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Biomedical subjects

P J Borm

Publications and source records attributed to P J Borm.

At least 19 recordsLinked to original sources
PubMed1999

Priming of cytokine release and increased levels of bactericidal permeability-increasing protein in the blood of animal facility workers.

OBJECTIVE: To investigate cellular immune responses in laboratory animal workers who are exposed to high levels of animal allergens but also to other biologically active substances containing lipopolysaccharides (LPS), i.e., endotoxins. METHODS: A survey among 20 animal facility workers and 20 matched (gender, smoking) controls was conducted using exposure measurements (endotoxin, colony-forming units of bacteria and fungi) and a questionnaire on respiratory symptoms. Blood samples were taken to determine the ex vivo whole-blood release of tumor necrosis factor-alpha (TNF) and interleukin-8 (IL-8) as well as plasma levels of LPS-binding protein (LBP), bactericidal permeability-increasing protein (BPI), the 75-kDa soluble TNF receptor (sTNFR75), and total/specific IgE. RESULTS: Although exposure to endotoxin was low (range 0.05-2.8 ng/m(3)), a significant (P < 0.05) increase in plasma BPI (4-fold) and srTNF75 (1.2-fold) was found, suggesting a response to inhalation of LPS. Also, the capacity of blood leukocytes to release TNF and IL-8 in response to ex vivo exposure to workplace dust was increased. Data were not confounded by specific allergies, levels of IgE, smoking, or respiratory symptoms. CONCLUSIONS: A profound effect on the cellular immune response was seen in animal workers with low endotoxin exposure and a high antigenic load. It remains to be determined which other biologically active substance(s) are involved in this effect.

Acute-Phase Proteins↗
PubMed1999

Mechanisms and mediators in coal dust induced toxicity: a review.

Chronic inhalation of coal dust can cause several lung disorders, including simple coal workers pneumoconiosis (CWP), progressive massive fibrosis (PMF), chronic bronchitis, lung function loss, and emphysema. This review focuses on the cellular actions and interactions of key inflammatory cells and target cells in coal dust toxicity and related lung disorders, i.e. macrophages and neutrophils, epithelial cells, and fibroblasts. Factors released from or affecting these cells are outlined in separate sections, i.e. (1) reactive oxygen species (ROS) and related antioxidant protection mechanisms, and (2) cytokines, growth factors and related proteins. Furthermore, (3) components of the extracellular matrix (ECM), including the modifying role of ROS, cytokines, proteases and antiproteases are discussed in relation to tissue damage and remodelling in the respiratory tract. It is recognised that inhaled coal dust particles are important non-cellular and cellular sources of ROS in the lung, and may be significantly involved in the damage of lung target cells as well as important macromolecules including alpha-1-antitrypsin and DNA. In vitro and in vivo studies with coal dusts showed the up-regulation of important leukocyte recruiting factors, e.g. Leukotriene-B4 (LTB4), Platelet Derived Growth Factor (PDGF), Monocyte Chemotactic Protein-1 (MCP-1), and Tumor Necrosis Factor-alpha (TNF alpha), as well as the neutrophil adhesion factor Intercellular Adhesion Molecule-1 (ICAM-1). Coal dust particles are also known to stimulate the (macrophage) production of various factors with potential capacity to modulate lung cells and/or extracellular matrix, including O2-., H2O2, and NO, fibroblast chemoattractants (e.g. Transforming Growth Factor-beta (TGF beta), PDGF, and fibronectin) and a number of factors that have been shown to stimulate and/or inhibit fibroblast growth or collagen production such as (TNF alpha, TGF beta, PDGF, Insulin Like Growth Factor, and Prostaglandin-E2). Further studies are needed to clarify the in vivo kinetics and relative impact of these factors.

Air Pollutants, Occupational↗
PubMed1999

Neutrophils cause oxidative DNA damage in alveolar epithelial cells.

