figure 1 Figure 4 PMID:10852845

Long-term air pollution exposure, genome-wide DNA methylation and lung function in the LifeLines cohort study.

EPA Science Inventory

BACKGROUND: Long-term air pollution exposure is negatively associated with lung function, yet the mechanisms underlying this association are not·­ fully clear.Differential DNA methylation may explain this association. OBJECTIVES: Our main aim was to study the associati...

Traffic-related Air Pollution, Lung Function, and Host Vulnerability. New Insights from the PARIS Birth Cohort.

PubMed

Bougas, Nicolas; Rancière, Fanny; Beydon, Nicole; Viola, Malika; Perrot, Xavier; Gabet, Stephan; Lezmi, Guillaume; Amat, Flore; De Blic, Jacques; Just, Jocelyne; Momas, Isabelle

2018-05-01

Although the effects of traffic-related air pollution on respiratory exacerbations have been well documented, its impact on lung function in childhood remains unclear. Our aim was to investigate the associations of prenatal, early, and lifetime traffic-related air pollution exposure with lung function at 8-9 years studying possible effect modification by sex, sensitization at 8-9 years, and early lower respiratory tract infections. We conducted this study among 788 children from the PARIS (Pollution and Asthma Risk: an Infant Study) birth cohort. Lung function tests were performed during the medical examination at 8-9 years. Traffic-related air pollution exposure during each trimester of pregnancy was estimated using nitrogen oxides background measurements. Postnatal traffic-related air pollution exposure was assessed by a nitrogen oxides air dispersion model at both residential and daycare/school addresses. Associations between lung function and traffic-related air pollution exposure were analyzed by multiple linear regression models. Higher prenatal nitrogen oxides levels, especially during the second trimester of pregnancy, were associated with a lower forced expiratory flow at 25-75% of the forced vital capacity, but there were no significant associations between prenatal nitrogen oxide levels and forced vital capacity, forced expiratory volume during 1 second, or the forced expiratory volume during 1 second/forced vital capacity ratio overall. Postnatal traffic-related air pollution exposure was associated with lower lung function among children with early lower respiratory tract infections or sensitization at 8-9 years, but not in the full cohort. In children with early repeated lower respiratory tract infections, an interquartile increase in lifetime nitrogen oxides exposure was associated with both a lower forced expiratory volume during 1 second (-62.6 ml; 95% confidence interval = -107.0 to -18.1) and forced vital capacity (-55.7 ml; 95% confidence interval = -109.5 to -1.8), but was not associated with the forced expiratory volume during 1 second/forced vital capacity ratio. There was an association between greater early postnatal nitrogen oxide exposure and a lower forced expiratory volume during 1 second/forced vital capacity ratio among sensitized children (-0.65%; 95% confidence interval = -1.25 to -0.05). This study sheds new light, suggesting associations between postnatal traffic-related air pollution exposure and reduced lung function may be enhanced by early, repeated lower respiratory tract infections or allergic sensitization.

Combined effect of urinary monohydroxylated polycyclic aromatic hydrocarbons and impaired lung function on diabetes.

PubMed

Hou, Jian; Sun, Huizhen; Xiao, Lili; Zhou, Yun; Yin, Wenjun; Xu, Tian; Cheng, Juan; Chen, Weihong; Yuan, Jing

2016-07-01

Associations of type 2 diabetes with exposure to polycyclic aromatic hydrocarbons and reduced lung function have been reported. The aim of the present study was to investigate effect of reduced lung function and exposure to background PAHs on diabetes. A total of 2730 individuals were drawn from the Wuhan-Zhuhai (WHZH) Cohort Study (n=3053). Participants completed physical examination, measurement of lung function and urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs). Risk factors for type 2 diabetes were identified by multiple logistic regression analysis, and the presence of additive interaction between levels of urinary OH-PAHs and lower lung function was evaluated by calculation of the relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP). Urinary OH-PAHs levels was positively associated with type 2 diabetes among individuals with impaired lung function (p<0.05). Forced expiratory volume in one second (FEV1, odd ratio (OR): 0.664, 95% confidence interval (CI): 0.491-0.900) and forced vital capacity (FVC, OR: 0.693, 95% CI: 0.537-0.893) were negatively associated with diabetes among individuals. Additive interaction of higher urinary levels of OH-PAHs and lower FVC (RERI: 0.679, 95% CI: 0.120-1.238); AP: 0.427, 95% CI: 0.072-0.782) was associated with diabetes. Exposure to background PAHs was related to diabetes among individuals with lower lung function. Urinary levels of OH-PAHs and reduced lung function had an additive effect on diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-Term Exposure to Primary Traffic Pollutants and Lung Function in Children: Cross-Sectional Study and Meta-Analysis.

PubMed

Barone-Adesi, Francesco; Dent, Jennifer E; Dajnak, David; Beevers, Sean; Anderson, H Ross; Kelly, Frank J; Cook, Derek G; Whincup, Peter H

2015-01-01

There is widespread concern about the possible health effects of traffic-related air pollution. Nitrogen dioxide (NO2) is a convenient marker of primary pollution. We investigated the associations between lung function and current residential exposure to a range of air pollutants (particularly NO2, NO, NOx and particulate matter) in London children. Moreover, we placed the results for NO2 in context with a meta-analysis of published estimates of the association. Associations between primary traffic pollutants and lung function were investigated in 4884 children aged 9-10 years who participated in the Child Heart and Health Study in England (CHASE). A systematic literature search identified 13 studies eligible for inclusion in a meta-analysis. We combined results from the meta-analysis with the distribution of the values of FEV1 in CHASE to estimate the prevalence of children with abnormal lung function (FEV1<80% of predicted value) expected under different scenarios of NO2 exposure. In CHASE, there were non-significant inverse associations between all pollutants except ozone and both FEV1 and FVC. In the meta-analysis, a 10 μg/m3 increase in NO2 was associated with an 8 ml lower FEV1 (95% CI: -14 to -1 ml; p: 0.016). The observed effect was not modified by a reported asthma diagnosis. On the basis of these results, a 10 μg/m3 increase in NO2 level would translate into a 7% (95% CI: 4% to 12%) increase of the prevalence of children with abnormal lung function. Exposure to traffic pollution may cause a small overall reduction in lung function and increase the prevalence of children with clinically relevant declines in lung function.

Long-term exposure to diesel engine exhaust induced lung function decline in a cross sectional study

PubMed Central

ZHANG, Li Ping; ZHANG, Xiao; DUAN, Hua Wei; MENG, Tao; NIU, Yong; HUANG, Chuan Feng; GAO, Wei Min; YU, Shan Fa; ZHENG, Yu Xin

2016-01-01

To clarify the effects of lung function following exposure to diesel engine exhaust (DEE), we recruited 137 diesel engine testing workers exposed to DEE and 127 non-DEE-exposed workers as study subjects. We performed lung function tests and measured cytokinesis-block micronucleus (CBMN) cytome index and levels of urinary polycyclic aromatic hydrocarbons (PAHs) metabolites. There was a significant decrease of forced expiratory volume in 1 second (FEV1), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/ FVC), maximal mid expiratory flow curve (MMF), forced expiratory flow at 50% of FVC (FEF50%), and forced expiratory flow at 75% of FVC (FEF75%) in the DEE-exposed workers than non-DEE-exposed workers (all p<0.05). Among all study subjects, the decreases of FEF75% were associated with the increasing levels of PAHs metabolites (p<0.05), and there were negative correlations between FEV1, FEV1/FVC, MMF, FEF50%, and FEF75% with CBMN cytome index (all p<0.05). Our results show that long-term exposure to DEE can induce lung function decline which shows mainly obstructive changes and influence of small airways function. The decreased lung function is associated with internal dosage of DEE exposure, and accompany with the increasing CBMN cytome index. PMID:27334424

Arsenic Compromises Conducting Airway Epithelial Barrier Properties in Primary Mouse and Immortalized Human Cell Cultures

PubMed Central

Sherwood, Cara L.; Liguori, Andrew E.; Olsen, Colin E.; Lantz, R. Clark; Burgess, Jefferey L.; Boitano, Scott

2013-01-01

Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb)] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE) cell model we found that both micromolar (3.9 μM) and submicromolar (0.8 μM) arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl) Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-). We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway. PMID:24349408

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinmaus, Craig, E-mail: craigs@berkeley.edu

Background: Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods: We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤ 10 μg/L. Results: Compared to adults never exposed > 10 μg/L, adults born in Antofagasta during the high exposuremore » period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 mL decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 mL). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions: Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. - Highlights: • Based on its unique geology, lifetime arsenic exposure can be assessed in north Chile. • Signs and symptoms of lung disease were associated with early-life arsenic exposure. • Evidence of lung disease was also associated with moderate arsenic exposure.« less

Effects of combinations of diesel exhaust and ozone exposure on lung function in human volunteers.

EPA Science Inventory

Ozone (03) exposure induces changes in human lung function, typically seen as a decrease in forced expiratory volume in one sec (FEV1) and forced vital capacity (FVC). Because people are usually exposed to other ambient air pollutants simultaneously with 03, there may be interact...

Acute effects of PM2.5 on lung function parameters in schoolchildren in Nanjing, China: a panel study.

PubMed

Xu, Dandan; Zhang, Yi; Zhou, Lian; Li, Tiantian

2018-03-17

The association between exposure to ambient particulate matter (PM) and reduced lung function parameters has been reported in many works. However, few studies have been conducted in developing countries with high levels of air pollution like China, and little attention has been paid to the acute effects of short-term exposure to air pollution on lung function. The study design consisted of a panel comprising 86 children from the same school in Nanjing, China. Four measurements of lung function were performed. A mixed-effects regression model with study participant as a random effect was used to investigate the relationship between PM 2.5 and lung function. An increase in the current day, 1-day and 2-day moving average PM 2.5 concentration was associated with decreases in lung function indicators. The greatest effect of PM 2.5 on lung function was detected at 1-day moving average PM 2.5 exposure. An increase of 10 μg/m 3 in the 1-day moving average PM 2.5 concentration was associated with a 23.22 mL decrease (95% CI: 13.19, 33.25) in Forced Vital Capacity (FVC), a 18.93 mL decrease (95% CI: 9.34, 28.52) in 1-s Forced Expiratory Volume (FEV 1 ), a 29.38 mL/s decrease (95% CI: -0.40, 59.15) in Peak Expiratory Flow (PEF), and a 27.21 mL/s decrease (95% CI: 8.38, 46.04) in forced expiratory flow 25-75% (FEF 25-75% ). The effects of PM 2.5 on lung function had significant lag effects. After an air pollution event, the health effects last for several days and we still need to pay attention to health protection.

Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust.

PubMed

Rudell, B; Ledin, M C; Hammarström, U; Stjernberg, N; Lundbäck, B; Sandström, T

1996-10-01

Diesel exhaust is a common air pollutant made up of several gases, hydrocarbons, and particles. An experimental study was carried out which was designed to evaluate if a particle trap on the tail pipe of an idling diesel engine would reduce effects on symptoms and lung function caused by the diesel exhaust, compared with exposure to unfiltered exhaust. Twelve healthy non-smoking volunteers (aged 20-37) were investigated in an exposure chamber for one hour during light work on a bicycle ergometer at 75 W. Each subject underwent three separate double blind exposures in a randomised sequence: to air and to diesel exhaust with the particle trap at the tail pipe and to unfiltered diesel exhaust. Symptoms were recorded according to the Borg scale before, every 10 minutes during, and 30 minutes after the exposure. Lung function was measured with a computerised whole body plethysmograph. The ceramic wall flow particle trap reduced the number of particles by 46%, whereas other compounds were relatively constant. It was shown that the most prominent symptoms during exposure to diesel exhaust were irritation of the eyes and nose and an unpleasant smell increasing during exposure. Both airway resistance (R(aw)) and specific airway resistance (SR(aw)) increased significantly during the exposures to diesel exhaust. Despite the 46% reduction in particle numbers by the trap effects on symptoms and lung function were not significantly attenuated. Exposure to diesel exhaust caused symptoms and bronchoconstriction which were not significantly reduced by a particle trap.

High-Resolution Computed Tomography and Pulmonary Function Findings of Occupational Arsenic Exposure in Workers.

PubMed

Ergün, Recai; Evcik, Ender; Ergün, Dilek; Ergan, Begüm; Özkan, Esin; Gündüz, Özge

2017-05-05

The number of studies where non-malignant pulmonary diseases are evaluated after occupational arsenic exposure is very few. To investigate the effects of occupational arsenic exposure on the lung by high-resolution computed tomography and pulmonary function tests. Retrospective cross-sectional study. In this study, 256 workers with suspected respiratory occupational arsenic exposure were included, with an average age of 32.9±7.8 years and an average of 3.5±2.7 working years. Hair and urinary arsenic levels were analysed. High-resolution computed tomography and pulmonary function tests were done. In workers with occupational arsenic exposure, high-resolution computed tomography showed 18.8% pulmonary involvement. In pulmonary involvement, pulmonary nodule was the most frequently seen lesion (64.5%). The other findings of pulmonary involvement were 18.8% diffuse interstitial lung disease, 12.5% bronchiectasis, and 27.1% bullae-emphysema. The mean age of patients with pulmonary involvement was higher and as they smoked more. The pulmonary involvement was 5.2 times higher in patients with skin lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was significantly lower in patients with pulmonary involvement. Besides lung cancer, chronic occupational inhalation of arsenic exposure may cause non-malignant pulmonary findings such as bronchiectasis, pulmonary nodules and diffuse interstitial lung disease. So, in order to detect pulmonary involvement in the early stages, workers who experience occupational arsenic exposure should be followed by diffusion test and high-resolution computed tomography.

Rubberwood dust and lung function among Thai furniture factory workers.

PubMed

Thetkathuek, Anamai; Yingratanasuk, Tanongsak; Demers, Paul A; Thepaksorn, Phayong; Saowakhontha, Sastri; Keifer, Matthew C

2010-01-01

The objective of this study was to assess factors affecting lung function among 685 workers in the rubberwood (Hevea brasiliensis) furniture industry in the Chonburi and Rayung provinces of eastern Thailand. Study data were gathered using questionnaires, by sampling wood dust, and by spirometry. The mean wood dust exposure level in the factories was 4.08 mg/m3 (SD = 1.42, range: 1.15-11.17 mg/m3). The mean overall percent of predicted forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and FEV1/FVC values were 84 % (SD = 13.41), 86 % (SD = 14.40), and 99% (SD = 10.42), respectively. Significant negative correlations were found between mean dust exposure levels and FVC (p = 0.0008), and FEV1/FVC% (p < 0.001), but not FEV1 (p = 0.074). An association between decline in lung function and wood dust levels among wood workers suggests that rubberwood dust exposure negatively affects lung function.

Pulmonary functions in plastic factory workers: a preliminary study.

PubMed

Khaliq, Farah; Singh, Pawan; Chandra, Prakash; Gupta, Keshav; Vaney, Neelam

2011-01-01

Exposure to long term air pollution in the work environment may result in decreased lung functions and various other health problems. A significant occupational hazard to lung functions is experienced by plastic factory workers. The present study is planned to assess the pulmonary functions of workers in the plastic factory where recycling of pastic material was done. These workers were constantly exposed to fumes of various chemicals throughout the day. Thirty one workers of plastic factory were assessed for their pulmonary functions. Parameters were compared with 31 age and sex matched controls not exposed to the same environment. The pulmonary function tests were done using Sibelmed Datospir 120 B portable spirometer. A significant decrease in most of the flow rates (MEF 25%, MEF 50%, MEF 75% and FEF 25-75%) and most of the lung volumes and capacities (FVC, FEV1, VC, TV, ERV, MVV) were observed in the workers. Smoking and duration of exposure were not affecting the lung functions as the non smokers also showed a similar decrement in pulmonary functions. Similarly the workers working for less than 5 years also had decrement in pulmonary functions indicating that their lungs are being affected even if they have worked for one year. Exposure to the organic dust in the work environment should be controlled by adequate engineering measures, complemented by effective personal respiratory protection.

Pulmonary health effects of agriculture.

PubMed

Nordgren, Tara M; Bailey, Kristina L

2016-03-01

Occupational exposures in the agricultural industry are associated with numerous lung diseases, including chronic obstructive pulmonary disease, asthma, hypersensitivity pneumonitis, lung cancer, and interstitial lung diseases. Efforts are ongoing to ascertain contributing factors to these negative respiratory outcomes and improve monitoring of environmental factors leading to disease. In this review, recently published studies investigating the deleterious effects of occupational exposures in the agricultural industry are discussed. Occupational exposures to numerous agricultural environment aerosols, including pesticides, fungi, and bacteria are associated with impaired respiratory function and disease. Increases in certain farming practices, including mushroom and greenhouse farming, present new occupational exposure concerns. Improved detection methods may provide opportunities to better monitor safe exposure levels to known lung irritants. In the agricultural industry, occupational exposures to organic and inorganic aerosols lead to increased risk for lung disease among workers. Increased awareness of respiratory risks and improved monitoring of agricultural environments are necessary to limit pulmonary health risks to exposed populations.

Effects of Bisphenol A Metabolite 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on Lung Function and Type 2 Pulmonary Alveolar Epithelial Cell Growth

PubMed Central

Liu, Shing-Hwa; Su, Chin-Chuan; Lee, Kuan-I; Chen, Ya-Wen

2016-01-01

Bisphenol A (BPA) is recognized as a major pollutant worldwide. 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is a major active metabolite of BPA. The epidemiological and animal studies have reported that BPA is harmful to lung function. The role of MBP in lung dysfunction after BPA exposure still remains unclear. This study investigated whether MBP would induce lung alveolar cell damage and evaluated the role of MBP in the BPA exposure-induced lung dysfunction. An in vitro type 2 alveolar epithelial cell (L2) model and an ex vivo isolated reperfused rat lung model were used to determine the effects of BPA or MBP on cell growth and lung function. MBP, but not BPA, dose-dependently increased the mean artery pressure (Pa), pulmonary capillary pressure (Pc), pulmonary capillary filtration coefficient (Kfc), and wet/dry weight ratio in isolated reperfused rat lungs. MBP significantly reduced cell viability and induced caspases-3/7 cleavage and apoptosis and increased AMP-activated protein kinas (AMPK) phosphorylation and endoplasmic reticulum (ER) stress-related molecules expression in L2 cells, which could be reversed by AMPK-siRNA transfection. These findings demonstrated for the first time that MBP exposure induced type 2 alveolar cell apoptosis and lung dysfunction through an AMPK-regulated ER stress signaling pathway. PMID:27982077

Effects of Bisphenol A Metabolite 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on Lung Function and Type 2 Pulmonary Alveolar Epithelial Cell Growth.

PubMed

Liu, Shing-Hwa; Su, Chin-Chuan; Lee, Kuan-I; Chen, Ya-Wen

2016-12-16

Bisphenol A (BPA) is recognized as a major pollutant worldwide. 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is a major active metabolite of BPA. The epidemiological and animal studies have reported that BPA is harmful to lung function. The role of MBP in lung dysfunction after BPA exposure still remains unclear. This study investigated whether MBP would induce lung alveolar cell damage and evaluated the role of MBP in the BPA exposure-induced lung dysfunction. An in vitro type 2 alveolar epithelial cell (L2) model and an ex vivo isolated reperfused rat lung model were used to determine the effects of BPA or MBP on cell growth and lung function. MBP, but not BPA, dose-dependently increased the mean artery pressure (Pa), pulmonary capillary pressure (Pc), pulmonary capillary filtration coefficient (K fc ), and wet/dry weight ratio in isolated reperfused rat lungs. MBP significantly reduced cell viability and induced caspases-3/7 cleavage and apoptosis and increased AMP-activated protein kinas (AMPK) phosphorylation and endoplasmic reticulum (ER) stress-related molecules expression in L2 cells, which could be reversed by AMPK-siRNA transfection. These findings demonstrated for the first time that MBP exposure induced type 2 alveolar cell apoptosis and lung dysfunction through an AMPK-regulated ER stress signaling pathway.

Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter.

PubMed

Lovinsky-Desir, Stephanie; Jung, Kyung Hwa; Jezioro, Jacqueline R; Torrone, David Z; de Planell-Saguer, Mariangels; Yan, Beizhan; Perera, Frederica P; Rundle, Andrew G; Perzanowski, Matthew S; Chillrud, Steven N; Miller, Rachel L

2017-01-01

Physical activity is associated with improvement in lung function; however, pollution exposure during physical activity can lead to a transient reduction in lung function. This paradoxical relationship may be linked to altered T regulatory (Treg) cell activity, which increases with exercise and suppresses airway inflammation, but decreases in association with exposure to air pollution. To clarify these relationships, we investigated buccal cell DNA methylation of the forkhead box p3 ( FOXP3 ) gene promoter, a proposed biomarker of Treg activity. We hypothesized that active urban children would have lower FOXP3 promoter methylation, associated with better lung function compared to non-active children. We also hypothesized that this relationship would be attenuated by high exposure to the air pollutant black carbon (BC). We performed a cross-sectional study of 135 children ages 9-14 who live in New York City. Activity was measured across 6 days. BC exposure was assessed by personal monitors worn for two 24-h periods, followed by lung function assessment. Buccal swabs were collected for DNA methylation analysis of three regions (six CpG sites) in the FOXP3 promoter. In multivariable regression models, overall, there was no significant relationship between physical activity and FOXP3 promoter methylation ( p  > 0.05). However, in stratified analyses, among children with higher BC exposure (≥1200 ng/m 3 ), physical activity was associated with 2.37% lower methylation in promoter 2 (CpGs -77, -65, and -58) ( β estimate  = -2.37%, p  < 0.01) but not among those with lower BC exposure ( β estimate  = 0.54%, p  > 0.05). Differences across strata were statistically significant ( p interaction  = 0.04). Among all children, after controlling for BC concentration, promoter 2 methylation was associated with reduced FEV 1 /FVC ( β estimate  = -0.40%, p  < 0.01) and reduced FEF 25-75% ( β estimate  = -1.46%, p  < 0.01). Physical activity in urban children appeared associated with lower FOXP3 promoter methylation, a possible indicator of greater Treg function, under conditions of high BC exposure. Reduced FOXP3 promoter methylation was associated with higher lung function. These findings suggest that physical activity may induce immunologic benefits, particularly for urban children with greater risk of impaired lung function due to exposure to higher air pollution. FOXP3 promoter buccal cell methylation may function as a useful biomarker of that benefit.

Effects of cannabis on lung function: a population-based cohort study.

PubMed

Hancox, R J; Poulton, R; Ely, M; Welch, D; Taylor, D R; McLachlan, C R; Greene, J M; Moffitt, T E; Caspi, A; Sears, M R

2010-01-01

The effects of cannabis on lung function remain unclear and may be different from those of tobacco. We compared the associations between use of these substances and lung function in a population-based cohort (n = 1,037). Cannabis and tobacco use were reported at ages 18, 21, 26 and 32 yrs. Spirometry, plethysmography and carbon monoxide transfer factor were measured at 32 yrs. Associations between lung function and exposure to each substance were adjusted for exposure to the other substance. Cumulative cannabis use was associated with higher forced vital capacity, total lung capacity, functional residual capacity and residual volume. Cannabis was also associated with higher airway resistance but not with forced expiratory volume in 1 s, forced expiratory ratio or transfer factor. These findings were similar among those who did not smoke tobacco. In contrast, tobacco use was associated with lower forced expiratory volume in 1 s, lower forced expiratory ratio, lower transfer factor and higher static lung volumes, but not with airway resistance. Cannabis appears to have different effects on lung function from those of tobacco. Cannabis use was associated with higher lung volumes, suggesting hyperinflation and increased large-airways resistance, but there was little evidence for airflow obstruction or impairment of gas transfer.

Global DNA hypomethylation has no impact on lung function or serum inflammatory and fibrosis cytokines in asbestos-exposed population.

PubMed

Yu, Min; Lou, Jianlin; Xia, Hailing; Zhang, Min; Zhang, Yixiao; Chen, Junqiang; Zhang, Xing; Ying, Shibo; Zhu, Lijin; Liu, Lihong; Jia, Guang

2017-04-01

To examine the effect of asbestos exposure on global DNA methylation and determine whether lung function and inflammatory and fibrosis biomarkers are correlated with the methylation state. A total of 26 healthy subjects without asbestos exposure (Group 1), 47 healthy subjects with exposure (Group 2), and 52 subjects with benign asbestos-related disorders (ARDs) (Group 3) participated in this cross-sectional study. Blood global 5-methylcytosine (5mC) and serum TNF-α, collagen IV, CCL5 and CC16 concentrations were analyzed using enzyme-linked immunosorbent assay-like assays. Spirometric maneuvers were performed to assess lung function. Decreased 5mC levels were observed in Groups 2 and 3 compared to Group 1, irrespective of lung function (p < 0.01). There was no significant change in 5mC between Groups 2 and 3. Overall, 5mC was negatively correlated with CCL5 and collagen IV (p < 0.05), but no significant inverse relationship was found between 5mC and CCL5 or collagen IV in each group. Additionally, both 5mC and CC16 were inversely associated with FEV1/FVC% (p = 0.001, adjusted R 2  = 0.145) for non-smokers, and consistently significant inverse relationships were found between CC16 and FEV1/FVC%, independent of asbestos exposure. Asbestos exposure causes global DNA hypomethylation. DNA hypomethylation has no influence on serum biomarkers and lung function in asbestos-exposed population with or without pleural and pulmonary parenchymal abnormalities.

Differential respirable dust related lung function effects between current and former South African coal miners.

PubMed

Naidoo, Rajen N; Robins, Thomas G; Seixas, Noah; Lalloo, Umesh G; Becklake, Margaret

2005-05-01

Dust-related dose-response decrements in lung function among coal miners have been reported in several studies, with varying magnitudes across populations. Few studies have compared differences between current and former coal miners. No studies on dose response relationships with lung function have been conducted in South African coal mines, one of the top three producers of coal internationally. The objectives of this study were (1) to describe the relationship between respirable dust exposure and lung function among current and former South African coal miners and to determine whether differential dust related effects were present between these employment categories; (2) to examine dust related dose response relationships, controlling for potential confounding by smoking and a history of tuberculosis (TB). Six hundred and eighty-four current and 188 ex-miners from three bituminous coal mines in Mpumalanga Province were studied. Interviews assessing work histories, smoking profiles and other risk factors were conducted. Work histories were also obtained from company records. Standardised spirometry was performed by trained technicians. Cumulative respirable dust exposure (CDE) estimates were constructed from company-collected sampling and measurements conducted by the researchers. Regression models examined the associations of CDE with per cent predicted FEV(1) and FVC, controlling for smoking, past history of TB and employment status. A statistically significant decline in FEV(1) of 1.1 and 2.2 ml/mg-year/m(3) was found in representative 40-year-old, 1.7-m tall current and former miners, respectively. Significant differences were found between the highest and medium exposure categories. Ex-miners had a lower mean per cent predicted lung function than current miners for each cumulative exposure category, suggesting a "healthy worker" effect. Past history of TB contributed to 21 and 14% declines in per cent predicted FEV(1) and FVC, respectively. Thus, in this cohort, a dose-related decline in lung function was associated with respirable dust exposure, with a magnitude of effect similar to that seen in other studies and important differences between current and former employees. A "healthy worker" effect may have attenuated the magnitude of this relationship. TB was a significant contributor to lung function loss.

Longitudinal and Cross-sectional Analyses of Lung Function in Toluene Diisocyanate Production Workers.

PubMed

Wang, Mei Lin; Storey, Eileen; Cassidy, Laura D; Doney, Brent; Conner, Patrick R; Collins, James J; Carson, Michael; Molenaar, Don

2017-12-01

The aim of this study was to investigate lung function among toluene diisocyanate (TDI) production workers. One hundred ninety-seven U.S workers performed spirometry from 2006 through 2012. Results were compared within the study cohort and with U.S. population measures. A mixed-effects model assessed factors affecting repeated forced expiratory volume in 1 second (FEV1) measurements. The cohort's mean FEV1 and forced vital capacity (FVC) percent reference values, although greater than 90%, were significantly lower and the prevalence of abnormal spirometry (predominantly restrictive pattern) was significantly higher than in the U.S. Differences in lung function among workers with higher cumulative TDI exposure were in the direction of an exposure effect, but not significant. We found little evidence of an adverse effect of TDI exposure on longitudinal spirometry in these workers. The association between TDI exposure and the increasing prevalence of a restrictive pattern needs further exploration.

Microarray-based analysis of the lung recovery process after stainless-steel welding fume exposure in Sprague-Dawley rats.

PubMed

Oh, Jung-Hwa; Yang, Mi-jin; Yang, Young-Su; Park, Han-Jin; Heo, Sun Hee; Lee, Eun-Hee; Song, Chang-Woo; Yoon, Seokjoo

2009-02-01

Repeated exposure to welding fumes promotes a reversible increase in pulmonary disease risk, but the molecular mechanisms by which welding fumes induce lung injury and how the lung recovers from such insults are unclear. In the present study, pulmonary function and gene-expression profiles in the lung were analyzed by Affymetrix GeneChip microarray after 30 days of consecutive exposure to manual metal arc welding combined with stainless-steel (MMA-SS) welding fumes, and again after 30 days of recovery from MMA-SS fume exposure. In total, 577 genes were identified as being either up-regulated or down-regulated (over twofold changes, p < 0.05) in the lungs of low-dose or high-dose groups. Differentially expressed genes were classified based on a k-means clustering algorithm and biological functions and molecular networks were further analyzed using Ingenuity Pathways Analysis. Among the genes affected by exposure to or recovery from MMA-SS fumes, the transcriptional changes of 13 genes that were highly altered by treatment were confirmed by quantitative real-time PCR. Notably, Mmp12, Cd5l, Ccl7, Cxcl5, and Spp1 related to the immune response were up-regulated only in the exposure group, whereas Trem2, IgG-2a, Igh-1a, and Igh were persistently up-regulated in both the exposure and recovery groups. In addition, several genes that might play a role in the repair process of the lung were up-regulated exclusively in the recovery group. Collectively, these data may help elucidate the molecular mechanism of the recovery process of the lung after welding fume exposure.

Long-term respiratory health effects in textile workers.

PubMed

Lai, Peggy S; Christiani, David C

2013-03-01

Over 60 million people worldwide work in the textile or clothing industry. Recent studies have recognized the contribution of workplace exposures to chronic lung diseases, in particular chronic obstructive pulmonary disease (COPD). Early studies in textile workers have focused on the relationship between hemp or cotton dust exposure and the development of a syndrome termed byssinosis. The purpose of this review is to evaluate the effect of long-term exposure to organic dust in textile workers on chronic respiratory disease in the broader context of disease classifications, such as reversible or irreversible obstructive lung disease (i.e. asthma or COPD), and restrictive lung disease. Cessation of exposure to cotton dust leads to improvement in lung function. Recent animal models have suggested a shift in the lung macrophage:dendritic cell population ratio as a potential mechanistic explanation for persistent inflammation in the lung due to repeated cotton dust-related endotoxin exposure. Other types of textile dust, such as silk, may contribute to COPD in textile workers. Textile dust-related obstructive lung disease has characteristics of both asthma and COPD. Significant progress has been made in the understanding of chronic lung disease due to organic dust exposure in textile workers.

Long term respiratory health effects in textile workers

PubMed Central

Lai, Peggy S.; Christiani, David C.

2013-01-01

Purpose of review Over 60 million people worldwide work in the textile or clothing industry. Recent studies have recognized the contribution of workplace exposures to chronic lung diseases, in particular chronic obstructive pulmonary disease (COPD). Early studies in textile workers have focused on the relationship between hemp or cotton dust exposure and the development of a syndrome termed Byssinosis. The purpose of this review is to evaluate the effect of long term exposure to organic dust in textile workers on chronic respiratory disease in the broader context of disease classifications such as reversible or irreversible obstructive lung disease (i.e. asthma or COPD), and restrictive lung disease. Recent findings Cessation of exposure to cotton dusts leads to improvement in lung function. Recent animal models have suggested a shift in the lung macrophage:dendritic cell population as a potential mechanistic explanation for persistent inflammation in the lung due to repeated cotton-dust related endotoxin exposure. Other types of textile dust, such as silk, may contribute to COPD in textile workers. Summary Textile dust related obstructive lung disease has characteristics of both asthma and COPD. Significant progress has been made in the understanding of chronic lung disease due to organic dust exposure in textile workers. PMID:23361196

Prenatal fine particulate exposure associated with reduced childhood lung function and nasal epithelia GSTP1 hypermethylation: Sex-specific effects.

PubMed

Lee, Alison G; Le Grand, Blake; Hsu, Hsiao-Hsien Leon; Chiu, Yueh-Hsiu Mathilda; Brennan, Kasey J; Bose, Sonali; Rosa, Maria José; Brunst, Kelly J; Kloog, Itai; Wilson, Ander; Schwartz, Joel; Morgan, Wayne; Coull, Brent A; Wright, Robert O; Baccarelli, Andrea A; Wright, Rosalind J

2018-04-27

In utero exposure to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM 2.5 ) has been linked to child lung function. Overlapping evidence suggests that child sex and exposure timing may modify effects and associations may be mediated through glutathione S-transferase P1 (GSTP1) methylation. We prospectively examined associations among prenatal PM 2.5 exposure and child lung function and GSTP1 methylation in an urban pregnancy cohort study. We employed a validated satellite-based spatiotemporally resolved prediction model to estimate daily prenatal PM 2.5 exposure over gestation. We used Baysian distributed lag interaction models (BDLIMs) to identify sensitive windows for prenatal PM 2.5 exposure on child lung function and nasal epithelia GSTP1 methylation at age 7 years, and to examine effect modification by child sex. BDLIMs identified a sensitive window for prenatal PM 2.5 exposure at 35-40 weeks gestation [cumulative effect estimate (CEE) = - 0.10, 95%CI = - 0.19 to - 0.01, per μg/m 3 increase in PM 2.5 ] and at 36-40 weeks (CEE = - 0.12, 95%CI = - 0.20 to - 0.01) on FEV 1 and FVC, respectively, in boys. BDLIMs also identified a sensitive window of exposure at 37-40 weeks gestation between higher prenatal PM 2.5 exposure and increased GSTP1 percent methylation. The association between higher GSTP1 percent methylation and decreased FEV1 was borderline significant in the sample as a whole (β = - 0.37, SE = 0.20, p = 0.06) and in boys in stratified analyses (β = - 0.56, SE = 0.29, p = 0.05). Prenatal PM 2.5 exposure in late pregnancy was associated with impaired early childhood lung function and hypermethylation of GSTPI in DNA isolated from nasal epithelial cells. There was a trend towards higher GSTP1 percent methylation being associated with reduced FEV1. All findings were most evident among boys.

Arsenic Exposure and Impaired Lung Function. Findings from a Large Population-based Prospective Cohort Study

PubMed Central

Parvez, Faruque; Chen, Yu; Yunus, Mahbub; Olopade, Christopher; Segers, Stephanie; Slavkovich, Vesna; Argos, Maria; Hasan, Rabiul; Ahmed, Alauddin; Islam, Tariqul; Akter, Mahmud M.; Graziano, Joseph H.

2013-01-01

Rationale: Exposure to arsenic through drinking water has been linked to respiratory symptoms, obstructive lung diseases, and mortality from respiratory diseases. Limited evidence for the deleterious effects on lung function exists among individuals exposed to a high dose of arsenic. Objectives: To determine the deleterious effects on lung function that exist among individuals exposed to a high dose of arsenic. Methods: In 950 individuals who presented with any respiratory symptom among a population-based cohort of 20,033 adults, we evaluated the association between arsenic exposure, measured by well water and urinary arsenic concentrations measured at baseline, and post-bronchodilator–administered pulmonary function assessed during follow-up. Measurements and Main Results: For every one SD increase in baseline water arsenic exposure, we observed a lower level of FEV1 (−46.5 ml; P < 0.0005) and FVC (−53.1 ml; P < 0.01) in regression models adjusted for age, sex, body mass index, smoking, socioeconomic status, betel nut use, and arsenical skin lesions status. Similar inverse relationships were observed between baseline urinary arsenic and FEV1 (−48.3 ml; P < 0.005) and FVC (−55.2 ml; P < 0.01) in adjusted models. Our analyses also demonstrated a dose-related decrease in lung function with increasing levels of baseline water and urinary arsenic. This association remained significant in never-smokers and individuals without skin lesions, and was stronger in male smokers. Among male smokers and individuals with skin lesions, every one SD increase in water arsenic was related to a significant reduction of FEV1 (−74.4 ml, P < 0.01; and −116.1 ml, P < 0.05) and FVC (−72.8 ml, P = 0.02; and −146.9 ml, P = 0.004), respectively. Conclusions: This large population-based study confirms that arsenic exposure is associated with impaired lung function and the deleterious effect is evident at low- to moderate-dose range. PMID:23848239

Adverse Respiratory Health and Hematological Alterations among Agricultural Workers Occupationally Exposed to Organophosphate Pesticides: A Cross-Sectional Study in North India

PubMed Central

Fareed, Mohd.; Pathak, Manoj Kumar; Bihari, Vipin; Kamal, Ritul; Srivastava, Anup Kumar; Kesavachandran, Chandrasekharan Nair

2013-01-01

Background Non-protective work practices followed by farm workers during spraying of pesticides lead to occupational exposure among them. Objective This study is designed to explore the respiratory health and hematological profile of agricultural workers occupationally exposed to OP pesticides. Materials and Methods A cross sectional study was undertaken among 166 pesticide sprayers working in mango orchards of Lucknow district in North India compared with 77 controls to assess the respiratory illness, lung functions, cholinesterase levels and hematological profile. A questionnaire based survey and clinical examination for respiratory health were conducted among study subjects. Lung function test was conducted among study subjects by using spirometer. Cholinesterase level as biomarker of OP pesticides and hematological profile of study subjects were investigated in the laboratory by following the standard protocols. Results Overall respiratory morbidity observed among exposed subjects was 36.75%. Symptoms for respiratory illness like dry cough, productive cough, wheezing, irritation of throat and blood stained sputum were found to be significantly more (p<0.05) among pesticide sprayers than controls. Lung function parameters viz. PEFR, FEV1, %PEFR predicted, %FEV1 predicted and FEV1/FVC were found to be significantly decreased (p<0.05) among pesticide sprayers as compared to controls. Exposure wise distribution of respiratory illness and lung functions among pesticide sprayers show that the exposure duration significantly elevates (p<0.05) the respiratory problems and significantly decreases (p<0.001) lung functions among pesticide sprayers. Activities of acetylcholinesterase and butyrylcholinesterase were found to be significantly depleted (p<0.001) among pesticide sprayers as compared to controls which show the exposure of OP pesticides among them. The hematological profile viz. RBC, WBC, monocytes, neutrophils, MCV, MCH, MCHC and platelet count were significantly altered (p<0.001) in pesticide sprayers than controls. Conclusion This study shows that the unsafe occupational exposure of OP pesticides causes respiratory illness, decreased lung functions and hematological alterations among pesticide sprayers. PMID:23936093

Adverse respiratory health and hematological alterations among agricultural workers occupationally exposed to organophosphate pesticides: a cross-sectional study in North India.

PubMed

Fareed, Mohd; Pathak, Manoj Kumar; Bihari, Vipin; Kamal, Ritul; Srivastava, Anup Kumar; Kesavachandran, Chandrasekharan Nair

2013-01-01

Non-protective work practices followed by farm workers during spraying of pesticides lead to occupational exposure among them. This study is designed to explore the respiratory health and hematological profile of agricultural workers occupationally exposed to OP pesticides. A cross sectional study was undertaken among 166 pesticide sprayers working in mango orchards of Lucknow district in North India compared with 77 controls to assess the respiratory illness, lung functions, cholinesterase levels and hematological profile. A questionnaire based survey and clinical examination for respiratory health were conducted among study subjects. Lung function test was conducted among study subjects by using spirometer. Cholinesterase level as biomarker of OP pesticides and hematological profile of study subjects were investigated in the laboratory by following the standard protocols. Overall respiratory morbidity observed among exposed subjects was 36.75%. Symptoms for respiratory illness like dry cough, productive cough, wheezing, irritation of throat and blood stained sputum were found to be significantly more (p<0.05) among pesticide sprayers than controls. Lung function parameters viz. PEFR, FEV1, %PEFR predicted, %FEV1 predicted and FEV1/FVC were found to be significantly decreased (p<0.05) among pesticide sprayers as compared to controls. Exposure wise distribution of respiratory illness and lung functions among pesticide sprayers show that the exposure duration significantly elevates (p<0.05) the respiratory problems and significantly decreases (p<0.001) lung functions among pesticide sprayers. Activities of acetylcholinesterase and butyrylcholinesterase were found to be significantly depleted (p<0.001) among pesticide sprayers as compared to controls which show the exposure of OP pesticides among them. The hematological profile viz. RBC, WBC, monocytes, neutrophils, MCV, MCH, MCHC and platelet count were significantly altered (p<0.001) in pesticide sprayers than controls. This study shows that the unsafe occupational exposure of OP pesticides causes respiratory illness, decreased lung functions and hematological alterations among pesticide sprayers.

Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.

PubMed

Whitehead, Gregory S; Grasman, Keith A; Kimmel, Edgar C

2003-02-01

Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the lavage fluid. Increased MIP-2 levels also preceded the maximum neutrophil infiltration. The differences in the time-course and primary site of TNF-alpha, MIP-2, and IFN-gamma expression; and the differences in the temporal relationship between their expression and infiltration of inflammatory cells may have accounted for the differences in lung function between paraquat treated and ACM smoke exposed animals.

Effects on symptoms and lung function in humans experimentally exposed to diesel exhaust.

PubMed Central

Rudell, B; Ledin, M C; Hammarström, U; Stjernberg, N; Lundbäck, B; Sandström, T

1996-01-01

OBJECTIVES: Diesel exhaust is a common air pollutant made up of several gases, hydrocarbons, and particles. An experimental study was carried out which was designed to evaluate if a particle trap on the tail pipe of an idling diesel engine would reduce effects on symptoms and lung function caused by the diesel exhaust, compared with exposure to unfiltered exhaust. METHODS: Twelve healthy non-smoking volunteers (aged 20-37) were investigated in an exposure chamber for one hour during light work on a bicycle ergometer at 75 W. Each subject underwent three separate double blind exposures in a randomised sequence: to air and to diesel exhaust with the particle trap at the tail pipe and to unfiltered diesel exhaust. Symptoms were recorded according to the Borg scale before, every 10 minutes during, and 30 minutes after the exposure. Lung function was measured with a computerised whole body plethysmograph. RESULTS: The ceramic wall flow particle trap reduced the number of particles by 46%, whereas other compounds were relatively constant. It was shown that the most prominent symptoms during exposure to diesel exhaust were irritation of the eyes and nose and an unpleasant smell increasing during exposure. Both airway resistance (R(aw)) and specific airway resistance (SR(aw)) increased significantly during the exposures to diesel exhaust. Despite the 46% reduction in particle numbers by the trap effects on symptoms and lung function were not significantly attenuated. CONCLUSION: Exposure to diesel exhaust caused symptoms and bronchoconstriction which were not significantly reduced by a particle trap. PMID:8943829

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile.

PubMed

Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Balmes, John R; Liaw, Jane; Troncoso, Patricia; Dauphiné, David C; Nardone, Anthony; Smith, Allan H

2016-12-15

Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860μg/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60μg/L; and Arica, with long-term water concentrations ≤10μg/L. Compared to adults never exposed >10μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath=5.56, 90% confidence interval (CI): 2.68-11.5), and decreases in pulmonary function (e.g., 224mL decrease in forced vital capacity in nonsmokers, 90% CI: 97-351mL). Subjects with long-term exposure to arsenic water concentrations near 60μg/L also had increases in some pulmonary symptoms and reduced lung function. Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. Copyright © 2016 Elsevier Inc. All rights reserved.

High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile

PubMed Central

Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Balmes, John R; Liaw, Jane; Troncoso, Patricia; Dauphiné, David C; Nardone, Anthony; Smith, Allan H

2016-01-01

Background Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited. Methods We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 μg/L) from 1958–1970; Iquique, which had long-term arsenic water concentrations near 60 μg/L; and Arica, with long-term water concentrations ≤10 μg/L. Results Compared to adults never exposed >10 μg/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68–11.5), and decreases in pulmonary function (e.g., 224 ml decrease in forced vital capacity in nonsmokers, 90% CI: 97–351 ml). Subjects with long-term exposure to arsenic water concentrations near 60 μg/L also had increases in some pulmonary symptoms and reduced lung function. Conclusions Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that long-term exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. PMID:27725189

Chronic effects on JP-8 jet fuel exposure on the lungs. Final technical report, 1 April 1991-31 March 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

Witten, M.L.

1994-06-02

There are four major findings from the three years of work devoted to the effects of chronic JP-8 jet fuel exposure on the lungs and secondary organs. These findings are the following chronic exposure to JP-8 jet fuel alters pulmonary function and lung structures with an acute response with as little as seven days of low dose, approximately 500 mg/m3, exposure to JP-8 jet fuel; chronic exposure to JP-8 jet fuel increased liver, spleen, and kidney weights compared to controls. Microscopic evaluation of liver sections were normal; however, kidney and spleen had histological changes consistent with organic solvent exposure. Theremore » is a correlation between JP-8 jet fuel exposure-induced decreases in lung Substance P levels and lung neutral endopeptidase levels. Chronic exposure to JP-8 jet fuel caused a decrease in lung Substance P levels with a corresponding increase in lung neutral endopeptidase levels; and, there is a recovery process in the 56 day low dose JP-8 jet fuel-exposed lungs as marked by a return to baseline and longitudinal control 99mTcDTPA values. The 99mTcDTPA data was very consistent with our pathologic findings of very little lung injury in the 56 day low dose JP-8 jet fuel-exposed rats. We speculate that this finding indicates that there is a 'threshold' level of JP-8 jet fuel exposure that the lungs' defense mechanism(s) can tolerate.« less

Focal exposure of limited lung volumes to high-dose irradiation down-regulated organ development-related functions and up-regulated the immune response in mouse pulmonary tissues.

PubMed

Kim, Bu-Yeo; Jin, Hee; Lee, Yoon-Jin; Kang, Ga-Young; Cho, Jaeho; Lee, Yun-Sil

2016-01-27

Despite the emergence of stereotactic body radiotherapy (SBRT) for treatment of medically inoperable early-stage non-small-cell lung cancer patients, the molecular effects of focal exposure of limited lung volumes to high-dose radiation have not been fully characterized. This study was designed to identify molecular changes induced by focal high-dose irradiation using a mouse model of SBRT. Central areas of the mouse left lung were focally-irradiated (3 mm in diameter) with a single high-dose of radiation (90 Gy). Temporal changes in gene expression in the irradiated and non-irradiated neighboring lung regions were analyzed by microarray. For comparison, the long-term effect (12 months) of 20 Gy radiation on a diffuse region of lung was also measured. The majority of genes were down-regulated in the focally-irradiated lung areas at 2 to 3 weeks after irradiation. This pattern of gene expression was clearly different than gene expression in the diffuse region of lungs exposed to low-dose radiation. Ontological and pathway analyses indicated these down-regulated genes were mainly associated with organ development. Although the number was small, genes that were up-regulated after focal irradiation were associated with immune-related functions. The temporal patterns of gene expression and the associated biological functions were also similar in non-irradiated neighboring lung regions, although statistical significance was greatly reduced when compared with those from focally-irradiated areas of the lung. From network analysis of temporally regulated genes, we identified inter-related modules associated with diverse functions, including organ development and the immune response, in both the focally-irradiated regions and non-irradiated neighboring lung regions. Focal exposure of lung tissue to high-dose radiation induced expression of genes associated with organ development and the immune response. This pattern of gene expression was also observed in non-irradiated neighboring areas of lung tissue, indicating a global lung response to focal high-dose irradiation.

Occupational airborne exposure in relation to Chronic Obstructive Pulmonary Disease (COPD) and lung function in individuals without childhood wheezing illness: A 50-year cohort study.

PubMed

Tagiyeva, Nara; Sadhra, Steven; Mohammed, Nuredin; Fielding, Shona; Devereux, Graham; Teo, Ed; Ayres, Jon; Graham Douglas, J

2017-02-01

Evidence from longitudinal population-based studies relating occupational exposure to the full range of different forms of airborne pollutants and lung function and airway obstruction is limited. To relate self-reported COPD and lung function impairment to occupational exposure to different forms of airborne chemical pollutants in individuals who did not have childhood wheeze. A prospective cohort study was randomly selected in 1964 at age 10-15 years and followed up in 1989, 1995, 2001 and 2014 (aged 58-64) by spirometry and respiratory questionnaire. Occupational histories were recorded in 2014 and occupational exposures assigned using an airborne chemical job exposure matrix. The risk of COPD and lung function impairment was analyzed in subjects, who did not have childhood wheeze, using logistic and linear regression and linear mixed effects models. 237 subjects without childhood wheeze (mean age 60.6 years, 47% male) were analyzed. There was no association between any respiratory outcomes and exposure to gases, fibers, mists or mineral dusts and no consistent associations with exposure to fumes. Reduced FEV 1 was associated with longer duration (years) of exposure to any of the six main pollutant forms - vapors, gases, dusts, fumes, fibers and mists (VGDFFiM) with evidence of a dose-response relationship (p-trend=0.004). Exposure to biological dusts was associated with self-reported COPD and FEV 1

Exposure to household air pollution from wood combustion and association with respiratory symptoms and lung function in nonsmoking women: results from the RESPIRE trial, Guatemala.

PubMed

Pope, Daniel; Diaz, Esperanza; Smith-Sivertsen, Tone; Lie, Rolv T; Bakke, Per; Balmes, John R; Smith, Kirk R; Bruce, Nigel G

2015-04-01

With 40% of the world's population relying on solid fuel, household air pollution (HAP) represents a major preventable risk factor for COPD (chronic obstructive pulmonary disease). Meta-analyses have confirmed this relationship; however, constituent studies are observational, with virtually none measuring exposure directly. We estimated associations between HAP exposure and respiratory symptoms and lung function in young, nonsmoking women in rural Guatemala, using measured carbon monoxide (CO) concentrations in exhaled breath and personal air to assess exposure. The Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) Guatemala study was a trial comparing respiratory outcomes among 504 women using improved chimney stoves versus traditional cookstoves. The present analysis included 456 women with data from postintervention surveys including interviews at 6, 12, and 18 months (respiratory symptoms) and spirometry and CO (ppm) in exhaled breath measurements. Personal CO was measured using passive diffusion tubes at variable times during the study. Associations between CO concentrations and respiratory health were estimated using random intercept regression models. Respiratory symptoms (cough, phlegm, wheeze, or chest tightness) during the previous 6 months were positively associated with breath CO measured at the same time of symptom reporting and with average personal CO concentrations during the follow-up period. CO in exhaled breath at the same time as spirometry was associated with lower lung function [average reduction in FEV1 (forced expiratory volume in 1 sec) for a 10% increase in CO was 3.33 mL (95% CI: -0.86, -5.81)]. Lung function measures were not significantly associated with average postintervention personal CO concentrations. Our results provide further support for the effects of HAP exposures on airway inflammation. Further longitudinal research modeling continuous exposure to particulate matter against lung function will help us understand more fully the impact of HAP on COPD.

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olivas-Calderón, Edgar, E-mail: edgar_olivascalderon@hotmail.com; School of Medicine, University Juarez of Durango, Gomez Palacio, Durango; Recio-Vega, Rogelio, E-mail: rrecio@yahoo.com

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero has been associated with an increase in respiratory symptoms or diseases in the adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that the exposure to arsenic during early childhood or in utero in children was associated with impairment in the lung function and suggested that this adverse effect could be due to a chronic inflammation response to the metalloid. Therefore, we designed this cross-sectional study in a cohort of children associating lung inflammatorymore » biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their arsenic urinary levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the soluble receptor for advanced glycation end products' (sRAGE) sputum level was significantly lower and matrix metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsonic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/tissue inhibitor of metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. Arsenic-induced alterations in inflammatory biomarkers may contribute to the development of restrictive lung diseases. - Highlights: • First study in children evaluating lung inflammatory biomarkers and As levels • In 275 children chronically exposed to As, 3 biomarkers were measured. • Negative associations were found between DMA, %MMA and %DMA with sRAGE. • Positive associations were found between %DMA with MMP-9 and with the MMP-9/TIMP-1 ratio. • Chronic arsenic exposure-induced alterations in lung inflammatory biomarkers in children.« less

Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leng, Shuguang; Thomas, Cynthia L.; Snider, Amanda M.

Background: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. Objectives: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas. Methods: Genetic associations were assessed in a case–control study of former uranium miners (242 cases and 336 controls). A replication study was performed usingmore » data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches. Results: We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments. Conclusions: An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. Lastly, the associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion« less

Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners

DOE PAGES

Leng, Shuguang; Thomas, Cynthia L.; Snider, Amanda M.; ...

2015-09-15

Background: High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development. Objectives: We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas. Methods: Genetic associations were assessed in a case–control study of former uranium miners (242 cases and 336 controls). A replication study was performed usingmore » data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches. Results: We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments. Conclusions: An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. Lastly, the associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion« less

Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment.

PubMed

Winkler-Heil, R; Hussain, M; Hofmann, W

2015-05-01

Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM(-1). If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas.

LONG TERM EFFECTS OF PRENATAL AND POSTNATAL AIRBORNE PAH EXPOSURE ON VENTILATORY LUNG FUNCTION OF NON-ASTHMATIC PREADOLESCENT CHILDREN. PROSPECTIVE BIRTH COHORT STUDY IN KRAKOW

PubMed Central

Jedrychowski, Wieslaw A.; Perera, Frederica P.; Maugeri, Umberto; Majewska, Renata; Mroz, Elzbieta; Flak, Elzbieta; Camman, David; Sowa, Agata; Jacek, Ryszard

2014-01-01

The main goal of the study was to test the hypothesis that prenatal and postnatal exposure to polycyclic aromatic hydrocarbons (PAH) is associated with depressed lung function in non-asthmatic children. The study sample comprises 195 non-asthmatic children of non-smoking mothers, among whom the prenatal PAH exposure was assessed by personal air monitoring in pregnancy. At the age of 3, residential air monitoring was carried out to evaluate the residential PAH exposure indoors and outdoors. At the age of 5 to 8, children were given allergic skin tests for indoor allergens; and between 5–9 years lung function testing (FVC, FEV05, FEV1 and FEF25–75) was performed. The effects of prenatal PAH exposure on lung function tests repeated over the follow-up were adjusted in the General Estimated Equation (GEE) model for the relevant covariates. No association between FVC with prenatal PAH exposure was found; however for the FEV1 deficit associated with higher prenatal PAH exposure (above 37ng/m3) amounted to 53 mL (p = 0.050) and the deficit of FEF25–75 reached 164 mL (p=0.013). The corresponding deficits related to postnatal residential indoor PAH level (above 42 ng/m3) were 59 mL of FEV1 (p=0.028) and 140 mL of FEF25–75 (p=0.031). At the higher residential outdoor PAH level (above 90 ng/m3) slightly greater deficit of FEV1 (71mL, p = 0.009) was observed. The results of the study suggest that transplacental exposure to PAH compromises the normal developmental process of respiratory airways and that this effect is compounded by postnatal PAH exposure. PMID:25300014

Respiratory symptoms and lung functional impairments associated with occupational exposure to asphalt fumes.

PubMed

Neghab, M; Zare Derisi, F; Hassanzadeh, J

2015-04-01

Controversy exists as to the potential of asphalt fumes to induce respiratory symptoms and lung functional impairments. To examine the respiratory effects, if any, of occupational inhalation exposure to asphalt fumes. In this cross-sectional study, 74 asphalt workers and 110 unexposed employees were investigated. The prevalence of respiratory symptoms among subjects was investigated by a standard questionnaire. Additionally, the parameters of pulmonary function were measured both, prior to exposure and at the end of work-shift. Furthermore, to assess the extent to which workers were exposed to asphalt fumes, total particulate and the benzene-soluble fraction were measured in different worksites. The mean levels of exposure to total particulate and benzene-soluble fraction in asphalt fumes were estimated to be 0.9 (SD 0.2) and 0.3 (SD 0.1) mg/m^3, respectively. Mean values of FEV1, both prior to the exposure (89.58% [SD 18.69%] predicted value) and at the end of shift (85.38% [SD 19.4%]), were significantly (p<0.05) smaller than those of the comparison subjects (93.88% [SD 13.93%]). Similarly, pre-shift (87.05 [SD 8.57]) and postexposure (89.95 [SD 6.85]) FEV1/FVC ratio were both significantly (p<0.01) lower than those of the unexposed employees (107.56 [SD 9.64]). Moreover, the prevalence of respiratory symptoms such as cough and wheezing in exposed employees were 41% and 42%, respectively. The corresponding values for comparison subjects were 10.0% and 3.6%, respectively (p<0.001). The pattern of changes in parameters of lung function in asphalt workers was consistent with that of chronic obstructive lung disease. Significant decrements in the parameters of pulmonary function as well as, a significant increase in the prevalence of respiratory symptoms in asphalt paving workers compared to their unexposed counterparts provided evidence in favor of a significant association between exposure to asphalt fumes and lung function impairments.

Comparison of the behavior of stainless and mild steel manual metal arc welding fumes in rat lung.

PubMed

Kalliomäki, P L; Junttila, M L; Kalliomäki, K K; Lakomaa, E L; Kivelä, R

1983-04-01

The lung retention and clearance of manual metal arc (MMA) stainless steel and mild steel welding fumes were determined in the rat. The exposure simulated the actual welding situation. The duration of exposure in the "nose-only" exposure chamber was 1 h/workday for one, two, three, or four weeks in the retention study and for four weeks in the clearance study. The concentration of exogenous iron was determined by the magnetic measuring method. Instrumental neutron activation analysis was applied to determine the concentration of total iron, chromium, and nickel in the lungs. The results indicated that the lung retention and clearance patterns for the two types of welding fumes were different. A linear relationship was observed between the amount of stainless steel MMA welding fume retained in the lungs and the duration of exposure, whereas the retention of mild steel MMA welding fume in the lung was saturated as a function of the cumulative exposure time rates. The maximum amount of lung-retained contaminants was 880 micrograms for stainless steel MMA welding fume and 220 micrograms for mild steel MMA fume.

Indoor exposure to formaldehyde and relation to asthma ...

EPA Pesticide Factsheets

Formaldehyde exposure is associated with asthma-like symptoms in occupational settings, but does exposure at lower concentrations in residential settings contribute to the current high burden of this respiratory disease? We conducted a systematic review and meta-analysis of asthma and lung function in humans, focusing on effects from long-term exposures. Our literature search through August 2013 identified 20 studies of asthma or asthma symptoms and 11 studies of lung function in PubMed and Web of Science meeting our inclusion criteria. For the asthma analysis, significant heterogeneity was present in the entire set of studies (p 0.051 mg/m3) and high occupational (> 0.1 mg/m3). Risk ratios (95% confidence interval) for these three categories, respectively, were 0.99 (0.93, 1.06), 1.5 (1.04, 2.1) and 6.3 (3.8, 10.6). The studies of lung function reported results as percent of predicted accounting for gender, age and height. These were occupational exposures with time-weighted formaldehyde concentrations of 0.1 – 1.5 mg/m3, primarily involving woodworking or chemical production. Overall, mean differences in lung function (95% confidence interval) between exposed and referent groups were -4.48 percent (-6.88, -2.09) for forced expiratory volume 1 second (FEV1), -4.08 percent (-6.33, -1.82) for forced vital capacity (FVC) and -7.29 percent (-11.

Lung inflammation biomarkers and lung function in children chronically exposed to arsenic

PubMed Central

Olivas-Calderón, Edgar; Recio-Vega, Rogelio; Gandolfi, A. Jay; Lantz, R. Clark; González-Cortes, Tania; Alba, Cesar Gonzalez-De; Froines, John R.; Espinosa-Fematt, Jorge A.

2016-01-01

Evidence suggests that exposure to arsenic in drinking water during early childhood or in utero is associated with an increase in respiratory symptoms and diseases in adulthood, however only a few studies have been carried out during those sensitive windows of exposure. Recently our group demonstrated that exposure to arsenic during early childhood or in utero was associated with impairment in the lung function in children and suggested that this adverse effect could be due to a chronic inflammatory response to the metalloid. Therefore, a cross-sectional study was designed in a cohort of children associating lung inflammatory biomarkers and lung function with urinary As levels. A total of 275 healthy children were partitioned into four study groups according with their As levels. Inflammation biomarkers were measured in sputum by ELISA and the lung function was evaluated by spirometry. Fifty eight percent of the studied children were found to have a restrictive spirometric pattern. In the two highest exposed groups, the Soluble Receptor for Advanced Glycation Endproducts (sRAGE) sputum level was significantly lower and Matrix Metalloproteinase-9 (MMP-9) concentration was higher. When the biomarkers were correlated to the urinary arsenic species, negative associations were found between dimethylarsinic (DMA), monomethylarsenic percentage (%MMA) and dimethylarsinic percentage (%DMA) with sRAGE and positive associations between %DMA with MMP-9 and with the MMP-9/Tissue Inhibitor of Metalloproteinase (TIMP-1) ratio. In conclusion, chronic arsenic exposure of children negatively correlates with sRAGE, and positively correlated with MMP-9 and MMP-9/TIMP-1 levels, and increases the frequency of an abnormal spirometric pattern. PMID:26048584

Diesel engine exhaust and lung cancer mortality: time-related factors in exposure and risk.

PubMed

Moolgavkar, Suresh H; Chang, Ellen T; Luebeck, Georg; Lau, Edmund C; Watson, Heather N; Crump, Kenny S; Boffetta, Paolo; McClellan, Roger

2015-04-01

To develop a quantitative exposure-response relationship between concentrations and durations of inhaled diesel engine exhaust (DEE) and increases in lung cancer risks, we examined the role of temporal factors in modifying the estimated effects of exposure to DEE on lung cancer mortality and characterized risk by mine type in the Diesel Exhaust in Miners Study (DEMS) cohort, which followed 12,315 workers through December 1997. We analyzed the data using parametric functions based on concepts of multistage carcinogenesis to directly estimate the hazard functions associated with estimated exposure to a surrogate marker of DEE, respirable elemental carbon (REC). The REC-associated risk of lung cancer mortality in DEMS is driven by increased risk in only one of four mine types (limestone), with statistically significant heterogeneity by mine type and no significant exposure-response relationship after removal of the limestone mine workers. Temporal factors, such as duration of exposure, play an important role in determining the risk of lung cancer mortality following exposure to REC, and the relative risk declines after exposure to REC stops. There is evidence of effect modification of risk by attained age. The modifying impact of temporal factors and effect modification by age should be addressed in any quantitative risk assessment (QRA) of DEE. Until there is a better understanding of why the risk appears to be confined to a single mine type, data from DEMS cannot reliably be used for QRA. © 2015 Society for Risk Analysis.

Ozone Exposure, Cardiopulmonary Health, and Obesity: A Substantive Review.

PubMed

Koman, Patricia D; Mancuso, Peter

2017-07-17

From 1999-2014, obesity prevalence increased among adults and youth. Obese individuals may be uniquely susceptible to the proinflammatory effects of ozone because obese humans and animals have been shown to experience a greater decline in lung function than normal-weight subjects. Obesity is independently associated with limitations in lung mechanics with increased ozone dose. However, few epidemiologic studies have examined the interaction between excess weight and ozone exposure among adults. Using PubMed keyword searches and reference lists, we reviewed epidemiologic evidence to identify potential response-modifying factors and determine if obese or overweight adults are at increased risk of ozone-related health effects. We initially identified 170 studies, of which seven studies met the criteria of examining the interaction of excess weight and ozone exposure on cardiopulmonary outcomes in adults, including four short-term ozone exposure studies in controlled laboratory settings and three community epidemiologic studies. In the studies identified, obesity was associated with decreased lung function and increased inflammatory mediators. Results were inconclusive about the effect modification when data were stratified by sex. Obese and overweight populations should be considered as candidate at-risk groups for epidemiologic studies of cardiopulmonary health related to air pollution exposures. Air pollution is a modifiable risk factor that may decrease lung function among obese individuals with implications for environmental and occupational health policy.

Consecutive Food and Respiratory Allergies Amplify Systemic and Gut but Not Lung Outcomes in Mice.

PubMed

Bouchaud, Gregory; Gourbeyre, Paxcal; Bihouée, Tiphaine; Aubert, Phillippe; Lair, David; Cheminant, Marie-Aude; Denery-Papini, Sandra; Neunlist, Michel; Magnan, Antoine; Bodinier, Marie

2015-07-22

Epidemiological data suggest a link between food allergies and the subsequent development of asthma. Although this progression may result from the additional effects of exposure to multiple allergens, whether both allergies amplify each other's effects remains unknown. This study investigated whether oral exposure to food allergens influences the outcomes of subsequent respiratory exposure to an asthma-inducing allergen. Mice were sensitized and orally challenged with wheat (FA) and then exposed to house dust mite (HDM) extract (RA). Immunoglobulin (Ig), histamine, and cytokine levels were assayed by ELISA. Intestinal and lung physiology was assessed. Ig levels, histamine release, and cytokine secretion were higher after exposure to both allergens than after separate exposure to each. Intestinal permeability was higher, although airway hyper-responsiveness and lung inflammation remained unchanged. Exposure to food and respiratory allergens amplifies systemic and gut allergy-related immune responses without any additional effect on lung function and inflammation.

Ozone personal exposures and health effects for selected groups residing in the Fraser Valley

NASA Astrophysics Data System (ADS)

Brauer, Michael; Brook, Jeffrey R.

Due to concern regarding poor ambient air quality in the Fraser Valley, a series of exposure and health effects assessments were performed to evaluate the impact of summer photochemical air pollution. In 1992 and 1993, three groups of individuals were selected for personal monitoring of ozone exposure, based on prior expectations of their activity patterns. The first group spent a majority of the work day indoors or commuting, the second group spent more time outdoors and the third group spent the entire personal monitoring period outdoors. Time-activity data were collected for the first two groups and differences in personal ozone exposures were found to be associated with the fraction of time a person spent outdoors. Similarly, differences among groups in the mean ozone exposure were associated with time spent outdoors. These results and other exposure information were used to design a study of the health impacts of summer ambient air pollution that was conducted during the time period of the Pacific'93 field campaign. Aerosol acidity levels in the Fraser Valley were observed to be very low in 1992 so the health study focused on the effects of ozone exposure. The subjects were adult farm workers (26 male, 32 female; mean age 44.4, range 10-69) who spent the entire working day outdoors (a subset of group 3 above). Lung function measurements were made twice daily on each subject, once before and once after their work shift, from 23 June-26 August 1993. Ambient O 3 concentrations were measured continuously at several nearby locations. In a regression model including individual lung function level, date, temperature and daily maximum O 3, a statistically significant ( p < 0.001) negative association was observed between ozone and lung function. This association between ozone and reduced lung function was still apparent the following day, suggesting a persistent ozone effect. These results indicate that exposure to ambient O 3 concentrations below either the U.S. NAAQS (120 ppb) or the Canadian Air Quality Objective (82 ppb) may have an adverse effect on the lung function of people engaged in outdoor work for several hours a day.

Effects of copper nanoparticle exposure on host defense in a murine pulmonary infection model

PubMed Central

2011-01-01

Background Human exposure to nanoparticles (NPs) and environmental bacteria can occur simultaneously. NPs induce inflammatory responses and oxidative stress but may also have immune-suppressive effects, impairing macrophage function and altering epithelial barrier functions. The purpose of this study was to assess the potential pulmonary effects of inhalation and instillation exposure to copper (Cu) NPs using a model of lung inflammation and host defense. Methods We used Klebsiella pneumoniae (K.p.) in a murine lung infection model to determine if pulmonary bacterial clearance is enhanced or impaired by Cu NP exposure. Two different exposure modes were tested: sub-acute inhalation (4 hr/day, 5 d/week for 2 weeks, 3.5 mg/m3) and intratracheal instillation (24 hr post-exposure, 3, 35, and 100 μg/mouse). Pulmonary responses were evaluated by lung histopathology plus measurement of differential cell counts, total protein, lactate dehydrogenase (LDH) activity, and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid. Results Cu NP exposure induced inflammatory responses with increased recruitment of total cells and neutrophils to the lungs as well as increased total protein and LDH activity in BAL fluid. Both inhalation and instillation exposure to Cu NPs significantly decreased the pulmonary clearance of K.p.-exposed mice measured 24 hr after bacterial infection following Cu NP exposure versus sham-exposed mice also challenged with K.p (1.4 × 105 bacteria/mouse). Conclusions Cu NP exposure impaired host defense against bacterial lung infections and induced a dose-dependent decrease in bacterial clearance in which even our lowest dose demonstrated significantly lower clearance than observed in sham-exposed mice. Thus, exposure to Cu NPs may increase the risk of pulmonary infection. PMID:21943386

Respiratory Effects of Fine and Ultrafine Particles from Indoor Sources—A Randomized Sham-Controlled Exposure Study of Healthy Volunteers

PubMed Central

Soppa, Vanessa J.; Schins, Roel P. F.; Hennig, Frauke; Hellack, Bryan; Quass, Ulrich; Kaminski, Heinz; Kuhlbusch, Thomas A. J.; Hoffmann, Barbara; Weinmayr, Gudrun

2014-01-01

Particulate air pollution is linked to impaired respiratory health. We analyzed particle emissions from common indoor sources (candles burning (CB), toasting bread (TB), frying sausages (FS)) and lung function in 55 healthy volunteers (mean age 33.0 years) in a randomized cross-over controlled exposure study. Lung-deposited particle surface area concentration (PSC), size-specific particle number concentration (PNC) up to 10 µm, and particle mass concentration (PMC) of PM1, PM2.5 and PM10 were determined during exposure (2 h). FEV1, FVC and MEF25%–75% was measured before, 4 h and 24 h after exposure. Wilcoxon-rank sum tests (comparing exposure scenarios) and mixed linear regression using particle concentrations and adjusting for personal characteristics, travel time and transportation means before exposure sessions were performed. While no effect was seen comparing the exposure scenarios and in the unadjusted model, inverse associations were found for PMC from CB and FS in relation to FEV1 and MEF25%–75%. with a change in 10 µg/m3 in PM2.5 from CB being associated with a change in FEV1 of −19 mL (95%-confidence interval:−43; 5) after 4 h. PMC from TB and PNC of UFP were not associated with lung function changes, but PSC from CB was. Elevated indoor fine particles from certain sources may be associated with small decreases in lung function in healthy adults. PMID:25000149

Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis.

PubMed

Adam, Martin; Schikowski, Tamara; Carsin, Anne Elie; Cai, Yutong; Jacquemin, Benedicte; Sanchez, Margaux; Vierkötter, Andrea; Marcon, Alessandro; Keidel, Dirk; Sugiri, Dorothee; Al Kanani, Zaina; Nadif, Rachel; Siroux, Valérie; Hardy, Rebecca; Kuh, Diana; Rochat, Thierry; Bridevaux, Pierre-Olivier; Eeftens, Marloes; Tsai, Ming-Yi; Villani, Simona; Phuleria, Harish Chandra; Birk, Matthias; Cyrys, Josef; Cirach, Marta; de Nazelle, Audrey; Nieuwenhuijsen, Mark J; Forsberg, Bertil; de Hoogh, Kees; Declerq, Christophe; Bono, Roberto; Piccioni, Pavilio; Quass, Ulrich; Heinrich, Joachim; Jarvis, Deborah; Pin, Isabelle; Beelen, Rob; Hoek, Gerard; Brunekreef, Bert; Schindler, Christian; Sunyer, Jordi; Krämer, Ursula; Kauffmann, Francine; Hansell, Anna L; Künzli, Nino; Probst-Hensch, Nicole

2015-01-01

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO₂, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m(-3) increase in NO₂ exposure was associated with lower levels of FEV₁ (-14.0 mL, 95% CI -25.8 to -2.1) and FVC (-14.9 mL, 95% CI -28.7 to -1.1). An increase of 10 μg·m(-3) in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV₁ (-44.6 mL, 95% CI -85.4 to -3.8) and FVC (-59.0 mL, 95% CI -112.3 to -5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe. Copyright ©ERS 2015.

Cyclist route choice, traffic-related air pollution, and lung function: a scripted exposure study

PubMed Central

2013-01-01

Background A travel mode shift to active transportation such as bicycling would help reduce traffic volume and related air pollution emissions as well as promote increased physical activity level. Cyclists, however, are at risk for exposure to vehicle-related air pollutants due to their proximity to vehicle traffic and elevated respiratory rates. To promote safe bicycle commuting, the City of Berkeley, California, has designated a network of residential streets as “Bicycle Boulevards.” We hypothesized that cyclist exposure to air pollution would be lower on these Bicycle Boulevards when compared to busier roads and this elevated exposure may result in reduced lung function. Methods We recruited 15 healthy adults to cycle on two routes – a low-traffic Bicycle Boulevard route and a high-traffic route. Each participant cycled on the low-traffic route once and the high-traffic route once. We mounted pollutant monitors and a global positioning system (GPS) on the bicycles. The monitors were all synced to GPS time so pollutant measurements could be spatially plotted. We measured lung function using spirometry before and after each bike ride. Results We found that fine and ultrafine particulate matter, carbon monoxide, and black carbon were all elevated on the high-traffic route compared to the low-traffic route. There were no corresponding changes in the lung function of healthy non-asthmatic study subjects. We also found that wind-speed affected pollution concentrations. Conclusions These results suggest that by selecting low-traffic Bicycle Boulevards instead of heavily trafficked roads, cyclists can reduce their exposure to vehicle-related air pollution. The lung function results indicate that elevated pollutant exposure may not have acute negative effects on healthy cyclists, but further research is necessary to determine long-term effects on a more diverse population. This study and broader field of research have the potential to encourage policy-makers and city planners to expand infrastructure to promote safe and healthy bicycle commuting. PMID:23391029

Cyclist route choice, traffic-related air pollution, and lung function: a scripted exposure study.

PubMed

Jarjour, Sarah; Jerrett, Michael; Westerdahl, Dane; de Nazelle, Audrey; Hanning, Cooper; Daly, Laura; Lipsitt, Jonah; Balmes, John

2013-02-07

A travel mode shift to active transportation such as bicycling would help reduce traffic volume and related air pollution emissions as well as promote increased physical activity level. Cyclists, however, are at risk for exposure to vehicle-related air pollutants due to their proximity to vehicle traffic and elevated respiratory rates. To promote safe bicycle commuting, the City of Berkeley, California, has designated a network of residential streets as "Bicycle Boulevards." We hypothesized that cyclist exposure to air pollution would be lower on these Bicycle Boulevards when compared to busier roads and this elevated exposure may result in reduced lung function. We recruited 15 healthy adults to cycle on two routes - a low-traffic Bicycle Boulevard route and a high-traffic route. Each participant cycled on the low-traffic route once and the high-traffic route once. We mounted pollutant monitors and a global positioning system (GPS) on the bicycles. The monitors were all synced to GPS time so pollutant measurements could be spatially plotted. We measured lung function using spirometry before and after each bike ride. We found that fine and ultrafine particulate matter, carbon monoxide, and black carbon were all elevated on the high-traffic route compared to the low-traffic route. There were no corresponding changes in the lung function of healthy non-asthmatic study subjects. We also found that wind-speed affected pollution concentrations. These results suggest that by selecting low-traffic Bicycle Boulevards instead of heavily trafficked roads, cyclists can reduce their exposure to vehicle-related air pollution. The lung function results indicate that elevated pollutant exposure may not have acute negative effects on healthy cyclists, but further research is necessary to determine long-term effects on a more diverse population. This study and broader field of research have the potential to encourage policy-makers and city planners to expand infrastructure to promote safe and healthy bicycle commuting.

DO CHILDREN BENEFIT FROM INCREASING CIGARETTE TAXES? ACCOUNTING FOR THE ENDOGENEITY OF LUNG HEALTH AND ENVIRONMENTAL TOBACCO SMOKE EXPOSURE

EPA Science Inventory

My research investigates the relationship between environmental tobacco smoke (ETS) exposure and lung function in children. I use detailed individual health data from the Third National Health and Nutrition Survey (NHANES III) to measure the effect of environmental tobacco smoke ...

Diesel exhaust particle promotes tumor lung metastasis via the induction of BLT1-mediated neutrophilic lung inflammation.

PubMed

Li, Wenjing; Liu, Ting; Xiong, Yingluo; Lv, Jiaoyan; Cui, Xinyi; He, Rui

2018-06-05

BLT1, the primary functional receptor of Leukotriene B4 (LTB4), is involved in tissue inflammation by mediating leukocyte recruitment, and recently LTB4-dependent inflammation was reported to promote lung tumor growth. Exposure to diesel exhaust particle (DEP), the major component of particulate matter 2.5 (PM 2.5 ), can elicit lung inflammation, which may increase the risk of lung cancer. However, it remains unknown about the critical factors mediating DEP-induced lung inflammation and the subsequent effect on tumor metastasis. In this study, we found that DEP exposure led to acute lung inflammation, characterized by abundant infiltration of neutrophils and elevated lung levels in LTB4, as well as several pro-inflammatory cytokines and chemokines, including IL-1β, IL-6, TNF-α, CXCL1/2. Furthermore, DEP exposure promoted lung metastasis of 3LL and 4T1 cells. BLT1 blockade by its specific antagonist U75302 significantly inhibited neutrophilic lung inflammation following DEP exposure. Importantly, BLT1 blockade before the onset of inflammation significantly reduced DEP-enhanced lung metastasis, which was associated with greatly decreased infiltrating neutrophils in lungs. Interestingly, BLT1 blockade after the occurrence of lung metastases had no effect on the magnitude of lung metastasis, suggesting that inhibition of BLT1-mediated lung inflammation was insufficient to suppress established metastatic tumor. Administration of BLT2 inhibitor LY255283 fails to inhibit DEP-induced lung inflammation and tumor metastasis. Collectively, our results demonstrate that DEP exposure causes BLT1-mediated lung neutrophilic inflammation, which is critical for tumor lung metastasis, and suggest that interruption of the LTB4-BLT1 axis could be useful for preventing PM 2.5 -induced inflammation and subsequent susceptible to lung metastasis. Copyright © 2018 Elsevier Ltd. All rights reserved.

In utero and postnatal exposure to arsenic alters pulmonary structure and function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lantz, R. Clark; Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ 85721; BIO5 Institute, University of Arizona, Tucson, AZ 85721

2009-02-15

In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airwaymore » reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 {mu}m in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.« less

Air Pollution and Lung Function in Dutch Children: A Comparison of Exposure Estimates and Associations Based on Land Use Regression and Dispersion Exposure Modeling Approaches

PubMed Central

Gehring, Ulrike; Hoek, Gerard; Keuken, Menno; Jonkers, Sander; Beelen, Rob; Eeftens, Marloes; Postma, Dirkje S.; Brunekreef, Bert

2015-01-01

Background There is limited knowledge about the extent to which estimates of air pollution effects on health are affected by the choice for a specific exposure model. Objectives We aimed to evaluate the correlation between long-term air pollution exposure estimates using two commonly used exposure modeling techniques [dispersion and land use regression (LUR) models] and, in addition, to compare the estimates of the association between long-term exposure to air pollution and lung function in children using these exposure modeling techniques. Methods We used data of 1,058 participants of a Dutch birth cohort study with measured forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) measurements at 8 years of age. For each child, annual average outdoor air pollution exposure [nitrogen dioxide (NO2), mass concentration of particulate matter with diameters ≤ 2.5 and ≤ 10 μm (PM2.5, PM10), and PM2.5 soot] was estimated for the current addresses of the participants by a dispersion and a LUR model. Associations between exposures to air pollution and lung function parameters were estimated using linear regression analysis with confounder adjustment. Results Correlations between LUR- and dispersion-modeled pollution concentrations were high for NO2, PM2.5, and PM2.5 soot (R = 0.86–0.90) but low for PM10 (R = 0.57). Associations with lung function were similar for air pollutant exposures estimated using LUR and dispersion modeling, except for associations of PM2.5 with FEV1 and FVC, which were stronger but less precise for exposures based on LUR compared with dispersion model. Conclusions Predictions from LUR and dispersion models correlated very well for PM2.5, NO2, and PM2.5 soot but not for PM10. Health effect estimates did not depend on the type of model used to estimate exposure in a population of Dutch children. Citation Wang M, Gehring U, Hoek G, Keuken M, Jonkers S, Beelen R, Eeftens M, Postma DS, Brunekreef B. 2015. Air pollution and lung function in Dutch children: a comparison of exposure estimates and associations based on land use regression and dispersion exposure modeling approaches. Environ Health Perspect 123:847–851; http://dx.doi.org/10.1289/ehp.1408541 PMID:25839747

Early Changes in Clinical, Functional, and Laboratory Biomarkers in Workers at Risk of Indium Lung Disease

PubMed Central

Virji, M. Abbas; Trapnell, Bruce C.; Carey, Brenna; Healey, Terrance; Kreiss, Kathleen

2014-01-01

Rationale: Occupational exposure to indium compounds, including indium–tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood. Objectives: To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities. Methods: Among indium–tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models. Measurements and Main Results: Eighty-seven (93%) of 94 indium–tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 μg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥ 1.0 μg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 μg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures. Conclusions: In indium–tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung disease. PMID:25295756

Decline in lung function related to exposure and selection processes among workers in the grain processing and animal feed industry.

