The Experts below are selected from a list of 216 Experts worldwide ranked by ideXlab platform
David A. Schwartz - One of the best experts on this subject based on the ideXlab platform.
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Endotoxin Responsiveness and Subchronic Grain Dust-Induced Airway Disease
American journal of physiology. Lung cellular and molecular physiology, 2001Co-Authors: Caroline L. S. George, Hong Jin, Christine L. Wohlford-lenane, Marsha E. O'neill, John C. Phipps, Patrick T. O'shaughnessy, Joel N. Kline, Peter S. Thorne, David A. SchwartzAbstract:Endotoxin is one of the principal components of Grain Dust that causes acute reversible airflow obstruction and airway inflammation. To determine whether endotoxin responsiveness influences the development of chronic Grain Dust-induced airway disease, physiological and airway inflammation remodeling parameters were evaluated after an 8-wk exposure to corn Dust extract (CDE) and again after a 4-wk recovery period in a strain of mice sensitive to (C3H/HeBFeJ) and one resistant to (C3H/HeJ) endotoxin. After the CDE exposure, both strains of mice had equal airway hyperreactivity to a methacholine challenge; however, airway hyperreactivity persisted only in the C3H/HeBFeJ mice after the recovery period. Only the C3H/HeBFeJ mice showed significant inflammation of the lower airway after the 8-wk exposure to CDE. After the recovery period, this inflammatory response completely resolved. Lung stereological measurements indicate that an 8-wk exposure to CDE resulted in persistent expansion of the airway submucosal cross-sectional area only in the C3H/HeBFeJ mice. Collagen type III and an influx of cells into the subepithelial area participated in the expansion of the submucosa. Our findings demonstrate that subchronic inhalation of Grain Dust extract results in the development of chronic airway disease only in mice sensitive to endotoxin but not in mice that are genetically hyporesponsive to endotoxin, suggesting that endotoxin is important in the development of chronic airway disease.
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Bronchial hyperreactivity is associated with enhanced Grain Dust-induced airflow obstruction
Journal of applied physiology (Bethesda Md. : 1985), 2000Co-Authors: Joel N. Kline, Paul J. Jagielo, Janet L. Watt, David A. SchwartzAbstract:Bronchial hyperreactivity (BHR) is associated with the presence of airway inflammation in asthma and is seen in individuals occupationally exposed to Grain Dust. To better understand the relationsh...
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IL-10 reduces Grain Dust-induced airway inflammation and airway hyperreactivity
Journal of applied physiology (Bethesda Md. : 1985), 2000Co-Authors: Timothy J. Quinn, Christine L. Wohlford-lenane, Somer Taylor, David A. SchwartzAbstract:To determine whether interleukin-10 (IL-10) could alter the development of Grain Dust-induced airway disease, we pretreated mice with either saline or IL-10 intravenously, exposed the mice to an in...
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Compartmentalization of the inflammatory response to inhaled Grain Dust.
American journal of respiratory and critical care medicine, 1999Co-Authors: Susanne Becker, Kathy L. Frees, William A. Clapp, Jacqueline Quay, Hillel S. Koren, David A. SchwartzAbstract:Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled Grain Dust. Previously, we found considerable production of these cytokines in the lower respiratory tract of workers exposed by inhalation to aqueous extracts of corn Dust extract. Alveolar macrophages (AM) have long been considered the cell type responsible for producing these cytokines, and only recently has it been realized that airway epithelial cells may also be involved in cytokine production. In order to determine whether airway epithelia are involved in the inflammatory response to inhaled corn Dust extract and to compare the magnitude of response of bronchial epithelial cells (BE) and bronchoalveolar lavage (BAL) cells, we used the reverse transcriptase/polymerase chain reaction (RT/PCR) technique in a semiquantitative manner to evaluate the concentration of IL-1beta, IL-6, IL-8, TNF-alpha, and sIL-1RA. Alveolar cells were obtained by BAL, and BE were obtained by endobronchial brush biopsy from 15 Grain handlers 6 h after experimental inhalation of saline or an aqueous corn Dust extract. After inhalation of saline, BE expressed low but detectable levels of IL-6, IL-8, and IL-1beta (> 1 complementary DNA [cDNA] molecule/cell). After inhalation of corn Dust extract, the expression of messenger RNA (mRNA) for IL-1beta and IL-8 in the BE were significantly increased, whereas no change was seen in IL-6, sIL-1RA, and TNF-alpha mRNA expression. Comparing cytokine mRNA levels in BE and BAL cells from the same subjects after inhalation of corn Dust extract, BE and BAL cells expressed equivalent amounts of IL-8 mRNA; IL-1beta was 11-fold higher in BAL cells; and TNF-alpha and sIL-1RA were expressed exclusively by BAL cells. Immunostaining for the cytokines in BAL cells showed cytokine protein expression in AMs but not in polymorphonuclear cells (PMNs). On the other hand, sIL-1RA was strongly expressed in both AMs and PMNs. Analysis of cytokine protein levels in endobronchial lavage (EBL) fluid demonstrated that only IL-8 was released in detectable amounts into the airway lumen, whereas all the other cytokines of interest were exclusively found in the BAL fluid. Thus, within 6 h after inhalation exposure to corn Dust extract, BE appear to contribute to airway inflammation by producing IL-8. AMs are responsible for most of the IL-1beta and IL-6 production in the alveolar region, whereas AMs and PMNs both produce sIL-1RA. Our findings suggest that the inflammatory response to inhaled Grain Dust is compartmentalized, involving specific mediators of inflammation released by macrophages, neutrophils, and airway epithelial cells.