Inflammation has been recognized as a contributing factor in the pathogenesis of some cancers. In the lung, inflammation is characterized by an influx of polymorphonuclear leukocytes (PMN) that release a variety of reactive oxygen species (ROS). The aim of the present study was to investigate the direct effect of PMN on oxidative DNA damage in lung target cells. Therefore, rat alveolar epithelial cells (RLE) were coincubated with PMN or hydrogen peroxide. Known to be correlated with the incidence of cancer, 7-hydro-8-oxo-2'deoxyguanosine (8-oxodG) was used as an effect marker for oxidative damage. Viability of the RLE, when coincubated with PMN, decreased to 43%, dependent on the ratio between PMN and RLE. After washing off PMN, 8-oxodG levels were significantly increased in RLE, but the highest levels were observed in the washed off PMN fraction. In addition, to avoid washing off procedures, immunohistochemical analysis was used to measure the 8-oxodG levels specifically in the RLE and similar results were obtained. In addition, inhibitor experiments showed that antioxidants ameliorated oxidative DNA damage. Our data provide evidence that ROS released by PMN as well as H2O2, cause oxidative DNA damage in epithelial cells.

Animals↗
PubMed1999

In vitro effects of coal fly ashes: hydroxyl radical generation, iron release, and DNA damage and toxicity in rat lung epithelial cells.

Oxygen radical generation due to surface radicals, inflammation, and iron release has been suggested as the mechanism of adverse effects of quartz, such as emphysema, fibrosis, and carcinogenic effects. Therefore, we measured iron release, acellular generation of hydroxyl radicals, and oxidative DNA damage and cytotoxicity in rat lung epithelial (RLE) cells by different coal fly ashes (CFA) that contain both quartz and iron. Seven samples of CFA with different particle size and quartz content (up to 14.1%) were tested along with silica (alpha-quartz), ground coal, and coal mine dust (respirable) as positive control particles, and fine TiO(2) (anatase) as a negative control. Five test samples were pulverized fuel ashes (PFA), two samples were coal gasification (SCG) ashes (quartz content <0.1%), and one sample was a ground coal. No marked differences between SCG and PFA fly ashes were observed, and toxicity did not correlate with physicochemical characteristics or effect parameters. Stable surface radicals were only detected in the reference particles silica and coal mine dust, but not in CFA. On the other hand, hydroxyl radical generation by all fly ashes was observed in the presence of hydrogen peroxide, which was positively correlated with iron mobilization and inhibited by deferoxamine, but not correlated with iron or quartz content. Also a relationship between acellular hydroxyl radical generation and oxidative DNA damage in RLE cells by CFA was observed. Differences in hydroxyl radical generation and oxidative damage by the CFA were not related to iron and quartz content, but the respirable ashes (MAT023, 38, and 41) showed a very extensive level of hydroxyl radical generation in comparison to nonrespirable fly ashes and respirable references. This radical generation was clearly related to the iron mobilization from these particles. In conclusion, the mechanisms by which CFA and the positive references (silica, coal mine dust) affect rat lung epithelial cells seem to be different, and the data suggest that quartz in CFA does not act the same as quartz in silica or coal mine dust. On the other hand, the results indicate an important role for size and iron release in generation and subsequent effects of reactive oxygen species caused by CFA.

Animals↗
PubMed1999

Changes in levels of catalase and glutathione in erythrocytes of patients with stable asthma, treated with beclomethasone dipropionate.