PubMed

Post, W; Heederik, D; Houba, R

1998-05-01

To follow up workers in the grain processing and animal feed industry five years after an initial survey, and to monitor exposures to organic dust and endotoxin and changes in prevalence of respiratory symptoms and lung function. Outcome measures in the present survey were decline in lung function over five years, rapid annual decline in forced expiratory volume in one second (FEV1) above 90 ml.s-1, and loss to follow up. Among 140 workers included in the longitudinal analysis, annual decline in FEV1 and maximal mid-expiratory flow (MMEF) were significantly related to occupational exposure to dust and endotoxin in the grain processing and animal feed industry. Assuming a cumulative exposure over a working life of 40 years with an exposure of 5 mg.m-3, the estimated effect on the FEV1 would be a decline of 157 ml.s-1 (95% CI 13 to 300)--that is, about 4% of the group mean FEV1 and 473 ml.s-1 (95% CI 127 to 800) of the MMEF (about 12%). Workers with a dust exposure > 4 mg.m-3 or endotoxin concentrations > 20 ng.m-3 at the 1986-8 survey had significantly higher risk of rapid decline in FEV1 (odds ratio (OR) 3.3, 95% CI 1.02 to 10.3). The relations between occupational exposure and decline in lung function in this study occurred, despite the selection through the healthy worker effect that occurred as well. Increasing working years was related to decreasing annual decline in FEV1 and fewer people with rapid decline in FEV1 (OR 0.04, 95% CI 0 to 0.61 for over 20 v < 5 working years in the grain processing and animal feed industry). The presence of respiratory symptoms at baseline was a strong predictor of subsequent loss to follow up. Baseline lung function was not found to be predictive of subsequent loss to follow up. However, among workers lost to follow up the number of working years was more strongly negatively related to baseline lung function than among the workers who were studied longitudinally. The existence of the healthy worker effect implies that an exposure-response relation in the grain processing and animal feed industry may well be underestimated. This should be taken into account when health based recommended limit values are to be developed.

Decline in lung function related to exposure and selection processes among workers in the grain processing and animal feed industry

PubMed Central

Post, W.; Heederik, D.; Houba, R.

1998-01-01

OBJECTIVES: To follow up workers in the grain processing and animal feed industry five years after an initial survey, and to monitor exposures to organic dust and endotoxin and changes in prevalence of respiratory symptoms and lung function. METHODS: Outcome measures in the present survey were decline in lung function over five years, rapid annual decline in forced expiratory volume in one second (FEV1) above 90 ml.s-1, and loss to follow up. RESULTS: Among 140 workers included in the longitudinal analysis, annual decline in FEV1 and maximal mid- expiratory flow (MMEF) were significantly related to occupational exposure to dust and endotoxin in the grain processing and animal feed industry. Assuming a cumulative exposure over a working life of 40 years with an exposure of 5 mg.m-3, the estimated effect on the FEV1 would be a decline of 157 ml.s-1 (95% CI 13 to 300)--that is, about 4% of the group mean FEV1 and 473 ml.s-1 (95% CI 127 to 800) of the MMEF (about 12%). Workers with a dust exposure > 4 mg.m-3 or endotoxin concentrations > 20 ng.m-3 at the 1986-8 survey had significantly higher risk of rapid decline in FEV1 (odds ratio (OR) 3.3, 95% CI 1.02 to 10.3). The relations between occupational exposure and decline in lung function in this study occurred, despite the selection through the healthy worker effect that occurred as well. Increasing working years was related to decreasing annual decline in FEV1 and fewer people with rapid decline in FEV1 (OR 0.04, 95% CI 0 to 0.61 for over 20 v < 5 working years in the grain processing and animal feed industry). The presence of respiratory symptoms at baseline was a strong predictor of subsequent loss to follow up. Baseline lung function was not found to be predictive of subsequent loss to follow up. However, among workers lost to follow up the number of working years was more strongly negatively related to baseline lung function than among the workers who were studied longitudinally. CONCLUSIONS: The existence of the healthy worker effect implies that an exposure-response relation in the grain processing and animal feed industry may well be underestimated. This should be taken into account when health based recommended limit values are to be developed.   PMID:9764113

Exposure to industrial air pollutant emissions and lung function in children: Canadian Health Measures Survey, 2007 to 2011.

PubMed

Wong, Suzy L; Coates, Allan L; To, Teresa

2016-02-01

Long-term exposure to ambient air pollution has been associated with adverse effects on children's lung function. Few studies have examined lung function in relation to industrial emissions of air pollutants. This cross-sectional study was based on 2,833 respondents aged 6 to 18 for whom spirometry data were collected by the Canadian Health Measures Survey, 2007 to 2011. The weighted sum of industrial air emissions of nitrogen oxides (NOₓ) and fine particulate matter (PM2.5) within 25 km of the respondent's residence was derived using National Pollutant Release Inventory data. Multivariate linear regression was used to examine the relationship between NOₓ and PM2.5 emissions and forced vital capacity (FVC), the forced expiratory volume in 1 sec (FEV₁), and the ratio of the two (FEV₁/FVC). Industrial air emissions of NOₓ were not significantly associated with lung function among males or females. Emissions of PM2.5 were negatively associated with FEV₁ and FEV₁/FVC, but not FVC, among males. PM2.5 was not significantly related to lung function among females. The associations that emerged between lung function and industrial emissions of PM2.5 among males were consistent with airway obstruction. Further research is warranted to investigate the gender differences observed in this study.

Cigarette Smoke Exposure during Pregnancy Alters Fetomaternal Cell Trafficking Leading to Retention of Microchimeric Cells in the Maternal Lung

PubMed Central

Vogelgesang, Anja; Scapin, Cristina; Barone, Caroline; Tam, Elaine

2014-01-01

Cigarette smoke exposure causes chronic oxidative lung damage. During pregnancy, fetal microchimeric cells traffic to the mother. Their numbers are increased at the site of acute injury. We hypothesized that milder chronic diffuse smoke injury would attract fetal cells to maternal lungs. We used a green-fluorescent-protein (GFP) mouse model to study the effects of cigarette smoke exposure on fetomaternal cell trafficking. Wild-type female mice were exposed to cigarette smoke for about 4 weeks and bred with homozygote GFP males. Cigarette smoke exposure continued until lungs were harvested and analyzed. Exposure to cigarette smoke led to macrophage accumulation in the maternal lung and significantly lower fetal weights. Cigarette smoke exposure influenced fetomaternal cell trafficking. It was associated with retention of GFP-positive fetal cells in the maternal lung and a significant reduction of fetal cells in maternal livers at gestational day 18, when fetomaternal cell trafficking peaks in the mouse model. Cells quickly clear postpartum, leaving only a few, difficult to detect, persisting microchimeric cells behind. In our study, we confirmed the postpartum clearance of cells in the maternal lungs, with no significant difference in both groups. We conclude that in the mouse model, cigarette smoke exposure during pregnancy leads to a retention of fetal microchimeric cells in the maternal lung, the site of injury. Further studies will be needed to elucidate the effect of cigarette smoke exposure on the phenotypic characteristics and function of these fetal microchimeric cells, and confirm its course in cigarette smoke exposure in humans. PMID:24832066

Deviations from Haber’s Law for Multiple Measures of Acute Lung Injury in Chlorine-Exposed Mice

PubMed Central

Hoyle, Gary W.; Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.

2010-01-01

Chlorine gas is considered a chemical threat agent that can cause acute lung injury. Studies in the early 20th century on war gases led Haber to postulate that the dose of an inhaled chemical expressed as the product of gas concentration and exposure time leads to a constant toxicological effect (Haber’s Law). In the present work, mice were exposed to a constant dose of chlorine (100 ppm-h) delivered using different combinations of concentration and time (800 ppm/7.5 min, 400 ppm/15 min, 200 ppm/30 min, and 100 ppm/60 min). Significant effects of exposure protocol on survival evaluated 6 h after exposure were observed, ranging from 0% for the 7.5-min exposure to 100% for the 30- and 60-min exposures. Multiple parameters indicative of lung injury were examined to determine if any aspects of lung injury were differentially affected by the exposure protocols. Most parameters (pulmonary edema, neutrophil influx, and levels of protein, immunoglobulin M, and the chemokine KC [Cxcl1] in lavage fluid) indicated that lung injury was most pronounced for the 15-min exposure and least for the 60-min exposure. In contrast, changes in pulmonary function at baseline and in response to inhaled methacholine were similar following the three exposure regimens. The results indicate that the extent of lung injury following chlorine inhalation depends not only on total dose but also on the specifics of exposure concentration and time, and they suggest that evaluation of countermeasures against chlorine-induced lung injury should be performed using multiple types of exposure scenarios. PMID:20819911

Clinically important FEV1 declines among coal miners: an exploration of previously unrecognised determinants

PubMed Central

Wang, M. L.; Petsonk, E. L.; Beeckman, L. A.; Wagner, G. R.

1999-01-01

OBJECTIVES: The relation between occupational exposure to dust and loss of ventilatory lung function is now well established. However, many exposures during work and other activities might also have important roles in determining clinically important losses of lung function. In this study, we attempted to explore additional plausible determinants of exposures and other potential risk factors for clinically important decline in forced expiratory volume in 1 second (FEV1) during work in dusty trades. METHODS: The study was performed in 264 underground coal miners whose lung function had been followed up for an average of 11 years. With an extensive follow up questionnaire, miners were asked about their occupational and non-occupational exposures, smoking, personal and family medical history, and living conditions during childhood. RESULTS: Several variables of the mine environment (as well as previously recognised effects of mining work and region) were found to be associated with excess decline in FEV1, including work in roof bolting, exposure to explosive blasting, and to control dust spraying water that had been stored in holding tanks. Use of respiratory protection seemed to reduce the risk of decline in FEV1. Other factors that were found to be associated with declines in pulmonary function included smoking, body mass, weight gain, childhood pneumonia, and childhood exposure in the home to passive tobacco smoke and possibly smoke due to wood and coal fuels. Miners with excessive decline in FEV1 were less likely to be working in mining jobs at follow up. CONCLUSIONS: These findings suggest the existence of additional risk factors for decline in lung function in dusty trades, and may be useful in developing additional approaches to the prevention of chronic respiratory disease.   PMID:10658541

Evaluation of vulnerable PM2.5-exposure individuals: a repeated-measure study in an elderly population.

PubMed

Chu, Haiyan; Xin, Junyi; Yuan, Qi; Zhang, Xu; Pan, Wang; Zeng, Xinying; Chen, Yaoyao; Ma, Gaoxiang; Ge, Yuqiu; Du, Mulong; Tong, Na; Li, Xiaobo; Zhang, Zhengdong; Wang, Meilin

2018-04-01

Numerous studies have shown that elderly people are susceptible to high-level particles with aerodynamic diameter ≤ 2.5 μm (PM 2.5 ) exposure. However, not all elderly people exposed to PM 2.5 suffer from diseases. In this study, we aim to establish a method to predict the vulnerable PM 2.5 -exposure individuals among elderly population. Fourteen elderly people were recruited from May 8 to July 4, 2016, in Nanjing, China. Ten physiological indicators were repeatedly measured for 15 times. Liner mixed-effects model, principal component analysis (PCA), and PM 2.5 lag score were used to estimate the effects of PM 2.5 on blood pressure, pulse, and lung function. As a result, each quartile increase of ambient PM 2.5 was significantly associated with increased pulse (P < 0.05 for lag0, 1, 4, 0-1, 0-2, 0-3, and 0-5 days), decreased blood pressure (P < 0.05 for lag4 and 0-3 days), and decreased lung function (P < 0.05 for lag0, 1, 0-1, and 0-2 days) among the 14 elderly people. In terms of pulse or lung function, three elderly people were considered as vulnerable PM 2.5 -exposure individuals. No vulnerable individual was found for blood pressure. Blood pressure, pulse, and lung function could be affected by high-level PM 2.5 exposure in elderly people. This method for screening three elderly people may provide a new insight on identifying the vulnerable PM 2.5 -exposure individuals.

Associations of children's lung function with ambient air pollution: joint effects of regional and near-roadway pollutants.

PubMed

Urman, Robert; McConnell, Rob; Islam, Talat; Avol, Edward L; Lurmann, Frederick W; Vora, Hita; Linn, William S; Rappaport, Edward B; Gilliland, Frank D; Gauderman, W James

2014-06-01

Previous studies have reported adverse effects of either regional or near-roadway air pollution (NRAP) on lung function. However, there has been little study of the joint effects of these exposures. To assess the joint effects of NRAP and regional pollutants on childhood lung function in the Children's Health Study. Lung function was measured on 1811 children from eight Southern Californian communities. NRAP exposure was assessed based on (1) residential distance to the nearest freeway or major road and (2) estimated near-roadway contributions to residential nitrogen dioxide (NO2), nitric oxide (NO) and total nitrogen oxides (NOx). Exposure to regional ozone (O3), NO2, particulate matter with aerodynamic diameter <10 µm (PM10) and 2.5 µm (PM2.5) was measured continuously at community monitors. An increase in near-roadway NOx of 17.9 ppb (2 SD) was associated with deficits of 1.6% in forced vital capacity (FVC) (p=0.005) and 1.1% in forced expiratory volume in 1 s (FEV1) (p=0.048). Effects were observed in all communities and were similar for NO2 and NO. Residential proximity to a freeway was associated with a reduction in FVC. Lung function deficits of 2-3% were associated with regional PM10 and PM2.5 (FVC and FEV1) and with O3 (FEV1), but not NO2 across the range of exposure between communities. Associations with regional pollution and NRAP were independent in models adjusted for each. The effects of NRAP were not modified by regional pollutant concentrations. The results indicate that NRAP and regional air pollution have independent adverse effects on childhood lung function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Dose-response relationships between occupational exposure to potash, diesel exhaust and nitrogen oxides and lung function: cross-sectional and longitudinal study in two salt mines.

PubMed

Lotz, Gabriele; Plitzko, Sabine; Gierke, Erhardt; Tittelbach, Ulrike; Kersten, Norbert; Schneider, W Dietmar

2008-08-01

Several studies have shown that underground salt miners may have an increased incidence of chest symptoms and sometimes decreased lung function. Miners of two salt mines were investigated to evaluate relationships between the lung function and the workplace exposure. The effect of nitrogen monoxide (NO) and nitrogen dioxide (NO(2)) was investigated in view of the recent debate on European occupational exposure limits. A total of 410/463 miners (mine A/mine B) were examined cross-sectional and 75/64% of the first cohort were examined after a 5-year period. Exposure was measured by personal sampling. Personal lifetime exposure doses of salt dust, diesel exhaust, NO(2) and NO were calculated for all miners. Dose-response relationships were calculated by multiple regression analysis. Each exposure component acted as an indicator for the complex exposure. Exposure response relationships were shown in the cross-sectional and longitudinal investigations in both mines. In the 5-year period, the adjusted (age, smoking, etc.) effect of the exposure indicators resulted in a mean decrease of FEV(1) between -18 ml/year (mine A) and -10 ml/year (mine B). The personal concentrations related to this effect were 12.6/7.1 mg/m(3) inhalable dust, 2.4/0.8 mg/m(3) respirable dust, 0.09/0.09 mg/m(3) diesel exhaust, 0.4/0.5 ppm NO(2) and 1.7/1.4 ppm NO (mine A/B). Exposure was related to symptoms of chronic bronchitis only in mine B. The effects found in both mines indicate that the mixed exposure can cause lung function disorders in salt miners exposed over a long time. Because of the high correlation of the concentrations it was not possible to determine the effects of a single exposure component separately or to recommend a specific occupational exposure limit. However, possible maximum effects associated with the mixed exposure can be evaluated in the ranges of concentrations of the individual substances in the mines.

Diesel exhaust exposure among adolescents in Harlem: a community-driven study.

PubMed

Northridge, M E; Yankura, J; Kinney, P L; Santella, R M; Shepard, P; Riojas, Y; Aggarwal, M; Strickland, P

1999-07-01

This study sought individual-level data on diesel exhaust exposure and lung function among adolescents in Harlem as part of a community-driven research agenda. High school students administered in-person surveys to seventh grade students to ascertain information on demographics, asthma history, and self-reported and maternal smoking. Urine samples were assayed for 1-hydroxypyrene (1-HP), a marker of diesel exhaust exposure, and cotinine, a marker of tobacco smoke exposure. Computer-assisted spirometry was used to measure lung function. Three quarters (76%) of the participating students had detectable levels of 1-HP. Three students (13%) had an FEF25-75 of less than or equal to 80% of their predicted measurements, and 4 students (17%) had results between 80% and 90% of the predicted value, all of which are suggestive of possible lung impairment. These data suggest that most adolescents in Harlem are exposed to detectable levels of diesel exhaust, a known exacerbator and possible cause of chronic lung disorders such as asthma. Community-driven research initiatives are important for empowering communities to make needed changes to improve their environments and health.

Reducing attenuation in exposure-response relationships by exposure modeling and grouping: the relationship between wood dust exposure and lung function.

PubMed

Teschke, Kay; Spierings, Judith; Marion, Stephen A; Demers, Paul A; Davies, Hugh W; Kennedy, Susan M

2004-12-01

In a study of wood dust exposure and lung function, we tested the effect on the exposure-response relationship of six different exposure metrics using the mean measured exposure of each subject versus the mean exposure based on various methods of grouping subjects, including job-based groups and groups based on an empirical model of the determinants of exposure. Multiple linear regression was used to examine the association between wood dust concentration and forced expiratory volume in 1s (FEV(1)), adjusting for age, sex, height, race, pediatric asthma, and smoking. Stronger point estimates of the exposure-response relationships were observed when exposures were based on increasing levels of aggregation, allowing the relationships to be found statistically significant in four of the six metrics. The strongest point estimates were found when exposures were based on the determinants of exposure model. Determinants of exposure modeling offers the potential for improvement in risk estimation equivalent to or beyond that from job-based exposure grouping.

Effect of Maternal Electroacupuncture on Perinatal Nicotine Exposure-Induced Lung Phenotype in Offspring.

PubMed

Ji, Bo; Zhao, Guo-Zhen; Sakurai, Reiko; Cao, Yu; Zhang, Zi-Jian; Wang, Dan; Yan, Ming-Na; Rehan, Virender K

2016-08-01

Pregnant women exposed to tobacco smoke predispose the offspring to many adverse consequences including an altered lung development and function. There is no effective therapeutic intervention to block the effects of smoke exposure on the developing lung. Clinical and animal studies demonstrate that acupuncture can modulate a variety of pathophysiological processes, including those involving the respiratory system; however, whether acupuncture affects the lung damage caused by perinatal smoke exposure is not known. To determine the effect of acupuncture on perinatal nicotine exposure on the developing lung, pregnant rat dams were administered (1) saline, (2) nicotine, or (3) nicotine + electroacupuncture (EA). Nicotine was administered (1 mg/kg subcutaneously) once a day and EA was applied to both "Zusanli" (ST 36) points. Both interventions were administered from gestational day 6 to postnatal day 21 (PND21), following which pups were sacrificed. Lungs, blood, and brain were collected to examine markers of lung injury, repair, and hypothalamic pituitary adrenal (HPA) axis. Concomitant EA application blocked nicotine-induced changes in lung morphology, lung peroxisome proliferator-activated receptor γ and wingless-int signaling, two key lung developmental signaling pathways, hypothalamic pituitary adrenal axis (hypothalamic corticotropic releasing hormone and lung glucocorticoid receptor levels), and plasma β-endorphin levels. Electroacupuncture blocks the nicotine-induced changes in lung developmental signaling pathways and the resultant myogenic lung phenotype, known to be present in the affected offspring. We conclude that EA is a promising novel intervention against the smoke exposed lung damage to the developing lung.

Lung function, atopy, specific hypersensitivity, and smoking of workers in the enzyme detergent industry over 11 years.

PubMed

Flood, D F; Blofeld, R E; Bruce, C F; Hewitt, J I; Juniper, C P; Roberts, D M

1985-01-01

A study of 2800 workers employed in three factories of the two major manufacturers of enzymatic products in the United Kingdom covering 11 years of operation from 1969 to 1980 showed that 2344 workers had sufficient lung function data to meet the operational criteria and these were analysed in three separate groups by factory locations. Spirometry and prick tests for specific skin reactions to standardised enzyme were performed at six monthly intervals for the first six years of the study and then annually. Factory enzyme dust and total dust measurements were made to determine the degree of dust exposure of the subjects. The lung function of the factory groups was analysed for the effects of working in the detergent industry, the degree of exposure to enzymes, skin prick test positivity to enzymes, atopicity, and smoking. The 4.5% of workers who had experienced respiratory effects from enzymes were analysed separately. Exposure to the enzyme allergen has had no significant long term effect on the lung function of the detergent workers. A higher proportion of atopics than non-atopics became skin test positive to the allergen and more smokers than non-smokers were sensitised. The overall lung function of detergent workers showed 39 ml/year loss in FEV1 on the 11 year longitudinal study and 51 ml/year loss on the lateral (cross sectional) analysis with better lung function in the south east than the north west of England. In the development of the methodology for the study several potential problems were discovered that could remain unrecognised in a cross sectional analysis performed in isolation.

The association between endotoxin and lung function among children and adolescents living in a rural area

PubMed Central

Lawson, Joshua A; Dosman, James A; Rennie, Donna C; Beach, Jeremy; Newman, Stephen C; Senthilselvan, Ambikaipakan

2011-01-01

BACKGROUND/OBJECTIVES: Knowledge of the effects of domestic endotoxin on children’s lung function is limited. The association between domestic endotoxin and asthma or wheeze and lung function among school-age children (six to 18 years of age) was examined. The interaction between endotoxin and other personal and environmental characteristics and lung function was also assessed. METHODS: A case-control study was conducted in and around the rural community of Humboldt, Saskatchewan, between 2005 and 2007. Parents of cases reported either doctor-diagnosed asthma or wheeze in the previous year. Controls were randomly selected from those not reporting these conditions. Data were collected by questionnaire to ascertain symptoms and conditions, while spirometry was used to measure lung function including forced vital capacity and forced expiratory volume in 1 s. Dust collected from the child’s play area floor and the child’s mattress was used to quantify endotoxin, and saliva was collected to quantify cotinine levels and assess tobacco smoke exposure. RESULTS: There were 102 cases and 207 controls included in the present study. Lower forced expiratory volume in 1 s was associated with higher mattress endotoxin load among female cases (beta=−0.25, SE=0.07 [P<0.01]). There was a trend toward lower forced vital capacity, which was associated with higher play area endotoxin load among cases with high tobacco smoke exposure (beta=−0.17, SE=0.09 [P<0.10]). CONCLUSIONS: Findings indicated that high endotoxin levels present in common household areas of rural children with asthma or wheeze may also affect their lung function. These associations may be potentiated by tobacco smoke exposure and female sex. PMID:22187693

In vitro particulate matter exposure causes direct and lung-mediated indirect effects on cardiomyocyte function.

PubMed

Gorr, Matthew W; Youtz, Dane J; Eichenseer, Clayton M; Smith, Korbin E; Nelin, Timothy D; Cormet-Boyaka, Estelle; Wold, Loren E

2015-07-01

Particulate matter (PM) exposure induces a pathological response from both the lungs and the cardiovascular system. PM is capable of both manifestation into the lung epithelium and entrance into the bloodstream. Therefore, PM has the capacity for both direct and lung-mediated indirect effects on the heart. In the present studies, we exposed isolated rat cardiomyocytes to ultrafine particulate matter (diesel exhaust particles, DEP) and examined their contractile function and calcium handling ability. In another set of experiments, lung epithelial cells (16HBE14o- or Calu-3) were cultured on permeable supports that allowed access to both the basal (serosal) and apical (mucosal) media; the basal media was used to culture cardiomyocytes to model the indirect, lung-mediated effects of PM on the heart. Both the direct and indirect treatments caused a reduction in contractility as evidenced by reduced percent sarcomere shortening and reduced calcium handling ability measured in field-stimulated cardiomyocytes. Treatment of cardiomyocytes with various anti-oxidants before culture with DEP was able to partially prevent the contractile dysfunction. The basal media from lung epithelial cells treated with PM contained several inflammatory cytokines, and we found that monocyte chemotactic protein-1 was a key trigger for cardiomyocyte dysfunction. These results indicate the presence of both direct and indirect effects of PM on cardiomyocyte function in vitro. Future work will focus on elucidating the mechanisms involved in these separate pathways using in vivo models of air pollution exposure. Copyright © 2015 the American Physiological Society.

Biomarkers for Pulmonary Inflammation and Fibrosis and Lung Ventilation Function in Chinese Occupational Refractory Ceramic Fibers-Exposed Workers.

PubMed

Zhu, Xiaojun; Gu, Yishuo; Ma, Wenjun; Gao, Panjun; Liu, Mengxuan; Xiao, Pei; Wang, Hongfei; Chen, Juan; Li, Tao

2017-12-27

Refractory ceramic fibers (RCFs) can cause adverse health effects on workers' respiratory system, yet no proper biomarkers have been used to detect early pulmonary injury of RCFs-exposed workers. This study assessed the levels of two biomarkers that are related to respiratory injury in RCFs-exposed workers, and explored their relations with lung function. The exposure levels of total dust and respirable fibers were measured simultaneously in RCFs factories. The levels of TGF-β1 and ceruloplasmin (CP) increased with the RCFs exposure level ( p < 0.05), and significantly increased in workers with high exposure level (1.21 ± 0.49 ng/mL, 115.25 ± 32.44 U/L) when compared with the control group (0.99 ± 0.29 ng/mL, 97.90 ± 35.01 U/L) ( p < 0.05). The levels of FVC and FEV₁ were significantly decreased in RCFs exposure group ( p < 0.05). Negative relations were found between the concentrations of CP and FVC (B = -0.423, p = 0.025), or FEV₁ (B = -0.494, p = 0.014). The concentration of TGF-β1 (B = 0.103, p = 0.001) and CP (B = 8.027, p = 0.007) were associated with respirable fiber exposure level. Occupational exposure to RCFs can impair lung ventilation function and may have the potential to cause pulmonary inflammation and fibrosis. TGF-β1 and CP might be used as sensitive and noninvasive biomarkers to detect lung injury in occupational RCFs-exposed workers. Respirable fiber concentration can better reflect occupational RCFs exposure and related respiratory injuries.

Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis

PubMed Central

Adam, Martin; Schikowski, Tamara; Carsin, Anne Elie; Cai, Yutong; Jacquemin, Benedicte; Sanchez, Margaux; Vierkötter, Andrea; Marcon, Alessandro; Keidel, Dirk; Sugiri, Dorothee; Al Kanani, Zaina; Nadif, Rachel; Siroux, Valérie; Hardy, Rebecca; Kuh, Diana; Rochat, Thierry; Bridevaux, Pierre-Olivier; Eeftens, Marloes; Tsai, Ming-Yi; Villani, Simona; Phuleria, Harish Chandra; Birk, Matthias; Cyrys, Josef; Cirach, Marta; de Nazelle, Audrey; Nieuwenhuijsen, Mark J.; Forsberg, Bertil; de Hoogh, Kees; Declerq, Christophe; Bono, Roberto; Piccioni, Pavilio; Quass, Ulrich; Heinrich, Joachim; Jarvis, Deborah; Pin, Isabelle; Beelen, Rob; Hoek, Gerard; Brunekreef, Bert; Schindler, Christian; Sunyer, Jordi; Krämer, Ursula; Kauffmann, Francine; Hansell, Anna L.; Künzli, Nino; Probst-Hensch, Nicole

2015-01-01

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO2, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m−3 increase in NO2 exposure was associated with lower levels of FEV1 (−14.0 mL, 95% CI −25.8 to −2.1) and FVC (−14.9 mL, 95% CI −28.7 to −1.1). An increase of 10 μg·m−3 in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV1 (−44.6 mL, 95% CI −85.4 to −3.8) and FVC (−59.0 mL, 95% CI −112.3 to −5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe. PMID:25193994

Long term effects of prenatal and postnatal airborne PAH exposures on ventilatory lung function of non-asthmatic preadolescent children. Prospective birth cohort study in Krakow.

PubMed

Jedrychowski, Wieslaw A; Perera, Frederica P; Maugeri, Umberto; Majewska, Renata; Mroz, Elzbieta; Flak, Elzbieta; Camann, David; Sowa, Agata; Jacek, Ryszard

2015-01-01

The main goal of the study was to test the hypothesis that prenatal and postnatal exposures to polycyclic aromatic hydrocarbons (PAH) are associated with depressed lung function in non-asthmatic children. The study sample comprises 195 non-asthmatic children of non-smoking mothers, among whom the prenatal PAH exposure was assessed by personal air monitoring in pregnancy. At the age of 3, residential air monitoring was carried out to evaluate the residential PAH exposure indoors and outdoors. At the age of 5 to 8, children were given allergic skin tests for indoor allergens; and between 5 and 9 years lung function testing (FVC, FEV05, FEV1 and FEF25-75) was performed. The effects of prenatal PAH exposure on lung function tests repeated over the follow-up were adjusted in the General Estimated Equation (GEE) model for the relevant covariates. No association between FVC with prenatal PAH exposure was found; however for the FEV1 deficit associated with higher prenatal PAH exposure (above 37 ng/m(3)) amounted to 53 mL (p=0.050) and the deficit of FEF25-75 reached 164 mL (p=0.013). The corresponding deficits related to postnatal residential indoor PAH level (above 42 ng/m(3)) were 59 mL of FEV1 (p=0.028) and 140 mL of FEF25-75 (p=0.031). At the higher residential outdoor PAH level (above 90 ng/m(3)) slightly greater deficit of FEV1 (71 mL, p=0.009) was observed. The results of the study suggest that transplacental exposure to PAH compromises the normal developmental process of respiratory airways and that this effect is compounded by postnatal PAH exposure. Copyright © 2014 Elsevier B.V. All rights reserved.

Inflammatory response in rat lungs with recurrent exposure to welding fumes: a transcriptomic approach.

PubMed

Oh, Jung-Hwa; Yang, Mi-Jin; Heo, Jeong-Doo; Yang, Young-Su; Park, Han-Jin; Park, Se-Myo; Kwon, Myung-Sang; Song, Chang-Woo; Yoon, Seokjoo; Yu, Il Je

2012-04-01

As chronic exposure to welding fumes causes pulmonary diseases, such as pneumoconiosis, public concern has increased regarding continued exposure to these hazardous gases in the workplace. In a previous study, the inflammatory response to welding fume exposure was analysed in rat lungs in the case of recurrent exposure and recovery periods. Thus using lung samples, well-annotated by histological observation and biochemical analysis, this study examines the gene expression profiles to identify phenotype-anchored genes corresponding to lung inflammation and the repair phenomenon after recurrent welding fume exposure. Seven genes (Mmp12, Cd5l, LOC50101, LOC69183, Spp1, and Slc26a4) were found to be significantly up-regulated according to the severity of the lung injury. In addition, the transcription and translation of Trem2, which was up-regulated in response to the repair process, were validated using a real-time polymerase chain reaction, Western blotting, and immunohistochemistry. The differentially expressed genes in the exposure and recovery groups were also classified using k-means and hierarchical clustering, plus their toxicological function and canonical pathways were further analysed using Ingenuity Pathways Analysis Software. As a result, this comprehensive and integrative analysis of the transcriptional changes that occur during repeated exposure provides important information on the inflammation and repair processes after welding-fume-induced lung injury.

Air pollution, airway inflammation and lung function in Mexico City school children

EPA Science Inventory

BACKGROUND: The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. OBJECTIVE: In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. METHODS: We studied a cohort...

Chronic Respiratory Symptoms and Lung Function in Agricultural Workers - Influence of Exposure Duration and Smoking.

PubMed

Stoleski, Saso; Minov, Jordan; Mijakoski, Dragan; Karadzinska-Bislimovska, Jovanka

2015-03-15

Job exposure in agricultural workers often leads to respiratory impairment. To assess the influence of exposure duration and smoking on chronic respiratory symptoms and ventilatory capacity in agricultural workers. A cross-sectional study covered 75 agricultural workers, compared with an equal number of office workers matched by age, exposure duration and smoking status. Standardized questionnaire was used to obtain data on chronic respiratory symptoms, job and smoking history. Lung functional testing was performed by spirometry. The prevalence of respiratory symptoms was higher in agricultural workers, with significant difference for cough (P = 0.034), and dyspnea (P = 0.028). Chronic respiratory symptoms among agricultural workers were significantly associated with duration of exposure (P < 0.05) and daily smoking (P < 0.01), as well as with daily smoking in controls (P < 0.01). The average values of spirometric parameters in exposed workers were significantly different for MEF50 (P = 0.002), MEF75 (P = 0.000), and MEF25-75 (P = 0.049). Obstructive changes in small airways in exposed workers were strongly related to exposure duration (P < 0.05) and smoking (P < 0.01). Agricultural workers with job exposure more than 15 years had more expressed adverse respiratory symptoms and lung function decline. The results confirmed the influence of agricultural exposure and daily smoking on chronic respiratory symptoms and airflow limitation, primarily targeting the small airways.

Lung function in adults following in utero and childhood exposure to arsenic in drinking water: preliminary findings.

PubMed

Dauphiné, David C; Ferreccio, Catterina; Guntur, Sandeep; Yuan, Yan; Hammond, S Katharine; Balmes, John; Smith, Allan H; Steinmaus, Craig

2011-08-01

Evidence suggests that arsenic in drinking water causes non-malignant lung disease, but nearly all data concern exposed adults. The desert city of Antofagasta (population 257,976) in northern Chile had high concentrations of arsenic in drinking water (>800 μg/l) from 1958 until 1970, when a new treatment plant was installed. This scenario, with its large population, distinct period of high exposure, and accurate data on past exposure, is virtually unprecedented in environmental epidemiology. We conducted a pilot study on early-life arsenic exposure and long-term lung function. We present these preliminary findings because of the magnitude of the effects observed. We recruited a convenience sample consisting primarily of nursing school employees in Antofagasta and Arica, a city with low drinking water arsenic. Lung function and respiratory symptoms in 32 adults exposed to >800 μg/l arsenic before age 10 were compared to 65 adults without high early-life exposure. Early-life arsenic exposure was associated with 11.5% lower forced expiratory volume in 1 s (FEV(1)) (P = 0.04), 12.2% lower forced vital capacity (FVC) (P = 0.04), and increased breathlessness (prevalence odds ratio = 5.94, 95% confidence interval 1.36-26.0). Exposure-response relationships between early-life arsenic concentration and adult FEV(1) and FVC were also identified (P trend = 0.03). Early-life exposure to arsenic in drinking water may have irreversible respiratory effects of a magnitude similar to smoking throughout adulthood. Given the small study size and non-random recruitment methods, further research is needed to confirm these findings.

Chemical exposure and respiratory health of children in an industrial setting.

PubMed

McCarty, Kathleen M; Cleveland, Rebecca J; Franklin, Peter; Sly, Peter D

2014-01-01

Parental exposures to chemicals, and the interplay between chemical exposures in utero and in infancy leading to respiratory disease in childhood, are not yet fully understood. In this study we investigated the impact of chemical exposures to the parent in occupational settings and to the child in the home and children's respiratory health. A cross-sectional study of lung function and respiratory health was conducted in primary school children in the Kwinana industrial area, south of Perth, Western Australia. Respiratory health was assessed using a standardized questionnaire and lung function was measured using the forced oscillation technique before and after inhaling 200 μg of salbutamol. Univariate logistic regression models were used to explore the relationship between the child's respiratory health (asthma, lung function, bronchodilator response) and exposures to ceramics, dry cleaning fluid, electroplating fluid, glues, leather, fabrics, dyes, insecticides, plastics, metal cleaning fluid, petrol, paint, photochemicals, electric wiring, machining, welding, X-rays, cleaning products, nail products, and "other exposures". The impact of cigarette smoking in the home and family history on respiratory health were also investigated. No associations were found between parental occupational exposures or child's exposures in the home and respiratory health. Significant associations were observed between current smoking in the home and cigarette exposure in the first year of life and poor respiratory health in the children. We found no strong evidence of main effects of occupational exposures in impairing the respiratory health of primary school-aged children.

Responses to sulfur dioxide and exercise by medication-depend asthmatics: Effect of varying medication levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linn, W.S.; Shamoo, D.A.; Peng, R.C.

Twenty-one volunteers with moderate to severe asthma were exposed to sulfur dioxide (SO{sub 2}) at concentrations of O (control), 0.3, and 0.6 ppm in each of three medication states: (1) low (much of their usual asthma medication withheld), (2) normal (each subject on his own usual medication schedule), and (3) high (usual medication supplemented by inhaled metaproterenol before exposure). Theophylline, the medication usually taken by subjects, was often supplemented by beta-adrenergics. Exposures were for 10 min and were accompanied by continuous heavy exercise (ventilation {approximately} 50 1/min). Lung function and symptoms were measured before and after exposure. With normal medication,more » symptomatic bronchoconstriction occurred with exercise and was exacerbated by 0.6 ppm SO{sub 2}, as reported for mildly unmedicated asthmatics studied previously. Both baseline and post-exposure lung function were noticeably worse in the low-medication state. High medication improved baseline lung function and prevented most broncho-constrictive effect of SO{sup 2}/exercise. High medication also increased heart rate and apparently induced tremor or nervousness in some individuals.« less

OZONE-INDUCED RESPIRATORY SYMPTOMS: EXPOSURE-RESPONSE MODELS AND ASSOCIATION WITH LUNG FUNCTION

EPA Science Inventory

Ozone-induced respiratory symptoms are known to be functions of concentration, minute ventilation, and duration of exposure. The purposes of this study were to identify an exposure-response model for symptoms, to determine whether response was related to age, and to assess the re...

Respiratory symptoms and lung function in relation to wood dust and monoterpene exposure in the wood pellet industry.

PubMed

Löfstedt, Håkan; Hagström, Katja; Bryngelsson, Ing-Liss; Holmström, Mats; Rask-Andersen, Anna

2017-06-01

Wood pellets are used as a source of renewable energy for heating purposes. Common exposures are wood dust and monoterpenes, which are known to be hazardous for the airways. The purpose of this study was to study the effect of occupational exposure on respiratory health in wood pellet workers. Thirty-nine men working with wood pellet production at six plants were investigated with a questionnaire, medical examination, allergy screening, spirometry, and nasal peak expiratory flow (nasal PEF). Exposure to wood dust and monoterpenes was measured. The wood pellet workers reported a higher frequency of nasal symptoms, dry cough, and asthma medication compared to controls from the general population. There were no differences in nasal PEF between work and leisure time. A lower lung function than expected (vital capacity [VC], 95%; forced vital capacity in 1 second [FEV 1 ], 96% of predicted) was noted, but no changes were noted during shifts. There was no correlation between lung function and years working in pellet production. Personal measurements of wood dust at work showed high concentrations (0.16-19 mg/m 3 ), and exposure peaks when performing certain work tasks. Levels of monoterpenes were low (0.64-28 mg/m 3 ). There was no association between exposure and acute lung function effects. In this study of wood pellet workers, high levels of wood dust were observed, and that may have influenced the airways negatively as the study group reported upper airway symptoms and dry cough more frequently than expected. The wood pellet workers had both a lower VC and FEV 1 than expected. No cross-shift changes were found.

Respiratory symptoms and lung function in relation to wood dust and monoterpene exposure in the wood pellet industry

PubMed Central

Löfstedt, Håkan; Hagström, Katja; Bryngelsson, Ing-Liss; Holmström, Mats; Rask-Andersen, Anna

2017-01-01

Introduction Wood pellets are used as a source of renewable energy for heating purposes. Common exposures are wood dust and monoterpenes, which are known to be hazardous for the airways. The purpose of this study was to study the effect of occupational exposure on respiratory health in wood pellet workers. Materials and methods Thirty-nine men working with wood pellet production at six plants were investigated with a questionnaire, medical examination, allergy screening, spirometry, and nasal peak expiratory flow (nasal PEF). Exposure to wood dust and monoterpenes was measured. Results The wood pellet workers reported a higher frequency of nasal symptoms, dry cough, and asthma medication compared to controls from the general population. There were no differences in nasal PEF between work and leisure time. A lower lung function than expected (vital capacity [VC], 95%; forced vital capacity in 1 second [FEV1], 96% of predicted) was noted, but no changes were noted during shifts. There was no correlation between lung function and years working in pellet production. Personal measurements of wood dust at work showed high concentrations (0.16–19 mg/m3), and exposure peaks when performing certain work tasks. Levels of monoterpenes were low (0.64–28 mg/m3). There was no association between exposure and acute lung function effects. Conclusions In this study of wood pellet workers, high levels of wood dust were observed, and that may have influenced the airways negatively as the study group reported upper airway symptoms and dry cough more frequently than expected. The wood pellet workers had both a lower VC and FEV1 than expected. No cross-shift changes were found. PMID:28276782

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sigaud, Samuel; Goldsmith, Carroll-Ann W.; Zhou Hongwei

Epidemiological studies reveal increased incidence of lung infection when air pollution particle levels are increased. We postulate that one risk factor for bacterial pneumonia, prior viral infection, can prime the lung for greater deleterious effects of particles via the interferon-gamma (IFN-{gamma}) characteristic of successful host anti-viral responses. To test this postulate, we developed a mouse model in which mice were treated with {gamma}-interferon aerosol, followed by exposure to concentrated ambient particles (CAPs) collected from urban air. The mice were then infected with Streptococcus pneumoniae and the effect of these treatments on the lung's innate immune response was evaluated. The combinationmore » of IFN-{gamma} priming and CAPs exposure enhanced lung inflammation, manifest as increased polymorphonuclear granulocyte (PMN) recruitment to the lung, and elevated expression of pro-inflammatory cytokine mRNAs. Combined priming and CAPs exposure resulted in impaired pulmonary bacterial clearance, as well as increased oxidant production and diminished bacterial uptake by alveolar macrophages (AMs) and PMNs. The data suggest that priming and CAPs exposure lead to an inflamed alveolar milieu where oxidant stress causes loss of antibacterial functions in AMs and recruited PMNs. The model reported here will allow further analysis of priming and CAPs exposure on lung sensitivity to infection.« less

Respiratory symptoms and lung function in bauxite miners.

PubMed

Beach, J R; de Klerk, N H; Fritschi, L; Sim, M R; Musk, A W; Benke, G; Abramson, M J; McNeil, J J

2001-09-01

To determine whether cumulative bauxite exposure is associated with respiratory symptoms or changes in lung function in a group of bauxite miners. Current employees at three bauxite mines in Australia were invited to participate in a survey comprising: questionnaire on demographic details, respiratory symptoms, and work history; skin prick tests for four common aeroallergens; and spirometry. A task exposure matrix was constructed for bauxite exposure in all tasks in all jobs based on monitoring data. Data were examined for associations between cumulative bauxite exposure, and respiratory symptoms and lung function, by regression analyses. The participation rate was 86%. Self-reported work-related respiratory symptoms were reported by relatively few subjects (1.5%-11.8%). After adjustment for age and smoking no significant differences in the prevalence of respiratory symptoms were identified between subjects, in the quartiles of cumulative bauxite exposure distribution. The forced expiratory volume in I s (FEV1) of the exposed group was found to be significantly lower than that for the unexposed group. After adjustment for age, height, and smoking there were no statistically significant differences between quartiles in FEVI, forced vital capacity (FVC) and FEVl/FVC ratio. These data provide little evidence of a serious adverse effect on respiratory health associated with exposure to bauxite in an open-cut bauxite mine in present day conditions.

Low-to-Moderate Arsenic Exposure and Respiratory Health in American Indian Communities.

PubMed

Powers, Martha; Sanchez, Tiffany R; Grau-Perez, Maria; Yeh, Fawn; Francesconi, Kevin; Goessler, Walter; George, Christine M; Heaney, Christopher; Best, Lyle G; Umans, Jason; Brown, Robert H; Navas-Acien, Ana

2018-04-01

Exposure to inorganic arsenic, through drinking naturally-contaminated water, is an established cause of lung cancer. Evidence on the impact of arsenic exposure on lung function, however, is less conclusive. The evidence available, mostly from populations exposed to water arsenic levels >100 μg/L, suggests that arsenic exposure is associated with lower lung function. Prospective studies and studies examining low-to-moderate levels of water arsenic exposure (<50 μg/L) the level relevant for U.S. populations, are very limited. We evaluated the association between chronic low-to-moderate arsenic exposure with lung function and disease in an American Indian population. The Strong Heart Study is a multicenter prospective study of cardiovascular disease and its risk factors among American Indian adults. The present analysis, in 2,166 adults, used urinary arsenic measurements at baseline (1989-1991) and lung symptoms and function assessment by standardized spirometry at the second examination (1993-1995). We evaluated associations between arsenic exposure and airflow obstruction, defined as ratio of forced expiratory volume in 1 second (FEV 1 ) to forced vital capacity (FVC) of less than 0.70, and restrictive pattern, defined as FEV 1 /FVC ratio greater than 0.70 and FVC less than 80% predicted; respiratory symptoms; and self-reported physician diagnosis of nonmalignant respiratory disease. The prevalence of airflow obstruction between 1993 and 1995 was 21.4% (463/2,166); restrictive pattern was 14.5% (314/2,166). Median urinary arsenic concentrations were higher in participants with airflow obstruction (11.0 μg/g creatinine) compared to those without obstruction (9.8 μg/g creatinine), and higher in those with restrictive pattern (12.0 μg/g) compared to those without restrictive pattern (9.4 μg/g). The odds ratio (95% confidence interval) for obstructive and restrictive patterns comparing the 75th to 25th percentile of arsenic was 1.13 (0.96-1.32) and 1.27 (1.01-1.60), respectively, after adjustment for age, sex, education, study site, smoking status, smoking pack-year, estimated glomerular filtration rate, tuberculosis, and body mass index. Emphysema, cough 4-6 times a day, phlegm, and stopping for breath were also positively associated with arsenic. In this American Indian population, exposure to low-to-moderate levels of inorganic arsenic, as measured in urine, was positively associated with restrictive pattern as measured by spirometry, self-reported emphysema diagnosis, self-reported shortness of breath, and more frequent cough and phlegm among those with cough, independent of smoking status. These findings suggest that low-to-moderate arsenic exposure can contribute to nonmalignant lung disease, and may be associated with restrictive lung disease.

Dust is in the air. Part II: Effects of occupational exposure to welding fumes on lung function in a 9-year study.

PubMed

Haluza, Daniela; Moshammer, Hanns; Hochgatterer, Karl

2014-02-01

Adverse health effects of work-related contact with respirable hazardous substances are of great public interest. Because related prospective and long-term follow-up studies are rare, the extent of acute and chronic pulmonary health risks of occupational exposure to welding fumes is discussed controversially in the scientific literature. The objective of the present longitudinal study during a 9-year period was to investigate the annual changes of lung function in welders. Anthropometric measures and smoking behaviour, and spirometric tests (FVC, FEV1, and MEF50) obtained during routine occupational health checkups of female and male workers (n = 1,982) in Austria during the years 2002-2010 were analyzed. The study participants displayed average lung function values lower than the age- and sex-specific norm. Decrease in respiratory capacity was dependent on smoking habits and duration of occupational exposure. Specifically for welders (n = 1,326), decrease of pulmonary function was significantly associated with heavy smoking (FVC -70.7 ml, p = 0.07; FEV1 -167.4 ml, p < 0.001; MEF50 -356.2 ml/s, p < 0.001), but not with moderate smoking habits, and also with duration of occupational exposure to welding fumes per year (FVC -0.89 ml, p = 0.36; FEV1 -2.91 ml, p < 0.001; MEF50 -4.7 ml/s, p = 0.047). Individual smoking habits as well as duration of occupational exposure to welding fumes showed a negative impact on lung function parameters. To reduce the risk of work-associated respiratory morbidity, smoking cessation is highly recommended to personnel engaged in welding fumes- and dust-exposed occupations.

Lifetime Exposure to Ambient Pollution and Lung Function in Children

PubMed Central

Rifas-Shiman, Sheryl L.; Litonjua, Augusto A.; Oken, Emily; Gillman, Matthew W.; Kloog, Itai; Luttmann-Gibson, Heike; Zanobetti, Antonella; Coull, Brent A.; Schwartz, Joel; Koutrakis, Petros; Mittleman, Murray A.; Gold, Diane R.

2016-01-01

Rationale: Few studies have examined associations between exposure to air pollution and childhood lung function after implementation of strict air quality regulations in the 1990s. Objectives: To assess traffic-related pollution exposure and childhood lung function. Methods: We geocoded addresses for 614 mother–child pairs enrolled during pregnancy in the Boston area 1999–2002 and followed them until a mid-childhood visit (median age, 7.7). We calculated the proximity of the home to the nearest major roadway. We estimated first year of life, lifetime, and prior-year exposure to particulate matter with a diameter smaller than 2.5 μm (PM2.5) by a hybrid model using satellite-derived aerosol optical depth, and to black carbon (BC) by a land-use regression model. Measurements and Main Results: Residential proximity to roadway and prior-year and lifetime PM2.5 and BC exposure were all associated with lower FVC. Associations with FEV1 were also negative and proportionally similar. Pollution exposures were not associated with the FEV1/FVC ratio or bronchodilator response. Compared with distances greater than or equal to 400 m, living less than 100 m from a major roadway was associated with lower FVC (−98.6 ml; −176.3 to −21.0). Each 2 μg/m3 increment in prior-year PM2.5 was associated with lower FVC (−21.8 ml; −43.9 to 0.2) and higher odds of FEV1 less than 80% predicted (1.41; 1.03–1.93). Each 0.2 μg/m3 increment in prior-year BC was associated with a 38.9 ml (−70.4 to −7.3) lower FVC. Conclusions: Estimates of long-term exposure to ambient pollution, including proximity to major roadway, PM2.5, and BC (a traffic-related PM2.5 constituent), were associated with lower lung function in this Boston-area cohort of children with relatively low pollution exposures. PMID:26575800

Lifetime Exposure to Ambient Pollution and Lung Function in Children.

PubMed

Rice, Mary B; Rifas-Shiman, Sheryl L; Litonjua, Augusto A; Oken, Emily; Gillman, Matthew W; Kloog, Itai; Luttmann-Gibson, Heike; Zanobetti, Antonella; Coull, Brent A; Schwartz, Joel; Koutrakis, Petros; Mittleman, Murray A; Gold, Diane R

2016-04-15

Few studies have examined associations between exposure to air pollution and childhood lung function after implementation of strict air quality regulations in the 1990s. To assess traffic-related pollution exposure and childhood lung function. We geocoded addresses for 614 mother-child pairs enrolled during pregnancy in the Boston area 1999-2002 and followed them until a mid-childhood visit (median age, 7.7). We calculated the proximity of the home to the nearest major roadway. We estimated first year of life, lifetime, and prior-year exposure to particulate matter with a diameter smaller than 2.5 μm (PM2.5) by a hybrid model using satellite-derived aerosol optical depth, and to black carbon (BC) by a land-use regression model. Residential proximity to roadway and prior-year and lifetime PM2.5 and BC exposure were all associated with lower FVC. Associations with FEV1 were also negative and proportionally similar. Pollution exposures were not associated with the FEV1/FVC ratio or bronchodilator response. Compared with distances greater than or equal to 400 m, living less than 100 m from a major roadway was associated with lower FVC (-98.6 ml; -176.3 to -21.0). Each 2 μg/m(3) increment in prior-year PM2.5 was associated with lower FVC (-21.8 ml; -43.9 to 0.2) and higher odds of FEV1 less than 80% predicted (1.41; 1.03-1.93). Each 0.2 μg/m(3) increment in prior-year BC was associated with a 38.9 ml (-70.4 to -7.3) lower FVC. Estimates of long-term exposure to ambient pollution, including proximity to major roadway, PM2.5, and BC (a traffic-related PM2.5 constituent), were associated with lower lung function in this Boston-area cohort of children with relatively low pollution exposures.

Chronic effects of air pollution on lung function after lung transplantation in the Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) study.

PubMed

Benmerad, Meriem; Slama, Rémy; Botturi, Karine; Claustre, Johanna; Roux, Antoine; Sage, Edouard; Reynaud-Gaubert, Martine; Gomez, Carine; Kessler, Romain; Brugière, Olivier; Mornex, Jean-François; Mussot, Sacha; Dahan, Marcel; Boussaud, Véronique; Danner-Boucher, Isabelle; Dromer, Claire; Knoop, Christiane; Auffray, Annick; Lepeule, Johanna; Malherbe, Laure; Meleux, Frederik; Nicod, Laurent; Magnan, Antoine; Pison, Christophe; Siroux, Valérie

2017-01-01

An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO 2 ), particulate matter with an aerodynamic cut-off diameter of x µm (PM x ) and ozone (O 3 )) at the patients' home address were averaged in the 12 months before each spirometry test. The effects of air pollutants on forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) in % predicted were estimated using mixed linear regressions. We assessed the effect modification of macrolide antibiotics in this relationship.Increased 12-month levels of pollutants were associated with lower levels of FVC % pred (-2.56%, 95% CI -3.86--1.25 for 5 µg·m -3 of PM 10 ; -0.75%, 95% CI -1.38--0.12 for 2 µg·m -3 of PM 2.5 and -2.58%, 95% CI -4.63--0.53 for 10 µg·m -3 of NO 2 ). In patients not taking macrolides, the deleterious association between PM and FVC tended to be stronger and PM 10 was associated with lower FEV 1 Our study suggests a deleterious effect of chronic exposure to air pollutants on lung function levels in LTRs, which might be modified with macrolides. Copyright ©ERS 2017.

Longitudinal lung function decline and wood dust exposure in the furniture industry.

PubMed

Jacobsen, G; Schlünssen, V; Schaumburg, I; Taudorf, E; Sigsgaard, T

2008-02-01

The aim of the present study was to investigate the relationship between change in lung function and cumulative exposure to wood dust. In total, 1,112 woodworkers (927 males, 185 females) and 235 reference workers (104 males, 185 females) participated in a 6-yr longitudinal study. Forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), height and weight were measured, and questionnaire data on respiratory symptoms, wood dust exposure and smoking habits were collected. Cumulative inhalable wood dust exposure was assessed using a study-specific job exposure matrix and exposure time. The median (range) for cumulative wood dust exposure was 3.75 (0-7.55) mg x year x m(-3). A dose-response relationship between cumulative wood dust exposure and percent annual decrease in FEV(1) was suggested for female workers. This was confirmed in a linear regression model adjusted for confounders, including smoking, height and age. An additional difference of -14.50 mL x yr(-1) and -27.97 mL x yr(-1) was revealed for females exposed to 3.75-4.71 mg x yr x m(-3) or to >4.71 mg x yr x m(-3), respectively, compared with non-/low-exposed females. For females, a positive trend between wood dust exposure and the cumulative incidence proportion of FEV(1)/FVC <70% was suggested. In conclusion, in the present low-exposed cohort, female woodworkers had an accelerated decline in lung function, which may be clinically relevant.

Phosgene- and chlorine-induced acute lung injury in rats: comparison of cardiopulmonary function and biomarkers in exhaled breath.

PubMed

Luo, Sa; Trübel, Hubert; Wang, Chen; Pauluhn, Jürgen

2014-12-04

This study compares changes in cardiopulmonary function, selected endpoints in exhaled breath, blood, and bronchoalveolar lavage fluid (BAL) following a single, high-level 30-min nose-only exposure of rats to chlorine and phosgene gas. The time-course of lung injury was systematically examined up to 1-day post-exposure with the objective to identify early diagnostic biomarkers suitable to guide countermeasures to accidental exposures. Chlorine, due to its water solubility, penetrates the lung concentration-dependently whereas the poorly water-soluble phosgene reaches the alveolar region without any appreciable extent of airway injury. Cardiopulmonary endpoints were continually recorded by telemetry and barometric plethysmography for 20h. At several time points blood was collected to evaluate evidence of hemoconcentration, changes in hemostasis, and osteopontin. One day post-exposure, protein, osteopontin, and cytodifferentials were determined in BAL. Nitric oxide (eNO) and eCO2 were non-invasively examined in exhaled breath 5 and 24h post-exposure. Chlorine-exposed rats elaborated a reflexively-induced decreased respiratory rate and bradycardia whereas phosgene-exposed rats developed minimal changes in lung function but a similar magnitude of bradycardia. Despite similar initial changes in cardiac function, the phosgene-exposed rats showed different time-course changes of hemoconcentration and lung weights as compared to chlorine-exposed rats. eNO/eCO2 ratios were most affected in chlorine-exposed rats in the absence of any marked time-related changes. This outcome appears to demonstrate that nociceptive reflexes with changes in cardiopulmonary function resemble typical patterns of mixed airway-alveolar irritation in chlorine-exposed rats and alveolar irritation in phosgene-exposed rats. The degree and time-course of pulmonary injury was reflected best by eNO/eCO2 ratios, hemoconcentration, and protein in BAL. Increased fibrin in blood occurred only in chlorine-exposed rats 1-day post-exposure. Hence, the analysis of NO and CO2 in exhaled breath, including endpoints in blood mirroring changes in the peripheral to pulmonary fluid distribution, seem to be sensitive diagnostic endpoints readily available for early prognostic assessment of severity of injury and efficacy of any chosen countermeasure. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Aerosol deposition in the human respiratory tract

NASA Astrophysics Data System (ADS)

Winchester, John W.; Jones, Donald L.; Mu-tian, Bi

1984-04-01

Rising sulfur dioxide emissions from increased coal combustion present risks, not only of acid rain, but also to health by inhalation of the SO 2 and acid to the lung. We are investigating human inhalation of ppm SO 2 concentrations mixed with aerosol of submicrometer aqueous salt droplets to determine the effects on lung function and body chemistry. Unlike some investigators, we emphasize ammonium sulfate and trace element aerosol composition which simulates ambient air; aerosol pH, relative humidity, and temperature control to reveal gas-particle reaction mechanisms; and dose estimates from length of exposure, SO 2 concentration, and a direct measurement of respiratory deposition of aerosol as a function of particle size by cascade impactor sampling and elemental analysis by PIXE. Exposures, at rest or during exercise, are in a walk-in chamber at body temperature and high humidity to simulate Florida's summer climate. Lung function measurement by spirometry is carried out immediately after exposure. The results are significant in relating air quality to athletic performance and to public health in the southeastern United States.

Cotton Dust Exposure and Resulting Respiratory Disorders Among Home-Based Garment Workers.

PubMed

Silpasuwan, Pimpan; Prayomyong, Somchit; Sujitrat, Dusit; Suwan-Ampai, Plernpit

2016-03-01

Cotton dust exposures and resulting respiratory disorders among Thai home-based garment workers in Bangkok were explored. Structured interviews focused on occupational health assessments of respiratory disorders; workflow process observations, lung function screening tests, and garment dust density assessments were used to gather data. Results revealed that garment workers in this study had worked in home-based tailoring an average of 14.88 years; 88.5% reported average health status, only 2.6% currently smoked cigarettes, and 8.6% had impaired lung function. The prevalence of respiratory disorders in this occupational group was 25%. Significant respiratory tract signs and symptoms were associated with lung function capacity (odds ratio [OR] = 52.15, 95% confidence interval [CI] = [6.49, 419.60]). Long work hours and few preventive behaviors were significantly associated with respiratory disorders (OR = 2.89 and OR = 10.183, respectively). Improving working conditions at home and minimizing fabric dust exposure among garment workers are recommended. © 2015 The Author(s).

Heavy metals found in the breathing zone, toenails and lung function of welders working in an air-conditioned welding workplace.

PubMed

Hariri, Azian; Mohamad Noor, Noraishah; Paiman, Nuur Azreen; Ahmad Zaidi, Ahmad Mujahid; Zainal Bakri, Siti Farhana

2017-09-22

Welding operations are rarely conducted in an air-conditioned room. However, a company would set its welding operations in an air-conditioned room to maintain the humidity level needed to reduce hydrogen cracks in the specimen being welded. This study intended to assess the exposure to metal elements in the welders' breathing zone and toenail samples. Heavy metal concentration was analysed using inductively coupled plasma mass spectrometry. The lung function test was also conducted and analysed using statistical approaches. Chromium and manganese concentrations in the breathing zone exceeded the permissible exposure limit stipulated by Malaysian regulations. A similar trend was obtained in the concentration of heavy metals in the breathing zone air sampling and in the welders' toenails. Although there was no statistically significant decrease in the lung function of welders, it is suggested that exposure control through engineering and administrative approaches should be considered for workplace safety and health improvement.

Hypersensitivity pneumonitis in a cluster of sawmill workers: a 10-year follow-up of exposure, symptoms, and lung function

PubMed Central

Færden, Karl; Lund, May Brit; Aaløkken, Trond Mogens; Eduard, Wijnand; Søstrand, Per; Langård, Sverre; Kongerud, Johny

2014-01-01

Background: The long-term prognosis of repeated acute episodes of hypersensitivity pneumonitis (HP) is not well described. We report on a 10-year follow-up of a 10-person cluster from a Norwegian sawmill who had all experienced relapsing episodes of HP. Objectives: To evaluate the health symptoms, work-related sick-leave, and lung function of 10 workers exposed to mold in a Norwegian sawmill. Methods: Participants were evaluated at baseline and 10 years later at follow-up. A structured interview, measurement of serum IgG antibodies to Rhizopus microsporus (R. microsporus) antigens, lung function tests, high resolution computed tomography (HRCT) of the chest, and personal measurements of exposure to mold spores and dust were completed for each participant. Results: At baseline, nearly all workers reported acute episodes of HP more than twice a month. At follow-up, both the frequency and intensity of symptoms had declined. Sick-leave was reduced and gas diffusing capacity improved – paralleling the gradually reduced air levels of mold spores. Conclusions: In spite of an initially high occurrence of symptoms, long-term clinical and physiological outcome was good. With reduced exposure to mold spores, symptoms declined and lung function was restored. PMID:24999852

Can Particulate Pollution Affect Lung Function in Healthy Adults?

EPA Science Inventory

Accompanying editorial to paper from Harvard by Rice et al. entitled "Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart StudyBy almost any measure the Clean Air Act and its amendments has to be considered as one...

Quartz exposure, retention, and early silicosis in sheep.

PubMed

Bégin, R; Dufresne, A; Cantin, A; Possmayer, F; Sébastien, P; Fabi, D; Bilodeau, G; Martel, M; Bisson, D; Pietrowski, B

1989-05-01

The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To investigate the heterogeneity in the individual response of sheep to the same exposure (susceptibility), individual quartz retention levels at month 12 were measured and found to correlate well with individual parameters of disease activity. We concluded that in early silicosis of sheep, cellular and biochemical changes in lung lavage preceded derangements of pulmonary function and radiographic abnormalities. Thereafter, parameters of lung lavage, lung function, and radiograph were significantly interrelated, but for a given exposure the degree of quartz retention appeared to determine the intensity of the silicotic process.

The effects of ozone exposure and associated injury mechanisms on the central nervous system.

PubMed

Martínez-Lazcano, Juan Carlos; González-Guevara, Edith; del Carmen Rubio, María; Franco-Pérez, Javier; Custodio, Verónica; Hernández-Cerón, Miguel; Livera, Carlos; Paz, Carlos

2013-01-01

Ozone (O3) is a component of photochemical smog, which is a major air pollutant and demonstrates properties that are harmful to health because of the toxic properties that are inherent to its powerful oxidizing capabilities. Environmental O3 exposure is associated with many symptoms related to respiratory disorders, which include loss of lung function, exacerbation of asthma, airway damage, and lung inflammation. The effects of O3 are not restricted to the respiratory system or function - adverse effects within the central nervous system (CNS) such as decreased cognitive response, decrease in motor activity, headaches, disturbances in the sleep-wake cycle, neuronal dysfunctions, cell degeneration, and neurochemical alterations have also been described; furthermore, it has also been proposed that O3 could have epigenetic effects. O3 exposure induces the reactive chemical species in the lungs, but the short half-life of these chemical species has led some authors to attribute the injurious mechanisms observed within the lungs to inflammatory processes. However, the damage to the CNS induced by O3 exposure is not well understood. In this review, the basic mechanisms of inflammation and activation of the immune system by O3 exposure are described and the potential mechanisms of damage, which include neuroinflammation and oxidative stress, and the signs and symptoms of disturbances within the CNS caused by environmental O3 exposure are discussed.

Biomarkers for Pulmonary Inflammation and Fibrosis and Lung Ventilation Function in Chinese Occupational Refractory Ceramic Fibers-Exposed Workers

PubMed Central

Gu, Yishuo; Ma, Wenjun; Gao, Panjun; Liu, Mengxuan; Xiao, Pei; Wang, Hongfei; Chen, Juan; Li, Tao

2017-01-01

Refractory ceramic fibers (RCFs) can cause adverse health effects on workers’ respiratory system, yet no proper biomarkers have been used to detect early pulmonary injury of RCFs-exposed workers. This study assessed the levels of two biomarkers that are related to respiratory injury in RCFs-exposed workers, and explored their relations with lung function. The exposure levels of total dust and respirable fibers were measured simultaneously in RCFs factories. The levels of TGF-β1 and ceruloplasmin (CP) increased with the RCFs exposure level (p < 0.05), and significantly increased in workers with high exposure level (1.21 ± 0.49 ng/mL, 115.25 ± 32.44 U/L) when compared with the control group (0.99 ± 0.29 ng/mL, 97.90 ± 35.01 U/L) (p < 0.05). The levels of FVC and FEV1 were significantly decreased in RCFs exposure group (p < 0.05). Negative relations were found between the concentrations of CP and FVC (B = −0.423, p = 0.025), or FEV1 (B = −0.494, p = 0.014). The concentration of TGF-β1 (B = 0.103, p = 0.001) and CP (B = 8.027, p = 0.007) were associated with respirable fiber exposure level. Occupational exposure to RCFs can impair lung ventilation function and may have the potential to cause pulmonary inflammation and fibrosis. TGF-β1 and CP might be used as sensitive and noninvasive biomarkers to detect lung injury in occupational RCFs-exposed workers. Respirable fiber concentration can better reflect occupational RCFs exposure and related respiratory injuries. PMID:29280967

Before the first breath: prenatal exposures to air pollution and lung development.

PubMed

Veras, Mariana Matera; de Oliveira Alves, Nilmara; Fajersztajn, Lais; Saldiva, Paulo

2017-03-01

Various environmental contaminants are known to impair the growth trajectories of major organs, indirectly (gestational exposure) or directly (postnatal exposure). Evidence associates pre-gestational and gestational exposure to air pollutants with adverse birth outcomes (e.g., low birth weight, prematurity) and with a wide range of diseases in childhood and later in life. In this review, we explore the way that pre-gestational and gestational exposure to air pollution affects lung development. We present results in topics underlining epidemiological and toxicological evidence. We also provide a summary of the biological mechanisms by which air pollution exposure possibly leads to adverse respiratory outcomes. We conclude that gestational and early life exposure to air pollutants are linked to alterations in lung development and function and to other negative respiratory conditions in childhood (wheezing, asthma) that may last into adulthood. Plausible mechanisms encompass changes in maternal physiology (e.g., hypoxia, oxidative stress and inflammation) and DNA alterations in the fetus. Evidence for pre-gestational and gestational effects on the lung is scarce compared with that on early life exposure and further studies are needed. However, the suggested mechanisms are credible and the evidence of pre-gestational and gestational air pollution exposure is robust for adverse birth outcomes. Air pollutants might change lung developmental trajectories of the unborn child predisposing it to diseases later in life highlighting the urgent need for controls on urban air pollution levels worldwide.

Effects of ambient air pollution from municipal solid waste landfill on children's non-specific immunity and respiratory health.

PubMed

Yu, Yunjiang; Yu, Ziling; Sun, Peng; Lin, Bigui; Li, Liangzhong; Wang, Zhengdong; Ma, Ruixue; Xiang, Mingdeng; Li, Hui; Guo, Shu

2018-05-01

This cross-sectional study investigated the association between air pollutant (AP) and respiratory health of 951 children residing near a municipal solid waste (MSW) landfill in Northern China. Results showed that students in non-exposure areas had significantly higher levels of lysozyme, secretory immunoglobulin A (SIgA), and better lung capacity than students in exposure areas (p < .05). Multiple regression model analysis indicated that lysozyme levels exhibited a consistent negative association with methane (CH 4 : β = -76.3, 95% CI -105 to -47.7) and sulfuretted hydrogen (H 2 S: β = -11.7, 95% CI -20.2 to -3.19). In addition, SIgA levels were negatively associated with H 2 S (β = -68.9, 95% CI -97.9 to -39.9) and ammonia (NH 3 : β = -30.3, 95% CI -51.7 to -8.96). Among all AP, H 2 S and sulfur dioxide (SO 2 ) were the most robustly related with reduced lung function. H 2 S exposure was negatively associated with six lung function indices, 1-s forced expiratory volume (FEV1%), mean forced expiratory flow between 25% and 75% (MMF), maximum voluntary ventilation (MVV), and forced expiratory flow at 25%, 50%, and 75% of the pulmonary volume (FEF25, FEF50, FEF75); and SO 2 was negatively associated with FEV1%, MVV, FEF25, FEF50 and FEF75. Our results suggested that AP exposure was negatively associated with more lung function parameters in boys than in girls. In conclusion, our findings suggested that children living adjacent to landfill sites were more likely to have deficient non-specific immunity and impaired lung function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India.

PubMed

Elango, Nithya; Kasi, Vallikkannu; Vembhu, Bhuvaneswari; Poornima, Jeyanthi Govindasamy

2013-09-11

We assessed indoor air quality in photocopier centers and investigated whether occupational exposure to emissions from photocopiers is associated with decline in lung function or changes in haematological parameters, oxidative stress and inflammatory status. Indoor air quality was monitored in five photocopier centers. Pulmonary function was assessed by spirometry in 81 photocopier operators (64 male and 17 female) and 43 healthy control (31 male and 12 female) subjects. Hematological status, serum thio-barbituric acid reactive substances (TBARS), total ferric reducing antioxidant capacity (FRAC), leukotriene B4 (LTB4), 8-isoprostane, C reactive protein (CRP), interleukin 8 (IL-8), clara cell protein (CC-16), intercellular adhesion molecule 1 (ICAM-1) and eosinophilic cationic protein (ECP) were analyzed. Relationships between cumulative exposure, lung function and inflammatory markers were assessed. PM10 and PM2.5 were above the permissible levels in all the photocopier centers, whereas the levels of carbon monoxide, nitrogen oxides, ozone, sulphur dioxide, lead, arsenic, nickel, ammonia, benzene and benzo(a)pyrene were within Indian ambient air quality standards. Lung function was similar in the photocopier operators and control subjects. Serum TBARS was significantly higher and FRAC was lower among photocopier operators when compared to healthy controls. Plasma IL-8, LTB4, ICAM-1 and ECP were significantly higher in the photocopier exposed group. Photocopiers emit high levels of particulate matter. Long term exposure to emissions from photocopiers was not associated with decreased lung function, but resulted in high oxidative stress and systemic inflammation leading to high risk of cardiovascular diseases.

Chronic exposure to emissions from photocopiers in copy shops causes oxidative stress and systematic inflammation among photocopier operators in India

PubMed Central

2013-01-01

Background We assessed indoor air quality in photocopier centers and investigated whether occupational exposure to emissions from photocopiers is associated with decline in lung function or changes in haematological parameters, oxidative stress and inflammatory status. Methods Indoor air quality was monitored in five photocopier centers. Pulmonary function was assessed by spirometry in 81 photocopier operators (64 male and 17 female) and 43 healthy control (31 male and 12 female) subjects. Hematological status, serum thio-barbituric acid reactive substances (TBARS), total ferric reducing antioxidant capacity (FRAC), leukotriene B4 (LTB4), 8-isoprostane, C reactive protein (CRP), interleukin 8 (IL-8), clara cell protein (CC-16), intercellular adhesion molecule 1 (ICAM-1) and eosinophilic cationic protein (ECP) were analyzed. Relationships between cumulative exposure, lung function and inflammatory markers were assessed. Results PM10 and PM2.5 were above the permissible levels in all the photocopier centers, whereas the levels of carbon monoxide, nitrogen oxides, ozone, sulphur dioxide, lead, arsenic, nickel, ammonia, benzene and benzo(a)pyrene were within Indian ambient air quality standards. Lung function was similar in the photocopier operators and control subjects. Serum TBARS was significantly higher and FRAC was lower among photocopier operators when compared to healthy controls. Plasma IL-8, LTB4, ICAM-1 and ECP were significantly higher in the photocopier exposed group. Conclusions Photocopiers emit high levels of particulate matter. Long term exposure to emissions from photocopiers was not associated with decreased lung function, but resulted in high oxidative stress and systemic inflammation leading to high risk of cardiovascular diseases. PMID:24025094

Occupational exposure to dust and lung disease among sheet metal workers.

PubMed Central

Hunting, K L; Welch, L S

1993-01-01

A previous large medical survey of active and retired sheet metal workers with 20 or more years in the trade indicated an unexpectedly high prevalence of obstructive pulmonary disease among both smokers and non-smokers. This study utilised interviews with a cross section of the previously surveyed group to explore occupational risk factors for lung disease. Four hundred and seven workers were selected from the previously surveyed group on the basis of their potential for exposure to fibreglass and asbestos. Selection was independent of health state, and excluded welders. A detailed history of occupational exposure was obtained by telephone interview for 333 of these workers. Exposure data were analysed in relation to previously collected data on chronic bronchitis, obstructive lung disease, and personal characteristics. Assessment of the effects of exposure to fibreglass as distinct from the effects of exposure to asbestos has been difficult in previous studies of construction workers. The experienced workers studied here have performed a diversity of jobs involving exposure to many different types of materials, and this enabled exposure to each dust to be evaluated separately. The risk of chronic bronchitis increased sharply by pack-years of cigarettes smoked; current smokers had a double risk compared with those who had never smoked or had stopped smoking. The occurrence of chronic bronchitis also increased with increasing duration of exposure to asbestos. Workers with a history of high intensity exposure to fibreglass had a more than doubled risk of chronic bronchitis. Obstructive lung disease, defined by results of pulmonary function tests at the medical survey, was also related to both smoking and occupational risk factors. Number of pack years smoked was the strongest predictor of obstructive lung disease. Duration of direct and indirect exposure to welding fume was also a positive predictor of obstructive lung disease. Duration of exposure to asbestos was significantly associated with obstructive lung disease but the dose-response relation was inconsistent, especially for those with higher pack-years of smoking exposure. Exposure to fibreglass was not a risk factor for obstructive lung disease. PMID:8507596

Pulmonary Function in Flight (PuFF) Experiment

NASA Technical Reports Server (NTRS)

2003-01-01

In this International Space Station (ISS) onboard photo, Expedition Six Science Officer Donald R. Pettit works to set up the Pulmonary Function in Flight (PuFF) experiment hardware in the Destiny Laboratory. Expedition Six is the fourth and final crew to perform the PuFF experiment. The PuFF experiment was developed to better understand what effects long term exposure to microgravity may have on the lungs. The focus is on measuring changes in the everness of gas exchange in the lungs, and on detecting changes in respiratory muscle strength. It allows astronauts to measure blood flow through the lungs, the ability of the lung to take up oxygen, and lung volumes. Each PuFF session includes five lung function tests, which involve breathing only cabin air. For each planned extravehicular (EVA) activity, a crew member performs a PuFF test within one week prior to the EVA. Following the EVA, those crew members perform another test to document the effect of exposure of the lungs to the low-pressure environment of the space suits. This experiment utilizes the Gas Analyzer System for Metabolic Analysis Physiology, or GASMAP, located in the Human Research Facility (HRF), along with a variety of other Puff equipment including a manual breathing valve, flow meter, pressure-flow module, pressure and volume calibration syringes, and disposable mouth pieces.

Ambient particulate matter and lung function growth in Chinese children.

PubMed

Roy, Ananya; Hu, Wei; Wei, Fusheng; Korn, Leo; Chapman, Robert S; Zhang, Junfeng Jim

2012-05-01

Exposure to particulate matter (PM) has been associated with deficits in lung function growth among children in Western countries. However, few studies have explored this association in developing countries, where PM levels are often substantially higher. Children (n = 3273) 6-12 years of age were recruited from 8 schools in 4 Chinese cities. The lung function parameters of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were measured using computerized spirometers twice a year for up to 3 years (1993-1996). Dichotomous samplers placed in each schoolyard were used to measure PM2.5 and PM10 (PM with diameter ≤ 2.5 μm and ≤ 10 μm, respectively). Multivariable generalized estimating equations were used to examine the association between the quarterly average PM levels and lung function growth during the period of follow-up. Annual average PM2.5 and PM10 levels in the 4 cities ranged from 57 to 158 μg/m and 95 to 268 μg/m, respectively. In multivariable models, an increase of 10 μg/m of PM2.5 was associated with decreases of 2.7 mL FEV1 (95% confidence interval = -3.5 to -2.0), 3.5 mL FVC (-4.3 to -2.7), 1.4 mL/year FEV1 growth (-1.8 to -0.9), and 1.5 mL/year FVC growth (-2.0 to -1.0). Similar results were seen with PM10 exposure. Exposure to ambient particulate matter was associated with decreased growth in lung function among Chinese children.

Lung function changes in coke oven workers during 12 years of follow up

PubMed Central

Wu, J; Griffiths, D; Kreis, I; Darling, C

2004-01-01

Aims: To investigate the effect of exposure to coke oven emissions on the lung function of coke oven workers. Methods: The study population, followed from 1978 and 1990, was 580 male workers with at least two sets of lung function measurements (FVC, FEV1, FEV1/FVC, and FEF25–75%). An annual rate of change (time slope) for age and height adjusted lung function index was estimated for each subject. This "time slope" was then treated as the response variable in a weighted multiple regression analysis with selected predictors. Results: For all 580 subjects, each year of working in the "operation" group (the most exposed) was found to increase the FVC decline by around 0.7 ml/year (95% CI 0.1 to 1.3 ml/year). After the exclusion of 111 subjects without detailed work history, the above finding was confirmed and each year of exposure in "operation" was also found to increase the FEV1 decline by around 0.8 ml/year (95% CI 0.1 to 1.4 ml/year). Conclusions: These findings are consistent with the results of previous cross-sectional studies. Work duration in the most exposed position in the coke ovens was associated with increased annual decline for FVC and FEV1. The estimated effect of one year of work exposure in "operation" is equivalent, in terms of the reduction in lung function, to an estimated 2.1 pack-years of smoking for FVC and 1.2 pack-years of smoking for FEV1. PMID:15258275

Association between lung function in adults and plasma DDT and DDE levels: results from the Canadian Health Measures Survey.

PubMed

Ye, Ming; Beach, Jeremy; Martin, Jonathan W; Senthilselvan, Ambikaipakan

2015-05-01

Although DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane] has been banned in many countries since the 1970s, it may still pose a risk to human respiratory health. In agriculture, DDT exposures have been associated with asthma and chronic bronchitis. However, little is known about the effect of DDT on lung function. We used data on 1,696 participants 20-79 years of age from the Canadian Health Measures Survey (CHMS) and conducted multiple regression analysis to estimate associations between plasma p,p´-DDT/DDE and lung function. Almost all participants (> 99.0%) had detectable concentrations of plasma p,p´-DDE, but only 10.0% had detectable p,p´-DDT. Participants with detectable p,p´-DDT had significantly lower mean FVC (difference = 311 mL; 95% CI: -492, -130; p = 0.003) and FEV1 (difference = 232 mL; 95% CI: -408, -55; p = 0.015) than those without. A 100-ng/g lipid increase in plasma p,p´-DDE was associated with an 18.8-mL decrease in mean FVC (95% CI: -29, -9) and an 11.8-mL decrease in mean FEV1 (95% CI: -21, -3). Neither exposure was associated with FEV1/FVC ratio or FEF25%-75%. DDT exposures, which may have occurred decades ago, were still detectable among Canadians. Plasma DDT and DDE were negatively associated with lung function parameters. Additional research on the potential effects of DDT use on lung function is warranted.

Effect of reducing indoor air pollution on women's respiratory symptoms and lung function: the RESPIRE Randomized Trial, Guatemala.

PubMed

Smith-Sivertsen, Tone; Díaz, Esperanza; Pope, Dan; Lie, Rolv T; Díaz, Anaite; McCracken, John; Bakke, Per; Arana, Byron; Smith, Kirk R; Bruce, Nigel

2009-07-15

Exposure to household wood smoke from cooking is a risk factor for chronic obstructive lung disease among women in developing countries. The Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) is a randomized intervention trial evaluating the respiratory health effects of reducing indoor air pollution from open cooking fires. A total of 504 rural Mayan women in highland Guatemala aged 15-50 years, all using traditional indoor open fires, were randomized to either receive a chimney woodstove (plancha) or continue using the open fire. Assessments of chronic respiratory symptoms and lung function and individual measurements of carbon monoxide exposure were performed at baseline and every 6 months up to 18 months. Use of a plancha significantly reduced carbon monoxide exposure by 61.6%. For all respiratory symptoms, reductions in risk were observed in the plancha group during follow-up; the reduction was statistically significant for wheeze (relative risk = 0.42, 95% confidence interval: 0.25, 0.70). The number of respiratory symptoms reported by the women at each follow-up point was also significantly reduced by the plancha (odds ratio = 0.7, 95% confidence interval: 0.50, 0.97). However, no significant effects on lung function were found after 12-18 months. Reducing indoor air pollution from household biomass burning may relieve symptoms consistent with chronic respiratory tract irritation.

