Organic dusts and airways inflammation. With reference to the specific agents endotoxin and (1-3)-ß-D-glucan

Abstract

Objective: Organic dusts may contain different amounts of endotoxin, an inflammatory agent, and glucans for which the effects on humans are largely unknown. In this thesis, endotoxin and (1(3)-ß-D-glucan were used as markers of biomass exposure in three different organic dust environments, i.e. wood and recycled paper handling, household waste handling and homes. In addition, inflammatory responses after acute exposures to lipopolysaccharide, LPS (pure endotoxin) and grifolan (a pure (1(3)-ß-D-glucan) were evaluated among healthy subjects.Methods: Participants in the field studies were 83 workers from a paper industry and 44 controls, 129 tenants from 75 houses in a rowhouse area, some of which had previous problems related to dampness and water leakage, and 25 household waste collectors and 24 controls. The field studies measured levels of airborne endotoxin and (1(3)-ß-D-glucan. To characterize the inflammatory response after inhalation of LPS and (1(3)-ß-D-glucan, 21 healthy subjects inhaled 40 (g LPS and 12 subjects inhaled 125 ng grifolan and were examined before and 24 hours and 72 hours (grifolan) after exposures. The effects of the exposures were evaluated using a questionnaire, spirometry measurements and levels of eosinophilic cationic protein (ECP) and myeloperoxidase (MPO) in serum. Atopy was determined using the Phadiatop test. Airway responsiveness (methacholine test) was determined in the field studies. Induced sputum was analyzed in the household waste collector study and among subjects challenged with LPS and grifolan and differential cell counts, ECP, MPO and cytokines (grifolan) were determined in blood and sputum. Results: The workers in the paper industry were exposed to high levels of airborne endotoxin and (1(3)-ß-D-glucan. Household waste collectors and tenants in the rowhouse area were exposed to moderate levels of (1(3)-ß-D-glucan and to low levels of airborne endotoxin. An increased prevalence of respiratory and general symptoms was observed among paper industry workers, and after inhalation of LPS. Airway responsiveness was increased among the paper industry workers as compared with controls. A decrease in baseline FEV1 related to the number of years lived in the houses with higher (1(3)-ß-D-glucan levels was found among tenants younger than 65 years. In the paper industry study, differences were found between exposed and unexposed in levels of ECP and MPO in serum and in the household waste collector study in the numbers of mononuclear cells in blood. Increased amounts of ECP and MPO in induced sputum and increased neutrophil numbers in blood and sputum were found after inhalation of LPS. The lymphocyte numbers in blood were decreased 72 hours after the challenge with (1(3)-ß-D-glucan.Conclusions: Among paper industry workers, several effects were found in terms of respiratory and general symptoms and inflammatory markers. It is not possible to conclude whether endotoxin and/or (1(3)-ß-D-glucan caused these effects. Inhalation of LPS caused an acute airways inflammation, as demonstrated by higher amounts of inflammatory markers in sputum and an increased prevalence of respiratory symptoms. Taken together, the results suggest the presence of an airways inflammation after exposure to endotoxin and to dusts containing endotoxin. The results also suggest that (1(3)-ß-D-glucan exposure may be associated with effects, but further field and challenge studies are needed.