In asthmatic patients, antioxidant defence is decreased. Although inhaled corticosteroids decrease asthmatic inflammation and modulate reactive oxygen species (ROS) generation, little is known of their effect on cellular antioxidant levels. The aim of this study was to evaluate the effect of inhaled beclomethasone dipropionate (BDP; 1,000 microg x day(-1)) on erythrocyte antioxidant levels in stable asthmatic patients. Forty patients with stable, mild asthma were treated in a double-blind, placebo-controlled, parallel-group study with BDP 250 microg, two puffs b.i.d. for 6 weeks. At entry and every 2 weeks during treatment, erythrocyte antioxidant levels, haematological parameters, pulmonary function tests and asthma symptoms were determined. The results show that during treatment with BDP, erythrocyte catalase levels increased (at entry (mean +/-SEM) 41+/-4, after 6 weeks 54+/-4 micromol H2O2 x min(-1) x g haemoglobin (Hb)(-1), p = 0.05 in comparison with placebo). Erythrocyte total glutathione levels significantly decreased after 6 weeks treatment with BDP (from 7.0+/-0.4 to 6.6+/-0.3 micromol x g Hb(-1) (p = 0.04)). In the BDP-treated patients, blood eosinophil counts were higher in patients who responded with an increase in erythrocyte catalase levels during BDP treatment, as compared to those not responding ((mean +/-SEM) 340+/-39 and 153+/-52x10(6) cells x L(-1), respectively, p = 0.05). The present study shows that treatment with inhaled bedomethasone dipropionate results in changes in antioxidant levels in erythrocytes of patients with stable, mild asthma.

Administration, Inhalation↗
PubMed1998

Induction of antioxidant enzyme activity by hyperoxia (60 % O2) in the developing chick embryo.

1. At premature birth, man and animals are exposed to relatively high oxygen levels, compared with intra-uterine conditions, at a time when their antioxidant enzyme (AOE) system is still immature. Using the chick embryo as a study model, we investigated changes in the AOE system in response to hyperoxia applied at different time points during the incubation period. Relations between hyperoxia and AOE activity were studied in selected organs (brain, heart, liver, intestine and lungs) of developing chick embryos (during the second half of the incubation period). 2. Incubated White Leghorn eggs were divided into four groups: control (n = 100) and three test groups exposed for 48 h to 60 % O2 on day 10 (test group 1, n = 80), day 14 (test group 2, n = 60) and day 18 (test group 3, n = 30). Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) enzyme activities were measured in homogenates of the brain, heart, liver, intestine and lungs. 3. Exposure to hyperoxia at different time points during incubation resulted in a 2- to 10-fold increase in SOD activity in all organs except the brain. Catalase and GPx enzyme activities were only induced in test group 1, 48 h after initiation of hyperoxia. 4. In the developing chick embryo, hyperoxia can produce a temporary induction of AOE activity, which is dependent on the AOE, organ, incubation time and time point of exposure.

Animals↗
PubMed1998

Polymorphisms in the promoter of the tumor necrosis factor-alpha gene in coal miners.

Tumor necrosis factor-alpha (TNF) is recognized as a central mediator of mineral dust-induced lung fibrosis, and genetic polymorphisms of the TNF promoter have been reported to influence levels of TNF production. To assess whether polymorphisms within the TNF promoter gene are associated with susceptibility to coal workers' pneumoconiosis (CWP), the DNA of 78 coal miners was typed for G-to-A transitions at positions -238 and -308. Our results show that frequency of A-308 genotype (T2) is significantly overpresented in coal miners with CWP (50%), as compared with miners without CWP (25%) and controls (29%). After correction for cumulative dust exposure and smoking, the A-308 transition genotype is still associated with the presence of CWP (OR = 3.0, 95% CI = 1.0-9.0). Both A-238 and A-308 transition genotypes were related to TNF release from endotoxin-stimulated blood monocytes; only the A-238 transition and not the A-308 transition was associated to coal dust-induced TNF release. In summary, this study shows that the A-308 transition is related to CWP, but this relation is not paralleled by a different TNF release in this genotype. A larger number of patients coupled to frequent TNF release are required to evaluate genotype screening to estimate individual health risks for effects of coal mine dust exposure.

Base Sequence↗
PubMed1998

Longitudinal changes in inflammatory markers in nasal lavage of cotton workers. Relation to endotoxin exposure and lung function changes.