Traffic-related air pollution exposure is associated with allergic sensitization, asthma, and poor lung function in middle age.

PubMed

Bowatte, Gayan; Lodge, Caroline J; Knibbs, Luke D; Lowe, Adrian J; Erbas, Bircan; Dennekamp, Martine; Marks, Guy B; Giles, Graham; Morrison, Stephen; Thompson, Bruce; Thomas, Paul S; Hui, Jennie; Perret, Jennifer L; Abramson, Michael J; Walters, Haydn; Matheson, Melanie C; Dharmage, Shyamali C

2017-01-01

Traffic-related air pollution (TRAP) exposure is associated with allergic airway diseases and reduced lung function in children, but evidence concerning adults, especially in low-pollution settings, is scarce and inconsistent. We sought to determine whether exposure to TRAP in middle age is associated with allergic sensitization, current asthma, and reduced lung function in adults, and whether these associations are modified by variants in Glutathione S-Transferase genes. The study sample comprised the proband 2002 laboratory study of the Tasmanian Longitudinal Health Study. Mean annual residential nitrogen dioxide (NO 2 ) exposure was estimated for current residential addresses using a validated land-use regression model. Associations between TRAP exposure and allergic sensitization, lung function, current wheeze, and asthma (n = 1405) were investigated using regression models. Increased mean annual NO 2 exposure was associated with increased risk of atopy (adjusted odds ratio [aOR], 1.14; 95% CI, 1.02-1.28 per 1 interquartile range increase in NO 2 [2.2 ppb]) and current wheeze (aOR, 1.14; 1.02-1.28). Similarly, living less than 200 m from a major road was associated with current wheeze (aOR, 1.38; 95% CI, 1.06-1.80) and atopy (aOR, 1.26; 95% CI, 0.99-1.62), and was also associated with having significantly lower prebronchodilator and postbronchodilator FEV 1 and prebronchodilator forced expiratory flow at 25% to 75% of forced vital capacity. We found evidence of interactions between living less than 200 m from a major road and GSTT1 polymorphism for atopy, asthma, and atopic asthma. Overall, carriers of the GSTT1 null genotype had an increased risk of asthma and allergic outcomes if exposed to TRAP. Even relatively low TRAP exposures confer an increased risk of adverse respiratory and allergic outcomes in genetically susceptible individuals. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Lung function impairment in women exposed to biomass fuels during cooking compared to cleaner fuels in Uttar Pradesh, India.

PubMed

Bihari, Vipin; Iqbal, S M; Srivastava, L P; Kesavachandran, C; Siddique, M J A

2013-11-01

A national survey has shown that approximately 75-80% use of fire wood and chips, 10% of dung cake rural women in Uttar Pradesh, India. Considering the respiratory health risk of biomass fuel exposure to women, a cross sectional study was conducted to elucidate the relationship between cooking smoke and lung function impairments. The present study showed significant decline in air flow limitation based on reduced PEFR (3.69 | sec(-1)) and FEV1 (1.34 | sec(-1)) in women cooking with biomass fuels compared to PEFR (4.26 | sec(-1)) and FEV1 (1.73 | sec(-1)) in women cooking with cleaner fuels. The noxious gases and particles generated from biomass fuels during cooking reported in earlier studies may be the reason for the slight decline in airway status PEFR (3.69 | sec(-1)) and lung volumes FEV1 (1.34 | sec(-1)). The higher mean bio-fuels exposure index (52.5 hr-yrs) can attribute to reduced lung function in rural women.

In utero and early childhood exposure to arsenic decreases lung function in children

PubMed Central

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R. Clark; Gandolfi, A. Jay; Gonzalez-De Alba, Cesar

2016-01-01

Background The lung is a target organ for adverse health outcomes following exposure to arsenic. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to arsenic through drinking water, however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of arsenic and its metabolites with lung function in children exposed in utero and in early childhood to high arsenic levels through drinking water. Methods A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic arsenic. Lung function was assessed by spirometry. Results Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 μg/L. The mean urinary arsenic level registered in the studied subjects was 141.2 μg/L and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percent of inorganic arsenic. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Conclusion Exposure to arsenic through drinking water during in utero and early life was associated with a decrease in FVC and with a restrictive spirometric pattern in the children evaluated. PMID:25131850

In utero and early childhood exposure to arsenic decreases lung function in children.

PubMed

Recio-Vega, Rogelio; Gonzalez-Cortes, Tania; Olivas-Calderon, Edgar; Lantz, R Clark; Gandolfi, A Jay; Gonzalez-De Alba, Cesar

2015-04-01

The lung is a target organ for adverse health outcomes following exposure to As. Several studies have reported a high prevalence of respiratory symptoms and diseases in subjects highly exposed to As through drinking water; however, most studies to date has been performed in exposed adults, with little information on respiratory effects in children. The objective of the study was to evaluate the association between urinary levels of As and its metabolites with lung function in children exposed in utero and in early childhood to high As levels through drinking water. A total of 358 healthy children were included in our study. Individual exposure was assessed based on urinary concentration of inorganic As. Lung function was assessed by spirometry. Participants were exposed since pregnancy until early childhood to an average water As concentration of 152.13 µg l⁻¹. The mean urinary As level registered in the studied subjects was 141.2 µg l⁻¹ and only 16.7% had a urinary concentration below the national concern level. Forced vital capacity was significantly decreased in the studied population and it was negatively associated with the percentage of inorganic As. More than 57% of the subjects had a restrictive spirometric pattern. The urinary As level was higher in those children with restrictive lung patterns when compared with the levels registered in subjects with normal spirometric patterns. Exposure to As through drinking water during in utero and early life was associated with a decrease in forced vital capacity and with a restrictive spirometric pattern in the children evaluated. Copyright © 2014 John Wiley & Sons, Ltd.

Cross-sectional study on the endotoxin exposure and lung function impairment in the workers of textile industry near Lahore, Pakistan.

PubMed

Ghani, Nadia; Khalid, Anum; Tahir, Arifa

2016-07-01

To examine the effects of airborne endotoxin on lung function impairment in exposure-response relationships among the workers of textile industry. The cross-sectional study was conducted at Lahore College for Women University, Lahore, Pakistan, from January to August 2014, and comprised textile mill workers. The participants were divided into exposed and control groups. A questionnaire was used to ask workers about the potential adverse health effects of their occupation. The pulmonary function test was carried out by spirometer. Endotoxin levels in the samples were determined using the key quality characteristics limulus amebocyte lysate. The data was analysed to determine the correlation between the endotoxin exposure duration and pulmonary function test parameters. There were 200 subjects subdivided into 100 each inexposed and control groups. Overall, 160(80%) were not aware of safety measures and the remaining 40(20%) were partially practising. Changes in pulmonary function due to endotoxin exposure showed decreased force vital capacity, flow rate and peak expiratory flow parameters significantly different (p<0.05, p<0.001). The endotoxin concentration was between 12EU/m3 and 300EU/m3. Airborne endotoxin concentrations in textile plants exceeded the Dutch health-based guidance limit of 90EU/m3 and was associated with respiratory health effects. Prolonged exposure to airborne endotoxin caused constant lung impairment. Proper safety measures should be adopted to avoid the inhalation of cotton dust.

Silicosis and lung function decrements among female ceramic workers in Italy.

PubMed

Forastiere, Francesco; Goldsmith, David F; Sperati, Alessandra; Rapiti, Elisabetta; Miceli, Maria; Cavariani, Fulvio; Perucci, Carlo A

2002-11-01

It is well known that male ceramic workers have elevated risks of chronic silicosis. The objective of this study was to assess whether female ceramic workers also have an increased risk of silicosis and whether these women have decreased lung function related to silica exposure. Ceramic workers from Civitacastellana, Italy, were enrolled in health surveillance during the 1970s. A total of 642 women were under surveillance; a respiratory monitoring program was conducted from 1974 to 1987, with follow-up through 1991 that included annual chest radiography and measurement of lung function. Radiography findings were defined as silicosis if the chest films were > or =1/0 with small, rounded opacities. Multiple linear regression models for repeated measures (generalized estimating equations) were run to evaluate associations of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV(1)) with years of exposure and radiograph opacities. Nine cases of silicosis were identified on the basis of radiographic evidence. Silicosis risk was not associated with smoking but was related to employment before 1970 and demonstrated a dose-response gradient for years of exposure. FVC and FEV(1) both showed significant (p < 0.05) associations with duration of exposure and with positive radiography findings. The results for female ceramic workers are consistent with those for male employees regarding exposure to fibrogenic dusts.

Respiratory symptoms, lung function, and sensitisation to flour in a British bakery.

PubMed Central

Musk, A W; Venables, K M; Crook, B; Nunn, A J; Hawkins, R; Crook, G D; Graneek, B J; Tee, R D; Farrer, N; Johnson, D A

1989-01-01

A survey of dust exposure, respiratory symptoms, lung function, and response to skin prick tests was conducted in a modern British bakery. Of the 318 bakery employees, 279 (88%) took part. Jobs were ranked from 0 to 10 by perceived dustiness and this ranking correlated well with total dust concentration measured in 79 personal dust samples. Nine samples had concentrations greater than 10 mg/m3, the exposure limit for nuisance dust. All participants completed a self administered questionnaire on symptoms and their relation to work. FEV1 and FVC were measured by a dry wedge spirometer and bronchial reactivity to methacholine was estimated. Skin prick tests were performed with three common allergens and with 11 allergens likely to be found in bakery dust, including mites and moulds. Of the participants in the main exposure group, 35% reported chest symptoms which in 13% were work related. The corresponding figures for nasal symptoms were 38% and 19%. Symptoms, lung function, bronchial reactivity, and response to skin prick tests were related to current or past exposure to dust using logistic or linear regression analysis as appropriate. Exposure rank was significantly associated with most of the response variables studied. The study shows that respiratory symptoms and sensitisation are common, even in a modern bakery. PMID:2789967

Detrimental effects of environmental tobacco smoke in relation to asthma severity.

PubMed

Comhair, Suzy A A; Gaston, Benjamin M; Ricci, Kristin S; Hammel, Jeffrey; Dweik, Raed A; Teague, W Gerald; Meyers, Deborah; Ampleford, Elizabeth J; Bleecker, Eugene R; Busse, William W; Calhoun, William J; Castro, Mario; Chung, Kian Fan; Curran-Everett, Douglas; Israel, Elliot; Jarjour, W Nizar; Moore, Wendy; Peters, Stephen P; Wenzel, Sally; Hazen, Stanley L; Erzurum, Serpil C

2011-05-04

Environmental tobacco smoke (ETS) has adverse effects on the health of asthmatics, however the harmful consequences of ETS in relation to asthma severity are unknown. In a multicenter study of severe asthma, we assessed the impact of ETS exposure on morbidity, health care utilization and lung functions; and activity of systemic superoxide dismutase (SOD), a potential oxidative target of ETS that is negatively associated with asthma severity. From 2002-2006, 654 asthmatics (non-severe 366, severe 288) were enrolled, among whom 109 non-severe and 67 severe asthmatics were routinely exposed to ETS as ascertained by history and validated by urine cotinine levels. ETS-exposure was associated with lower quality of life scores; greater rescue inhaler use; lower lung function; greater bronchodilator responsiveness; and greater risk for emergency room visits, hospitalization and intensive care unit admission. ETS-exposure was associated with lower levels of serum SOD activity, particularly in asthmatic women of African heritage. ETS-exposure of asthmatic individuals is associated with worse lung function, higher acuity of exacerbations, more health care utilization, and greater bronchial hyperreactivity. The association of diminished systemic SOD activity to ETS exposure provides for the first time a specific oxidant mechanism by which ETS may adversely affect patients with asthma.

Emodin mitigates diesel exhaust particles-induced increase in airway resistance, inflammation and oxidative stress in mice.

PubMed

Nemmar, Abderrahim; Al-Salam, Suhail; Yuvaraju, Priya; Beegam, Sumaya; Ali, Badreldin H

2015-08-15

Clinical and experimental studies have reported that short-term exposure to particulate air pollution is associated with inflammation, oxidative stress and impairment of lung function. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) has a strong antioxidant and anti-inflammatory actions. Therefore, in the present study, we evaluated the possible ameliorative effect of emodin on diesel exhaust particles (DEP)-induced impairment of lung function, inflammation and oxidative stress in mice. Mice were intratracheally instilled with DEP (20 μg/mouse) or saline (control). Emodin was administered intraperitoneally 1h before and 7h after pulmonary exposure to DEP. Twenty-four hours following DEP exposure, we evaluated airway resistance measured by forced oscillation technique, lung inflammation and oxidative stress. Emodin treatment abated the DEP-induced increase in airway resistance, and prevented the influx of neutrophils in bronchoalveolar lavage fluid. Similarly, lung histopathology confirmed the protective effect of emodin on DEP-induced lung inflammation. DEP induced a significant increase of proinflammatory cytokines in the lung including tumor necrosis factor α, interleukin 6 and interleukin 1β. The latter effect was significantly ameliorated by emodin. DEP caused a significant increase in lung lipid peroxidation, reactive oxygen species and a significant decrease of reduced glutathione concentration. These effects were significantly mitigated by emodin. We conclude that emodin significantly mitigated DEP-induced increase of airway resistance, lung inflammation and oxidative stress. Pending further pharmacological and toxicological studies, emodin may be considered a potentially useful pulmonary protective agent against particulate air pollution-induced lung toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Risk Evaluation of Construction Workers' Exposure to Silica Dust and the Possible Lung Function Impairments.

PubMed

Tavakol, Elahe; Azari, Mansour; Zendehdel, Rezvan; Salehpour, Sousan; Khodakrim, Soheila; Nikoo, Saeed; Saranjam, Behzad

2017-06-01

Aerosols generated during construction activities are an integral part of building operations. Considering the nature of materials used in construction activities, respirable dust contains crystalline silica and particulates not otherwise specified (PNOS). Due to lack of data regarding the occupational health status of Iranian construction workers, the objective of this study was to evaluate occupational exposure to silica and to examine their respiratory health status. In this cross sectional study, 85 construction workers and 40 controls (without active exposure to construction dust) were studied. The workers' exposure to PNOS and silica aerosols was monitored by the NIOSH method No.0600 and a new Fourier transform infrared spectroscopy (FTIR)-based method, respectively. All subjects were also monitored for lung function parameters, such as forced expiratory volume/forced vital capacity (FEV 1 /FVC), peak expiratory flow rate (PEFR), forced expiratory flow (FEF 25-75 ), FVC, and FEV 1 . The mean exposure of workers to respirable PNOS and silica was 9.8 (0.35) and 0.13 (0.019) mg/m 3 , respectively. The groups of construction workers showed significant differences in exposure to PNOS ( P < 0.001) and silica ( P = 0.007). The mean pulmonary function parameters, including FEV 1 % and FVC%, were significantly lower among construction workers, compared to the control group ( P < 0.001 and P = 0.009, respectively). The pulmonary status of 51.8% of construction workers showed moderate restriction, while 4.70% exhibited obstruction. Considering the construction workers' excessive exposure to PNOS and silica, besides depressed lung function parameters, they can be classified as a high-risk group for respiratory diseases.

Effect of surface functionalizations of multi-walled carbon nanotubes on neoplastic transformation potential in primary human lung epithelial cells.

PubMed

Stueckle, Todd A; Davidson, Donna C; Derk, Ray; Wang, Peng; Friend, Sherri; Schwegler-Berry, Diane; Zheng, Peng; Wu, Nianqiang; Castranova, Vince; Rojanasakul, Yon; Wang, Liying

2017-06-01

Functionalized multi-walled carbon nanotube (fMWCNT) development has been intensified to improve their surface activity for numerous applications, and potentially reduce toxic effects. Although MWCNT exposures are associated with lung tumorigenesis in vivo, adverse responses associated with exposure to different fMWCNTs in human lung epithelium are presently unknown. This study hypothesized that different plasma-coating functional groups determine MWCNT neoplastic transformation potential. Using our established model, human primary small airway epithelial cells (pSAECs) were continuously exposed for 8 and 12 weeks at 0.06 μg/cm 2 to three-month aged as-prepared-(pMWCNT), carboxylated-(MW-COOH), and aminated-MWCNTs (MW-NH x ). Ultrafine carbon black (UFCB) and crocidolite asbestos (ASB) served as particle controls. fMWCNTs were characterized during storage, and exposed cells were assessed for several established cancer cell hallmarks. Characterization analyses conducted at 0 and 2 months of aging detected a loss of surface functional groups over time due to atmospheric oxidation, with MW-NH x possessing less oxygen and greater lung surfactant binding affinity. Following 8 weeks of exposure, all fMWCNT-exposed cells exhibited significant increased proliferation compared to controls at 7 d post-treatment, while UFCB- and ASB-exposed cells did not differ significantly from controls. UFCB, pMWCNT, and MW-COOH exposure stimulated significant transient invasion behavior. Conversely, aged MW-NH x -exposed cells displayed moderate increases in soft agar colony formation and morphological transformation potential, while UFCB cells showed a minimal effect compared to all other treatments. In summary, surface properties of aged fMWCNTs can impact cell transformation events in vitro following continuous, occupationally relevant exposures.

Exposure-Response Estimates for Diesel Engine Exhaust and Lung Cancer Mortality Based on Data from Three Occupational Cohorts

PubMed Central

Silverman, Debra T.; Garshick, Eric; Vlaanderen, Jelle; Portengen, Lützen; Steenland, Kyle

2013-01-01

Background: Diesel engine exhaust (DEE) has recently been classified as a known human carcinogen. Objective: We derived a meta-exposure–response curve (ERC) for DEE and lung cancer mortality and estimated lifetime excess risks (ELRs) of lung cancer mortality based on assumed occupational and environmental exposure scenarios. Methods: We conducted a meta-regression of lung cancer mortality and cumulative exposure to elemental carbon (EC), a proxy measure of DEE, based on relative risk (RR) estimates reported by three large occupational cohort studies (including two studies of workers in the trucking industry and one study of miners). Based on the derived risk function, we calculated ELRs for several lifetime occupational and environmental exposure scenarios and also calculated the fractions of annual lung cancer deaths attributable to DEE. Results: We estimated a lnRR of 0.00098 (95% CI: 0.00055, 0.0014) for lung cancer mortality with each 1-μg/m3-year increase in cumulative EC based on a linear meta-regression model. Corresponding lnRRs for the individual studies ranged from 0.00061 to 0.0012. Estimated numbers of excess lung cancer deaths through 80 years of age for lifetime occupational exposures of 1, 10, and 25 μg/m3 EC were 17, 200, and 689 per 10,000, respectively. For lifetime environmental exposure to 0.8 μg/m3 EC, we estimated 21 excess lung cancer deaths per 10,000. Based on broad assumptions regarding past occupational and environmental exposures, we estimated that approximately 6% of annual lung cancer deaths may be due to DEE exposure. Conclusions: Combined data from three U.S. occupational cohort studies suggest that DEE at levels common in the workplace and in outdoor air appear to pose substantial excess lifetime risks of lung cancer, above the usually acceptable limits in the United States and Europe, which are generally set at 1/1,000 and 1/100,000 based on lifetime exposure for the occupational and general population, respectively. Citation: Vermeulen R, Silverman DT, Garshick E, Vlaanderen J, Portengen L, Steenland K. 2014. Exposure-response estimates for diesel engine exhaust and lung cancer mortality based on data from three occupational cohorts. Environ Health Perspect 122:172–177; http://dx.doi.org/10.1289/ehp.1306880 PMID:24273233

Radon-induced lung cancer deaths may be overestimated due to failure to account for confounding by exposure to diesel engine exhaust in BEIR VI miner studies.

PubMed

Cao, Xiaodong; MacNaughton, Piers; Laurent, Jose Cedeno; Allen, Joseph G

2017-01-01

EPA reported that radon is the second leading cause of lung cancer in the United States, killing 21,100 people per year. EPA relies on the BEIR VI models, based on an evaluation of radon exposure and lung cancer risk in studies of miners. But these models did not account for co-exposure to diesel exhaust, a known human carcinogen recently classified by IARC. It is probable then that a portion of the lung cancer deaths in the miner cohorts are originally attributable to the exposure to diesel rather than radon. To re-evaluate EPA's radon attributable lung cancer estimates accounting for diesel exposure information in the miner cohorts. We used estimates of historical diesel concentrations, combined with diesel exposure-response functions, to estimate the risks of lung cancer attributable to diesel engine exhaust (DEE) exposure in the miner studies. We re-calculated the fatal lung cancer risk attributable to radon after accounting for risk from diesel and re-estimated the number of U.S. deaths associated with radon in the U.S. using EPA's methodology. Considering the probable confounding with DEE exposure and using the same estimate of baseline mortality from 1989-91 that the EPA currently uses in their calculations, we estimate that radon-induced lung cancer deaths per year are 15,600 (95% CI: 14,300, 17,000)- 19,300 (95% CI: 18,800, 20,000) in the U.S. population, a reduction of 9%-26%. The death estimates would be 12,900-15,900 using 2014 baseline vital statistics. We recommend further research on re-evaluating the health effects of exposure to radon that accounts for new information on diesel exhaust carcinogenicity in BEIR VI models, up-to-date vital statistics and new epidemiological evidence from residential studies.

Radon-induced lung cancer deaths may be overestimated due to failure to account for confounding by exposure to diesel engine exhaust in BEIR VI miner studies

PubMed Central

MacNaughton, Piers; Laurent, Jose Cedeno; Allen, Joseph G.

2017-01-01

Background EPA reported that radon is the second leading cause of lung cancer in the United States, killing 21,100 people per year. EPA relies on the BEIR VI models, based on an evaluation of radon exposure and lung cancer risk in studies of miners. But these models did not account for co-exposure to diesel exhaust, a known human carcinogen recently classified by IARC. It is probable then that a portion of the lung cancer deaths in the miner cohorts are originally attributable to the exposure to diesel rather than radon. Objective To re-evaluate EPA’s radon attributable lung cancer estimates accounting for diesel exposure information in the miner cohorts. Methods We used estimates of historical diesel concentrations, combined with diesel exposure-response functions, to estimate the risks of lung cancer attributable to diesel engine exhaust (DEE) exposure in the miner studies. We re-calculated the fatal lung cancer risk attributable to radon after accounting for risk from diesel and re-estimated the number of U.S. deaths associated with radon in the U.S. using EPA’s methodology. Results Considering the probable confounding with DEE exposure and using the same estimate of baseline mortality from 1989–91 that the EPA currently uses in their calculations, we estimate that radon-induced lung cancer deaths per year are 15,600 (95% CI: 14,300, 17,000)– 19,300 (95% CI: 18,800, 20,000) in the U.S. population, a reduction of 9%–26%. The death estimates would be 12,900–15,900 using 2014 baseline vital statistics. Conclusions We recommend further research on re-evaluating the health effects of exposure to radon that accounts for new information on diesel exhaust carcinogenicity in BEIR VI models, up-to-date vital statistics and new epidemiological evidence from residential studies. PMID:28886109

Impact of geocoding methods on associations between long-term exposure to urban air pollution and lung function.

PubMed

Jacquemin, Bénédicte; Lepeule, Johanna; Boudier, Anne; Arnould, Caroline; Benmerad, Meriem; Chappaz, Claire; Ferran, Joane; Kauffmann, Francine; Morelli, Xavier; Pin, Isabelle; Pison, Christophe; Rios, Isabelle; Temam, Sofia; Künzli, Nino; Slama, Rémy; Siroux, Valérie

2013-09-01

Errors in address geocodes may affect estimates of the effects of air pollution on health. We investigated the impact of four geocoding techniques on the association between urban air pollution estimated with a fine-scale (10 m × 10 m) dispersion model and lung function in adults. We measured forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) in 354 adult residents of Grenoble, France, who were participants in two well-characterized studies, the Epidemiological Study on the Genetics and Environment on Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Home addresses were geocoded using individual building matching as the reference approach and three spatial interpolation approaches. We used a dispersion model to estimate mean PM10 and nitrogen dioxide concentrations at each participant's address during the 12 months preceding their lung function measurements. Associations between exposures and lung function parameters were adjusted for individual confounders and same-day exposure to air pollutants. The geocoding techniques were compared with regard to geographical distances between coordinates, exposure estimates, and associations between the estimated exposures and health effects. Median distances between coordinates estimated using the building matching and the three interpolation techniques were 26.4, 27.9, and 35.6 m. Compared with exposure estimates based on building matching, PM10 concentrations based on the three interpolation techniques tended to be overestimated. When building matching was used to estimate exposures, a one-interquartile range increase in PM10 (3.0 μg/m3) was associated with a 3.72-point decrease in FVC% predicted (95% CI: -0.56, -6.88) and a 3.86-point decrease in FEV1% predicted (95% CI: -0.14, -3.24). The magnitude of associations decreased when other geocoding approaches were used [e.g., for FVC% predicted -2.81 (95% CI: -0.26, -5.35) using NavTEQ, or 2.08 (95% CI -4.63, 0.47, p = 0.11) using Google Maps]. Our findings suggest that the choice of geocoding technique may influence estimated health effects when air pollution exposures are estimated using a fine-scale exposure model.

Association between Lung Function in Adults and Plasma DDT and DDE Levels: Results from the Canadian Health Measures Survey

PubMed Central

Ye, Ming; Beach, Jeremy; Martin, Jonathan W.

2014-01-01

Background Although DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane] has been banned in many countries since the 1970s, it may still pose a risk to human respiratory health. In agriculture, DDT exposures have been associated with asthma and chronic bronchitis. However, little is known about the effect of DDT on lung function. Methods We used data on 1,696 participants 20–79 years of age from the Canadian Health Measures Survey (CHMS) and conducted multiple regression analysis to estimate associations between plasma p,p´-DDT/DDE and lung function. Results Almost all participants (> 99.0%) had detectable concentrations of plasma p,p´-DDE, but only 10.0% had detectable p,p´-DDT. Participants with detectable p,p´-DDT had significantly lower mean FVC (difference = 311 mL; 95% CI: –492, –130; p = 0.003) and FEV1 (difference = 232 mL; 95% CI: –408, –55; p = 0.015) than those without. A 100-ng/g lipid increase in plasma p,p´-DDE was associated with an 18.8-mL decrease in mean FVC (95% CI: –29, –9) and an 11.8-mL decrease in mean FEV1 (95% CI: –21, –3). Neither exposure was associated with FEV1/FVC ratio or FEF25%–75%. Conclusions DDT exposures, which may have occurred decades ago, were still detectable among Canadians. Plasma DDT and DDE were negatively associated with lung function parameters. Additional research on the potential effects of DDT use on lung function is warranted. Citation Ye M, Beach J, Martin JW, Senthilselvan A. 2015. Association between lung function in adults and plasma DDT and DDE levels: results from the Canadian Health Measures Survey. Environ Health Perspect 123:422–427; http://dx.doi.org/10.1289/ehp.1408217 PMID:25536373

Analysis of pulmonary surfactant by Fourier-transform infrared spectroscopy following exposure to Stachybotrys chartarum (atra) spores.

PubMed

McCrae, K C; Rand, T; Shaw, R A; Mason, C; Oulton, M R; Hastings, C; Cherlet, T; Thliveris, J A; Mantsch, H H; MacDonald, J; Scott, J E

2001-03-01

Lung cells are among the first tissues of the body to be exposed to air-borne environmental contaminants. Consequently the function of these cells may be altered before other cells are affected. As gas exchange takes place in the lungs, changes in cellular function may have serious implications for the processes of oxygen uptake and carbon dioxide elimination. In order for these processes to occur, the lung must maintain a high degree of expandability. This latter function is accomplished in part by the pulmonary surfactant which is synthesized and released by alveolar type II cells. Earlier studies have shown that exposure to gas phase materials such as smoke or organic solvents can alter the composition and function of the surfactant. The present study examines the ability of highly toxigenic mold spores to alter surfactant composition. Stachybotrys chartarum spores suspended in saline were instilled into mouse trachea as described earlier. After 24 h, the lungs were lavaged and the different processing stages of surfactant isolated by repeated centrifugation. Intracellular surfactant was isolated from the homogenized lung tissue by centrifugation on a discontinuous sucrose gradient. Samples were extracted into chloroform-methanol, dried and analyzed by Fourier-Transform infrared spectroscopy (FTIR). Exposure to S. chartarum induced an overall reduction of phospholipid among the three surfactant subfractions. The intermediate and spent surfactant fractions in particular were reduced to about half of the values observed in the saline-treated group. The relative distribution of phospholipid was also altered by spore exposure. Within the intracellular surfactant pool, higher levels of phospholipid were detected after spore exposure. In addition, changes were observed in the nature of the phospholipids. In particular strong intramolecular hydrogen bonding, together with other changes, suggested that spore exposure was associated with absence of an acyl chain esterified on the glycerol backbone, resulting in elevated levels of lysophospholipid in the samples. This study shows that mold spores and their products induce changes in regulation of both secretion and synthesis of surfactant, as well as alterations in the pattern of phospholipid targeting to the pulmonary surfactant pools.

M2 polarization of macrophages facilitates arsenic-induced cell transformation of lung epithelial cells

PubMed Central

Li, Hui; Dai, Lu; Frank, Jacqueline A.; Peng, Shaojun; Wang, Siying; Chen, Gang

2017-01-01

The alterations in microenvironment upon chronic arsenic exposure may contribute to arsenic-induced lung carcinogenesis. Immune cells, such as macrophages, play an important role in mediating the microenvironment in the lungs. Macrophages carry out their functions after activation. There are two activation status for macrophages: classical (M1) or alternative (M2); the latter is associated with tumorigenesis. Our previous work showed that long-term arsenic exposure induces transformation of lung epithelial cells. However, the crosstalk between epithelial cells and macrophages upon arsenic exposure has not been investigated. In this study, using a co-culture system in which human lung epithelial cells are cultured with macrophages, we determined that long-term arsenic exposure polarizes macrophages towards M2 status through ROS generation. Co-culture with epithelial cells further enhanced the polarization of macrophages as well as transformation of epithelial cells, while blocking macrophage M2 polarization decreased the transformation. In addition, macrophage M2 polarization decreased autophagy activity, which may account for increased cell transformation of epithelial cells with co-culture of macrophages. PMID:28423485

Impact of Geocoding Methods on Associations between Long-term Exposure to Urban Air Pollution and Lung Function

PubMed Central

Jacquemin, Bénédicte; Lepeule, Johanna; Boudier, Anne; Arnould, Caroline; Benmerad, Meriem; Chappaz, Claire; Ferran, Joane; Kauffmann, Francine; Morelli, Xavier; Pin, Isabelle; Pison, Christophe; Rios, Isabelle; Temam, Sofia; Künzli, Nino; Slama, Rémy

2013-01-01

Background: Errors in address geocodes may affect estimates of the effects of air pollution on health. Objective: We investigated the impact of four geocoding techniques on the association between urban air pollution estimated with a fine-scale (10 m × 10 m) dispersion model and lung function in adults. Methods: We measured forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) in 354 adult residents of Grenoble, France, who were participants in two well-characterized studies, the Epidemiological Study on the Genetics and Environment on Asthma (EGEA) and the European Community Respiratory Health Survey (ECRHS). Home addresses were geocoded using individual building matching as the reference approach and three spatial interpolation approaches. We used a dispersion model to estimate mean PM10 and nitrogen dioxide concentrations at each participant’s address during the 12 months preceding their lung function measurements. Associations between exposures and lung function parameters were adjusted for individual confounders and same-day exposure to air pollutants. The geocoding techniques were compared with regard to geographical distances between coordinates, exposure estimates, and associations between the estimated exposures and health effects. Results: Median distances between coordinates estimated using the building matching and the three interpolation techniques were 26.4, 27.9, and 35.6 m. Compared with exposure estimates based on building matching, PM10 concentrations based on the three interpolation techniques tended to be overestimated. When building matching was used to estimate exposures, a one-interquartile range increase in PM10 (3.0 μg/m3) was associated with a 3.72-point decrease in FVC% predicted (95% CI: –0.56, –6.88) and a 3.86-point decrease in FEV1% predicted (95% CI: –0.14, –3.24). The magnitude of associations decreased when other geocoding approaches were used [e.g., for FVC% predicted –2.81 (95% CI: –0.26, –5.35) using NavTEQ, or 2.08 (95% CI –4.63, 0.47, p = 0.11) using Google Maps]. Conclusions: Our findings suggest that the choice of geocoding technique may influence estimated health effects when air pollution exposures are estimated using a fine-scale exposure model. Citation: Jacquemin B, Lepeule J, Boudier A, Arnould C, Benmerad M, Chappaz C, Ferran J, Kauffmann F, Morelli X, Pin I, Pison C, Rios I, Temam S, Künzli N, Slama R, Siroux V. 2013. Impact of geocoding methods on associations between long-term exposure to urban air pollution and lung function. Environ Health Perspect 121:1054–1060; http://dx.doi.org/10.1289/ehp.1206016 PMID:23823697

The β-glucan receptor dectin-1 promotes lung immunopathology during fungal allergy via IL-22.

PubMed

Lilly, Lauren M; Gessner, Melissa A; Dunaway, Chad W; Metz, Allison E; Schwiebert, Lisa; Weaver, Casey T; Brown, Gordon D; Steele, Chad

2012-10-01

Sensitization to fungi, such as the mold Aspergillus fumigatus, is increasingly becoming linked with asthma severity. We have previously shown that lung responses generated via the β-glucan receptor Dectin-1 are required for lung defense during acute, invasive A. fumigatus infection. Unexpectedly, in an allergic model of chronic lung exposure to live A. fumigatus conidia, β-glucan recognition via Dectin-1 led to the induction of multiple proallergic (Muc5ac, Clca3, CCL17, CCL22, and IL-33) and proinflammatory (IL-1β and CXCL1) mediators that compromised lung function. Attenuated proallergic and proinflammatory responses in the absence of Dectin-1 were not associated with changes in Ido (IDO), Il12p35/Ebi3 (IL-35), IL-10, or TGF-β levels. Assessment of Th responses demonstrated that purified lung CD4(+) T cells produced IL-4, IL-13, IFN-γ, and IL-17A, but not IL-22, in a Dectin-1-dependent manner. In contrast, we observed robust, Dectin-1-dependent IL-22 production by unfractionated lung digest cells. Intriguingly, the absence of IL-22 alone mimicked the attenuated proallergic and proinflammatory responses observed in the absence of Dectin-1, suggesting that Dectin-1-mediated IL-22 production potentiated responses that led to decrements in lung function. To this end, neutralization of IL-22 improved lung function in normal mice. Collectively, these results indicate that the β-glucan receptor Dectin-1 contributes to lung inflammation and immunopathology associated with persistent fungal exposure via the production of IL-22.

Lung function impact from working in the pre-revolution Libyan quarry industry.

PubMed

Draid, Marwan M; Ben-Elhaj, Khaled M; Ali, Ashraf M; Schmid, Kendra K; Gibbs, Shawn G

2015-05-07

The purpose of this study was to determine the lung impact from working within the Libyan quarry industry, and if the length of work impacted the degree of degradation. Eighty three workers from eight silica quarries in the Nafusa Mountains of Libya opted to participate. These quarries were working the upper cretaceous geological structure. Eighty-five individuals who lived in Gharyan City with no affiliation to quarry operations participated as controls. Spirometry variables evaluated were Forced Vital Capacity (FVC), Forced Expiratory Volume at 1.0 second (FEV1), FVC/FEV1 and Peak Expiratory Flow (PEF). Control and exposed groups had no differences in terms of height, weight, or smoking status (p = 0.18, 0.20, 0.98, respectively). Prior to adjustment for other variables, FVC, FEV1, and PEF are all significantly lower in the exposed group (p = 0.003, 0.009, 0.03, respectively). After adjustment for age, height, weight, and smoking status, there remain significant differences between the control and exposed groups for FVC, FEV1, and PEF. This analysis demonstrated that exposure to quarry dust has a detrimental effect on lung function, and that pre-revolution Libyan quarry workers were being exposed. This study shows that any exposure is harmful, as the reduction in lung function was not significantly associated with years of exposure.

Lung Function and Inflammatory responses in healthy young adults exposed to 0.06 ppm Ozone for 6.6 hours

EPA Science Inventory

Rationale: Exposure to ozone causes a decrease in spirometric lung function and an increase in airway inflammation in healthy young adults at concentrations as low as 0.08 ppm close to the the National Ambient Air Quality Standard for ground level ozone. Objectives: To test wheth...

Receptor for advanced glycation end-products and World Trade Center particulate induced lung function loss: A case-cohort study and murine model of acute particulate exposure

PubMed Central

Haider, Syed H.; Crowley, George; Lee, Audrey; Ebrahim, Minah; Zhang, Liqun; Chen, Lung-Chi; Gordon, Terry; Liu, Mengling; Prezant, David J.; Schmidt, Ann Marie

2017-01-01

World Trade Center-particulate matter(WTC-PM) exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI). The receptor for advanced glycation end-products (RAGE) is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV). Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-induced lung disease. We know from previous work that early intense exposure at the time of the WTC collapse was most predictive of WTC-LI therefore we utilized a murine model of intense acute PM-exposure to determine if loss of RAGE is protective and to identify signaling/cytokine intermediates. This study builds on a continuing effort to identify serum biomarkers that predict the development of WTC-LI. A case-cohort design was used to analyze a focused cohort of male never-smokers with normal pre-9/11 lung function. Odds of developing WTC-LI increased by 1.2, 1.8 and 1.0 in firefighters with soluble RAGE (sRAGE)≥97pg/mL, CRP≥2.4mg/L, and MMP-9≤397ng/mL, respectively, assessed in a multivariate logistic regression model (ROCAUC of 0.72). Wild type(WT) and RAGE-deficient(Ager-/-) mice were exposed to PM or PBS-control by oropharyngeal aspiration. Lung function, airway hyperreactivity, bronchoalveolar lavage, histology, transcription factors and plasma/BAL cytokines were quantified. WT-PM mice had decreased FEV and compliance, and increased airway resistance and methacholine reactivity after 24-hours. Decreased IFN-γ and increased LPA were observed in WT-PM mice; similar findings have been reported for firefighters who eventually develop WTC-LI. In the murine model, lack of RAGE was protective from loss of lung function and airway hyperreactivity and was associated with modulation of MAP kinases. We conclude that in a multivariate adjusted model increased sRAGE is associated with WTC-LI. In our murine model, absence of RAGE mitigated acute deleterious effects of PM and may be a biologically plausible mediator of PM-related lung disease. PMID:28926576

Inhalation exposure to JP-8 jet fuel alters pulmonary function and substance P levels in Fischer 344 rats.

PubMed

Pfaff, J; Parton, K; Lantz, R C; Chen, H; Hays, A M; Witten, M L

1995-01-01

In a simulated military flightline exposure protocol, Fischer 344 rats (F344) were used to investigate the pulmonary effects of JP-8 jet fuel inhalation. Exposures were nose only and for 1 h daily. Groups were exposed for 7 days (7D) or 28 days (28D). Each exposure group had a matched longitudinal control group (LC7 and LC28). Exposure concentrations of 520 mg m-3 caused an increase in dynamic compliance after 7 days of exposure, but compliance changes were not seen with continued exposure (28D, 495 mg m-3). Pulmonary resistance was increased in both 7- and 28-day JP-8-exposed groups. Changes in pulmonary function were accompanied by a decrease in substance P concentrations from the bronchoalveolar lavage fluid (BALF). No significant change was observed in BALF levels of 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, which is a marker of endothelial cell function. The JP-8-exposed rats gained significantly less weight during the study period than the LC7 and LC28 groups, and the lungs of the 7D group were heavier by wet lung/body weight ratio (WtL/WtB). Alveolar clearance of technetium-labelled diethylenetriamine pentaacetate ([99mTc]DTPA) was increased in jet fuel-exposed groups. Light microscopy showed no pathological evidence of lung injury. Recovery from the early pulmonary effects of JP-8 inhalation occurred with continued exposure, as seen by recovery of pulmonary compliance and WtL/WtB.

Exposure to ammonia and acute respiratory effects in a urea fertilizer factory.

PubMed

Rahman, Md Hamidur; Bråtveit, Magne; Moen, Bente E

2007-01-01

Personal exposures to ammonia and acute respiratory effects were determined in workers at a urea fertilizer factory in Bangladesh. Full-shift personal exposure to ammonia was measured using a PAC III direct reading instrument and Drager diffusion tubes. Respiratory symptoms were elicited by a questionnaire study (n = 113), and preshift and postshift lung function (FVC, FEV1, and PEFR) were tested using spirometry (n = 88). Urea plant workers had higher mean exposure to ammonia and prevalence of acute respiratory symptoms than did workers in the ammonia plant. The symptoms with highest prevalence in the urea plant were chest tightness (33%) and cough (28%). FVC and FEV1 decreased significantly across the work shift among urea plant workers. The higher level of exposure to ammonia in the urea plant was associated with an increased prevalence of respiratory symptoms and an acute decline in lung function.

Assessment of respiratory symptoms and lung function values among the brick field workers of West Bengal, India.

PubMed

Das, Banibrata

2016-07-03

Brick manufacturing process releases large amounts of silica dust into the work environment due to the use of silica-containing materials. The main aim of the study was to investigate the impairment of lung function and prevalence of respiratory symptoms among the different groups of brick field workers in comparison with control subjects. A total of 250 brick field workers and 130 unexposed control subjects were randomly selected in which demographic characteristics, respiratory symptoms, and lung function values were recorded. The result showed significantly lower p value (<.001) in lung function and respiratory symptoms among brick field workers when compared with control group. The prevalence of respiratory symptoms was dyspnea (46.8%), phlegm (39.2%), and chest tightness (27.6%). Dust exposure in working environment affected the lung function values and increased the respiratory symptoms among the brick field workers.

Effect of a smoking ban on respiratory health in nonsmoking hospitality workers: a prospective cohort study.

PubMed

Rajkumar, Sarah; Stolz, Daiana; Hammer, Jürg; Moeller, Alexander; Bauer, Georg F; Huynh, Cong Khanh; Röösli, Martin

2014-10-01

The aim of this study was to examine the effect of a smoking ban on lung function, fractional exhaled nitric oxide, and respiratory symptoms in nonsmoking hospitality workers. Secondhand smoke exposure at the workplace, spirometry, and fractional exhaled nitric oxide were measured in 92 nonsmoking hospitality workers before as well as twice after a smoking ban. At baseline, secondhand smoke-exposed hospitality workers had lung function values significantly below the population average. After the smoking ban, the covariate-adjusted odds ratio for cough was 0.59 (95% confidence interval, 0.36 to 0.93) and for chronic bronchitis 0.75 (95% confidence interval, 0.55 to 1.02) compared with the preban period. The below-average lung function before the smoking ban indicates chronic damages from long-term exposure. Respiratory symptoms such as cough decreased within 12 months after the ban.

Biology Based Lung Cancer Model for Chronic Low Radon Exposures

NASA Astrophysics Data System (ADS)

TruÅ£ǎ-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

2008-08-01

Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival. To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates.

Low level CO2 effects on pulmonary function in humans

NASA Technical Reports Server (NTRS)

Sexton, J.; Mueller, K.; Elliott, A.; Gerzer, D.; Strohl, K. P.; West, J. B. (Principal Investigator)

1998-01-01

The purpose of the study was to determine whether chamber exposure to low levels of CO2 results in functional alterations in gas mixing and closing volume in humans. Four healthy volunteer subjects were exposed to 0.7% CO2 and to 1.2% CO2. Spirometry, lung volumes, single breath nitrogen washout, diffusing capacity for carbon monoxide (DLCO) by two methods, and cardiac output were measured in triplicate. Values were obtained over two non-consecutive days during the training period (control) and on days 2 or 3, 4, 6, 10, 13, and 23 of exposure to each CO2 level. Measurements were made during the same time of day. There was one day of testing after exposure, while still in the chamber but off carbon dioxide. The order of testing, up until measurements of DLCO and cardiac output, were randomized to avoid presentation effects. The consistent findings were a reduction in diffusing capacity for carbon monoxide and a fall in cardiac output, occurring to a similar degree with both exposures. For the group as a whole, there was no indication of major effects on spirometry, lung volumes, gas mixing or dead space. We conclude that small changes may occur in the function of distal gas exchanging units; however, these effects were not associated with any adverse health effects. The likelihood of pathophysiologic changes in lung function or structure with 0.7 or 1.2% CO2 exposure for this period of time, is therefore, low.

Pleural plaques and their effect on lung function in Libby vermiculite miners.

PubMed

Clark, Kathleen A; Flynn, J Jay; Goodman, Julie E; Zu, Ke; Karmaus, Wilfried J J; Mohr, Lawrence C

2014-09-01

Multiple studies have investigated the relationship between asbestos-related pleural plaques (PPs) and lung function, with disparate and inconsistent results. Most use chest radiographs to identify PPs and simple spirometry to measure lung function. High-resolution CT (HRCT) scanning improves the accuracy of PP identification. Complete pulmonary function tests (PFTs), including spirometry, lung volumes, and diffusing capacity of the lung for carbon monoxide, provide a more definitive assessment of lung function. The goal of this study was to determine, using HRCT scanning and complete PFTs, the effect of PPs on lung function in Libby vermiculite miners. The results of HRCT scanning and complete PFTs performed between January 2000 and August 2012 were obtained from the medical records of 166 Libby vermiculite miners. Multivariate regression analyses with Tukey multivariate adjustment were used to assess statistical associations between the presence of PPs and lung function. Adjustments were made for age, BMI, smoking history, duration of employment, and years since last occupational asbestos exposure. Nearly 90% of miners (n = 149) had evidence of PPs on HRCT scan. No significant differences in spirometry results, lung volumes, or diffusing capacity of the lung for carbon monoxide were found between miners with PPs alone and miners with normal HRCT scans. Miners with both interstitial fibrosis and the presence of PPs had a significantly decreased total lung capacity in comparison with miners with normal HRCT scans (P = .02). Age, cumulative smoking history, and BMI were significant covariates that contributed to abnormal lung function. Asbestos-related PPs alone have no significant effect on lung function in Libby vermiculite miners.

The effect of CSF-1 administration on lung maturation in a mouse model of neonatal hyperoxia exposure.

PubMed

Jones, Christina V; Alikhan, Maliha A; O'Reilly, Megan; Sozo, Foula; Williams, Timothy M; Harding, Richard; Jenkin, Graham; Ricardo, Sharon D

2014-09-06

Lung immaturity due to preterm birth is a significant complication affecting neonatal health. Despite the detrimental effects of supplemental oxygen on alveolar formation, it remains an important treatment for infants with respiratory distress. Macrophages are traditionally associated with the propagation of inflammatory insults, however increased appreciation of their diversity has revealed essential functions in development and regeneration. Macrophage regulatory cytokine Colony-Stimulating Factor-1 (CSF-1) was investigated in a model of neonatal hyperoxia exposure, with the aim of promoting macrophages associated with alveologenesis to protect/rescue lung development and function. Neonatal mice were exposed to normoxia (21% oxygen) or hyperoxia (Hyp; 65% oxygen); and administered CSF-1 (0.5 μg/g, daily × 5) or vehicle (PBS) in two treatment regimes; 1) after hyperoxia from postnatal day (P)7-11, or 2) concurrently with five days of hyperoxia from P1-5. Lung structure, function and macrophages were assessed using alveolar morphometry, barometric whole-body plethysmography and flow cytometry. Seven days of hyperoxia resulted in an 18% decrease in body weight and perturbation of lung structure and function. In regime 1, growth restriction persisted in the Hyp + PBS and Hyp + CSF-1 groups, although perturbations in respiratory function were resolved by P35. CSF-1 increased CSF-1R+/F4/80+ macrophage number by 34% at P11 compared to Hyp + PBS, but was not associated with growth or lung structural rescue. In regime 2, five days of hyperoxia did not cause initial growth restriction in the Hyp + PBS and Hyp + CSF-1 groups, although body weight was decreased at P35 with CSF-1. CSF-1 was not associated with increased macrophages, or with functional perturbation in the adult. Overall, CSF-1 did not rescue the growth and lung defects associated with hyperoxia in this model; however, an increase in CSF-1R+ macrophages was not associated with an exacerbation of lung injury. The trophic functions of macrophages in lung development requires further elucidation in order to explore macrophage modulation as a strategy for promoting lung maturation.

Effect of exposure to diesel exhaust particles on the susceptibility of the lung to infection.

PubMed

Castranova, V; Ma, J Y; Yang, H M; Antonini, J M; Butterworth, L; Barger, M W; Roberts, J; Ma, J K

2001-08-01

There are at least three mechanisms by which alveolar macrophages play a critical role in protecting the lung from bacterial or viral infections: production of inflammatory cytokines that recruit and activate lung phagocytes, production of antimicrobial reactive oxidant species, and production of interferon (an antiviral agent). In this article we summarize data concerning the effect of exposure to diesel exhaust particles on these alveolar macrophage functions and the role of adsorbed organic chemicals compared to the carbonaceous core in the toxicity of diesel particles. In vitro exposure of rat alveolar macrophages to diesel exhaust particles decreased the ability of lipopolysaccharide (LPS), a bacterial product] to stimulate the production of inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). Methanol extract exhibited this potential but methanol-washed diesel particles did not. Exposure of rats to diesel exhaust particles by intratracheal instillation also decreased LPS-induced TNF-alpha and IL-1 production from alveolar macrophages. In contrast, carbon black did not exhibit this inhibitory effect. Exposure of rats to diesel exhaust particles by inhalation decreased the ability of alveolar macrophages to produce antimicrobial reactive oxidant species in response to zymosan (a fungal component). In contrast, exposure to coal dust increased zymosan-stimulated oxidant production. In vivo exposure to diesel exhaust particles but not to carbon black decreased the ability of the lungs to clear bacteria. Inhalation exposure of mice to diesel exhaust particles but not to coal dust depressed the ability of the lung to produce the antiviral agent interferon and increased viral multiplication in the lung. These results support the hypothesis that exposure to diesel exhaust particles increases the susceptibility of the lung to infection by depressing the antimicrobial potential of alveolar macrophages. This inhibitory effect appears to be due to adsorbed organic chemicals rather than the carbonaceous core of the diesel particles.

Effect of exposure to diesel exhaust particles on the susceptibility of the lung to infection.

PubMed Central

Castranova, V; Ma, J Y; Yang, H M; Antonini, J M; Butterworth, L; Barger, M W; Roberts, J; Ma, J K

2001-01-01

There are at least three mechanisms by which alveolar macrophages play a critical role in protecting the lung from bacterial or viral infections: production of inflammatory cytokines that recruit and activate lung phagocytes, production of antimicrobial reactive oxidant species, and production of interferon (an antiviral agent). In this article we summarize data concerning the effect of exposure to diesel exhaust particles on these alveolar macrophage functions and the role of adsorbed organic chemicals compared to the carbonaceous core in the toxicity of diesel particles. In vitro exposure of rat alveolar macrophages to diesel exhaust particles decreased the ability of lipopolysaccharide (LPS), a bacterial product] to stimulate the production of inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha). Methanol extract exhibited this potential but methanol-washed diesel particles did not. Exposure of rats to diesel exhaust particles by intratracheal instillation also decreased LPS-induced TNF-alpha and IL-1 production from alveolar macrophages. In contrast, carbon black did not exhibit this inhibitory effect. Exposure of rats to diesel exhaust particles by inhalation decreased the ability of alveolar macrophages to produce antimicrobial reactive oxidant species in response to zymosan (a fungal component). In contrast, exposure to coal dust increased zymosan-stimulated oxidant production. In vivo exposure to diesel exhaust particles but not to carbon black decreased the ability of the lungs to clear bacteria. Inhalation exposure of mice to diesel exhaust particles but not to coal dust depressed the ability of the lung to produce the antiviral agent interferon and increased viral multiplication in the lung. These results support the hypothesis that exposure to diesel exhaust particles increases the susceptibility of the lung to infection by depressing the antimicrobial potential of alveolar macrophages. This inhibitory effect appears to be due to adsorbed organic chemicals rather than the carbonaceous core of the diesel particles. PMID:11544172

Perinatal stress and early life programming of lung structure and function

PubMed Central

Wright, Rosalind J.

2010-01-01

Exposure to environmental toxins during critical periods of prenatal and/or postnatal development may alter the normal course of lung morphogenesis and maturation, potentially resulting in changes that affect both structure and function of the respiratory system. Moreover, these early effects may persist into adult life magnifying the potential public health impact. Aberrant or excessive pro-inflammatory immune responses, occurring both locally and systemically, that result in inflammatory damage to the airway are a central determinant of lung structure-function changes throughout life. Disruption of neuroendocrine function in early development, specifically the hypothalamic-pituitary-adrenal (HPA) axis, may alter functional status of the immune system. Autonomic nervous system (ANS) function (sympathovagal imbalance) is another integral component of airway function and immunity in childhood. This overview discusses the evidence linking psychological factors to alterations in these interrelated physiological processes that may, in turn, influence childhood lung function and identifies gaps in our understanding. PMID:20080145

Effect of indoor air pollution on the respiratory system of women using different fuels for cooking in an urban slum of Pondicherry.

PubMed

Dutt, D; Srinivasa, D K; Rotti, S B; Sahai, A; Konar, D

1996-01-01

Some of the highest exposures to air pollutants in developing countries occur inside homes where biofuels are used for daily cooking. Inhalation of these pollutants may cause deleterious effects on health. We studied the effects of exposure to indoor air pollution from the use of cooking fuels on lung functions and respiratory symptoms in women aged 15-60 years. The study was conducted in Kuruchikuppam, an urban slum in Pondicherry. The study participants were 105 women using biofuels, 105 using kerosene and 105 using liquid petroleum gas (LPG), selected from among 1117 women aged 15-60 years, by a stratified random sampling technique. These women were interviewed at home to collect information about exposure to fuel smoke and presence of respiratory symptoms. Lung functions were assessed by measuring forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak expiratory flow rate (PEFR). Occurrence of respiratory symptoms over six months was noted by making monthly follow up visits. Women using biofuels experienced more respiratory symptoms (23%) than those using kerosene (13%;p > 0.05) or LPG (8%; p < 0.05). Lung functions-FVC, FEV1, FEV1% and PEFR-were significantly lower in biofuel users compared with both kerosene (p < 0.01) and LPG users (p < 0.001). Lung functions in kerosene users also were significantly poorer when compared with LPG users (p < 0.01). Predicted pulmonary functions using multiple regression equations, derived from the data set of the present study, indicated that women using biofuels were more liable to have reduced pulmonary functions than women using kerosene or LPG. Women exposed to biofuel smoke suffer more from respiratory illnesses and have decreased pulmonary functions compared with women exposed to kerosene or LPG smoke. To reduce pollutant exposures we recommend the use of smokeless chullas or cleaner fuels such as charcoal, biogas and kerosene.

Evaluation of an exposure setup for studying effects of diesel exhaust in humans.

PubMed

Rudell, B; Sandström, T; Hammarström, U; Ledin, M L; Hörstedt, P; Stjernberg, N

1994-01-01

Diesel exhaust is a common air pollutant and work exposure has been reported to cause discomfort and affect lung function. The aim of this study was to develop an experimental setup which would allow investigation of acute effects on symptoms and lung function in humans exposed to diluted diesel exhaust. Diluted diesel exhaust was fed from an idling lorry through heated tubes into an exposure chamber. During evaluations of the setup we found the size and the shape of the exhaust particles to appear unchanged during the transport from the tail pipe to the exposure chamber. The composition of the diesel exhaust expressed as the ratios CO/NO, total hydrocarbons/NO, particles/NO, NO2/NO, and formaldehyde/NO were almost constant at different dilutions. The concentrations of NO2 and particles in the exposure chamber showed no obvious gradients. New steady state concentrations in the exposure chamber were obtained within 5-7 min. In a separate experiment eight healthy nonsmoking subjects were exposed to diluted exhaust at a median steady state concentration of 1.6 ppm NO2 for the duration of 1 h in the exposure chamber. All subjects experienced unpleasant smell, eye irritation, and nasal irritation. Throat irritation, headache, dizziness, nausea, tiredness, and coughing were experienced by some subjects. Lung function was not found to be affected during the exposure. The experimental setup was found to be appropriate for creating different predetermined steady state concentrations in the exposure chamber of diluted exhaust from a continuously idling vehicle. The acute symptoms reported by the subjects were relatively similar to what patients reported at different workplaces.

Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh

PubMed Central

Smith, Allan H; Yunus, Mohammad; Khan, Al Fazal; Ercumen, Ayse; Yuan, Yan; Smith, Meera Hira; Liaw, Jane; Balmes, John; von Ehrenstein, Ondine; Raqib, Rubhana; Kalman, David; Alam, Dewan S; Streatfield, Peter K; Steinmaus, Craig

2013-01-01

Background Arsenic exposure via drinking water increases the risk of chronic respiratory disease in adults. However, information on pulmonary health effects in children after early life exposure is limited. Methods This population-based cohort study set in rural Matlab, Bangladesh, assessed lung function and respiratory symptoms of 650 children aged 7–17 years. Children with in utero and early life arsenic exposure were compared with children exposed to less than 10 µg/l in utero and throughout childhood. Because most children drank the same water as their mother had drunk during pregnancy, we could not assess only in utero or only childhood exposure. Results Children exposed in utero to more than 500 µg/l of arsenic were more than eight times more likely to report wheezing when not having a cold [odds ratio (OR) = 8.41, 95% confidence interval (CI): 1.66–42.6, P < 0.01] and more than three times more likely to report shortness of breath when walking on level ground (OR = 3.86, 95% CI: 1.09–13.7, P = 0.02) and when walking fast or climbing (OR = 3.19, 95% CI: 1.22–8.32, P < 0.01]. However, there was little evidence of reduced lung function in either exposure category. Conclusions Children with high in utero and early life arsenic exposure had marked increases in several chronic respiratory symptoms, which could be due to in utero exposure or to early life exposure, or to both. Our findings suggest that arsenic in water has early pulmonary effects and that respiratory symptoms are a better marker of early life arsenic toxicity than changes in lung function measured by spirometry. PMID:24062297

Endotoxin and gender modify lung function recovery after occupational organic dust exposure: a 30-year study.

PubMed

Lai, Peggy S; Hang, Jing-Qing; Valeri, Linda; Zhang, Feng-Ying; Zheng, Bu-Yong; Mehta, Amar J; Shi, Jing; Su, Li; Brown, Dan; Eisen, Ellen A; Christiani, David C

2015-08-01

The purpose of this study is to determine the trajectory of lung function change after exposure cessation to occupational organic dust exposure, and to identify factors that modify improvement. The Shanghai Textile Worker Study is a longitudinal study of 447 cotton workers exposed to endotoxin-containing dust and 472 silk workers exposed to non-endotoxin-containing dust. Spirometry was performed at 5-year intervals. Air sampling was performed to estimate individual cumulative exposures. The effect of work cessation on forced expiratory volume in 1 s (FEV1) was modelled using generalised additive mixed effects models to identify the trajectory of FEV1 recovery. Linear mixed effects models incorporating interaction terms were used to identify modifiers of FEV1 recovery. Loss to follow-up was accounted for with inverse probability of censoring weights. 74.2% of the original cohort still alive participated in 2011. Generalised additive mixed models identified a non-linear improvement in FEV1 for all workers after exposure cessation, with no plateau noted 25 years after retirement. Linear mixed effects models incorporating interaction terms identified prior endotoxin exposure (p=0.01) and male gender (p=0.002) as risk factors for impaired FEV1 improvement after exposure cessation. After adjusting for gender, smoking delayed the onset of FEV1 gain but did not affect the overall magnitude of change. Lung function improvement after cessation of exposure to organic dust is sustained. Endotoxin exposure and male gender are risk factors for less FEV1 improvement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cumulative exposure to dust causes accelerated decline in lung function in tunnel workers

PubMed Central

Ulvestad, B; Bakke, B; Eduard, W; Kongerud, J; Lund, M

2001-01-01

OBJECTIVES—To examine whether underground construction workers exposed to tunnelling pollutants over a follow up period of 8 years have an increased risk of decline in lung function and respiratory symptoms compared with reference subjects working outside the tunnel atmosphere, and relate the findings to job groups and cumulative exposure to dust and gases.
METHODS—96 Tunnel workers and a reference group of 249 other heavy construction workers were examined in 1991 and re-examined in 1999. Exposure measurements were carried out to estimate personal cumulative exposure to total dust, respirable dust, α-quartz, oil mist, and nitrogen dioxide. The subjects answered a questionnaire on respiratory symptoms and smoking habits, performed spirometry, and had chest radiographs taken. Radiological signs of silicosis were evaluated (International Labour Organisation (ILO) classification). Atopy was determined by a multiple radioallergosorbent test (RAST).
RESULTS—The mean exposure to respirable dust and α-quartz in tunnel workers varied from 1.2-3.6 mg/m3 (respirable dust) and 0.019-0.044 mg/m3 (α-quartz) depending on job task performed. Decrease in forced expiratory volume in 1 second (FEV1) was associated with cumulative exposure to respirable dust (p<0.001) and α-quartz (p=0.02). The multiple regression model predicted that in a worker 40 years of age, the annual decrease in FEV1 would be 25 ml in a non-exposed non-smoker, 35 ml in a non-exposed smoker, and 50-63 ml in a non-smoking tunnel worker (depending on job). Compared with the reference group the odds ratio for the occurrence of new respiratory symptoms during the follow up period was increased in the tunnel workers and associated with cumulative exposure to respirable dust.
CONCLUSIONS—Cumulative exposures to respirable dust and α-quartz are the most important risk factors for airflow limitation in underground heavy construction workers, and cumulative exposure to respirable dust is the most important risk factor for respiratory symptoms. The finding of accelerated decline in lung function in tunnel workers suggests that better control of exposures is needed.


Keywords: heavy construction; respirable dust; lung function PMID:11555688

Cumulative exposure to dust and gases as determinants of lung function decline in tunnel construction workers

PubMed Central

Bakke, B; Ulvestad, B; Stewart, P; Eduard, W

2004-01-01

Aims: To study the relation between lung function decrease and cumulative exposure to dust and gases in tunnel construction workers. Methods: A total of 651 male construction workers (drill and blast workers, tunnel concrete workers, shotcreting operators, and tunnel boring machine workers) were followed up by spirometric measurements in 1989–2002 for an average of six years. Outdoor concrete workers, foremen, and engineers served as a low exposed referent population. Results: The between worker component of variability was considerably reduced within the job groups compared to the whole population, suggesting that the workers within job groups had similar exposure levels. The annual decrease in FEV1 in low-exposed non-smoking workers was 21 ml and 24 ml in low-exposed ever smokers. The annual decrease in FEV1 in tunnel construction workers was 20–31 ml higher than the low exposed workers depending on job group for both non-smokers and ever smokers. After adjustment for age and observation time, cumulative exposure to nitrogen dioxide showed the strongest association with a decrease in FEV1 in both non-smokers, and ever smokers. Conclusion: Cumulative exposure to nitrogen dioxide appeared to be a major risk factor for lung function decreases in these tunnel construction workers, although other agents may have contributed to the observed effect. Contact with blasting fumes should be avoided, diesel exhaust emissions should be reduced, and respiratory devices should be used to protect workers against dust and nitrogen dioxide exposure. PMID:14985522

Enhanced alveolar growth and remodeling in Guinea pigs raised at high altitude.

PubMed

Hsia, Connie C W; Carbayo, Juan J Polo; Yan, Xiao; Bellotto, Dennis J

2005-05-12

To examine the effects of chronic high altitude (HA) exposure on lung structure during somatic maturation, we raised male weanling guinea pigs at HA (3800m) for 1, 3, or 6 months, while their respective male littermates were simultaneously raised at low altitude (LA, 1200m). Under anaesthesia, airway pressure was measured at different lung volumes. The right lung was fixed at a constant airway pressure for morphometric analysis under light and electron microscopy. In animals raised at HA for 1 month, lung volume, alveolar surface area and alveolar-capillary blood volume (V(c)) were elevated above LA control values. Following 3-6 months of HA exposure, increases in lung volume and alveolar surface area persisted while the initial increase in V(c) normalized. Additional adaptation occurred, including a higher epithelial cell volume, septal tissue volume and capillary surface area, a lower alveolar duct volume and lower harmonic mean diffusion barrier resulting in higher membrane and lung diffusing capacities. These data demonstrate enhanced alveolar septal growth and progressive acinar remodeling during chronic HA exposure with long-term augmentation of alveolar dimensions as well as functional compensation in lung compliance and diffusive gas transport.

Chest circumference and birth weight are good predictors of lung function in preschool children from an e-waste recycling area.

PubMed

Zeng, Xiang; Xu, Xijin; Zhang, Yuling; Li, Weiqiu; Huo, Xia

2017-10-01

The purpose of this study was to investigate the associations between birth weight, chest circumference, and lung function in preschool children from e-waste exposure area. A total of 206 preschool children from Guiyu (an e-waste recycling area) and Haojiang and Xiashan (the reference areas) in China were recruited and required to undergo physical examination, blood tests, and lung function tests during the study period. Birth outcome such as birth weight and birth height were obtained by questionnaire. Children living in the e-waste-exposed area have a lower birth weight, chest circumference, height, and lung function when compare to their peers from the reference areas (all p value <0.05). Both Spearman and partial correlation analyses showed that birth weight and chest circumference were positively correlated with lung function levels including forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ). After adjustment for the potential confounders in further linear regression analyses, birth weight, and chest circumference were positively associated with lung function levels, respectively. Taken together, birth weight and chest circumference may be good predictors for lung function levels in preschool children.

[Cohort study of effects on lung function of coke oven workers exposured to coke oven emissions].

PubMed

Zhi, Yongfen; Zhang, Hongming; Li, Weixing; Hu, Zhipeng; Liu, Weihua; Li, Yangfan; Zheng, Jinpin

2015-07-01

Through comparative study on pulmonary function damage of coke oven workers exposed to coke oven emissions with the same group before and after five years, and further explore the relationship between the coke oven emissions and injury in pulmonary function of coke oven worker. Select a coking plant in Shanxi 165 coke oven workers (exposed group) and 52 auxiliary workers (control group) for the study, using a uniform questionnaire to collect workers' personal information. Fixed workplace air samples collected periodically. Air samples of benzo (a) pyrene concentrations was measured by high pressure liquid chromatograph. Pulmonary function of research object was measured by portable spirometer respectively in 2009 and 2013, and comparative analysis on it. The concentration of B(a)P was no significant difference in the same area between 5 years in 2009-2013. Compared with 2009, 2013 control workers lung function index and the abnormal rate had no significant difference (P > 0.05). But FVC%, FEV1.0%, MVV%, VC% and FEF25% of exposed workers in 2013 was significantly lower than in 2009, FVC%, FEV1.0%, VC% and FEF25% pulmonary dysfunction rate in 2013 was also significantly higher than in 2009, difference was statistically significant (P < 0.05). Workers emerging pulmonary function abnormalities mainly distributed in furnace roof and side. furnace roof group FVC%, FEV1.0%, VC% additional abnormal number (rate) was significantly higher than furnace floor and the control group (P < 0.05), and furnace side groop was significantly higher than the control group, the difference was statistically significant (P < 0.05). Multivariate Logistic regression analysis showed that after 5 years FVC%, FEV1% and VC% of abnormal lung function emerging adjusted OR of furnace roof workers were 7.939, 5.966 and 4.956. For abnormal of FVC%, FEV1%, VC% and MVV%, the contacting coke seniority is a risk factor. There is a positive interaction between contacting coke seniority and furnace roof (P < 0.05). Coke oven workers lung function damage associated with exposureing to coke oven emissions, coke oven emissions exposure level and exposure time are the main factors of coke oven workers in lung function damage, there is a positive interaction between the two factors.

System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snyder-Talkington, Brandi N.; Dymacek, Julian; Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300

2013-10-15

The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 μg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chainmore » simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and was used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. - Highlights: • A novel computational model identified toxicity pathways matching in vivo pathology. • Systematic identification of MWCNT-induced biological processes in mouse lungs • MWCNT-induced functional networks of lung inflammation and fibrosis were revealed. • Two functional, representative genes, ccl2 and vegfa, were validated in vitro.« less

Occupation, smoking, and chronic obstructive respiratory disorders: a cross sectional study in an industrial area of Catalonia, Spain

PubMed Central

Jaén, Ángeles; Zock, Jan Paul; Kogevinas, Manolis; Ferrer, Antonio; Marín, Albert

2006-01-01

Background Few studies have investigated the independent effects of occupational exposures and smoking on chronic bronchitis and airflow obstruction. We assessed the association between lifetime occupational exposures and airflow obstruction in a cross-sectional survey in an urban-industrial area of Catalonia, Spain. Methods We interviewed 576 subjects of both sexes aged 20–70 years (response rate 80%) randomly selected from census rolls, using the ATS questionnaire. Forced spirometry was performed by 497 subjects according to ATS normative. Results Lifetime occupational exposure to dust, gases or fumes was reported by 52% of the subjects (63% in men, 41% in women). Textile industry was the most frequently reported job in relation to these exposures (39%). Chronic cough, expectoration and wheeze were more prevalent in exposed subjects with odds ratios ranging from 1.7 to 2.0 being highest among never-smokers (2.1 to 4.3). Lung function differences between exposed and unexposed subjects were dependent on duration of exposure, but not on smoking habits. Subjects exposed more than 15 years to dusts, gases or fumes had lower lung function values (FEV1 -80 ml, 95% confidence interval (CI) -186 to 26; MMEF -163 ml, CI -397 to 71; FEV1/FVC ratio -1.7%, CI -3.3 to -0.2) than non-exposed. Conclusion Chronic bronchitis symptoms and airflow obstruction are associated with occupational exposures in a population with a high employment in the textile industry. Lung function impairment was related to the duration of occupational exposure, being independent of the effect of smoking. PMID:16476167

Respiratory and skin effects of exposure to wood dust from the rubber tree Hevea brasiliensis.

PubMed

Sripaiboonkij, P; Phanprasit, W; Jaakkola, M S

2009-07-01

Potential health effects related to wood dust from the rubber tree, which produces natural rubber latex, have not been previously investigated. The main aim of this study was to investigate the relations of rubber tree dust exposure to respiratory and skin symptoms, asthma and lung function. A cross-sectional study was conducted among 103 workers (response rate 89%) in a rubber tree furniture factory and 76 office workers (73%) in four factories in Thailand. All participants answered a questionnaire and performed spirometry. Inhalable dust levels were measured in different work areas. Factory workers showed increased risk of wheezing, nasal symptoms and asthma compared to office workers. There was a dose-dependent increase in wheeze and skin symptoms in relation to dust level. Significantly increased risks of nasal symptoms (adj OR 3.67, 95% CI 1.45 to 9.28) and asthma (8.41, 1.06 to 66.60) were detected in the low exposure category. Workers exposed to ethyl cyanoacrylate glue had significantly increased risk of cough, breathlessness and nasal symptoms. There was dose-dependent reduction in spirometric lung function with wood dust level. This study provides new evidence that workers exposed to wood dust from the rubber tree experience increased risk of nasal symptoms, wheeze, asthma and skin symptoms and have reduced spirometric lung function. Exposure to cyanoacrylate is related to significantly increased respiratory symptoms. Results suggest that the furniture industry using rubber tree wood should implement appropriate exposure control measures to reduce wood dust exposure and cyanoacrylate glue exposure to protect their employees.

Terpene exposure and respiratory effects among workers in Swedish joinery shops.

PubMed

Eriksson, K A; Levin, J O; Sandström, T; Lindström-Espeling, K; Lindén, G; Stjernberg, N L

1997-04-01

Exposure to monoterpenes (alpha-pinene, beta-pinene and delta 3-carene) in joinery shops was studied in Sweden during the processing of Scot's pine, and the acute respiratory effects among the employees were evaluated. A cross-sectional study of 38 workers was carried out in 4 joinery shops. The investigation included personal air sampling of monoterpenes, biological monitoring of metabolites of alpha-pinene in the workers' urine, interviews following a standardized questionnaire, and dynamic spirometry. The personal exposure to monoterpenes in the joinery shops was 10-214 mg/m3. The correlation (correlation coefficient = 0.69) between exposure to alpha-pinene and verbenols (metabolites from alpha-pinene) in urine was relatively good. No acute effects on forced vital capacity or forced expiratory volume during 1 s were detected. The workers had significantly reduced preshift lung function values when compared with the values of a local reference group, even when smokers and ex-smokers were excluded. Personal exposure to the monoterpenes alpha-pinene, and delta 3-carene in joinery shops may exceed the present Swedish occupational exposure limit of 150 mg/m3 during the winter season when workroom air is commonly recirculated. The determination of metabolites of alpha-pinene (verbenols) in urine can be used as an index of exposure to fumes released during wood-treating processes. The results from the lung function tests indicate chronic rather than acute reactions in the airways. The fact that there were no major changes in lung function over a workshift indicates chronic reaction in the airways.

Respiratory health effects of long-term exposure to different chromium species in stainless steel production.

PubMed

Huvinen, M; Uitti, J; Oksa, P; Palmroos, P; Laippala, P

2002-06-01

The aim of this study was to determine whether occupational exposure to chromite, trivalent chromium (Cr(3+)) or hexavalent chromium (Cr(6+)) causes respiratory diseases, an excess of respiratory symptoms, a decrease in pulmonary function or signs of pneumoconiosis among workers in stainless steel production. Altogether, 203 exposed workers and 81 referents with an average employment of 23 years were investigated for indicators of respiratory health on two occasions, in 1993 and in 1998. Data collection with a self-administered questionnaire, flow volume spirometry, measurement of diffusing capacity, chest radiography and laboratory tests were carried out by a mobile research unit. Exposure to different chromium species and other metals was monitored regularly and studied separately. No adverse respiratory health effects were observed in the group exposed to Cr(6+), either in comparison with the control group in the first cross-sectional study or during the additional 5 year follow-up. Among the Cr (3+) exposed people, the production of phlegm, shortness of breath and breathlessness on exertion were significantly more frequent than in the control group, but the frequency of the symptoms did not increase during the follow-up; no differences were observed in the lung function tests and the radiographic findings did not progress. In the chromite group, the prevalence of breathlessness on exertion was higher than in the control group. However, in the follow-up, the occurrence of symptoms did not differ from 1993 to 1998. In the first study, most parameters of lung function were lower among the smokers in the chromite group than among the smoking controls, but in 1998 the difference was less marked. An average exposure time of 23 years in modern ferrochromium and stainless steel production and low exposure to dusts and fumes containing Cr(6+), Cr(3+), nickel and molybdenum do not lead to respiratory changes detectable by lung function tests or radiography. The workers exposed to Cr(3+) had more respiratory symptoms than those in the control group. The workers in the chromite mine had lower lung function test results than the control group due to earlier exposure to higher dust concentrations.

The association of exposure to hepatitis B and C viruses with lung function and respiratory disease: a population based study from the NHANES III database.

PubMed

Goh, Li Yen; Card, Tim; Fogarty, Andrew W; McKeever, Tricia M

2014-12-01

Globally, 500 million people are chronically infected with Hepatitis B virus (HBV) and Hepatitis C virus (HCV). While these viruses are notorious for their detrimental effect on the liver they are also known to affect multiple organs in the body including the lungs. To investigate if exposure to HBV and HCV is associated with lung function and respiratory diseases. Data from the Third National Health and Nutrition Examination Survey (NHANES III) was analysed using multiple linear regressions to investigate the association between exposure to HBV and HCV with the various measures of lung function, while multiple logistic regressions were used to evaluate the association with the respiratory diseases asthma and chronic obstructive pulmonary disease (COPD). Exposure to HCV was significantly associated with an increase in Forced Expiratory Volume in 1 s, FEV1 (Coef: 97.94 ml, 95% CI: 38.87 to 157.01) and Full Vital Capacity, FVC (Coef: 90 ml, 95% CI: 14.50 to 166.24). Individuals who had been exposed to both HBV and HCV also had a significantly higher FEV1 (Coef: 145.82, CI: 60.68 to 230.94) and FVC (Coef: 195.09, CI: 78.91 to 311.26). There was also a significant association between exposure to HBV and asthma (OR: 1.28, 95% CI: 1.05 to 1.58). These associations were no longer significant after additionally adjusting for cocaine and marijuana use as well as poverty income ratio. Our research implies that hepatotropic viruses may affect the respiratory system, but more work at a population level is needed to further explore these associations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Temporal Profile of Gene Expression Alterations in Primary Human Bronchial Epithelial Cells Following In Vivo Exposure to Ozone

EPA Science Inventory

RATIONALE: Ozone (Os) isa ubiquitous air pollutant that has been shown to have a detrimental effect on human health. Controlled exposure studies in humans have demonstrated that acute exposure to 03 results in reversible reduction in lung function immediately post-exposure, incre...

Lung function in asphalt pavers: a longitudinal study.

PubMed

Ulvestad, Bente; Randem, Britt Grethe; Skare, Øivind; Aaløkken, Trond Mogens; Myranek, Georg Karl; Elihn, Karine; Lund, May Brit

2017-01-01

To study longitudinal changes in lung function in asphalt pavers and a reference group of road maintenance workers, and to detect possible signs of lung disease by high-resolution computed tomography (HRCT) scans. Seventy-five asphalt pavers and 71 road maintenance workers were followed up with questionnaires and measurements of lung function. Not every worker was tested every year, but most of them had four or more measurement points. The 75 asphalt pavers were also invited to have HRCT scans of the lungs at the end of the follow-up period. Mean annual decline in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ) of the asphalt pavers was 58 and 35 ml, respectively. Adjusted for age at baseline, packyears of smoking and BMI, the asphalt pavers had a significant excess annual decline in FVC and FEV 1 compared to the references. The screedmen, the most exposed group of the asphalt pavers, showed a significantly larger decline in FVC than the other asphalt pavers (P = 0.029). Fine intralobular fibrosis without evident cysts was identified with HRCT in three subjects (4 %). We conclude that our findings may indicate an excess annual decline in FVC and FEV 1 related to exposure to asphalt fumes. The screedmen, who carry out their work behind and close to the paving machine, had the largest decline in lung function. The finding of adverse pulmonary effects in asphalt pavers calls for better technological solutions to prevent exposure.

Associations between Ambient Particulate Matter and Nitrogen Dioxide and Chronic Obstructive Pulmonary Diseases in Adults and Effect Modification by Demographic and Lifestyle Factors

PubMed Central

Leem, Jong Han; Kim, Hwan Cheol

2018-01-01

This study was undertaken to investigate the associations between chronic exposure to particulate matter of medium aerodynamic diameter ≤10 or ≤2.5 µm (PM10 or PM2.5) and nitrogen dioxide (NO2) levels and lung function and to examine a possible change in these relationships by demographic and lifestyle factors. Chronic obstructive pulmonary disease (COPD) was defined using the Global Initiative for COPD criteria (forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of <70%). Associations of lung function and COPD with PM10 or PM2.5 or NO2 were examined using linear and logistic regression analyses among 1264 Korean adults. The highest tertiles of PM2.5 (≥37.1 μg/m3) and NO2 (≥53.8 μg/m3) exposure were significantly associated with COPD (highest versus lowest tertile of PM2.5: adjusted odds ratio (OR) = 1.79, 95% CI: 1.02–3.13; highest versus lowest tertile of NO2: adjusted OR = 1.83, 95% CI: 1.04–3.21). A 10 μg/m3 increase in PM10 concentration was associated with a 1.85 L (95% CI –3.65 to –0.05) decrease in FEV1 and a 1.73 L (95% CI –3.35 to –0.12) decrease in FVC, with the strongest negative association among older people and those with less education. Reduced lung function was associated with PM2.5 exposure in subjects with no physical activity. This study provides evidence that exposure to ambient air pollution has adverse effects on lung function in adults. PMID:29463050

Short-term changes in respiratory biomarkers after swimming in a chlorinated pool.

PubMed

Font-Ribera, Laia; Kogevinas, Manolis; Zock, Jan-Paul; Gómez, Federico P; Barreiro, Esther; Nieuwenhuijsen, Mark J; Fernandez, Pilar; Lourencetti, Carolina; Pérez-Olabarría, Maitane; Bustamante, Mariona; Marcos, Ricard; Grimalt, Joan O; Villanueva, Cristina M

2010-11-01

Swimming in chlorinated pools involves exposure to disinfection by-products (DBPs) and has been associated with impaired respiratory health. We evaluated short-term changes in several respiratory biomarkers to explore mechanisms of potential lung damage related to swimming pool exposure. We measured lung function and biomarkers of airway inflammation [fractional exhaled nitric oxide (FeNO), eight cytokines, and vascular endothelial growth factor (VEGF) in exhaled breath condensate], oxidative stress (8-isoprostane in exhaled breath condensate), and lung permeability [surfactant protein D (SP-D) and the Clara cell secretory protein (CC16) in serum] in 48 healthy nonsmoking adults before and after they swam for 40 min in a chlorinated indoor swimming pool. We measured trihalomethanes in exhaled breath as a marker of individual exposure to DBPs. Energy expenditure during swimming, atopy, and CC16 genotype (rs3741240) were also determined. Median serum CC16 levels increased from 6.01 to 6.21 microg/L (average increase, 3.3%; paired Wilcoxon test p = 0.03), regardless of atopic status and CC16 genotype. This increase was explained both by energy expenditure and different markers of DBP exposure in multivariate models. FeNO was unchanged overall but tended to decrease among atopics. We found no significant changes in lung function, SP-D, 8-isoprostane, eight cytokines, or VEGF. We detected a slight increase in serum CC16, a marker of lung epithelium permeability, in healthy adults after they swam in an indoor chlorinated pool. Exercise and DBP exposure explained this association, without involving inflammatory mechanisms. Further research is needed to confirm the results, establish the clinical relevance of short-term serum CC16 changes, and evaluate the long-term health impacts.