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Grain Dust-induced lung inflammation is reduced byRhodobacter sphaeroides diphosphoryl lipid A
The American journal of physiology, 1998Co-Authors: Paul J. Jagielo, Timothy J. Quinn, Nilofer Qureshi, David A. SchwartzAbstract:To further determine the importance of endotoxin in Grain Dust-induced inflammation of the lower respiratory tract, we evaluated the efficacy of pentaacylated diphosphoryl lipid A derived from the ...
Wijnand Eduard - One of the best experts on this subject based on the ideXlab platform.
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on behalf of the British Occupational Hygiene Society. Exposure to Grain Dust and Microbial Components in the Norwegian Grain and Compound Feed InDustry
2016Co-Authors: Ann Occup Hyg, Kari Kulvik Heldal, Inge M Wouters, Anne Straumfors Halstensen, Marit Skogstad, Dag G Ellingsen, Wijnand EduardAbstract:Objectives: The aim of this study was to extensively characterize Grain workers ’ personal expo-sure during work in Norwegian Grain elevators and compound feed mills, to identify differences in exposures between the workplaces and seasons, and to study the correlations between different microbial components. Methods: Samples of airborne Dust (n = 166) were collected by full-shift personal sampling during work in 20 Grain elevators and compound feed mills during one autumn season and two winter seasons. The personal exposure to Grain Dust, endotoxins, β-1→3-glucans, bacteria, and fungal spores was quantified. Correlations between Dust and microbial components and differences between workplaces and seasons were investigated. Determinants of endotoxin and β-1→3-glucan exposure were evaluated by linear mixed-effect regression modeling. Results: The workers were exposed to an overall geometric mean of 1.0 mg m−3 inhalable Grain Dust [geometric standard deviation (GSD) = 3.7], 628 endotoxin units m−3 (GSD = 5.9), 7.4 µg m−3 of β-1→3-glucan (GSD = 5.6), 21 × 104 bacteria m−3 (GSD = 7.9) and 3.6 × 104 fungal spores m−3 (GSD = 3.4). The Grain Dust exposure levels were similar across workplaces and seasons, but the microbial content of the Grain Dust varied substantially between workplaces. Exposure level
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work tasks as determinants of Grain Dust and microbial exposure in the norwegian Grain and compound feed inDustry
Annals of Occupational Hygiene, 2015Co-Authors: Anne Straumfors, Kari Kulvik Heldal, Inge M Wouters, Wijnand EduardAbstract:OBJECTIVES: The Grain and compound feed inDustry entails inevitable risks of exposure to Grain Dust and its microbial content. The objective of this study was therefore to investigate task-dependent exposure differences in order to create knowledge basis for awareness and exposure reducing measures in the Norwegian Grain and compound feed inDustry. METHODS: A total of 166 samples of airborne Dust were collected by full-shift personal sampling during work in 20 Grain elevators and compound feed mills during one autumn season and two winter seasons. The personal exposure to Grain Dust, endotoxins, β-1→3-glucans, bacteria, and fungal spores was quantified and used as individual outcomes in mixed models with worker nested in company as random effect and different departments and tasks as fixed effects. RESULTS: The exposure levels were highest in Grain elevator departments. Exposure to endotoxins was particularly high. Tasks that represented the highest and lowest exposures varied depending on the bioaerosol component. The most important determinants for elevated Dust exposure were cleaning and process controlling. Cleaning increased the Dust exposure level by a factor of 2.44 of the reference, from 0.65 to 1.58mg m(-3), whereas process controlling increased the Dust exposure level by a factor of 2.97, from 0.65 to 1.93mg m(-3). Process controlling was associated with significantly less Grain Dust exposure in compound feed mills and the combined Grain elevators and compound feed mills, than in Grain elevators. The exposure was reduced by a factor of 0.18 and 0.22, from 1.93 to 0.34mg m(-3) and to 0.42mg m(-3), respectively, compared with the Grain elevators. Inspection/maintenance, cleaning, and Grain rotation and emptying were determinants of higher exposure to both endotoxin and β-1→3-glucans. Seed winnowing was in addition a strong determinant for endotoxin, whereas mixing of animal feed implied higher β-1→3-glucan exposure. Cleaning was the only task that contributed significantly to higher exposure to bacteria and fungal spores. CONCLUSION: Cleaning in all companies and process controlling in Grain elevators were the strongest determinants for overall exposure, whereas seed winnowing was a particular strong determinant of endotoxin exposure. Exposure reduction by technical intervention or personal protective equipment should therefore be considered at work places with identified high exposure tasks.