OBJECTIVES: The aim of this study was to evaluate time-related changes in inflammatory markers in nasal lavage (NAL) in relation to endotoxin exposure and lung function changes. METHODS: Endotoxin in cotton dust is well known to elicit proinflammatory mediators involved in acute or chronic respiratory inflammation due to cotton dust. We applied nasal lavage as well as lung function and exposure measurements in a small group (n = 11) of cotton workers during 6 weeks of observation (after 2 weeks free of exposure). Several inflammatory markers in NAL, such as interleukin 8 (IL-8), IL-6, and down-stream mediators, including soluble tumor necrosis factor receptor 75 (sTNF-R75) and soluble intercellular adhesion molecule 1 (ICAM-1), cell counts, marker of epithelial response (uric acid), and marker of plasma exudation (albumin) were measured. RESULTS: At the exposure levels examined in this study [cotton dust, geometric mean (GM) = 1.10 mg/m3; endotoxin, GM = 2,869 EU/m3], several inflammatory markers in NAL such as IL-8, sTNF-R75, and albumin tended to increase through the measurement period with increasing airborne endotoxin concentration (in six workers who had paired measurements in weeks 1 and 6). Although no statistical significance was reached, airborne endotoxin exposure and all inflammatory markers in NAL were relatively higher in cotton workers with a 6-week lung function decrease. CONCLUSION: The data suggest that inflammatory markers in NAL are associated with repeated airborne endotoxin exposure.

Adult↗
PubMed1998

The quartz hazard: a variable entity.

An IARC Working Group recently classified crystalline silica (quartz) into IARC's Group 1, i.e. a carcinogen. This classification is based on evidence of carcinogenicity in experimental animals and in humans. However, the evaluation stated that in making the overall evaluation, the Working Group noted that carcinogenicity to humans was not detected in all industrial circumstances studied and that carcinogenicity may be dependent on inherent characteristics of the crystalline silica or on external factors affecting its biological activity. The present review seeks to put the apparently conflicting findings of cancer incidence in quartz-exposed industries into a unifying thesis, based on mechanistic studies. These mechanistic studies have enabled the events leading from deposition of quartz to silicosis and cancer to be partially elucidated and have demonstrated that the biological effects of quartz can be understood in terms of surface reactivity. We particularly emphasise the ability of quartz to generate free radicals and cause oxidative stress and the fact that this could be modified by a range of substances that affect the quartz surface; some of these modifying substances could originate from other minerals. We therefore propose that the hazard posed by quartz is not a constant entity, but one that may vary dramatically depending on the origin of the silica sample or its contact with other chemicals/minerals within its complex constitution. The mechanistic data described here could assist in the interpretation of epidemiological studies and pose further hypotheses that could be tested in order to help resolve the quartz carcinogenesis anomaly. The data suggest that quartz cannot be death with as a single hazard entity, as is the case with most other chemicals.

Animals↗
PubMed1998

The effect of hyperoxia on embryonic and organ mass in the developing chick embryo.

It is known that hyperoxia stimulates growth late in incubation when the chick embryo outgrows the O2 diffusion capacity. We wondered whether hyperoxia could have an effect in the early period prior to the stage where metabolism exceeds the oxygen diffusion capacity of the eggshell. For this we studied four groups of chicken eggs: control group (CG; n = 100) and three test groups (TGs) exposed during 48 h to 60% O2 on days 10, 14, and 18. In the CG, embryonic and organ mass (brain, heart, lungs, liver and intestine) were measured from day 10 until day 21 of incubation. In the TGs embryonic and organ mass were obtained from 24 h after the start of hyperoxia exposure until the end of incubation. In all TGs the most striking growth rate acceleration was observed in the liver and intestine, maximum growth rate accelerations were respectively, 19 and 42% in TG1, 43 and 173% in TG2 and 39% and 84 in TG3. In contrast, the brain was little affected by the hyperoxia exposure, the maximum growth rate acceleration was 14% in TG2. The results suggest that also in the middle of the incubation period O2 availability can be a limiting factor for growth, before metabolism exceeds the oxygen diffusion capacity of the eggshell.

