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.

Respiratory symptoms and lung function in animal feed workers.

In a study among 194 male workers exposed to endotoxin-containing organic dust in animal feed mills, lung function was measured by flow volume curves and impedance measurements and respiratory symptoms were recorded by means of a validated questionnaire. The aims were to detect and localize airway obstruction caused by fodder dust and endotoxin, and to relate respiratory symptoms to both types of lung function measurements. Flow volume and impedance parameters were significantly related to present exposure. All impedance parameters, of the spirometric measures only FEF25, were significantly related to cumulative dust or endotoxin exposure. The changes in impedance parameters were for overall increasing resistance at 8 Hz and decreasing reactance at 8 Hz, reflecting an increase in peripheral airflow obstruction, with increasing exposure. The changes in all lung function parameters were more strongly related to (cumulative) endotoxin exposure than to inspirable dust exposure. All impedance parameters and FEV1 showed a good correlation with complaints of chronic bronchitis and breathlessness. Impedance measurement of the respiratory system proved to be a useful tool for objectively assessing (early) airflow obstruction in workers exposed to inspirable dust and endotoxin and in localizing airflow obstruction.

Respiratory effects of coal dust exposure: clinical effects and diagnosis.

During the past two decades, growing evidence has been reported on the role of respirable inorganic dust in the development of airflow obstruction, impaired diffusion capacity, chronic bronchitis, and emphysema, irrespective of the extent of possible pneumoconiotic abnormalities. These nonpneumoconiotic effects associated with dust exposure in miners and the relationship between dust exposure and mortality are reviewed. When pneumoconiotic changes can be visualized by different radiologic techniques, including computed tomography (CT) and high-resolution CT, assessment of the respiratory impairment in coal workers at present requires evaluation of the ventilatory and gas exchange capacity.

Airflow obstruction and monocyte TNF release in coal workers.

Respiratory health of 102 retired coal miners was assessed by chest radiographs, lung function measurements, and questionnaires, and related to tumor necrosis factor-alpha (TNF-alpha) production by blood monocytes upon priming with different stimuli. The objective was to assess a possible relationship between airflow obstruction and TNF-alpha production in retired coal workers. No significant differences in lung function were observed between cases of coal workers' pneumoconiosis (CWP) (n = 27; > %) and references (n = 75; = > %), nor was the effect of cumulative exposure on flow volume or impedance parameters significant. TNF-alpha release upon stimulation of blood monocytes with coal mine dust was significantly increased in cases with International Labour Organisation (ILO) score 0/1 (doubtful cases) compared to references and cases with a higher ILO score. Airflow limitation defined either as a FEV1 < 80% (N = 10; 5 cases of CWP) or as a resonance frequency > 15 Hz accompanied by a negative frequency dependence of resistance (N = 9; 4 cases of CWP) was significantly related to high levels of TNF-alpha release upon stimulation with endotoxin and silica, with silica showing the strongest relation. These data suggest that in this group airflow limitation is associated with an increased expression of inflammatory mediators indifferent of the presence of pneumoconiosis.

Respiratory effects and serum type III procollagen in potato sorters exposed to diatomaceous earth.

Exposure to diatomaceous earth with low crystalline silica content (< 1%) is rarely reported to cause pneumoconiotic disease, whereas airway obstruction and bronchitis are more frequently reported. We investigated the occurrence of pneumoconiosis and airflow limitation in 172 male workers from 5 potato sorting plants (55 controls, 29 salesmen, 72 currently exposed, and 16 retired exposed) exposed to inorganic dust from former sea terraces (7.7-15.4 mg/m3), high in diatomaceous earth. The presence of fibrosis was evaluated by chest radiographs (exposed only) and serum levels of type III procollagen (P-III-P) were measured as an estimate of fibrogenetic activity. Lung function was assessed by flow volume curves and impedance measurements. A validated questionnaire was used to record respiratory symptoms. No pneumoconiotic abnormalities were demonstrated by chest radiographs. In line with this finding, serum P-III-P levels were not elevated in exposed workers as compared to controls, suggesting no differences in fibrogenetic activity. In fact, serum P-III-P levels decreased significantly (P < 0.03) with increasing cumulative exposure. Flow volume parameters indicated airflow obstruction, dose-related to (cumulative) dust exposure; the annual decline in forced expiratory flow volume (FEV1) was estimated at 10.5 ml/year (P < 0.05). Airway obstruction was confirmed by impedance analysis: In the retired group impedance changes were compatible with airway obstruction extending into the peripheral airways. We conclude that this exposure to quartz during potato sorting does not result in an increased risk for pneumoconiosis, but that (prolonged) surveillance in this group is desirable in order to detect early indications of airflow obstruction.

Setting acceptable exposure limits for toluene diisocyanate on the basis of different airway effects observed in animals.

Little epidemiological data are available to enable the development of a dose-response relationship for the effects of isocyanates, powerful sensitizing agents in humans. Remarkably, most classes of effects have been reproduced in some animal models and parallels between animals and man are impressive. In this paper animal data concerning different effects of TDI on the respiratory system were used to calculate acceptable exposure levels for humans. Animal data on respiratory irritation, sensitization, airway hyperresponsiveness, and gradual loss of pulmonary function are discussed. Two different approaches for extrapolation to man were applied to these data. The two models used to extrapolate animal data to man gave similar results. The extrapolations lead to acceptable exposure varying from 6 to 46 ppb. Most international acceptable levels for occupational airborne TDI exposure are within this range. Interestingly, the lowest standard is obtained using the data on respiratory irritation. It is, however, concluded that there is no critical (adverse) effect to define acceptable toluene diisocyanate exposure since the data were obtained from different studies and the accuracy of the applied extrapolation approach might depend on the biological effect considered. We recommend prior testing of "alternative" diisocyanates in one of the animal models described and calibrated for TDI.