Endothelial disruptive proinflammatory effects of nicotine and e-cigarette vapor exposures.

PubMed

Schweitzer, Kelly S; Chen, Steven X; Law, Sarah; Van Demark, Mary; Poirier, Christophe; Justice, Matthew J; Hubbard, Walter C; Kim, Elena S; Lai, Xianyin; Wang, Mu; Kranz, William D; Carroll, Clinton J; Ray, Bruce D; Bittman, Robert; Goodpaster, John; Petrache, Irina

2015-07-15

The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the lung microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated the contribution of nicotine in CS or e-cigarettes (e-Cig) to lung endothelial injury. Primary lung microvascular endothelial cells were exposed to nicotine, e-Cig solution, or condensed e-Cig vapor (1-20 mM nicotine) or to nicotine-free CS extract or e-Cig solutions. Compared with nicotine-containing extract, nicotine free-CS extract (10-20%) caused significantly less endothelial permeability as measured with electric cell-substrate impedance sensing. Nicotine exposures triggered dose-dependent loss of endothelial barrier in cultured cell monolayers and rapidly increased lung inflammation and oxidative stress in mice. The endothelial barrier disruptive effects were associated with increased intracellular ceramides, p38 MAPK activation, and myosin light chain (MLC) phosphorylation, and was critically mediated by Rho-activated kinase via inhibition of MLC-phosphatase unit MYPT1. Although nicotine at sufficient concentrations to cause endothelial barrier loss did not trigger cell necrosis, it markedly inhibited cell proliferation. Augmentation of sphingosine-1-phosphate (S1P) signaling via S1P1 improved both endothelial cell proliferation and barrier function during nicotine exposures. Nicotine-independent effects of e-Cig solutions were noted, which may be attributable to acrolein, detected along with propylene glycol, glycerol, and nicotine by NMR, mass spectrometry, and gas chromatography, in both e-Cig solutions and vapor. These results suggest that soluble components of e-Cig, including nicotine, cause dose-dependent loss of lung endothelial barrier function, which is associated with oxidative stress and brisk inflammation.

DNA damage response at telomeres contributes to lung aging and chronic obstructive pulmonary disease

PubMed Central

Birch, Jodie; Anderson, Rhys K.; Correia-Melo, Clara; Jurk, Diana; Hewitt, Graeme; Marques, Francisco Madeira; Green, Nicola J.; Moisey, Elizabeth; Birrell, Mark A.; Belvisi, Maria G.; Black, Fiona; Taylor, John J.; Fisher, Andrew J.; De Soyza, Anthony

2015-01-01

Cellular senescence has been associated with the structural and functional decline observed during physiological lung aging and in chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the first line of defense in the lungs and are important to COPD pathogenesis. However, the mechanisms underlying airway epithelial cell senescence, and particularly the role of telomere dysfunction in this process, are poorly understood. We aimed to investigate telomere dysfunction in airway epithelial cells from patients with COPD, in the aging murine lung and following cigarette smoke exposure. We evaluated colocalization of γ-histone protein 2A.X and telomeres and telomere length in small airway epithelial cells from patients with COPD, during murine lung aging, and following cigarette smoke exposure in vivo and in vitro. We found that telomere-associated DNA damage foci increase in small airway epithelial cells from patients with COPD, without significant telomere shortening detected. With age, telomere-associated foci increase in small airway epithelial cells of the murine lung, which is accelerated by cigarette smoke exposure. Moreover, telomere-associated foci predict age-dependent emphysema, and late-generation Terc null mice, which harbor dysfunctional telomeres, show early-onset emphysema. We found that cigarette smoke accelerates telomere dysfunction via reactive oxygen species in vitro and may be associated with ataxia telangiectasia mutated-dependent secretion of inflammatory cytokines interleukin-6 and -8. We propose that telomeres are highly sensitive to cigarette smoke-induced damage, and telomere dysfunction may underlie decline of lung function observed during aging and in COPD. PMID:26386121

Reduced Lung Function and Cerebral Small Vessel Disease in Japanese Men: the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).

PubMed

Seto-Yukimura, Ruriko; Ogawa, Emiko; Hisamatsu, Takashi; Torii, Sayuki; Shiino, Akihiko; Nozaki, Kazuhiko; Fujiyoshi, Akira; Miura, Katsuyuki; Nakano, Yasutaka; Ueshima, Hirotsugu

2018-02-16

We aimed to investigate the association between reduced lung function and cerebral small vessel diseases via cranial magnetic resonance imaging (MRI) in the cross-sectional study of the general Japanese population. We recruited participants aged ≥40 years from the general population of a single city in Japan. We clarified the comorbidities and treatments, smoking habits, second-hand smoke exposure, current alcohol consumption, education level, exercise habits, and occupation. The pulmonary function test was performed to assess the forced expiratory volume in 1 second (FEV 1 ) % predicted and forced vital capacity (FVC) % predicted values. Cranial MRI was performed to evaluate the white matter lesions (WMLs) and lacunar infarcts. We examined the association of the WMLs and lacunar infarcts with a 1-standard deviation (SD) lower in the FEV 1 % predicted and FVC % predicted, on the basis of the smoking status. A total of 473 men were examined. The association of WMLs and lacunar infarcts with the spirometry-based indices were significant only in never smokers. The association between lung function impairment and cerebral small vessel disease did not change after further adjusting for second-hand smoke exposure. In a community-based sample of Japanese men, we found an association between reduced lung function and WMLs and lacunar infarcts in never smokers.

The Influence of Large-Scale Airborne Particle Decline and Traffic-Related Exposure on Children’s Lung Function

PubMed Central

Sugiri, Dorothea; Ranft, Ulrich; Schikowski, Tamara; Krämer, Ursula

2006-01-01

Between 1991 and 2000, ambient air pollution in East Germany changed to resemble West German pollution levels: The concentration of total suspended particles (TSPs) decreased on a broad scale while traffic increased. During that time, we analyzed total lung capacity (TLC) and airway resistance (Raw) of East and West German children. We tested children 5–7 years of age (n = 2,574) with cooperation-independent body plethysmography in repeated cross sections. We used random-effect models to determine the mutually adjusted association between lung function and short-term and chronic particle exposure and its interaction with living near a busy road. Annual averages of TSPs declined from 77 to 44 μg/m3; averages on the day of investigation declined from 133 to 30 μg/m3. Differences in lung function between East and West German children vanished during the investigation time. The association of TSPs with Raw and TLC was stronger in children living > 50 m away from busy roads. East German children from this group had an Raw 2.5% higher [95% confidence interval (CI), 0.0–5.1%] per 40-μg/m3 increase of daily TSP averages. TLC decreased by 6.2% (95% CI, 0.04–11.6%) per 40-μg/m3 increase in annual mean TSPs, and this effect was equally pronounced in East and West Germany. TSP exposure decreased on a broad scale between 1991 and 2000. Lower concentrations of TSPs were associated with better measures of lung function in 6-year-old children. For children living near busy roads, this effect was diminished. PMID:16451868

World Trade Center dyspnea: bronchiolitis obliterans with functional improvement: a case report.

PubMed

Mann, Jack M; Sha, Kenneth K; Kline, Gary; Breuer, Frank-Uwe; Miller, Albert

2005-09-01

Bronchiolitis obliterans is a severe, often progressive, lung disease characterized by cough, exertional dyspnea, and airflow obstruction. It has been ascribed to specific causes such as lung or bone marrow transplant, medications for rheumatoid disease, and most recently in association with exposure to environmental agents. A 42-year-old, previously healthy New York City Highway Patrol officer who arrived at the World Trade Center (WTC), "ground zero," early on September 11, 2001 was evaluated. He has been followed for over 2 years with serial chest radiographs, CT scans, and pulmonary function studies. He eventually underwent an open lung biopsy. His dyspnea started on September 12, 2001 and progressed despite aggressive therapy with inhaled bronchodilator as well as oral and inhaled corticosteroids. At no time did he have any radiographic evidence of pulmonary disease. His forced vital capacity (FVC) decreased from 5.32 L in October 2001 to 2.86 L in January 2003. He underwent an open lung biopsy because of the persistent exertional dyspnea coupled with the loss of over 2 L of lung volume. The pathological findings were chronic bronchiolitis with focal obliterative bronchiolitis and rare non-necrotizing granuloma. Symptoms and pulmonary function improved after therapy with Azithromycin was added to his treatment. This process is believed to be secondary to his massive exposure to the cloud of dust that followed the collapse of the WTC. It is our conviction that many of those present at the WTC on September 11 who have persistent dyspnea and deterioration of pulmonary function may have a similar pathologic process despite absence of abnormalities on CT of the chest. In view of the many signs and symptoms seen in first responders we feel that these findings provide important information about the pathophysiology and treatment of progressive disease resulting from this exposure.

International Space Station (ISS)

NASA Image and Video Library

2003-01-16

In this International Space Station (ISS) onboard photo, Expedition Six Science Officer Donald R. Pettit works to set up the Pulmonary Function in Flight (PuFF) experiment hardware in the Destiny Laboratory. Expedition Six is the fourth and final crew to perform the PuFF experiment. The PuFF experiment was developed to better understand what effects long term exposure to microgravity may have on the lungs. The focus is on measuring changes in the everness of gas exchange in the lungs, and on detecting changes in respiratory muscle strength. It allows astronauts to measure blood flow through the lungs, the ability of the lung to take up oxygen, and lung volumes. Each PuFF session includes five lung function tests, which involve breathing only cabin air. For each planned extravehicular (EVA) activity, a crew member performs a PuFF test within one week prior to the EVA. Following the EVA, those crew members perform another test to document the effect of exposure of the lungs to the low-pressure environment of the space suits. This experiment utilizes the Gas Analyzer System for Metabolic Analysis Physiology, or GASMAP, located in the Human Research Facility (HRF), along with a variety of other Puff equipment including a manual breathing valve, flow meter, pressure-flow module, pressure and volume calibration syringes, and disposable mouth pieces.

Lung Function Impact from Working in the Pre-Revolution Libyan Quarry Industry

PubMed Central

Draid, Marwan M.; Ben-Elhaj, Khaled M.; Ali, Ashraf M.; Schmid, Kendra K.; Gibbs, Shawn G.

2015-01-01

The purpose of this study was to determine the lung impact from working within the Libyan quarry industry, and if the length of work impacted the degree of degradation. Eighty three workers from eight silica quarries in the Nafusa Mountains of Libya opted to participate. These quarries were working the upper cretaceous geological structure. Eighty-five individuals who lived in Gharyan City with no affiliation to quarry operations participated as controls. Spirometry variables evaluated were Forced Vital Capacity (FVC), Forced Expiratory Volume at 1.0 second (FEV1), FVC/FEV1 and Peak Expiratory Flow (PEF). Control and exposed groups had no differences in terms of height, weight, or smoking status (p = 0.18, 0.20, 0.98, respectively). Prior to adjustment for other variables, FVC, FEV1, and PEF are all significantly lower in the exposed group (p = 0.003, 0.009, 0.03, respectively). After adjustment for age, height, weight, and smoking status, there remain significant differences between the control and exposed groups for FVC, FEV1, and PEF. This analysis demonstrated that exposure to quarry dust has a detrimental effect on lung function, and that pre-revolution Libyan quarry workers were being exposed. This study shows that any exposure is harmful, as the reduction in lung function was not significantly associated with years of exposure. PMID:25961801

Racial difference in lung function in African-American and White children: effect of anthropometric, socioeconomic, nutritional, and environmental factors.

PubMed

Harik-Khan, Raida I; Muller, Denis C; Wise, Robert A

2004-11-01

African-American children have lower lung volumes than White children. However, the contributions of anthropometric, socioeconomic, nutritional, and environmental factors to this difference are unknown. From participants in the Third National Health and Nutrition Examination Survey (1988-1994), the authors selected 1,462 healthy nonsmoking children (623 White and 839 African-American) aged 8-17 years. The African-American children were taller and heavier but had lower lung function. African Americans were poorer and had lower levels of the antioxidant vitamins A and C and alpha-carotene. The authors performed regression analyses using data on anthropometric, socioeconomic, and nutritional factors and smoke exposure. Adjustment for sitting height explained 42-53% of the racial difference. Socioeconomic factors and antioxidant vitamin levels accounted for an additional 7-10%. Overall, the authors could account for only 50-63% of the racial difference. Exposure to tobacco in the home was weakly associated with forced expiratory volume in 1 second in girls, accounting for 1% of the difference. In children aged 8-12 years (n = 752), birth weight explained 3-5% of the racial difference, whereas in-utero exposure to maternal smoking had no significant effect. The authors conclude that in healthy children, the major explanatory variable for the racial difference in lung function is body habitus; socioeconomic, nutritional, and environmental confounders play a smaller role.

Indoor NO2 air pollution and lung function of professional cooks.

PubMed

Arbex, M A; Martins, L C; Pereira, L A A; Negrini, F; Cardoso, A A; Melchert, W R; Arbex, R F; Saldiva, P H N; Zanobetti, A; Braga, A L F

2007-04-01

Studies of cooking-generated NO2 effects are rare in occupational epidemiology. In the present study, we evaluated the lung function of professional cooks exposed to NO2 in hospital kitchens. We performed spirometry in 37 cooks working in four hospital kitchens and estimated the predicted FVC, FEV1 and FEF(25-75), based on age, sex, race, weight, and height, according to Knudson standards. NO2 measurements were obtained for 4 consecutive days during 4 different periods at 20-day intervals in each kitchen. Measurements were performed inside and outside the kitchens, simultaneously using Palm diffusion tubes. A time/exposure indicator was defined as representative of the cumulative exposure of each cook. No statistically significant effect of NO2 exposure on FVC was found. Each year of work as a cook corresponded to a decrease in predicted FEV1 of 2.5% (P = 0.046) for the group as a whole. When smoking status and asthma were included in the analysis the effect of time/exposure decreased about 10% and lost statistical significance. On predicted FEF(25-75), a decrease of 3.5% (P = 0.035) was observed for the same group and the inclusion of controllers for smoking status and asthma did not affect the effects of time/exposure on pulmonary function parameter. After a 10-year period of work as cooks the participants of the study may present decreases in both predicted FEV1 and FEF(25-75) that can reach 20 and 30%, respectively. The present study showed small but statistically significant adverse effects of gas stove exposure on the lung function of professional cooks.

Lung function association with outdoor temperature and relative humidity and its interaction with air pollution in the elderly.

PubMed

Lepeule, Johanna; Litonjua, Augusto A; Gasparrini, Antonio; Koutrakis, Petros; Sparrow, David; Vokonas, Pantel S; Schwartz, Joel

2018-04-21

While the effects of weather variability on cardio-respiratory mortality are well described, research examining the effects on morbidity, especially for vulnerable populations, is warranted. We investigated the associations between lung function and outdoor temperature (T in Celsius degrees (°C)) and relative humidity (RH), in a cohort of elderly men, the Normative Aging Study. Our study included 1103 participants whose forced vital capacity (FVC), forced expiratory volume in one second (FEV 1 ), and weather exposures were assessed one to five times during the period 1995-2011 (i.e. 3162 observations). Temperature and relative humidity were measured at one location 4 h to 7 days before lung function tests. We used linear mixed-effects models to examine the associations with outdoor T and RH. A 5-degree increase in the 3-day moving average T was associated with a significant 0.7% decrease (95%CI: -1.24, -0.20) in FVC and a 5% increase in the 7-day moving average RH was associated with a significant 0.2% decrease (95%CI: -0.40, -0.02) in FVC and FEV 1 . The associations with T were greater when combined with higher exposures of black carbon with a 1.6% decrease (95%CI -2.2; -0.9) in FVC and a 1% decrease (95%CI -1.7; -0.4) in FEV 1 . The relationships between T and RH and lung function were linear. No synergistic effect of T and RH was found. Heat and lung function are two predictors of mortality. Our findings suggest that increases in temperature and relative humidity are related to decreases in lung function, and such observations might be amplified by high black carbon levels. Copyright © 2018 Elsevier Inc. All rights reserved.

TRPV4 inhibition counteracts edema and inflammation and improves pulmonary function and oxygen saturation in chemically induced acute lung injury

PubMed Central

Balakrishna, Shrilatha; Song, Weifeng; Achanta, Satyanarayana; Doran, Stephen F.; Liu, Boyi; Kaelberer, Melanie M.; Yu, Zhihong; Sui, Aiwei; Cheung, Mui; Leishman, Emma; Eidam, Hilary S.; Ye, Guosen; Willette, Robert N.; Thorneloe, Kevin S.; Bradshaw, Heather B.; Matalon, Sadis

2014-01-01

The treatment of acute lung injury caused by exposure to reactive chemicals remains challenging because of the lack of mechanism-based therapeutic approaches. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), an ion channel expressed in pulmonary tissues, is a crucial mediator of pressure-induced damage associated with ventilator-induced lung injury, heart failure, and infarction. Here, we examined the effects of two novel TRPV4 inhibitors in mice exposed to hydrochloric acid, mimicking acid exposure and acid aspiration injury, and to chlorine gas, a severe chemical threat with frequent exposures in domestic and occupational environments and in transportation accidents. Postexposure treatment with a TRPV4 inhibitor suppressed acid-induced pulmonary inflammation by diminishing neutrophils, macrophages, and associated chemokines and cytokines, while improving tissue pathology. These effects were recapitulated in TRPV4-deficient mice. TRPV4 inhibitors had similar anti-inflammatory effects in chlorine-exposed mice and inhibited vascular leakage, airway hyperreactivity, and increase in elastance, while improving blood oxygen saturation. In both models of lung injury we detected increased concentrations of N-acylamides, a class of endogenous TRP channel agonists. Taken together, we demonstrate that TRPV4 inhibitors are potent and efficacious countermeasures against severe chemical exposures, acting against exaggerated inflammatory responses, and protecting tissue barriers and cardiovascular function. PMID:24838754

Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling

PubMed Central

Sellamuthu, Rajendran; Umbright, Christina; Li, Shengqiao; Kashon, Michael; Joseph, Pius

2015-01-01

A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure. PMID:22087542

Lung function status of some Nigerian men and women chronically exposed to fish drying using burning firewood.

PubMed

Peters, E J; Esin, R A; Immananagha, K K; Siziya, S; Osim, E E

1999-05-01

To determine the lung function status of some Nigerian men and women chronically exposed to fish drying using burning firewood. Case control study. Ibaka, Utaewa and Ikanga fishing settlements. 183 males and 192 females engaged in fishing, aged 20 to 45 years who have been exposed for a minimum of five years as cases. The control group comprised sex matched male (142) and female (152) Nigerians from the same area who were not exposed to any known air pollutant. Lung function indices: FVC, FEV1, FEV1% and PEFR. Lung function indices were significantly lower in men engaged in fishing than in their controls: FVC [mean (SD): 2.98 (0.20) vs 3.52 (0.29), p < 0.001]; FEV1 [2.08 (0.18) vs 2.82 (0.25), p < 0.001]; FEV1% [69.8 (3.1) vs 80.2 (6.7), p < 0.001]; and PEFR [335 (22) vs 592 (99), p < 0.001], respectively. Similarly, lung function indices were lower in females in the fishing industry than in their controls; FVC [2.42 (0.17) vs 3.02 (0.24), p < 0.001]; FEV1 [1.70 (0.19) vs 2.55 (0.21), p < 0.001]; FEV1% [72.9 (3.2) vs 84.4 (6.7), p < 0.001]; and PEFR [298 (22) vs 418 (34), p < 0.001]. All the lung function indices (except FEV1%) of the fishermen and women declined significantly (p < 0.001) with their duration of exposure. The results showed a predominantly mixed pattern (restrictive and obstructive) of respiratory defect. There were higher prevalences of respiratory and other symptoms among the cases than the controls. The respiratory symptoms included cough with sputum, chest pain, dyspnoea catarrh and sneezing and unproductive cough. Other symptoms were eye and skin irritation, internal heat and headache. Chronic exposure to fish drying using burning firewood can impair lung function and cause respiratory and other symptoms.

A Comparison of the Inflammatory and Proteolytic Effects of Dung Biomass and Cigarette Smoke Exposure in the Lung

PubMed Central

Mehra, Divya; Geraghty, Patrick M.; Hardigan, Andrew A.; Foronjy, Robert

2012-01-01

Rationale Biomass is the energy source for cooking and heating for billions of people worldwide. Despite their prevalent use and their potential impact on global health, the effects of these fuels on lung biology and function remain poorly understood. Methods We exposed human small airway epithelial cells and C57BL/6 mice to dung biomass smoke or cigarette smoke to compare how these exposures impacted lung signaling and inflammatory and proteolytic responses that have been linked with disease pathogenesis. Results The in vitro exposure and siRNA studies demonstrated that biomass and cigarette smoke activated ERK to up regulate IL-8 and MMP-1 expression in human airway epithelial cells. In contrast to cigarette smoke, biomass also activated p38 and JNK within these lung cells and lowered the expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1). Similarly, in the lungs of mice, both biomass and cigarette smoke exposure increased macrophages, activated ERK and p38 and up regulated MMP-9 and MMP-12 expression. The main differences seen in the exposure studies was that mice exposed to biomass exhibited more perivascular inflammation and had higher G-CSF and GM-CSF lavage fluid levels than mice exposed identically to cigarette smoke. Conclusion Biomass activates similar pathogenic processes seen in cigarette smoke exposure that are known to result in the disruption of lung structure. These findings provide biological evidence that public health interventions are needed to address the harm associated with the use of this fuel source. PMID:23285217

Hypergravity Alters the Susceptibility of Cells to Anoxia-Reoxygenation Injury

NASA Technical Reports Server (NTRS)

McCloud, Henry; Pink, Yulondo; Harris-Hooker, Sandra A.; Melhado, Caroline D.; Sanford, Gary L.

1997-01-01

Gravity is a physical force, much like shear stress or mechanical stretch, and should affect organ and cellular function. Researchers have shown that gravity plays a role in ventilation and blood flow distribution, gas exchange, alveolar size and mechanical stresses within the lung. Short exposure to microgravity produced marked alterations in lung blood flow and ventilation distribution while hypergravity exaggerated the regional differences in lung structure and function resulting in reduced ventilation at the base and no ventilation of the upper half of the lung. Microgravity also decreased metabolic activity in cardiac cells, WI-38 embryonic lung cells, and human lymphocytes. Rats, in the tail-suspended head-down tilt model, experienced transient loss of lung water, contrary to an expected increase due to pooling of blood in the pulmonary vasculature. Hypergravity has also been found to increase the proliferation of several different cell lines (e.g., chick embryo fibroblasts) while decreasing cell motility and slowing liver regeneration following partial hepatectomy. These studies show that changes in the gravity environment will affect several aspects of organ and cellular function and produce major change in blood flow and tissue/organ perfusion. However, these past studies have not addressed whether ischemia-reperfusion injury will be exacerbated or ameliorated by changes in the gravity environment, e.g., space flight. Currently, nothing is known about how gravity will affect the susceptibility of different lung and vascular cells to this type of injury. We conducted studies that addressed the following question: Does the susceptibility of lung fibroblasts, vascular smooth muscle, and endothelial cells to anoxia/reoxygenation injury change following exposure to hypergravity conditions?

Upregulation of autophagy decreases chlorine-induced mitochondrial injury and lung inflammation.

PubMed

Jurkuvenaite, Asta; Benavides, Gloria A; Komarova, Svetlana; Doran, Stephen F; Johnson, Michelle; Aggarwal, Saurabh; Zhang, Jianhua; Darley-Usmar, Victor M; Matalon, Sadis

2015-08-01

The mechanisms of toxicity during exposure of the airways to chlorinated biomolecules generated during the course of inflammation and to chlorine (Cl2) gas are poorly understood. We hypothesized that lung epithelial cell mitochondria are damaged by Cl2 exposure and activation of autophagy mitigates this injury. To address this, NCI-H441 (human lung adenocarcinoma epithelial) cells were exposed to Cl2 (100 ppm/15 min) and bioenergetics were assessed. One hour after Cl2, cellular bioenergetic function and mitochondrial membrane potential were decreased. These changes were associated with increased MitoSOX signal, and treatment with the mitochondrial redox modulator MitoQ attenuated these bioenergetic defects. At 6h postexposure, there was significant increase in autophagy, which was associated with an improvement of mitochondrial function. Pretreatment of H441 cells with trehalose (an autophagy activator) improved bioenergetic function, whereas 3-methyladenine (an autophagy inhibitor) resulted in increased bioenergetic dysfunction 1h after Cl2 exposure. These data indicate that Cl2 induces bioenergetic dysfunction, and autophagy plays a protective role in vitro. Addition of trehalose (2 vol%) to the drinking water of C57BL/6 mice for 6 weeks, but not 1 week, before Cl2 (400 ppm/30 min) decreased white blood cells in the bronchoalveolar lavage fluid at 6h after Cl2 by 70%. Acute administration of trehalose delivered through inhalation 24 and 1h before the exposure decreased alveolar permeability but not cell infiltration. These data indicate that Cl2 induces bioenergetic dysfunction associated with lung inflammation and suggests that autophagy plays a protective role. Published by Elsevier Inc.

Cotton dust, endotoxin and cancer mortality among the Shanghai textile workers cohort: a 30-year analysis

PubMed Central

Fang, S C; Mehta, A J; Hang, J Q; Eisen, E A; Dai, H L; Zhang, H X; Su, L; Christiani, D C

2013-01-01

Background Although occupational exposure to cotton dust and endotoxin is associated with adverse respiratory health, associations with cancer are unclear. We investigated cancer mortality in relation to cotton dust and endotoxin exposure in the Shanghai textile workers cohort. Methods We followed 444 cotton textile and a reference group of 467 unexposed silk workers for 30 years (26 777 person-years). HRs for all cancers combined (with and without lung cancer) and gastrointestinal cancer were estimated in Cox regression models as functions of cotton textile work and categories of cumulative exposure (low, medium, high), after adjustment for covariates including pack-years smoked. Different lag years accounted for disease latency. Results Risks of mortality from gastrointestinal cancers and all cancers combined, with the exclusion of lung cancer, were increased in cotton workers relative to silk workers. When stratified by category of cumulative cotton exposure, in general, risks were greatest for 20-year lagged medium exposure (all cancers HR=2.7 (95% CI 1.4 to 5.2); cancer excluding lung cancer HR=3.4 (1.7–7.0); gastrointestinal cancer HR=4.1 (1.8–9.7)). With the exclusion of lung cancer, risks of cancer were more pronounced. When stratified by category of cumulative endotoxin exposure, consistent associations were not observed for all cancers combined. However, excluding lung cancer, medium endotoxin exposure was associated with all cancers and gastrointestinal cancer in almost all lag models. Conclusions Cotton dust may be associated with cancer mortality, especially gastrointestinal cancer, and endotoxin may play a causative role. Findings also indirectly support a protective effect of endotoxin on lung cancer. PMID:23828454

The alpha2-adrenoreceptor agonist dexmedetomidine protects against lipopolysaccharide-induced apoptosis via inhibition of gap junctions in lung fibroblasts.

PubMed

Zhang, Yuan; Tan, Xiaoming; Xue, Lianfang

2018-01-01

The α2-adrenoceptor inducer dexmedetomidine protects against acute lung injury (ALI), but the mechanism of this effect is largely unknown. The present study investigated the effect of dexmedetomidine on apoptosis induced by lipopolysaccharide (LPS) and the relationship between this effect and gap junction intercellular communication in human lung fibroblast cell line. Flow cytometry was used to detect apoptosis induced by LPS. Parachute dye coupling assay was used to measure gap junction function, and western blot analysis was used to determine the expression levels of connexin43 (Cx43). The results revealed that exposure of human lung fibroblast cell line to LPS for 24 h increased the apoptosis, and pretreatment of dexmedetomidine and 18α-GA significantly reduced LPS-induced apoptosis. Dexmedetomidine exposure for 1 h inhibited gap junction function mainly via a decrease in Cx43 protein levels in human lung fibroblast cell line. These results demonstrated that the inhibition of gap junction intercellular communication by dexmedetomidine affected the LPS-induced apoptosis through inhibition of gap junction function by reducing Cx43 protein levels. The present study provides evidence of a novel mechanism underlying the effects of analgesics in counteracting ALI. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of duration of exposure to polluted air environment on lung function in subjects exposed to crude oil spill into sea water.

PubMed

Meo, Sultan Ayoub; Al-Drees, Abdul Majeed; Rasheed, Shahzad; Meo, Imran Mu; Khan, Muhammad Mujahid; Al-Saadi, Muslim M; Alkandari, Jasem Ramadan

2009-01-01

Oil spill in sea water represents a huge environmental disaster for marine life and humans in the vicinity. The aim was to investigate the effect of duration of exposure to polluted air environment on lung function in subjects exposed to crude oil spill into sea water. The present study was conducted under the supervision of Department of Physiology, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia, during the period July 2003 - December 2004. This was a comparative study of spirometry in 31 apparently healthy, non smoking, male workers, exposed to crude oil spill environment during the oil cleaning operation. The exposed group was matched with similar number of male, non smoking control subjects. Pulmonary function test was performed by using an electronic spirometer. Subjects exposed to polluted air for periods longer than 15 days showed a significant reduction in Forced Vital Capacity (FVC), Forced Expiratory Volume in First Second (FEV1), Forced Expiratory Flow in 25-25% (FEF25-75%) and Maximal Voluntary Ventilation (MVV). Air environment polluted due to crude oil spill into sea water caused impaired lung function and this impairment was associated with dose response effect of duration of exposure to air polluted by crude oil spill into sea water.

Exposure of healthy subjects with emissions from a gas metal arc welding process: part 3--biological effect markers and lung function.

PubMed

Brand, P; Bischof, K; Siry, L; Bertram, J; Schettgen, T; Reisgen, U; Kraus, T; Gube, M

2013-01-01

Metal active gas welding (MAG) is a widely-used welding technique resulting in high emissions of welding fume particles. This study investigated whether short-term exposure to these fume particles results in changes in lung function and early stages of inflammatory reactions. Twelve healthy, young male subjects were exposed to MAG fumes for 6 h with three different exposure concentrations in a three-fold cross-over study design. Exposure was performed in the "Aachen Workplace Simulation Laboratory" under controlled conditions with constant fume concentration. Fume concentrations were 0, 1, and 2.5 mg m(-3) in randomized order. Before and after each exposure, spirometry, and impulse oscillometry were performed and breath condensate samples were collected in order to quantify inflammatory markers like Nitrate, Nitrite, Nitrotyrosine, Hydroxyprolin and Malondialdehyde. A significant dependency on the exposure concentration could not be established for any of the endpoint parameters. In healthy, young subjects neither changes in spirometry nor changes in inflammatory markers measured in exhaled breath condensate could be detected after short-term exposure.

Differential susceptibility of inbred mouse strains to chlorine-induced airway fibrosis

PubMed Central

Mo, Yiqun; Chen, Jing; Schlueter, Connie F.

2013-01-01

Chlorine is a reactive gas that is considered a chemical threat agent. Humans who develop acute lung injury from chlorine inhalation typically recover normal lung function; however, a subset can experience chronic airway disease. To examine pathological changes following chlorine-induced lung injury, mice were exposed to a single high dose of chlorine, and repair of the lung was analyzed at multiple times after exposure. In FVB/NJ mice, chlorine inhalation caused pronounced fibrosis of larger airways that developed by day 7 after exposure and was associated with airway hyperreactivity. In contrast, A/J mice had little or no airway fibrosis and had normal lung function at day 7. Unexposed FVB/NJ mice had less keratin 5 staining (basal cell marker) than A/J mice in large intrapulmonary airways where epithelial repair was poor and fibrosis developed after chlorine exposure. FVB/NJ mice had large areas devoid of epithelium on day 1 after exposure leading to fibroproliferative lesions on days 4 and 7. A/J mice had airways covered by squamous keratin 5-stained cells on day 1 that transitioned to a highly proliferative reparative epithelium by day 4 followed by the reappearance of ciliated and Clara cells by day 7. The data suggest that lack of basal cells in the large intrapulmonary airways and failure to effect epithelial repair at these sites are factors contributing to the development of airway fibrosis in FVB/NJ mice. The observed differences in susceptibility to chlorine-induced airway disease provide a model in which mechanisms and treatment of airway fibrosis can be investigated. PMID:23171502

Differential susceptibility of inbred mouse strains to chlorine-induced airway fibrosis.

PubMed

Mo, Yiqun; Chen, Jing; Schlueter, Connie F; Hoyle, Gary W

2013-01-15

Chlorine is a reactive gas that is considered a chemical threat agent. Humans who develop acute lung injury from chlorine inhalation typically recover normal lung function; however, a subset can experience chronic airway disease. To examine pathological changes following chlorine-induced lung injury, mice were exposed to a single high dose of chlorine, and repair of the lung was analyzed at multiple times after exposure. In FVB/NJ mice, chlorine inhalation caused pronounced fibrosis of larger airways that developed by day 7 after exposure and was associated with airway hyperreactivity. In contrast, A/J mice had little or no airway fibrosis and had normal lung function at day 7. Unexposed FVB/NJ mice had less keratin 5 staining (basal cell marker) than A/J mice in large intrapulmonary airways where epithelial repair was poor and fibrosis developed after chlorine exposure. FVB/NJ mice had large areas devoid of epithelium on day 1 after exposure leading to fibroproliferative lesions on days 4 and 7. A/J mice had airways covered by squamous keratin 5-stained cells on day 1 that transitioned to a highly proliferative reparative epithelium by day 4 followed by the reappearance of ciliated and Clara cells by day 7. The data suggest that lack of basal cells in the large intrapulmonary airways and failure to effect epithelial repair at these sites are factors contributing to the development of airway fibrosis in FVB/NJ mice. The observed differences in susceptibility to chlorine-induced airway disease provide a model in which mechanisms and treatment of airway fibrosis can be investigated.

Bioanalytical techniques for detecting biomarkers of response to human asbestos exposure.

PubMed

Mesaros, Clementina; Worth, Andrew J; Snyder, Nathaniel W; Christofidou-Solomidou, Melpo; Vachani, Anil; Albelda, Steven M; Blair, Ian A

2015-01-01

Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented. The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far. We aimed to summarize the state of knowledge on biomarkers of response to asbestos exposure. Asbestos is not present in human biological fluids; rather it is inhaled and trapped in lung tissue. Biomarkers of response, which reflect a change in biologic function in response to asbestos exposure, are analyzed. Several classes of molecules have been studied and evaluated for their potential utility as biomarkers of asbestos exposure. These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses.

Bioanalytical techniques for detecting biomarkers of response to human asbestos exposure

PubMed Central

Mesaros, Clementina; Worth, Andrew J; Snyder, Nathaniel W; Christofidou-Solomidou, Melpo; Vachani, Anil; Albelda, Steven M; Blair, Ian A

2015-01-01

Asbestos exposure is known to cause lung cancer and mesothelioma and its health and economic impacts have been well documented. The exceptionally long latency periods of most asbestos-related diseases have hampered preventative and precautionary steps thus far. We aimed to summarize the state of knowledge on biomarkers of response to asbestos exposure. Asbestos is not present in human biological fluids; rather it is inhaled and trapped in lung tissue. Biomarkers of response, which reflect a change in biologic function in response to asbestos exposure, are analyzed. Several classes of molecules have been studied and evaluated for their potential utility as biomarkers of asbestos exposure. These studies range from small molecule oxidative stress biomarkers to proteins involved in immune responses. PMID:26039812

Multiple exposures to swine barn air induce lung inflammation and airway hyper-responsiveness

PubMed Central

Charavaryamath, Chandrashekhar; Janardhan, Kyathanahalli S; Townsend, Hugh G; Willson, Philip; Singh, Baljit

2005-01-01

Background Swine farmers repeatedly exposed to the barn air suffer from respiratory diseases. However the mechanisms of lung dysfunction following repeated exposures to the barn air are still largely unknown. Therefore, we tested a hypothesis in a rat model that multiple interrupted exposures to the barn air will cause chronic lung inflammation and decline in lung function. Methods Rats were exposed either to swine barn (8 hours/day for either one or five or 20 days) or ambient air. After the exposure periods, airway hyper-responsiveness (AHR) to methacholine (Mch) was measured and rats were euthanized to collect bronchoalveolar lavage fluid (BALF), blood and lung tissues. Barn air was sampled to determine endotoxin levels and microbial load. Results The air in the barn used in this study had a very high concentration of endotoxin (15361.75 ± 7712.16 EU/m3). Rats exposed to barn air for one and five days showed increase in AHR compared to the 20-day exposed and controls. Lungs from the exposed groups were inflamed as indicated by recruitment of neutrophils in all three exposed groups and eosinophils and an increase in numbers of airway epithelial goblet cells in 5- and 20-day exposure groups. Rats exposed to the barn air for one day or 20 days had more total leukocytes in the BALF and 20-day exposed rats had more airway epithelial goblet cells compared to the controls and those subjected to 1 and 5 exposures (P < 0.05). Bronchus-associated lymphoid tissue (BALT) in the lungs of rats exposed for 20 days contained germinal centers and mitotic cells suggesting activation. There were no differences in the airway smooth muscle cell volume or septal macrophage recruitment among the groups. Conclusion We conclude that multiple exposures to endotoxin-containing swine barn air induce AHR, increase in mucus-containing airway epithelial cells and lung inflammation. The data also show that prolonged multiple exposures may also induce adaptation in AHR response in the exposed subjects. PMID:15932644

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Musah, Sadiatu; Schlueter, Connie F.; Humphrey, Da

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbitsmore » were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was developed. • Acute effects of chlorine were pulmonary edema, hypoxemia and impaired lung function. • Persistent small airway disease developed following recovery from acute injury. • Small airway disease included inflammation and bronchiolitis obliterans lesions. • The model should be useful for studying chlorine lung injury and testing treatments.« less

Pulmonary function and respiratory symptoms in a population of airport workers.

PubMed

Tunnicliffe, W S; O'Hickey, S P; Fletcher, T J; Miles, J F; Burge, P S; Ayres, J G

1999-02-01

To assess the prevalence of respiratory symptoms and to measure spirometry in a sample of employees of Birmingham International Airport, United Kingdom, to examine whether occupational exposure to aircraft fuel or jet stream exhaust might be associated with respiratory symptoms or abnormalities of lung function. Cross sectional survey by questionnaire and on site measurement of lung function, skin prick tests, and exhaled carbon monoxide concentrations. Occupational exposure was assigned by job title, between group comparison were made by logistic regression analysis. 222/680 full time employees were studied (mean age 38.6 y, 63% male, 28% current smokers, 6% self reported asthma, 19% self reported hay fever). Upper and lower respiratory tract symptoms were common and 51% had one or more positive skin tests. There were no significant differences in lung function tests between exposure groups. Between group comparisons of respiratory symptoms were restricted to male members of the medium and high exposure groups. The adjusted odds ratio (OR) for cough with phlegm and runny nose were found to be significantly associated with high exposure (OR 3.5, 95% confidence interval (95% CI) 1.23 to 9.74 and 2.9, 1.32 to 6.40 respectively) when the measured confounding effects of age and smoking, and in the case of runny nose, self reported hay fever had been taken into account. There was no obvious association between high exposure and the presence of shortness of breath or wheeze, or for the symptoms of watering eyes or stuffy nose. These findings support an association in male airport workers, between high occupational exposures to aviation fuel or jet stream exhaust and excess upper and lower respiratory tract symptoms, in keeping with a respiratory irritant. It is more likely that these effects reflect exposure to exhaust rather than fuel, although the effects of an unmeasured agent cannot be discounted.

Pulmonary function and respiratory symptoms in a population of airport workers

PubMed Central

Tunnicliffe, W. S.; O'Hickey, S. P.; Fletcher, T. J.; Miles, J. F.; Burge, P. S.; Ayres, J. G.

1999-01-01

OBJECTIVES: To assess the prevalence of respiratory symptoms and to measure spirometry in a sample of employees of Birmingham International Airport, United Kingdom, to examine whether occupational exposure to aircraft fuel or jet stream exhaust might be associated with respiratory symptoms or abnormalities of lung function. METHODS: Cross sectional survey by questionnaire and on site measurement of lung function, skin prick tests, and exhaled carbon monoxide concentrations. Occupational exposure was assigned by job title, between group comparison were made by logistic regression analysis. RESULTS: 222/680 full time employees were studied (mean age 38.6 y, 63% male, 28% current smokers, 6% self reported asthma, 19% self reported hay fever). Upper and lower respiratory tract symptoms were common and 51% had one or more positive skin tests. There were no significant differences in lung function tests between exposure groups. Between group comparisons of respiratory symptoms were restricted to male members of the medium and high exposure groups. The adjusted odds ratio (OR) for cough with phlegm and runny nose were found to be significantly associated with high exposure (OR 3.5, 95% confidence interval (95% CI) 1.23 to 9.74 and 2.9, 1.32 to 6.40 respectively) when the measured confounding effects of age and smoking, and in the case of runny nose, self reported hay fever had been taken into account. There was no obvious association between high exposure and the presence of shortness of breath or wheeze, or for the symptoms of watering eyes or stuffy nose. CONCLUSIONS: These findings support an association in male airport workers, between high occupational exposures to aviation fuel or jet stream exhaust and excess upper and lower respiratory tract symptoms, in keeping with a respiratory irritant. It is more likely that these effects reflect exposure to exhaust rather than fuel, although the effects of an unmeasured agent cannot be discounted.   PMID:10448317

Recovery from welding-fume-exposure-induced lung fibrosis and pulmonary function changes in sprague dawley rats.

PubMed

Sung, Jae Hyuck; Choi, Byung-Gil; Maeng, Seung-Hee; Kim, Soo-Jin; Chung, Yong Hyun; Han, Jeong Hee; Song, Kyung Seuk; Lee, Yong Hwan; Cho, Yong Bong; Cho, Myung-Haing; Kim, Kwang Jong; Hyun, Jin Suk; Yu, Il Je

2004-12-01

Welder's pneumoconiosis has generally been determined as benign based on the absence of pulmonary function abnormalities in welders with marked radiographic abnormalities. Yet, there have also been several reports on welders with respiratory symptoms, indicating lung function impairment, X-ray abnormalities, and extensive fibrosis. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during a 60-day welding-fume-inhalation exposure period to elucidate the process of fibrosis. The rats were exposed to manual metal-arc stainless-steel welding fumes (MMA-SS) with total suspended particulate concentrations of 64.8 +/- 0.9 (low dose) and 107.8 +/- 2.6 mg/m3 (high dose) for 2 h per day in an inhalation chamber for 60 days. Animals were sacrificed after the initial 2-h exposure and after 15, 30, and 60 days, and the pulmonary function was also measured every week after the daily exposure. Elevated cellular differential counts were also measured in the acellular bronchoalveolar lavage fluid of the rats exposed to the MMA-SS fumes for 60 days. Among the pulmonary function test parameters, only the tidal volume showed a statistically significant and dose-dependent decrease after 35 to 60 days of MMA-SS welding-fume exposure. When the rats exposed to the welding fumes were left for 60 days to recover their lung function and cellular differentiation, recovery was observed in both the high and low-dose rats exposed up to 30 days, resulting in the disappearance of inflammatory cells and restoration of the tidal volume. The rats exposed for 60 days at the low dose also recovered from the inflammation and tidal volume loss, yet the rats exposed for 60 days at the high dose did not fully recover even after a 60-day recovery period. Therefore, when taken together, the results of the current study suggest that a decrease in the tidal volume could be used as an early indicator of pulmonary fibrosis induced by welding-fume exposure in Sprague Dawley rats, and fibrosis would seem to be preventable if the exposure is short-term and moderate.

OBSTRUCTIVE LUNG DISEASE AND EXPOSURE TO BURNING BIOMASS FUEL IN THE INDOOR ENVIRONMENT.

PubMed

Diette, Gregory B; Accinelli, Roberto A; Balmes, John R; Buist, A Sonia; Checkley, William; Garbe, Paul; Hansel, Nadia N; Kapil, Vikas; Gordon, Stephen; Lagat, David K; Yip, Fuyuen; Mortimer, Kevin; Perez-Padilla, Rogelio; Roth, Christa; Schwaninger, Julie M; Punturieri, Antonello; Kiley, James

2012-09-01

It is estimated that up to half of the world's population burns biomass fuel (wood, crop residues, animal dung and coal) for indoor uses such as cooking, lighting and heating. As a result, a large proportion of women and children are exposed to high levels of household air pollution (HAP). The short and long term effects of these exposures on the respiratory health of this population are not clearly understood. On May 9-11, 2011 NIH held an international workshop on the "Health Burden of Indoor Air Pollution on Women and Children," in Arlington, VA. To gather information on the knowledge base on this topic and identify research gaps, ahead of the meeting we conducted a literature search using PubMed to identify publications that related to HAP, asthma, and chronic obstructive pulmonary disease (COPD). Abstracts were all analyzed and we report on those considered by the respiratory sub study group at the meeting to be most relevant to the field. Many of the studies published are symptom-based studies (as opposed to objective measures of lung function or clinical examination etc.) and measurement of HAP was not done. Many found some association between indoor exposures to biomass smoke as assessed by stove type (e.g., open fire vs. liquid propane gas) and respiratory symptoms such as wheeze and cough. Among the studies that examined objective measures (e.g. spirometry) as a health outcome, the data supporting an association between biomass smoke exposure and COPD in adult women are fairly robust, but the findings for asthma are mixed. If an association was observed between the exposures and lung function, most data seemed to demonstrate mild to moderate reductions in lung function, the pathophysiological mechanisms of which need to be investigated. In the end, the group identified a series of scientific gaps and opportunities for research that need to be addressed to better understand the respiratory effects of exposure to indoor burning of the different forms of biomass fuels.

Early life rhinovirus infection exacerbates house-dust-mite induced lung disease more severely in female mice.

PubMed

Phan, Jennifer A; Kicic, Anthony; Berry, Luke J; Sly, Peter D; Larcombe, Alexander N

2016-01-01

Recent studies have employed animal models to investigate links between rhinovirus infection and allergic airways disease, however, most do not involve early life infection, and none consider the effects of sex on responses. Here, we infected male and female mice with human rhinovirus 1B (or control) on day 7 of life. Mice were then subjected to 7 weeks of exposure to house-dust-mite prior to assessment of bronchoalveolar inflammation, serum antibodies, lung function, and responsiveness to methacholine. There were significant differences in responses between males and females in most outcomes. In males, chronic house-dust-mite exposure increased bronchoalveolar inflammation, house-dust-mite specific IgG1 and responsiveness of the lung parenchyma, however, there was no additional impact of rhinovirus infection. Conversely, in females, there were additive and synergistic effects of rhinovirus infection and house-dust-mite exposure on neutrophilia, airway resistance, and responsiveness of the lung parenchyma. We conclude that early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice.

Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to Residual Oil Fly Ashes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Magnani, Natalia D.; Marchini, Timoteo; Vanasco, Virginia

2013-07-01

Reactive O{sub 2} species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O{sub 2} species involved in lung O{sub 2} metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight), and lung samples were analysed 1 h after instillation. Tissue O{sub 2} consumption and NADPH oxidase (Nox) activity were evaluated in tissuemore » homogenates. Mitochondrial respiration, respiratory chain complexes activity, H{sub 2}O{sub 2} and ATP production rates, mitochondrial membrane potential and oxidative damage markers were assessed in isolated mitochondria. ROFA exposure was found to be associated with 61% increased tissue O{sub 2} consumption, a 30% increase in Nox activity, a 33% increased state 3 mitochondrial O{sub 2} consumption and a mitochondrial complex II activity increased by 25%. During mitochondrial active respiration, mitochondrial depolarization and a 53% decreased ATP production rate were observed. Neither changes in H{sub 2}O{sub 2} production rate, nor oxidative damage in isolated mitochondria were observed after the instillation. After an acute ROFA exposure, increased tissue O{sub 2} consumption may account for an augmented Nox activity, causing an increased O{sub 2}{sup ·−} production. The mitochondrial function modifications found may prevent oxidative damage within the organelle. These findings provide new insights to the understanding of the mechanisms involving reactive O{sub 2} species production in the lung triggered by ROFA exposure. - Highlights: • Exposure to ROFA alters the oxidative metabolism in mice lung. • The augmented Nox activity contributes to the high tissue O{sub 2} consumption. • Exposure to ROFA produces alterations in mitochondrial function. • ΔΨ{sub m} decrease in state 3 may be responsible for the decreased ATP production. • Mild uncoupling prevents mitochondrial oxidative damage.« less

Sensitization to sunflower pollen and lung functions in sunflower processing workers.

PubMed

Atis, S; Tutluoglu, B; Sahin, K; Yaman, M; Küçükusta, A R; Oktay, I

2002-01-01

This study aimed to investigate whether exposure to sunflower pollen (Helianthus annuus) increases both sensitization and respiratory symptoms, and whether or not it affects lung functions in sunflower processing workers. The largest sunflower processing factories in the Thrace region of Turkey participated in this study. Workers from the units directly exposed to sunflower seed enrolled as the study group (n = 102) and workers who were not directly exposed to Helianthus annuus pollen (n = 102) were the control group. Detailed questionnaires covering respiratory and allergic symptoms were completed, and skin prick tests and lung function tests were performed. We found a very high rate (23.5%) of sensitization to Helianthus annuus in the study group compared to the controls (P<0.001). Logistic regression analysis showed that the risk of sensitization to H. annuus was increased 4.7-fold (odds ratio = 4.17, 95%) confidence interval = 1.3-16.7) if subjects were exposed to sunflower pollen in the workplace. While asthmatic symptoms and allergic skin diseases were not different between the two groups, workers in the study group had a higher rate of allergic rhinitis and conjunctivitis (P<0.05). We found that pulmonary function was significantly impaired in the study group (P<0.01). Using a multivariate analysis model, inclusion in the study group was found to be a predictive factor for impairment of lung function (P=0.002). We conclude that sunflower pollen has high allergenic potential, especially when there is close contact, and exposure to sunflower pollen in the workplace can result in impairment in lung function.

Evaluation of Trigeminal Sensitivity to Ammonia in Asthmatics and Healthy Human Volunteers

PubMed Central

Petrova, Maja; Diamond, Jeanmarie; Schuster, Benno; Dalton, Pamela

2009-01-01

Background Asthmatics often report the triggering or exacerbation of respiratory symptoms following exposure to airborne irritants, which in some cases may result from stimulation of irritant receptors in the upper airways inducing reflexive broncho-constriction. Ammonia (NH3) is a common constituent of commercially available household products, and in high concentration has the potential to elicit sensory irritation in the eyes and upper respiratory tract of humans. The goal of the present study was to evaluate the irritation potential of ammonia in asthmatics and healthy volunteers and to determine whether differences in nasal or ocular irritant sensitivity to ammonia between these two groups could account for the exacerbation of symptoms reported by asthmatics following exposure to an irritant. Methods 25 healthy and 15 mild/moderate persistent asthmatic volunteers, with reported sensitivity to household cleaning products, were evaluated for their sensitivity to the ocular and nasal irritancy of NH3. Lung function was evaluated at baseline and multiple time points following exposure. Results Irritation thresholds did not differ between asthmatics and healthy controls, nor did ratings of odor intensity, annoyance and irritancy following exposure to NH3 concentrations at and above the irritant threshold for longer periods of time (30 sec).Importantly, no changes in lung function occurred following exposure to NH3 for any individuals in either group. Conclusion Despite heightened symptom reports to environmental irritants among asthmatics, the ocular and nasal trigeminal system of mild-moderate asthmatics does not appear to be more sensitive or more reactive than that of non-asthmatics, nor does short duration exposure to ammonia at irritant levels induce changes in lung function. At least in brief exposures, the basis for some asthmatics to experience adverse responses to volatile compounds in everyday life may arise from factors other than trigeminally-mediated reflexes. PMID:18728993

Lung function growth in children with long-term exposure to air pollutants in Mexico City.

PubMed

Rojas-Martinez, Rosalba; Perez-Padilla, Rogelio; Olaiz-Fernandez, Gustavo; Mendoza-Alvarado, Laura; Moreno-Macias, Hortensia; Fortoul, Teresa; McDonnell, William; Loomis, Dana; Romieu, Isabelle

2007-08-15

Although short-term exposure to air pollution has been associated with acute, reversible lung function decrements, the impact of long-term exposure has not been well established. To evaluate the association between long-term exposure to ozone (O(3)), particulate matter less than 10 mum in diameter (PM(10)), and nitrogen dioxide (NO(2)) and lung function growth in Mexico City schoolchildren. A dynamic cohort of 3,170 children aged 8 years at baseline was followed from April 23, 1996, through May 19, 1999. The children attended 39 randomly selected elementary schools located near 10 air quality monitoring stations and were visited every 6 months. Statistical analyses were performed using general linear mixed models. After adjusting for acute exposure and other potential confounding factors, deficits in FVC and FEV(1) growth over the 3-year follow-up period were significantly associated with exposure to O(3), PM(10), and NO(2). In multipollutant models, an interquartile range (IQR) increase in mean O(3) concentration (IQR, 11.3 ppb) was associated with an annual deficit in FEV(1) of 12 ml in girls and 4 ml in boys, an IQR range (IQR, 36.4 microg/m(3)) increase in PM(10) with an annual deficit in FEV(1) of 11 ml in girls and 15 ml in boys, and an IQR range (IQR, 12.0 ppb) increase in NO(2) with an annual deficit in FEV(1) of 30 ml in girls and 25 ml in boys. We conclude that long-term exposure to O(3), PM(10), and NO(2) is associated with a deficit in FVC and FEV(1) growth among schoolchildren living in Mexico City.

Acute high-level exposure to WTC particles alters expression of genes associated with oxidative stress and immune function in the lung

PubMed Central

Cohen, Mitchell D.; Vaughan, Joshua M.; Garrett, Brittany; Prophete, Colette; Horton, Lori; Sisco, Maureen; Kodavanti, Urmila P.; Ward, William O.; Peltier, Richard E.; Zelikoff, Judith; Chen, Lung-chi

2015-01-01

First responders (FR) present at Ground Zero in the first 72 h after the World Trade Center (WTC) collapsed have progressively exhibited significant respiratory injuries. The few toxicology studies performed to date evaluated effects from just fine (<2.5 µm) WTC dusts; none examined health effects/toxicities from atmospheres bearing larger particle sizes, despite the fact the majority (496%) of dusts were >10µm and most FR likely entrained dusts by mouth breathing. Using a system that generated/delivered supercoarse (10–53 µm) WTC dusts to F344 rats (in a manner that mimicked FR exposures), this study sought to examine potential toxicities in the lungs. In this exploratory study, rats were exposed for 2 h to 100 mg WTC dust/m3 (while under isoflurane [ISO] anesthesia) or an air/ISO mixture; this dose conservatively modeled likely exposures by mouth-breathing FR facing ≈750–1000 mg WTC dust/m3. Lungs were harvested 2 h post-exposure and total RNA extracted for subsequent global gene expression analysis. Among the > 1000 genes affected by WTC dust (under ISO) or ISO alone, 166 were unique to the dust exposure. In many instances, genes maximally-induced by the WTC dust exposure (relative to in naïve rats) were unchanged/inhibited by ISO only; similarly, several genes maximally inhibited in WTC dust rats were largely induced/unchanged in rats that received ISO only. These outcomes reflect likely contrasting effects of ISO and the WTC dust on lung gene expression. Overall, the data show that lungs of rats exposed to WTC dust (under ISO) – after accounting for any impact from ISO alone – displayed increased expression of genes related to lung inflammation, oxidative stress, and cell cycle control, while several involved in anti-oxidant function were inhibited. These changes suggested acute inflammogenic effects and oxidative stress in the lungs of WTC dust-exposed rats. This study, thus, concludes that a single very high exposure to WTC dusts could potentially have adversely affected the respiratory system – in terms of early inflammatory and oxidative stress processes. As these changes were not compared with other types of dusts, the uniqueness of these WTC-mediated effects remains to be confirmed. It also still remains to be determined if these effects might have any relevance to chronic lung pathologies that became evident among FR who encountered the highest dust levels on September 11, 2001 and the 2 days thereafter. Ongoing studies using longer-range post-exposure analyses (up to 1-year or more) will help to determine if effects seen here on genes were acute, reversible, or persistent, and associated with corresponding histopathologic/ biochemical changes in situ. PMID:24911330

Respiratory Symptoms and Lung Function among Greek Cotton Industry Workers: A Cross-Sectional Study.

PubMed

Anyfantis, Ioannis D; Rachiotis, Georgios; Hadjichristodoulou, Cristos; Gourgoulianis, Konstantinos I

2017-01-01

Workers in cotton industry are occupationally exposed to various dust-related hazards. The nature of these agents and the respective exposure levels depend on the cotton industry specific sector. These exposures could be associated with respiratory symptoms and changes in lung function parameters. To evaluate associations between occupational exposure and respiratory function as well as reported symptoms in several groups of workers at different stages of the cotton industry in a vertical approach that covers all the major sectors-from cotton ginning to weaving and fabric production. A questionnaire on respiratory symptoms and individual as well as workplace characteristics was completed by 256 workers at the cotton industry and 148 office workers (control group). Both groups underwent spirometry. Workers in cotton industry reported a higher prevalence of severe dyspnea (p=0.002) and wheezing (p=0.004) compared to the control group. Also they were found to have a lower predicted FEV 1 % (p<0.029) and lower FEV 1 /FVC (p<0.001) values. In addition, a higher prevalence of FEV 1 % <80% (p<0.001) and FEV 1 /FVC <70% (p=0.041) were found among textile workers. Similar results were found for non-smoker textile workers compared to non-smoker control group workers. Those working in cotton ginning mills recorded the highest decrease of spirometric values. Duration of employment in cotton industry and smoking use were found to be predictors of lung function decline for cotton industry workers. Occupational exposure to cotton dust was associated with increased prevalence of respiratory symptoms and obstructive pattern in pulmonary function test.

Chronic Alcohol Induces M2 Polarization Enhancing Pulmonary Disease Caused by Exposure to Particulate Air Pollution

PubMed Central

Thevenot, Paul; Saravia, Jordy; Giaimo, Joseph; Happel, Kyle I.; Dugas, Tammy R.; Cormier, Stephania A.

2013-01-01

Background Chronic alcohol consumption causes persistent oxidative stress in the lung, leading to impaired alveolar macrophage (AM) function and impaired immune responses. AMs play a critical role in protecting the lung from particulate matter (PM) inhalation by removing particulates from the airway and secreting factors which mediate airway repair. We hypothesized AM dysfunction caused by chronic alcohol consumption increases the severity of injury caused by particulate matter inhalation. Methods Age- and sex-matched C57BL6 mice were fed the Lieber-DeCarli liquid diet containing either alcohol or an iso-caloric substitution (control diet) for 8 weeks. Mice from both diet groups were exposed to combustion derived PM (CDPM) for the final 2 weeks. AM number, maturation, and polarization status were assessed by flow cytometry. Noninvasive and invasive strategies were used to assess pulmonary function and correlated with histomorphological assessments of airway structure and matrix deposition. Results Co-exposure to alcohol and CDPM decreased AM number and maturation status (CD11c expression) while increasing markers of M2 activation (IL-4Rα, Ym1, Fizz1 expression and IL-10 and TGF-β production). Changes in AM function were accompanied by decreased airway compliance and increased elastance. Altered lung function was attributable to elevated collagen content localized to the small airways and loss of alveolar integrity. Intranasal administration of neutralizing antibody to TGF-β during the CDPM exposure period improved changes in airway compliance and elastance while reducing collagen content caused by co-exposure. Conclusion CDPM inhalation causes enhanced disease severity in the alcoholic lung by stimulating the release of latent TGF-β stores in AMs. The combinatorial effect of elevated TGF-β, M2 polarization of AMs, and increased oxidative stress impairs pulmonary function by increasing airway collagen content and compromising alveolar integrity. PMID:23763452

Effects of conventional tobacco smoke and nicotine-free cigarette smoke on airway inflammation, airway remodelling and lung function in a triple allergen model of severe asthma.

PubMed

Tilp, C; Bucher, H; Haas, H; Duechs, M J; Wex, E; Erb, K J

2016-07-01

Patients with asthma who smoke have reduced lung function, increased exacerbation rates and increased steroid resistance compared to non-smoking asthmatics. In mice, cigarette smoke has been reported to have both pro- and anti-Th2 response effects. We hypothesized that combining tobacco cigarette smoke (tCS) with allergen exposure increases inflammation, airway remodelling and lung function in mice. To test this hypothesis, we combined a severe triple allergen model with tCS exposure and investigated whether effects were due to Toll-like receptor 4 signalling and/or nicotine and also observed when nicotine-free cigarettes were used. Mice were sensitized with ovalbumin, cockroach and house dust mite allergen in alum followed by intratracheal challenges with allergen twice a week for 6 weeks or additionally exposed to tCS during the allergen challenge period. Nicotine or nicotine-free herbal cigarette smoke was also applied to allergen challenged mice. tCS significantly reduced eosinophil numbers, IL-4 and IL-5 concentrations in the lung, total and allergen-specific IgE in serum, improved lung function and reduced collagen I levels. With the exception of collagen I all parameters reduced by tobacco cigarette smoke were also reduced in Toll-like receptor 4-deficient mice. Nicotine-free cigarette smoke also had significant anti-inflammatory effects on eosinophils, IL-4 and IL-5 concentrations in the lung and reduced airway hyperreactivity, albeit weaker than tobacco smoke. Applying nicotine alone also reduced Th2 cytokine levels and eosinophil numbers in the airways. Our experiments show that tCS exposure reduces allergen-induced Th2 response in the lung and associated collagen I production and development of airway hyperreactivity. With the exception on collagen I formation, these effects were not dependent on Toll-like receptor 4. The observed anti-Th2 effects of both nicotine and nicotine-free herbal cigarette smoke together suggests that tCS reduces the Th2 responses through nicotine and other products released by burning tobacco. © 2015 John Wiley & Sons Ltd.

Determinants of early-life lung function in African infants

PubMed Central

Willemse, Lauren; Visagie, Ane; Czövek, Dorottya; Nduru, Polite; Vanker, Aneesa; Stein, Dan J; Koen, Nastassja; Sly, Peter D; Hantos, Zoltán; Hall, Graham L; Zar, Heather J

2017-01-01

Background Low lung function in early life is associated with later respiratory illness. There is limited data on lung function in African infants despite a high prevalence of respiratory disease. Aim To assess the determinants of early lung function in African infants. Method Infants enrolled in a South African birth cohort, the Drakenstein child health study, had lung function measured at 6–10 weeks of age. Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, sulfur hexafluoride multiple breath washout and the forced oscillation technique. Information on antenatal and early postnatal exposures was collected using questionnaires and urine cotinine. Household benzene exposure was measured antenatally. Results Successful tests were obtained in 645/675 (95%) infants, median (IQR) age of 51 (46–58) days. Infant size, age and male gender were associated with larger tidal volume. Infants whose mothers smoked had lower tidal volumes (−1.6 mL (95% CI −3.0 to −0.1), p=0.04) and higher lung clearance index (0.1 turnovers (95% CI 0.01 to 0.3), p=0.03) compared with infants unexposed to tobacco smoke. Infants exposed to alcohol in utero or household benzene had lower time to peak tidal expiratory flow over total expiratory time ratios, 10% (95% CI −15.4% to −3.7%), p=0.002) and 3.0% (95% CI −5.2% to −0.7%, p=0.01) lower respectively compared with unexposed infants. HIV-exposed infants had higher tidal volumes (1.7 mL (95% CI 0.06 to 3.3) p=0.04) compared with infants whose mothers were HIV negative. Conclusion We identified several factors including infant size, sex, maternal smoking, maternal alcohol, maternal HIV and household benzene associated with altered early lung function, many of which are factors amenable to public health interventions. Long-term study of lung function and respiratory disease in these children is a priority to develop strategies to strengthen child health. PMID:27856821

Xeroderma Pigmentosum Group C Deficiency Alters Cigarette Smoke DNA Damage Cell Fate and Accelerates Emphysema Development.

PubMed

Sears, Catherine R; Zhou, Huaxin; Justice, Matthew J; Fisher, Amanda J; Saliba, Jacob; Lamb, Isaac; Wicker, Jessica; Schweitzer, Kelly S; Petrache, Irina

2018-03-01

Cigarette smoke (CS) exposure is a major risk factor for the development of emphysema, a common disease characterized by loss of cells comprising the lung parenchyma. The mechanisms of cell injury leading to emphysema are not completely understood but are thought to involve persistent cytotoxic or mutagenic DNA damage induced by CS. Using complementary cell culture and mouse models of CS exposure, we investigated the role of the DNA repair protein, xeroderma pigmentosum group C (XPC), on CS-induced DNA damage repair and emphysema. Expression of XPC was decreased in mouse lungs after chronic CS exposure and XPC knockdown in cultured human lung epithelial cells decreased their survival after CS exposure due to activation of the intrinsic apoptosis pathway. Similarly, cell autophagy and apoptosis were increased in XPC-deficient mouse lungs and were further increased by CS exposure. XPC deficiency was associated with structural and functional changes characteristic of emphysema, which were worsened by age, similar to levels observed with chronic CS exposure. Taken together, these findings suggest that repair of DNA damage by XPC plays an important and previously unrecognized role in the maintenance of alveolar structures. These findings support that loss of XPC, possibly due to chronic CS exposure, promotes emphysema development and further supports a link between DNA damage, impaired DNA repair, and development of emphysema.

ANTIOXIDANT SUPPLEMENTATION AND LUNG FUNCTIONS AMONG ASTHMATIC CHILDREN EXPOSED TO HIGH LEVELS OF AIR POLLUTANTS

EPA Science Inventory

Abstract

Air pollutant exposure has been related to adverse respiratory effects, in particular, in asthmatics. This effect could be the consequence of the oxidative stress caused by air pollutants on the lung. Antioxidant vitamins are free- radical scavengers, and could ha...

Single-Photon Emission Computed Tomography/Computed Tomography Imaging in a Rabbit Model of Emphysema Reveals Ongoing Apoptosis In Vivo

PubMed Central

Goldklang, Monica P.; Tekabe, Yared; Zelonina, Tina; Trischler, Jordis; Xiao, Rui; Stearns, Kyle; Romanov, Alexander; Muzio, Valeria; Shiomi, Takayuki; Johnson, Lynne L.

2016-01-01

Evaluation of lung disease is limited by the inability to visualize ongoing pathological processes. Molecular imaging that targets cellular processes related to disease pathogenesis has the potential to assess disease activity over time to allow intervention before lung destruction. Because apoptosis is a critical component of lung damage in emphysema, a functional imaging approach was taken to determine if targeting apoptosis in a smoke exposure model would allow the quantification of early lung damage in vivo. Rabbits were exposed to cigarette smoke for 4 or 16 weeks and underwent single-photon emission computed tomography/computed tomography scanning using technetium-99m–rhAnnexin V-128. Imaging results were correlated with ex vivo tissue analysis to validate the presence of lung destruction and apoptosis. Lung computed tomography scans of long-term smoke–exposed rabbits exhibit anatomical similarities to human emphysema, with increased lung volumes compared with controls. Morphometry on lung tissue confirmed increased mean linear intercept and destructive index at 16 weeks of smoke exposure and compliance measurements documented physiological changes of emphysema. Tissue and lavage analysis displayed the hallmarks of smoke exposure, including increased tissue cellularity and protease activity. Technetium-99m–rhAnnexin V-128 single-photon emission computed tomography signal was increased after smoke exposure at 4 and 16 weeks, with confirmation of increased apoptosis through terminal deoxynucleotidyl transferase dUTP nick end labeling staining and increased tissue neutral sphingomyelinase activity in the tissue. These studies not only describe a novel emphysema model for use with future therapeutic applications, but, most importantly, also characterize a promising imaging modality that identifies ongoing destructive cellular processes within the lung. PMID:27483341

Malondialdehyde-acetaldehyde (MAA) adducted protein inhalation causes lung injury

PubMed Central

Wyatt, T. A.; Kharbanda, K. K.; McCaskill, M. L.; Tuma, D. J.; Yanov, D.; DeVasure, J.; Sisson, J. H.

2011-01-01

In addition to cigarette smoking, alcohol exposure is also associated with increased lung infections and decreased mucociliary clearance. However, little research has been conducted on the combination effects of alcohol and cigarette smoke on lungs. Previously, we have demonstrated in a mouse model that the combination of cigarette smoke and alcohol exposure results in the formation of a very stable hybrid malondialdehyde-acetaldehyde (MAA)-adducted protein in the lung. In in vitro studies, MAA-adducted protein stimulates bronchial epithelial cell interleukin-8 via the activation of protein kinase C epsilon (PKCε). We hypothesized that direct MAA-adducted protein exposure in the lungs would mimic such a combination of smoke and alcohol exposure leading to airway inflammation. To test this hypothesis, C57BL/6J female mice were intranasally instilled with either saline, 30 µL of 50 µg/mL BSA-MAA, or unadducted BSA for up to 3 wk. Likewise, human lung surfactant proteins A and D (SPA, SPD) were purified from human pulmonary proteinosis lung lavage fluid and successfully MAA-adducted in vitro. Similar to BSA-MAA, SPD-MAA was instilled into mouse lungs. Lungs were necropsied and assayed for histopathology, PKCε activation, and lung lavage chemokines. In control mice instilled with saline, normal lungs had few inflammatory cells. No significant effects were observed in un-adducted BSA- or SPD-instilled mice. However, when mice were instilled with BSA-MAA or SPD-MAA for 3 wk, a significant peribronchiolar localization of inflammatory cells was observed. Both BSA-MAA and SPD-MAA stimulated increased lung lavage neutrophils and caused a significant elevation in the chemokine, KC, which is a functional homologue to human interleukin-8. Likewise, MAA-adducted protein stimulated the activation of airway and lung slice PKCε. These data support that MAA-adducted protein induces a pro-inflammatory response in the lungs and that lung surfactant protein is a biologically relevant target for malondialdehyde and acetaldehyde adduction. These data further implicate MAA-adduct formation as a potential mechanism for smoke and alcohol induced lung injury. PMID:21958604

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

PubMed Central

2010-01-01

Background Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level. Methods Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done. Results Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as CCL3, CCL4, CXCL2, and MMP12 in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as S100A8, S100A9 and MMP9. Conclusions Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume. PMID:20525249

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice.

PubMed

Zeidler-Erdely, Patti C; Kashon, Michael L; Li, Shengqiao; Antonini, James M

2010-06-03

Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level. Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done. Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as CCL3, CCL4, CXCL2, and MMP12 in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as S100A8, S100A9 and MMP9. Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume.

Development of a Zealand White Rabbit Deposition Model to Study Inhalation Anthrax

PubMed Central

Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, A.P.; Corley, Richard A.

2016-01-01

Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits. PMID:26895308

IN VIVO COMPARISON OF EPITHELIAL RESPONSES FOR S-8 VERSUS JP-8 JET FUELS BELOW PERMISSIBLE EXPOSURE LIMIT

PubMed Central

Wong, Simon S.; Vargas, Jason; Thomas, Alana; Fastje, Cindy; McLaughlin, Michael; Camponovo, Ryan; Lantz, R. Clark; Heys, Jeffrey; Witten, Mark L.

2010-01-01

This study was designed to characterize and compare the pulmonary effects in distal lung from a low-level exposure to jet propellant-8 fuel (JP-8) and a new synthetic-8 fuel (S-8). It is hypothesized that both fuels have different airway epithelial deposition and responses. Consequently, male C57BL/6 mice were nose-only exposed to S-8 and JP-8 at average concentrations of 53 mg/m3 for 1 hour/day for 7 days. A pulmonary function test performed 24 hr after the final exposure indicated that there was a significant increase in expiratory lung resistance in the S-8 mice, whereas JP-8 mice had significant increases in both inspiratory and expiratory lung resistance compared to control values. Neither significant S-8 nor JP-8 respiratory permeability changes were observed compared to controls, suggesting no loss of epithelial barrier integrity. Morphological examination and morphometric analysis of airway tissue demonstrated that both fuels showed different patterns of targeted epithelial cells: bronchioles in S-8 and alveoli/terminal bronchioles in JP-8. Collectively, our data suggest that both fuels may have partially different deposition patterns, which may possibly contribute to specific different adverse effects in lung ventilatory function. PMID:18930109

Space radiation-associated lung injury in a murine model.

PubMed

Christofidou-Solomidou, Melpo; Pietrofesa, Ralph A; Arguiri, Evguenia; Schweitzer, Kelly S; Berdyshev, Evgeny V; McCarthy, Maureen; Corbitt, Astrid; Alwood, Joshua S; Yu, Yongjia; Globus, Ruth K; Solomides, Charalambos C; Ullrich, Robert L; Petrache, Irina

2015-03-01

Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy (56)Fe or (28)Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions. Copyright © 2015 the American Physiological Society.

Spirometry: a predictor of lung cancer among asbestos workers.

PubMed

Świątkowska, Beata; Szeszenia-Dąbrowska, Neonila

2017-01-01

The significance of lung function as an independent risk factor for lung cancer remains unclear. The objective of the study is to answer the question if spirometry can identify patients at risk for lung cancer among people occupationally exposed to asbestos dust in the past. In order to identify a group of individuals with the highest risk of lung cancer incidence based on lung function levels of FEV 1 % predicted value, we examined 6882 subjects enrolled in the health surveillance program for asbestos related diseases over the years 2000-2014. We found a total of 110 cases confirmed as primary lung cancer. Using Cox's proportional hazards model after adjustment for age, gender, number of cigarettes, duration of smoking and cumulative asbestos exposure, we estimated that compared with the subjects with FEV 1 ≥90% pred, the HR of lung cancer was 1.40 (95%CI: 0.94-2.08) for the subjects with FEV 1 less than 90% and 1.95 (HR = 1.86; 95%CI: 1.12-3.08) for those with FEV 1 less than 70%. In addition, probability of the occurrence of lung cancer for FEV 1 <90% of the predicted value was HR = 2.19 (95%CI: 1.04-4.61) in the subjects whose time since spirometry and cancer diagnosis was three years or less. The results strongly support the hypothesis that spirometry can identify patients at a risk of lung cancer development. Regular spirometry should be offered to all patients with a history of asbestos exposure, at least once every three years.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Jing; Mo, Yiqun; Schlueter, Connie F.

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-inducedmore » neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. - Highlights: • Chlorine causes lung injury when inhaled and is considered a chemical threat agent. • Corticosteroids may inhibit lung injury through their anti-inflammatory actions. • Corticosteroids inhibited chlorine-induced pneumonitis and pulmonary edema. • Mometasone and budesonide are potential rescue treatments for chlorine lung injury.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunil, Vasanthi R., E-mail: sunilvr@eohsi.rutgers.edu; Patel, Kinal J., E-mail: kinalv5@gmail.com; Shen, Jianliang, E-mail: jianliangs@gmail.com

Nitrogen mustard is a vesicant that causes damage to the respiratory tract. In these studies, we characterized the acute effects of nitrogen mustard on lung structure, inflammatory mediator expression, and pulmonary function, with the goal of identifying mediators potentially involved in toxicity. Treatment of rats (male Wistar, 200-225 g) with nitrogen mustard (mechlorethamine hydrochloride, i.t., 0.25 mg/kg) resulted in marked histological changes in the respiratory tract, including necrotizing bronchiolitis, thickening of alveolar septa, and inflammation which was evident within 24 h. This was associated with increases in bronchoalveolar lavage protein and cells, confirming injury to alveolar epithelial regions of themore » lung. Nitrogen mustard administration also resulted in increased expression of inducible nitric oxide synthase and cyclooxygenase-2, pro-inflammatory proteins implicated in lung injury, in alveolar macrophages and alveolar and bronchial epithelial cells. Expression of connective tissue growth factor and matrix metalloproteinase-9, mediators regulating extracellular matrix turnover was also increased, suggesting that pathways leading to chronic lung disease are initiated early in the pathogenic process. Following nitrogen mustard exposure, alterations in lung mechanics and function were also observed. These included decreases in baseline static compliance, end-tidal volume and airway resistance, and a pronounced loss of methacholine responsiveness in resistance, tissue damping and elastance. Taken together, these data demonstrate that nitrogen mustard induces rapid structural and inflammatory changes in the lung which are associated with altered lung functioning. Understanding the nature of the injury induced by nitrogen mustard and related analogs may aid in the development of efficacious therapies for treatment of pulmonary injury resulting from exposure to vesicants.« less

Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide

PubMed Central

Chen, Jing; Mo, Yiqun; Schlueter, Connie F.; Hoyle, Gary W.

2013-01-01

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1 h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6 h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. PMID:23800689

Inhibition of chlorine-induced pulmonary inflammation and edema by mometasone and budesonide.

PubMed

Chen, Jing; Mo, Yiqun; Schlueter, Connie F; Hoyle, Gary W

2013-10-15

Chlorine gas is a widely used industrial compound that is highly toxic by inhalation and is considered a chemical threat agent. Inhalation of high levels of chlorine results in acute lung injury characterized by pneumonitis, pulmonary edema, and decrements in lung function. Because inflammatory processes can promote damage in the injured lung, anti-inflammatory therapy may be of potential benefit for treating chemical-induced acute lung injury. We previously developed a chlorine inhalation model in which mice develop epithelial injury, neutrophilic inflammation, pulmonary edema, and impaired pulmonary function. This model was used to evaluate nine corticosteroids for the ability to inhibit chlorine-induced neutrophilic inflammation. Two of the most potent corticosteroids in this assay, mometasone and budesonide, were investigated further. Mometasone or budesonide administered intraperitoneally 1h after chlorine inhalation caused a dose-dependent inhibition of neutrophil influx in lung tissue sections and in the number of neutrophils in lung lavage fluid. Budesonide, but not mometasone, reduced the levels of the neutrophil attractant CXCL1 in lavage fluid 6h after exposure. Mometasone or budesonide also significantly inhibited pulmonary edema assessed 1 day after chlorine exposure. Chlorine inhalation resulted in airway hyperreactivity to inhaled methacholine, but neither mometasone nor budesonide significantly affected this parameter. The results suggest that mometasone and budesonide may represent potential treatments for chemical-induced lung injury. © 2013.

Ventilatory function in rubber processing workers: acute changes over the workshift.

PubMed

Governa, M; Comai, M; Valentino, M; Antonicelli, L; Rinaldi, F; Pisani, E

1987-02-01

When considering rubber tyre manufacturing from an occupational health viewpoint, three areas may be identified in which exposure to respirable materials are potentially harmful: the processing, curing, and talc areas. A study of the ventilatory function of the entire work force employed in the processing area in a rubber tyre manufacturing plant was undertaken to determine whether an acute reduction in lung function occurs over the course of their working shift (the plant worked a three shift system) and whether a chronic exposure to the occupational airborne contaminants causes permanent changes in lung function. The ventilatory function was measured at the worksite at the beginning and immediately after the end of the workshift. No evidence of chronic obstructive pulmonary disease was found and in most cases no significant decline in FEV1 was observed. Only one of the 79 individuals showed a moderate obstruction, measured by the ratio FEV1/FVC which gave the value of 0.55, with no variation over the shift. For non-smokers, the FVC, FEV1, and FEF25-75% were lower in those exposed for more than five years than in those exposed for five years or less. A similar pattern was also observed in the FVC and FEV1 of the smokers. None of these differences was statistically significant. Within each exposure group the pulmonary function of the smokers was lower than that of the non-smokers, but the only significant difference was found in the values of FEF25-75%. Only one man showed a decline in the FEV1/FVC ratio over the shift, but during each shift, a decrease in all the lung function tests was observed. The decrease was smallest during the first of the three shifts. These results are thought to support the hypothesis that there are acute adverse effects over an eight hour shift. Further investigations are needed to discover whether these acute changes in lung function result from a chemical stimulation or irritant receptors in the airways.

Lung cancer mortality and airways obstruction among metal miners exposed to silica and low levels of radon daughters.