Animals↗
PubMed1998

Differences in aromatic-DNA adduct levels between alveolar macrophages and subpopulations of white blood cells from smokers.

The 32P-post-labelling assay for DNA adduct quantification gives the opportunity to examine endogenous exposure to DNA reactive compounds. Most human biomonitoring studies applied white blood cells (WBC) or cells obtained by broncho-alveolar lavages (BAL) as source of DNA, but still it is not clear what cell type represents the most reliable indicator for exposure to cigarette smoke-associated genotoxins. At first, we examined DNA adduct levels by means of nuclease P1 (NP1) enriched 32P-post-labelling in separated WBC subpopulations after in vitro incubations for 18 h with 10 microM benzo[a]pyrene (B[a]P). DNA adduct levels were highest in monocytes (10.7 +/- 2.9 adducts/10(8) nucleotides, n = 8), followed by lymphocytes (5.9 +/- 1.7, n = 8), and granulocytes (0.5 +/- 0.2, n = 8). Secondly, aromatic-DNA adduct levels were determined in BAL cells and WBC-subsets from (non-)smoking volunteers. In smoking individuals, adduct levels were in the ranking order: BAL cells (3.7 +/- 1.0, n = 5) > monocytes (2.0 +/- 0.5, n = 8) > or = lymphocytes (1.6 +/- 0.4, n = 8) > granulocytes (0.8 +/- 0.2, n = 8) by NP1-enrichment and monocytes (9.0 +/- 3.2, n = 5) > or = lymphocytes (8.0 +/- 2.1, n = 6) > granulocytes (2.1 +/- 0.3, n = 7) by butanol-enriched 32P-post-labelling. Aromatic-DNA adduct levels were significantly higher in WBC-subsets of smokers as compared with non-smokers, except for DNA adducts in granulocytes using butanol enrichment. Thirdly, dose-response relationships were investigated in mononuclear white blood cells (MNC, i.e. monocytes plus lymphocytes) and BAL-cells of a larger group of smoking individuals (n = 78). Adduct levels in MNC were related to daily exposure to cigarette-tar (r = 0.31, P < 0.01). Adduct levels in BAL cells seemed to be correlated with pack-years, but after correction for age this relationship was lost. Butanol extraction resulted in 5-6-fold higher DNA adduct levels in MNC, whereas butanol extraction of BAL-DNA of the same individuals yielded only 2-fold higher adduct levels. The two enrichment procedures of 32P-post-labelling were correlated in BAL cells (r = 0.86, P < 0.001, n = 12). We conclude that particularly MNC are good surrogates for the detection of smoking-related DNA adducts.

Adult↗
PubMed1997

Blood interleukin-8 production is increased in chemical workers with bronchitic symptoms.

Chemical exposure may result in respiratory conditions such as chronic bronchitis, bronchial hyperresponsiveness, and chronic airway obstruction. Clinical studies have shown that during the course of disease, cytokine networks are changed. In order to study the relationship between blood cytokines and respiratory symptoms in an occupational setting, we investigated 106 chemical workers during a routine yearly medical examination in 1995. Lung function was measured with flow volume curves and impedance using the forced oscillation technique (FOT). Smoking-status and respiratory symptoms were determined by questionnaires. Cytokines were selected on biological plausibility and measured both in a whole blood assay (TNF-alpha, IL-8) and in serum (IL-4, IL-5, IL-6, IFN-gamma). The hypothesis is that blood levels of TNF-alpha and IL-8 are increased in bronchitis, while serum levels of IL4, IL-5 are increased and IFN-gamma is decreased in asthmatic workers. Spontaneous IL-8 release was significantly higher in workers with bronchitis (P < 0.05) or chronic bronchitis (P < 0.01) compared to workers without those respiratory symptoms, also after correction for age, pack-years, and blood lymphocyte numbers or compared to a matched control group. No correlation was present between specific cytokines and asthmatic symptoms. These data suggest that blood IL-8 may be considered as a useful marker for bronchitis.