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Work Tasks as Determinants of Grain Dust and Microbial Exposure in the Norwegian Grain and Compound Feed InDustry
The Annals of occupational hygiene, 2015Co-Authors: Anne Straumfors, Kari Kulvik Heldal, Inge M Wouters, Wijnand EduardAbstract:The Grain and compound feed inDustry entails inevitable risks of exposure to Grain Dust and its microbial content. The objective of this study was therefore to investigate task-dependent exposure differences in order to create knowledge basis for awareness and exposure reducing measures in the Norwegian Grain and compound feed inDustry. A total of 166 samples of airborne Dust were collected by full-shift personal sampling during work in 20 Grain elevators and compound feed mills during one autumn season and two winter seasons. The personal exposure to Grain Dust, endotoxins, β-1→3-glucans, bacteria, and fungal spores was quantified and used as individual outcomes in mixed models with worker nested in company as random effect and different departments and tasks as fixed effects. The exposure levels were highest in Grain elevator departments. Exposure to endotoxins was particularly high. Tasks that represented the highest and lowest exposures varied depending on the bioaerosol component. The most important determinants for elevated Dust exposure were cleaning and process controlling. Cleaning increased the Dust exposure level by a factor of 2.44 of the reference, from 0.65 to 1.58mg m(-3), whereas process controlling increased the Dust exposure level by a factor of 2.97, from 0.65 to 1.93mg m(-3). Process controlling was associated with significantly less Grain Dust exposure in compound feed mills and the combined Grain elevators and compound feed mills, than in Grain elevators. The exposure was reduced by a factor of 0.18 and 0.22, from 1.93 to 0.34mg m(-3) and to 0.42mg m(-3), respectively, compared with the Grain elevators. Inspection/maintenance, cleaning, and Grain rotation and emptying were determinants of higher exposure to both endotoxin and β-1→3-glucans. Seed winnowing was in addition a strong determinant for endotoxin, whereas mixing of animal feed implied higher β-1→3-glucan exposure. Cleaning was the only task that contributed significantly to higher exposure to bacteria and fungal spores. Cleaning in all companies and process controlling in Grain elevators were the strongest determinants for overall exposure, whereas seed winnowing was a particular strong determinant of endotoxin exposure. Exposure reduction by technical intervention or personal protective equipment should therefore be considered at work places with identified high exposure tasks. © The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.
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Mycotoxins and other fungal metabolites in Grain Dust from Norwegian Grain elevators and compound feed mills
World Mycotoxin Journal, 2015Co-Authors: Anne Straumfors, Kari Kulvik Heldal, Wijnand Eduard, S. Uhlig, Gunnar Sundstøl Eriksen, Rudolf Krska, Michael SulyokAbstract:Employees at Grain elevators and compound feed mills are exposed to large amounts of Grain Dust during work, frequently leading to airway symptoms and asthma. Although the exposure to Grain Dust, microorganisms, β-1→3-glucans and endotoxins has been extensively studied, the focus on the mycotoxin content of Grain Dust has previously been limited to one or few mycotoxins. Our objective was therefore to screen settled Grain Dust from Grain elevators and compound feed mills for fungal metabolites by LC/MS-MS and explore differences between work places, seasons and climatic zones. Seventy fungal metabolites and two bacterial metabolites were detected. Trichothecenes, depsipeptides, ergot alkaloids, and other metabolites from Fusarium, Claviceps, Alternaria, Penicillium, Aspergillus, and other fungi were represented. The prevalence of individual metabolites was highly variable, and the concentration of each metabolite varied considerably between samples. The prevalence and concentration of most metabolites wer...
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exposure to Grain Dust and microbial components in the norwegian Grain and compound feed inDustry
Annals of Occupational Hygiene, 2013Co-Authors: Anne Straumfors Halstensen, Kari Kulvik Heldal, Inge M Wouters, Marit Skogstad, Dag G Ellingsen, Wijnand EduardAbstract:Objectives: The aim of this study was to extensively characterize Grain workers’ personal exposure during work in Norwegian Grain elevators and compound feed mills, to identify differences in exposures between the workplaces and seasons, and to study the correlations between different microbial components. Methods: Samples of airborne Dust (n = 166) were collected by full-shift personal sampling during work in 20 Grain elevators and compound feed mills during one autumn season and two winter seasons. The personal exposure to Grain Dust, endotoxins, β-1→3-glucans, bacteria, and fungal spores was quantified. Correlations between Dust and microbial components and differences between workplaces and seasons were investigated. Determinants of endotoxin and β-1→3-glucan exposure were evaluated by linear mixed-effect regression modeling. Results: The workers were exposed to an overall geometric mean of 1.0 mg m −3 inhalable Grain Dust [geometric standard deviation (GSD) = 3.7], 628 endotoxin units m −3 (GSD = 5.9), 7.4 µg m −3 of β-1→3-glucan (GSD = 5.6), 21 × 10 4 bacteria m −3 (GSD = 7.9) and 3.6 × 10 4 fungal spores m −3 (GSD = 3.4). The Grain Dust exposure levels were similar across workplaces and seasons, but the microbial content of the Grain Dust varied substantially between workplaces. Exposure levels of all microbial components were significantly higher in Grain elevators compared with all other workplaces. The Grain Dust exposure was significantly correlated (Pearson’s r) with endotoxin (r p = 0.65), β-1→3-glucan (r p = 0.72), bacteria (r p = 0.44) and fungal spore (r p = 0.48) exposure, whereas the explained variances were strongly dependent on the workplace. Bacteria, Grain Dust, and workplace were important determinants for endotoxin exposure, whereas fungal spores, Grain Dust, and workplace were important determinants for β-1→3-glucan exposure. Conclusions: Although the workers were exposed to a relatively low mean Dust level, the microbial exposure was high. Furthermore, the exposure levels of microbial components varied between workplaces although the Dust levels were similar. We therefore recommend that exposure levels at different workplaces should be assessed separately and a task-based assessment should be done for detailed evaluation of efficient Dust-reducing measures. The microbial content and knowledge of health effects of the microbial components should be considered in health risk evaluations of these workplaces.