PubMed

Carta, P; Cocco, P; Picchiri, G

1994-04-01

Starting from a cross-sectional survey in 1973, the mortality of two cohorts of Sardinian metal miners was followed through December 31, 1988. In mine A, the quartz concentration in respirable dust ranged between 0.2% and 2.0% and the exposure to radon daughters averaged 0.13 working level (WL), with the highest estimated cumulative exposure around 80-120 WLM. In mine B, the silica content was much higher (6.5-29%), but exposure to radon daughters was significantly lower than in mine A. More than 98% of the overall work force in 1973 (1,741 miners) entered the cohort, providing 25,842.5 person-years. Smoking, occupational history, chest radiographs, and lung function tests were available for the cohort members at admission. Mortality for all causes was slightly lower than expected. A significant excess for nonmalignant chronic respiratory diseases was noticed in both mines. Twenty-four subjects died of lung cancer, 17 from mine A (SMR: 128; 95% confidence interval [CI]: 75-205) and 7 from mine B (SMR: 85; 95% CI: 34-175). The SMR for lung cancer was highest among the underground workers from mine A (SMR: 148; 95% CI: 74-265), with a significant upward trend by duration of employment in underground jobs. Mine B underground miners showed lung cancer SMRs close to 100 without a significant trend by duration of employment. Among underground miners with spirometric airways obstruction in 1973, those from mine A showed the highest risk (SMR: 316; 95% CI: 116-687). The relationship did not change after adjusting for age and smoking. Based on the present findings, crystalline silica per se does not appear to affect lung cancer mortality. A slight association between lung cancer mortality and exposure to radon daughters, though within relatively low levels, may be considered for underground miners from mine A. Impaired pulmonary function may be an independent predictor of lung cancer and an important risk factor enhancing the residence time of inhaled carcinogens, i.e., alpha particles or PAHs, by impairing their bronchial and alveolar clearance.

Functional genomics of chlorine-induced acute lung injury in mice.

PubMed

Leikauf, George D; Pope-Varsalona, Hannah; Concel, Vincent J; Liu, Pengyuan; Bein, Kiflai; Brant, Kelly A; Dopico, Richard A; Di, Y Peter; Jang, An-Soo; Dietsch, Maggie; Medvedovic, Mario; Li, Qian; Vuga, Louis J; Kaminski, Naftali; You, Ming; Prows, Daniel R

2010-07-01

Acute lung injury can be induced indirectly (e.g., sepsis) or directly (e.g., chlorine inhalation). Because treatment is still limited to supportive measures, mortality remains high ( approximately 74,500 deaths/yr). In the past, accidental (railroad derailments) and intentional (Iraq terrorism) chlorine exposures have led to deaths and hospitalizations from acute lung injury. To better understand the molecular events controlling chlorine-induced acute lung injury, we have developed a functional genomics approach using inbred mice strains. Various mouse strains were exposed to chlorine (45 ppm x 24 h) and survival was monitored. The most divergent strains varied by more than threefold in mean survival time, supporting the likelihood of an underlying genetic basis of susceptibility. These divergent strains are excellent models for additional genetic analysis to identify critical candidate genes controlling chlorine-induced acute lung injury. Gene-targeted mice then could be used to test the functional significance of susceptibility candidate genes, which could be valuable in revealing novel insights into the biology of acute lung injury.

Lung function, atopy, and chronic exposure to air pollution in schoolchildren living in two cities of different air quality

NASA Astrophysics Data System (ADS)

Gurzau, Eugen S.; Gurzau, Anca; Muresan, Marius; Bodor, Ecaterina; Zehan, Zoe; Radulescu, Nicolae

1993-03-01

The question of a causative interrelation between air pollution and respiratory status has received considerable attention by the mass media in our country. Schoolchildren aged 7 to 11 living in two communities with different levels of air pollution were studied. The parents of these children filled out a health questionnaire. The prevalence of respiratory symptoms and pulmonary diseases was found to be significantly higher among children growing up in the polluted area (Tirnaveni) as compared with the low-pollution area (Dej). Lung function tests point out FEF25-75 disorders (and other lung disorders) at higher frequencies in schoolchildren living in the polluted area. Over 90% of schoolchildren living in the polluted area. Over 90% of schoolchildren with lung function disorders had a positive response to bronchodilatation. Of the schoolchildren with lung function disorders, 75.47% (p < 0,001) were atopic all of whom were sensitized to the down and house-dust.

Lung transplantation in adults and children: putting lung function into perspective.

PubMed

Thompson, Bruce Robert; Westall, Glen Philip; Paraskeva, Miranda; Snell, Gregory Ian

2014-11-01

The number of lung transplants performed globally continues to increase year after year. Despite this growing experience, long-term outcomes following lung transplantation continue to fall far short of that described in other solid-organ transplant settings. Chronic lung allograft dysfunction (CLAD) remains common and is the end result of exposure to a multitude of potentially injurious insults that include alloreactivity and infection among others. Central to any description of the clinical performance of the transplanted lung is an assessment of its physiology by pulmonary function testing. Spirometry and the evaluation of forced expiratory volume in 1 s and forced vital capacity, remain core indices that are measured as part of routine clinical follow-up. Spirometry, while reproducible in detecting lung allograft dysfunction, lacks specificity in differentiating the different complications of lung transplantation such as rejection, infection and bronchiolitis obliterans. However, interpretation of spirometry is central to defining the different 'chronic rejection' phenotypes. It is becoming apparent that the maximal lung function achieved following transplantation, as measured by spirometry, is influenced by a number of donor and recipient factors as well as the type of surgery performed (single vs double vs lobar lung transplant). In this review, we discuss the wide range of variables that need to be considered when interpreting lung function testing in lung transplant recipients. Finally, we review a number of novel measurements of pulmonary function that may in the future serve as better biomarkers to detect and diagnose the cause of the failing lung allograft. © 2014 Asian Pacific Society of Respirology.

[Lipoid pneumonia related to workplace exposure to paint].

PubMed

Abad Fernández, A; de Miguel Díez, J; López Vime, R; Gómez Santos, D; Nájera Botello, L; Jara Chinarro, B

2003-03-01

A 49-year-old man with no known history of pulmonary disease was treated at our hospital after observation of an interstitial pattern on a chest film. The patient was a smoker and professional painter. Computed tomography of the chest showed a diffuse bilateral ground-glass pattern. The lung biopsy showed intra-alveolar lipid accumulation in the form of vacuoles of varying sizes surrounded by numerous focally multinucleated macrophages, establishing a definitive diagnosis of exogenous lipoid pneumonia. Given the patient's profession, he was recommended to avoid workplace exposure to paraffins and oily sprays. The clinical course was favorable after exposure was stopped, with improved lung function and symptoms.

Assessing exposure risk for dust storm events-associated lung function decrement in asthmatics and implications for control

NASA Astrophysics Data System (ADS)

Hsieh, Nan-Hung; Liao, Chung-Min

2013-04-01

Asian dust storms (ADS) events are seasonally-based meteorological phenomena that exacerbate chronic respiratory diseases. The purpose of this study was to assess human health risk from airborne dust exposure during ADS events in Taiwan. A probabilistic risk assessment framework was developed based on exposure and experimental data to quantify ADS events induced lung function decrement. The study reanalyzed experimental data from aerosol challenge in asthmatic individuals to construct the dose-response relationship between inhaled dust aerosol dose and decreasing percentage of forced expiratory volume in 1 s (%FEV1). An empirical lung deposition model was used to predict deposition fraction for size specific dust aerosols in pulmonary regions. The toxicokinetic and toxicodynamic models were used to simulate dust aerosols binding kinetics in lung airway in that %FEV1 change was also predicted. The mask respirators were applied to control the inhaled dose under dust aerosols exposure. Our results found that only 2% probability the mild ADS events were likely to cause %FEV1 decrement higher than 5%. There were 50% probability of decreasing %FEV1 exceeding 16.9, 18.9, and 7.1% in north, center, and south Taiwan under severe ADS events, respectively. Our result implicates that the use of activated carbon of mask respirators has the best efficacy for reducing inhaled dust aerosol dose, by which the %FEV1 decrement can be reduced up to less than 1%.

Welding, longitudinal lung function decline and chronic respiratory symptoms: a systematic review of cohort studies.

PubMed

Szram, Joanna; Schofield, Susie J; Cosgrove, Martin P; Cullinan, Paul

2013-11-01

While the acute respiratory risks of welding are well characterised, more chronic effects, including those on lung function, are less clear. We carried out a systematic review of published longitudinal studies of lung function decline in welders. Original cohort studies documenting two or more sequential measurements of lung function were reviewed. Meta-analysis was carried out on studies with suitable data on forced expiratory volume in 1 s (FEV1). Seven studies were included; their quality (measured on the Newcastle-Ottawa scale) was good, although exposure assessment was limited and the studies showed significant heterogeneity. Five had data suitable for meta-analysis; the pooled estimate of the difference in FEV1 decline between welders and nonwelders was -9.0 mL · year(-1) (95% CI -22.5-4.5; p=0.193). The pooled estimates of difference in annual FEV1 decline between welders and referents who smoked was -13.7 mL · year(-1) (95% CI -33.6-6.3; p=0.179). For welders and referents who did not smoke the estimated difference was -3.8 mL · year(-1) (95% CI -20.2-12.6; p=0.650). Symptom prevalence data were mainly narrative; smoking appeared to have the greatest effect on symptom evolution. Collectively, available longitudinal data on decline of lung function in welders and respiratory symptoms suggest a greater effect in those who smoke, supporting a focus on smoking cessation as well as control of fume exposure in this trade. Further prospective studies are required to confirm these findings.

Respiratory health effects of the indoor environment in a population of Dutch children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dijkstra, L.; Houthuijs, D.; Brunekreef, B.

1990-11-01

The effect of indoor exposure to nitrogen dioxide on respiratory health was studied over a period of 2 yr in a population of nonsmoking Dutch children 6 to 12 yr of age. Lung function was measured at the schools, and information on respiratory symptoms was collected from a self-administered questionnaire completed by the parents of the children. Nitrogen dioxide was measured in the homes of all children with Palmes' diffusion tubes. In addition, information on smoking and dampness in the home was collected by questionnaire. There was no relationship between exposure to nitrogen dioxide in the home and respiratory symptoms.more » Respiratory symptoms were found to be associated with exposure to tobacco smoke and home dampness. There was a weak, negative association between maximal midexpiratory flow (MMEF) and exposure to nitrogen dioxide. FEV1, peak expiratory flow, and MMEF were all negatively associated with exposure to tobacco smoke. Home dampness was not associated with pulmonary function. Lung function growth, measured over a period of 2 yr, was not consistently associated with any of the indoor exposure variables. The development of respiratory symptoms over time was not associated with indoor exposure to nitrogen dioxide. There was a significant association between exposure to environmental tobacco smoke in the home and the development of wheeze. There was also a significant association between home dampness and the development of cough.« less

Detection of early changes in lung cell cytology by flow-systems analysis techniques. Progress report, July 1--December 31, 1977

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinkamp, J.A.; Hansen, K.M.; Wilson, J.S.

1978-04-01

This report summarizes ongoing experiments to develop cytological and biochemical indicators for measuring damage to respiratory tract cells exposed by inhalation of environmental toxic agents. The specific goal of this project is to apply flow cytometric methods to analyze and detect changes in lung epithelium as a function of exposure to toxic agents such as those associated with the production of synthetic fuels from oil shale and coal. The objectives during the past 6 months were to complete modifications to the multiparameter cell separator by adding a krypton laser with an output capability of specific wavelengths ranging from the uvmore » to the ir; analyze and separate lung cells based on their DNA content; evaluate some new fluorescent DNA and protein stains; and treat hamster lung cells with proteolytic enzymes for increasing cell yield. Future experiments will involve the continued analysis and characterization of exfoliated lung cells based primarily on cellular DNA content, protein, morphological features, and specific enzyme activities; quantitation of macrophage activity; exposure of hamsters to toxic agents such as oil shale particulates and ozone; and continued analysis of cells based on DNA content. As this new technology becomes adapted to analyzing respiratory tract cells, the measurement of physical and biochemical cell properties as a function of exposure to toxic agents will be increased. This analytical approach is designed to assist in the establishment of guidelines for estimating risks to exposed humans.« less

Impaired lung function in individuals chronically exposed to biomass combustion.

PubMed

da Silva, Luiz Fernando Ferraz; Saldiva, Silvia Regina Dias Médici; Saldiva, Paulo Hilário Nascimento; Dolhnikoff, Marisa

2012-01-01

The use of biomass for cooking and heating is considered an important factor associated with respiratory diseases. However, few studies evaluate the amount of particulate matter less than 2.5 μm in diameter (PM2.5), symptoms and lung function in the same population. To evaluate the respiratory effects of biomass combustion and compare the results with those of individuals from the same community in Brazil using liquefied petroleum gas (Gas). 1402 individuals in 260 residences were divided into three groups according to exposure (Gas, Indoor-Biomass, Outside-Biomass). Respiratory symptoms were assessed using questionnaires. Reflectance of paper filters was used to assess particulate matter exposure. In 48 residences the amount of PM2.5 was also quantified. Pulmonary function tests were performed in 120 individuals. Reflectance index correlated directly with PM2.5 (r=0.92) and was used to estimate exposure (ePM2.5). There was a significant increase in ePM2.5 in Indoor-Biomass and Outside-Biomass, compared to Gas. There was a significantly increased odds ratio (OR) for cough, wheezing and dyspnea in adults exposed to Indoor-Biomass (OR=2.93, 2.33, 2.59, respectively) and Outside-Biomass (OR=1.78, 1.78, 1.80, respectively) compared to Gas. Pulmonary function tests revealed both Non-Smoker-Biomass and Smoker-Gas individuals to have decreased %predicted-forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) as compared to Non-Smoker-Gas. Pulmonary function tests data was inversely correlated with duration and ePM2.5. The prevalence of airway obstruction was 20% in both Non-Smoker-Biomass and Smoker-Gas subjects. Chronic exposure to biomass combustion is associated with increased prevalence of respiratory symptoms, reduced lung function and development of chronic obstructive pulmonary disease. These effects are associated with the duration and magnitude of exposure and are exacerbated by tobacco smoke. Copyright © 2011 Elsevier Inc. All rights reserved.

Lung pathology in response to repeated exposure to Staphylococcus aureus in congenic residual function cystic fibrosis mice does not increase in response to decreased CFTR levels or increased bacterial load.

PubMed

Davidson, Donald J; Webb, Sheila; Teague, Peter; Govan, John R W; Dorin, Julia R

2004-01-01

To establish the role of defects in murine Cftr in the susceptibility to Staphylococcus aureus lung disease using mouse models of cystic fibrosis (CF), congenic or inbred strains. We describe the histopathological analyses of CF mice repeatedly exposed by aerosolisation to a CF isolate of S. aureus, using residual function Cftr mice and compound heterozygotes generated by intercrossing these with Cftr 'null' mice, all congenic on the C57Bl6/N background. We demonstrate that mice congenic on the C57Bl/6 background develop significantly more severe lung pathology than non-CF littermates in response to repeated exposure to the most frequent early CF lung pathogen S. aureus. Furthermore, reducing the level of Cftr by half in compound heterozygote mice does not impact upon disease severity, even in response to an increased bacterial dose. These results are consistent with an airway clearance defect, or abnormal inflammatory response secondary to Cftr mutation. These studies confirm the primary role for Cftr mutation in the development of this lung phenotype. In addition, these results demonstrate that a further 50% decrease in residual wild-type Cftr mRNA levels in this model does not impact the severity of the histopathological response to S. aureus, suggesting a critical threshold level for functional CFTR. Copyright 2004 S. Karger AG, Basel

Excess longitudinal decline in lung function in grain farmers.

PubMed

Senthilselvan, Ambikaipakan; Chénard, Liliane; Grover, Vaneeta; Kirychuk, Shelley P; Hagel, Louise; Ulmer, Kendra; Hurst, Thomas S; Dosman, James A

2010-04-01

Workers in intensive agricultural operations are exposed to dust and endotoxin that are associated with respiratory effects. The authors investigated the longitudinal changes in lung function in male grain farmers. In this study, male grain farmers (n = 263) and male nonfarming control subjects (n = 261) studies initially in 1990/91 were followed-up in 1994/95 and 2003/04. After controlling for potential confounders, grain farmers had an excess annual decline of 9.2 ml/year (95% confidence interval [CI]: 2.7, 15.8, p = .006) in forced vital capacity (FVC) in comparison to control. Long-term exposure to grain dust and other substances in lifetime grain farmers results in progressive loss in lung function.

Stochastic dosimetry model for radon progeny in the rat lung.

PubMed

Winkler-HeiI, R; Hofmann, W; Hussain, M

2014-07-01

The stochastic dosimetry model presented here considers the distinctly asymmetric, stochastic branching pattern reported in morphometric measurements. This monopodial structure suggests that an airway diameter is a more appropriate morphometric parameter to classify bronchial dose distributions for inhaled radon progeny than the commonly assigned airway generation numbers. Bronchial doses were calculated for the typical exposure conditions reported for the Pacific Northwest National Laboratory rat inhalation studies, yielding an average bronchial dose of 7.75 mGy WLM(-1). If plotted as functions of airway generations, the resulting dose distributions are highest in the central bronchial airways, while significantly decreasing towards peripheral generations. However, if plotted as functions of airway diameters, doses are much more uniformly distributed among bronchial airways. The comparison between rat and human lungs indicates that dose conversion coefficients for the rat lung are higher than the corresponding values for the human lung by a factor of 1.34 for the experimental PNNL exposure conditions, and of 1.25 for typical human indoor conditions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A panel study of airborne particulate matter concentration and impaired cardiopulmonary function in young adults by two different exposure measurement

NASA Astrophysics Data System (ADS)

Hu, Li-Wen; Qian, Zhengmin (Min); Bloom, Michael S.; Nelson, Erik J.; Liu, Echu; Han, Bin; Zhang, Nan; Liu, Yimin; Ma, Huimin; Chen, Duo-Hong; Yang, Bo-Yi; Zeng, Xiao-Wen; Chen, Wen; Komppula, Mika; Leskinen, Ari; Hirvonen, Maija-Riitta; Roponen, Marjut; Jalava, Pasi; Bai, Zhipeng; Dong, Guang-Hui

2018-05-01

This study sought to clarify the correlation of individual exposure measurements and PM2.5 measurements collected at regulatory monitoring sites in short-term panel study settings. To achieve this goal, 30 young, healthy adult participants were assigned to three groups with 4 samplers in each group to collect individual exposures during four weekends in March 2016. Participants also completed cardiopulmonary function tests during the same periods. For comparison, ambient air pollution data were obtained from the Air Pollution Surveillance Network in Guangzhou, China. The 8-h ambient pollutant averages and group sampler concentrations were used as separate indicators of air pollution exposure. Results showed that the 8-h mean concentration of personal PM2.5 exposure was 65.09 ± 22.18 μg/m3, which was 24.34 μg/m3 statistically higher than the ambient concentrations over the same period (p < 0.05). However, these concentrations were strongly correlated (Spearman's r = 0.937, p < 0.01). Separate mixed-effect models were fit for ambient and personal exposures to estimate their associations with cardiopulmonary outcomes. Higher PM2.5 and PM10 exposures were related to lower lung function of maximal mid-expiratory flow (MMEF). A 10 μg/m3 higher PM was associated with 0.11 L/S to 0.52 L/S lower MMEF. No effects on cardiovascular function were found. In conclusion, personal PM2.5 exposure might be higher than ambient concentrations. Young, healthy adults in urban areas may experience reduced lung function (lower MMEF), even after just 8 h of exposure to PM2.5 and PM10.

Atopic asthmatic subjects but not atopic subjects without ...

EPA Pesticide Factsheets

BACKGROUND: Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of ozone-induced inflammation has not been determined. OBJECTIVE: We sought to determine whether atopic status modulates ozone response phenotypes in human subjects. METHODS: Fifty volunteers (25 healthy volunteers, 14 atopic nonasthmatic subjects, and 11 atopic asthmatic subjects not requiring maintenance therapy) underwent a 0.4-ppm ozone exposure protocol. Ozone response was determined based on changes in lung function and induced sputum composition, including airway inflammatory cell concentration, cell-surface markers, and cytokine and hyaluronic acid concentrations. RESULTS: All cohorts experienced similar decreases in lung function after ozone. Atopic and atopic asthmatic subjects had increased sputum neutrophil numbers and IL-8 levels after ozone exposure; values did not significantly change in healthy volunteers. After ozone exposure, atopic asthmatic subjects had significantly increased sputum IL-6 and IL-1beta levels and airway macrophage Toll-like receptor 4, Fc(epsilon)RI, and CD23 expression; values in healthy volunteers and atopic nonasthmatic subjects showed no significant change. Atopic asthmatic subjects had significantly decreased IL-10 levels at baseline compared with healthy volunteers; IL-10 levels did not significa

Silica inhalation altered telomere length and gene expression of telomere regulatory proteins in lung tissue of rats.

PubMed

Shoeb, Mohammad; Joseph, Pius; Kodali, Vamsi; Mustafa, Gul; Farris, Breanne Y; Umbright, Christina; Roberts, Jenny R; Erdely, Aaron; Antonini, James M

2017-12-11

Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT. Lung tissues and blood samples were collected from rats at 4, 32, and 44 wk after exposure to 15 mg/m 3 of silica × 6 h/d × 5 d. Controls were exposed to air. At all-time points, RTEL1 expression was significantly decreased in lung tissue of the silica-exposed animals compared to controls. Also, significant increases in telomere length and TERT were observed in the silica group at 4 and 32 wk. Telomere length, RTEL1 and TERT expression may serve as potential biomarkers related to silica exposure and may offer insight into the molecular mechanism of silica-induced lung disease and tumorigeneses.

TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema.

PubMed

An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C; Ifedigbo, Emeka; Washko, George R; Ryter, Stefan W; Choi, Augustine M K

2012-11-01

Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.

TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema

PubMed Central

An, Chang Hyeok; Wang, Xiao Mei; Lam, Hilaire C.; Ifedigbo, Emeka; Washko, George R.; Ryter, Stefan W.

2012-01-01

Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS. PMID:22983353

Common cold decreases lung function in infants with recurrent wheezing.

PubMed

Mallol, J; Aguirre, V; Wandalsen, G

2010-01-01

Common acute viral respiratory infections (colds) are the most frequent cause of exacerbations in infants with recurrent wheezing (RW). However, there is no quantitative information about the effect of colds on the lung function of infants with RW. This study was undertaken to determine the effect of common cold on forced expiratory parameters measured from raised lung volume in infants with RW. Spirometric lung function (expiratory flows from raised lung volume) was randomly assessed in 28 infants with RW while they had a common cold and when asymptomatic. It was found that during colds there was a significant decrease in all forced expiratory parameters and this was much more evident for flows (FEF(50%), FEF(75%) and FEF(25-75%)) which were definitively abnormal (less than -1.65 z-score) in the majority of infants. There was not association between family asthma, tobacco exposure, and other factors, with the extent of lung function decrease during colds. Tobacco during pregnancy but not a history of family asthma was significantly associated to lower expiratory flows; however, the association was significant only when infants were asymptomatic. This study shows that common colds cause a marked reduction of lung function in infants with RW. 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

Inhalation exposure of rats to asphalt fumes generated at paving temperatures alters pulmonary xenobiotic metabolism pathways without lung injury.

PubMed Central

Ma, Jane Y C; Rengasamy, Apavoo; Frazer, Dave; Barger, Mark W; Hubbs, Ann F; Battelli, Lori; Tomblyn, Seith; Stone, Samuel; Castranova, Vince

2003-01-01

Asphalt fumes are complex mixtures of various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). PAHs require bioactivation by the cytochrome P-450 monooxygenase system to exert toxic/carcinogenic effects. The present study was carried out to characterize the acute pulmonary inflammatory responses and the alterations of pulmonary xenobiotic pathways in rats exposed to asphalt fumes by inhalation. Rats were exposed at various doses and time periods to air or to asphalt fumes generated at paving temperatures. To assess the acute damage and inflammatory responses, differential cell counts, acellular lactate dehydrogenase (LDH) activity, and protein content of bronchoalveolar lavage fluid were determined. Alveolar macrophage (AM) function was assessed by monitoring generation of chemiluminescence and production of tumor necrosis factor-alpha and interleukin-1. Alteration of pulmonary xenobiotic pathways was determined by monitoring the protein levels and activities of P-450 isozymes (CYP1A1 and CYP2B1), glutathioneS-transferase (GST), and NADPH:quinone oxidoreductase (QR). The results show that acute asphalt fume exposure did not cause neutrophil infiltration, alter LDH activity or protein content, or affect AM function, suggesting that short-term asphalt fume exposure did not induce acute lung damage or inflammation. However, acute asphalt fume exposure significantly increased the activity and protein level of CYP1A1 whereas it markedly reduced the activity and protein level of CYP2B1 in the lung. The induction of CYP1A1 was localized in nonciliated bronchiolar epithelial (Clara) cells, alveolar septa, and endothelial cells by immunofluorescence microscopy. Cytosolic QR activity was significantly elevated after asphalt fume exposure, whereas GST activity was not affected by the exposure. This induction of CYP1A1 and QR with the concomitant down-regulation of CYP2B1 after asphalt fume exposure could alter PAH metabolism and may lead to potential toxic effects in the lung. PMID:12842776

Effects of theatrical smokes and fogs on respiratory health in the entertainment industry.

PubMed

Varughese, Sunil; Teschke, Kay; Brauer, Michael; Chow, Yat; van Netten, Chris; Kennedy, Susan M

2005-05-01

Theatrical fogs (glycol or mineral oil aerosols) are widely used in the entertainment industry to create special effects and make lighting visible. We studied 101 employees at 19 sites using fogs and measured personal fog exposures, across work shift lung function, and acute and chronic symptoms. Results were also compared to an external control population, studied previously. Chronic work-related wheezing and chest tightness were significantly associated with increased cumulative exposure to fogs (mineral oil and glycols) over the previous 2 years. Acute cough and dry throat were associated with acute exposure to glycol-based fogs; increased acute upper airway symptoms were associated with increased fog aerosol overall. Lung function was significantly lower among those working closest to the fog source. Mineral oil- and glycol-based fogs are associated with acute and chronic adverse effects on respiratory health among employees. Reducing exposure, through controls, substitution, and elimination where possible, is likely to reduce these effects. (c) 2005 Wiley-Liss, Inc.

Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

PubMed Central

Botelho, Danielle; Leo, Bey F.; Massa, Christopher; Sarkar, Srijata; Tetley, Terry; Chung, Kian F.; Chen, Shu; Ryan, Mary P.; Porter, Alexandra; Atochina-Vasserman, Elena N.; Zhang, Junfeng; Schwander, Stephan; Gow, Andrew J.

2018-01-01

Here we examine the organ level toxicology of both carbon black (CB) and silver nanoparticles (AgNP). We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF). C57Bl6/J male mice were intratracheally instilled with saline (control), low (0.05 μg/g) or high (0.5 μg/g) doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D) content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function. PMID:29632485

Health hazard evaluation report HETA 88-391-2156, Morton Salt Company, Weeks Island, Louisiana. (Revised April 1993)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferguson, R.P.; Knutti, E.B.

1993-04-01

In response to a request from the International Chemical Workers Union, an investigation was made of exposures to asbestos and diesel emissions at the Morton Salt Company, Weeks Island, Louisiana. The most significant source of particulates was diesel exhaust. None of the 20 personal breathing zone or area air samples collected in the mill exceeded limits for asbestos. An increased prevalence of chronic cough and phlegm was reported by workers. More complaints of eye irritation and tearing of the eyes were noted in underground workers, consistent with diesel byproduct exposure. Pulmonary function studies indicated that four workers had mild obstructivemore » lung disease and one had moderate obstructive lung disease. Three workers with mild restriction of lung volume were also noted. None of the 61 chest films taken was positive for pneumoconiosis. The authors conclude that a potential hazard existed from exposure to diesel exhaust.« less

Comparative cardiopulmonary effects of size-fractionated airborne particulate matter.

PubMed

Amatullah, Hajera; North, Michelle L; Akhtar, Umme S; Rastogi, Neeraj; Urch, Bruce; Silverman, Frances S; Chow, Chung-Wai; Evans, Greg J; Scott, Jeremy A

2012-02-01

Strong epidemiological evidence exists linking particulate matter (PM) exposures with hospital admissions of individuals for cardiopulmonary symptoms. The PM size is important in influencing the extent of infiltration into the respiratory tract and systemic circulation and directs the differential physiological impacts. To investigate the differential effects of the quasi-ultrafine (PM(0.2)), fine (PM(0.15-2.5)), and coarse PM (PM(2.5-10)) size fractions on pulmonary and cardiac function. Female BALB/c mice were exposed to HEPA-filtered laboratory air or concentrated coarse, fine, or quasi-ultrafine PM using Harvard Ambient Particle Concentrators in conjunction with our nose-only exposure system. These exposures were conducted as part of the "Health Effects of Aerosols in Toronto (HEAT)" campaign. Following a 4 h exposure, mice underwent assessment of respiratory function and recording of electrocardiograms using the flexiVent® system. Exposure to coarse and fine PM resulted in a significant reduction in quasistatic compliance of the lung. Baseline total respiratory resistance and maximum responsiveness to methacholine were augmented after coarse PM exposures but were not affected by quasi-ultrafine PM exposures. In contrast, quasi-ultrafine PM alone had a significant effect on heart rate and in reducing heart rate variability. These findings indicate that coarse and fine PM influence lung function and airways responsiveness, while ultrafine PM can perturb cardiac function. This study supports the hypothesis that coarse and fine PM exerts its predominant physiologic effects at the site of deposition in the airways, whereas ultrafine PM likely crosses the alveolar epithelial barrier into the systemic circulation to affect cardiovascular function.

Atomic layer deposition coating of carbon nanotubes with zinc oxide causes acute phase immune responses in human monocytes in vitro and in mice after pulmonary exposure.

PubMed

Dandley, Erinn C; Taylor, Alexia J; Duke, Katherine S; Ihrie, Mark D; Shipkowski, Kelly A; Parsons, Gregory N; Bonner, James C

2016-06-08

Atomic layer deposition (ALD) is a method for applying conformal nanoscale coatings on three-dimensional structures. We hypothesized that surface functionalization of multi-walled carbon nanotubes (MWCNTs) with polycrystalline ZnO by ALD would alter pro-inflammatory cytokine expression by human monocytes in vitro and modulate the lung and systemic immune response following oropharyngeal aspiration in mice. Pristine (U-MWCNTs) were coated with alternating doses of diethyl zinc and water over increasing ALD cycles (10 to 100 ALD cycles) to yield conformal ZnO-coated MWCNTs (Z-MWCNTs). Human THP-1 monocytic cells were exposed to U-MWCNTs or Z-MWCNTs in vitro and cytokine mRNAs measured by Taqman real-time RT-PCR. Male C57BL6 mice were exposed to U- or Z-MWCNTs by oropharyngeal aspiration (OPA) and lung inflammation evaluated at one day post-exposure by histopathology, cytokine expression and differential counting of cells in bronchoalveolar lavage fluid (BALF) cells. Lung fibrosis was evaluated at 28 days. Cytokine mRNAs (IL-6, IL-1β, CXCL10, TNF-α) in lung, heart, spleen, and liver were quantified at one and 28 days. DNA synthesis in lung tissue was measured by bromodeoxyuridine (BrdU) uptake. ALD resulted in a conformal coating of MWCNTs with ZnO that increased proportionally to the number of coating cycles. Z-MWCNTs released Zn(+2) ions in media and increased IL-6, IL-1β, CXCL10, and TNF-α mRNAs in THP-1 cells in vitro. Mice exposed to Z-MWCNTs by OPA had exaggerated lung inflammation and a 3-fold increase in monocytes and neutrophils in BALF compared to U-MWCNTs. Z-MWCNTs, but not U-MWCNTs, induced IL-6 and CXCL10 mRNA and protein in the lungs of mice and increased IL-6 mRNA in heart and liver. U-MWCNTs but not Z-MWCNTs stimulated airway epithelial DNA synthesis in vivo. Lung fibrosis at 28 days was not significantly different between mice treated with U-MWCNT or Z-MWCNT. Pulmonary exposure to ZnO-coated MWCNTs produces a systemic acute phase response that involves the release of Zn(+2), lung epithelial growth arrest, and increased IL-6. ALD functionalization with ZnO generates MWCNTs that possess increased risk for human exposure.

Acidic Mammalian Chitinase Negatively Affects Immune Responses during Acute and Chronic Aspergillus fumigatus Exposure.

PubMed

Garth, Jaleesa M; Mackel, Joseph J; Reeder, Kristen M; Blackburn, Jonathan P; Dunaway, Chad W; Yu, Zhihong; Matalon, Sadis; Fitz, Lori; Steele, Chad

2018-07-01

Chitin is a polysaccharide that provides structure and rigidity to the cell walls of fungi and insects. Mammals possess multiple chitinases, which function to degrade chitin, thereby supporting a role for chitinases in immune defense. However, chitin degradation has been implicated in the pathogenesis of asthma. Here, we determined the impact of acidic mammalian chitinase (AMCase) ( Chia ) deficiency on host defense during acute exposure to the fungal pathogen Aspergillus fumigatus as well as its contribution to A. fumigatus -associated allergic asthma. We demonstrate that chitin in the fungal cell wall was detected at low levels in A. fumigatus conidia, which emerged at the highest level during hyphal transition. In response to acute A. fumigatus challenge, Chia -/- mice unexpectedly demonstrated lower A. fumigatus lung burdens at 2 days postchallenge. The lower fungal burden correlated with decreased lung interleukin-33 (IL-33) levels yet increased IL-1β and prostaglandin E 2 (PGE 2 ) production, a phenotype that we reported previously to promote the induction of IL-17A and IL-22. During chronic A. fumigatus exposure, AMCase deficiency resulted in lower dynamic and airway lung resistance than in wild-type mice. Improved lung physiology correlated with attenuated levels of the proallergic chemokines CCL17 and CCL22. Surprisingly, examination of inflammatory responses during chronic exposure revealed attenuated IL-17A and IL-22 responses, but not type 2 responses, in the absence of AMCase. Collectively, these data suggest that AMCase functions as a negative regulator of immune responses during acute fungal exposure and is a contributor to fungal asthma severity, putatively via the induction of proinflammatory responses. Copyright © 2018 American Society for Microbiology.

Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

PubMed

Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

2018-04-18

Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

Differential responses of targeted lung redox enzymes to rat exposure to 60 or 85% oxygen

PubMed Central

Gan, Zhuohui; Roerig, David L.; Clough, Anne V.

2011-01-01

Rat exposure to 60% O2 (hyper-60) or 85% O2 (hyper-85) for 7 days confers susceptibility or tolerance, respectively, of the otherwise lethal effects of exposure to 100% O2. The objective of this study was to determine whether activities of the antioxidant cytosolic enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III are differentially altered in hyper-60 and hyper-85 lungs. Duroquinone (DQ), an NQO1 substrate, or its hydroquinone (DQH2), a complex III substrate, was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of DQH2 and DQ were measured. Based on inhibitor effects and kinetic modeling, capacities of NQO1-mediated DQ reduction (Vmax1) and complex III-mediated DQH2 oxidation (Vmax2) increased by ∼140 and ∼180% in hyper-85 lungs, respectively, compared with rates in lungs of rats exposed to room air (normoxic). In hyper-60 lungs, Vmax1 increased by ∼80%, with no effect on Vmax2. Additional studies revealed that mitochondrial complex I activity in hyper-60 and hyper-85 lung tissue homogenates was ∼50% lower than in normoxic lung homogenates, whereas mitochondrial complex IV activity was ∼90% higher in only hyper-85 lung tissue homogenates. Thus NQO1 activity increased in both hyper-60 and hyper-85 lungs, whereas complex III activity increased in hyper-85 lungs only. This increase, along with the increase in complex IV activity, may counter the effects the depression in complex I activity might have on tissue mitochondrial function and/or reactive oxygen species production and may be important to the tolerance of 100% O2 observed in hyper-85 rats. PMID:21551015

Differential responses of targeted lung redox enzymes to rat exposure to 60 or 85% oxygen.

PubMed

Gan, Zhuohui; Roerig, David L; Clough, Anne V; Audi, Said H

2011-07-01

Rat exposure to 60% O(2) (hyper-60) or 85% O(2) (hyper-85) for 7 days confers susceptibility or tolerance, respectively, of the otherwise lethal effects of exposure to 100% O(2). The objective of this study was to determine whether activities of the antioxidant cytosolic enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III are differentially altered in hyper-60 and hyper-85 lungs. Duroquinone (DQ), an NQO1 substrate, or its hydroquinone (DQH(2)), a complex III substrate, was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of DQH(2) and DQ were measured. Based on inhibitor effects and kinetic modeling, capacities of NQO1-mediated DQ reduction (V(max1)) and complex III-mediated DQH(2) oxidation (V(max2)) increased by ∼140 and ∼180% in hyper-85 lungs, respectively, compared with rates in lungs of rats exposed to room air (normoxic). In hyper-60 lungs, V(max1) increased by ∼80%, with no effect on V(max2). Additional studies revealed that mitochondrial complex I activity in hyper-60 and hyper-85 lung tissue homogenates was ∼50% lower than in normoxic lung homogenates, whereas mitochondrial complex IV activity was ∼90% higher in only hyper-85 lung tissue homogenates. Thus NQO1 activity increased in both hyper-60 and hyper-85 lungs, whereas complex III activity increased in hyper-85 lungs only. This increase, along with the increase in complex IV activity, may counter the effects the depression in complex I activity might have on tissue mitochondrial function and/or reactive oxygen species production and may be important to the tolerance of 100% O(2) observed in hyper-85 rats.

Acute high-level exposure to WTC particles alters expression of genes associated with oxidative stress and immune function in the lung.

PubMed

Cohen, Mitchell D; Vaughan, Joshua M; Garrett, Brittany; Prophete, Colette; Horton, Lori; Sisco, Maureen; Kodavanti, Urmila P; Ward, William O; Peltier, Richard E; Zelikoff, Judith; Chen, Lung-chi

2015-01-01

First responders (FR) present at Ground Zero in the first 72 h after the World Trade Center (WTC) collapsed have progressively exhibited significant respiratory injuries. The few toxicology studies performed to date evaluated effects from just fine (< 2.5 µm) WTC dusts; none examined health effects/toxicities from atmospheres bearing larger particle sizes, despite the fact the majority (> 96%) of dusts were > 10 µm and most FR likely entrained dusts by mouth breathing. Using a system that generated/delivered supercoarse (10-53 µm) WTC dusts to F344 rats (in a manner that mimicked FR exposures), this study sought to examine potential toxicities in the lungs. In this exploratory study, rats were exposed for 2 h to 100 mg WTC dust/m(3) (while under isoflurane [ISO] anesthesia) or an air/ISO mixture; this dose conservatively modeled likely exposures by mouth-breathing FR facing ≈750-1000 mg WTC dust/m(3). Lungs were harvested 2 h post-exposure and total RNA extracted for subsequent global gene expression analysis. Among the >  1000 genes affected by WTC dust (under ISO) or ISO alone, 166 were unique to the dust exposure. In many instances, genes maximally-induced by the WTC dust exposure (relative to in naïve rats) were unchanged/inhibited by ISO only; similarly, several genes maximally inhibited in WTC dust rats were largely induced/unchanged in rats that received ISO only. These outcomes reflect likely contrasting effects of ISO and the WTC dust on lung gene expression. Overall, the data show that lungs of rats exposed to WTC dust (under ISO) - after accounting for any impact from ISO alone - displayed increased expression of genes related to lung inflammation, oxidative stress, and cell cycle control, while several involved in anti-oxidant function were inhibited. These changes suggested acute inflammogenic effects and oxidative stress in the lungs of WTC dust-exposed rats. This study, thus, concludes that a single very high exposure to WTC dusts could potentially have adversely affected the respiratory system - in terms of early inflammatory and oxidative stress processes. As these changes were not compared with other types of dusts, the uniqueness of these WTC-mediated effects remains to be confirmed. It also still remains to be determined if these effects might have any relevance to chronic lung pathologies that became evident among FR who encountered the highest dust levels on September 11, 2001 and the 2 days thereafter. Ongoing studies using longer-range post-exposure analyses (up to 1-year or more) will help to determine if effects seen here on genes were acute, reversible, or persistent, and associated with corresponding histopathologic/biochemical changes in situ.

Association between Traffic Air Pollution and Reduced Forced Vital Capacity: A Study Using Personal Monitors for Outdoor Workers.

PubMed

Santos, Ubiratan Paula; Garcia, Maria Lúcia Siqueira Bueno; Braga, Alfésio Luís Ferreira; Pereira, Luiz Alberto Amador; Lin, Chin An; de André, Paulo Afonso; de André, Carmen Diva Saldiva; Singer, Julio da Motta; Saldiva, Paulo Hilário Nascimento

2016-01-01

The effects of outdoor air pollution on lung function in adults are still controversial. Evaluate the effects of exposure to different levels of traffic-generated PM2.5 on workers' lung functions in São Paulo, Brazil. To cover a wide range of exposures, 101 non-smoking workers from three occupations (taxi drivers, traffic controllers, and forest rangers) were selected for the study. After clinical evaluation, the participants were scheduled to attend four consecutive weekly visits in which they received a 24-hour personal PM2.5 sampler and had lung function tests measured on the following day. The association between the spirometric variables and the averaged PM2.5 levels was assessed using robust regression models adjusted for age, waist circumference, time at the job, daily work hours, diabetes or hypertension and former smoking habits. Relative to workers in the lowest exposed group (all measures < 25 μg/m3), those with the highest level of exposure (all measures > 39.6 μg/m3) showed a reduction of predicted FVC (-12.2%; CI 95%: [-20.0% to -4.4%]), a marginal reduction of predicted FEV1 (-9.1%; CI 95%: [-19.1% to 0.9%]) and an increase of predicted FEF25-75%/FVC (14.9%; CI 95%: [2.9% to 26.8%]) without changes of FEV1/FVC. Exposure to vehicular traffic air pollution is associated with a small but significant reduction of FVC without a reduction of FEV1/FVC.

Considering the effects of ambient particulate matter on the lung function of motorcycle taxi drivers in Bangkok, Thailand.

PubMed

Arphorn, Sara; Ishimaru, Tomohiro; Hara, Kunio; Mahasandana, Suwisa

2018-02-01

The motorcycle taxi drivers of Bangkok have been heavily exposed to high concentrations of PM 10 (particulate matter with an aerodynamic diameter ≤10 μm), and the impact of this on their lungs has been neither documented nor studied. This study examines the association between exposure to PM 10 and lung function decline among motorcycle taxi drivers. A cross-sectional study was conducted in Bangkok between two groups: a subject group of motorcycle taxi drivers and control group of enclosed vehicle taxi drivers. The findings of the Thailand Pollution Control Department were used to estimate the annual ambient PM 10 concentration levels in the metropolis. Pulmonary functions of motorcycle taxi drivers and enclosed vehicle taxi drivers were measured and compared using the Mann-Whitney test. Multiple linear regression analysis was applied to estimate the effects of PM 10 exposure on the lung function of motorcycle taxi drivers. A total of 1283 motorcycle taxi drivers and 600 taxi drivers were investigated. The mean forced expiratory volume in 1 sec/forced vital capacity (FEV 1 /FVC) of the motorcycle taxi drivers was significantly lower than that of the taxi drivers (P < 0.001). The mean FEV 1 /FVC of motorcycle taxi drivers exposed to ≥50 µg/m 3 PM 10 was statistically lower (-2.82%; 95% confidence interval [CI]: -4.54% to -1.09%) and the mean % vital capacity (%VC) of those exposed to 40-49.9 µg/m 3 PM 10 was statistically lower than that of motorcycle taxi drivers exposed to <30 µg/m 3 PM 10 (-3.33%; 95% CI: -5.79% to -0.87%). Motorcycle taxi drivers were directly exposed to air pollution in their working environment. As a result, their lung function might decrease more than that of enclosed vehicle taxi drivers. With the possible exposure to ≥50 µg/m 3 PM 10 , the vehicular emission standards should be vigorously enforced. Further investigation is warranted to clarify the effect of lung dysfunction on the work and lifestyle of motorcycle taxi drivers. Motorcycle taxi drivers are directly exposed to air pollution in their work environment; therefore, their lung function might decrease more than that of enclosed vehicle taxi drivers, especially when exposed to ≥50 µg/m 3 PM 10 . World Health Organization (WHO) vehicular emission standards should be recognized and eventually enforced.

Cannabis, tobacco smoking, and lung function: a cross-sectional observational study in a general practice population

PubMed Central

Macleod, John; Robertson, Roy; Copeland, Lorraine; McKenzie, James; Elton, Rob; Reid, Peter

2015-01-01

Background Health concerns around cannabis use have focused on the potential relationship with psychosis but the effect of cannabis smoking on respiratory health has received less attention. Aim To investigate the association between tobacco-only smoking compared with tobacco plus cannabis smoking and adverse outcomes in respiratory health and lung function. Design and setting The design was cross-sectional with two groups recruited: cigarette smokers with tobacco pack-years; cannabis smokers with cannabis joint-years. Recruitment occurred in a general practice in Scotland with 12 500 patients. Method Exposures measured were tobacco smoking (pack-years) and cannabis smoking (joint-years). Cannabis type (resin, herbal, or both) was recorded by self-report. Respiratory symptoms were recorded using NHANES and MRC questionnaires. Lung function was measured by spirometry (FEV1/FVC ratio). Results Participants consisted of 500 individuals (242 males). Mean age of tobacco-only smokers was 45 years; median tobacco exposure was 25 pack-years. Mean age of cannabis and tobacco smokers was 37 years; median tobacco exposure was 19 pack-years, rising to 22.5 when tobacco smoked with cannabis. Although tobacco and cannabis use were associated with increased reporting of respiratory symptoms, this was higher among those who also smoked cannabis. Both tobacco and cannabis users had evidence of impaired lung function but, in fully adjusted analyses, each additional joint-year of cannabis use was associated with a 0.3% (95% confidence interval = 0.0 to 0.5) increase in prevalence of chronic obstructive pulmonary disease. Conclusion In adults who predominantly smoked resin cannabis mixed with tobacco, additional adverse effects were observed on respiratory health relating to cannabis use. PMID:25624312

Cannabis, tobacco smoking, and lung function: a cross-sectional observational study in a general practice population.

PubMed

Macleod, John; Robertson, Roy; Copeland, Lorraine; McKenzie, James; Elton, Rob; Reid, Peter

2015-02-01

Health concerns around cannabis use have focused on the potential relationship with psychosis but the effect of cannabis smoking on respiratory health has received less attention. To investigate the association between tobacco-only smoking compared with tobacco plus cannabis smoking and adverse outcomes in respiratory health and lung function. The design was cross-sectional with two groups recruited: cigarette smokers with tobacco pack-years; cannabis smokers with cannabis joint-years. Recruitment occurred in a general practice in Scotland with 12 500 patients. Exposures measured were tobacco smoking (pack-years) and cannabis smoking (joint-years). Cannabis type (resin, herbal, or both) was recorded by self-report. Respiratory symptoms were recorded using NHANES and MRC questionnaires. Lung function was measured by spirometry (FEV1/FVC ratio). Participants consisted of 500 individuals (242 males). Mean age of tobacco-only smokers was 45 years; median tobacco exposure was 25 pack-years. Mean age of cannabis and tobacco smokers was 37 years; median tobacco exposure was 19 pack-years, rising to 22.5 when tobacco smoked with cannabis. Although tobacco and cannabis use were associated with increased reporting of respiratory symptoms, this was higher among those who also smoked cannabis. Both tobacco and cannabis users had evidence of impaired lung function but, in fully adjusted analyses, each additional joint-year of cannabis use was associated with a 0.3% (95% confidence interval = 0.0 to 0.5) increase in prevalence of chronic obstructive pulmonary disease. In adults who predominantly smoked resin cannabis mixed with tobacco, additional adverse effects were observed on respiratory health relating to cannabis use. © British Journal of General Practice 2015.

[Impact of the legislation for smoke-free workplaces on respiratory health in hospitality workers--review of epidemiological studies].

PubMed

Polańska, Kinga; Hanke, Wojciech; Konieczko, Katarzyna

2011-01-01

Environmental tobacco smoke exposure (ETS) is a significant risk factor for the development of many diseases, including lung cancer, lower respiratory tract infections, asthma and eye, throat and nasal irritations. Hospitality workers form an occupational group with high exposure to ETS in their workplace. Taking into account the health consequences of ETS exposure and high prevalence of exposure in public places, including workplaces, many countries have implemented the smoking ban that prohibits or restricts smoking in workplaces, including restaurants and bars. The epidemiological studies have indicated a significant reduction in the exposure level after implementation of the smoking ban. Most studies have also indicated a significant reduction in respiratory and sensory symptoms. The impact of the smoking ban on the lung function measurements is still not clear.

Epidemiological study of respiratory disease in workers exposed to polyvinylchloride dust.

PubMed Central

Soutar, C A; Copland, L H; Thornley, P E; Hurley, J F; Ottery, J; Adams, W G; Bennett, B

1980-01-01

The respiratory health of workers exposed to polyvinylchloride (PVC) dust has been investigated in 818 men sampled from the work force of a factory manufacturing PVC. In a cross-sectional survey, the lung function and prevalences of respiratory symptoms and chest radiographic abnormalities were compared with estimates of individual PVC dust exposures based on detailed occupational histories and current measurements of respirable PVC dust. Complaints of slight exertional dyspnoea were associated with PVC dust exposure, though age and smoking effects were much stronger. The forced expired volume in one second (FEV1) and forced vital capacity (FVC) were inversely related to dust exposure after age, height, and smoking effects had been taken into account. This effect was seen principally in cigarette smokers, and there was suggestive evidence that PVC dust exposure and cigarette smoking interacted in the reduction of FEV1 and FVC. Gas transfer factor was not related to dust exposure. The chest radiographs were read according to the ILO U/C classification by three experienced readers. One reader recorded a low prevalence of small rounded opacities, and these were not related to age or dust exposure. Another reader recorded a higher prevalence of small rounded opacities category 0/1 or more, and these were related to age but not to dust exposure. The third reader recorded the highest prevalence of small rounded opacities (though none greater than category 1/1), and these were independently related both to age and to PVC dust exposure, indicating an effect of PVC dust on the appearance of the chest radiography. These appearances were so slight that only the higher sensitivity of this reader in the interpretation of profusion of small rounded opacities on the ILO U/C scale enabled detection of this effect of PVC dust. In conclusion, exposure to PVC dust is associated with some deterioration of lung function, slight abnormalities of the chest radiograph, and complaints of slight dyspnoea. The mean decline in FEV1 associated with the average dust exposure experienced in the study was small, though some of the men with higher dust exposures may have suffered clinically important loss of lung function as a result of their occupation. PMID:7444838

Association of ambient air quality with children's lung function in urban and rural Iran.

PubMed

Asgari, M M; DuBois, A; Asgari, M; Gent, J; Beckett, W S

1998-01-01

During the summer of 1994, a cross-sectional epidemiological study, in which the pulmonary function of children in Tehran was compared with pulmonary function in children in a rural town in Iran, was conducted. Four hundred children aged 5-11 y were studied. Daytime ambient nitrogen dioxide, sulfur dioxide, and particulate matter were measured with portable devices, which were placed in the children's neighborhoods on the days of study. Levels of these ambient substances were markedly higher in urban Tehran than in rural areas. Children's parents were questioned about home environmental exposures (including heating source and environmental tobacco smoke) and the children's respiratory symptoms. Pulmonary function was assessed, both by spirometry and peak expiratory flow meter. Forced expiratory volume in 1 s and forced vital capacity-as a percentage of predicted for age, sex and height-were significantly lower in urban children than in rural children. Both measurements evidenced significant reverse correlations with levels of sulfur dioxide, nitrogen dioxide, and particulate matter. Differences in spirometric lung function were not explained by nutritional status, as assessed by height and weight for age, or by home environmental exposures. Reported airway symptoms (i.e., cough, phlegm, and wheeze) were higher among rural children, whereas reported physician diagnosis of bronchitis and asthma were higher among urban children. The association between higher pollutant concentrations and reduced pulmonary function in this urban-rural comparison suggests that there is an effect of urban air pollution on short-term lung function and/or lung growth and development during the preadolescent years.

Association of ambient air quality with children`s lung function in urban and rural Iran

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asgari, M.M.; Dubois, A.; Beckett, W.S.

During the summer of 1994, a cross-sectional epidemiological study, in which the pulmonary function of children in Tehran was compared with pulmonary function in children in a rural town in Iran, was conducted. Four hundred children aged 5--11 y were studied. Daytime ambient nitrogen dioxide, sulfur dioxide, and particulate matter were measured with portable devices, which were placed in the children`s neighborhoods on the days of study. Levels of these ambient substances were markedly higher in urban Tehran than in rural areas. Children`s parents were questioned about home environmental exposures (including heating source and environmental tobacco smoke) and the children`smore » respiratory symptoms. Pulmonary function was assessed, both by spirometry and peak expiratory flow meter. Forced expiratory volume in 1 s and forced vital capacity--as a percentage of predicted for age, sex and height--were significantly lower in urban children than in rural children. Both measurements evidenced significant reverse correlations with levels of sulfur dioxide, nitrogen dioxide, and particulate matter. Differences in spirometric lung function were not explained by nutritional status, as assessed by height and weight for age, or by home environmental exposures. Reported airway symptoms were higher among rural children, whereas reported physician diagnosis of bronchitis and asthma were higher among urban children. The association between higher pollutant concentrations and reduced pulmonary function in this urban-rural comparison suggests that there is an effect of urban air pollution on short-term lung function and/or lung growth and development during the preadolescent years.« less

Chronic Cigarette Smoke Mediated Global Changes in Lung Mucoepidermoid Cells: A Phosphoproteomic Analysis.

PubMed

Solanki, Hitendra S; Advani, Jayshree; Khan, Aafaque Ahmad; Radhakrishnan, Aneesha; Sahasrabuddhe, Nandini A; Pinto, Sneha M; Chang, Xiaofei; Prasad, Thottethodi Subrahmanya Keshava; Mathur, Premendu Prakash; Sidransky, David; Gowda, Harsha; Chatterjee, Aditi

2017-08-01

Proteomics analysis of chronic cigarette smoke exposure is a rapidly emerging postgenomics research field. While smoking is a major cause of lung cancer, functional studies using proteomics approaches could enrich our mechanistic understanding of the elusive lung cancer global molecular signaling and cigarette smoke relationship. We report in this study on a stable isotope labeling by amino acids in cell culture-based quantitative phosphoproteomic analysis of a human lung mucoepidermoid carcinoma cell line, H292 cells, chronically exposed to cigarette smoke. Using high resolution Orbitrap Velos mass spectrometer, we identified the hyperphosphorylation of 493 sites, which corresponds to 341 proteins and 195 hypophosphorylated sites, mapping to 142 proteins upon smoke exposure (2.0-fold change). We report differential phosphorylation of multiple kinases, including PAK6, EPHA4, LYN, mitogen-activated protein kinase, and phosphatases, including TMEM55B, PTPN14, TIGAR, among others, in response to chronic cigarette smoke exposure. Bioinformatics analysis revealed that the molecules differentially phosphorylated upon chronic exposure of cigarette smoke are associated with PI3K/AKT/mTOR and CDC42-PAK signaling pathways. These signaling networks are involved in multiple cellular processes, including cell polarity, cytoskeletal remodeling, cellular migration, protein synthesis, autophagy, and apoptosis. The present study contributes to emerging proteomics insights on cigarette smoke mediated global signaling in lung cells, which in turn may aid in development of precision medicine therapeutics and postgenomics biomarkers.

ROLE OF TACHYKININS IN OZONE-INDUCED ACUTE LUNG INJURY

EPA Science Inventory

To examine the hypothesis that the acute, reversible changes caused by O3 exposure are mediated by techykinin release, guinea pigs were depleted of tachykinins using repeated capsaicin (CAP) injections prior to O3 exposure, in an attempt to prevent O3-induced functional changes. ...

SMALL AIRWAYS FUNCTION RESPONSE IN SMOKERS AND PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASE FOLLOWING EXPOSURE TO CONCENTRATED AMBIENT AIR PARTICLES

EPA Science Inventory

Numerous field and epidemiological studies have shown significant associations between particulate matter (PM) exposure and various morbidity outcomes including hospital admissions for bronchitis and asthma. These population based studies indicate that persons with chronic obstru...

Multi-walled carbon nanotube-induced gene signatures in the mouse lung: potential predictive value for human lung cancer risk and prognosis

PubMed Central

Guo, Nancy L; Wan, Ying-Wooi; Denvir, James; Porter, Dale W; Pacurari, Maricica; Wolfarth, Michael G; Castranova, Vincent; Qian, Yong

2012-01-01

Concerns over the potential for multi-walled carbon nanotubes (MWCNT) to induce lung carcinogenesis have emerged. This study sought to (1) identify gene expression signatures in the mouse lungs following pharyngeal aspiration of well-dispersed MWCNT and (2) determine if these genes were associated with human lung cancer risk and progression. Genome-wide mRNA expression profiles were analyzed in mouse lungs (n=160) exposed to 0, 10, 20, 40, or 80 µg of MWCNT by pharyngeal aspiration at 1, 7, 28, and 56 days post-exposure. By using pairwise-Statistical Analysis of Microarray (SAM) and linear modeling, 24 genes were selected, which have significant changes in at least two time points, have a more than 1.5 fold change at all doses, and are significant in the linear model for the dose or the interaction of time and dose. Additionally, a 38-gene set was identified as related to cancer from 330 genes differentially expressed at day 56 post-exposure in functional pathway analysis. Using the expression profiles of the cancer-related gene set in 8 mice at day 56 post-exposure to 10 µg of MWCNT, a nearest centroid classification accurately predicts human lung cancer survival with a significant hazard ratio in training set (n=256) and test set (n=186). Furthermore, both gene signatures were associated with human lung cancer risk (n=164) with significant odds ratios. These results may lead to development of a surveillance approach for early detection of lung cancer and prognosis associated with MWCNT in the workplace. PMID:22891886

Diesel exhaust and lung cancer in the trucking industry: exposure-response analyses and risk assessment.

PubMed

Steenland, K; Deddens, J; Stayner, L

1998-09-01

Diesel exhaust is considered a probable human carcinogen by the International Agency for Research on Cancer (IARC). The epidemiologic evidence rests on studies of lung cancer among truck drivers, bus drivers, shipyard workers, and railroad workers. The general public is exposed to diesel exhaust in ambient air. Two regulatory agencies are now considering regulating levels of diesel exhaust: the California EPA (ambient levels) and the Mine Safety Health Administration (MSHA) (occupational levels). To date, there have been few quantitative exposure-response analyses of diesel and lung cancer based on human data. We conducted exposure-response analyses among workers in the trucking industry, adjusted for smoking. Diesel exhaust exposure was estimated based on a 1990 industrial hygiene survey. Past exposures were estimated assuming that they were a function of 1) the number of heavy duty trucks on the road, 2) the particulate emissions (grams/mile) of diesel engines over time, and 3) leaks from trucks' exhaust systems for long-haul drivers. Regardless of assumptions about past exposure, all analyses resulted in significant positive trends in lung cancer risk with increasing cumulative exposure. A male truck driver exposed to 5 micrograms/m3 of elemental carbon (a typical exposure in 1990, approximately five times urban background levels) would have a lifetime excess risk of lung cancer of 1-2% above a background risk of 5%. We found a lifetime excess risk ten times higher than the 1 per 1,000 excess risk allowed by OSHA in setting regulations. There are about 2.8 million truck drivers in the U.S. Our results depend on estimates about unknown past exposures, and should be viewed as exploratory. They conform reasonably well to recent estimates for diesel-exposed railroad workers done by the California EPA, although those results themselves have been disputed.

Receptor for advanced glycation endproducts (RAGE) maintains pulmonary structure and regulates the response to cigarette smoke.

PubMed

Wolf, Lisa; Herr, Christian; Niederstraßer, Julia; Beisswenger, Christoph; Bals, Robert

2017-01-01

The receptor for advanced glycation endproducts (RAGE) is highly expressed in the lung but its physiological functions in this organ is still not completely understood. To determine the contribution of RAGE to physiological functions of the lung, we analyzed pulmonary mechanics and structure of wildtype and RAGE deficient (RAGE-/-) mice. RAGE deficiency spontaneously resulted in a loss of lung structure shown by an increased mean chord length, increased respiratory system compliance, decreased respiratory system elastance and increased concentrations of serum protein albumin in bronchoalveolar lavage fluids. Pulmonary expression of RAGE was mainly localized on alveolar epithelial cells and alveolar macrophages. Primary murine alveolar epithelial cells isolated from RAGE-/- mice revealed an altered differentiation and defective barrier formation under in vitro conditions. Stimulation of interferone-y (IFNy)-activated alveolar macrophages deficient for RAGE with Toll-like receptor (TLR) ligands resulted in significantly decreased release of proinflammatory cytokines and chemokines. Exposure to chronic cigarette smoke did not affect emphysema-like changes in lung parenchyma in RAGE-/- mice. Acute cigarette smoke exposure revealed a modified inflammatory response in RAGE-/- mice that was characterized by an influx of macrophages and a decreased keratinocyte-derived chemokine (KC) release. Our data suggest that RAGE regulates the differentiation of alveolar epithelial cells and impacts on the development and maintenance of pulmonary structure. In cigarette smoke-induced lung pathology, RAGE mediates inflammation that contributes to lung damage.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia.

PubMed

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-10-24

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia

PubMed Central

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-01-01

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic. PMID:27783043

Development of a Zealand white rabbit deposition model to study inhalation anthrax

DOE Office of Scientific and Technical Information (OSTI.GOV)

Asgharian, Bahman; Price, Owen; Kabilan, Senthil

Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits asmore » a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.« less

Esophageal motor disease and reflux patterns in patients with advanced pulmonary disease undergoing lung transplant evaluation.

PubMed

Seccombe, J; Mirza, F; Hachem, R; Gyawali, C P

2013-08-01

Advanced pulmonary disorders are linked to esophageal hypomotility and reflux disease. However, characterization of esophageal function using high resolution manometry (HRM) and ambulatory pH monitoring, segregation by pulmonary pathology, and comparison to traditional reflux disease are all limited in the literature. Over a 4 year period, 73 patients (55.2 ± 1.3 years, 44F) were identified who underwent esophageal function testing as part of lung transplant evaluation for advanced pulmonary disease (interstitial lung disease, ILD = 47, obstructive lung disease, OLD = 24, other = 2). Proportions of patients with motor dysfunction (≥ 80% failed sequences = severe hypomotility) and/or abnormal reflux parameters (acid exposure time, AET ≥ 4%) were determined, and compared to a cohort of 1081 patients (48.4 ± 0.4 years, 613F) referred for esophageal function testing prior to antireflux surgery (ARS). The proportion of esophageal body hypomotility was significantly higher within advanced pulmonary disease categories (35.6%), particularly ILD (44.7%), compared to ARS patients (12.1%, P < 0.0001). Abnormal AET was noted in 56.5%, and was similar between ILD and OLD, but less frequent than in the ARS group (P = 0.04). Post-transplant chronic rejection trended towards association with pretransplant elevated AET in OLD (P = 0.08) but not ILD. Mortality was not predicted by esophageal motor pattern or reflux evidence. Interstitial lung disease has a highly significant association with esophageal body hypomotility. Consequently, prevalence of abnormal esophageal acid exposure is high, but implications for post lung transplant chronic rejection remain unclear. © 2013 John Wiley & Sons Ltd.

OBSTRUCTIVE LUNG DISEASE AND EXPOSURE TO BURNING BIOMASS FUEL IN THE INDOOR ENVIRONMENT

PubMed Central

Diette, Gregory B.; Accinelli, Roberto A.; Balmes, John R.; Buist, A. Sonia; Checkley, William; Garbe, Paul; Hansel, Nadia N.; Kapil, Vikas; Gordon, Stephen; Lagat, David K.; Yip, Fuyuen; Mortimer, Kevin; Perez-Padilla, Rogelio; Roth, Christa; Schwaninger, Julie M.; Punturieri, Antonello; Kiley, James

2012-01-01

It is estimated that up to half of the world’s population burns biomass fuel (wood, crop residues, animal dung and coal) for indoor uses such as cooking, lighting and heating. As a result, a large proportion of women and children are exposed to high levels of household air pollution (HAP). The short and long term effects of these exposures on the respiratory health of this population are not clearly understood. On May 9–11, 2011 NIH held an international workshop on the "Health Burden of Indoor Air Pollution on Women and Children," in Arlington, VA. To gather information on the knowledge base on this topic and identify research gaps, ahead of the meeting we conducted a literature search using PubMed to identify publications that related to HAP, asthma, and chronic obstructive pulmonary disease (COPD). Abstracts were all analyzed and we report on those considered by the respiratory sub study group at the meeting to be most relevant to the field. Many of the studies published are symptom-based studies (as opposed to objective measures of lung function or clinical examination etc.) and measurement of HAP was not done. Many found some association between indoor exposures to biomass smoke as assessed by stove type (e.g., open fire vs. liquid propane gas) and respiratory symptoms such as wheeze and cough. Among the studies that examined objective measures (e.g. spirometry) as a health outcome, the data supporting an association between biomass smoke exposure and COPD in adult women are fairly robust, but the findings for asthma are mixed. If an association was observed between the exposures and lung function, most data seemed to demonstrate mild to moderate reductions in lung function, the pathophysiological mechanisms of which need to be investigated. In the end, the group identified a series of scientific gaps and opportunities for research that need to be addressed to better understand the respiratory effects of exposure to indoor burning of the different forms of biomass fuels. PMID:23139916

Lung Oxidative Damage by Hypoxia

PubMed Central

Araneda, O. F.; Tuesta, M.

2012-01-01

One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described. PMID:22966417

Study of the prevalence of chronic, non-specific lung disease and related health problems in the grain-handling industry. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rankin, J.; Bates, J.; Claremont, A.

1986-10-01

A total of 310 grain handlers was studied, with attention to prevalence and characteristics of clinical, psychological, immunological, radiological, serological blood and urine parameters to determine any apparent effects from grain-dust exposure. Grain handlers had a higher prevalence of respiratory symptoms and signs than did the city workers who comprised the comparison group. Evidence of accumulative respiratory effect due to recurring exposures to grain dust was found. Acute and chronic airway reactions were induced by exposure to grain dust. Wheezing and dyspnea on exposure were related to length of employment. Grain fever syndrome was prevalent. Cases of acute recurrent conjunctivitismore » and rhinitis were found along with skin pruritus, mainly on exposure to barley dust. Pesticide exposure caused temporary disabling symptoms. Lung function was adversely affected by grain-dust exposure. Exposure to grain mites and insects in contaminated cereal grain caused a reaction among grain workers.« less

Prevalence and determinants of airflow limitation in urban and rural children exposed to cooking fuels in South-East Nigeria.

PubMed

Oguonu, Tagbo; Obumneme-Anyim, Ijeoma N; Eze, Joy N; Ayuk, Adaeze C; Okoli, Chinyere V; Ndu, Ikenna K

2018-05-01

Background Biofuels and other cooking fuels are used in households in low- and middle-income countries. Aim To investigate the impact of cooking fuels on lung function in children in urban and rural households in South-East Nigeria. Methods The multi-stage sampling method was used to enroll children exposed to cooking fuel in the communities. Lung function values FEV1, FVC and the FEV1/FVC ratio, were measured with ndd EasyOne R spirometer. Airflow limitation was determined with FEV1/FVC Z-score values at -1.64 as the lower limit of normal (LLN5). The Global Lung Function Initiative 2012 software was used to calculate the lung function indices. Results The median age (range) of the 912 children enrolled was 10.6 years (6-18). Altogether, 468 (51.6%) children lived in rural areas. Seven hundred and thirty-seven (80.7%) were directly exposed to cooking fuels (418/737, 56.5% in rural areas). Wood and kerosene were the dominant fuels in rural and urban households. The respective mean Z-scores of the exposed children in rural and urban were zFEV1 -0.62, FVC -0.21, FEV1/FVC -0.83 and zFEV1 -0.57, zFVC -0.14, FEV1/FVC -0.75. Few (5.2%, 38/737) of the children had airflow limitation. Most of them (60.5%, 25/38) lived in the rural community; the lowest FEV1/FVC Z-scores were those of exposed to a combination of fuels. Conclusion Exposure to cooking fuels affects lung function in children with airway limitation in a small proportion, Control measures are advocated to reduce the morbidity related to cooking fuels exposure.

Cleaning at Home and at Work in Relation to Lung Function Decline and Airway Obstruction.

PubMed

Svanes, Øistein; Bertelsen, Randi J; Lygre, Stein H L; Carsin, Anne E; Antó, Josep M; Forsberg, Bertil; García-García, José M; Gullón, José A; Heinrich, Joachim; Holm, Mathias; Kogevinas, Manolis; Urrutia, Isabel; Leynaert, Bénédicte; Moratalla, Jesús M; Le Moual, Nicole; Lytras, Theodore; Norbäck, Dan; Nowak, Dennis; Olivieri, Mario; Pin, Isabelle; Probst-Hensch, Nicole; Schlünssen, Vivi; Sigsgaard, Torben; Skorge, Trude D; Villani, Simona; Jarvis, Debbie; Zock, Jan P; Svanes, Cecilie

2018-05-01

Cleaning tasks may imply exposure to chemical agents with potential harmful effects to the respiratory system, and increased risk of asthma and respiratory symptoms among professional cleaners and in persons cleaning at home has been reported. Long-term consequences of cleaning agents on respiratory health are, however, not well described. This study aimed to investigate long-term effects of occupational cleaning and cleaning at home on lung function decline and airway obstruction. The European Community Respiratory Health Survey (ECRHS) investigated a multicenter population-based cohort at three time points over 20 years. A total of 6,235 participants with at least one lung function measurement from 22 study centers, who in ECRHS II responded to questionnaire modules concerning cleaning activities between ECRHS I and ECRHS II, were included. The data were analyzed with mixed linear models adjusting for potential confounders. As compared with women not engaged in cleaning (ΔFEV 1  = -18.5 ml/yr), FEV 1 declined more rapidly in women responsible for cleaning at home (-22.1; P = 0.01) and occupational cleaners (-22.4; P = 0.03). The same was found for decline in FVC (ΔFVC = -8.8 ml/yr; -13.1, P = 0.02; and -15.9, P = 0.002; respectively). Both cleaning sprays and other cleaning agents were associated with accelerated FEV 1 decline (-22.0, P = 0.04; and -22.9, P = 0.004; respectively). Cleaning was not significantly associated with lung function decline in men or with FEV 1 /FVC decline or airway obstruction. Women cleaning at home or working as occupational cleaners had accelerated decline in lung function, suggesting that exposures related to cleaning activities may constitute a risk to long-term respiratory health.

Detrimental effects of secondhand smoke exposure on infants with cystic fibrosis.

PubMed

Kopp, Benjamin T; Sarzynski, Lisa; Khalfoun, Sabrina; Hayes, Don; Thompson, Rohan; Nicholson, Lisa; Long, Frederick; Castile, Robert; Groner, Judith

2015-01-01

Secondhand smoke (SHS) has deleterious respiratory, immune, and nutritional effects in children, but there is little data regarding the effects of SHS exposure in infants with cystic fibrosis (CF). A retrospective chart review was undertaken from 2008 to 2012 of 75 infants with CF. Growth, lung function, Chest CT imaging, and microbiologic characteristics were compared between 4 and 12 months for SHS and non-SHS exposed patients. SHS exposed infants with CF had decreased growth between 4 and 12 months compared to non-SHS exposed infants. SHS exposure was associated with increased bronchodilator responsiveness and air trapping, but no other lung function or radiologic differences. SHS exposure was also associated with increased methicillin resistant Staphylococcus aureus (MRSA) and anaerobic growth on respiratory culture. There was no difference in Pseudomonas aeruginosa between groups. There were no differences in antibiotic use or hospitalizations between the groups. SHS exposure in CF infants is associated with diminished growth, increased air trapping and bronchodilator responsiveness, and propensity to culture MRSA and facultative anaerobic bacteria, suggesting the need for early, aggressive parental smoking cessation interventions to prevent SHS exposure complications. © 2014 Wiley Periodicals, Inc.

Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections

PubMed Central

Domm, William; Misra, Ravi S.; O’Reilly, Michael A.

2015-01-01

Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses. Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured. Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity. Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense. This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health. PMID:26322310

AMD3100 ameliorates cigarette smoke-induced emphysema-like manifestations in mice.

PubMed

Barwinska, Daria; Oueini, Houssam; Poirier, Christophe; Albrecht, Marjorie E; Bogatcheva, Natalia V; Justice, Matthew J; Saliba, Jacob; Schweitzer, Kelly S; Broxmeyer, Hal E; March, Keith L; Petrache, Irina

2018-05-10

We have shown that cigarette smoke (CS)-induced pulmonary emphysema-like manifestations are preceded by marked suppression of the number and function of bone marrow hematopoietic progenitor cells (HPC). To investigate if a limited availability of HPC may contribute to CS-induced lung injury, we used an FDA-approved antagonist of the interactions of SDF-1 with its receptor CXCR4 to promote intermittent HPC mobilization and tested its ability to limit emphysema-like injury following chronic CS. We administered AMD3100 (5mg/kg) to mice during a chronic CS exposure protocol of up to 24 weeks. AMD3100 treatment did not affect either lung SDF-1 levels, which were reduced by CS, or lung inflammatory cell counts. However, AMD3100 markedly improved CS-induced bone marrow HPC suppression and significantly ameliorated emphysema-like endpoints such as alveolar airspace size, lung volumes, and lung static compliance. These results suggest that antagonism of SDF-1 binding to CXCR4 is associated with protection of both bone marrow and lungs during chronic CS exposure, thus encouraging future studies of potential therapeutic benefit of AMD3100 in emphysema.

Cold stress aggravates inflammatory responses in an LPS-induced mouse model of acute lung injury

NASA Astrophysics Data System (ADS)

Joo, Su-Yeon; Park, Mi-Ju; Kim, Kyun-Ha; Choi, Hee-Jung; Chung, Tae-Wook; Kim, Yong Jin; Kim, Joung Hee; Kim, Keuk-Jun; Joo, Myungsoo; Ha, Ki-Tae

2016-08-01

Although the relationship between environmental cold temperature and susceptibility to respiratory infection is generally accepted, the effect of ambient cold temperature on host reactivity in lung inflammation has not been fully studied. To examine the function of ambient cold temperature on lung inflammation, mice were exposed to 4 °C for 8 h each day for 14 days. In the lungs of mice exposed to cold stress, inflammatory cells in bronchoalveolar lavage (BAL) fluid and lung tissues were slightly increased by about twofold. However, the structures of pulmonary epithelial cells were kept within normal limits. Next, we examined the effect of cold stress on the inflammatory responses in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The infiltration of neutrophils and inflammation of lung tissue determined by histology were significantly increased by exposure to ambient cold temperature. In addition, the production of pro-inflammatory cytokines including interleukin (IL)-12, IL-17, and monokine induced by gamma interferon (MIG) was elevated by exposure to cold stress. Therefore, we suggest that cold stress is a factor that exacerbates lung inflammation including ALI. To our knowledge, this is the first report on the relationship between cold stress and severity of lung inflammation.

Exposure to hyperoxia in the neonatal period alters bone marrow function

USDA-ARS?s Scientific Manuscript database

Oxygen is often life saving in preterm infants, however, excessive exposure may lead to blood vessel and tissue injury in the lung and retina. Oxygen-treated neonates often exhibit bone marrow (BM) suppression requiring blood product transfusions. However, we do not know whether oxygen is directly t...

Prediction of lung function response for populations exposed to a wide range of ozone conditions

EPA Science Inventory

Abstract Context: A human exposure-response (E-R) model that has previously been demonstrated to accurately predict population mean FEV1 response to ozone exposure has been proposed as the foundation for future risk assessments for ambient ozone. Objective: Fit the origi...

Decreased lung function with mediation of blood parameters linked to e-waste lead and cadmium exposure in preschool children.

PubMed

Zeng, Xiang; Xu, Xijin; Boezen, H Marike; Vonk, Judith M; Wu, Weidong; Huo, Xia

2017-11-01

Blood lead (Pb) and cadmium (Cd) levels have been associated with lower lung function in adults and smokers, but whether this also holds for children from electronic waste (e-waste) recycling areas is still unknown. To investigate the contribution of blood heavy metals and lung function levels, and the relationship among living area, the blood parameter levels, and the lung function levels, a total of 206 preschool children from Guiyu (exposed area), and Haojiang and Xiashan (reference areas) were recruited and required to undergo blood tests and lung function tests during the study period. Preschool children living in e-waste exposed areas were found to have a 1.37 μg/dL increase in blood Pb, 1.18 μg/L increase in blood Cd, and a 41.00 × 10 9 /L increase in platelet counts, while having a 2.82 g/L decrease in hemoglobin, 92 mL decrease in FVC and 86 mL decrease in FEV 1 . Each unit of hemoglobin (1 g/L) decline was associated with 5 mL decrease in FVC and 4 mL decrease in FEV 1 . We conclude that children living in e-waste exposed area have higher levels of blood Pb, Cd and platelets, and lower levels of hemoglobin and lung function. Hemoglobin can be a good predictor for lung function levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure

PubMed Central

Razvi, Shehla S.; Richards, Jeremy B.; Malik, Farhan; Cromar, Kevin R.; Price, Roger E.; Bell, Cynthia S.; Weng, Tingting; Atkins, Constance L.; Spencer, Chantal Y.; Cockerill, Katherine J.; Alexander, Amy L.; Blackburn, Michael R.; Alcorn, Joseph L.; Haque, Ikram U.

2015-01-01

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines—including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1β)—promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1β, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-β-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology. PMID:26386120

Influenza A virus-dependent remodeling of pulmonary clock function in a mouse model of COPD

PubMed Central

Sundar, Isaac K.; Ahmad, Tanveer; Yao, Hongwei; Hwang, Jae-woong; Gerloff, Janice; Lawrence, B. Paige; Sellix, Michael T.; Rahman, Irfan

2015-01-01

Daily oscillations of pulmonary function depend on the rhythmic activity of the circadian timing system. Environmental tobacco/cigarette smoke (CS) disrupts circadian clock leading to enhanced inflammatory responses. Infection with influenza A virus (IAV) increases hospitalization rates and death in susceptible individuals, including patients with Chronic Obstructive Pulmonary Disease (COPD). We hypothesized that molecular clock disruption is enhanced by IAV infection, altering cellular and lung function, leading to severity in airway disease phenotypes. C57BL/6J mice exposed to chronic CS, BMAL1 knockout (KO) mice and wild-type littermates were infected with IAV. Following infection, we measured diurnal rhythms of clock gene expression in the lung, locomotor activity, pulmonary function, inflammatory, pro-fibrotic and emphysematous responses. Chronic CS exposure combined with IAV infection altered the timing of clock gene expression and reduced locomotor activity in parallel with increased lung inflammation, disrupted rhythms of pulmonary function, and emphysema. BMAL1 KO mice infected with IAV showed pronounced detriments in behavior and survival, and increased lung inflammatory and pro-fibrotic responses. This suggests that remodeling of lung clock function following IAV infection alters clock-dependent gene expression and normal rhythms of lung function, enhanced emphysematous and injurious responses. This may have implications for the pathobiology of respiratory virus-induced airway disease severity and exacerbations. PMID:25923474

Type 2 Immune Mechanisms in Carbon Nanotube-Induced Lung Fibrosis.

PubMed

Dong, Jie; Ma, Qiang

2018-01-01

T helper (Th) 2-dependent type 2 immune pathways have been recognized as an important driver for the development of fibrosis. Upon stimulation, activated Th2 immune cells and type 2 cytokines interact with inflammatory and tissue repair functions to stimulate an overzealous reparative response to tissue damage, leading to organ fibrosis and destruction. In this connection, type 2 pathways are activated by a variety of insults and pathological conditions to modulate the response. Carbon nanotubes (CNTs) are nanomaterials with a wide range of applications. However, pulmonary exposure to CNTs causes a number of pathologic outcomes in animal lungs, dominated by inflammation and fibrosis. These findings, alongside the rapidly expanding production and commercialization of CNTs and CNT-containing materials in recent years, have raised concerns on the health risk of CNT exposure in humans. The CNT-induced pulmonary fibrotic lesions resemble those of human fibrotic lung diseases, such as idiopathic pulmonary fibrosis and pneumoconiosis, to a certain extent with regard to disease development and pathological features. In fibrotic scenarios, immune cells are activated including varying immune pathways, ranging from innate immune cell activation to autoimmune disease. These events often precede and/or accompany the occurrence of fibrosis. Upon CNT exposure, significant induction and activation of Th2 cells and type 2 cytokines in the lungs are observed. Moreover, type 2 pathways are shown to play important roles in promoting CNT-induced lung fibrosis by producing type 2 pro-fibrotic factors and inducing the reparative phenotypes of macrophages in response to CNTs. In light of the vastly increased demand for nanosafety and the apparent induction and multiple roles of type 2 immune pathways in lung fibrosis, we review the current literature on CNT-induced lung fibrosis, with a focus on the induction and activation of type 2 responses by CNTs and the stimulating function of type 2 signaling on pulmonary fibrosis development. These analyses provide new insights into the mechanistic understanding of CNT-induced lung fibrosis, as well as the potential of using type 2 responses as a monitoring target and therapeutic strategy for human fibrotic lung disease.