Adult↗
PubMed1997

Toxicity and occupational health hazards of coal fly ash (CFA). A review of data and comparison to coal mine dust.

Coal fly ashes (CFA) are complex particles of a variable composition, which is mainly dependent on the combustion process, the source of coal and the precipitation technique. Toxic constituents in these particles are considered to be metals, polycyclic aromatic hydrocarbons and silica. The purpose of this review was to study the in vitro and in vivo data on coal fly ash and relate the studied endpoints to the role of (crystalline) silica, considering its recent classification as a human carcinogen. For most of the effects coal mine dust was chosen as a reference, since it contains up to 10% of crystalline silica (alpha-quartz) and is well studied both in vivo and in vitro. Most studies on fly ash toxicity were not designed to elucidate the effect of its silica-content nor did they include coal mine dust as a reference. Taking this into account, both in vitro and in vivo experimental studies show lower toxicity, inflammatory potential and fibrogenicity of CFA compared to silica and coal mine dust. Although in vitro and in vivo studies suggest genotoxic effects of fly ash, the data are limited and do not clarify the role of silica. Epidemiological studies in fly ash exposed working populations have found no evidence for effects commonly seen in coal workers (pneumoconiosis, emphysema) with the exception of airway obstruction at high exposure. In conclusion, the available data suggest that the hazard of coal fly ash is not to be assessed by merely adding the hazards of individual components. A closer investigation of 'matrix' effects on silica's toxicity in general seems an obligatory step in future risk assessment on fly ashes and other particles that incorporate silica as a component.

Animals↗
PubMed1997

Neutrophils amplify the formation of DNA adducts by benzo[a]pyrene in lung target cells.

Inflammatory cells and their reactive oxygen metabolites can cause mutagenic effects in lung cells. The purpose of this study was to investigate the ability of activated neutrophils to modulate DNA binding of benzo[a]pyrene (B[a]P), a known carcinogen, in lung target cells. Equivalent numbers of rat lung epithelial cells (RLE-6TN cell line) and freshly isolated human blood neutrophils (PMN) were coincubated in vitro for 2 hr after addition of benzo[a]pyrene (0.5 microM) or two of its trans-diol metabolites, with or without stimulation with phorbol myristate acetate (PMA). DNA adducts of B[a]P-metabolites were determined in target cells using 32P-postlabeling; oxidative DNA damage (7-hydro-8-oxo-2'-deoxyguanosine [8-oxodG]) was evaluated by high performance liquid chromatography with electrochemical detection. Increased DNA adducts were observed in lung cells coincubated with polymorphonuclear leukocytes (PMN). Activation of PMN with PMA, or addition of more activated PMN in relation to the number of lung cells, further increased the number of adducts, the latter in a dose-response manner. Incubation with B[a]P-4,5-diol did not result in any adduct formation, while B[a]P-7,8-diol led to a significant number of adducts. Moreover, PMA-activated PMN strongly enhanced adduct formation by B[a]P-7,8-diol, but not 8-oxodG, in lung cells. The addition of antioxidants to the coincubations significantly reduced the number of adducts. Results suggest that an inflammatory response in the lung may increase the biologically effective dose of polycyclic aromatic hydrocarbons (PAHs), and may be relevant to data interpretation and risk assessment of PAH-containing particulates.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

Particles, inflammation and respiratory tract carcinogenesis.

Particle-induced carcinogenesis is a non-specific outcome of many different particles. It was the purpose of this study, (i) to comprehensively review some of the mechanisms through which particles and particle-associated carcinogens can cause mutagenic/carcinogenic effects, and (ii) to indicate how this affects risk assessment studies. Data are presented that demonstrate the crucial role of a chronic inflammatory response in mutagenic effects of both silica and carbon black particles on the HPRT gene in lung target cells. The concept of inflammation in particle-induced genotoxicity is put into the context of other mechanisms, such as the release of cytokines and reactive oxygen species. It is concluded that interpretation of rat inhalation studies should certainly include this concept.