Peter S. Thorne - One of the best experts on this subject based on the ideXlab platform.
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Endotoxin Responsiveness and Subchronic Grain Dust-Induced Airway Disease
American journal of physiology. Lung cellular and molecular physiology, 2001Co-Authors: Caroline L. S. George, Hong Jin, Christine L. Wohlford-lenane, Marsha E. O'neill, John C. Phipps, Patrick T. O'shaughnessy, Joel N. Kline, Peter S. Thorne, David A. SchwartzAbstract:Endotoxin is one of the principal components of Grain Dust that causes acute reversible airflow obstruction and airway inflammation. To determine whether endotoxin responsiveness influences the development of chronic Grain Dust-induced airway disease, physiological and airway inflammation remodeling parameters were evaluated after an 8-wk exposure to corn Dust extract (CDE) and again after a 4-wk recovery period in a strain of mice sensitive to (C3H/HeBFeJ) and one resistant to (C3H/HeJ) endotoxin. After the CDE exposure, both strains of mice had equal airway hyperreactivity to a methacholine challenge; however, airway hyperreactivity persisted only in the C3H/HeBFeJ mice after the recovery period. Only the C3H/HeBFeJ mice showed significant inflammation of the lower airway after the 8-wk exposure to CDE. After the recovery period, this inflammatory response completely resolved. Lung stereological measurements indicate that an 8-wk exposure to CDE resulted in persistent expansion of the airway submucosal cross-sectional area only in the C3H/HeBFeJ mice. Collagen type III and an influx of cells into the subepithelial area participated in the expansion of the submucosa. Our findings demonstrate that subchronic inhalation of Grain Dust extract results in the development of chronic airway disease only in mice sensitive to endotoxin but not in mice that are genetically hyporesponsive to endotoxin, suggesting that endotoxin is important in the development of chronic airway disease.
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the kinetics of Grain Dust induced inflammation of the lower respiratory tract
American Journal of Respiratory and Critical Care Medicine, 1997Co-Authors: Daniel C Deetz, Peter S. Thorne, Paul J. Jagielo, Timothy J. Quinn, Shari A Bleuer, David A. SchwartzAbstract:To characterize the kinetics of Grain Dust-induced airflow obstruction and inflammation in the lower respiratory tract, we performed serial spirometry and bronchoalveolar lavage (BAL) in human subjects and whole-lung lavage in mice following a single inhalation exposure to comparable dosages of corn Dust extract (CDE). Following inhalation of CDE, our human study subjects developed significant airflow obstruction 10 min postexposure which persisted for 48 h. Human subjects and mice had similar acute and persistent changes in lavage cellularity after exposure to CDE. A profound increase in the concentration of lavage neutrophils was present in the initial postexposure lavage in both human subjects and mice. This increase persisted for 96 h in human subjects and 48 h in mice. Small but significant increases in lavage macrophage concentration were present 48 h postexposure in human subjects and at 96 h postexposure in mice. Inhalation of CDE resulted in a significant increase in the concentration of proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the lavage fluid of both human subjects and mice. Similarly, significant increases in lavage concentrations of IL-8 in humans and macrophage inflammatory protein-2 (MIP-2) in mice occurred after inhalation of CDE. The lavage concentration of all measured proinflammatory cytokines returned to baseline levels by 168 h in humans and 96 h in mice. These findings suggest that a single inhalation challenge of CDE results in airflow obstruction and lower respiratory tract inflammation that may last for several days. These physiologic and inflammatory responses appear to be self-limited with no evidence of persistent injury 1 wk after the inhalation challenge. Moreover, the inflammatory response in the lower respiratory tract after inhalation of Grain Dust is similar in human subjects and mice, suggesting that the mouse may be an appropriate model for further investigation of Grain Dust-induced inflammation.
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The role of atopy in Grain Dust-induced airway disease.
American journal of respiratory and critical care medicine, 1996Co-Authors: C A Blaski, Peter S. Thorne, W D Clapp, T J Quinn, J L Watt, K L Fress, S J Yagla, David A. SchwartzAbstract:To determine whether atopy influences the physiologic or inflammatory response to Grain Dust, we compared spirometric measures of airflow and bronchoalveolar lavage (BAL) measures of lower respiratory tract inflammation between demographically similar nonatopic (n = 10) and atopic (n = 10) study subjects after each of two inhalation exposures: Hanks' balanced salt solution (HBSS) and corn Dust extract (CDE; 0.4 microgram of endotoxin/kg body weight). Subjects were healthy nonsmokers with similar baseline pulmonary function, without bronchial hyperreactivity, and had not participated in agriculture. Atopic subjects had two or more positive skin responses to 10 common environmental allergens. Both groups developed significant airflow obstruction and lower airway inflammation after CDE inhalation. Importantly, the magnitude of the post-CDE exposure airflow decrements, BAL cellularity, and BAL concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-6, and IL-8 did not significantly differ between atopics and nonatopics. The concentrations of histamine and eosinophils in the BAL fluid were unaffected by CDE inhalation and did not significantly differ between atopics and nonatopics. Atopic status does not appear to be a significant determinant of airflow obstruction or lower airway inflammation following CDE inhalation. Our findings suggest that atopy may play, at most, a minor role in the development of Grain Dust-induced airway disease.