Antioxidant airway responses following experimental exposure to wood smoke in man

PubMed Central

2010-01-01

Background Biomass combustion contributes to the production of ambient particulate matter (PM) in rural environments as well as urban settings, but relatively little is known about the health effects of these emissions. The aim of this study was therefore to characterize airway responses in humans exposed to wood smoke PM under controlled conditions. Nineteen healthy volunteers were exposed to both wood smoke, at a particulate matter (PM2.5) concentration of 224 ± 22 μg/m3, and filtered air for three hours with intermittent exercise. The wood smoke was generated employing an experimental set-up with an adjustable wood pellet boiler system under incomplete combustion. Symptoms, lung function, and exhaled NO were measured over exposures, with bronchoscopy performed 24 h post-exposure for characterisation of airway inflammatory and antioxidant responses in airway lavages. Results Glutathione (GSH) concentrations were enhanced in bronchoalveolar lavage (BAL) after wood smoke exposure vs. air (p = 0.025), together with an increase in upper airway symptoms. Neither lung function, exhaled NO nor systemic nor airway inflammatory parameters in BAL and bronchial mucosal biopsies were significantly affected. Conclusions Exposure of healthy subjects to wood smoke, derived from an experimental wood pellet boiler operating under incomplete combustion conditions with PM emissions dominated by organic matter, caused an increase in mucosal symptoms and GSH in the alveolar respiratory tract lining fluids but no acute airway inflammatory responses. We contend that this response reflects a mobilisation of GSH to the air-lung interface, consistent with a protective adaptation to the investigated wood smoke exposure. PMID:20727160

Lung cancer mortality and occupational exposure to asbestos among telephone linemen: a historical cohort study in France.

PubMed

Meguellati-Hakkas, Djamila; Cyr, Diane; Stücker, Isabelle; Févotte, Joëlle; Pilorget, Corinne; Luce, Danièle; Guénel, Pascal

2006-11-01

The authors studied the mortality by lung cancer in telephone linemen exposed to asbestos at low levels during installation of telephone cables. Three hundred eight lung cancers deaths were identified in the cohort. Exposure to asbestos and to other occupational carcinogens was assessed using a job-exposure matrix. The relative risk for lung cancer death associated with an estimated exposure of approximately 2 f/cc-years was 2.1 (95% confidence interval = 1.1-4.0) as compared with workers exposed to less than 0.5 f/cc-years. Mean annual exposure or exposure duration were not clearly related to lung cancer. Adjustment for other occupational lung carcinogens did not change this finding. The observed mortality by lung cancer associated with asbestos exposure at low levels is higher than the prediction based on linear downward extrapolations from highly exposed occupational cohorts.

The risk of lung cancer after cessation of asbestos exposure in construction workers using pleural malignant mesothelioma as a marker of exposure.

PubMed

Järvholm, Bengt; Aström, Evelina

2014-12-01

To study the risk of lung cancer in heavily asbestos-exposed workers after the exposure to asbestos has ended. Lung cancer was studied in a cohort of 189,896 Swedish construction workers through a linkage with the Swedish Cancer Registry. Asbestos exposure was estimated by the incidence of malignant mesothelioma in the occupational group. There were in total 2835 cases of lung cancer. Workers with heavy exposure to asbestos had an increased risk of lung cancer (relative risks = 1.74; 95% confidence interval, 1.25 to 2.41) before exposure ended and a similar risk to those with low exposure 20 years after the exposure had ceased (relative risks = 0.94; 95% confidence interval, 0.77 to 1.15). Workers with heavy exposure to asbestos have a similar risk of lung cancer as persons with low or no exposure 20 years after the exposure has ended.

Metabolic Syndrome Biomarkers Predict Lung Function Impairment

PubMed Central

Naveed, Bushra; Weiden, Michael D.; Kwon, Sophia; Gracely, Edward J.; Comfort, Ashley L.; Ferrier, Natalia; Kasturiarachchi, Kusali J.; Cohen, Hillel W.; Aldrich, Thomas K.; Rom, William N.; Kelly, Kerry; Prezant, David J.

2012-01-01

Rationale: Cross-sectional studies demonstrate an association between metabolic syndrome and impaired lung function. Objectives: To define if metabolic syndrome biomarkers are risk factors for loss of lung function after irritant exposure. Methods: A nested case-control study of Fire Department of New York personnel with normal pre–September 11th FEV1 and who presented for subspecialty pulmonary evaluation before March 10, 2008. We correlated metabolic syndrome biomarkers obtained within 6 months of World Trade Center dust exposure with subsequent FEV1. FEV1 at subspecialty pulmonary evaluation within 6.5 years defined disease status; cases had FEV1 less than lower limit of normal, whereas control subjects had FEV1 greater than or equal to lower limit of normal. Measurements and Main Results: Clinical data and serum sampled at the first monitoring examination within 6 months of September 11, 2001, assessed body mass index, heart rate, serum glucose, triglycerides and high-density lipoprotein (HDL), leptin, pancreatic polypeptide, and amylin. Cases and control subjects had significant differences in HDL less than 40 mg/dl with triglycerides greater than or equal to 150 mg/dl, heart rate greater than or equal to 66 bpm, and leptin greater than or equal to 10,300 pg/ml. Each increased the odds of abnormal FEV1 at pulmonary evaluation by more than twofold, whereas amylin greater than or equal to 116 pg/ml decreased the odds by 84%, in a multibiomarker model adjusting for age, race, body mass index, and World Trade Center arrival time. This model had a sensitivity of 41%, a specificity of 86%, and a receiver operating characteristic area under the curve of 0.77. Conclusions: Abnormal triglycerides and HDL and elevated heart rate and leptin are independent risk factors of greater susceptibility to lung function impairment after September 11, 2001, whereas elevated amylin is protective. Metabolic biomarkers are predictors of lung disease, and may be useful for assessing risk of impaired lung function in response to particulate inhalation. PMID:22095549

Single-cell RNA sequencing reveals an altered gene expression pattern as a result of CRISPR/cas9-mediated deletion of Gene 33/Mig6 and chronic exposure to hexavalent chromium in human lung epithelial cells.

PubMed

Park, Soyoung; Zhang, Xiaowen; Li, Cen; Yin, Changhong; Li, Jiangwei; Fallon, John T; Huang, Weihua; Xu, Dazhong

2017-09-01

Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently reported that depletion of this protein promotes lung epithelial cell transformation induced by hexavalent chromium [Cr(VI)]. However, the early molecular events that mediate this process are not clear. In the present study, we used single-cell RNA sequencing to compare gene expression profiles between BEAS-2B lung epithelial cells chronically exposed to a sublethal dose of Cr(VI) with or without CRISPR/cas9-mediated deletion of Gene 33. Our data reveal 83 differentially expressed genes. The most notable changes are genes associated with cell adhesion, oxidative stresses, protein ubiquitination, epithelial-mesenchymal transition/metastasis, and WNT signaling. Up-regulation of some neuro-specific genes is also evident, particularly ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a deubiquitinase and potential biomarker for lung cancer. Gene 33 deletion and/or Cr(VI) exposure did not cause discernable changes in cell morphology. However, Gene 33 deletion led to a modest but significant reduction of cells in the G2/M phase of the cell cycle regardless of Cr(VI) exposure. Gene 33 deletion also significantly reduced cell proliferation. Interestingly, Cr(VI) exposure eliminated the difference in cell proliferation between the two genotypes. Gene 33 deletion also significantly elevated cell migration. Our data indicate that combined Gene 33 deletion and chronic Cr(VI) exposure produces a gene expression pattern and a phenotype resemble those of the transformed lung epithelial cells. Given the known association of UCHL1 with lung cancer, we propose that UCHL1 is an important player in the early stage of lung epithelial cell transformation and tumorigenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frank, Evan A.; Birch, M. Eileen; Yadav, Jagjit S., E-mail: Jagjit.Yadav@uc.edu

Carbon nanotubes (CNTs) are rapidly emerging as high-priority occupational toxicants. CNT powders contain fibrous particles that aerosolize readily in places of manufacture and handling, posing an inhalation risk for workers. Studies using animal models indicate that lung exposure to CNTs causes prolonged inflammatory responses and diffuse alveolar injury. The mechanisms governing CNT-induced lung inflammation are not fully understood but have been suggested to involve alveolar macrophages (AMs). In the current study, we sought to systematically assess the effector role of AMs in vivo in the induction of lung inflammatory responses to CNT exposures and investigate their cell type-specific mechanisms. Multi-wallmore » CNTs characterized for various physicochemical attributes were used as the CNT type. Using an AM-specific depletion and repopulation approach in a mouse model, we unambiguously demonstrated that AMs are major effector cells necessary for the in vivo elaboration of CNT-induced lung inflammation. We further investigated in vitro AM responses and identified molecular targets which proved critical to pro-inflammatory responses in this model, namely MyD88 as well as MAPKs and Ca{sup 2} {sup +}/CamKII. We further demonstrated that MyD88 inhibition in donor AMs abrogated their capacity to reconstitute CNT-induced inflammation when adoptively transferred into AM-depleted mice. Taken together, this is the first in vivo demonstration that AMs act as critical effector cell types in CNT-induced lung inflammation and that MyD88 is required for this in vivo effector function. AMs and their cell type-specific mechanisms may therefore represent potential targets for future therapeutic intervention of CNT-related lung injury. - Highlights: • Demonstrated in vivo effector role of alveolar macrophages (AMs) in CNT toxicity • MyD88, MAPKs, and Ca{sup 2} {sup +}/CamKII are required for AM inflammatory responses in vitro. • MyD88 signaling is required for in vivo effector function of AMs. • MyD88 may be a potential target for intervention in CNT lung exposures.« less

Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats

PubMed Central

Zeidler-Erdely, Patti C.; Meighan, Terence G.; Erdely, Aaron; Fedan, Jeffrey S.; Thompson, Janet A.; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B.; Afshari, Aliakbar; McKinney, Walter; Frazer, David G.; Antonini, James M.

2015-01-01

Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m3 to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (RL) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline RL was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased RL and result in endothelial dysfunction, but otherwise had minor effects on the lung. PMID:25140454

Occupational radon exposure and lung cancer mortality: estimating intervention effects using the parametric g-formula.

PubMed

Edwards, Jessie K; McGrath, Leah J; Buckley, Jessie P; Schubauer-Berigan, Mary K; Cole, Stephen R; Richardson, David B

2014-11-01

Traditional regression analysis techniques used to estimate associations between occupational radon exposure and lung cancer focus on estimating the effect of cumulative radon exposure on lung cancer. In contrast, public health interventions are typically based on regulating radon concentration rather than workers' cumulative exposure. Estimating the effect of cumulative occupational exposure on lung cancer may be difficult in situations vulnerable to the healthy worker survivor bias. Workers in the Colorado Plateau Uranium Miners cohort (n = 4,134) entered the study between 1950 and 1964 and were followed for lung cancer mortality through 2005. We use the parametric g-formula to compare the observed lung cancer mortality to the potential lung cancer mortality had each of 3 policies to limit monthly radon exposure been in place throughout follow-up. There were 617 lung cancer deaths over 135,275 person-years of follow-up. With no intervention on radon exposure, estimated lung cancer mortality by age 90 was 16%. Lung cancer mortality was reduced for all interventions considered, and larger reductions in lung cancer mortality were seen for interventions with lower monthly radon exposure limits. The most stringent guideline, the Mine Safety and Health Administration standard of 0.33 working-level months, reduced lung cancer mortality from 16% to 10% (risk ratio = 0.67 [95% confidence interval = 0.61 to 0.73]). This work illustrates the utility of the parametric g-formula for estimating the effects of policies regarding occupational exposures, particularly in situations vulnerable to the healthy worker survivor bias.

An indoor air filtration study in homes of elderly: cardiovascular and respiratory effects of exposure to particulate matter

PubMed Central

2013-01-01

Background Exposure to particulate air pollution increases respiratory and cardiovascular morbidity and mortality, especially in elderly, possibly through inflammation and vascular dysfunction. Methods We examined potential beneficial effects of indoor air filtration in the homes of elderly, including people taking vasoactive drugs. Forty-eight nonsmoking subjects (51 to 81 years) in 27 homes were included in this randomized, double-blind, crossover intervention study with consecutive two-week periods with or without the inclusion of a high-efficiency particle air filter in re-circulating custom built units in their living room and bedroom. We measured blood pressure, microvascular and lung function and collected blood samples for hematological, inflammation, monocyte surface and lung cell damage markers before and at day 2, 7 and 14 during each exposure scenario. Results The particle filters reduced the median concentration of PM2.5 from approximately 8 to 4 μg/m3 and the particle number concentration from 7669 to 5352 particles/cm3. No statistically significant effects of filtration as category were observed on microvascular and lung function or the biomarkers of systemic inflammation among all subjects, or in the subgroups taking (n = 11) or not taking vasoactive drugs (n = 37). However, the filtration efficacy was variable and microvascular function was within 2 days significantly increased with the actual PM2.5 decrease in the bedroom, especially among 25 subjects not taking any drugs. Conclusion Substantial exposure contrasts in the bedroom and no confounding by drugs appear required for improved microvascular function by air filtration, whereas no other beneficial effect was found in this elderly population. PMID:24373585

Impact assessment of repeated exposure of organotypic 3D bronchial and nasal tissue culture models to whole cigarette smoke.

PubMed

Kuehn, Diana; Majeed, Shoaib; Guedj, Emmanuel; Dulize, Remi; Baumer, Karine; Iskandar, Anita; Boue, Stephanie; Martin, Florian; Kostadinova, Radina; Mathis, Carole; Ivanov, Nikolai V; Frentzel, Stefan; Hoeng, Julia; Peitsch, Manuel C

2015-02-12

Cigarette smoke (CS) has a major impact on lung biology and may result in the development of lung diseases such as chronic obstructive pulmonary disease or lung cancer. To understand the underlying mechanisms of disease development, it would be important to examine the impact of CS exposure directly on lung tissues. However, this approach is difficult to implement in epidemiological studies because lung tissue sampling is complex and invasive. Alternatively, tissue culture models can facilitate the assessment of exposure impacts on the lung tissue. Submerged 2D cell cultures, such as normal human bronchial epithelial (NHBE) cell cultures, have traditionally been used for this purpose. However, they cannot be exposed directly to smoke in a similar manner to the in vivo exposure situation. Recently developed 3D tissue culture models better reflect the in vivo situation because they can be cultured at the air-liquid interface (ALI). Their basal sides are immersed in the culture medium; whereas, their apical sides are exposed to air. Moreover, organotypic tissue cultures that contain different type of cells, better represent the physiology of the tissue in vivo. In this work, the utilization of an in vitro exposure system to expose human organotypic bronchial and nasal tissue models to mainstream CS is demonstrated. Ciliary beating frequency and the activity of cytochrome P450s (CYP) 1A1/1B1 were measured to assess functional impacts of CS on the tissues. Furthermore, to examine CS-induced alterations at the molecular level, gene expression profiles were generated from the tissues following exposure. A slight increase in CYP1A1/1B1 activity was observed in CS-exposed tissues compared with air-exposed tissues. A network-and transcriptomics-based systems biology approach was sufficiently robust to demonstrate CS-induced alterations of xenobiotic metabolism that were similar to those observed in the bronchial and nasal epithelial cells obtained from smokers.

Respiratory Morbidity in a Coffee Processing Workplace With Sentinel Obliterative Bronchiolitis Cases

PubMed Central

Bailey, Rachel L.; Cox-Ganser, Jean M.; Duling, Matthew G.; LeBouf, Ryan F.; Martin, Stephen B.; Bledsoe, Toni A.; Green, Brett J.; Kreiss, Kathleen

2016-01-01

Rationale Obliterative bronchiolitis in former coffee workers prompted a cross-sectional study of current workers. Diacetyl and 2,3-pentanedione levels were highest in areas for flavoring and grinding/packaging unflavored coffee. Methods We interviewed 75 (88%) workers, measured lung function, and created exposure groups based on work history. We calculated standardized morbidity ratios (SMRs) for symptoms and spirometric abnormalities. We examined health outcomes by exposure groups. Results SMRs were elevated 1.6-fold for dyspnea and 2.7-fold for obstruction. The exposure group working in both coffee flavoring and grinding/packaging of unflavored coffee areas had significantly lower mean ratio of forced expiratory volume in 1 s to forced vital capacity and percent predicted mid-expiratory flow than workers without such exposure. Conclusion Current workers have occupational lung morbidity associated with high diacetyl and 2,3-pentanedione exposures, which were not limited to flavoring areas. PMID:26523478

Chronic hypersensitivity pneumonitis

PubMed Central

Pereira, Carlos AC; Gimenez, Andréa; Kuranishi, Lilian; Storrer, Karin

2016-01-01

Hypersensitivity pneumonitis (HSP) is a common interstitial lung disease resulting from inhalation of a large variety of antigens by susceptible individuals. The disease is best classified as acute and chronic. Chronic HSP can be fibrosing or not. Fibrotic HSP has a large differential diagnosis and has a worse prognosis. The most common etiologies for HSP are reviewed. Diagnostic criteria are proposed for both chronic forms based on exposure, lung auscultation, lung function tests, HRCT findings, bronchoalveolar lavage, and biopsies. Treatment options are limited, but lung transplantation results in greater survival in comparison to idiopathic pulmonary fibrosis. Randomized trials with new antifibrotic agents are necessary. PMID:27703382

Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Cardiovascular Links

PubMed Central

Laratta, Cheryl R.; van Eeden, Stephan

2014-01-01

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease resulting from exposure to cigarette smoke, noxious gases, particulate matter, and air pollutants. COPD is exacerbated by acute inflammatory insults such as lung infections (viral and bacterial) and air pollutants which further accelerate the steady decline in lung function. The chronic inflammatory process in the lung contributes to the extrapulmonary manifestations of COPD which are predominantly cardiovascular in nature. Here we review the significant burden of cardiovascular disease in COPD and discuss the clinical and pathological links between acute exacerbations of COPD and cardiovascular disease. PMID:24724085

The effect of pollutional haze on pulmonary function

PubMed Central

Liu, Shao-Kun; Cai, Shan; Chen, Yan; Xiao, Bing; Chen, Ping

2016-01-01

Detrimental health effects of atmospheric exposure to ambient particulate matter (PM) have been investigated in numerous studies. Exposure to pollutional haze, the carrier of air pollutants such as PM and nitrogen dioxide (NO2) has been linked to lung and cardiovascular disease, resulting increases in both hospital admissions and mortality. This review focuses on the constituents of pollutional haze and its effects on pulmonary function. The article presents the available information and seeks to correlate pollutional haze and pulmonary function. PMID:26904252

Effects of indoor air pollution on lung function of primary school children in Kuala Lumpur

DOE Office of Scientific and Technical Information (OSTI.GOV)

Azizi, B.H.; Henry, R.L.

1990-01-01

In a cross-sectional study of 7-12 year-old primary school children in Kuala Lumpur city, lung function was assessed by spirometric and peak expiratory flow measurements. Spirometric and peak expiratory flow measurements were successfully performed in 1,214 and 1,414 children, respectively. As expected, the main predictors of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and peak expiratory flow rate (PEFR) were standing height, weight, age, and sex. In addition, lung function values of Chinese and Malays were generally higher than those of Indians. In multiple regressionmore » models which included host and environmental factors, asthma was associated with significant decreases in FEV1, FEF25-75, and PEFR. However, family history of chest illness, history of allergies, low paternal education, and hospitalization during the neonatal period were not independent predictors of lung function. Children sharing rooms with adult smokers had significantly lower levels of FEF25-75. Exposures to wood or kerosene stoves were, but to mosquito repellents were not, associated with decreased lung function.« less

Tobacco use among designated air pollution victims and its association with lung function and respiratory symptoms: a retrospective cross-sectional study

PubMed Central

Kotaki, Kenji; Senjyu, Hideaki; Tanaka, Takako; Yano, Yudai; Miyamoto, Naomi; Nishinakagawa, Tsuyoshi; Yanagita, Yorihide; Asai, Masaharu; Kozu, Ryo; Tabusadani, Mitsuru; Sawai, Terumitsu; Honda, Sumihisa

2014-01-01

Objectives We sought to elucidate the long-term association of tobacco use and respiratory health in designated pollution victims with and without obstructive pulmonary defects. Design A retrospective cross-sectional study. Setting The register of pollution victims in Kurashiki, Japan. Participants 730 individuals over 65 years of age previously diagnosed with pollution-related respiratory disease. Patients were classified into four groups according to their smoking status and whether they had obstructive pulmonary disease. We then compared the prevalence of respiratory symptoms and lung function over time between groups. Primary outcome measures Spirometry was performed and a respiratory health questionnaire completed in the same season each year for up to 30 years. Results Rates of smoking and respiratory disease were high in our sample. Although respiratory function in non-smoking patients did not completely recover, the annual rate of change in lung function was within the normal range (p<0.01). However, smokers had worse lung function and were more likely to report more severe pulmonary symptoms (p<0.01). Conclusions Patients’ respiratory function did not fully recover despite improved air quality. Our results suggest that, in the context of exposure to air pollution, tobacco use causes additional loss of lung function and exacerbates respiratory symptoms. PMID:25082419

Ventilatory function in rubber processing workers: acute changes over the workshift.

PubMed Central

Governa, M; Comai, M; Valentino, M; Antonicelli, L; Rinaldi, F; Pisani, E

1987-01-01

When considering rubber tyre manufacturing from an occupational health viewpoint, three areas may be identified in which exposure to respirable materials are potentially harmful: the processing, curing, and talc areas. A study of the ventilatory function of the entire work force employed in the processing area in a rubber tyre manufacturing plant was undertaken to determine whether an acute reduction in lung function occurs over the course of their working shift (the plant worked a three shift system) and whether a chronic exposure to the occupational airborne contaminants causes permanent changes in lung function. The ventilatory function was measured at the worksite at the beginning and immediately after the end of the workshift. No evidence of chronic obstructive pulmonary disease was found and in most cases no significant decline in FEV1 was observed. Only one of the 79 individuals showed a moderate obstruction, measured by the ratio FEV1/FVC which gave the value of 0.55, with no variation over the shift. For non-smokers, the FVC, FEV1, and FEF25-75% were lower in those exposed for more than five years than in those exposed for five years or less. A similar pattern was also observed in the FVC and FEV1 of the smokers. None of these differences was statistically significant. Within each exposure group the pulmonary function of the smokers was lower than that of the non-smokers, but the only significant difference was found in the values of FEF25-75%. Only one man showed a decline in the FEV1/FVC ratio over the shift, but during each shift, a decrease in all the lung function tests was observed. The decrease was smallest during the first of the three shifts. These results are thought to support the hypothesis that there are acute adverse effects over an eight hour shift. Further investigations are needed to discover whether these acute changes in lung function result from a chemical stimulation or irritant receptors in the airways. PMID:3814549

Early Life Wildfire Smoke Exposure Is Associated with Immune Dysregulation and Lung Function Decrements in Adolescence.

PubMed

Black, Carolyn; Gerriets, Joan E; Fontaine, Justin H; Harper, Richart W; Kenyon, Nicholas J; Tablin, Fern; Schelegle, Edward S; Miller, Lisa A

2017-05-01

The long-term health effects of wildfire smoke exposure in pediatric populations are not known. The objectives of this study were to determine if early life exposure to wildfire smoke can affect parameters of immunity and airway physiology that are detectable with maturity. We studied a mixed-sex cohort of rhesus macaque monkeys that were exposed as infants to ambient wood smoke from a series of Northern California wildfires in the summer of 2008. Peripheral blood mononuclear cells (PBMCs) and pulmonary function measures were obtained when animals were approximately 3 years of age. PBMCs were cultured with either LPS or flagellin, followed by measurement of secreted IL-8 and IL-6 protein. PBMCs from a subset of female animals were also evaluated by Toll-like receptor (TLR) pathway mRNA analysis. Induction of IL-8 protein synthesis with either LPS or flagellin was significantly reduced in PBMC cultures from wildfire smoke-exposed female monkeys. In contrast, LPS- or flagellin-induced IL-6 protein synthesis was significantly reduced in PBMC cultures from wildfire smoke-exposed male monkeys. Baseline and TLR ligand-induced expression of the transcription factor, RelB, was globally modulated in PBMCs from wildfire smoke-exposed monkeys, with additional TLR pathway genes affected in a ligand-dependent manner. Wildfire smoke-exposed monkeys displayed significantly reduced inspiratory capacity, residual volume, vital capacity, functional residual capacity, and total lung capacity per unit of body weight relative to control animals. Our findings suggest that ambient wildfire smoke exposure during infancy results in sex-dependent attenuation of systemic TLR responses and reduced lung volume in adolescence.

Estimation of quantitative levels of diesel exhaust exposure and the health impact in the contemporary Australian mining industry.

PubMed

Peters, Susan; de Klerk, Nicholas; Reid, Alison; Fritschi, Lin; Musk, Aw Bill; Vermeulen, Roel

2017-03-01

To estimate quantitative levels of exposure to diesel exhaust expressed by elemental carbon (EC) in the contemporary mining industry and to describe the excess risk of lung cancer that may result from those levels. EC exposure has been monitored in Western Australian miners since 2003. Mixed-effects models were used to estimate EC levels for five surface and five underground occupation groups (as a fixed effect) and specific jobs within each group (as a random effect). Further fixed effects included sampling year and duration, and mineral mined. On the basis of published risk functions, we estimated excess lifetime risk of lung cancer mortality for several employment scenarios. Personal EC measurements (n=8614) were available for 146 different jobs at 124 mine sites. The mean estimated EC exposure level for surface occupations in 2011 was 14 µg/m 3 for 12 hour shifts. Levels for underground occupation groups ranged from 18 to 44 µg/m 3 . Underground diesel loader operators had the highest exposed specific job: 59 µg/m 3 . A lifetime career (45 years) as a surface worker or underground miner, experiencing exposure levels as estimated for 2011 (14 and 44 µg/m 3 EC), was associated with 5.5 and 38 extra lung cancer deaths per 1000 males, respectively. EC exposure levels in the contemporary Australian mining industry are still substantial, particularly for underground workers. The estimated excess numbers of lung cancer deaths associated with these exposures support the need for implementation of stringent occupational exposure limits for diesel exhaust. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Occupational risk factors of lung cancer: a hospital based case-control study

PubMed Central

Droste, J. H.; Weyler, J. J.; Van Meerbeeck, J. P.; Vermeire, P. A.; van Sprundel, M. P.

1999-01-01

OBJECTIVES: To investigate the relation between lung cancer and exposure to occupational carcinogens in a highly industrialised region in western Europe. METHODS: In a case-control study 478 cases and 536 controls, recruited from 10 hospitals in the Antwerp region, were interviewed. Cases were male patients with histologically confirmed lung cancer; controls were male patients without cancer or primary lung diseases. Data were collected by questionnaires to obtain information on occupations, exposures, and smoking history. Job titles were coded with the Office of Populations, Censuses and Surveys industrial classification. Exposure was assessed by self report and by job-task exposure matrix. Exposure odds ratios were calculated with logistic regression analysis adjusted for age, smoking history, and marital and socio-economic status. RESULTS: A job history in the categories manufacturing of transport equipment other than automobiles (for example, shipyard workers), transport support services (for example, dockers), and manufacturing of metal goods (for example, welders) was significantly associated with lung cancer (odds ratios (ORs) 2.3, 1.6, and 1.6 respectively). These associations were independent of smoking, education, civil, and economic status. Self reported exposure to potential carcinogens did not show significant associations with lung cancer, probably due to nondifferential misclassification. When assessed by job-task exposure matrix, exposure to molybdenum, mineral oils, and chromium were significantly associated with lung cancer. A strong association existed between smoking and lung cancer: OR of ex- smokers 4.2, OR of current smokers 14.5 v non-smokers. However, smoking did not confound the relation between occupational exposure and lung cancer. CONCLUSIONS: The study has shown a significant excess risk of lung cancer among workers in manufacturing of metal goods, manufacturing of transport equipment (other than automobiles), and transport support services. Assessment of exposure to specific carcinogens resulted in significant associations of chromium, mineral oils, and molybdenum with lung cancer. This study is, to our knowledge, the first study reporting a significant association between occupational exposure to molybdenum and lung cancer.   PMID:10472306

Review of refractory ceramic fiber (RCF) toxicity, epidemiology and occupational exposure.

PubMed

Maxim, L Daniel; Utell, Mark J

2018-02-01

This literature review on refractory ceramic fibers (RCF) summarizes relevant information on manufacturing, processing, applications, occupational exposure, toxicology and epidemiology studies. Rodent toxicology studies conducted in the 1980s showed that RCF caused fibrosis, lung cancer and mesothelioma. Interpretation of these studies was difficult for various reasons (e.g. overload in chronic inhalation bioassays), but spurred the development of a comprehensive product stewardship program under EPA and later OSHA oversight. Epidemiology studies (both morbidity and mortality) were undertaken to learn more about possible health effects resulting from occupational exposure. No chronic animal bioassay studies on RCF have been conducted since the 1980s. The results of the ongoing epidemiology studies confirm that occupational exposure to RCF is associated with the development of pleural plaques and minor decrements in lung function, but no interstitial fibrosis or incremental lung cancer. Evidence supporting a finding that urinary tumors are associated with RCF exposure remains, but is weaker. One reported, but unconfirmed, mesothelioma was found in an individual with prior occupational asbestos exposure. An elevated SMR for leukemia was found, but was absent in the highly exposed group and has not been observed in studies of other mineral fibers. The industry will continue the product stewardship program including the mortality study.

CHANGES IN LUNG FUNCTION OBSERVED IN A STUDY OF PM AND AIR TOXICS EXPOSURE TO NC HIGHWAY PATROL TROOPERS (COPP-STUDY)

EPA Science Inventory

Introduction: Car emissions have been identified as a major source of respirable particles. Individuals whose jobs involve being on the road, such as patrol troopers, may be exposed to high cencentrations of toxic air pollutants from vehicle emissions. This exposure might a...

Health effects of acute exposure to air polllution. Part II: Healthy subjects exposed to cencentrated ambient particles

EPA Science Inventory

The purpose of this study was to assess the impact of short-term exposure to concentrated ambient particles (CAPs*) on lung function and on inflammatory parameters in blood and airways of healthy human subjects. Particles were concentrated from the ambient air in Chapel Hill, Nor...

Pulmonary responses in current smokers and ex-smokers following a two hour exposure at rest to clean air and fine ambient air particles.

EPA Science Inventory

BACKGROUND: Increased susceptibility of smokers to ambient PM may potentially promote development of COPD and accelerate already present disease. OBJECTIVES: To characterize the acute and subacute lung function response and inflammatory effects of controlled chamber exposure t...

The effects of indoor pollution on Arizona children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dodge, R.

1982-05-01

The respiratory health of a large group of Arizona school children who have been exposed to indoor pollutants-tobacco smoke and home cooking fumes-is reported. A significant relationship was found between parental smoking and symptoms of cough, wheeze, and sputum production. Also, children in homes where gas cooking fuel was used had higher rates of cough than children in homes where electricity was used. No differences in pulmonary function or yearly lung growth rates occurred among subjects grouped by exposure to tobacco smoke or cooking fuel. Thus, parental smoking and home cooking fuel affected cross-sectional respiratory symptom rates in a largemore » group of Arizona school children. Study of pulmonary function, however, revealed no lung function or lung growth effects during 4 yr of study.« less

ESR evidence for in vivo formation of free radicals in tissue of mice exposed to single-walled carbon nanotubes.

PubMed

Shvedova, A A; Kisin, E R; Murray, A R; Mouithys-Mickalad, A; Stadler, K; Mason, R P; Kadiiska, M

2014-08-01

Nanomaterials are being utilized in an increasing variety of manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNTs) have found numerous applications in the electronics, aerospace, chemical, polymer, and pharmaceutical industries. Previously, we have reported that pharyngeal exposure of C57BL/6 mice to SWCNTs caused dose-dependent formation of granulomatous bronchial interstitial pneumonia, fibrosis, oxidative stress, acute inflammatory/cytokine responses, and a decrease in pulmonary function. In the current study, we used electron spin resonance (ESR) to directly assess whether exposure to respirable SWCNTs caused formation of free radicals in the lungs and in two distant organs, the heart and liver. Here we report that exposure to partially purified SWCNTs (HiPco technique, Carbon Nanotechnologies, Inc., Houston, TX, USA) resulted in the augmentation of oxidative stress as evidenced by ESR detection of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone spin-trapped carbon-centered lipid-derived radicals recorded shortly after the treatment. This was accompanied by a significant depletion of antioxidants and elevated biomarkers of inflammation presented by recruitment of inflammatory cells and an increase in proinflammatory cytokines in the lungs, as well as development of multifocal granulomatous pneumonia, interstitial fibrosis, and suppressed pulmonary function. Moreover, pulmonary exposure to SWCNTs also caused the formation of carbon-centered lipid-derived radicals in the heart and liver at later time points (day 7 postexposure). Additionally, SWCNTs induced a significant accumulation of oxidatively modified proteins, increase in lipid peroxidation products, depletion of antioxidants, and inflammatory response in both the heart and the liver. Furthermore, the iron chelator deferoxamine noticeably reduced lung inflammation and oxidative stress, indicating an important role for metal-catalyzed species in lung injury caused by SWCNTs. Overall, we provide direct evidence that lipid-derived free radicals are a critical contributor to tissue damage induced by SWCNTs not only in the lungs, but also in distant organs. Published by Elsevier Inc.

Maternal exposure to fine particulate air pollution induces epithelial-to-mesenchymal transition resulting in postnatal pulmonary dysfunction mediated by transforming growth factor-β/Smad3 signaling.

PubMed

Tang, Wenting; Du, Lili; Sun, Wen; Yu, Zhiqiang; He, Fang; Chen, Jingsi; Li, Xiaomei; Li, Xiuying; Yu, Lin; Chen, Dunjin

2017-02-05

Fine particles from air pollution, also called particulate matter, less than 2.5 micrometers in diameter (PM2.5), are a threat to child health. Epidemiological investigations have related maternal exposure to PM2.5 to postnatal respiratory symptoms, such as frequent wheezing, chronic cough, and lung function decrements. However, only few experimental animal studies have been performed to study the effects of PM2.5.The aim of this study was to investigate the effects of maternal exposure to PM2.5 on postnatal pulmonary dysfunction in a rat model and to examine the mechanism of PM2.5-induced morphological pulmonary changes.Timed pregnant Sprague-Dawley rats were treated with PM2.5 (0.1, 0.5, 2.5, or 7.5mg/kg) once every three days from day 0 to 18 of pregnancy. After delivery, pups were sacrificed on postnatal day (PND)1 and 28. The effects of transforming growth factor-beta (TGF-β) on epithelial-mesenchymal transition (EMT) were determined by immunohistochemistry, Western blotting, and quantitative RT-PCR. The offspring underwent pulmonary function measurements on PND28, lung tissues were histopathologically examined, and markers of oxidative stress were measured. Maternally PM2.5-exposed offspring pups displayed significant decreases in lung volume parameters, compliance, and airflow during expiration on PND28. The PM2.5-exposed group showed interstitial proliferation in lung histology, significant oxidative stress in lungs, and up-regulation of TGF-β-induced EMT via increased vimentin and α-smooth muscle actin and decreased E-cadherin levels on PND1 and PND28.These results suggest that EMT up-regulation mediated by the TGF-β/Smad3 pathway plays a role in postnatal pulmonary dysfunction associated with maternal exposure to PM2.5. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Dynamics and Characteristics of Aeolian Dust in Dryland Central Asia: Possible Impacts on Respiratory Health in the Aral Sea Basin

NASA Astrophysics Data System (ADS)

Wiggs, G. F.; O'Hara, S.; Wegerdt, J.; van der Meer, J.; Small, I.; Hubbard, R.

2003-12-01

Over the last 40 years over 36,000 km2 of the former Aral Sea bed have been exposed creating a potentially significant aeolian dust source. It is widely believed, but little researched, that increased dust storm activity in the region has had a major impact on human health. In this paper we report the findings of a study into the link between dust exposure and respiratory health amongst children in the Autonomous Republic of Karakalpakstan, located on the southern shore of the Aral Sea. Data were collected over a 12 month period at 16 sites located within a broad transect running north to south through Karakalpakstan. At each site monthly measurements of dust deposition were undertaken linked with daily meteorological data at 6 stations. At 3 sites weekly measurements of PM10 were also carried out. Approximately 100 children (aged 7-10 years) were randomly selected within 5 km of each dust trap site and data were collected on their respiratory health and environmental exposures. Lung function data were also collected using a handheld spirometer. A linear regression model was used to predict lung function for the children incorporating variables for Forced Expiratory Volume in one second (FEV1), age, gender, height and weight and we estimated the impact of dust deposition rates on the odds of having abnormal lung function using logistic regression. The findings indicate that dust deposition rates across the region are high with sites located near the former shore of the sea being the worst affected. For these northerly regions the former Aral Sea bed is the most likely source of dust. The situation for the rest of the country seems to be far more complex. In these regions it appears that local sources (agricultural fields, abandoned irrigation grounds, overgrazed dunes, and unpaved roads) and more distant sources to the south and south-west represent significant sediment providers, particularly in the early summer when agricultural fields are ploughed. We found some evidence of a dose-related impact of dust levels on lung function. These associations were statistically significant for all measures of dust exposure but were most marked for levels of winter dust exposure and level of PM2.5 exposure. The results from this study suggest that aeolian dust dynamics in the region are spatially and temporally highly variable and, counter to local and regional perceptions, the former bed of the Aral Sea does not appear to be the only significant source. Nevertheless, there is also evidence of a dose-related impact of airborne dust on the risk of having abnormally low lung function in children living in the Aral Sea Area.

Potential for Chlorine Gas–induced Injury in the Extrapulmonary Vasculature

PubMed Central

Samal, Andrey; Honovar, Jaideep; White, C. Roger; Patel, Rakesh P.

2010-01-01

Exposure to chlorine gas (Cl2) primarily causes injury to the lung and is characterized by inflammation and oxidative stress mediated by reactive chlorine species. Reducing lung injury and improving respiratory function are the principal therapeutic goals in treating individuals exposed to Cl2 gas. Less is known on the potential for Cl2 gas exposure to cause injury to extrapulmonary tissues and specifically to mediate endothelial dysfunction. This concept is forwarded in this article on the basis that (1) many irritant gases whose reactivity is limited to the lung have now been shown to have effects that promote endothelial dysfunction in the systemic vasculature, and as such lead to the acute and chronic cardiovascular disease events (e.g., myocardial infarctions and atherosclerosis); and (2) that endogenously produced reactive chlorine species are now considered to be central in the development of cardiovascular diseases. This article discusses these two areas with the view of providing a framework in which potential extrapulmonary toxic effects of Cl2 gas exposure may be considered. PMID:20601634

Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway

PubMed Central

Hwang, Jae-Woong; Sundar, Isaac K.; Yao, Hongwei; Sellix, Michael T.; Rahman, Irfan

2014-01-01

Patients with obstructive lung diseases display abnormal circadian rhythms in lung function. We determined the mechanism whereby environmental tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1, through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung function, and inflammatory and emphysematous responses in the lungs. CS exposure (100–300 mg/m3 particulates) altered clock gene expression and reduced locomotor activity by disrupting the central and peripheral clocks and increased lung inflammation, causing emphysema in mice. BMAL1 was acetylated and degraded in the lungs of mice exposed to CS and in patients with chronic obstructive pulmonary disease (COPD), compared with lungs of the nonsmoking controls, linking it mechanistically to CS-induced reduction of SIRT1. Targeted deletion of Bmal1 in lung epithelium augmented inflammation in response to CS, which was not attenuated by the selective SIRT1 activator SRT1720 (EC50=0.16 μM) in these mice. Thus, the circadian clock, specifically the enhancer BMAL1 in epithelium, plays a pivotal role, mediated by SIRT1-dependent BMAL1, in the regulation of CS-induced lung inflammatory and injurious responses.— Hwang, J.-W., Sundar, I. K., Yao, H., Sellix, M. T., Rahman, I. Circadian clock function is disrupted by environmental tobacco/cigarette smoke, leading to lung inflammation and injury via a SIRT1-BMAL1 pathway. PMID:24025728

Effects of exposure to ambient ultrafine particles on respiratory health and systemic inflammation in children.

PubMed

Clifford, Sam; Mazaheri, Mandana; Salimi, Farhad; Ezz, Wafaa Nabil; Yeganeh, Bijan; Low-Choy, Samantha; Walker, Katy; Mengersen, Kerrie; Marks, Guy B; Morawska, Lidia

2018-05-01

It is known that ultrafine particles (UFP, particles smaller than 0.1 μm) can penetrate deep into the lungs and potentially have adverse health effects. However, epidemiological data on the health effects of UFP is limited. Therefore, our objective was to test the hypothesis that exposure to UFPs is associated with respiratory health status and systemic inflammation among children aged 8 to 11 years. We conducted a cross-sectional study among 655 children (43.3% male) attending 25 primary (elementary) schools in the Brisbane Metropolitan Area, Australia. Ultrafine particle number concentration (PNC) was measured at each school and modelled at homes using Land Use Regression to derive exposure estimates. Health outcomes were respiratory symptoms and diagnoses, measured by parent-completed questionnaire, spirometric lung function, exhaled nitric oxide (FeNO), and serum C reactive protein (CRP). Exposure-response models, adjusted for potential personal and environmental confounders measured at the individual, home and school level, were fitted using Bayesian methods. PNC was not independently associated with respiratory symptoms, asthma diagnosis or spirometric lung function. However, PNC was positively associated with an increase in CRP (1.188-fold change per 1000 UFP cm -3 day/day (95% credible interval 1.077 to 1.299)) and an increase in FeNO among atopic participants (1.054 fold change per 1000 UFP cm -3 day/day (95% CrI 1.005 to 1.106)). UFPs do not affect respiratory health outcomes in children but do have systemic effects, detected here in the form of a positive association with a biomarker for systemic inflammation. This is consistent with the known propensity of UFPs to penetrate deep into the lung and circulatory system. Copyright © 2018 Elsevier Ltd. All rights reserved.

The potential impacts of climate variability and change on air pollution-related health effects in the United States.

PubMed Central

Bernard, S M; Samet, J M; Grambsch, A; Ebi, K L; Romieu, I

2001-01-01

Climate change may affect exposures to air pollutants by affecting weather, anthropogenic emissions, and biogenic emissions and by changing the distribution and types of airborne allergens. Local temperature, precipitation, clouds, atmospheric water vapor, wind speed, and wind direction influence atmospheric chemical processes, and interactions occur between local and global-scale environments. If the climate becomes warmer and more variable, air quality is likely to be affected. However, the specific types of change (i.e., local, regional, or global), the direction of change in a particular location (i.e., positive or negative), and the magnitude of change in air quality that may be attributable to climate change are a matter of speculation, based on extrapolating present understanding to future scenarios. There is already extensive evidence on the health effects of air pollution. Ground-level ozone can exacerbate chronic respiratory diseases and cause short-term reductions in lung function. Exposure to particulate matter can aggravate chronic respiratory and cardiovascular diseases, alter host defenses, damage lung tissue, lead to premature death, and possibly contribute to cancer. Health effects of exposures to carbon monoxide, sulfur dioxide, and nitrogen dioxide can include reduced work capacity, aggravation of existing cardiovascular diseases, effects on pulmonary function, respiratory illnesses, lung irritation, and alterations in the lung's defense systems. Adaptations to climate change should include ensuring responsiveness of air quality protection programs to changing pollution levels. Research needs include basic atmospheric science work on the association between weather and air pollutants; improving air pollution models and their linkage with climate change scenarios; and closing gaps in the understanding of exposure patterns and health effects. PMID:11359687

The potential impacts of climate variability and change on air pollution-related health effects in the United States.

PubMed

Bernard, S M; Samet, J M; Grambsch, A; Ebi, K L; Romieu, I

2001-05-01

Climate change may affect exposures to air pollutants by affecting weather, anthropogenic emissions, and biogenic emissions and by changing the distribution and types of airborne allergens. Local temperature, precipitation, clouds, atmospheric water vapor, wind speed, and wind direction influence atmospheric chemical processes, and interactions occur between local and global-scale environments. If the climate becomes warmer and more variable, air quality is likely to be affected. However, the specific types of change (i.e., local, regional, or global), the direction of change in a particular location (i.e., positive or negative), and the magnitude of change in air quality that may be attributable to climate change are a matter of speculation, based on extrapolating present understanding to future scenarios. There is already extensive evidence on the health effects of air pollution. Ground-level ozone can exacerbate chronic respiratory diseases and cause short-term reductions in lung function. Exposure to particulate matter can aggravate chronic respiratory and cardiovascular diseases, alter host defenses, damage lung tissue, lead to premature death, and possibly contribute to cancer. Health effects of exposures to carbon monoxide, sulfur dioxide, and nitrogen dioxide can include reduced work capacity, aggravation of existing cardiovascular diseases, effects on pulmonary function, respiratory illnesses, lung irritation, and alterations in the lung's defense systems. Adaptations to climate change should include ensuring responsiveness of air quality protection programs to changing pollution levels. Research needs include basic atmospheric science work on the association between weather and air pollutants; improving air pollution models and their linkage with climate change scenarios; and closing gaps in the understanding of exposure patterns and health effects.

Role of CYP1A2 polymorphisms on lung cancer risk in a prospective study.

PubMed

Pavanello, Sofia; Fedeli, Ugo; Mastrangelo, Giuseppe; Rota, Federica; Overvad, Kim; Raaschou-Nielsen, Ole; Tjønneland, Anne; Vogel, Ulla

2012-06-01

Cytochrome P4501A2 (CYP1A2) is a key enzyme for lung carcinogen activation and lung inflammation. We studied the interactions of the CYP1A2 functional variants -3860G/A(rs2069514),-2467T/delT(rs3569413),-163C/A(rs762551)] with occupational/environmental carcinogenic exposures in the development of lung cancer in a case-control study nested in the Danish prospective cohort "Diet, Cancer and Health." At enrollment (1993-1997), blood samples for genotype analyses and information on lifestyle were collected 5 (mean value) years before the onset of the disease. The study population included 425 lung cancer cases and 786 subcohort members, who were gender- and age-matched. We found that -163A carriers were at increased risk of lung cancer (P=0.035) in a multivariate COX regression model, which was adjusted for personal habits (i.e., cumulative smoking, passive smoke at home, alcohol intake, and fruit intake) and occupational exposure. Additionally, the interaction between -2467delT and smoking increases lung cancer risk in males, especially light smokers (<21.5 pack-years, P=0.004). The increased lung cancer risk found in -163C carriers, independent of smoking status, and in -2467delT male smokers, suggests that these variants could influence lung cancer development through different mechanisms (i.e. lung carcinogen activation and lung inflammation). Copyright © 2012 Elsevier Inc. All rights reserved.

Occupational Pesticide Exposures and Respiratory Health

PubMed Central

Ye, Ming; Beach, Jeremy; Martin, Jonathan W.; Senthilselvan, Ambikaipakan

2013-01-01

Pesticides have been widely used to control pest and pest-related diseases in agriculture, fishery, forestry and the food industry. In this review, we identify a number of respiratory symptoms and diseases that have been associated with occupational pesticide exposures. Impaired lung function has also been observed among people occupationally exposed to pesticides. There was strong evidence for an association between occupational pesticide exposure and asthma, especially in agricultural occupations. In addition, we found suggestive evidence for a link between occupational pesticide exposure and chronic bronchitis or COPD. There was inconclusive evidence for the association between occupational pesticide exposure and lung cancer. Better control of pesticide uses and enforcement of safety behaviors, such as using personal protection equipment (PPE) in the workplace, are critical for reducing the risk of developing pesticide-related symptoms and diseases. Educational training programs focusing on basic safety precautions and proper uses of personal protection equipment (PPE) are possible interventions that could be used to control the respiratory diseases associated with pesticide exposure in occupational setting. PMID:24287863

Lung function indices of children exposed to wood smoke in a fishing port in South-South Nigeria.

PubMed

Oloyede, Iso P; Ekrikpo, Udeme E; Ekanem, Emmanuel E

2013-10-01

Children in the warm rain forest are at risk of having their lung function compromised by a variety of factors, including smoke from wood fires. A total of 358 children from a fishing port and 400 children living in a farm settlement were tested to determine their peak expiratory flow rate (PEFR), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory volume in 1 s per cent and forced expiratory flow between 25 and 75%. The values for the PEFR, FVC, FEV1, forced expiratory volume in 1 s per cent and forced expiratory flow between 25 and 75% of the subjects were significantly lower than those of the controls (P value for males = <0.001, 0.01, 0.002, 0.01 and <0.001, respectively, whereas for their female counterparts = <0.001, 0.003, 0.001, 0.04 and <0.001, respectively). These deficits were observed to be more with increasing duration of exposure to wood smoke for PEFR, FVC and FEV1. Chronic exposure to fish drying using firewood can impair lung function in children. There is a need for alternative methods of fish preservation for those engaged in fish drying.

Predictors of microbial agents in dust and respiratory health in the Ecrhs.

PubMed

Tischer, Christina; Zock, Jan-Paul; Valkonen, Maria; Doekes, Gert; Guerra, Stefano; Heederik, Dick; Jarvis, Deborah; Norbäck, Dan; Olivieri, Mario; Sunyer, Jordi; Svanes, Cecilie; Täubel, Martin; Thiering, Elisabeth; Verlato, Giuseppe; Hyvärinen, Anne; Heinrich, Joachim

2015-05-02

Dampness and mould exposure have been repeatedly associated with respiratory health. However, less is known about the specific agents provoking or arresting health effects in adult populations. We aimed to assess predictors of microbial agents in mattress dust throughout Europe and to investigate associations between microbial exposures, home characteristics and respiratory health. Seven different fungal and bacterial parameters were assessed in mattress dust from 956 adult ECRHS II participants in addition to interview based home characteristics. Associations between microbial parameters and the asthma score and lung function were examined using mixed negative binomial regression and linear mixed models, respectively. Indoor dampness and pet keeping were significant predictors for higher microbial agent concentrations in mattress dust. Current mould and condensation in the bedroom were significantly associated with lung function decline and current mould at home was positively associated with the asthma score. Higher concentrations of muramic acid were associated with higher mean ratios of the asthma score (aMR 1.37, 95%CI 1.17-1.61). There was no evidence for any association between fungal and bacterial components and lung function. Indoor dampness was associated with microbial levels in mattress dust which in turn was positively associated with asthma symptoms.

Toxicity of Paraquat and Diquat Aerosols Generated by a Size-selective Cyclone: Effect of Particle Size Distribution

PubMed Central

Gage, J. C.

1968-01-01

The toxicity of paraquat and diquat aerosols to several species has been investigated. In order to obtain an atmosphere of `respirable' particles, an atomizer has been constructed with an upper cut-off of size by a cyclone separator, and with a calibrated reservoir to enable the concentration output to be estimated by inspection. Paraquat has an irritant action on the lungs, and at lethal concentrations death is delayed and is associated with pulmonary haemorrhage and oedema. After single exposures the LC50 appears to be a function of the duration and of the concentration; in the rat the lethal concentration-time product (CT) is about 6 μg./l.hr. Guinea-pigs and male mice are about as sensitive as rats. Female mice and rabbits are less sensitive. The dog can tolerate a CT product of 25 μg./l. hr without ill-effects. The toxicity is a complex function of particle size. In the rat it appears that the most effective size is in the region of 3 μ, as larger particles do not reach the alveolar regions and finer particles are probably not retained there. Repeated daily 6-hr exposures of rats to paraquat aerosols over a three-week period produce signs of lung irritation but no deaths at 0·4 μg./l., and the no-effect level is about 0·1 μg./litre. Paraquat appears to be poorly absorbed from the lungs. After single exposures death is associated with a paraquat content of about 6 μg. in the lungs. Paraquat is subsequently cleared from the lung with a half-life of about 36 hr. Diquat is much less irritant to the lungs than is paraquat; the no-effect levels on single and repeated exposure are at least five times larger. It is concluded that paraquat and diquat do not present an inhalation hazard under normal conditions of application, but with paraquat under abnormal conditions it may be desirable to provide respiratory protection. Images PMID:5723352

[Effect of dust aerosol exposure on lung function and lung histopathology in rats].

PubMed

Lei, Fengfeng; Wang, Xuebin; Liu, Hua; Chen, Qizhang; Ma, Hui; Dong, Zhibao; Sang, Yingzhu

2015-08-25

To investigate the effect of dust aerosol exposure on lung function and lung histopathology in rats. According to random number table method, 120 Wistar male rats were divided into untreated control group, treated control group and experimental group, with 40 rats in each group. Experimental group were exposed to the wind tunnel simulation of sandstorm for 5 hours in every day; the untreated control group were put in the standard living environment next to the wind tunnel; the treated control group were exposed to the same wind tunnel simulation of sandstorm for 5 hours in every day, and the speed of wind was the same as the experimental group, but excluding dust. At different time points, the lung function and electron microscopy were performed in all rats. The level of Dynamic Compliance (Cdyn) ((0.227 ± 0.023), (0.198 ± 0.022) ml/cmH₂O, 1 cmH₂O=0.098 kPa) and forced vital capacity (FVC) ((6.24 ± 0.29), (5.59 ± 0.19) ml) were lower in the experimental group at 90 and 120 days, as compared to the untreated control group (Cdyn: (0.266 ± 0.014), (0.265 ± 0.018) ml/cmH2O; FVC: (7.15 ± 0.23), (7.17 ± 0.20) ml) and treated control group (Cdyn: (0.269 ± 0.015), (0.264 ± 0.019) ml/cmH2O; FVC: (7.14 ± 0.19), (7.15 ± 0.21) ml) (all P<0.05). At 120 days, The level of the forced expiratory flow after 50% of the FVC ((12.3 ± 2.2) ml/s) and peak expiratory flow ((25.79 ± 0.42) ml/s) were lower in the experimental group, as compared to the untreated control group ((15.9 ± 2.5), (27.99 ± 0.36) ml/s) and treated control group ((15.8 ± 2.1), (27.90 ± 0.38) ml/s) (all P<0.01). The FVC rate of 0.2 second in the experimental group was higher than that in the untreated control group and treated control group ( (85 ± 5)%, (73 ± 4)%, (73 ± 4)%, all P<0.05). The electron microscopy showed that the lung tissues had no obvious abnormalities at 30, 60, 90 and 120 days in untreated control group and treated control group. But in the experimental group, at 30 days, the endothelial cells of alveolar type I cells were swelled and the number of alveolar type II cells were increased; at 60 days, alveolar type II cells hyperplastic, basement membrane thinned and destructed; at 90 days, the number of alveolar type II cells decreased, Lamellar body evacuation; at 120 days, a lot of collagen fiber was formed in the alveolar septa. The strong sandstorm environmental exposure to a certain period of time can cause the decline of lung function and the damage of lung histopathology in rats. Exposure time was positively correlated with the damage of lung tissue.

Association between lung function in school children and exposure to three transition metals from an e-waste recycling area.

PubMed

Zheng, Guina; Xu, Xijin; Li, Bin; Wu, Kusheng; Yekeen, Taofeek Akangbe; Huo, Xia

2013-01-01

The informal processing of electronic waste or e-waste contributes to the release of high concentrations of transition metals into the ambient air. The damage caused by chromium, nickel and manganese exposure on lung function in school children from an e-waste recycling area and the role of oxidative stress in this process were evaluated. We recruited school children (n=144, 8-13 years) from an e-waste recycling area in China compared with the control. Spirometry was performed to assess lung function status. The blood levels of chromium, nickel and manganese, antioxidant enzyme activities and lipid peroxidation of the subjects were examined. The concentrations of blood manganese (bMn) and serum nickel (sNi) in the exposed group were significantly higher than those in controls for all three age groups. The forced vital capacity value of boys aged 8-9 years was significantly lower than that of the control. Malondialdehyde levels and superoxide dismutase activities increased significantly in children aged 8-9 years from e-waste environment, but catalase activities declined. School children from an e-waste recycling area were exposed to high levels of the three transition metals. The accumulation of bMn and sNi may be risk factors for oxidative damage and decreased pulmonary function.

Welding fume exposure and chronic obstructive pulmonary disease in welders.

PubMed

Koh, D-H; Kim, J-I; Kim, K-H; Yoo, S-W

2015-01-01

Occupational exposure is estimated to contribute 15% to the burden of chronic obstructive pulmonary disease (COPD). Welding fumes are suspected to accelerate the decline of lung function and development of COPD. To examine the relationship between welding fume exposure and COPD in Korean shipyard welders. The study involved a group of male welders working at two shipyards who underwent an annual health examination in 2010. Subjects completed a questionnaire about smoking habits and occupational history and a pulmonary function test (PFT) was carried out with strict quality control measures. Welding fume exposure concentrations were estimated using 884 measurements taken between 2002 and 2009 in one of the shipyards. Multiple linear and logistic regression was employed to evaluate the association between cumulative fume exposure and lung function parameters, controlling for age, height and cigarette smoking. Two hundred and forty subjects participated, with a mean age of 48 and mean work duration of 15 years. The mean cumulative fume exposure was 7.7mg/m(3). The prevalence of COPD was 15%. FEV1 and FVC showed non-significant negative correlations with cumulative fume exposure. Odds ratios of COPD were significantly elevated for the middle (3.9; 95% CI 1.4-13.3) and high exposure groups (3.8; 95% CI 1.03-16.2) compared with the low fume exposure group. Our findings support an association between welding fume exposure and increased risk of COPD. Further prospective study is needed to investigate whether this is a causal relationship. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lung cancer risk, silica exposure, and silicosis in Chinese mines and pottery factories: the modifying role of other workplace lung carcinogens.

PubMed

Cocco, P; Rice, C H; Chen, J Q; McCawley, M A; McLaughlin, J K; Dosemeci, M

2001-12-01

Aims of our study were to explore whether and to what extent exposure to other lung carcinogens, or staging and clinical features of silicosis modify or confound the association between silica and lung cancer. We used data from a nested case-control study, conducted in the late 1980s in 29 Chinese mines and potteries (10 tungsten mines, 6 copper and iron mines, 4 tin mines, 8 pottery factories, and 1 clay mine), that included 316 lung cancer cases and 1,356 controls, matched by decade of birth and facility type. The previous analysis of these data presented results by type of mine or factory. In our study, pooling all 29 Chinese work sites, lung cancer risk showed a modest association with silica exposure. Risk did not vary after excluding subjects with silicosis or adjusting the risk estimates by radiological staging of silicosis. Strong correlation among exposures prevented a detailed evaluation of the role of individual exposures. However, lung cancer risk was for the most part absent when concomitant exposure to other workplace lung carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), nickel or radon-daughters, was considered. The cross classification of lung cancer risk by categories of exposure to respirable silica and total respirable dust did not show an independent effect of total respirable dust. Silicosis showed a modest association with lung cancer, which did not vary by severity of radiological staging, or by radiological evidence of disease progression, or by level of silica exposure. However, among silicotic subjects, lung cancer risk was significantly elevated only when exposure to cadmium and PAH had occurred. Our results suggest that, among silica-exposed Chinese workers, numerous occupational and non-occupational risk factors interact in a complex fashion to modify lung cancer risk. Future epidemiological studies on silica and lung cancer should incorporate detailed information on exposure to other workplace lung carcinogens, total respirable dust, and on surface size and age of silica particles to understand whether and to what extent they affect the carcinogenic potential of silica. Copyright 2001 Wiley-Liss, Inc

Lung function in retired coke oven plant workers.

PubMed Central

Chau, N; Bertrand, J P; Guenzi, M; Mayer, L; Téculescu, D; Mur, J M; Patris, A; Moulin, J J; Pham, Q T

1992-01-01

Lung function was studied in 354 coke oven plant workers in the Lorraine collieries (Houillères du Bassin de Lorraine, France) who retired between 1963 and 1982 and were still alive on 1 January 1988. A spirometric examination was performed on 68.4% of them in the occupational health service. Occupational exposure to respiratory hazards throughout their career was retraced for each subject. No adverse effect of occupational exposure on ventilatory function was found. Ventilatory function was, however negatively linked with smoking and with the presence of a respiratory symptom or discrete abnormalities visible on pulmonary x ray films. The functional values were mostly slightly lower than predicted values and the most reduced index was the mean expiratory flow, FEF25-75%. The decrease in forced expiratory volume in one second (FEV1) was often parallel to that in forced vital capacity (FVC), but it was more pronounced for subjects who had worked underground, for smokers of more than 30 pack-years, and for subjects having a respiratory symptom. Pulmonary function indices were probably overestimated because of the exclusion of deceased subjects and the bias of the participants. PMID:1599869

[Comparative studies on toxicity of various dielectrics, petroleum derivatives, used in electroerosion technology. IV. Morphological and cytoenzymatic changes in the lungs and acid-base imbalance in rats chronically exposed to petroleum hydrocarbons].

PubMed

Starek, A; Kamiński, M

1981-01-01

In rats exposed to odourless kerosene of 75 and 300 mg/m3 concentration, for 14 weeks, morphologic and cytoenzymatic examinations of lungs have been carried out and acid-base equilibrium indices in blood have been determined. Passive congestion of lung parenchyma, subpleural blood extravasation, atelectasis foci, thickened interalveolar septa with infiltrates from neutrophils, lymphocytes, eosinophils and macrophages have been found. In addition a decrease in succinic dehydrogenase activity, NADPH -- tetrazolium reductase, and Mg++-ATP-ase and increase in acid phosphatase activity have been revealed. Those have been focal changes, involving, apart from bronchial tree (low exposure -- 75 mg/m3), the remaining lung parenchyma segments (high exposure -- 300 mg/m3). In addition, disturbances in acid-base equilibrium in form of compensated metabolic alkalosis (75 mg/m3) and compensated metabolic acidosis (300 mg/m3) have occurred. The obtained results demonstrate toxic effects of kerosene hydrocarbons on the function and structure of lungs.

Lung cancer incidence attributable to residential radon exposure in Alberta in 2012

PubMed Central

Grundy, Anne; Brand, Kevin; Khandwala, Farah; Poirier, Abbey; Tamminen, Sierra; Friedenreich, Christine M.; Brenner, Darren R.

2017-01-01

Background: Radon is carcinogenic, and exposure to radon has been shown to increase the risk of lung cancer. The objective of this study was to quantify the proportion and number of lung cancer cases in Alberta in 2012 that could be attributed to residential radon exposure. Methods: We estimated the population attributable risk of lung cancer for residential radon using radon exposure data from the Cross-Canada Survey of Radon Concentrations in Homes from 2009-2011 and data on all-cause and lung cancer mortality from Statistics Canada from 2008-2012. We used cancer incidence data from the Alberta Cancer Registry for 2012 to estimate the total number of lung cancers attributable to residential radon exposure. Estimates were also stratified by sex and smoking status. Results: The mean geometric residential radon level in Alberta in 2011 was 71.0 Bq/m3 (geometric standard deviation 2.14). Overall, an estimated 16.6% (95% confidence interval 9.4%-29.8%) of lung cancers were attributable to radon exposure, corresponding to 324 excess attributable cancer cases. The estimated population attributable risk of lung cancer due to radon exposure was higher among those who had never smoked (24.8%) than among ever smokers (15.6%). However, since only about 10% of cases of lung cancer occur in nonsmokers, the estimated total number of excess cases was higher for ever smokers (274) than for never smokers (48). Interpretation: With about 17% of lung cancer cases in Alberta in 2012 attributable to residential radon exposure, exposure reduction has the potential to substantially reduce Alberta's lung cancer burden. As such, home radon testing and remediation techniques represent important cancer prevention strategies. PMID:28663187

Cardiovascular Disease Biomarkers Predict Susceptibility or Resistance to Lung Injury in World Trade Center Dust Exposed Firefighters

PubMed Central

Weiden, Michael D.; Naveed, Bushra; Kwon, Sophia; Cho, Soo Jung; Comfort, Ashley L.; Prezant, David J.; Rom, William N.; Nolan, Anna

2013-01-01

Pulmonary vascular loss is an early feature of chronic obstructive pulmonary disease. Biomarkers of inflammation and of metabolic syndrome, predicts loss of lung function in World Trade Center Lung Injury (WTC-LI). We investigated if other cardiovascular disease (CVD) biomarkers also predicted WTC-LI. This nested case-cohort study used 801 never smoker, WTC exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March, 2008. A representative sub-cohort of 124/801 with serum drawn within six months of 9/11 defined CVD biomarker distribution. Post-9/11/01 FEV1 at subspecialty exam defined cases: susceptible WTC-LI cases with FEV1≤77% predicted (66/801) and resistant WTC-LI cases with FEV1≥107% (68/801). All models were adjusted for WTC exposure intensity, BMI at SPE, age at 9/11, and pre-9/11 FEV1. Susceptible WTC-LI cases had higher levels of Apo-AII, CRP, and MIP-4 with significant RRs of 3.85, 3.93, and 0.26 respectively with an area under the curve (AUC) of 0.858. Resistant WTC-LI cases had significantly higher sVCAM and lower MPO with RRs of 2.24, and 2.89 respectively; AUC 0.830. Biomarkers of CVD in serum six-month post-9/11 predicted either susceptibility or resistance to WTC-LI. These biomarkers may define pathways producing or protecting subjects from pulmonary vascular disease and associated loss of lung function after an irritant exposure. PMID:22903969

Effect of radon on the immune system: alterations in the cellularity and functions of T cells in lymphoid organs of mouse.

PubMed

Nagarkatti, M; Nagarkatti, P S; Brooks, A

1996-04-19

Exposure to radon and its progeny induces significant damage to the cells of the respiratory tract and causes lung cancer. Whether a similar exposure to radon would alter the functions of the immune system has not been previously investigated. In the current study, we investigated the effect of exposure of C57BL/6 mice to 1000 or 2500 working-level months (WLM) of radon and its progeny by inhalation, on the number and function of T lymphocytes in lymphoid organs. The control mice received uranium ore dust carrier aerosol by inhalation. Exposure to radon induced marked decrease in the total cellularity of most lymphoid organs such as thymus, peripheral lymph nodes (PLN), and lung-associated lymph nodes (LALN), when compared to the controls. The percentage of T cells increased, while that of non-T cells decreased, in all peripheral lymphoid organs at both the doses of radon. In the thymus, particularly at 2500 WLM of radon exposure, there was a marked decrease in CD4+CD8+ T cells and an increase in the immature CD4-CD8- T cells. Such alterations in both the numbers and percentages of lymphocytes and macrophages in radon-exposed mice may have resulted from the cell killing by the alpha particles as the immune cells were migrating through the lungs, or it may have been caused by altered migration of cells, inasmuch as expression of CD44, a molecule involved in migration and homing of immune cells, was significantly altered on cells found in different lymphoid organs. In the LALN, where one would predict the largest number of damaged cells to be present, there was a significant decrease in the T-cell responsiveness to mitogens while the B-cell response was not affected. Such alterations may have resulted from the direct effect of alpha-particle exposure on the migrating lymphocytes, altered percentage of lymphocytes as seen in secondary lymphoid organs, or altered expression of adhesion molecules involved in cell activation such as CD44 and CD3. Interestingly, radon exposure caused and increase in the T- and B-cell responsiveness to mitogens in the spleen and PLN. Since there is little evidence of direct radiation dose from radon in lymphoid organs, our studies demonstrating immunological alterations suggest an indirect effect of radon exposure that may have significant repercussions on the development of hypersensitivity and increased susceptibility to infections and cancer in the lung.

Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides.

PubMed

Schweitzer, Kelly S; Hatoum, Hadi; Brown, Mary Beth; Gupta, Mehak; Justice, Matthew J; Beteck, Besem; Van Demark, Mary; Gu, Yuan; Presson, Robert G; Hubbard, Walter C; Petrache, Irina

2011-12-01

The epithelial and endothelial cells lining the alveolus form a barrier essential for the preservation of the lung respiratory function, which is, however, vulnerable to excessive oxidative, inflammatory, and apoptotic insults. Whereas profound breaches in this barrier function cause pulmonary edema, more subtle changes may contribute to inflammation. The mechanisms by which cigarette smoke (CS) exposure induce lung inflammation are not fully understood, but an early alteration in the epithelial barrier function has been documented. We sought to investigate the occurrence and mechanisms by which soluble components of mainstream CS disrupt the lung endothelial cell barrier function. Using cultured primary rat microvascular cell monolayers, we report that CS induces endothelial cell barrier disruption in a dose- and time-dependent manner of similar magnitude to that of the epithelial cell barrier. CS exposure triggered a mechanism of neutral sphingomyelinase-mediated ceramide upregulation and p38 MAPK and JNK activation that were oxidative stress dependent and that, along with Rho kinase activation, mediated the endothelial barrier dysfunction. The morphological changes in endothelial cell monolayers induced by CS included actin cytoskeletal rearrangement, junctional protein zonula occludens-1 loss, and intercellular gap formation, which were abolished by the glutathione modulator N-acetylcysteine and ameliorated by neutral sphingomyelinase inhibition. The direct application of ceramide recapitulated the effects of CS, by disrupting both endothelial and epithelial cells barrier, by a mechanism that was redox and apoptosis independent and required Rho kinase activation. Furthermore, ceramide induced dose-dependent alterations of alveolar microcirculatory barrier in vivo, measured by two-photon excitation microscopy in the intact rat. In conclusion, soluble components of CS have direct endothelial barrier-disruptive effects that could be ameliorated by glutathione modulators or by inhibitors of neutral sphingomyelinase, p38 MAPK, JNK, and Rho kinase. Amelioration of endothelial permeability may alleviate lung and systemic vascular dysfunction associated with smoking-related chronic obstructive lung diseases.

Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury.

PubMed

Hong, Ji Young; Shin, Mi Hwa; Douglas, Ivor S; Chung, Kyung Soo; Kim, Eun Young; Jung, Ji Ye; Kang, Young Ae; Kim, Se Kyu; Chang, Joon; Kim, Young Sam; Park, Moo Suk

2016-11-01

Eph-Ephrin signalling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homoeostasis and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signalling are unknown. In the present study, we evaluated the role of EphA2 signalling in mice with lipopolysaccharide (LPS)-induced lung injury. Acute LPS exposure significantly up-regulated EphA2 and EphrinA1 expression. Compared with LPS+IgG mice (IgG instillation after LPS exposure), LPS+EphA2 mAb mice [EphA2 monoclonal antibody (mAb) instillation posttreatment after LPS exposure] had attenuated lung injury and reduced cell counts and protein concentration of bronchoalveolar lavage fluid (BALF). EphA2 mAb posttreatment down-regulated the expression of phosphoinositide 3-kinases (PI3K) 110γ, phospho-Akt, phospho-NF-κB p65, phospho-Src and phospho-S6K in lung lysates. In addition, inhibiting the EphA2 receptor augmented the expression of E-cadherin, which is involved in cell-cell adhesion. Our study identified EphA2 receptor as an unrecognized modulator of several signalling pathways-including PI3K-Akt-NF-kB, Src-NF-κB, E-cadherin and mTOR-in LPS-induced lung injury. These results suggest that EphA2 receptor inhibitors may function as novel therapeutic agents for LPS-induced lung injury. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Lung Macrophages “Digest” Carbon Nanotubes Using a Superoxide/Peroxynitrite Oxidative Pathway

PubMed Central

2015-01-01

In contrast to short-lived neutrophils, macrophages display persistent presence in the lung of animals after pulmonary exposure to carbon nanotubes. While effective in the clearance of bacterial pathogens and injured host cells, the ability of macrophages to “digest” carbonaceous nanoparticles has not been documented. Here, we used chemical, biochemical, and cell and animal models and demonstrated oxidative biodegradation of oxidatively functionalized single-walled carbon nanotubes via superoxide/NO* → peroxynitrite-driven oxidative pathways of activated macrophages facilitating clearance of nanoparticles from the lung. PMID:24871084

Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices.

PubMed

Kim, Yong Ho; Tong, Haiyan; Daniels, Mary; Boykin, Elizabeth; Krantz, Q Todd; McGee, John; Hays, Michael; Kovalcik, Kasey; Dye, Janice A; Gilmour, M Ian

2014-06-16

Emissions from a large peat fire in North Carolina in 2008 were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments. Size-fractionated particulate matter (PM; ultrafine, fine, and coarse) were obtained from the peat fire while smoldering (ENCF-1) or when nearly extinguished (ENCF-4). Extracted samples were analyzed for chemical constituents and endotoxin content. Female CD-1 mice were exposed via oropharyngeal aspiration to 100 μg/mouse, and assessed for relative changes in lung and systemic markers of injury and inflammation. At 24 h post-exposure, hearts were removed for ex vivo functional assessments and ischemic challenge. Lastly, 8 mm diameter lung slices from CD-1 mice were exposed (11 μg) ± co-treatment of PM with polymyxin B (PMB), an endotoxin-binding compound. On an equi-mass basis, coarse ENCF-1 PM had the highest endotoxin content and elicited the greatest pro-inflammatory responses in the mice including: increases in bronchoalveolar lavage fluid protein, cytokines (IL-6, TNF-α, and MIP-2), neutrophils and intracellular reactive oxygen species (ROS) production. Exposure to fine or ultrafine particles from either period failed to elicit significant lung or systemic effects. In contrast, mice exposed to ENCF-1 ultrafine PM developed significantly decreased cardiac function and greater post-ischemia-associated myocardial infarction. Finally, similar exposures to mouse lung slices induced comparable patterns of cytokine production; and these responses were significantly attenuated by PMB. The findings suggest that exposure to coarse PM collected during a peat fire causes greater lung inflammation in association with endotoxin and ROS, whereas the ultrafine PM preferentially affected cardiac responses. In addition, lung tissue slices were shown to be a predictive, alternative assay to assess pro-inflammatory effects of PM of differing size and composition. Importantly, these toxicological findings were consistent with the cardiopulmonary health effects noted in epidemiologic reports from exposed populations.

Cardiopulmonary toxicity of peat wildfire particulate matter and the predictive utility of precision cut lung slices

PubMed Central

2014-01-01

Background Emissions from a large peat fire in North Carolina in 2008 were associated with increased hospital admissions for asthma and the rate of heart failure in the exposed population. Peat fires often produce larger amounts of smoke and last longer than forest fires, however few studies have reported on their toxicity. Moreover, reliable alternatives to traditional animal toxicity testing are needed to reduce the number of animals required for hazard identification and risk assessments. Methods Size-fractionated particulate matter (PM; ultrafine, fine, and coarse) were obtained from the peat fire while smoldering (ENCF-1) or when nearly extinguished (ENCF-4). Extracted samples were analyzed for chemical constituents and endotoxin content. Female CD-1 mice were exposed via oropharyngeal aspiration to 100 μg/mouse, and assessed for relative changes in lung and systemic markers of injury and inflammation. At 24 h post-exposure, hearts were removed for ex vivo functional assessments and ischemic challenge. Lastly, 8 mm diameter lung slices from CD-1 mice were exposed (11 μg) ± co-treatment of PM with polymyxin B (PMB), an endotoxin-binding compound. Results On an equi-mass basis, coarse ENCF-1 PM had the highest endotoxin content and elicited the greatest pro-inflammatory responses in the mice including: increases in bronchoalveolar lavage fluid protein, cytokines (IL-6, TNF-α, and MIP-2), neutrophils and intracellular reactive oxygen species (ROS) production. Exposure to fine or ultrafine particles from either period failed to elicit significant lung or systemic effects. In contrast, mice exposed to ENCF-1 ultrafine PM developed significantly decreased cardiac function and greater post-ischemia-associated myocardial infarction. Finally, similar exposures to mouse lung slices induced comparable patterns of cytokine production; and these responses were significantly attenuated by PMB. Conclusions The findings suggest that exposure to coarse PM collected during a peat fire causes greater lung inflammation in association with endotoxin and ROS, whereas the ultrafine PM preferentially affected cardiac responses. In addition, lung tissue slices were shown to be a predictive, alternative assay to assess pro-inflammatory effects of PM of differing size and composition. Importantly, these toxicological findings were consistent with the cardiopulmonary health effects noted in epidemiologic reports from exposed populations. PMID:24934158

Temporal Trend in Lung Cancer Burden Attributed to Ambient Fine Particulate Matter in Guangzhou, China.

PubMed

Liao, Yu; Xu, Lin; Lin, Xiao; Hao, Yuan Tao

2017-10-01

To estimate the lung cancer burden that may be attributable to ambient fine particulate matter (PM2.5) pollution in Guangzhou city in China from 2005 to 2013. The data regarding PM2.5 exposure were obtained from the 'Ambient air pollution exposure estimation for the Global Burden of Disease 2013' dataset at 0.1° ×0.1° spatial resolution. Disability-adjusted life years (DALYs) were estimated based on the information of mortality and incidence of lung cancer. Comparative risk analysis and integrated exposure-response function were used to estimate attributed disease burden. The population-weighted average concentration of PM2.5 was increased by 34.6% between 1990 and 2013, from 38.37 μg/m3 to 51.31 μg/m3. The lung cancer DALYs in both men and women were increased by 36.2% from 2005 to 2013. The PM2.5 attributed lung cancer DALYs increased from 12105.0 (8181.0 for males and 3924.0 for females) in 2005 to 16489.3 (11291.7 for males and 5197.6 for females) in 2013. An average of 23.1% lung cancer burden was attributable to PM2.5 pollution in 2013. PM2.5 has caused serious but under-appreciated public health burden in Guangzhou and the trend deteriorates. Effective strategies are needed to tackle this major public health problem. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Occupational exposures to leaded and unleaded gasoline engine emissions and lung cancer risk.

PubMed

Xu, Mengting; Siemiatycki, Jack; Lavoué, Jérôme; Pasquet, Romain; Pintos, Javier; Rousseau, Marie-Claude; Richardson, Lesley; Ho, Vikki

2018-04-01

To determine whether occupational exposure to gasoline engine emissions (GEE) increased the risk of lung cancer and more specifically whether leaded or unleaded GEE increased the risk. Two population-based case-control studies were conducted in Montreal, Canada. The first was conducted in the early 1980s and included many types of cancer including lung cancer. The second was conducted in the late 1990s and focused on lung cancer. Population controls were used in both studies. Altogether, there were 1595 cases and 1432 population controls. A comprehensive expert-based exposure assessment procedure was implemented and exposure was assessed for 294 agents, including unleaded GEE, leaded GEE and diesel engine emissions (DEE). Logistic regression analyses were conducted to estimate ORs between various metrics of GEE exposure and lung cancer, adjusting for smoking, DEE and other potential confounders. About half of all controls were occupationally exposed to GEE. Irrespective of the metrics of exposure (any exposure, duration of exposure and cumulative exposure) and the type of lung cancer, and the covariates included in models, none of the point estimates of the ORs between occupational exposure to leaded or unleaded GEE and lung cancer were above 1.0. Pooling two studies, the OR for any exposure to leaded GEE was 0.82 (0.68-1.00). Our results do not support the hypothesis that occupational exposure to GEE increases the risk of lung cancer. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure.

PubMed

Park, Robert M; Stayner, Leslie T; Petersen, Martin R; Finley-Couch, Melissa; Hornung, Richard; Rice, Carol

2012-05-01

Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940-2002), a revised cadmium (Cd) exposure matrix and improved work history information. Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure-response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m(3) Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20-25 years. These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 μg/m(3) Cd.

Household Air Pollution Exposure and Influence of Lifestyle on Respiratory Health and Lung Function in Belizean Adults and Children: A Field Study.

PubMed

Kurti, Stephanie P; Kurti, Allison N; Emerson, Sam R; Rosenkranz, Richard R; Smith, Joshua R; Harms, Craig A; Rosenkranz, Sara K

2016-06-28

Household air pollution (HAP) contributes to the global burden of disease. Our primary purpose was to determine whether HAP exposure was associated with reduced lung function and respiratory and non-respiratory symptoms in Belizean adults and children. Our secondary purpose was to investigate whether lifestyle (physical activity (PA) and fruit and vegetable consumption (FV)) is associated with reported symptoms. Belizean adults (n = 67, 19 Male) and children (n = 23, 6 Male) from San Ignacio Belize and surrounding areas participated in this cross-sectional study. Data collection took place at free walk-in clinics. Investigators performed initial screenings and administered questionnaires on (1) sources of HAP exposure; (2) reported respiratory and non-respiratory symptoms and (3) validated lifestyle questionnaires. Participants then performed pulmonary function tests (PFTs) and exhaled breath carbon monoxide (CO). There were no significant associations between HAP exposure and pulmonary function in adults. Increased exhaled CO was associated with a significantly lower forced expiratory volume in 1-s divided by forced vital capacity (FEV₁/FVC) in children. Exposed adults experienced headaches, burning eyes, wheezing and phlegm production more frequently than unexposed adults. Adults who met PA guidelines were less likely to experience tightness and pressure in the chest compared to those not meeting guidelines. In conclusion, adults exposed to HAP experienced greater respiratory and non-respiratory symptoms, which may be attenuated by lifestyle modifications.

Hypersensitivity pneumonitis and related conditions in the work environment.

PubMed

Zacharisen, Michael C; Fink, Jordan N

2011-11-01

Hypersensitivity pneumonitis can occur from a wide variety of occupational exposures. Although uncommon and difficult to recognize, through a detailed work exposure history, physical examination, radiography, pulmonary function studies, and selected laboratory studies using sera and bronchoalveolar lavage fluid, workers can be identified early to effect avoidance of the antigen and institute pharmacologic therapy, if necessary. A lung biopsy may be necessary to rule out other interstitial lung diseases. Despite the varied organic antigen triggers, the presentation is similar with acute, subacute, or chronic forms. Systemic corticosteroids are the only reliable pharmacologic treatment but do not alter the long-term outcome. Copyright © 2011 Elsevier Inc. All rights reserved.

