Objectives

(A)To assess the oxidant and proinflammatory effects of particles from gasoline powered engines, in relationship to diesel engine exhaust PM in healthy humans (preceding asthma and COPD studies)

(B) To use selected PM samples from WP1-4 for human instillation challenge experiments and compare these with the previously documented effects of controlled chamber exposure with continuously generated fresh diesel exhaust.

© To link the oxidative and inflammatory responses locally within the human airways, to the in-vitro, animal screening and mechanistic study results in WP2-4. By doing this, the human studies will improve on the complementary knowledge provided, as well as providing feed back and supporting information to the in-vitro and animal models

Description of work (A) Diesel exhaust exposure with freshly generated particulates will be performed using an established and well characterised exposure set-up. This is complementary rigged for using gasoline powered engine. Exposures of humans are performed using standard protocol with engine exhaust with PM10 of 100ug/m3 during 2 hours. Symptoms, lung function, blood samples and bronchoscopy are performed with bronchoalveolar lavage and bronchial mucosal biopsies, evaluated state of the art with a variety of techniques to link with investigations in-vitro and in animals, to delineate the free radical and oxidative stress in the airways, the extent and site of epithelial injury, the consequences of injury, the consequence of epithelial activation by transcription factors for the cytokine response. (B) Local instillations in sub-segmental bronchi of ambient PM selected from WP2-4 will be compared with equal amounts of gasoline and diesel exhaust PM. Evaluation of effects as under (A).

Deliverables (A) New complementary information of the extent and mechanisms of fresh DE PM effects in humans, which furthermore is compared with gasoline PM bioactivity. (B) Information of local airway response of selected ambient PM in humans in comparison with (A). © Link of data to in-vitro and animal research.

Milestones and expected results (A) The first milestone is delivering report of DE and gasoline PM effects 21 months into the study. (B) The second milestone is comparison of local airway instillations of PM at 33 months. © Furthermore an evaluation of the synergistic effect of in-vitro, animal and human experimental research is given at termination of project.