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The role of endotoxin in Grain Dust-induced lung disease
American journal of respiratory and critical care medicine, 1995Co-Authors: David A. Schwartz, Stephen A. Olenchock, Peter S. Thorne, Janet L. Watt, S J Yagla, Leon F. Burmeister, Timothy J. QuinnAbstract:To identify the role of endotoxin in Grain Dust-induced lung disease, we conducted a population-based, cross-sectional investigation among Grain handlers and postal workers. The study subjects were selected by randomly sampling all Grain facilities and post offices within 100 miles of Iowa City. Our study population consisted of 410 Grain workers and 201 postal workers. Grain workers were found to be exposed to higher concentrations of airborne Dust (p = 0.0001) and endotoxin (p = 0.0001) when compared with postal workers. Grain workers had a significantly higher prevalence of work-related (cough, phlegm, wheezing, chest tightness, and dyspnea) and chronic (usual cough or phlegm production) respiratory symptoms than postal workers. Moreover, after controlling for age, gender, and cigarette smoking status, work-related respiratory symptoms were strongly associated with the concentration of endotoxin in the bioaerosol in the work setting. The concentration of total Dust in the bioaerosol was marginally related to these respiratory problems. After controlling for age, gender, and cigarette smoking status, Grain workers were found to have reduced spirometric measures of airflow (FEV1, FEV1/FVC, and FEF25-75) and enhanced airway reactivity to inhaled histamine when compared with postal workers. Although the total Dust concentration in the work environment appeared to have little effect on these measures of airflow obstruction, higher concentrations of endotoxin in the bioaerosol were associated with diminished measures of airflow and enhanced bronchial reactivity. Our results indicate that the concentration of endotoxin in the bioaerosol may be particularly important in the development of Grain Dust-induced lung disease.
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endotoxin responsiveness and Grain Dust induced inflammation in the lower respiratory tract
American Journal of Physiology-lung Cellular and Molecular Physiology, 1994Co-Authors: David A. Schwartz, Peter S. Thorne, Paul J. Jagielo, Shari A Bleuer, G E White, Kathy L. FreesAbstract:To identify the role of endotoxin responsiveness in Grain Dust-induced airway disease, we used two models of extotoxin hyporesponsiveness to perform inhalation exposure studies in mice. In the first model, we investigated whether genetic resistance to endotoxin would alter the inflammatory response to inhaled Grain Dust by comparing the inflammatory response in the lower respiratory tract of endotoxin-sensitive and -resistant male mice after inhalation of pyrogen-free saline, corn Dust extract (CDE), sterile CDE (SCDE), or lipopolysaccharide (LPS). Endotoxin-sensitive and -resistant mice were exposed for 4 h to nebulized solutions of LPS, SCDE, or CDE. Another group of endotoxin-sensitive and -resistant mice was sham exposed for 4 h to nebulized sterile saline. Dose-response relationships for endotoxin were explored for LPS, SCDE, and CDE. Bronchoalveolar lavage (BAL) 5 h after the start of exposure demonstrated a higher concentration of total cells, neutrophils (PMNs), and tumor necrosis factor-alpha (TNF-alpha) in BAL fluid after inhalation of CDE, SCDE, or LPS in endotoxin-sensitive than in endotoxin-resistant mice. Whereas endotoxin-sensitive mice demonstrated a dose-response relationship between the endotoxin concentration in each of the solutions and the concentration of cells, PMNs, and TNF-alpha in BAL fluid, concentrations of TNF-alpha were significantly higher only in BAL fluid of endotoxin-resistant mice exposed to higher concentrations of SCDE or CDE. In the second model, we investigated whether acquired endotoxin tolerance would alter the inflammatory response to SCDE.(ABSTRACT TRUNCATED AT 250 WORDS)
Kathy L. Frees - One of the best experts on this subject based on the ideXlab platform.
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Compartmentalization of the inflammatory response to inhaled Grain Dust.