Cystic Fibrosis Transmembrane Conductance Regulator Controls Lung Proteasomal Degradation and Nuclear Factor-κB Activity in Conditions of Oxidative Stress

PubMed Central

Boncoeur, Emilie; Roque, Telma; Bonvin, Elise; Saint-Criq, Vinciane; Bonora, Monique; Clement, Annick; Tabary, Olivier; Henrion-Caude, Alexandra; Jacquot, Jacky

2008-01-01

Cystic fibrosis is a lethal inherited disorder caused by mutations in a single gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, resulting in progressive oxidative lung damage. In this study, we evaluated the role of CFTR in the control of ubiquitin-proteasome activity and nuclear factor (NF)-κB/IκB-α signaling after lung oxidative stress. After a 64-hour exposure to hyperoxia-mediated oxidative stress, CFTR-deficient (cftr−/−) mice exhibited significantly elevated lung proteasomal activity compared with wild-type (cftr+/+) animals. This was accompanied by reduced lung caspase-3 activity and defective degradation of NF-κB inhibitor IκB-α. In vitro, human CFTR-deficient lung cells exposed to oxidative stress exhibited increased proteasomal activity and decreased NF-κB-dependent transcriptional activity compared with CFTR-sufficient lung cells. Inhibition of the CFTR Cl− channel by CFTRinh-172 in the normal bronchial immortalized cell line 16HBE14o− increased proteasomal degradation after exposure to oxidative stress. Caspase-3 inhibition by Z-DQMD in CFTR-sufficient lung cells mimicked the response profile of increased proteasomal degradation and reduced NF-κB activity observed in CFTR-deficient lung cells exposed to oxidative stress. Taken together, these results suggest that functional CFTR Cl− channel activity is crucial for regulation of lung proteasomal degradation and NF-κB activity in conditions of oxidative stress. PMID:18372427

Accumulated exposure to ozone and measurement of health effects in children and counselors at two summer camps

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berry, M.; Lioy, P.J.; Gelperin, K.

1991-04-01

In the summer of 1988 a multiorganizational field health study was conducted at two summer day camps in suburban-central New Jersey. Thirty-four campers and counselors had daily pulmonary function tests performed each afternoon while attending camp during the month of July. The subjects ranged from 9 to 35 years of age. A mobile medical screening van was used to house the spirometric equipment and travel to each camp. Continuous ozone measurements were collected over the 19-test day study period. An intense ozone episode was recorded just prior to and during the first 2 weeks of the study. The campers hadmore » an increase in respiratory symptoms with increases in ozone concentrations above 120 ppb. Exposures below 120 ppb ozone were not significantly associated with symptoms. Peak expiratory flow rate in children was the only lung function measure associated with increasing ozone concentrations, with an average loss of 4.74 ml/sec/ppb (P-value = 0.05) for the 8-hr ozone exposure measure. Furthermore, it appears that the early intense exposure to ozone produced a persistent decrease in lung function and baseline shift for three days after the episode that obscured the daily dose-response relationship.« less

Reducing Children's Exposure to School Bus Diesel Exhaust in One School District in North Carolina

ERIC Educational Resources Information Center

Mazer, Mary E.; Jacobson Vann, Julie C.; Lamanna, Beth F.; Davison, Jean

2014-01-01

Children who are exposed to diesel exhaust from idling school buses are at increased risk of asthma exacerbation, decreased lung function, immunologic reactions, leukemia, and increased susceptibility to infections. Policies and initiatives that aim to protect school children from the harmful effects of exposure to diesel exhaust range from…

In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice.

PubMed

Ramsey, Kathryn A; Larcombe, Alexander N; Sly, Peter D; Zosky, Graeme R

2013-02-18

Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100 μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations.

In utero exposure to low dose arsenic via drinking water impairs early life lung mechanics in mice

PubMed Central

2013-01-01

Background Exposure to arsenic via drinking water is a significant environmental issue affecting millions of people around the world. Exposure to arsenic during foetal development has been shown to impair somatic growth and increase the risk of developing chronic respiratory diseases. The aim of this study was to determine if in utero exposure to low dose arsenic via drinking water is capable of altering lung growth and postnatal lung mechanics. Methods Pregnant C57BL/6 mice were given drinking water containing 0, 10 (current World Health Organisation (WHO) maximum contaminant level) or 100μg/L arsenic from gestational day 8 to birth. Birth outcomes and somatic growth were monitored. Plethysmography and the forced oscillation technique were used to collect measurements of lung volume, lung mechanics, pressure-volume curves and the volume dependence of lung mechanics in male and female offspring at two, four, six and eight weeks of age. Results In utero exposure to low dose arsenic via drinking water resulted in low birth weight and impaired parenchymal lung mechanics during infancy. Male offspring were more susceptible to the effects of arsenic on growth and lung mechanics than females. All alterations to lung mechanics following in utero arsenic exposure were recovered by adulthood. Conclusions Exposure to arsenic at the current WHO maximum contaminant level in utero impaired somatic growth and the development of the lungs resulting in alterations to lung mechanics during infancy. Deficits in growth and lung development in early life may contribute to the increased susceptibility of developing chronic respiratory disease in arsenic exposed human populations. PMID:23419080

The Impacts of Dust Storm Particles on Human Lung Cells - an Analysis at the Single Cell Level

NASA Astrophysics Data System (ADS)

Ardon-Dryer, K.; Mock, C.; Reyes, J.; Lahav, G.

2017-12-01

Aerosols particles (Natural and anthropogenic) are a key component of our atmosphere, their presence defines air quality levels and they can affect our health. Small particles penetrate into our lungs and this exposure can cause our lung cells to stress and in some cases leads to the death of the cells and to inflammation. During dust storm events there is an increase in particle concentration, many of them are breathable particles that can penetrate deep into our lungs. Exposure to dust particles can lead to respiratory problems, particularly for people with asthma. Therefore, during and after a dust storm event the number of people who are hospitalized with inflammation and respiratory problems increase. However, the exact mechanism that causes these health problems is still unclear. In this project, we are investigating the impacts that dust storm particles from different sources and of different concentrations (doses) have on human lung cells, performing a new and unique analysis at the single cell level. To accomplish this, each individual lung cell is continuously tracked after being exposed to dust particles. We monitor the behavior of the cell over time, identify the cells time of death and type of death (e.g. cell explosion). With this analysis, we can quantify cell death as a function of dust concertation (doses); to our surprise, an increase in cells death was not observed only as a function of an increase of dust concertation. In addition, we noticed that the way particles come in contact with cells, by sticking to or being engulfed by, and the interaction duration has an effect; cells that interact with dust particles for a longer period died earlier compared to cells with a shorter interaction period. These findings will help us to better understand the health related consequences of exposure to dust storm events and serve as a baseline for when evaluating other aerosol.

Carbonaceous particulate matter on the lung surface from adults living in São Paulo, Brazil.

PubMed

Padovan, Michele Galhardoni; Whitehouse, Abigail; Gouveia, Nelson; Habermann, Mateus; Grigg, Jonathan

2017-01-01

We therefore sought to identify the exposures associated with lung surface in long-term residents of São Paulo, Brazil. Lung surface carbon were analyzed in 72 autopsy specimens by image analysis. Smoking history, measured PM10 nearest to the home, distance to main road, and distance-weighted traffic density were used as exposure variables. Data are summarized as median (IQR), and compared by Mann Whitney Test, with correlations done by Spearman's correlation. There was no association between lung surface and age or gender. There was no statistically significant association in lung surface between smokers and non-smokers 6.74 cm2 (3.47 to 10.02) versus 5.20cm2 (2.29 to 7.54), and there was no significant association between lung surface carbon and exposure to environmental PM and markers of traffic exposure. We did not find a statistically significant association between lung surface and smokers and non-smokers, and no statistically significant association between lung surface carbon and environmental exposure variables. These results suggest that lung surface carbon in long-term residents of São Paulo may predominately be from environmental PM, but the most appropriate environmental exposure marker remains unclear.

Prolonged Injury and Altered Lung Function after Ozone Inhalation in Mice with Chronic Lung Inflammation

PubMed Central

Groves, Angela M.; Gow, Andrew J.; Massa, Christopher B.; Laskin, Jeffrey D.

2012-01-01

Surfactant protein–D (Sftpd) is a pulmonary collectin important in down-regulating macrophage inflammatory responses. In these experiments, we analyzed the effects of chronic macrophage inflammation attributable to loss of Sftpd on the persistence of ozone-induced injury, macrophage activation, and altered functioning in the lung. Wild-type (Sftpd+/+) and Sftpd−/− mice (aged 8 wk) were exposed to air or ozone (0.8 parts per million, 3 h). Bronchoalveolar lavage (BAL) fluid and tissue were collected 72 hours later. In Sftpd−/− mice, but not Sftpd+/+ mice, increased BAL protein and nitrogen oxides were observed after ozone inhalation, indicating prolonged lung injury and oxidative stress. Increased numbers of macrophages were also present in BAL fluid and in histologic sections from Sftpd−/− mice. These cells were enlarged and foamy, suggesting that they were activated. This conclusion was supported by findings of increased BAL chemotactic activity, and increased expression of inducible nitric oxide synthase in lung macrophages. In both Sftpd+/+ and Sftpd−/− mice, inhalation of ozone was associated with functional alterations in the lung. Although these alterations were limited to central airway mechanics in Sftpd+/+ mice, both central airway and parenchymal mechanics were modified by ozone exposure in Sftpd−/− mice. The most notable changes were evident in resistance and elastance spectra and baseline lung function, and in lung responsiveness to changes in positive end-expiratory pressure. These data demonstrate that a loss of Sftpd is associated with prolonged lung injury, oxidative stress, and macrophage accumulation and activation in response to ozone, and with more extensive functional changes consistent with the loss of parenchymal integrity. PMID:22878412

Toxicological and epidemiological evidence for health risks from inhaled engine emissions.

PubMed Central

Mauderly, J L

1994-01-01

Information from toxicological and epidemiological studies of the cancer and noncancer health risks from inhaled diesel engine exhaust (DE) and gasoline engine exhaust (GE) was reviewed. The toxicological database is more extensive for DE than for GE. Animal studies have shown that heavy, chronic exposures to both DE and GE can cause lung pathology and associated physiological effects. Inhaled GE has not been shown to be carcinogenic in animals. Chronically inhaled DE at high concentrations is a pulmonary carcinogen in rats, but the response is questionable in mice and negative in Syrian hamsters. The response in rats is probably not attributable to the DE soot-associated organic compounds, as previously assumed, and the usefulness of the rat data for predicting risk in humans is uncertain. Experimental human exposures to DE show that lung inflammatory and other cellular effects can occur after single exposures, and sparse data suggest that occupational exposures might affect respiratory function and symptoms. Epidemiology suggests that heavy occupational exposures to exhaust probably increase the risks for mortality from both lung cancer and noncancer pulmonary disease. The small magnitudes of the increases in these risks make the studies very sensitive to confounding factors and uncertainties of exposure; thus, it may not be possible to resolve exposure-response relationships conclusively by epidemiology. Our present knowledge suggests that heavy occupational exposures to DE and GE are hazardous but does not allow quantitative estimates of risk with a high degree of certainty. PMID:7529701

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maneckjee, R.; Minna, J.D.

Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for {mu}, {delta}, and {kappa} opioid agonists and for nicotine and {alpha}-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas {mu}, {delta}, and {kappa} opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptidesmore » ({beta}-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.« less

Pulmonary Evaluation of Permissible Exposure Limit of Syntroleum S-8 Synthetic Jet Fuel in Mice

PubMed Central

Wong, Simon S.; Thomas, Alana; Barbaris, Brian; Lantz, R. Clark; Witten, Mark L.

2009-01-01

No current studies have systematically examined pulmonary health effects associated with Syntroleum S-8 synthetic jet fuel (S-8). In order to gain an understanding about the threshold concentration in which lung injury is observed, C57BL/6 male mice were nose-only exposed to S-8 for 1 h/day for 7 days at average concentrations of 0 (control), 93, 352, and 616 mg/m3. Evaluation of pulmonary function, airway epithelial barrier integrity, and pathohistology was performed 24 h after the final exposures. Significant decreases were detected in expiratory lung resistance and total lung compliance of the 352 mg/m3 group, for which no clear concentration-dependent alterations could be determined. No significant changes in respiratory permeability were exhibited, indicating that there was no loss of epithelial barrier integrity following S-8 exposure. However, morphological examination and morphometric analysis of distal lung tissue, by using transmission electron microscopy, revealed cellular damage in alveolar type II epithelial cells, with significant increases in volume density of lamellar bodies/vacuoles at 352 and 616 S-8 mg/m3. Moreover, terminal bronchiolar Clara injury, as evidenced by apical membrane blebs, was observed at relatively low concentrations, suggesting if this synthetic jet fuel is utilized, the current permissible exposure limit of 350 mg/m3 for hydrocarbon fuels should cautiously be applied. PMID:19357071

Pulmonary evaluation of permissible exposure limit of syntroleum S-8 synthetic jet fuel in mice.

PubMed

Wong, Simon S; Thomas, Alana; Barbaris, Brian; Lantz, R Clark; Witten, Mark L

2009-06-01

No current studies have systematically examined pulmonary health effects associated with Syntroleum S-8 synthetic jet fuel (S-8). In order to gain an understanding about the threshold concentration in which lung injury is observed, C57BL/6 male mice were nose-only exposed to S-8 for 1 h/day for 7 days at average concentrations of 0 (control), 93, 352, and 616 mg/m(3). Evaluation of pulmonary function, airway epithelial barrier integrity, and pathohistology was performed 24 h after the final exposures. Significant decreases were detected in expiratory lung resistance and total lung compliance of the 352 mg/m(3) group, for which no clear concentration-dependent alterations could be determined. No significant changes in respiratory permeability were exhibited, indicating that there was no loss of epithelial barrier integrity following S-8 exposure. However, morphological examination and morphometric analysis of distal lung tissue, by using transmission electron microscopy, revealed cellular damage in alveolar type II epithelial cells, with significant increases in volume density of lamellar bodies/vacuoles at 352 and 616 S-8 mg/m(3). Moreover, terminal bronchiolar Clara injury, as evidenced by apical membrane blebs, was observed at relatively low concentrations, suggesting if this synthetic jet fuel is utilized, the current permissible exposure limit of 350 mg/m(3) for hydrocarbon fuels should cautiously be applied.

Ozone exposure, antioxidant genes, and lung function in an elderly cohort: VA Normative Aging Study

PubMed Central

Alexeeff, Stacey E.; Litonjua, Augusto A.; Wright, Robert O.; Baccarelli, Andrea; Suh, Helen; Sparrow, David; Vokonas, Pantel S.; Schwartz, Joel

2008-01-01

Background Ozone exposure is known to cause oxidative stress. We investigated the acute effects of ozone (O3) on lung function in the elderly, a suspected risk group. We then investigated whether genetic polymorphisms of antioxidant genes (heme oxygenase-1 [HMOX1] and glutathione S-transferase pi [GSTP1]) modified these associations. Methods We studied 1,100 elderly men from the Normative Aging Study whose lung function (forced vital capacity [FVC] and forced expiratory volume in one second [FEV1]) was measured every 3 years from 1995–2005. We genotyped the GSTP1 Ile105Val and Ala114Val polymorphisms and the (GT)n repeat polymorphism in the HMOX1 promoter, classifying repeats as short (n<25) or long (n 25). Ambient O3 was measured continuously at locations in the Greater Boston area. We used mixed linear models, adjusting for known confounders. Results A 15 ppb increase in O3 during the previous 48 hours was associated with a 1.25% decrease in FEV1 (95% CI: −1.96%, −0.54%). This estimated effect was worsened with either the presence of a long (GT)n repeat in HMOX1 (−1.38%, 95% CI: −2.11%, −0.65) or the presence of an allele coding for Val105 in GSTP1 (−1.69%, 95% CI: −2.63%, −0.75). A stronger estimated effect of O3 on FEV1 was found in subjects carrying both the GSTP1 105Val variant and the HMOX1 long (GT)n repeat (−1.94%, 95% CI: −2.89%, −0.98%). Similar associations were also found between FVC and ozone exposure. Conclusions Our results suggest that ozone has an acute effect on lung function in the elderly, and the effects may be modified by the presence of specific polymorphisms in antioxidant genes. PMID:18524839

[Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy].

PubMed

Gómez Tejada, Ricardo A; Legarreta, Cora G; Enghelmayer, Juan Ignacio; Dianti, Milagros; Acuña, Silvana; Olmedo, Gloria

2017-01-01

In a series of nine patients with histopathological diagnosis of hypersensitivity pneumonitis, we retrospectively evaluated clinical data, exposure related factors, pulmonary function tests and chest computed tomography scans. A restrictive abnormality with reduction of diffusion capacity for carbon monoxide was mainly found. Chest scans showed fibrotic patterns in most cases; ground glass attenuation areas with mosaic pattern and consolidation in the rest. Exposure to avian antigens, cereal grains and air conditioners contaminated with fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the cases. Since there are no unique features that allow differentiation from other interstitial lung diseases, a high clinical suspicion is required and a careful search of environmental exposure to possible antigens is needed that, together with clinical, radiological and pathological data, may lead to diagnosis.

High-Mobility Group Box 1 Disrupts Metabolic Function with Cigarette Smoke Exposure in a Ceramide-Dependent Manner.

PubMed

Taylor, Oliver J; Thatcher, Mikayla O; Carr, Sheryl T; Gibbs, Jonathan L; Trumbull, Annie M; Harrison, Mitchell E; Winden, Duane R; Pearson, Mackenzie J; Tippetts, Trevor S; Holland, William L; Reynolds, Paul R; Bikman, Benjamin T

2017-05-20

We have previously found that cigarette smoke disrupts metabolic function, in part, by increasing muscle ceramide accrual. To further our understanding of this, we sought to determine the role of the cytokine high-mobility group box 1 (HMGB1), which is increased with smoke exposure, in smoke-induced muscle metabolic perturbations. To test this theory, we determined HMGB1 from lungs of human smokers, as well as from lung cells from mice exposed to cigarette smoke. We also treated cells and mice directly with HMGB1, in the presence or absence of myriocin, an inhibitor of serine palmitoyltransferase, the rate-limiting enzyme in ceramide biosynthesis. Outcomes included assessments of insulin resistance and muscle mitochondrial function. HMGB1 was significantly increased in both human lungs and rodent alveolar macrophages. Further testing revealed that HMGB1 treatment elicited a widespread increase in ceramide species and reduction in myotube mitochondrial respiration, an increase in reactive oxygen species, and reduced insulin-stimulated Akt phosphorylation. Inhibition of ceramide biosynthesis with myriocin was protective. In mice, by comparing treatments of HMGB1 injections with or without myriocin, we found that HMGB1 injections resulted in increased muscle ceramides, especially C16 and C24, which were necessary for reduced muscle mitochondrial respiration and compromised insulin and glucose tolerance. In conclusion, HMGB1 may be a necessary intermediate in the ceramide-dependent metabolic consequences of cigarette smoke exposure.

High-Mobility Group Box 1 Disrupts Metabolic Function with Cigarette Smoke Exposure in a Ceramide-Dependent Manner

PubMed Central

Taylor, Oliver J.; Thatcher, Mikayla O.; Carr, Sheryl T.; Gibbs, Jonathan L.; Trumbull, Annie M.; Harrison, Mitchell E.; Winden, Duane R.; Pearson, Mackenzie J.; Tippetts, Trevor S.; Holland, William L.; Reynolds, Paul R.; Bikman, Benjamin T.

2017-01-01

We have previously found that cigarette smoke disrupts metabolic function, in part, by increasing muscle ceramide accrual. To further our understanding of this, we sought to determine the role of the cytokine high-mobility group box 1 (HMGB1), which is increased with smoke exposure, in smoke-induced muscle metabolic perturbations. To test this theory, we determined HMGB1 from lungs of human smokers, as well as from lung cells from mice exposed to cigarette smoke. We also treated cells and mice directly with HMGB1, in the presence or absence of myriocin, an inhibitor of serine palmitoyltransferase, the rate-limiting enzyme in ceramide biosynthesis. Outcomes included assessments of insulin resistance and muscle mitochondrial function. HMGB1 was significantly increased in both human lungs and rodent alveolar macrophages. Further testing revealed that HMGB1 treatment elicited a widespread increase in ceramide species and reduction in myotube mitochondrial respiration, an increase in reactive oxygen species, and reduced insulin-stimulated Akt phosphorylation. Inhibition of ceramide biosynthesis with myriocin was protective. In mice, by comparing treatments of HMGB1 injections with or without myriocin, we found that HMGB1 injections resulted in increased muscle ceramides, especially C16 and C24, which were necessary for reduced muscle mitochondrial respiration and compromised insulin and glucose tolerance. In conclusion, HMGB1 may be a necessary intermediate in the ceramide-dependent metabolic consequences of cigarette smoke exposure. PMID:28531105

Mortality from lung cancer among silicotic patients in Sardinia: an update study with 10 more years of follow up

PubMed Central

Carta, P; Aru, G; Manca, P

2001-01-01

OBJECTIVES—To evaluate the association between silica, silicosis and lung cancer, the mortality of 724 patients with silicosis, first diagnosed by standard chest x ray film between 1964 and 1970, has been analysed by a cohort study extended to 31 December 1997.
METHODS—Smoking and detailed occupational histories were available for each member of the cohort as well as the estimated lifetime exposure to respirable silica dust and radon daughters. Two independent readers blindly classified standard radiographs according to the 12 point International Labour Organisation (ILO) scale. Lung function tests meeting the American Thoracic Society's criteria were available for 665 patients. Standardised mortality ratios (SMRs) for selected causes of death were based on the age specific Sardinian regional death rates.
RESULTS—The mortality for all causes was significantly higher than expected (SMR 1.35, 95% confidence interval (95% CI) 1.24 to 1.46) mainly due to tuberculosis (SMR 22.0) and to non-malignant chronic respiratory diseases (NMCRD) (SMR 6.03). All cancer deaths were within the expected numbers (SMR 0.93; 95% CI 0.76 to 1.14). The SMR for lung cancer was 1.37 (95% CI 0.98 to 1.91, 34 observed), increasing to 1.65 (95% CI 0.98 to 2.77) allowing for 20 years of latency since the first diagnosis of silicosis. Although mortality from NMCRD was strongly associated to the severity of radiological silicosis and to the extent of the cumulative exposure to silica, SMR for lung cancer was weakly related to the ILO categories and to the cumulative exposure to silica dust only after 20 years of lag interval. A significant excess of deaths from lung cancer (SMR 2.35) was found among silicotic patients previously employed in underground metal mines characterised by a relatively high airborne concentration of radon daughters and among ever smokers who showed an airflow obstruction at the time of the first diagnosis of silicosis (SMR 3.29). Mortality for lung cancer related to exposure was evaluated with both the Cox's proportional hazards modelling within the entire cohort and a nested case-control study (34 cases of lung cancer and 136 matched controls). Both multivariate analyses did not show any significant association with cumulative exposure to silica or severity of silicosis, but confirmed the association between mortality for lung cancer and relatively high exposure to radon, smoking, and airflow obstruction as significant covariates.
CONCLUSIONS—The findings indicate that the slightly increased mortality for lung cancer in this cohort of silicotic patients was significantly associated with other risk factors—such as cigarette smoking, airflow obstruction, and estimated exposure to radon daughters in underground mines—rather than to the severity of radiological silicosis or to the cumulative exposure to crystalline silica dust itself.


Keywords: silicosis; crystalline silica; lung cancer mortality PMID:11706145

The Pulmonary Surfactant: Impact of Tobacco Smoke and Related Compounds on Surfactant and Lung Development

PubMed Central

Scott, J Elliott

2004-01-01

Cigarette smoking, one of the most pervasive habits in society, presents many well established health risks. While lung cancer is probably the most common and well documented disease associated with tobacco exposure, it is becoming clear from recent research that many other diseases are causally related to smoking. Whether from direct smoking or inhaling environmental tobacco smoke (ETS), termed secondhand smoke, the cells of the respiratory tissues and the lining pulmonary surfactant are the first body tissues to be directly exposed to the many thousands of toxic chemicals in tobacco. Considering the vast surface area of the lung and the extreme attenuation of the blood-air barrier, it is not surprising that this organ is the primary route for exposure, not just to smoke but to most environmental contaminants. Recent research has shown that the pulmonary surfactant, a complex mixture of phospholipids and proteins, is the first site of defense against particulates or gas components of smoke. However, it is not clear what effect smoke has on the surfactant. Most studies have demonstrated that smoking reduces bronchoalveolar lavage phospholipid levels. Some components of smoke also appear to have a direct detergent-like effect on the surfactant while others appear to alter cycling or secretion. Ultimately these effects are reflected in changes in the dynamics of the surfactant system and, clinically in changes in lung mechanics. Similarly, exposure of the developing fetal lung through maternal smoking results in postnatal alterations in lung mechanics and higher incidents of wheezing and coughing. Direct exposure of developing lung to nicotine induces changes suggestive of fetal stress. Furthermore, identification of nicotinic receptors in fetal lung airways and corresponding increases in airway connective tissue support a possible involvement of nicotine in postnatal asthma development. Finally, at the level of the alveoli of the lung, colocalization of nicotinic receptors and surfactant-specific protein in alveolar cells is suggestive of a role in surfactant metabolism. Further research is needed to determine the mechanistic effects of smoke and its components on surfactant function and, importantly, the effects of smoke components on the developing pulmonary system. PMID:19570267

The Pulmonary Surfactant: Impact of Tobacco Smoke and Related Compounds on Surfactant and Lung Development

PubMed Central

Scott, J Elliott

2004-01-01

Cigarette smoking, one of the most pervasive habits in society, presents many well established health risks. While lung cancer is probably the most common and well documented disease associated with tobacco exposure, it is becoming clear from recent research that many other diseases are causally related to smoking. Whether from direct smoking or inhaling environmental tobacco smoke (ETS), termed secondhand smoke, the cells of the respiratory tissues and the lining pulmonary surfactant are the first body tissues to be directly exposed to the many thousands of toxic chemicals in tobacco. Considering the vast surface area of the lung and the extreme attenuation of the blood-air barrier, it is not surprising that this organ is the primary route for exposure, not just to smoke but to most environmental contaminants. Recent research has shown that the pulmonary surfactant, a complex mixture of phospholipids and proteins, is the first site of defense against particulates or gas components of smoke. However, it is not clear what effect smoke has on the surfactant. Most studies have demonstrated that smoking reduces bronchoalveolar lavage phospholipid levels. Some components of smoke also appear to have a direct detergent-like effect on the surfactant while others appear to alter cycling or secretion. Ultimately these effects are reflected in changes in the dynamics of the surfactant system and, clinically in changes in lung mechanics. Similarly, exposure of the developing fetal lung through maternal smoking results in postnatal alterations in lung mechanics and higher incidents of wheezing and coughing. Direct exposure of developing lung to nicotine induces changes suggestive of fetal stress. Furthermore, identification of nicotinic receptors in fetal lung airways and corresponding increases in airway connective tissue support a possible involvement of nicotine in postnatal asthma development. Finally, at the level of the alveoli of the lung, colocalization of nicotinic receptors and surfactant-specific protein in alveolar cells is suggestive of a role in surfactant metabolism. Further research is needed to determine the mechanistic effects of smoke and its components on surfactant function and, importantly, the effects of smoke components on the developing pulmonary system.

Lung cancer and exposure to diesel exhaust among bus garage workers.

PubMed

Gustavsson, P; Plato, N; Lidström, E B; Hogstedt, C

1990-10-01

Mortality and cancer incidence was investigated among the 695 bus garage workers employed as mechanics, servicemen, or hostlers for at least six months in five bus garages in Stockholm between 1945 and 1970. The exposure to diesel exhaust and asbestos was estimated by industrial hygienists. A small excess of lung cancer mortality was found in the cohort when occupationally active men in Stockholm were used as the reference group. A case-referent study was performed within the cohort, six referents being selected for each of the 20 lung cancer cases. The lung cancer risk increased with increasing cumulative exposure to diesel exhaust, but not with cumulative asbestos exposure. The relative risk for lung cancer among the highly exposed men was 2.4 (95% CI 1.3-4.5) as compared with those with low exposure. The study indicates that exposure to diesel exhaust increases the risk for lung cancer.

Asbestos-related lung cancer and malignant mesothelioma of the pleura: selected current issues.

PubMed

Markowitz, Steven

2015-06-01

Asbestos-related diseases persist, because millions of workers have had prior exposure and many industrializing countries continue to use asbestos. Globally, an estimated 107,000 people die annually from lung cancer, malignant mesothelioma, and asbestosis due to occupational asbestos exposure. Malignant mesothelioma and lung cancer are caused by all major types of asbestos. Asbestos causes more lung cancer deaths than malignant mesothelioma of the pleura; most cases of the latter are due to asbestos exposure. The cancer risk increases with cumulative asbestos exposure, with increased risk even at low levels of exposure to asbestos. Based on empirical studies, an estimated cumulative occupational exposure to asbestos of 1 fiber/mL-year substantially raises malignant mesothelioma risk. No safe threshold for asbestos exposure has been established for lung cancer and mesothelioma. The validity of fiber-type risk assessments depends critically on the quality of exposure assessments, which vary considerably, leading to a high degree of uncertainty. Asbestos exposure without asbestosis and smoking increases the risk of lung cancer. The joint effect of asbestos and smoking is supra-additive, which may depend in part on the presence of asbestosis. Asbestos workers who cease smoking experience a dramatic drop in lung cancer risk, which approaches that of nonsmokers after 30 years. Studies to date show that longer, thinner fibers have a stronger association with lung cancer than shorter, less thin fibers, but the latter nonetheless also show an association with lung cancer and mesothelioma. Low-dose chest computed tomographic scanning offers an unprecedented opportunity to detect early-stage lung cancers in asbestos-exposed workers. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Early Life Wildfire Smoke Exposure Is Associated with Immune Dysregulation and Lung Function Decrements in Adolescence

PubMed Central

Black, Carolyn; Gerriets, Joan E.; Fontaine, Justin H.; Harper, Richart W.; Kenyon, Nicholas J.; Tablin, Fern; Schelegle, Edward S.

2017-01-01

The long-term health effects of wildfire smoke exposure in pediatric populations are not known. The objectives of this study were to determine if early life exposure to wildfire smoke can affect parameters of immunity and airway physiology that are detectable with maturity. We studied a mixed-sex cohort of rhesus macaque monkeys that were exposed as infants to ambient wood smoke from a series of Northern California wildfires in the summer of 2008. Peripheral blood mononuclear cells (PBMCs) and pulmonary function measures were obtained when animals were approximately 3 years of age. PBMCs were cultured with either LPS or flagellin, followed by measurement of secreted IL-8 and IL-6 protein. PBMCs from a subset of female animals were also evaluated by Toll-like receptor (TLR) pathway mRNA analysis. Induction of IL-8 protein synthesis with either LPS or flagellin was significantly reduced in PBMC cultures from wildfire smoke–exposed female monkeys. In contrast, LPS- or flagellin-induced IL-6 protein synthesis was significantly reduced in PBMC cultures from wildfire smoke–exposed male monkeys. Baseline and TLR ligand–induced expression of the transcription factor, RelB, was globally modulated in PBMCs from wildfire smoke–exposed monkeys, with additional TLR pathway genes affected in a ligand-dependent manner. Wildfire smoke–exposed monkeys displayed significantly reduced inspiratory capacity, residual volume, vital capacity, functional residual capacity, and total lung capacity per unit of body weight relative to control animals. Our findings suggest that ambient wildfire smoke exposure during infancy results in sex-dependent attenuation of systemic TLR responses and reduced lung volume in adolescence. PMID:28208028

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology.

PubMed

Bodas, Manish; Vij, Neeraj

2017-05-04

Chronic obstructive pulmonary disease (COPD) is foremost among the non-reversible fatal ailments where exposure to tobacco/biomass-smoke and aging are the major risk factors for the initiation and progression of the obstructive lung disease. The role of smoke-induced inflammatory-oxidative stress, apoptosis and cellular senescence in driving the alveolar damage that mediates the emphysema progression and severe lung function decline is apparent, although the central mechanism that regulates these processes was unknown. To fill in this gap in knowledge, the central role of proteostasis and autophagy in regulating chronic lung disease causing mechanisms has been recently described. Recent studies demonstrate that cigarette/nicotine exposure induces proteostasis/autophagy-impairment that leads to perinuclear accumulation of polyubiquitinated proteins as aggresome-bodies, indicative of emphysema severity. In support of this concept, autophagy inducing FDA-approved anti-oxidant drugs control tobacco-smoke induced inflammatory-oxidative stress, apoptosis, cellular senescence and COPD-emphysema progression in variety of preclinical models. Hence, we propose that precise and early detection of aggresome-pathology can allow the timely assessment of disease severity in COPD-emphysema subjects for prognosis-based intervention. While intervention with autophagy-inducing drugs is anticipated to reduce alveolar damage and lung function decline, resulting in a decrease in the current mortality rates in COPD-emphysema subjects.

Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in two unique rat models of hyperoxic lung injury

PubMed Central

Roerig, David L.; Haworth, Steven T.; Clough, Anne V.

2012-01-01

Rat exposure to 60% oxygen (O2) for 7 days (hyper-60) or to >95% O2 for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O2. The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function. HMPAO was injected intravenously in anesthetized rats, and planar images were acquired. We investigated the role of GSH in the lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl maleate (DEM) prior to imaging. We also measured GSH content and activities of mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO increased by ∼50% and ∼250% in hyper-60 and hyper-95R rats, respectively, compared with retention in rats exposed to room air (normoxic). DEM decreased retention in normoxic (∼26%) and hyper-95R (∼56%) rats compared with retention in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper-95R lung homogenate compared with normoxic lung homogenate. Complex I activity decreased by ∼50% in hyper-60 and hyper-95R lung homogenate compared with activity in normoxic lung homogenate. However, complex IV activity was increased by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations between the GSH content in lung homogenate and the DEM-sensitive fraction of HMPAO retention and between the complex IV/complex I activity ratio and the DEM-insensitive fraction of HMPAO retention. These results suggest that an increase in the GSH-dependent component of the lung retention of HMPAO may be a marker of tolerance to sustained exposure to hyperoxia. PMID:22628374

Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in two unique rat models of hyperoxic lung injury.

PubMed

Audi, Said H; Roerig, David L; Haworth, Steven T; Clough, Anne V

2012-08-15

Rat exposure to 60% oxygen (O(2)) for 7 days (hyper-60) or to >95% O(2) for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O(2). The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function. HMPAO was injected intravenously in anesthetized rats, and planar images were acquired. We investigated the role of GSH in the lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl maleate (DEM) prior to imaging. We also measured GSH content and activities of mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO increased by ≈ 50% and ≈ 250% in hyper-60 and hyper-95R rats, respectively, compared with retention in rats exposed to room air (normoxic). DEM decreased retention in normoxic (≈ 26%) and hyper-95R (≈ 56%) rats compared with retention in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper-95R lung homogenate compared with normoxic lung homogenate. Complex I activity decreased by ≈ 50% in hyper-60 and hyper-95R lung homogenate compared with activity in normoxic lung homogenate. However, complex IV activity was increased by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations between the GSH content in lung homogenate and the DEM-sensitive fraction of HMPAO retention and between the complex IV/complex I activity ratio and the DEM-insensitive fraction of HMPAO retention. These results suggest that an increase in the GSH-dependent component of the lung retention of HMPAO may be a marker of tolerance to sustained exposure to hyperoxia.

Fetal Onset of Aberrant Gene Expression Relevant to Pulmonary Carcinogenesis in Lung Adenocarcinoma Development Induced by In Utero Arsenic Exposure

PubMed Central

Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A.; Waalkes, Michael P.

2009-01-01

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-α (ER-α) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-β-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. in utero arsenic exposure also induced overexpression of α-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-α expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-α expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-α activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood. PMID:17077188

Fetal onset of aberrant gene expression relevant to pulmonary carcinogenesis in lung adenocarcinoma development induced by in utero arsenic exposure.

PubMed

Shen, Jun; Liu, Jie; Xie, Yaxiong; Diwan, Bhalchandra A; Waalkes, Michael P

2007-02-01

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-alpha (ER-alpha) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-beta-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. In utero arsenic exposure also induced overexpression of alpha-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-alpha expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-alpha expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-alpha activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood.

Drillers and mill operators in an open-pit gold mine are at risk for impaired lung function.

PubMed

Vinnikov, Denis

2016-01-01

Occupational studies of associations of exposures with impaired lung function in mining settings are built on exposure assessment and far less often on workplace approach, so the aim of this study was to identify vulnerable occupational groups for early lung function reduction in a cohort of healthy young miners. Data from annual screening lung function tests in gold mining company in Kyrgyzstan were linked to occupations. We compared per cent predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC between occupational groups and tested selected occupations in multivariate regression adjusted for smoking and work duration for the following outcomes: FEV1 < 80 %, FEV1/FVC < 70 % and both. 1550 tests of permanent workers of 41 occupations (mean age 40.5 ± 9.2 years, 29.8 % never smokers) were included in the analysis. The mean overall VC was 103.0 ± 12.9 %; FVC 109.1 ± 13.0 % and FEV1 100.2 ± 25.9 %. Drillers and smoking food handlers had the lowest FEV1%. In non-smokers, the lowest FEV1 was in drillers (94.9 ± 11.3 % compared to 115.2 ± 17.7 % in engineers). Drillers (adjusted odds ratio (OR) 1.53 (95 % confidence interval (CI) 1.11-2.09)) and mill operators (OR 2.01 (1.13-3.57)) were at greater risk of obstructive ventilation pattern (FEV1/FVC < 70 %). Drilling and mill operations are the highest risk jobs in an open-pit mine for reduced lung function. Occupational medical clinic at site should follow-up workers in these occupations with depth and strongly recommend smoking cessation.

Occupational exposure to crystalline silica and the risk of lung cancer in Canadian men.

PubMed

Kachuri, Linda; Villeneuve, Paul J; Parent, Marie-Élise; Johnson, Kenneth C; Harris, Shelley A

2014-07-01

Crystalline silica is a recognized carcinogen, but the association with lung cancer at lower levels of exposure has not been well characterized. This study investigated the relationship between occupational silica exposure and lung cancer and the combined effects of cigarette smoking and silica exposure on lung cancer risk. A population-based case-control study was conducted in eight Canadian provinces between 1994 and 1997. Self-reported questionnaires were used to obtain a lifetime occupational history and information on other risk factors. Occupational hygienists assigned silica exposures to each job based on concentration, frequency and reliability. Data from 1681 incident lung cancer cases and 2053 controls were analyzed using logistic regression to estimate odds ratios (OR) and their 95% confidence intervals (CI). Models included adjustments for cigarette smoking, lifetime residential second-hand smoke and occupational exposure to diesel and gasoline engine emissions. Relative to the unexposed, increasing duration of silica exposure at any concentration was associated with a significant trend in lung cancer risk (OR ≥ 30 years: 1.67, 1.21-2.24; ptrend  = 0.002). The highest tertile of cumulative silica exposure was associated with lung cancer (OR = 1.81, 1.34-2.42; ptrend  = 0.004) relative to the lowest. Men exposed to silica for ≥30 years with ≥40 cigarette pack-years had the highest risk relative to those unexposed with <10 pack-years (OR = 42.53, 23.54-76.83). The joint relationship with smoking was consistent with a multiplicative model. Our findings suggest that occupational exposure to silica is a risk factor for lung cancer, independently from active and passive smoking, as well as from exposure to other lung carcinogens. © 2013 UICC.

A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.

PubMed

Sørli, Jorid B; Da Silva, Emilie; Bäckman, Per; Levin, Marcus; Thomsen, Birthe L; Koponen, Ismo K; Larsen, Søren T

2016-03-01

The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function.

Early pulmonary events of nose-only water pipe (shisha) smoking exposure in mice

PubMed Central

Nemmar, Abderrahim; Hemeiri, Ahmed Al; Hammadi, Naser Al; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Elwasila, Mohamed; Ali, Badreldin H; Adeghate, Ernest

2015-01-01

Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored “moasel” tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are early markers of WPS exposure that precede airway dysfunction. Our data provide information on the initial steps involved in the respiratory effects of WPS, which constitute the underlying causal chain of reactions leading to the long-term effects of WPS. PMID:25780090

Interaction Effects of Temperature and Ozone on Lung Function and Markers of Systemic Inflammation, Coagulation, and Fibrinolysis: A Crossover Study of Healthy Young Volunteers

PubMed Central

Kahle, Juliette J.; Neas, Lucas M.; Devlin, Robert B.; Case, Martin W.; Schmitt, Michael T.; Madden, Michael C.

2014-01-01

Background: Trends in climate suggest that extreme weather events such as heat waves will become more common. High levels of the gaseous pollutant ozone are associated with elevated temperatures. Ozone has been associated with respiratory diseases as well as cardiovascular morbidity and mortality and can reduce lung function and alter systemic markers of fibrinolysis. The interaction between ozone and temperature is unclear. Methods: Sixteen healthy volunteers were exposed in a randomized crossover study to 0.3 ppm ozone and clean air for 2 hr at moderate (22°C) temperature and again at an elevated temperature (32.5°C). In each case lung function was performed and blood taken before and immediately after exposure and the next morning. Results: Ozone exposure at 22°C resulted in a decrease in markers of fibrinolysis the next day. There was a 51.8% net decrease in PAI-1 (plasminogen activator inhibitor-1), a 12.1% net decrease in plasminogen, and a 17.8% net increase in D-dimer. These significantly differed from the response at 32.5°C, where there was a 44.9% (p = 0.002) and a 27.9% (p = 0.001) increase in PAI-1 and plasminogen, respectively, and a 12.5% (p = 0.042) decrease in D-dimer. In contrast, decrements in lung function following ozone exposure were comparable at both moderate and elevated temperatures (forced expiratory volume in 1 sec, –12.4% vs. –7.5%, p > 0.05). No changes in systemic markers of inflammation were observed for either temperature. Conclusion: Ozone-induced systemic but not respiratory effects varied according to temperature. Our study suggests that at moderate temperature ozone may activate the fibrinolytic pathway, while at elevated temperature ozone may impair it. These findings provide a biological basis for the interaction between temperature and ozone on mortality observed in some epidemiologic studies. Citation: Kahle JJ, Neas LM, Devlin RB, Case MW, Schmitt MT, Madden MC, Diaz-Sanchez D. 2015. Interaction effects of temperature and ozone on lung function and markers of systemic inflammation, coagulation, and fibrinolysis: a crossover study of healthy young volunteers. Environ Health Perspect 123:310–316; http://dx.doi.org/10.1289/ehp.1307986 PMID:25514459

Association between right ventricular dysfunction and restrictive lung disease in childhood cancer survivors as measured by quantitative echocardiography.

PubMed

Patel, Amee; Weismann, Constance; Weiss, Pnina; Russell, Kerry; Bazzy-Asaad, Alia; Kadan-Lottick, Nina S

2014-11-01

Restrictive lung disease is a complication in childhood cancer survivors who received lung-toxic chemotherapy and/or thoracic radiation. Left ventricular dysfunction is documented in these survivors, but less is known about right ventricular (RV) function. Quantitative echocardiography may help detect subclinical RV dysfunction. The aim of this study was to assess RV function quantitatively in childhood cancer survivors after lung-toxic therapy. We identified records of 33 childhood cancer survivors who (1) were treated with lung-toxic therapy and/or radiation, (2) were cancer-free for ≥ one year after therapy, and (3) had pulmonary function tests and echocardiograms from their most recent follow-up visit. Participants' mean age was 11.6 ± 4.5 years at cancer diagnosis and 23 ± 8.6 years at evaluation. The most common diagnosis was lymphoma/leukemia (n = 27). Twenty-nine subjects had anthracycline exposure. Eleven of the 33 subjects demonstrated restrictive pulmonary impairment (total lung capacity 3.69 ± 1.5 L [69.3 ± 22.4% predicted]). Among quantitative measures of RV function, isovolumetric acceleration (IVA), a measure of contractility, was significantly lower in the group with restrictive lung disease (2.42 ± 0.56 vs. 1.83 ± 0.78 m/sec(2); P < 0.05). There was a trend towards lower tissue Doppler derived S' and tricuspid annular plane systolic excursion in the group with restrictive lung disease. Subjects with restrictive lung disease were found to have ≥ 2 abnormal parameters (P < 0.01). IVA may detect early RV dysfunction in childhood cancer survivors with restrictive lung disease. Our findings require confirmation in a larger study population and validation by cardiac MRI. © 2014 Wiley Periodicals, Inc.

Pulmonary arterial hypertension and cor pulmonale associated with chronic domestic woodsmoke inhalation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandoval, J.; Salas, J.; Martinez-Guerra, M.L.

1993-01-01

We describe the clinical, radiologic, functional, and pulmonary hemodynamic characteristics of a group of 30 nonsmoking patients with a lung disease that may be related to intense, long-standing indoor wood-smoke exposure. The endoscopic and some of the pathologic findings are also presented. Intense and prolonged wood-smoke inhalation may produce a chronic pulmonary disease that is similar in many aspects to other forms of inorganic dust-exposure interstitial lung disease. It affects mostly country women in their 60s, and severe dyspnea and cough are the outstanding complaints. The chest roentgenograms show a diffuse, bilateral, reticulonodular pattern, combined with normalized or hyperinflated lungs,more » as well as indirect signs of pulmonary arterial hypertension (PAH). On the pulmonary function test the patients show a mixed restrictive-obstructive pattern with severe hypoxemia and variable degrees of hypercapnia. Endoscopic findings are those of acute and chronic bronchitis and intense anthracotic staining of the airways appears to be quite characteristic. Fibrous and inflammatory focal thickening of the alveolar septa as well as diffuse parenchymal anthracotic deposits are the most prominent pathologic findings, although inflammatory changes of the bronchial epithelium are also present. The patients had severe PAH in which, as in other chronic lung diseases, chronic alveolar hypoxia may play the main pathogenetic role. However, PAH in wood-smoke inhalation-associated lung disease (WSIALD) appears to be more severe than in other forms of interstitial lung disease and tobacco-related COPD. The patients we studied are a selected group and they may represent one end of the spectrum of the WSIALD.« less

Respiratory symptoms, lung function decrement and chronic obstructive pulmonary disease in pre-menopausal Indian women exposed to biomass smoke.

PubMed

Mukherjee, Sayali; Roychoudhury, Sanghita; Siddique, Shabana; Banerjee, Madhuchanda; Bhattacharya, Purba; Lahiri, Twisha; Ray, Manas Ranjan

2014-12-01

The impact of chronic exposure to smoke from biomass burning on respiratory health has been examined. Six-hundred and eighty-one non-smoking women (median age 35 years) from eastern India who cook exclusively with biomass (wood, dung and crop residues) and 438 age-matched women from similar neighborhood who cook with liquefied petroleum gas (LPG) were examined. Pulmonary function test was done by spirometry. The concentrations of particulate matter having diameter of < 10 µm (PM10) and < 2.5 µm (PM2.5) in indoor air was measured by real-time aerosol monitor. Compared with LPG users, biomass users had greater prevalence of upper (50.9 versus 28.5%) and lower respiratory symptoms (71.8 versus 30.8%) and dyspnea (58.4 versus 19.9%). They showed reduction in all parameters measured by spirometer especially in mid-expiratory volume. PM10 and PM2.5 concentration in biomass using kitchen were 2-3-times more than LPG-using kitchen, and the decline in spirometry values was positively associated PM10 and PM2.5 levels in indoor air after controlling education, family income and kitchen location as potential confounders. Overall, 29.7% of biomass users and 16.4% of LPG users had deficient lung function, and restrictive type of deficiency was predominant. Chronic obstructive pulmonary disease (COPD) was diagnosed in 4.6% of biomass and 0.9% of LPG users. Women who predominantly used dung cake and did not possess separate kitchen had poorer lung function. Cumulative exposure to biomass smoke causes lung function decrement and facilitates COPD development even in non-smoking and relatively young pre-menopausal women.

Lung cancer mortality among workers at a nuclear materials fabrication plant.

PubMed

Richardson, David B; Wing, Steve

2006-02-01

The Oak Ridge, Tennessee Y-12 plant has operated as a nuclear materials fabrication plant since the 1940s. Given the work environment, and prior findings that lung cancer mortality was elevated among white male Y-12 workers relative to US white males, we investigated whether lung cancer mortality was associated with occupational radiation exposures. A cohort of 3,864 workers hired between 1947 and 1974 who had been monitored for internal radiation exposure was identified. Vital status was ascertained through 1990. Over the study period 111 lung cancer deaths were observed. Cumulative external radiation dose under a 5-year lag assumption was positively associated with lung cancer mortality (0.54% increase in lung cancer mortality per 10 mSv, se=0.16, likelihood ratio test (LRT)=5.84, 1 degree of freedom [df]); cumulative internal radiation dose exhibited a highly-imprecise negative association with lung cancer mortality. The positive association between external radiation dose and lung cancer mortality was primarily due to exposure occurring in the period 5-14 years after exposure (0.97% increase in lung cancer mortality rate per 10 mSv, se=0.28, LRT=6.35, 1 df). The association between external radiation dose and lung cancer mortality was negative for exposures occurring at ages<35 years and positive for exposures occurring at ages 35-50 and 50+years. There is evidence of a positive association between cumulative external radiation dose and lung cancer mortality in this population. However, a causal interpretation of this association is constrained by the uncertainties in external and internal radiation dose estimates, the lack of information about exposures to other lung carcinogens, and the limited statistical power of the study. Copyright (c) 2005 Wiley-Liss, Inc.

Effects of acute inhalation of aerosols generated during resistance spot welding with mild-steel on pulmonary, vascular and immune responses in rats.

PubMed

Zeidler-Erdely, Patti C; Meighan, Terence G; Erdely, Aaron; Fedan, Jeffrey S; Thompson, Janet A; Bilgesu, Suzan; Waugh, Stacey; Anderson, Stacey; Marshall, Nikki B; Afshari, Aliakbar; McKinney, Walter; Frazer, David G; Antonini, James M

2014-10-01

Spot welding is used in the automotive and aircraft industries, where high-speed, repetitive welding is needed to join thin sections of metal. Epoxy adhesives are applied as sealers to the metal seams. Pulmonary function abnormalities and airway irritation have been reported in spot welders, but no animal toxicology studies exist. Therefore, the goal of this study was to investigate vascular, immune and lung toxicity measures after exposure to these metal fumes in an animal model. Male Sprague-Dawley rats were exposed by inhalation to 25 mg/m³ to either mild-steel spot welding aerosols with sparking (high metal, HM) or without sparking (low metal, LM) for 4 h/d for 3, 8 and 13 d. Shams were exposed to filtered air. Bronchoalveolar lavage (BAL), lung gene expression and ex vivo BAL cell challenge were performed to assess lung toxicity. Lung resistance (R(L)) was evaluated before and after challenge with inhaled methacholine (MCh). Functional assessment of the vascular endothelium in isolated rat tail arteries and leukocyte differentiation in the spleen and lymph nodes via flow cytometry was also done. Immediately after exposure, baseline R(L) was significantly elevated in the LM spot welding aerosols, but returned to control level by 24 h postexposure. Airway reactivity to MCh was unaffected. Lung inflammation and cytotoxicity were mild and transient. Lung epithelial permeability was significantly increased after 3 and 8 d, but not after 13 d of exposure to the HM aerosol. HM aerosols also caused vascular endothelial dysfunction and increased CD4+, CD8+ and B cells in the spleen. Only LM aerosols caused increased IL-6 and MCP-1 levels compared with sham after ex vivo LPS stimulation in BAL macrophages. Acute inhalation of mild-steel spot welding fumes at occupationally relevant concentrations may act as an irritant as evidenced by the increased R(L) and result in endothelial dysfunction, but otherwise had minor effects on the lung.

Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis.

PubMed

Erickson, Michelle A; Jude, Joseph; Zhao, Hengjiang; Rhea, Elizabeth M; Salameh, Therese S; Jester, William; Pu, Shelley; Harrowitz, Jenna; Nguyen, Ngan; Banks, William A; Panettieri, Reynold A; Jordan-Sciutto, Kelly L

2017-09-01

Accumulating evidence suggests that O 3 exposure may contribute to CNS dysfunction. Here, we posit that inflammatory and acute-phase proteins in the circulation increase after O 3 exposure and systemically convey signals of O 3 exposure to the CNS. To model acute O 3 exposure, female Balb/c mice were exposed to 3 ppm O 3 or forced air for 2 h and were studied after 6 or 24 h. Of 23 cytokines and chemokines, only KC/CXCL1 was increased in blood 6 h after O 3 exposure. The acute-phase protein serum amyloid A (A-SAA) was significantly increased by 24 h, whereas C-reactive protein was unchanged. A-SAA in blood correlated with total leukocytes, macrophages, and neutrophils in bronchoalveolar lavage from O 3 -exposed mice. A-SAA mRNA and protein were increased in the liver. We found that both isoforms of A-SAA completely crossed the intact blood-brain barrier, although the rate of SAA2.1 influx was approximately 5 times faster than that of SAA1.1. Finally, A-SAA protein, but not mRNA, was increased in the CNS 24 h post-O 3 exposure. Our findings suggest that A-SAA is functionally linked to pulmonary inflammation in our O 3 exposure model and that A-SAA could be an important systemic signal of O 3 exposure to the CNS.-Erickson, M. A., Jude, J., Zhao, H., Rhea, E. M., Salameh, T. S., Jester, W., Pu, S., Harrowitz, J., Nguyen, N., Banks, W. A., Panettieri, R. A., Jr., Jordan-Sciutto, K. L. Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis. © FASEB.

Endogenous osteopontin promotes ozone-induced neutrophil recruitment to the lungs and airway hyperresponsiveness to methacholine

PubMed Central

Barreno, Ramon X.; Richards, Jeremy B.; Schneider, Daniel J.; Cromar, Kevin R.; Nadas, Arthur J.; Hernandez, Christopher B.; Hallberg, Lance M.; Price, Roger E.; Hashmi, Syed S.; Blackburn, Michael R.; Haque, Ikram U.

2013-01-01

Inhalation of ozone (O3), a common environmental pollutant, causes pulmonary injury, pulmonary inflammation, and airway hyperresponsiveness (AHR) in healthy individuals and exacerbates many of these same sequelae in individuals with preexisting lung disease. However, the mechanisms underlying these phenomena are poorly understood. Consequently, we sought to determine the contribution of osteopontin (OPN), a hormone and a pleiotropic cytokine, to the development of O3-induced pulmonary injury, pulmonary inflammation, and AHR. To that end, we examined indices of these aforementioned sequelae in mice genetically deficient in OPN and in wild-type, C57BL/6 mice 24 h following the cessation of an acute (3 h) exposure to filtered room air (air) or O3 (2 parts/million). In wild-type mice, O3 exposure increased bronchoalveolar lavage fluid (BALF) OPN, whereas immunohistochemical analysis demonstrated that there were no differences in the number of OPN-positive alveolar macrophages between air- and O3-exposed wild-type mice. O3 exposure also increased BALF epithelial cells, protein, and neutrophils in wild-type and OPN-deficient mice compared with genotype-matched, air-exposed controls. However, following O3 exposure, BALF neutrophils were significantly reduced in OPN-deficient compared with wild-type mice. When airway responsiveness to inhaled acetyl-β-methylcholine chloride (methacholine) was assessed using the forced oscillation technique, O3 exposure caused hyperresponsiveness to methacholine in the airways and lung parenchyma of wild-type mice, but not OPN-deficient mice. These results demonstrate that OPN is increased in the air spaces following acute exposure to O3 and functionally contributes to the development of O3-induced pulmonary inflammation and airway and lung parenchymal hyperresponsiveness to methacholine. PMID:23666750

A novel approach to analyzing lung cancer mortality disparities: Using the exposome and a graph-theoretical toolchain

PubMed Central

Juarez, Paul D; Hood, Darryl B; Rogers, Gary L; Baktash, Suzanne H; Saxton, Arnold M; Matthews-Juarez, Patricia; Im, Wansoo; Cifuentes, Myriam Patricia; Phillips, Charles A; Lichtveld, Maureen Y; Langston, Michael A

2017-01-01

Objectives The aim is to identify exposures associated with lung cancer mortality and mortality disparities by race and gender using an exposome database coupled to a graph theoretical toolchain. Methods Graph theoretical algorithms were employed to extract paracliques from correlation graphs using associations between 2162 environmental exposures and lung cancer mortality rates in 2067 counties, with clique doubling applied to compute an absolute threshold of significance. Factor analysis and multiple linear regressions then were used to analyze differences in exposures associated with lung cancer mortality and mortality disparities by race and gender. Results While cigarette consumption was highly correlated with rates of lung cancer mortality for both white men and women, previously unidentified novel exposures were more closely associated with lung cancer mortality and mortality disparities for blacks, particularly black women. Conclusions Exposures beyond smoking moderate lung cancer mortality and mortality disparities by race and gender. Policy Implications An exposome approach and database coupled with scalable combinatorial analytics provides a powerful new approach for analyzing relationships between multiple environmental exposures, pathways and health outcomes. An assessment of multiple exposures is needed to appropriately translate research findings into environmental public health practice and policy. PMID:29152601

Deaths in Canada from lung cancer due to involuntary smoking.

PubMed Central

Wigle, D T; Collishaw, N E; Kirkbride, J; Mao, Y

1987-01-01

Recently published evidence indicates that involuntary smoking causes an increased risk of lung cancer among nonsmokers. Information was compiled on the proportion of people who had never smoked among victims of lung cancer, the risk of lung cancer for nonsmokers married to smokers and the prevalence of such exposure. On the basis of these data we estimate that 50 to 60 of the deaths from lung cancer in Canada in 1985 among people who had never smoked were caused by spousal smoking; about 90% occurred in women. The total number of deaths from lung cancer attributable to exposure to tobacco smoke from spouses and other sources (mainly the workplace) was derived by applying estimated age- and sex-specific rates of death from lung cancer attributable to such exposure to the population of Canadians who have never smoked; about 330 deaths from lung cancer annually are attributable to such exposure. PMID:3567810

Occupational exposures and lung cancer risk among Minnesota taconite mining workers.

PubMed

Allen, Elizabeth M; Alexander, Bruce H; MacLehose, Richard F; Nelson, Heather H; Ryan, Andrew D; Ramachandran, Gurumurthy; Mandel, Jeffrey H

2015-09-01

To examine the association between employment duration, elongate mineral particle (EMP) exposure, silica exposure and the risk of lung cancer in the taconite mining industry. We conducted a nested case-control study of lung cancer within a cohort of Minnesota taconite iron mining workers employed by any of the mining companies in operation in 1983. Lung cancer cases were identified by vital records and cancer registry data through 2010. Two age-matched controls were selected from risk sets of cohort members alive and lung cancer free at the time of case diagnosis. Calendar time-specific exposure estimates were made for every job and were used to estimate workers' cumulative exposures. ORs and 95% CIs were estimated using conditional logistic regression. We evaluated total lung cancer risk and risk of histological subtype by total work duration and by cumulative EMP, and silica exposure by quartile of the exposure distribution. A total of 1706 cases and 3381 controls were included in the analysis. After adjusting for work in haematite mining, asbestos exposure and sex, the OR for total duration of employment was 0.99 (95% CI 0.96 to 1.01). The ORs for quartile 4 versus 1 of EMP and silica exposure were 0.82 (95% CI 0.57 to 1.19) and 0.97 (95% CI 0.70 to 1.35), respectively. The risk of each histological subtype of lung cancer did not change with increasing exposure. This study suggests that the estimated taconite mining exposures do not increase the risk of developing lung cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Occupational Exposures and Lung Cancer Risk among Minnesota Taconite Mining Workers

PubMed Central

Allen, Elizabeth M; Alexander, Bruce H; MacLehose, Richard F; Nelson, Heather H; Ryan, Andrew D; Ramachandran, Gurumurthy; Mandel, Jeffrey H

2015-01-01

Objective To examine the association between employment duration, elongate mineral particle (EMP) exposure, and silica exposure and the risk of lung cancer in the taconite mining industry. Methods We conducted a nested case control study of lung cancer within a cohort of Minnesota taconite iron mining workers employed by any of the mining companies in operation in 1983. Lung cancer cases were identified by vital records and cancer registry data through 2010. Two age-matched controls were selected from risk sets of cohort members alive and lung cancer free at the time of case diagnosis. Calendar time-specific exposure estimates were made for every job and were used to estimate workers’ cumulative exposures. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. We evaluated total lung cancer risk and risk of histological subtype by total work duration and by cumulative EMP and silica exposure by quartile of the exposure distribution. Results A total of 1,706 cases and 3,381 controls were included in the analysis. After adjusting for work in hematite mining, asbestos exposure, and sex, the OR for total duration of employment was 0.99 (95% CI: 0.96–1.01). The ORs for quartile 4 versus 1 of EMP and silica exposure were 0.82 (95% CI: 0.57–1.19) and 0.97 (95% CI: 0.70–1.35) respectively. The risk of each histological subtype of lung cancer did not change with increasing exposure. Conclusions This study suggests that the estimated taconite mining exposures do not increase the risk for the development of lung cancer. PMID:25977445

Relationship between pulmonary function and indoor air pollution from coal combustion among adult residents in an inner-city area of southwest China

PubMed Central

Jie, Y.; Houjin, H.; Xun, M.; Kebin, L.; Xuesong, Y.; Jie, X.

2014-01-01

Few studies evaluate the amount of particulate matter less than 2.5 mm in diameter (PM2.5) in relation to a change in lung function among adults in a population. The aim of this study was to assess the association of coal as a domestic energy source to pulmonary function in an adult population in inner-city areas of Zunyi city in China where coal use is common. In a cross-sectional study of 104 households, pulmonary function measurements were assessed and compared in 110 coal users and 121 non-coal users (≥18 years old) who were all nonsmokers. Several sociodemographic factors were assessed by questionnaire, and ventilatory function measurements including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio, and peak expiratory flow rate (PEFR) were compared between the 2 groups. The amount of PM2.5 was also measured in all residences. There was a significant increase in the relative concentration of PM2.5 in the indoor kitchens and living rooms of the coal-exposed group compared to the non-coal-exposed group. In multivariate analysis, current exposure to coal smoke was associated with a 31.7% decrease in FVC, a 42.0% decrease in FEV1, a 7.46% decrease in the FEV1/FVC ratio, and a 23.1% decrease in PEFR in adult residents. The slope of lung function decrease for Chinese adults is approximately a 2-L decrease in FVC, a 3-L decrease in FEV1, and an 8 L/s decrease in PEFR per count per minute of PM2.5 exposure. These results demonstrate the harmful effects of indoor air pollution from coal smoke on the lung function of adult residents and emphasize the need for public health efforts to decrease exposure to coal smoke. PMID:25296361

Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure

PubMed Central

Park, Robert M; Stayner, Leslie T; Petersen, Martin R; Finley-Couch, Melissa; Hornung, Richard; Rice, Carol

2015-01-01

Objectives Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. Methods A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940–2002), a revised cadmium (Cd) exposure matrix and improved work history information. Results Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure–response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m3 Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20–25 years. Conclusions These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 μg/m3 Cd. PMID:22271639

Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory and immune response genes

PubMed Central

Loose, David S.; Gottipati, Koteswara R.; Natarajan, Kartiga; Mitchell, Courtney T.

2016-01-01

The intensification and concentration of animal production operations expose workers to high levels of organic dusts in the work environment. Exposure to organic dusts is a risk factor for the development of acute and chronic respiratory symptoms and diseases. Lung epithelium plays important roles in the control of immune and inflammatory responses to environmental agents to maintain lung health. To better understand the effects of organic dust on lung inflammatory responses, we characterized the gene expression profiles of A549 alveolar and Beas2B bronchial epithelial and THP-1 monocytic cells influenced by exposure to poultry dust extract by DNA microarray analysis using Illumina Human HT-12 v4 Expression BeadChip. We found that A549 alveolar and Beas2B bronchial epithelial and THP-1 cells responded with unique changes in the gene expression profiles with regulation of genes encoding inflammatory cytokines, chemokines, and other inflammatory proteins being common to all the three cells. Significantly induced genes included IL-8, IL-6, IL-1β, ICAM-1, CCL2, CCL5, TLR4, and PTGS2. Validation by real-time qRT-PCR, ELISA, Western immunoblotting, and immunohistochemical staining of lung sections from mice exposed to dust extract validated DNA microarray results. Pathway analysis indicated that dust extract induced changes in gene expression influenced functions related to cellular growth and proliferation, cell death and survival, and cellular development. These data show that a broad range of inflammatory mediators produced in response to poultry dust exposure can modulate lung immune and inflammatory responses. This is the first report on organic dust induced changes in expression profiles in lung epithelial and THP-1 monocytic cells. PMID:26884459

Insulation workers in Belfast. 2. Morbidity in men still at work

PubMed Central

Langlands, Jean H. M.; Wallace, William F. M.; Simpson, Marion J. C.

1971-01-01

Langlands, Jean H. M., Wallace, W. F. M., and Simpson, Marion J. C. (1971).Brit. J. industr. Med.,28, 217-225. Insulation workers in Belfast. 2. Morbidity in men still at work. Two hundred and fifty-two (93%) of the insulation workers in Belfast were examined by chest ϰ-ray, questionnaire, clinical examination, and tests of respiratory function. The frequency of chest ϰ-ray abnormality, lung field or pleural, increased from 13% in men who had worked for less than 10 years to 85% in men who had worked for 30 or more years in the industry. Pleural calcification was found in 15 ϰ-rays. There was evidence suggesting that some men had pleural fibrosis or calcification due to exposure to asbestos in childhood. Rales were present in 61% and clubbing in 11% of men with lung field abnormality, but these were not common when the ϰ-rays showed only pleural abnormality. Where the lung fields were involved there was a restrictive defect with impairment in lung function most marked in the forced vital capacity and single breath carbon monoxide transfer factor, but where the pleura was involved without lung field involvement there was a tendency to impairment of ventilatory function with a normal transfer factor. Cigarette smoking was associated with a greater impairment of lung function than was ϰ-ray abnormality. PMID:5557842

[The dose response decrease of lung function associated with the urinary polycyclic aromatic hydrocarbons metabolites in coke oven workers].

PubMed

Hu, Die; Deng, Qi-fei; Huang, Su-li; He, Yun-feng; Guo, Huan; Wu, Tang-chun

2012-12-01

To analyze the relationship between metabolites of polycyclic aromatic hydrocarbons (PAHs) and lung function in coke oven workers, and to provide scientific basis for further exploring the potential mechanism and developing the preventing strategies of the workers' early lung damage. We measured carbon monoxide, sulfur dioxide, benzene soluble matter, particulate matters, and PAHs at different workplaces of a coke oven plant. Detailed information on demography and occupational health condition of 912 workers were collected. We divided these workers into control group and coke oven group according to their workplaces and the different concentrations of COEs in the environment. We detected 10 urinary PAH metabolites and lung function using gas chromatography-mass spectrometry and spirometric tests, respectively. FEV(1.0) (91.12 ± 13.31) and FEV(1.0)/FVC (108.61 ± 20.37) of the coke oven group is significantly lower than the control group (94.16 ± 15.57, 113.45 ± 19.70). In the coke oven group, the hydroxyphenanthrene and 1-hydroxypyrene are negatively correlated with FEV(1.0)/FVC (β = -0.136, β = -0.100), Ptrend < 0.05 for all. The dose response decrease of lung function is associated with the urinary PAH metabolites in coke oven workers. Indicated that the long exposure to PAHs may cause the early lung damage in coke oven workers, phenanthrene and pyrene may be the main factors.

Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies.

PubMed

Olsson, Ann C; Vermeulen, Roel; Schüz, Joachim; Kromhout, Hans; Pesch, Beate; Peters, Susan; Behrens, Thomas; Portengen, Lützen; Mirabelli, Dario; Gustavsson, Per; Kendzia, Benjamin; Almansa, Josue; Luzon, Veronique; Vlaanderen, Jelle; Stücker, Isabelle; Guida, Florence; Consonni, Dario; Caporaso, Neil; Landi, Maria Teresa; Field, John; Brüske, Irene; Wichmann, Heinz-Erich; Siemiatycki, Jack; Parent, Marie-Elise; Richiardi, Lorenzo; Merletti, Franco; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Plato, Nils; Tardón, Adonina; Zaridze, David; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Stanescu Dumitru, Rodica; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Bueno-de-Mesquita, Bas; Forastiere, Francesco; Brüning, Thomas; Straif, Kurt

2017-03-01

Evidence is limited regarding risk and the shape of the exposure-response curve at low asbestos exposure levels. We estimated the exposure-response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies. We pooled 14 case-control studies conducted in 1985-2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends. The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women. Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure-response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.).

Pulmonary responses in current smokers and ex-smokers following a two hour exposure at rest to clean air and fine ambient air particles

PubMed Central

2013-01-01

Background Increased susceptibility of smokers to ambient PM may potentially promote development of COPD and accelerate already present disease. Objectives To characterize the acute and subacute lung function response and inflammatory effects of controlled chamber exposure to concentrated ambient fine particles (CAFP) with MMAD ≤ 2.5 microns in ex-smokers and lifetime smokers. Methods Eleven subjects, aged 35–74 years, came to the laboratory 5 times; a training day and two exposure days separated by at least 3 weeks, each with a post-exposure visit 22 h later. Double-blind and counterbalanced exposures to “clean air” (mean 1.5 ± 0.6 μg/m3) or CAFP (mean 108.7 ± 24.8 μg/m3 ) lasted 2 h with subjects at rest. Results At 3 h post-exposure subjects’ DTPA clearance half-time significantly increased by 6.3 min per 100 μg/m3 of CAFP relative to “clean air”. At 22 h post-exposure they showed significant reduction of 4.3% per 100 μg/m3 in FEV1 and a significant DLCO decrease by 11.1% per 100 μg/m3 of CAFP relative to “clean air”. At both 3 h and 22 h the HDL cholesterol level significantly decreased by 4.5% and 4.1%, respectively. Other blood chemistries and markers of lung injury, inflammation and procoagulant activity were within the normal range of values at any condition. Conclusions The results suggest that an acute 2 h resting exposure of smokers and ex-smokers to fine ambient particulate matter may transiently affect pulmonary function (spirometry and DLCO) and increase DTPA clearance half-time. Except for a post exposure decrease in HDL no other markers of pulmonary inflammation, prothrombotic activity and lung injury were significantly affected under the conditions of exposure. PMID:24245863

PM2.5 and mortality in long-term prospective cohort studies: cause-effect or statistical associations?

PubMed Central

Gamble, J F

1998-01-01

Concentrations of ambient PM2.5 (particulate matter <2.5 microm in aerodynamic diameter) were associated with increased mortality in two prospective cohort studies. In this paper, I assess whether the weight of the evidence supports a causal association. I assumed the study population in each city to have the same exposure; therefore, these are ecologic studies because exposure is at the group level. Health outcome and confounding data are at the individual level. Ambient PM concentrations are inadequate surrogates for personal exposure because they are at the group level and comprise only a small proportion of personal exposure, they change over time, and they constitute only a small proportion of a life span. The strength of association and exposure-response relationships cannot be determined because the ecologic group-level risks of PM2.5 are overestimated 150- to 300-fold based on an analogy with individual-level exposure to inhaled cigarette smoke. Risk estimates may also be high because of confounding from factors such as physical activity and lung function. The evidence is not coherent because the stronger associations are expected to be with morbidity, but instead are with mortality. For example, PM2.5 was associated with mortality but not with measurable reductions in lung function. Biological plausibility is lacking because lifetime exposure of rats to combustion products at concentrations two to three orders of magnitude higher than air pollution levels cause lung overloading but no consistent reduction in survival. Criteria for quantitative risk assessment are not met so the data are not useful for setting air quality standards. The weight of evidence suggests there is no substantive basis for concluding that a cause-effect relationship exists between long-term ambient PM2.5 and increased mortality. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:9721253

Diesel Exhaust Exposure and the Risk of Lung Cancer—A Review of the Epidemiological Evidence

PubMed Central

Sun, Yi; Bochmann, Frank; Nold, Annette; Mattenklott, Markus

2014-01-01

To critically evaluate the association between diesel exhaust (DE) exposure and the risk of lung cancer, we conducted a systematic review of published epidemiological evidences. To comprehensively identify original studies on the association between DE exposure and the risk of lung cancer, literature searches were performed in literature databases for the period between 1970 and 2013, including bibliographies and cross-referencing. In total, 42 cohort studies and 32 case-control studies were identified in which the association between DE exposures and lung cancer was examined. In general, previous studies suffer from a series of methodological limitations, including design, exposure assessment methods and statistical analysis used. A lack of objective exposure information appears to be the main problem in interpreting epidemiological evidence. To facilitate the interpretation and comparison of previous studies, a job-exposure matrix (JEM) of DE exposures was created based on around 4,000 historical industrial measurements. The values from the JEM were considered during interpretation and comparison of previous studies. Overall, neither cohort nor case-control studies indicate a clear exposure-response relationship between DE exposure and lung cancer. Epidemiological studies published to date do not allow a valid quantification of the association between DE and lung cancer. PMID:24473109

Relationship between birth weight, maternal smoking during pregnancy and childhood and adolescent lung function: A path analysis.

PubMed

Balte, Pallavi; Karmaus, Wilfried; Roberts, Graham; Kurukulaaratchy, Ramesh; Mitchell, Frances; Arshad, Hasan

2016-12-01

Low birth weight and gestational maternal smoking have been linked with reduced lung function in children in many cross sectional studies. However, these associations have not yet been assessed with repeated measurements of lung function. Our aim was to investigate the effects of birth weight, gestational age, and gestational maternal smoking on lung function in children at age 10 and 18 years. In the Isle of Wight birth cohort spirometry was performed at age 10 and 18 years. Information on birth weight and gestational age were obtained from hospital records. Mothers were asked about smoking during pregnancy. We employed linear mixed models to estimate the effect of these risk factors on repeated measurements of lung function. We considered maternal asthma, sex, neonatal intensive care unit admission, height, socio-economic status, personal smoking in participants at age 18, body mass index and environmental tobacco smoke exposure as potential confounders. Finally, we used path analysis to determine links between birth weight, gestational age and gestational maternal smoking on lung function at age 10 and 18 years. Linear mixed models showed that with every 1 kg increase in birth weight, Forced expiratory volume in one second (FEV 1 ) increased by 42.6 ± 17.2 mL and Forced expiratory flow between 25% and 75% (FEF 25-75 ) of Forced vital capacity (FVC) increased by 95.5 ± 41.2 mL at age 18 years after adjusting for potential confounders. Path analysis suggested that birth weight had positive direct effects on FEV 1 and FEF 25-75 and positive indirect effect on FVC at 10 years which were carried forward to 18 years. Additionally, results also suggested a positive association between gestational age and FEV 1 , FVC and FEF 25-75  at ages 10 and 18 years and an inverse association between gestational smoke exposure and FEV 1 /FVC ratio and FEF 25-75  at age 18 years. Higher birth weight and gestational age were associated with higher FEV 1 , FVC and FEF 25-75 and maternal smoking during pregnancy was associated with reduced FEV 1 /FVC ratio and FEF 25-75 . The use of path analysis can improve our understanding of underlying "causal" pathways among different prenatal and childhood factors that affect lung function in both pre-adolescent and adolescent periods. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lung function in insulation workers.

PubMed Central

Clausen, J; Netterstrøm, B; Wolff, C

1993-01-01

To evaluate the effects of working with modern insulation materials (rock and glass wool), the members of the Copenhagen Union of Insulation Workers were invited to participate in a study based on a health examination that included lung function tests. Three hundred and forty men (74%) agreed to participate, and 166 bus drivers served as the control group. Age distribution, height, and smoking habits were similar in the two groups. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were used as tests for lung function. There were no differences in FVC between the study and control groups, but the insulation workers had significantly lower values of FEV1 (mean 2.51) compared with the controls (mean 3.4 1), independent of smoking habits. Six years before the present study, 114 of the insulation workers participated in a similar study, and eight years after the initial study, the lung function of 59 of the bus drivers was tested. The decline in FVC in insulation workers who smoked was significantly higher (7.7 cl/year) than in bus drivers who smoked (3.1 cl/year); the decline in FEV1 was significantly higher in insulation workers independent of smoking habits (17.0 cl/year v 2.9 cl/year). Self assessed former exposure to asbestos was not associated with lung function in insulation workers. The study concludes that working with modern insulation materials is associated with increased risk of developing obstructive lung disease. PMID:8457492

[Impacts of airborne particulate matter and its components on respiratory system health].

PubMed

Cao, L M; Zhou, Y; Zhang, Z; Sun, W W; Mu, G; Chen, W H

2016-12-06

Nowadays, particulate air pollution has been a global environmental problem. Numerous studies has shown that long-term exposure to high level of airborne particulate matter (PM) can damage human health. Respiratory system, as a direct portal to contact with particulate matter, can be more susceptible to airborne particulates. Summarizing latest five-year epidemiological research, the present review is focused on the effects of PM on respiratory system health in different age groups. In detail, we investigated the harmful effect of PM, or its components on three common respiratory diseases, including lung function decline, chronic obstructive pulmonary disease (COPD) and asthma. The result showed that, to a certain degree, PM could induce the decline of lung function, the development and the exacerbation of COPD and asthma by oxidative stress and inflammatory reaction. And it may prompt that exposure to PM can be an improtant risk factor for the respiratory system health.

The influence of polycyclic aromatic hydrocarbons on lung function in a representative sample of the Canadian population.

PubMed

Cakmak, Sabit; Hebbern, Chris; Cakmak, Jasmine D; Dales, Robert E

2017-09-01

We investigated the associations between exposure to polycyclic aromatic hydrocarbons (PAHs) and selected respiratory physiologic measures in cycles 2 and 3 of the Canadian Health Measures Survey, a nationally representative population sample. Using generalized linear mixed models, we tested the association between selected PAH metabolites and 1-second forced expiratory volume (FEV 1 ), forced vital capacity (FVC), and the ratio between the two (FEV 1 /FVC) in 3531 people from 6 to 79 years of age. An interquartile change in urinary PAH metabolite was associated with significant decrements in FEV 1 and FVC for eight PAHs, 2-hydroxynapthalene, 1-, and 2-hydroxyphenanthrene, 2-, 3-, and 9-hydroxyfluorene and 3- and 4-hydroxyphenanthrene. Exposure to PAH may negatively affect lung function in the Canadian population. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Biological monitoring of glazers exposed to lead in the ceramics industry in Iran.

PubMed

Shouroki, Fatemeh Kargar; Shahtaheri, Seyed Jamaleddin; Golbabaei, Farideh; Barkhordari, Abolfazle; Rahimi-Froushani, Abbas

2015-01-01

Exposure to heavy metals, particularly lead, takes place in the ceramics industry. Lead is used in glaze to produce smooth and brilliant surfaces; thus, there is a likelihood of occupational adverse effects on humans. Urine samples were collected from 49 glazers at the start and end of the work shifts (98 samples). Solid phase extraction was used for separation and pre-concentration of the analyte. Samples were analysed by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). Lung function tests were performed on both control and lead exposed subjects. Statistical analysis of covariance (ANCOVA) was used to evaluate the data obtained. The concentration of lead in glazers was 6.37 times higher than in the control group. Lung functions were significantly lower in the glazers compared to the control group (p < 0.001). Results showed that poor ventilation systems, overtime work and work history are effective determinants of high exposure levels.

Indium Lung Disease

PubMed Central

Nakano, Makiko; Omae, Kazuyuki; Takeuchi, Koichiro; Chonan, Tatsuya; Xiao, Yong-long; Harley, Russell A.; Roggli, Victor L.; Hebisawa, Akira; Tallaksen, Robert J.; Trapnell, Bruce C.; Day, Gregory A.; Saito, Rena; Stanton, Marcia L.; Suarthana, Eva; Kreiss, Kathleen

2012-01-01

Background: Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. Methods: To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. Results: Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Conclusions: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies. PMID:22207675

Which early life events or current environmental and lifestyle factors influence lung function in adolescents? - results from the GINIplus & LISAplus studies.

PubMed

Luzak, Agnes; Fuertes, Elaine; Flexeder, Claudia; Standl, Marie; von Berg, Andrea; Berdel, Dietrich; Koletzko, Sibylle; Heinrich, Joachim; Nowak, Dennis; Schulz, Holger

2017-07-12

Various factors may affect lung function at different stages in life. Since investigations that simultaneously consider several factors are rare, we examined the relative importance of early life, current environmental/lifestyle factors and allergic diseases on lung function in 15-year-olds. Best subset selection was performed for linear regression models to investigate associations between 21 diverse early life events and current factors with spirometric parameters (forced vital capacity, forced expiratory volume in 1 s and maximal mid-expiratory flow (FEF 25-75 )) in 1326 participants of the German GINIplus and LISAplus birth cohorts. To reduce model complexity, one model for each spirometric parameter was replicated 1000 times in random subpopulations (N = 884). Only those factors that were included in >70% of the replication models were retained in the final analysis. A higher peak weight velocity and early lung infections were the early life events prevalently associated with airflow limitation and FEF 25-75 . Current environmental/lifestyle factors at age 15 years and allergic diseases that were associated with lung function were: indoor second-hand smoke exposure, vitamin D concentration, body mass index (BMI) and asthma status. Sex and height captured the majority of the explained variance (>75%), followed by BMI (≤23.7%). The variance explained by early life events was comparatively low (median: 4.8%; range: 0.2-22.4%), but these events were consistently negatively associated with airway function. Although the explained variance was mainly captured by well-known factors included in lung function prediction equations, our findings indicate early life and current factors that should be considered in studies on lung health among adolescents.