Air Pollutants↗
PubMed1996

A five year follow-up of lung function among chemical workers using flow-volume and impedance measurements.

Impedance of the respiratory system, measured using the forced oscillation technique (FOT), has repeatedly been proposed as a tool for occupational health screening. The aim of this study was to compare the outcome of impedance measurements and flow-volume curves, and to study relationships between lung function decline and specific exposures and smoking. Both measurements were applied in 136 chemical workers from seven main production/personnel groups during a 5 year follow-up (1990-1995). The prevalence of airway obstruction (forced expiratory volume in one second (FEV1) < 80% of predicted) at both time-points was about 5% but did not necessarily include the same subjects. The average decline in FEV1 over 5 yrs was 200 mL (predicted decline 160 mL). Although most impedance parameters correlated to flow-volume parameters in both years, a rapid 5 year decline of FEV1 (> 330 mL) was only accompanied by a significant decrease in the reactance at 8 Hz (X8) and an increase in the resonance frequency (f0). Interestingly, decline in FEV1 was significantly dependent on age, years of employment, pack-years, FEV1, and all impedance parameters at the start in 1990 (r = 0.35; p = 0.01). Similarly, the increase in f0 was significantly dependent on age, years of employment, pack-years, f0, FEV1, forced vital capacity (FVC), peak expiratory flow (PEF) and maximal mid-expiratory flow (MMEF) at the start (r = 0.56; p < 0.01). Those with a rapid decline in FEV1, were relatively more represented among acid workers (relative risk (RR) = 2.14), maintenance workers (RR = 2.1) and bulk/transport workers (RR = 1.78), but none of these was significant. Lung function, however, was significantly lower in the bulk/transport workers (n = 14) compared to the rest, based both on flow-volume (FEV1, FVC) and impedance (X8, f0) measurements. Smoking had a significant effect on most flow-volume parameters but only for frequency dependence among the impedance outcomes. It is concluded that alterations in impedance parameters do reflect changes in flow-volume curves induced by age. smoking and occupational exposure. Therefore, these data are a valuable extension to current cross-sectional data.

Acids↗
PubMed1996

Cross-shift changes in blood inflammatory markers occur in the absence of airway obstruction in workers exposed to grain dust.

Grain dust is well known to cause both acute and chronic respiratory disorders, and endotoxins are considered key components in this. Since endotoxins are known to elicit proinflammatory mediators, we investigated cytokine (tumor necrosis factor [TNF], interleukin-6, interleukin-8) release and a number of proinflammatory and anti-inflammatory proteins (soluble TNF receptors, lipopolysaccharide (LPS) binding protein, bactericidal permeability increasing protein (BPI), C-reactive protein) in plasma of workers exposed to grain dust. In two surveys during 1 week, lung function was measured daily before and after the shift, using flow-volume curves and/or forced oscillation measurements. On Monday and Friday, blood samples (30 mL) were drawn and cytokine release was determined by enzyme-linked immunosorbent assay in supernatant of isolated monocytes or whole blood culture, either unstimulated or on the ex vivo stimulation with 3 ng/mL or 1,000 ng/mL endotoxin. Individual exposures were determined from stationary dust measurements at every workplace combined with personal task analysis during all shifts. In both surveys, no cross-week change in lung function parameters was observed. In the first survey (average exposure: 20.2 mg/m3), monocyte spontaneous TNF release was increased sevenfold cross week (p<0.001) and was significantly related both to individual dust exposure (r=0.62) of that week and the increase in soluble TNF receptor 75 kD (r=0.85). In the second survey, where average exposure was much lower (3.67 mg/m3), impedance parameters indicated a significant improvement of airway function, and cross-week changes in inflammatory markers were minimal. Therefore, we conclude that inflammatory events can be used to monitor adverse respiratory effects of moderate grain dust exposure.

Acute-Phase Proteins↗