American journal of respiratory and critical care medicine, 1999Co-Authors: Susanne Becker, Kathy L. Frees, William A. Clapp, Jacqueline Quay, Hillel S. Koren, David A. SchwartzAbstract:Interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha, and the secreted form of the IL-1 receptor antagonist (sIL-1RA) are involved in the inflammatory response to inhaled Grain Dust. Previously, we found considerable production of these cytokines in the lower respiratory tract of workers exposed by inhalation to aqueous extracts of corn Dust extract. Alveolar macrophages (AM) have long been considered the cell type responsible for producing these cytokines, and only recently has it been realized that airway epithelial cells may also be involved in cytokine production. In order to determine whether airway epithelia are involved in the inflammatory response to inhaled corn Dust extract and to compare the magnitude of response of bronchial epithelial cells (BE) and bronchoalveolar lavage (BAL) cells, we used the reverse transcriptase/polymerase chain reaction (RT/PCR) technique in a semiquantitative manner to evaluate the concentration of IL-1beta, IL-6, IL-8, TNF-alpha, and sIL-1RA. Alveolar cells were obtained by BAL, and BE were obtained by endobronchial brush biopsy from 15 Grain handlers 6 h after experimental inhalation of saline or an aqueous corn Dust extract. After inhalation of saline, BE expressed low but detectable levels of IL-6, IL-8, and IL-1beta (> 1 complementary DNA [cDNA] molecule/cell). After inhalation of corn Dust extract, the expression of messenger RNA (mRNA) for IL-1beta and IL-8 in the BE were significantly increased, whereas no change was seen in IL-6, sIL-1RA, and TNF-alpha mRNA expression. Comparing cytokine mRNA levels in BE and BAL cells from the same subjects after inhalation of corn Dust extract, BE and BAL cells expressed equivalent amounts of IL-8 mRNA; IL-1beta was 11-fold higher in BAL cells; and TNF-alpha and sIL-1RA were expressed exclusively by BAL cells. Immunostaining for the cytokines in BAL cells showed cytokine protein expression in AMs but not in polymorphonuclear cells (PMNs). On the other hand, sIL-1RA was strongly expressed in both AMs and PMNs. Analysis of cytokine protein levels in endobronchial lavage (EBL) fluid demonstrated that only IL-8 was released in detectable amounts into the airway lumen, whereas all the other cytokines of interest were exclusively found in the BAL fluid. Thus, within 6 h after inhalation exposure to corn Dust extract, BE appear to contribute to airway inflammation by producing IL-8. AMs are responsible for most of the IL-1beta and IL-6 production in the alveolar region, whereas AMs and PMNs both produce sIL-1RA. Our findings suggest that the inflammatory response to inhaled Grain Dust is compartmentalized, involving specific mediators of inflammation released by macrophages, neutrophils, and airway epithelial cells.
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The Effect of Glucocorticoids on Grain Dust-Induced Airway Disease
Chest, 1998Co-Authors: John F. Trapp, Janet L. Watt, Timothy J. Quinn, Kathy L. Frees, Matthew W. Nonnenmann, David A. SchwartzAbstract:Study objectives To determine the effect of glucocorticoids on Grain Dust-induced airflow obstruction and airway inflammation. Design Randomized controlled trial. Setting University hospital. Participants Health volunteers. Interventions Two randomized, placebo-controlled trials, each studying 10 healthy volunteers who were pretreated with either triamcinolone acetonide (Azmacort) oral inhaler 4 puffs twice daily (800 μg daily) for 7 consecutive days or IV hydrocortisone (3 μg/kg/min) as a 14-h continuous infusion, then subjected to a controlled inhalation exposure to corn Dust extract (CDE) (endotoxin exposure dose of 3 pg/kg). A single-blind, crossover study design was performed for each trial enrolling 10 healthy, lifetime nonsmokers, with no history of lung disease or environmental exposure to Grain Dust. Measurements and results Following each inhalation exposure to CDE, spirometry was performed at regular intervals and BAL was performed at 4 h. Both treatment and placebo groups demonstrated significant decrements in spirometry and increments in BAL cellularity following CDE inhalation compared with placebo. Inhaled steroid treatment resulted in a significantly higher FEV 1 only at the 2-h time point following CDE inhalation with no significant differences observed in the BAL total cell concentration or cellular differential compared with placebo. IV hydrocortisone treatment resulted in a significantly higher FEV 1 and FVC between 2 and 4 h after CDE inhalation, as well as significant reductions in the BAL total cell, macrophage, and eosinophil concentrations. Interestingly, the concentration of tumor necrosis factor-α and interleukin-8 in the BAL fluid was also decreased following treatment with IV glucocorticoids. Conclusions These results demonstrate that glucocorticoids, administered IV and perhaps by inhalation, have a mildly protective effect on airflow obstruction and airway inflammation induced by inhalation of Grain Dust.
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endotoxin responsiveness and Grain Dust induced inflammation in the lower respiratory tract