Air Pollution from Livestock Farms Is Associated with Airway Obstruction in Neighboring Residents.

PubMed

Borlée, Floor; Yzermans, C Joris; Aalders, Bernadette; Rooijackers, Jos; Krop, Esmeralda; Maassen, Catharina B M; Schellevis, François; Brunekreef, Bert; Heederik, Dick; Smit, Lidwien A M

2017-11-01

Livestock farm emissions may not only affect respiratory health of farmers but also of neighboring residents. To explore associations between spatial and temporal variation in pollutant emissions from livestock farms and lung function in a general, nonfarming, rural population in the Netherlands. We conducted a cross-sectional study in 2,308 adults (age, 20-72 yr). A pulmonary function test was performed measuring prebronchodilator and post-bronchodilator FEV 1 , FVC, FEV 1 /FVC, and maximum mid-expiratory flow (MMEF). Spatial exposure was assessed as (1) number of farms within 500 m and 1,000 m of the home, (2) distance to the nearest farm, and (3) modeled annual average fine dust emissions from farms within 500 m and 1,000 m of the home address. Temporal exposure was assessed as week-average ambient particulate matter <10 μm in diameter and ammonia (NH 3 ) concentrations before lung function measurements. Data were analyzed with generalized additive models (smoothing). A negative association was found between the number of livestock farms within a 1,000-m buffer from the home address and MMEF, which was more pronounced in participants without atopy. No associations were found with other spatial exposure variables. Week-average particulate matter <10 μm in diameter and NH 3 levels were negatively associated with FEV 1 , FEV 1 /FVC, and MMEF. In a two-pollutant model, only NH 3 remained associated. A 25-μg/m 3 increase in NH 3 was associated with a 2.22% lower FEV 1 (95% confidence interval, -3.69 to -0.74), FEV 1 /FVC of -1.12% (-1.96 to -0.28), and MMEF of -5.67% (-8.80 to -2.55). Spatial and temporal variation in livestock air pollution emissions are associated with lung function deficits in nonfarming residents.

Detection of early changes in lung cell cytology by flow-systems analysis techniques. Progress report, January 1--December 31, 1978. [Resulting from exposure to toxic agents associated with production and use of synthetic fuels from oil shale and coal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinkamp, J.A.; Wilson, J.S.; Svitra, Z.V.

1979-02-01

This report summarizes ongoing experiments to develop cytological and biochemical indicators for measuring damage to respiratory tract cells of experimental animals exposed by inhalation to environmental toxic agents. The specific goal is to apply flow cytometric methods to analyze and detect changes in lung epithelium as a function of exposure to toxic agents associated with the production and utilization of synthetic fuels from oil shale and coal. During the past 6 months, hamsters were exposed to raw and spent oil shale particulates, silica dust, and ozone, and DNA content measurements were performed on lung cell samples. Although initial shale exposuresmore » did not yield the expected results, recent data show atypical changes in DNA content per cell distributions. Ozone exposures also were expanded to include DNA measurements and cytology, ranging up to 72 h postexposure. Progress was achieved in developing a new method for quantitating pulmonary macrophage phagocytosis in rats using micron-sized fluorescent spheres. New methods for determining alkaline phosphatase, DNA content, and protein also were under development. Plans are to continue developing cytological and biochemical markers for measuring atypical cellular changes, including macrophage function, and to emphasize exposing experimental animals to particulates and gaseous agents for studying dose-damage relationships.« less

Exposure-specific lung cancer risks in Chinese chrysotile textile workers and mining workers.

PubMed

Wang, Xiaorong; Lin, Sihao; Yano, Eiji; Yu, Ignatius T S; Courtice, Midori; Lan, Yajia; Christiani, David C

2014-08-01

Whether there is a difference in the exposure-response slope for lung cancer between mining workers and textile workers exposed to chrysotile has not been well documented. This study was carried out to evaluate exposure-specific lung cancer risks in Chinese chrysotile textile workers and mining workers. A chrysotile mining worker cohort and a chrysotile textile worker cohort were observed concurrently for 26 years. Information on workers' vital status, occupational history and smoking habits were collected, and causes and dates of deaths were verified from death registries. Individual cumulative fiber exposures were estimated based on periodic dust/fiber measurements from different workshops, job title and duration, and categorized into four levels (Q1-Q4). Standardized mortality ratios (SMRs) for lung cancer were calculated and stratified by industry and job title with reference of the national rates. Cox proportional hazard models were fit to estimate the exposure-specific lung cancer risks upon adjustment for age and smoking, in which an external control cohort consisting of industrial workers without asbestos exposure was used as reference group for both textile and mining workers. SMRs were almost consistent with exposure levels in terms of job titles and workshops. A clear exposure-response relationship between lung cancer mortality and exposure levels was observed in both cohorts. At low exposure levels (Q1 and Q2), textile workers displayed higher death risks of lung cancer than mining workers. However, similarly considerably high risks were observed at higher exposure levels, with hazard ratios of over 8 and 11 at Q3 and Q4, respectively, for both textile and mining workers, after both age and smoking were adjusted. The chrysotile textile workers appeared to have a higher risk of lung cancer than the mining workers at a relatively low exposure level, but no difference was observed at a high exposure level, where both cohorts displayed a considerably high risk. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Mortality of iron miners in Lorraine (France): relations between lung function and respiratory symptoms and subsequent mortality.

PubMed Central

Chau, N; Benamghar, L; Pham, Q T; Teculescu, D; Rebstock, E; Mur, J M

1993-01-01

An increased mortality from lung and stomach cancer was found in previous studies on Lorraine iron miners. A detailed analysis, however, was not possible due to the lack of data for survivors. In this study the cohort included 1178 workers selected at random from all the 5300 working miners aged between 35 and 55 at the start of the follow up period, which ranged from 1975 to 1985. Occupational exposures and tobacco consumption, lung function tests, and respiratory symptoms were assessed for each subject in 1975, 1980, and 1985. This study confirmed the excess of lung cancer (standardised mortality ratio (SMR) = 389, p < 0.001) and of stomach cancer (SMR = 273, p < 0.05). There was no excess of lung cancer in non-smokers and moderate smokers (< 20 pack-years) or the miners who worked only at the surface or underground for less than 20 years. A significant excess (SMR = 349, p < 0.001) was found in moderate smokers when they worked underground for between 20 and 29 years. Heavy smokers (over 30 pack-years) or subjects who worked underground for more than 30 years experienced a high risk: SMR = 478 (p < 0.001) for moderate smokers who worked underground for over 30 years; 588 (p < 0.001) for heavy smokers who worked underground for between 20 and 29 years; and 877 (p < 0.001) for heavy smokers who worked underground for over 30 years. This showed an interaction between smoking and occupational exposure. The excess mortality from lung cancer was because there were some subjects who died young (from 45 years old). Comparison with the results of a previous study showed that additional hazards produced by diesel engines and explosives increased the mortality from lung cancer. The SMR was higher than 400 (p < 0.001) from 45 years old instead of from 56 years. A relation was found between a decrease in vital capacity (VC), forced expiratory volume in one second (FEV1) and of FEV1/VC and mortality from all causes and from lung cancer in heavy smokers or men who had worked underground for more than 20 years. Respiratory symptoms were related to mortality from lung cancer among smokers (moderate and heavy) who worked underground for more than 20 years. It is considered that the risk of lung cancer in the Lorraine iron miners was mainly due to dust, diesel engines, and explosives although the role of low exposure to radon daughters could not be totally excluded. PMID:8280627

Corticosteroid treatment inhibits airway hyperresponsiveness and lung injury in a murine model of chemical-induced airway inflammation.

PubMed

Wigenstam, Elisabeth; Jonasson, Sofia; Koch, Bo; Bucht, Anders

2012-11-15

Exposure to toxic alkylating mustard agents causes both acute and long-term effects to the lungs as indicated by increased number of inflammatory cells in airways, lung edema and lung tissue fibrosis. We have previously demonstrated that treatment with the corticosteroid dexamethasone 1 h after lung exposure to the nitrogen mustard analog melphalan protects mice from acute and sub-acute inflammatory responses, as well as from lung tissue fibrosis. In order to address the importance of early anti-inflammatory treatment, we investigated the therapeutic effect of dexamethasone administered 1, 2 or 6 h following exposure to melphalan. C57BL/6 mice were exposed to melphalan and treated with dexamethasone 1, 2 or 6 h after exposure. Twenty hours or 14 days post exposure mice were subjected to analysis of respiratory mechanics where the effects of incremental doses of methacholine on central and peripheral lung components were measured. We also determined the amount of inflammatory cells in the bronchoalveolar lavage fluid and measured the amount of collagen content in the lungs. Melphalan exposure increased airway hyperresponsiveness in both central and peripheral airways and induced an airway inflammation dominated by infiltration of macrophages and neutrophils. Dexamethasone given 1 h after exposure to melphalan provided better protection against airway inflammation than administration 2 or 6 h after exposure. Collagen deposition 14 days after exposure was decreased due to dexamethasone treatment. Early treatment with dexamethasone is important in order to reduce the airway hyperresponsiveness and inflammation caused by toxic alkylating mustards such as melphalan. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The effects of electromagnetic pulse on the protein levels of tight junction associated-proteins in the cerebral cortex, hippocampus, heart, lung, and testis of rats.

PubMed

Qiu, LianBo; Chen, Chen; Ding, GuiRong; Zhou, Yan; Zhang, MengYao

2011-08-01

To investigate changes in the expression of tight junction (TJ) proteins in the cerebral cortex, hippocampus, heart, lung, and testes of rats after exposure to electromagnetic pulse (EMP). Eighteen adult male Sprague-Dawley rats were divided into sham and exposure groups. The exposure groups received EMP at 200 kV/m for 200 pulses with a repetition rate of 1 Hz. The expression of TJ proteins (ZO-1, occludin, actin) in the several organs was examined by western blotting. ZO-1 levels in the cerebral cortex decreased 1 h and 3 h after EMP exposure compared with sham group (P<0.05). No significant difference was observed for occludin and actin. ZO-1 levels in the hippocampus increased 1 h and 3 h post-exposure (P<0.05), and occludin decreased after 3 h (P<0.05); however, actin was unaffected. ZO-1 levels in the heart increased 3 h post-exposure (P<0.05), occludin decreased 3 h post-exposure (P<0.05), and actin increased 1 h and 3 h post-exposure (P<0.05). ZO-1, occludin and actin levels in the lung decreased compared with those in the sham group (P<0.05). ZO-1 and occludin levels in the testes decreased 1 h and 3 h post-exposure (P<0.05), but actin showed no significant change. Exposure to EMP altered the expression levels of TJ proteins, particularly ZO-1, in the organs of adult male rats, which may induce changes in barrier structure and function. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

Mortality Among Workers Exposed to Toluene Diisocyanate in the US Polyurethane Foam Industry: Update and Exposure-Response Analyses

PubMed Central

Pinkerton, Lynne E.; Yiin, James H.; Daniels, Robert D.; Fent, Kenneth W.

2017-01-01

Background Mortality among 4,545 toluene diisocyante (TDI)-exposed workers was updated through 2011. The primary outcome of interest was lung cancer. Methods Life table analyses, including internal analyses by exposure duration and cumulative TDI exposure, were conducted. Results Compared with the US population, all cause and all cancer mortality was increased. Lung cancer mortality was increased but was not associated with exposure duration or cumulative TDI exposure. In post hoc analyses, lung cancer mortality was associated with employment duration in finishing jobs, but not in finishing jobs involving cutting polyurethane foam. Conclusions Dermal exposure, in contrast to inhalational exposure, to TDI is expected to be greater in finishing jobs and may play a role in the observed increase in lung cancer mortality. Limitations include the lack of smoking data, uncertainty in the exposure estimates, and exposure estimates that reflected inhalational exposure only. PMID:27346061

Household Air Pollution Exposure and Influence of Lifestyle on Respiratory Health and Lung Function in Belizean Adults and Children: A Field Study

PubMed Central

Kurti, Stephanie P.; Kurti, Allison N.; Emerson, Sam R.; Rosenkranz, Richard R.; Smith, Joshua R.; Harms, Craig A.; Rosenkranz, Sara K.

2016-01-01

Household air pollution (HAP) contributes to the global burden of disease. Our primary purpose was to determine whether HAP exposure was associated with reduced lung function and respiratory and non-respiratory symptoms in Belizean adults and children. Our secondary purpose was to investigate whether lifestyle (physical activity (PA) and fruit and vegetable consumption (FV)) is associated with reported symptoms. Belizean adults (n = 67, 19 Male) and children (n = 23, 6 Male) from San Ignacio Belize and surrounding areas participated in this cross-sectional study. Data collection took place at free walk-in clinics. Investigators performed initial screenings and administered questionnaires on (1) sources of HAP exposure; (2) reported respiratory and non-respiratory symptoms and (3) validated lifestyle questionnaires. Participants then performed pulmonary function tests (PFTs) and exhaled breath carbon monoxide (CO). There were no significant associations between HAP exposure and pulmonary function in adults. Increased exhaled CO was associated with a significantly lower forced expiratory volume in 1-s divided by forced vital capacity (FEV1/FVC) in children. Exposed adults experienced headaches, burning eyes, wheezing and phlegm production more frequently than unexposed adults. Adults who met PA guidelines were less likely to experience tightness and pressure in the chest compared to those not meeting guidelines. In conclusion, adults exposed to HAP experienced greater respiratory and non-respiratory symptoms, which may be attenuated by lifestyle modifications. PMID:27367712

Cement Dust Exposure and Perturbations in Some Elements and Lung and Liver Functions of Cement Factory Workers

PubMed Central

Richard, Egbe Edmund; Augusta Chinyere, Nsonwu-Anyanwu; Jeremaiah, Offor Sunday; Opara, Usoro Chinyere Adanna; Henrieta, Etukudo Maise; Ifunanya, Egbe Deborah

2016-01-01

Background. Cement dust inhalation is associated with deleterious health effects. The impact of cement dust exposure on the peak expiratory flow rate (PEFR), liver function, and some serum elements in workers and residents near cement factory were assessed. Methods. Two hundred and ten subjects (50 workers, 60 residents, and 100 controls) aged 18–60 years were studied. PEFR, liver function {aspartate and alanine transaminases (AST and ALT) and total and conjugated bilirubin (TB and CB)}, and serum elements {lead (Pb), copper (Cu), manganese (Mn), iron (Fe), cadmium (Cd), selenium (Se), chromium (Cr), zinc (Zn), and arsenic (As)} were determined using peak flow meter, colorimetry, and atomic absorption spectrometry, respectively. Data were analysed using ANOVA and correlation at p = 0.05. Results. The ALT, TB, CB, Pb, As, Cd, Cr, Se, Mn, and Cu were significantly higher and PEFR, Fe, and Zn lower in workers and residents compared to controls (p < 0.05). Higher levels of ALT, AST, and Fe and lower levels of Pb, Cd, Cr, Se, Mn, and Cu were seen in cement workers compared to residents (p < 0.05). Negative correlation was observed between duration of exposure and PEFR (r = −0.416, p = 0.016) in cement workers. Conclusions. Cement dust inhalation may be associated with alterations in serum elements levels and lung and liver functions while long term exposure lowers peak expiratory flow rate. PMID:26981118

Tobacco use among designated air pollution victims and its association with lung function and respiratory symptoms: a retrospective cross-sectional study.

PubMed

Kotaki, Kenji; Senjyu, Hideaki; Tanaka, Takako; Yano, Yudai; Miyamoto, Naomi; Nishinakagawa, Tsuyoshi; Yanagita, Yorihide; Asai, Masaharu; Kozu, Ryo; Tabusadani, Mitsuru; Sawai, Terumitsu; Honda, Sumihisa

2014-07-31

We sought to elucidate the long-term association of tobacco use and respiratory health in designated pollution victims with and without obstructive pulmonary defects. A retrospective cross-sectional study. The register of pollution victims in Kurashiki, Japan. 730 individuals over 65 years of age previously diagnosed with pollution-related respiratory disease. Patients were classified into four groups according to their smoking status and whether they had obstructive pulmonary disease. We then compared the prevalence of respiratory symptoms and lung function over time between groups. Spirometry was performed and a respiratory health questionnaire completed in the same season each year for up to 30 years. Rates of smoking and respiratory disease were high in our sample. Although respiratory function in non-smoking patients did not completely recover, the annual rate of change in lung function was within the normal range (p<0.01). However, smokers had worse lung function and were more likely to report more severe pulmonary symptoms (p<0.01). Patients' respiratory function did not fully recover despite improved air quality. Our results suggest that, in the context of exposure to air pollution, tobacco use causes additional loss of lung function and exacerbates respiratory symptoms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Pesticide exposures and respiratory health in general populations.

PubMed

Ye, Ming; Beach, Jeremy; Martin, Jonathan W; Senthilselvan, Ambikaipakan

2017-01-01

Human exposures to pesticides can occur in the workplace, in the household and through the ambient environment. While several articles have reviewed the impact of pesticide exposures on human respiratory health in occupational settings, to the best of our knowledge, this article is the first one to review published studies on the association between pesticide exposures and human respiratory health in the general populations. In this article, we critically reviewed evidences up to date studying the associations between non-occupational pesticide exposures and respiratory health in general populations. This article also highlighted questions arising from these studies, including our recent analyses using the data from the Canadian Health Measures Survey (CHMS), for future research. We found few studies have addressed the impact of environmental pesticide exposures on respiratory health, especially on lung function, in general populations. In the studies using the data from CHMS Cycle 1, exposures to OP insecticides, pyrethroid insecticides, and the organochlorine pesticide DDT were associated with impaired lung function in the Canadian general population, but no significant associations were observed for the herbicide 2,4-D. Future research should focus on the potential age-specific and pesticide-specific effect on respiratory health in the general population, and repeated longitudinal study design is critical for assessing the temporal variations in pesticide exposures. Research findings from current studies of non-occupational pesticide exposures and their health impact in general population will help to improve the role of regulatory policies in mitigating pesticide-related public health problems, and thereafter providing greater benefit to the general population. Copyright © 2016. Published by Elsevier B.V.

Association between environmental factors including second-hand smoke and primary lung cancer in dogs.

PubMed

Zierenberg-Ripoll, A; Pollard, R E; Stewart, S L; Allstadt, S D; Barrett, L E; Gillem, J M; Skorupski, K A

2018-06-01

To estimate prevalence of exposure to environmental tobacco smoke and other environmental toxins in dogs with primary lung tumours and to analyse association between exposure and lung tumour development. In this case-control study, an owner survey was developed to collect data on patient characteristics, general health care and environmental exposures. Dogs diagnosed with primary lung carcinomas formed the Case group. Dogs diagnosed with mast cell tumours served as Control Group 1 and dogs diagnosed with neurologic disease served as Control Group 2. Associations between diagnosis of primary lung tumour and patient and environmental exposure variables were analysed using bivariate and multivariate statistical methods. A total of 1178 owner surveys were mailed and 470 surveys were returned and included in statistical analysis, including 135 Cases, 169 dogs in Control Group 1 and 166 dogs in Control Group 2. An association between exposure to second-hand smoke and prevalence of primary lung cancer was not identified in this study. Second-hand smoke is associated with primary lung cancer in people but a definitive association has not been found in dogs. The results of this study suggest that tobacco smoke exposure may not be associated with primary lung cancer development in dogs but study limitations may have precluded detection of an association. © 2017 British Small Animal Veterinary Association.

Effects of ozone on the defense to a respiratory Listeria monocytogenes infection in the rat. Suppression of macrophage function and cellular immunity and aggravation of histopathology in lung and liver during infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Loveren, H.; Rombout, P.J.; Wagenaar, S.S.

1988-07-01

We have investigated the effect of exposure to ozone on defense mechanisms to a respiratory infection with Listeria monocytogenes in the rat. For this purpose rats were continuously exposed to O/sub 3/ concentrations ranging from 0.25 to 2.0 mg/m3 for a period of 1 week. In this model defense to a respiratory infection with Listeria depends on acquired specific cellular immune responses, as well as on natural nonspecific defense mechanisms. The results confirm earlier findings that show that ozone exposure can suppress the capacity of macrophages to ingest and kill Listeria. Moreover, the results show that ozone can also havemore » a suppressive effect on the development of cellular immune responses to a respiratory Listeria infection, i.e., on T/B ratios in lung draining lymph nodes, delayed-type hypersensitivity responses to Listeria antigen, and lymphoproliferative responses in spleen and lung draining lymph nodes to Listeria antigen. The effects on the specific immune responses are especially overt if exposure to the oxidant gas occurs during an ongoing primary infection. The pathological lesions induced by a pulmonary Listeria monocytogenes infection were characterized by multifocal infiltrates of histiocytic and lymphoid cells. The foci sometimes had a granulomatous appearance. Moreover, the cellularity of the interstitial tissues was increased. In the lung many diffuse alveolar macrophages could be seen in the alveoli. Ozone exposure greatly increased the severity of the lung lesions and also of liver lesions resulting from the pulmonary infection. A prominent finding was the formation of granulomas in ozone-exposed and Listeria-infected rats.« less

Inactivation, Clearance, and Functional Effects of Lung-Instilled Short and Long Silver Nanowires in Rats

PubMed Central

2017-01-01

There is a potential for silver nanowires (AgNWs) to be inhaled, but there is little information on their health effects and their chemical transformation inside the lungs in vivo. We studied the effects of short (S-AgNWs; 1.5 μm) and long (L-AgNWs; 10 μm) nanowires instilled into the lungs of Sprague–Dawley rats. S- and L-AgNWs were phagocytosed and degraded by macrophages; there was no frustrated phagocytosis. Interestingly, both AgNWs were internalized in alveolar epithelial cells, with precipitation of Ag2S on their surface as secondary Ag2S nanoparticles. Quantitative serial block face three-dimensional scanning electron microscopy showed a small, but significant, reduction of NW lengths inside alveolar epithelial cells. AgNWs were also present in the lung subpleural space where L-AgNWs exposure resulted in more Ag+ve macrophages situated within the pleura and subpleural alveoli, compared with the S-AgNWs exposure. For both AgNWs, there was lung inflammation at day 1, disappearing by day 21, but in bronchoalveolar lavage fluid (BALF), L-AgNWs caused a delayed neutrophilic and macrophagic inflammation, while S-AgNWs caused only acute transient neutrophilia. Surfactant protein D (SP-D) levels in BALF increased after S- and L-AgNWs exposure at day 7. L-AgNWs induced MIP-1α and S-AgNWs induced IL-18 at day 1. Large airway bronchial responsiveness to acetylcholine increased following L-AgNWs, but not S-AgNWs, exposure. The attenuated response to AgNW instillation may be due to silver inactivation after precipitation of Ag2S with limited dissolution. Our findings have important consequences for the safety of silver-based technologies to human health. PMID:28221763

BIO 300, a nanosuspension of genistein, mitigates pneumonitis/fibrosis following high-dose radiation exposure in the C57L/J murine model.

PubMed

Jackson, Isabel L; Zodda, Andrew; Gurung, Ganga; Pavlovic, Radmila; Kaytor, Michael D; Kuskowski, Michael A; Vujaskovic, Zeljko

2017-12-01

BIO 300 nanosuspension (Humanetics Corporation) is being developed as a medical countermeasure (MCM) for the mitigation of the delayed effects of acute radiation exposure, specifically pneumonitis and fibrosis of the lung. The objective of this study was to determine the best dose and treatment duration of BIO 300 to mitigate lung injury and improve the likelihood for survival in C57L/J mice exposed to whole thorax lung irradiation (WTLI). Age- and sex-matched C57L/J mice received a single dose of 11.0 or 12.5 Gy WTLI. BIO 300 (200 or 400 mg·kg -1 , oral gavage) was administered daily starting 24 h post-exposure for a duration of 2, 4, 6 or, in some cases, 10 weeks. Non-treated controls were included for comparison in both sexes. Animals were observed daily for signs of major morbidity. Respiratory function was assessed biweekly. Lungs were collected, weighed and paraffin embedded for histological evaluation post mortem. BIO 300 administered at an oral dose of 400 mg·kg -1 for 4 to 6 weeks starting 24 h post-WTLI reduced morbidity associated with WTLI. The improvement in survival correlated with reduced respiratory frequency and enhanced pause. The irradiated lungs of mice treated with BIO 300 (400 mg·kg -1 ) for 4 to 6 weeks displayed less morphological damage and airway loss due to oedema, congestion and fibrotic scarring than the untreated, irradiated controls. BIO 300 is a promising MCM candidate to mitigate pneumonitis/fibrosis when administered daily for 4-6 weeks starting 24 h post-exposure. © 2017 The British Pharmacological Society.

Air pollution, airway inflammation, and lung function in a cohort study of Mexico City schoolchildren.

PubMed

Barraza-Villarreal, Albino; Sunyer, Jordi; Hernandez-Cadena, Leticia; Escamilla-Nuñez, Maria Consuelo; Sienra-Monge, Juan Jose; Ramírez-Aguilar, Matiana; Cortez-Lugo, Marlene; Holguin, Fernando; Diaz-Sánchez, David; Olin, Anna Carin; Romieu, Isabelle

2008-06-01

The biological mechanisms involved in inflammatory response to air pollution are not clearly understood. In this study we assessed the association of short-term air pollutant exposure with inflammatory markers and lung function. We studied a cohort of 158 asthmatic and 50 nonasthmatic school-age children, followed an average of 22 weeks. We conducted spirometric tests, measurements of fractional exhaled nitric oxide (Fe(NO)), interleukin-8 (IL-8) in nasal lavage, and pH of exhaled breath condensate every 15 days during follow-up. Data were analyzed using linear mixed-effects models. An increase of 17.5 microg/m(3) in the 8-hr moving average of PM(2.5) levels (interquartile range) was associated with a 1.08-ppb increase in Fe(NO) [95% confidence interval (CI), 1.01-1.16] and a 1.07-pg/mL increase in IL-8 (95% CI 0.98-1.19) in asthmatic children and a 1.16 pg/ml increase in IL-8 (95% CI, 1.00-1.36) in nonasthmatic children. The 5-day accumulated average of exposure to particulate matter <2.5 microm in aerodynamic diamter (PM(2.5)) was significantly inversely associated with forced expiratory volume in 1 sec (FEV(1)) (p=0.048) and forced vital capacity (FVC) (p=0.012) in asthmatic children and with FVC (p=0.021) in nonasthmatic children. Fe(NO) and FEV(1) were inversely associated (p=0.005) in asthmatic children. Exposure to PM(2.5) resulted in acute airway inflammation and decrease in lung function in both asthmatic and nonasthmatic children.

System-based Identification of Toxicity Pathways Associated With Multi-Walled Carbon Nanotube-Induced Pathological Responses

PubMed Central

Snyder-Talkington, Brandi N.; Dymacek, Julian; Porter, Dale W.; Wolfarth, Michael G.; Mercer, Robert R.; Pacurari, Maricica; Denvir, James; Castranova, Vincent; Qian, Yong; Guo, Nancy L.

2014-01-01

The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 µg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chain simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and were used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. PMID:23845593

Respiratory health effects of occupational exposure to charcoal dust in Namibia

PubMed Central

Kgabi, Nnenesi

2016-01-01

Background Charcoal processing activities can increase the risk of adverse respiratory outcomes. Objective To determine dose–response relationships between occupational exposure to charcoal dust, respiratory symptoms and lung function among charcoal-processing workers in Namibia. Methods A cross-sectional study was conducted with 307 workers from charcoal factories in Namibia. All respondents completed interviewer-administered questionnaires. Spirometry was performed, ambient and respirable dust levels were assessed in different work sections. Multiple logistic regression analysis estimated the overall effect of charcoal dust exposure on respiratory outcomes, while linear regression estimated the exposure-related effect on lung function. Workers were stratified according to cumulative dust exposure category. Results Exposure to respirable charcoal dust levels was above occupational exposure limits in most sectors, with packing and weighing having the highest dust exposure levels (median 27.7 mg/m3, range: 0.2–33.0 for the 8-h time-weighted average). The high cumulative dust exposure category was significantly associated with usual cough (OR: 2.1; 95% CI: 1.1–4.0), usual phlegm (OR: 2.1; 95% CI: 1.1–4.1), episodes of phlegm and cough (OR: 2.8; 95% CI: 1.1–6.1), and shortness of breath. A non-statistically significant lower adjusted mean-predicted % FEV1 was observed (98.1% for male and 95.5% for female) among workers with greater exposure. Conclusions Charcoal dust levels exceeded the US OSHA recommended limit of 3.5 mg/m3 for carbon-black-containing material and study participants presented with exposure-related adverse respiratory outcomes in a dose–response manner. Our findings suggest that the Namibian Ministry of Labour introduce stronger enforcement strategies of existing national health and safety regulations within the industry. PMID:27687528

Pulmonary function abnormalities and airway irritation symptoms of metal fumes exposure on automobile spot welders.

PubMed

Luo, Jiin-Chyuan John; Hsu, Kuang-Hung; Shen, Wu-Shiun

2006-06-01

Spot or resistance welding has been considered less hazardous than other types of welding. Automobile manufacturing is a major industry in Taiwan. Spot and arc welding are common processes in this industry. The respiratory effects on automobile spot welders exposed to metal fumes are investigated. The cohort consisted of 41 male auto-body spot welders, 76 male arc welders, 71 male office workers, and 59 assemblers without welding exposure. Inductivity Coupled Plasma Mass Spectrophotometer (ICP-MS) was applied to detect metals' (zinc, copper, nickel) levels in the post-shift urine samples. Demographic data, work history, smoking status, and respiratory tract irritation symptoms were gathered by a standard self-administered questionnaire. Pulmonary function tests were also performed. There were significantly higher values for average urine metals' (zinc, copper, nickel) levels in spot welders and arc welders than in the non-welding controls. There were 4 out of 23 (17.4%) abnormal forced vital capacity (FVC) among the high-exposed spot welders, 2 out of 18 (11.1%) among the low-exposed spot welders, and 6 out of 130 (4.6%) non-welding-exposed workers. There was a significant linear trend between spot welding exposure and the prevalence of restrictive airway abnormalities (P = 0.036) after adjusting for other factors. There were 9 out of 23 (39.1%) abnormal peak expiratory flow rate (PEFR) among high-exposed spot welders, 5 out of 18 (27.8%) among the low-exposed spot welders, and 28 out of 130 (21.5%) non-welding-exposed workers. There was a borderline significant linear trend between spot welding exposure and the prevalence of obstructive lung function abnormalities (P = 0.084) after adjusting for other factors. There was also a significant dose-response relationship of airway irritation symptoms (cough, phlegm, chronic bronchitis) among the spot welders. Arc welders with high exposure status also had a significant risk of obstructive lung abnormalities (PEFR reduction). There was also a significant dose-response relationship of airway irritation symptoms (cough, phlegm, chest tightness, and chronic bronchitis) among the arc welders. These findings suggest that restrictive and obstructive lung abnormalities, and airway irritation symptoms are associated with spot and arc welding exposures.

IRON HOMEOSTATIS IN THE LUNG

EPA Science Inventory

Iron is essential for many aspects of cellular function. However, it can also generate oxygen-based free radicals that result in injury to biological molecules. For this reason, iron acquisition and distribution are tightly regulated. Constant exposure to the atmosphere result...

Cross shift changes in lung function among bar and restaurant workers before and after implementation of a smoking ban

PubMed Central

Skogstad, M; Kjærheim, K; Fladseth, G; Gjølstad, M; Daae, H L; Olsen, R; Molander, P; Ellingsen, D G

2006-01-01

Objective To study possible cross shift effects of environmental tobacco smoke (ETS) on pulmonary function among bar and restaurant employees before and after the implementation of a smoking ban in Norway. Methods The study included 93 subjects employed in 13 different establishments in Oslo. They were examined at the beginning and end of a workshift both while ETS exposure was present and when smoking was banned. The mean exposure level of nicotine and total dust before the ban was 28 μg/m3 (range 3–65) and 275 μg/m3 (range 81–506), respectively. Following the smoking ban, the mean level of nicotine and total dust was 0.6 μg/m3 and 77 μg/m3, respectively. Assessment of lung function included dynamic lung volumes and flows. Results The cross shift reduction in forced vital capacity (FVC) among 69 subjects participating in both examinations changed from 81 ml (SD 136) during exposure to ETS to 52 ml (SD 156) (p = 0.24) following the smoking ban. The reduction in forced expired volume in one second (FEV1) during a workshift, was borderline significantly reduced when comparing the situation before and after the intervention, by 89 ml (SD = 132) compared to 46 ml (SD = 152) (p = 0.09), respectively. The reduction in forced mid‐expiratory flow rate (FEF25–75%) changed significantly from 199 ml/s (SD = 372) to 64 ml/s (SD = 307) (p = 0.01). Among 26 non‐smokers and 11 asthmatics, the reduction in FEV1 and FEF25–75% was significantly larger during ETS exposure compared to after the smoking ban. There was an association between the dust concentration and decrease in FEF25–75% before the ban among non‐smokers (p = 0.048). Conclusions This first study of cross shift changes before and after the implementation of a smoking ban in restaurants and bars shows a larger cross shift decrease in lung function before compared with after the implementation of the ban. PMID:16551754

The lung in paracoccidioidomycosis: new insights into old problems

PubMed Central

Costa, Andre Nathan; Benard, Gil; Albuquerque, Andre Luis Pereira; Fujita, Carmem Lucia; Magri, Adriana Satie Kono; Salge, João Marcos; Shikanai-Yasuda, Maria Aparecida; Carvalho, Carlos Roberto Ribeiro

2013-01-01

OBJECTIVES: Chronic paracoccidioidomycosis can diffusely affect the lungs. Even after antifungal therapy, patients may present with residual respiratory abnormalities due to fungus-induced lung fibrosis. METHODS: A cross-sectional analysis of 50 consecutive inactive, chronic paracoccidioidomycosis patients was performed using high resolution computed tomography, pulmonary function tests, ergospirometry, the six-minute walk test and health-related quality of life questionnaires. RESULTS: Radiological abnormalities were present in 98% of cases, the most frequent of which were architectural distortion (90%), reticulate and septal thickening (88%), centrilobular and paraseptal emphysema (84%) and parenchymal bands (74%). Patients typically presented with a mild obstructive disorder and a mild reduction in diffusion capacity with preserved exercise capacity, including VO2max and six-minute walking distance. Patient evaluation with the Saint-George Respiratory Questionnaire showed low impairment in the health-related quality of life, and the Medical Research Council questionnaire indicated a low dyspnea index. There were, however, patients with significant oxygen desaturation upon exercise that was associated with respiratory distress compared with the non-desaturated patients. The initial counterimmunoelectrophoresis of these patients was higher and lung emphysema was more prominent; however, there were no differences in the interstitial fibrotic tomographic abnormalities, tobacco exposure, functional responses, exercise capacity or quality of life. CONCLUSIONS: Inactive, chronic paracoccidioidomycosis patients show persistent and disseminated radiological abnormalities by high resolution computed tomography, short impairments in pulmonary function and low impacts on aerobic capacity and quality of life. However, there was a subset of individuals whose functional impairment was more severe. These patients present with higher initial serology and more severe emphysema, stressing the importance of adequate treatment associated with tobacco exposure cessation. PMID:23778339

Silica, compensated silicosis, and lung cancer in Western Australian goldminers

PubMed Central

de Klerk, N. H.; Musk, A. W.

1998-01-01

OBJECTIVES: Silica has recently been reclassified as carcinogenic to humans based largely on the observed increase in rates of lung cancer in subjects with silicosis. Other recent reviews have arrived at different conclusions as to whether silicosis or silica itself is carcinogenic. This study aims to examine exposure-response relations between exposure to silica and subsequent silicosis and lung cancer in a cohort of goldminers. METHODS: 2,297 goldminers from Kalgoorlie in Western Australia were examined in 1961, 1974, and 1975. Data were collected on respiratory symptoms, smoking habits, and employment history. Subjects were followed up to the end of 1993. Survival analyses for lung cancer mortality and incidence of compensated silicosis were performed with age and year matched conditional logistic regression analyses. RESULTS: 89% of the cohort were traced to the end of 1993. 84% of the men had smoked at some time and 66% were current smokers. 1386 deaths occurred during the follow up period, 138 from lung cancer, and 631 subjects were compensated for silicosis. A strong effect of smoking on mortality from lung cancer, and a smaller effect on the incidence of compensated silicosis was found. There was a strong effect of duration and intensity of exposure on the incidence of silicosis. The risk of mortality from lung cancer increased after compensation for silicosis. Of all direct measures of exposure to silica, only log cumulative exposure was significantly related to incidence of lung cancer, but this effect disappeared once the onset of silicosis was taken into account. CONCLUSIONS: The incidence of silicosis was clearly related to exposure to silica and the onset of silicosis conferred a significant increase in risk for subsequent lung cancer, but there was no evidence that exposure to silica caused lung cancer in the absence of silicosis.   PMID:9624278

Ozone, air pollution, and respiratory health.

PubMed Central

Beckett, W. S.

1991-01-01

Of the outdoor air pollutants regulated by the Clean Air Act of 1970 (and recently revised in 1990), ozone has been the one pollutant most difficult to control within the federal standards. The known human health effects are all on the respiratory system. At concentrations of ozone which occur during summer air-pollution episodes in many urban metropolitan areas of the United States, a portion of the healthy population is likely to experience symptoms and reversible effects on lung function, particularly if exercising heavily outdoors. More prolonged increase in airway responsiveness and the presence of inflammatory cells and mediators in the airway lining fluid may also result from these naturally occurring exposures. Serial exposures to peak levels of ozone on several consecutive days are more characteristic of pollution episodes in the Northeast United States and may be associated with recurrent symptoms. No "high-risk" or more sensitive group has been found, in contrast to the case of sulfur dioxide, to which asthmatics are more susceptible than normals. The occurrence of multiple exposure episodes within a single year over many years in some areas of California has led to studies looking for chronic effects of ozone exposure on the lung. To date, no conclusive studies have been reported, although further work is under way. Much of what we know about the effects of this gas on the lung are based on controlled exposures to pure gas within an environmental exposure laboratory. Interactions between substances which commonly co-occur in air-pollution episodes are also under investigation. PMID:1750227

Signals for a promoting action of radiation in cancer incidence data.

PubMed

Heidenreich, W F

2002-09-01

The two-stage clonal expansion model allows us in principle to separate the initiating and promoting action of radiation. Features of the relative risk functions which indicate the action of promotion most clearly are identified for acute and for protracted exposures. They are compared with data: for acute exposure, some results of a preliminary analysis of the atomic-bomb survivor data are given; for protracted exposure, patterns in the fatal lung tumours of radon-exposed rats are discussed.

Effects of alpha-tocopherol treatment on newborn rat lung development and injury in hyperoxia.

PubMed

Bucher, J R; Roberts, R J

1982-01-01

The efficacy of alpha-tocopherol treatment to influence the pattern or extent of lung injury resulting during exposure of newborn rats to hyperoxia was assessed following six-day exposures to FIO2 0.21, 0.4, and greater than 0.95. Alpha-Tocopherol treatment was found incapable of preventing the developmental arrest of the lung that occurs during hyperoxic exposure, shown by assessments of wet lung weights, lung DNA, lung volumes, and the progress of secondary septal and capillary development. However alpha-tocopherol treatment was found effective in preventing the hyperoxic-induced lessening of lung compliance and in preventing the deterioration of gas exchange capacity in the lung of the hyperoxic-exposed newborn rat. These findings suggest alpha-tocopherol treatment may not be capable of preventing major alterations in lung morphology in infants with chronic lung disease may be lessened by preserving gas exchange capabilities.

Impact of occupational carcinogens on lung cancer risk in a general population

PubMed Central

De Matteis, Sara; Consonni, Dario; Lubin, Jay H; Tucker, Margaret; Peters, Susan; Vermeulen, Roel CH; Kromhout, Hans; Bertazzi, Pier Alberto; Caporaso, Neil E; Pesatori, Angela C; Wacholder, Sholom; Landi, Maria Teresa

2012-01-01

Background Exposure to occupational carcinogens is an important preventable cause of lung cancer. Most of the previous studies were in highly exposed industrial cohorts. Our aim was to quantify lung cancer burden attributable to occupational carcinogens in a general population. Methods We applied a new job–exposure matrix (JEM) to translate lifetime work histories, collected by personal interview and coded into standard job titles, into never, low and high exposure levels for six known/suspected occupational lung carcinogens in the Environment and Genetics in Lung cancer Etiology (EAGLE) population-based case–control study, conducted in Lombardy region, Italy, in 2002–05. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in men (1537 cases and 1617 controls), by logistic regression adjusted for potential confounders, including smoking and co-exposure to JEM carcinogens. The population attributable fraction (PAF) was estimated as impact measure. Results Men showed an increased lung cancer risk even at low exposure to asbestos (OR: 1.76; 95% CI: 1.42–2.18), crystalline silica (OR: 1.31; 95% CI: 1.00–1.71) and nickel–chromium (OR: 1.18; 95% CI: 0.90–1.53); risk increased with exposure level. For polycyclic aromatic hydrocarbons, an increased risk (OR: 1.64; 95% CI: 0.99–2.70) was found only for high exposures. The PAFs for any exposure to asbestos, silica and nickel–chromium were 18.1, 5.7 and 7.0%, respectively, equivalent to an overall PAF of 22.5% (95% CI: 14.1–30.0). This corresponds to about 1016 (95% CI: 637–1355) male lung cancer cases/year in Lombardy. Conclusions These findings support the substantial role of selected occupational carcinogens on lung cancer burden, even at low exposures, in a general population. PMID:22467291

Impact of occupational carcinogens on lung cancer risk in a general population.

PubMed

De Matteis, Sara; Consonni, Dario; Lubin, Jay H; Tucker, Margaret; Peters, Susan; Vermeulen, Roel Ch; Kromhout, Hans; Bertazzi, Pier Alberto; Caporaso, Neil E; Pesatori, Angela C; Wacholder, Sholom; Landi, Maria Teresa

2012-06-01

Exposure to occupational carcinogens is an important preventable cause of lung cancer. Most of the previous studies were in highly exposed industrial cohorts. Our aim was to quantify lung cancer burden attributable to occupational carcinogens in a general population. We applied a new job-exposure matrix (JEM) to translate lifetime work histories, collected by personal interview and coded into standard job titles, into never, low and high exposure levels for six known/suspected occupational lung carcinogens in the Environment and Genetics in Lung cancer Etiology (EAGLE) population-based case-control study, conducted in Lombardy region, Italy, in 2002-05. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in men (1537 cases and 1617 controls), by logistic regression adjusted for potential confounders, including smoking and co-exposure to JEM carcinogens. The population attributable fraction (PAF) was estimated as impact measure. Men showed an increased lung cancer risk even at low exposure to asbestos (OR: 1.76; 95% CI: 1.42-2.18), crystalline silica (OR: 1.31; 95% CI: 1.00-1.71) and nickel-chromium (OR: 1.18; 95% CI: 0.90-1.53); risk increased with exposure level. For polycyclic aromatic hydrocarbons, an increased risk (OR: 1.64; 95% CI: 0.99-2.70) was found only for high exposures. The PAFs for any exposure to asbestos, silica and nickel-chromium were 18.1, 5.7 and 7.0%, respectively, equivalent to an overall PAF of 22.5% (95% CI: 14.1-30.0). This corresponds to about 1016 (95% CI: 637-1355) male lung cancer cases/year in Lombardy. These findings support the substantial role of selected occupational carcinogens on lung cancer burden, even at low exposures, in a general population.

Burden of lung cancer attributable to occupational diesel engine exhaust exposure in Canada.

PubMed

Kim, Joanne; Peters, Cheryl E; Arrandale, Victoria H; Labrèche, France; Ge, Calvin B; McLeod, Christopher B; Song, Chaojie; Lavoué, Jérôme; Davies, Hugh W; Nicol, Anne-Marie; Pahwa, Manisha; Demers, Paul A

2018-04-28

To estimate the population attributable fraction (PAF) and number of incident and fatal lung cancers in Canada from occupational exposure to diesel engine exhaust (DEE). DEE exposure prevalence and level estimates were used with Canadian Census and Labour Force Survey data to model the exposed population across the risk exposure period (REP, 1961-2001). Relative risks of lung cancer were calculated based on a meta-regression selected from the literature. PAFs were calculated using Levin's equation and applied to the 2011 lung cancer statistics obtained from the Canadian Cancer Registry. We estimated that 2.4% (95% CI 1.6% to 6.6%) of lung cancers in Canada are attributable to occupational DEE exposure, corresponding to approximately 560 (95% CI 380 to 1570) incident and 460 (95% CI 310 to 1270) fatal lung cancers in 2011. Overall, 1.6 million individuals alive in 2011 were occupationally exposed to DEE during the REP, 97% of whom were male. Occupations with the highest burden were underground miners, truck drivers and mechanics. Half of the attributable lung cancers occurred among workers with low exposure. This is the first study to quantify the burden of lung cancer attributable to occupational DEE exposure in Canada. Our results underscore a large potential for prevention, and a large public health impact from occupational exposure to low levels of DEE. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Lung volumes identify an at-risk group in persons with prolonged secondhand tobacco smoke exposure but without overt airflow obstruction.

PubMed

Arjomandi, Mehrdad; Zeng, Siyang; Geerts, Jeroen; Stiner, Rachel K; Bos, Bruce; van Koeverden, Ian; Keene, Jason; Elicker, Brett; Blanc, Paul D; Gold, Warren M

2018-01-01

Exposure to secondhand smoke (SHS) is associated with occult obstructive lung disease as evident by abnormal airflow indices representing small airway disease despite having preserved spirometry (normal forced expiratory volume in 1 s-to-forced vital capacity ratio, FEV 1 /FVC). The significance of lung volumes that reflect air trapping in the presence of preserved spirometry is unclear. To investigate whether lung volumes representing air trapping could determine susceptibility to respiratory morbidity in people with SHS exposure but without spirometric chronic obstructive pulmonary disease, we examined a cohort of 256 subjects with prolonged occupational SHS exposure and preserved spirometry. We elicited symptom prevalence by structured questionnaires, examined functional capacity (maximum oxygen uptake, VO 2max ) by exercise testing, and estimated associations of those outcomes with air trapping (plethysmography-measured residual volume-to-total lung capacity ratio, RV/TLC), and progressive air trapping with exertion (increase in fraction of tidal breathing that is flow limited on expiration during exercise (per cent of expiratory flow limitation, %EFL)). RV/TLC was within the predicted normal limits, but was highly variable spanning 22%±13% and 16%±8% across the increments of FEV 1 /FVC and FEV 1 , respectively. Respiratory complaints were prevalent (50.4%) with the most common symptom being ≥2 episodes of cough per year (44.5%). Higher RV/TLC was associated with higher OR of reporting respiratory symptoms (n=256; r 2 =0.03; p=0.011) and lower VO 2max (n=179; r 2 =0.47; p=0.013), and %EFL was negatively associated with VO 2max (n=32; r 2 =0.40; p=0.017). In those at risk for obstruction due to SHS exposure but with preserved spirometry, higher RV/TLC identifies a subgroup with increased respiratory symptoms and lower exercise capacity.

Pulmonary effects of active smoking and secondhand smoke exposure among adolescent students in Juárez, Mexico.

PubMed

Bird, Yelena; Staines-Orozco, Hugo

2016-01-01

Youth smoking trends among Latin American countries, including Mexico, are on the rise. Notably, although the high prevalence of smoking in teens has been well documented in the literature, few studies have evaluated the impact of smoking and secondhand smoke (SHS) exposure on their respiratory system. To investigate the effects of smoking and SHS exposure on the respiratory health and lung function among eighth-grade students in Juárez, Mexico. A cross-sectional study was undertaken on a sample of convenience. The study outcomes centered on evaluating 300 students' lung function by spirometry (forced expiratory volume in 1 second [FEV1], forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC], and forced mid-expiratory flow rate [FEF25%-75%]) and their respiratory health (smoking behavior and SHS exposure) by their self-reported responses to a standardized respiratory questionnaire. The study outcomes were compared among three distinct groups: 1) nonsmokers/nonexposed to SHS; 2) nonsmokers/exposed to SHS; and 3) smokers. The majority of the study participants were 14 years old (85%), females (54%), who attended eighth grade in a public school setting (56%). Approximately, half reported being of low socioeconomic status (49%) and nonsmokers/exposed to SHS (49%). The lung function parameters of smokers were found to be lower (FEV1 =62.88±10.25; FEV1/FVC =83.50±14.15; and FEF25%-75% =66.35±12.55) than those recorded for the nonsmokers/exposed to SHS (FEV1 =69.41±11.35; FEV1/FVC =88.75±15.75; and FEF25%-75% =78.90±14.65) and significantly reduced when compared to the nonsmokers/nonexposed to SHS (FEV1 =79.14±13.61; FEV1/FVC =94.88±21.88; and FEF25%-75% =87.36±17.02) (P<0.001). Similarly, respiratory complaints were more prevalent among smokers and those exposed to SHS when compared to nonsmokers/nonexposed to SHS. Our findings suggest that initiation of cigarette smoking and, to a lesser extent, exposure to SHS in adolescence leads to increased respiratory symptoms and reduction of pulmonary function test values. Public health initiatives that aim to prevent smoking initiation, assist in cessation, and lessen SHS exposure of adolescents need to be school-based and employed as early as middle school.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Batal, Mohamed; Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche, BP87, F-38702 La Tronche Cedex; Boudry, Isabelle

Sulphur mustard (SM) is a chemical warfare agent that attacks mainly skin, eye and lungs. Due to its lipophilic properties, SM is also able to diffuse through the skin and reach internal organs. DNA represents one of the most critical molecular targets of this powerful alkylating agent which modifies DNA structure by forming monoadducts and biadducts. These DNA lesions are involved in the acute toxicity of SM as well as its long-term carcinogenicity. In the present work we studied the formation and persistence of guanine and adenine monoadducts and guanine biadducts in the DNA of brain, lungs, kidneys, spleen, andmore » liver of SKH-1 mice cutaneously exposed to 2, 6 and 60 mg/kg of SM. SM-DNA adducts were detected in all studied organs, except in liver at the two lowest doses. Brain and lungs were the organs with the highest level of SM-DNA adducts, followed by kidney, spleen and liver. Monitoring the level of adducts for three weeks after cutaneous exposure showed that the lifetime of adducts were not the same in all organs, lungs being the organ with the longest persistence. Diffusion from skin to internal organs was much more efficient at the highest compared to the lowest dose investigated as the result of the loss of the skin barrier function. These data provide novel information on the distribution of SM in tissues following cutaneous exposures and indicate that brain is an important target. - Highlights: • Sulphur mustard reaches internal organs after skin exposure • Adducts are detected in the DNA of internal organs • Brain is the organ with the highest level of DNA damage • The barrier function of skin is lost at high dose of sulphur mustard • DNA adducts persist in organs for 2 or 3 weeks.« less

Genome-wide gene–environment interaction analysis for asbestos exposure in lung cancer susceptibility

PubMed Central

Wei, Qingyi Wei

2012-01-01

Asbestos exposure is a known risk factor for lung cancer. Although recent genome-wide association studies (GWASs) have identified some novel loci for lung cancer risk, few addressed genome-wide gene–environment interactions. To determine gene–asbestos interactions in lung cancer risk, we conducted genome-wide gene–environment interaction analyses at levels of single nucleotide polymorphisms (SNPs), genes and pathways, using our published Texas lung cancer GWAS dataset. This dataset included 317 498 SNPs from 1154 lung cancer cases and 1137 cancer-free controls. The initial SNP-level P-values for interactions between genetic variants and self-reported asbestos exposure were estimated by unconditional logistic regression models with adjustment for age, sex, smoking status and pack-years. The P-value for the most significant SNP rs13383928 was 2.17×10–6, which did not reach the genome-wide statistical significance. Using a versatile gene-based test approach, we found that the top significant gene was C7orf54, located on 7q32.1 (P = 8.90×10–5). Interestingly, most of the other significant genes were located on 11q13. When we used an improved gene-set-enrichment analysis approach, we found that the Fas signaling pathway and the antigen processing and presentation pathway were most significant (nominal P < 0.001; false discovery rate < 0.05) among 250 pathways containing 17 572 genes. We believe that our analysis is a pilot study that first describes the gene–asbestos interaction in lung cancer risk at levels of SNPs, genes and pathways. Our findings suggest that immune function regulation-related pathways may be mechanistically involved in asbestos-associated lung cancer risk. Abbreviations:CIconfidence intervalEenvironmentFDRfalse discovery rateGgeneGSEAgene-set-enrichment analysisGWASgenome-wide association studiesi-GSEAimproved gene-set-enrichment analysis approachORodds ratioSNPsingle nucleotide polymorphism PMID:22637743

Post-9/11/2001 lung function trajectories by sex and race in World Trade Center-exposed New York City emergency medical service workers.

PubMed

Vossbrinck, Madeline; Zeig-Owens, Rachel; Hall, Charles B; Schwartz, Theresa; Moir, William; Webber, Mayris P; Cohen, Hillel W; Nolan, Anna; Weiden, Michael D; Christodoulou, Vasilios; Kelly, Kerry J; Aldrich, Thomas K; Prezant, David J

2017-03-01

To determine whether lung function trajectories after 9/11/2001 (9/11) differed by sex or race/ethnicity in World Trade Center-exposed Fire Department of the City of New York emergency medical service (EMS) workers. Serial cross-sectional study of pulmonary function tests (PFTs) taken between 9/11 and 9/10/2015. We used data from routine PFTs (forced expiratory volume in 1 s (FEV 1 ) and FEV 1 % predicted), conducted at 12-18 month intervals. FEV 1 and FEV 1 % predicted were assessed over time, stratified by sex, and race/ethnicity. We also assessed FEV 1 and FEV 1 % predicted in current, former and never-smokers. Among 1817 EMS workers, 334 (18.4%) were women, 979 (53.9%) self-identified as white and 939 (51.6%) were never-smokers. The median follow-up was 13.1 years (IQR 10.5-13.6), and the median number of PFTs per person was 11 (IQR 7-13). After large declines associated with 9/11, there was no discernible recovery in lung function. In analyses limited to never-smokers, the trajectory of decline in adjusted FEV 1 and FEV 1 % predicted was relatively parallel for men and women in the 3 racial/ethnic groups. Similarly, small differences in FEV 1 annual decline between groups were not clinically meaningful. Analyses including ever-smokers were essentially the same. 14 years after 9/11, most EMS workers continued to demonstrate a lack of lung function recovery. The trajectories of lung function decline, however, were parallel by sex and by race/ethnicity. These findings support the use of routine, serial measures of lung function over time in first responders and demonstrate no sex or racial sensitivity to exposure-related lung function decline. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Pulmonary function test in formalin exposed and nonexposed subjects: A comparative study

PubMed Central

Uthiravelu, P.; Saravanan, A.; Kumar, C. Kishor; Vaithiyanandane, V.

2015-01-01

Background: The main function of the lung is gas exchange, which can be assessed in several ways. A spirometer measures the flow and the volumes of the inspired and expired air. The thoracic and abdominal muscle strength plays an important role in pulmonary function and diffusing lung capacity. Aims and Objectives: The aim of this study was to assess the effects of formalin exposure on the pulmonary function to compare with healthy individuals. To assess the chronic effects of formalin exposure on Pulmonary function tests (PFTs) in the faculties, lab technicians and attender of the Department of Anatomy and Pathology of SRM Medical Hospital and Research Centre, Kattankulathur. Materials and Methods: This prospective study was carried out in 50 healthy formalin exposed subjects (at least 5 years exposure) from Department of Anatomy and Pathology of SRM Medical College Hospital and Research Centre, Kattankulathur and 50 healthy controls of same age group of this study were included after obtaining ethical clearance and consent ‘Easy One Pro Spirometer (Ndd Medical Technologies, Cheshire SK 101LT, United Kingdom) was used to find out the PFT. Results: Student's t-test was applied to compare the PFT parameters between formalin exposed and formalin nonexposed group. There was a significant difference in mean and standard deviation of pulmonary parameters with the P < 0.005 in formalin exposed, which shows that they have lesser ventilatory drive. Conclusion: The formalin exposed subjects in our study presented with a mixed disorder of both obstructive and restrictive type. We also found that there was a negative correlation of pulmonary function with that of the degree and duration of exposure to formalin. PMID:26015743

Silica dust and lung cancer in the German stone, quarrying, and ceramics industries: results of a case-control study

PubMed Central

Ulm, K; Waschulzik, B; Ehnes, H; Guldner, K; Thomasson, B; Schwebig, A; Nuss, H

1999-01-01

BACKGROUND—A work force based case-control study of lung cancer was performed in non-silicotic subjects exposed to crystalline silica to investigate the association between silica dust and lung cancer excluding the influence of silicosis.
METHODS—Two hundred and forty seven patients with lung cancer and 795 control subjects were enrolled, all of whom had been employed in the German stone, quarrying, or ceramics industries. Smoking was used as a matching criterion. Exposure to silica was quantified by measurements, if available, or otherwise by industrial hygienists. Several indices (peak, average and cumulative exposure) were used to analyse the relationship between the level of exposure and risk of lung cancer as odds ratios (OR).
RESULTS—The risk of lung cancer is associated with the year of and age at first exposure to silica, duration of exposure, and latency. All odds ratios were adjusted for these factors. Considering the peak exposure, the OR for workers exposed to high levels (⩾0.15 mg/m3 respirable silica dust which is the current occupational threshold value for Germany) compared with those exposed to low levels (<0.15 mg/m3) was 0.85 (95% CI 0.58 to 1.25). For the time weighted average exposure the OR was 0.91 (95% CI 0.57 to 1.46). The OR for the cumulative exposure was 1.02 (95% CI 0.67 to 1.55). No increase in risk was evident with increasing exposure.
CONCLUSIONS—This study shows no association between exposure to crystalline silica and lung cancer. The exclusion of subjects with silicosis may have led to dilution with respect to the level of exposure and therefore reduced the power to detect a small risk. Alternatively, the risk of getting lung cancer may be restricted to subjects with silicosis and is not directly linked to silica dust.

 PMID:10092697

Lung cancer incidence among Norwegian silicon carbide industry workers: associations with particulate exposure factors

PubMed Central

Kjærheim, Kristina; Føreland, Solveig; Eduard, Wijnand; Kjuus, Helge

2012-01-01

Objectives An increased lung cancer risk associated with total dust exposure in the silicon carbide (SiC) industry has previously been reported. The aim of the present study was to examine the relative importance of specific exposure factors by using a comprehensive, historic job exposure matrix based on about 8000 measurements. Methods Cumulative exposure to total and respirable dust, respirable quartz, cristobalite, and SiC particles and SiC fibres was assessed for 1687 long-term workers employed during 1913–2003 in the Norwegian SiC industry. Standardised incidence ratios for lung cancer, with follow-up during 1953–2008, were calculated stratified by cumulative exposure categories. Poisson regression analyses were performed using both categorised and log-transformed cumulative exposure variables. Results The lung cancer incidence was about twofold increased at the highest level of exposure to each of the exposure factors (standardised incidence ratios 1.9–2.3 for all agents). Internal analyses showed associations between exposure level and lung cancer incidence for all investigated factors, but a significant trend only for total dust and cristobalite. In multivariate analyses, cristobalite showed the most consistent associations, followed by SiC fibres. Conclusions The results indicated that crystalline silica in the form of cristobalite was the most important occupational exposure factor responsible for lung cancer excess in the Norwegian SiC industry. SiC fibres seemed to have an additional effect. PMID:22611173

Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.

2006-02-15

Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs.more » On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-{alpha} levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later.« less

Pulmonary tolerance in man to continuous oxygen exposure at 3.0, 2.5, 2.0, and 1.5 ATA in Predictive Studies V

NASA Technical Reports Server (NTRS)

Clark, J. M.; Gelfand, R.; Flores, N. D.; Lambertsen, C. J.; Pisarello, J. B.

1987-01-01

Oxygen effects on pulmonary function were measured in normal, resting men who breathed oxygen continuously at 3.0, 2.5, 2.0, and 1.5 ATA to predefined limits of CNS, cardiac, or pulmonary tolerance. Rates of pulmonary symptom intensification and decrease in vital capacity (VC) increased progressively with elevation of inspired oxygen pressure. Although VC decrements occurred concurrently with symptoms, the lung volume changes became prominent when symptoms were still mild. The observed effects were consistent with the interpretation that small airway function is impaired more selectively by oxygen exposure at 3.0 and 2.5 ATA than by exposure at 2.0 and 1.5 ATA. Despite similar VC changes after oxygen exposure at 2.0 ATA for nearly 10 hr and exposure at 1.5 ATA for almost 18 hr, the 2.0 ATA exposure caused greater impairment of pulmonary function and required a longer recovery period.

Experimental PVC Material Challenge in Subjects with Occupational PVC Exposure

PubMed Central

Tuomainen, Anneli; Stark, Harri; Seuri, Markku; Hirvonen, Maija-Riitta; Linnainmaa, Markku; Sieppi, Anne; Tukiainen, Hannu

2006-01-01

Background Polyvinyl chloride (PVC) materials have been linked to asthma in several epidemiologic studies, but the possible causal factors remain unknown. Participants We challenged 10 subjects experimentally to degraded PVC products under controlled conditions. All of the subjects had previously experienced respiratory symptoms suspected to be caused by this kind of exposure in their work place. Five subjects had doctor-diagnosed asthma. Methods The subjects were exposed to degraded PVC material in an exposure chamber; a challenge with ceramic tile was used as the control test. We followed exhaled nitric oxide, nasal NO, lung functions, cytokines [tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-6, and IL-12] and NO in nasal lavage fluid (NAL) during and after the exposures. We also measured 2-ethylhexanol in exhaled breath samples and NAL. Results On the morning after the PVC exposure, subjects reported respiratory tract symptoms significantly more often than they did after the control test (50% vs. 0%, respectively; p = 0.029; n = 10). We did not detect any changes in lung functions or levels of exhaled NO, nasal NO, or NO in NAL after PVC challenge compared with the control test. Cytokine levels increased after both exposures, with no statistically significant difference between situations. All of the exhaled breath samples collected during the PVC exposure contained 2-ethylhexanol. Conclusions PVC flooring challenge can evoke respiratory tract symptoms in exposed subjects. Our results do not support the hypothesis that PVC materials themselves evoke immediate asthmatic reactions. The chamber test used is well suited to this type of exposure study. PMID:16966097

Immunotoxicity of gallium arsenide on antigen presentation: comparative study of intratracheal and intraperitoneal exposure routes.

PubMed

Hartmann, Constance B; Harrison, M Travis; McCoy, Kathleen L

2005-01-01

Gallium arsenide (GaAs) is a semiconductor utilized in electronics and computer industries. GaAs exposure of animals causes local inflammation and systemic immune suppression. Mice were administered 2 to 200 mg/kg GaAs. On day 5, intratracheal instillation increased lung weights in a dose-dependent manner and induced pulmonary inflammation exemplified by mononuclear cell infiltration and mild epithelial hyperplasia. No fibrosis, pneumocyte hyperplasia, proteinosis, or bronchial epithelial damage was observed in the lungs. Splenic cellularity and composition were unaffected. GaAs' effect on antigen presentation by macrophages was similar after intratracheal and intraperitoneal exposure, although the lowest observable adverse effect levels differed. Macrophages from the exposure site displayed an enhanced ability to activate an antigen-specific CD4(+) helper T-cell hybridoma compared with vehicle controls, whereas splenic macrophages were defective in this function. The chemical's impact on peritoneal macrophages depended on the exposure route. GaAs exposure augmented thiol cathepsins B and L activities in macrophages from the exposure site, but decreased proteolytic activities in splenic macrophages. Alveolar macrophages had increased expression of major histocompatibility complex (MHC) Class II molecules, whereas MHC Class II expression on splenic and peritoneal macrophages was unaffected. Modified thiol cathepsin activities statistically correlated with altered efficiency of antigen presentation, whereas MHC Class II expression did not. Our study is the first one to examine the functional capability of alveolar macrophages after intratracheal GaAs instillation. Therefore, thiol cathepsins may be potential target molecules by which GaAs exposure modulates antigen presentation.

Local and Systemic Inflammation May Mediate Diesel Engine Exhaust-Induced Lung Function Impairment in a Chinese Occupational Cohort.

PubMed

Wang, Haitao; Duan, Huawei; Meng, Tao; Yang, Mo; Cui, Lianhua; Bin, Ping; Dai, Yufei; Niu, Yong; Shen, Meili; Zhang, Liping; Zheng, Yuxin; Leng, Shuguang

2018-04-01

Diesel exhaust (DE) as the major source of vehicle-emitted particle matter in ambient air impairs lung function. The objectives were to assess the contribution of local (eg, the fraction of exhaled nitric oxide [FeNO] and serum Club cell secretory protein [CC16]) and systemic (eg, serum C-reaction protein [CRP] and interleukin-6 [IL-6]) inflammation to DE-induced lung function impairment using a unique cohort of diesel engine testers (DETs, n = 137) and non-DETs (n = 127), made up of current and noncurrent smokers. Urinary metabolites, FeNO, serum markers, and spirometry were assessed. A 19% reduction in CC16 and a 94% increase in CRP were identified in DETs compared with non-DETs (all p values <10-4), which were further corroborated by showing a dose-response relationship with internal dose for DE exposure (all p values <.04) and a time-course relationship with DE exposure history (all p values <.005). Mediation analysis showed that 43% of the difference in FEV1 between DETs and non-DETs can be explained by circulating CC16 and CRP (permuted p < .001). An inverse dose-dependent relationship between FeNO and internal dose for cigarette smoke was identified (p = .0003). A range of 95% lower bounds of benchmark dose of 1.0261-1.4513 μg phenanthrols/g creatinine in urine as an internal dose was recommended for regulatory risk assessment. Local and systemic inflammation may be key processes that contribute to the subsequent development of obstructive lung disease in DE-exposed populations.

Biological and statistical approaches to predicting human lung cancer risk from silica.

PubMed

Kuempel, E D; Tran, C L; Bailer, A J; Porter, D W; Hubbs, A F; Castranova, V

2001-01-01

Chronic inflammation is a key step in the pathogenesis of particle-elicited fibrosis and lung cancer in rats, and possibly in humans. In this study, we compute the excess risk estimates for lung cancer in humans with occupational exposure to crystalline silica, using both rat and human data, and using both a threshold approach and linear models. From a toxicokinetic/dynamic model fit to lung burden and pulmonary response data from a subchronic inhalation study in rats, we estimated the minimum critical quartz lung burden (Mcrit) associated with reduced pulmonary clearance and increased neutrophilic inflammation. A chronic study in rats was also used to predict the human excess risk of lung cancer at various quartz burdens, including mean Mcrit (0.39 mg/g lung). We used a human kinetic lung model to link the equivalent lung burdens to external exposures in humans. We then computed the excess risk of lung cancer at these external exposures, using data of workers exposed to respirable crystalline silica and using Poisson regression and lifetable analyses. Finally, we compared the lung cancer excess risks estimated from male rat and human data. We found that the rat-based linear model estimates were approximately three times higher than those based on human data (e.g., 2.8% in rats vs. 0.9-1% in humans, at mean Mcrit lung burden or associated mean working lifetime exposure of 0.036 mg/m3). Accounting for variability and uncertainty resulted in 100-1000 times lower estimates of human critical lung burden and airborne exposure. This study illustrates that assumptions about the relevant biological mechanism, animal model, and statistical approach can all influence the magnitude of lung cancer risk estimates in humans exposed to crystalline silica.

Prenatal exposure to perfluoralkyl substances (PFASs) associated with respiratory tract infections but not allergy- and asthma-related health outcomes in childhood.

PubMed

Impinen, A; Nygaard, U C; Lødrup Carlsen, K C; Mowinckel, P; Carlsen, K H; Haug, L S; Granum, B

2018-01-01

Prenatal exposure to perfluoralkyl substances (PFASs) has been reported to be associated with immunosuppression in early childhood, but with contradictory findings related to atopic and lung diseases. We aimed to determine if prenatal exposure to PFASs is associated with asthma or other allergic diseases or respiratory tract infections in childhood. Nineteen PFASs were measured in cord blood available from 641 infants in the Environment and Childhood Asthma (ECA) prospective birth cohort study. The six most abundant PFASs were perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonamide (PFOSA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA). Health outcomes were assessed at two and ten years of age, and included reported obstructive airways disease (wheeze by 10 years; asthma by 2 and 10 years; reduced lung function at birth; allergic rhinitis by 10 years), atopic dermatitis (AD) by 2 and 10 years, allergic sensitization by 10 years, and episodes of common respiratory tract infections (common cold by 2 years, lower respiratory tract infections (LRTI) by 10 years). The associations between exposure and health outcomes were examined using logistic and Poisson regression. The number of reported airways infections were significantly associated with cord blood concentrations of PFAS; common colds by two years with PFUnDA (β = 0.11 (0.08-0.14)) and LRTIs from 0 to 10 years of age with PFOS (β = 0.50 (0.42-0.57)), PFOA (β = 0.28 (0.22-0.35)), PFOSA (β = 0.10 (0.06-0.14)), PFNA (β = 0.09 (0.03-0.14)) and PFUnDA (β = 0.18 (0.13-0.23)) concentrations. Neither reduced lung function at birth, asthma, allergic rhinitis, AD nor allergic sensitization were significantly associated with any of the PFASs. Although prenatal exposure to PFASs was not associated with atopic or lung manifestations by 10 years of age, several PFASs were associated with an increased number of respiratory tract infections in the first 10 years of life, suggesting immunosuppressive effects of PFASs. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of nitrogen dioxide on respiratory tract clearance in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rasmussen, R.E.; Mannix, R.C.; Oldham, M.J.

1994-01-01

During growth and development, young children are periodically exposed to relatively high concentrations of various air contaminants, including tobacco smoke and environmental pollutants generated by fossil fuel use. The effects of these exposures on respiratory function and lung development are difficult to determine because of interindividual variation and lack of accurate dosimetry. To provide information on the effects of chronic exposure to a common indoor and outdoor pollutant during lung development, a study was performed to assess the effects of exposure to two concentrations of nitrogen dioxide (NO[sub 2]; 0.5 or 10 ppm) on tracer particle clearance from the airwaysmore » of ferrets exposed during postnatal respiratory tract development. Separate groups of ferrets were exposed nose-only to the test atmospheres or clean air 4 h/d, 5 d/wk, for either 8 or 15 wk. Those animals exposed for 8 wk were subsequently housed in a filtered air environment until the particle clearance measurements commenced at 3 wk prior to the end of the 15-wk exposure protocol. Radiolabeled ([sup 51]Cr) tracer particles were deposited in the respiratory tract of all animals by inhalation, and the clearance rates from the head and thoracic regions were separately monitored for 18 d. No significant effects of the NO[sub 2] exposure on head airways clearance were seen. In contrast, the rates of particle clearance from the thorax of both the 8- and 15-wk groups exposed to 10 ppm NO[sub 2] were significantly reduced, and did not differ from each other. Thoracic clearance was also reduced in animals exposed to 0.5 ppm, but the rate was not significantly different from that of the clean air exposed controls. These results show that NO[sub 2] at moderate concentrations caused highly significant changes in the deep lung of the juvenile ferret, and suggest that impairment of the clearance function may be only slowly recovered after chronic exposure. 35 refs., 1 fig., 1 tab.« less

Biomarkers of World Trade Center Particulate Matter Exposure: Physiology of distal airway and blood biomarkers that predict FEV1 decline

PubMed Central

Weiden, Michael D.; Kwon, Sophia; Caraher, Erin; Berger, Kenneth I.; Reibman, Joan; Rom, William N.; Prezant, David J.; Nolan, Anna

2016-01-01

Biomarkers can be important predictors of disease severity and progression. The intense exposure to particulates and other toxins from the destruction of the World Trade Center (WTC) overwhelmed the lung’s normal protective barriers. The Fire Department of New York (FDNY) cohort not only had baseline pre-exposure lung function measures but also had serum samples banked soon after their WTC exposure. This well phenotyped group of highly exposed first responders is an ideal cohort for biomarker discovery and eventual validation. Disease progression was heterogeneous in this group in that some individuals subsequently developed abnormal lung function while others recovered. Airflow obstruction predominated in WTC exposed patients who were symptomatic. Multiple independent disease pathways may cause this abnormal FEV1 after irritant exposure. WTC exposure activates one or more of these pathways causing abnormal FEV1 in an individual. Our hypothesis was that serum biomarkers expressed within 6 months after World Trade Center (WTC) exposure reflect active disease pathways and predict subsequent development or protection from abnormal FEV1

Chronic obstructive pulmonary disease and occupational exposure to silica.

PubMed

Rushton, Lesley

2007-01-01

Prolonged exposure to high levels of silica has long been known to cause silicosis This paper evaluates the evidence for an increased risk of chronic obstructive pulmonary disease (COPD) in occupations and industries in which exposure to crystalline silica is the primary exposure, with a focus on the magnitude of risks and levels of exposure causing disabling health effects. The literature suggests consistently elevated risks of developing COPD associated with silica exposure in several occupations, including the construction industry; tunneling; cement industry; brick manufacturing; pottery and ceramic work; silica sand, granite and diatomaceous earth industries; gold mining; and iron and steel founding, with risk estimates being high in some, even after taking into account the effect of confounders like smoking. Average dust levels vary from about 0.5 mg.m3 to over 10 mg.m3 and average silica levels from 0.04 to over 5 mg.m3, often well above occupational standards. Factors influencing the variation from industry to industry in risks associated with exposure to silica-containing dusts include (a) the presence of other minerals in the dust, particularly when associated with clay minerals; (b) the size of the particles and percentage of quartz; (c) the physicochemical characteristics, such as whether the dust is freshly fractured. Longitudinal studies suggest that loss of lung function occurs with exposure to silica dust at concentrations of between 0.1 and 0.2 mg.m3, and that the effect of cumulative silica dust exposure on airflow obstruction is independent of silicosis. Nevertheless, a disabling loss of lung function in the absence of silicosis would not occur until between 30 and 40 years exposure.

Curbing the burden of lung cancer.

PubMed

Urman, Alexandra; Hosgood, H Dean

2016-06-01

Lung cancer contributes substantially to the global burden of disease and healthcare costs. New screening modalities using low-dose computerized tomography are promising tools for early detection leading to curative surgery. However, the screening and follow-up diagnostic procedures of these techniques may be costly. Focusing on prevention is an important factor to reduce the burden of screening, treatment, and lung cancer deaths. The International Agency for Research on Cancer has identified several lung carcinogens, which we believe can be considered actionable when developing prevention strategies. To curb the societal burden of lung cancer, healthcare resources need to be focused on early detection and screening and on mitigating exposure(s) of a person to known lung carcinogens, such as active tobacco smoking, household air pollution (HAP), and outdoor air pollution. Evidence has also suggested that these known lung carcinogens may be associated with genetic predispositions, supporting the hypothesis that lung cancers attributed to differing exposures may have developed from unique underlying genetic mechanisms attributed to the exposure of interest. For instance, smokingattributed lung cancer involves novel genetic markers of risk compared with HAP-attributed lung cancer. Therefore, genetic risk markers may be used in risk stratification to identify subpopulations that are at a higher risk for developing lung cancer attributed to a given exposure. Such targeted prevention strategies suggest that precision prevention strategies may be possible in the future; however, much work is needed to determine whether these strategies will be viable.

Lung cancer in relation to exposure to silica dust, silicosis and uranium production in South African gold miners

PubMed Central

Hnizdo, E.; Murray, J.; Klempman, S.

1997-01-01

BACKGROUND: A nested case-control study for lung cancer was performed on a cohort of 2260 South African gold miners in whom an association between exposure to silica dust and risk of lung cancer was previously reported. The objective was to investigate an expanded set of risk factors and also cancer cell type. METHODS: The 78 cases of lung cancer found during the follow up period from 1970 to 1986 were matched with 386 controls. Risk of lung cancer was related to smoking, exposure to silica dust, incidence of silicosis, and uranium production and the uranium content of the mine ore. RESULTS: The risk of lung cancer was associated with tobacco smoking, cumulative dust exposure, duration of underground mining, and with silicosis. The best predictive model included pack years of cigarette consumption (adjusted relative risk (RR) = 1.0 for < 6.5 pack years, 3.5 (95% confidence interval (CI) 0.7 to 16.8) for 6.5-20 pack years, 5.7 (95% CI 1.3 to 25.8) for 21-30 pack years, and 13.2 (95% CI 3.1 to 56.2) for more than 30 pack years) and silicosis (RR = 2.45 (95% CI 1.2 to 5.2)). No association was found with uranium production. The lung tumour cell type distribution was 40.3% small cell carcinoma, 38.8% squamous cell, 16.4% adenocarcinoma, and 4.5% large cell carcinoma. Small and large cell cancer combined were associated with exposure to dust. CONCLUSIONS: The results cannot be interpreted definitively in terms of causal association. Possible interpretations are: (1) subjects with high dust exposure who develop silicosis are at increased risk of lung cancer; (2) high levels of exposure to silica dust on its own is important in the pathogenesis of lung cancer and silicosis is coincidental; and (3) high levels of silica dust exposure may be a surrogate for the exposure to radon daughters. 


 PMID:9093345

Crystalline silica exposure and lung cancer mortality in diatomaceous earth industry workers: a quantitative risk assessment.

PubMed

Rice, F L; Park, R; Stayner, L; Smith, R; Gilbert, S; Checkoway, H

2001-01-01

To use various exposure-response models to estimate the risk of mortality from lung cancer due to occupational exposure to respirable crystalline silica dust. Data from a cohort mortality study of 2342 white male California diatomaceous earth mining and processing workers exposed to crystalline silica dust (mainly cristobalite) were reanalyzed with Poisson regression and Cox's proportional hazards models. Internal and external adjustments were used to control for potential confounding from the effects of time since first observation, calendar time, age, and Hispanic ethnicity. Cubic smoothing spline models were used to assess the fit of the models. Exposures were lagged by 10 years. Evaluations of the fit of the models were performed by comparing their deviances. Lifetime risks of lung cancer were estimated up to age 85 with an actuarial approach that accounted for competing causes of death. Exposure to respirable crystalline silica dust was a significant predictor (p<0.05) in nearly all of the models evaluated and the linear relative rate model with a 10 year exposure lag seemed to give the best fit in the Poisson regression analysis. For those who died of lung cancer the linear relative rate model predicted rate ratios for mortality from lung cancer of about 1.6 for the mean cumulative exposure to respirable silica compared with no exposure. The excess lifetime risk (to age 85) of mortality from lung cancer for white men exposed for 45 years and with a 10 year lag period at the current Occupational Safety and Health Administration (OSHA) standard of about 0.05 mg/m(3) for respirable cristobalite dust is 19/1000 (95% confidence interval (95% CI) 5/1000 to 46/1000). There was a significant risk of mortality from lung cancer that increased with cumulative exposure to respirable crystalline silica dust. The predicted number of deaths from lung cancer suggests that current occupational health standards may not be adequately protecting workers from the risk of lung cancer.

Impact of exposure to insulation wool on lung function and cough in Swedish construction workers

PubMed Central

Albin, M.; Engholm, G.; Hallin, N.; Hagmar, L.

1998-01-01

OBJECTIVES: To investigate whether application of insulation wool adversely affects lung volumes and increases the occurrence of symptoms of airway irritation. METHODS: Data from nationwide health check ups in 1981-93 of male construction workers born in 1955 or later were used to investigate cross sectional (n = 96,004) and longitudinal (n = 26,298) associations between lung volumes, vital capacity (VC), and forced expiratory volume in one second (FEV1) and exposure to insulation wool by combining a job exposure matrix (JEM) and self reported exposure. Data on 12 month prevalence of persistent cough not associated with the common cold was available for the period 1989-92. Potential confounding from smoking, exposure to asbestos, silica, and isocyanates, was considered in the analyses. RESULTS: For those in the highest exposure category (self reported duration of exposure of > or = 11 years, and high exposure according to the JEM) VC was on average 2.5 cl lower (95% CI -6.5 to 1.5) than in those with no exposure. The corresponding figures for FEV1 was -2.4 cl (95% CI -6.1 to 1.3). In the longitudinal analyses, the yearly change in VC between the first and last spirometry for those in the highest exposure category was 0.50 cl (95% CI -0.97 to 1.98) less than in the unexposed category. The corresponding figure for FEV1 was 0.89 cl (95% CI - 0.70 to 2.06). High exposure to insulation wool, asbestos, or silica, during the 12 months preceding the check up was associated with increased odds ratios (ORs) for persistent cough of the same magnitude as current smoking. CONCLUSIONS: The results indicate no effects on VC or FEV1 from exposure to insulation wool. Recent exposure to insulation wool, asbestos, and silica was associated with an increased prevalence of persistent cough.   PMID:9930086