Endotoxin-binding proteins in nasal lavage: evaluation as biomarkers to occupational endotoxin exposure.

Exposure to endotoxin (LPS) can cause chronic respiratory disease, with symptoms that are more pronounced after exposure-free periods. The aim of this study was to evaluate LPS-response modulating proteins in nasal lavage and plasma as biomarkers for exposure to airborne endotoxin. We applied nasal lavage, lung function and exposure measurements in a small group (n = 11) of cotton workers during 6 weeks of observation (after 2 weeks free from exposure) and ten external controls. Lipopolysaccharide binding protein (LBP) and bactericidal/permeability increasing protein (BPI) were measured in nasal lavage fluid (NALF) along with classic markers such as differential cell counts, Interleukin-8 (IL-8) and albumin, to evaluate their use as markers in endotoxin exposure. In all control subjects and cotton workers LBP and BPI were readily detectable in NALF, although a high intra- and intervariability was noted. At the exposure levels in this study (cotton dust, geometric mean (GM) = 1.10 mg m(-3); endotoxin, GM = 2869 EU m(-3)), plasma BPI and BPI and LBP in NALF were significantly (P < 0.05) different from external controls. In addition, within the group of cotton workers, during the measurement period a significant increase was noted in BPI, albumin and BPI/LBP ratio in NALF (P < 0.05), while a significant decrease in total cell numbers was noted. However, none of the markers in NALF was correlated to the different exposure indices used, based on personal endotoxin or dust exposure measurements. The data show that LBP and BPI are present in nasal lavage fluid and that these markers as well as their ratio increase during airborne endotoxin exposure in cotton workers.

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.

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.

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.