American Journal of Physiology-lung Cellular and Molecular Physiology, 1994Co-Authors: David A. Schwartz, Peter S. Thorne, Paul J. Jagielo, Shari A Bleuer, G E White, Kathy L. FreesAbstract:To identify the role of endotoxin responsiveness in Grain Dust-induced airway disease, we used two models of extotoxin hyporesponsiveness to perform inhalation exposure studies in mice. In the first model, we investigated whether genetic resistance to endotoxin would alter the inflammatory response to inhaled Grain Dust by comparing the inflammatory response in the lower respiratory tract of endotoxin-sensitive and -resistant male mice after inhalation of pyrogen-free saline, corn Dust extract (CDE), sterile CDE (SCDE), or lipopolysaccharide (LPS). Endotoxin-sensitive and -resistant mice were exposed for 4 h to nebulized solutions of LPS, SCDE, or CDE. Another group of endotoxin-sensitive and -resistant mice was sham exposed for 4 h to nebulized sterile saline. Dose-response relationships for endotoxin were explored for LPS, SCDE, and CDE. Bronchoalveolar lavage (BAL) 5 h after the start of exposure demonstrated a higher concentration of total cells, neutrophils (PMNs), and tumor necrosis factor-alpha (TNF-alpha) in BAL fluid after inhalation of CDE, SCDE, or LPS in endotoxin-sensitive than in endotoxin-resistant mice. Whereas endotoxin-sensitive mice demonstrated a dose-response relationship between the endotoxin concentration in each of the solutions and the concentration of cells, PMNs, and TNF-alpha in BAL fluid, concentrations of TNF-alpha were significantly higher only in BAL fluid of endotoxin-resistant mice exposed to higher concentrations of SCDE or CDE. In the second model, we investigated whether acquired endotoxin tolerance would alter the inflammatory response to SCDE.(ABSTRACT TRUNCATED AT 250 WORDS)
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Grain Dust induced airflow obstruction and inflammation of the lower respiratory tract
American Journal of Respiratory and Critical Care Medicine, 1994Co-Authors: W D Clapp, Peter S. Thorne, Janet L. Watt, Kathy L. Frees, Jacqueline Quay, Hillel S. Koren, Susan Becker, Xiaoyu Zhang, Christine R Lux, David A. SchwartzAbstract:To investigate the relationship between the physiologic and biologic effects of Grain Dust inhalation, we exposed 15 nonsmoking, nonasthmatic, nonatopic male Grain handlers to buffered saline and aqueous corn Dust extract by inhalation challenge in a crossover study. The inhalation challenges to buffered saline and corn Dust extract were separated by at least 14 d. Compared with buffered saline, inhalation of corn Dust extract resulted in significant airflow obstruction, which was observed within 30 min of exposure and persisted for 5 h. Inhalation of corn Dust extract resulted in an acute inflammatory response characterized by higher concentrations of neutrophils (p = 0.001), IL-1 beta (p = 0.001), IL-1RA (p = 0.001), IL-6 (p = 0.001), IL-8 (p = 0.001), and TNF-alpha (p = 0.04) in bronchoalveolar lavage (BAL) fluid. mRNA levels specific for IL-1 beta, IL-1RA, IL-6, and IL-8 from cells present in the BAL fluid were significantly greater after challenge with corn Dust extract than after challenge with buff...
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The Effects of Inhalation of Grain Dust Extract and Endotoxin on Upper and Lower Airways
Chest, 1993Co-Authors: W D Clapp, Peter S. Thorne, Kathy L. Frees, Xiaouji Zhang, Cheri Lux, David A. SchwartzAbstract:To characterize the short-term effects of Grain Dusts on pulmonary function, mucosal inflammation, and systemic responses, four women and three men inhaled nebulized corn and soybean Dust extracts, endotoxin diluted with Hanks' balanced salt solution (HBSS), and HBSS. Subjects were volunteers recruited via newspaper advertisement and were required to be healthy, nonasthmatic, nonatopic never-smokers. The mean age was 26.9 years (range, 19 to 36 years). Using a randomized, double-blind, crossover design, each subject was challenged with each of the 4 substances with at least 10 days between challenges. Serial spirometry, peripheral blood leukocyte and differential cell counts, and 24-h postchallenge nasal lavages were performed. Extracts were produced by mixing 3 g of the corn or soybean Dust with 30 ml HBSS followed by shaking for 60 min, centrifugation, then filter sterilization. The endotoxin solution was produced by mixing lyophilized Escherichia coli endotoxin (serotype 0111:B4) with HBSS to attain a final concentration of 7 mg/L, which was the same as the concentration of endotoxin in both Grain Dust solutions. The pH of all solutions and unmixed HBSS was adjusted to 5.8, which was the native pH of the soybean Dust extract. Subjects were challenged with 0.08 ml/kg of each substance, resulting in a range of endotoxin doses of 30 to 60 micrograms, similar to that which a worker might inhale over the course of one workshift. The lowest mean percentage baseline FEV1 (+/- SD) after inhalation challenge was 99.2 +/- 2.1 for HBSS, and it was significantly lower for endotoxin (90.1 +/- 8.5, p = 0.03), corn Dust extract (93.1 +/- 4.3, p = 0.02), and soybean Dust extract (96.2 +/- 3.7, p = 0.03). In addition, a peripheral blood leukocytosis developed after exposure to all three endotoxin-containing solutions (p < 0.05), yet a lower peripheral blood lymphocyte count was found only after inhalation of corn Dust extract (p = 0.02). Interestingly, this was associated with a higher nasal lavage lymphocyte count after inhalation of corn Dust extract (p = 0.03). Neither the decrease in peripheral blood lymphocytes nor the increase in nasal lymphocytes were found after inhalation of soybean Dust extract or endotoxin. Our results indicate that extracts of Grain Dusts have physiologic effects similar to endotoxin. However, in spite of the same endotoxin levels, the effects of corn Dust extract appear to have different biologic activity than either soybean Dust extract or endotoxin.
Paul J. Jagielo - One of the best experts on this subject based on the ideXlab platform.
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Bronchial hyperreactivity is associated with enhanced Grain Dust-induced airflow obstruction
Journal of applied physiology (Bethesda Md. : 1985), 2000Co-Authors: Joel N. Kline, Paul J. Jagielo, Janet L. Watt, David A. SchwartzAbstract:Bronchial hyperreactivity (BHR) is associated with the presence of airway inflammation in asthma and is seen in individuals occupationally exposed to Grain Dust. To better understand the relationsh...
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Grain Dust-induced lung inflammation is reduced byRhodobacter sphaeroides diphosphoryl lipid A
The American journal of physiology, 1998Co-Authors: Paul J. Jagielo, Timothy J. Quinn, Nilofer Qureshi, David A. SchwartzAbstract:To further determine the importance of endotoxin in Grain Dust-induced inflammation of the lower respiratory tract, we evaluated the efficacy of pentaacylated diphosphoryl lipid A derived from the ...
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occupational and environmental lung disease pentoxifylline does not alter the response to inhaled Grain Dust
Chest, 1997Co-Authors: Paul J. Jagielo, Janet L. Watt, Timothy J. Quinn, Howard R. Knapp, David A. SchwartzAbstract:Pentoxifylline (PTX) has been shown to reduce sepsis-induced neutrophil sequestration in the lung and inhibit endotoxin-mediated release of tumor necrosis factor-α (TNF-α). Previously, we have shown that endotoxin appears to be the principal agent in Grain Dust causing airway inflammation and airflow obstruction following Grain Dust inhalation. To determine whether PTX affects the physiologic and inflammatory events following acute Grain Dust inhalation, 10 healthy, nonsmoking subjects with normal airway reactivity were treated with PTX or placebo (PL) followed by corn Dust extract (CDE) inhalation (0.08 mL/kg), using a single-blinded, crossover design. Subjects received PTX (1,200 mg/d) or PL for 4 days prior to CDE inhalation and 400 mg PTX or PL on the exposure day. Both respiratory symptoms and declines in FEV1 and FVC occurred following CDE exposure in both groups, but there were no significant differences in the frequency of symptoms or percent declines from baseline in the FEV1 and FVC at any of the time points measured in the study. Elevations in peripheral blood leukocyte and neutrophil concentrations and BAL total cell, neutrophil, TNF-α, and interleukin-8 concentrations were measured 4 h following exposure to CDE in both the PTX- and PL-treated subjects, but no significant differences were found between treatment groups. These results suggest that pretreatment with PTX prior to inhalation of CDE, in the doses used in this study, does not alter the acute physiologic or inflammatory events following exposure to inhaled CDE.
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Pentoxifylline does not alter the response to inhaled Grain Dust.
Chest, 1997Co-Authors: Paul J. Jagielo, Janet L. Watt, Timothy J. Quinn, Howard R. Knapp, David A. SchwartzAbstract:Pentoxifylline (PTX) has been shown to reduce sepsis-induced neutrophil sequestration in the lung and inhibit endotoxin-mediated release of tumor necrosis factor-α (TNF-α). Previously, we have shown that endotoxin appears to be the principal agent in Grain Dust causing airway inflammation and airflow obstruction following Grain Dust inhalation. To determine whether PTX affects the physiologic and inflammatory events following acute Grain Dust inhalation, 10 healthy, nonsmoking subjects with normal airway reactivity were treated with PTX or placebo (PL) followed by corn Dust extract (CDE) inhalation (0.08 mL/kg), using a single-blinded, crossover design. Subjects received PTX (1,200 mg/d) or PL for 4 days prior to CDE inhalation and 400 mg PTX or PL on the exposure day. Both respiratory symptoms and declines in FEV 1 and FVC occurred following CDE exposure in both groups, but there were no significant differences in the frequency of symptoms or percent declines from baseline in the FEV 1 and FVC at any of the time points measured in the study. Elevations in peripheral blood leukocyte and neutrophil concentrations and BAL total cell, neutrophil, TNF-α, and interleukin-8 concentrations were measured 4 h following exposure to CDE in both the PTX- and PL-treated subjects, but no significant differences were found between treatment groups. These results suggest that pretreatment with PTX prior to inhalation of CDE, in the doses used in this study, does not alter the acute physiologic or inflammatory events following exposure to inhaled CDE.
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the kinetics of Grain Dust induced inflammation of the lower respiratory tract
American Journal of Respiratory and Critical Care Medicine, 1997Co-Authors: Daniel C Deetz, Peter S. Thorne, Paul J. Jagielo, Timothy J. Quinn, Shari A Bleuer, David A. SchwartzAbstract:To characterize the kinetics of Grain Dust-induced airflow obstruction and inflammation in the lower respiratory tract, we performed serial spirometry and bronchoalveolar lavage (BAL) in human subjects and whole-lung lavage in mice following a single inhalation exposure to comparable dosages of corn Dust extract (CDE). Following inhalation of CDE, our human study subjects developed significant airflow obstruction 10 min postexposure which persisted for 48 h. Human subjects and mice had similar acute and persistent changes in lavage cellularity after exposure to CDE. A profound increase in the concentration of lavage neutrophils was present in the initial postexposure lavage in both human subjects and mice. This increase persisted for 96 h in human subjects and 48 h in mice. Small but significant increases in lavage macrophage concentration were present 48 h postexposure in human subjects and at 96 h postexposure in mice. Inhalation of CDE resulted in a significant increase in the concentration of proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in the lavage fluid of both human subjects and mice. Similarly, significant increases in lavage concentrations of IL-8 in humans and macrophage inflammatory protein-2 (MIP-2) in mice occurred after inhalation of CDE. The lavage concentration of all measured proinflammatory cytokines returned to baseline levels by 168 h in humans and 96 h in mice. These findings suggest that a single inhalation challenge of CDE results in airflow obstruction and lower respiratory tract inflammation that may last for several days. These physiologic and inflammatory responses appear to be self-limited with no evidence of persistent injury 1 wk after the inhalation challenge. Moreover, the inflammatory response in the lower respiratory tract after inhalation of Grain Dust is similar in human subjects and mice, suggesting that the mouse may be an appropriate model for further investigation of Grain Dust-induced inflammation.
