- Author
-
M. Berger
- Title
- Bronchial segmental challenges with environmental exposures in humans
- Supervisors
-
P.J. Sterk
- Co-supervisors
-
J.S. van der Zee
E.M. Kemper - Award date
- 4 September 2020
- Number of pages
- 228
- ISBN
- 9789090334127
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
People all over the world are daily exposed to environmental agents, such as traffic-related air pollution, allergens and house dust. These exposures can cause serious health effects. Subjects with pulmonary diseases or allergies are more susceptible to these environmental agents, which often increase symptoms. Interventional research to investigate the underlying pathophysiological mechanisms is warranted. The aim of this thesis was threefold, first: to review currently used inhalation provocation models in humans in vivo with a specific interest in the efficacy and safety of the bronchial segmental challenge research model, using single- or multiple agent provocations. Secondly, to investigate the effects of traffic-related air pollution by challenging healthy males with carbon nanoparticles. Thirdly, we examined the effects on pulmonary and systemic inflammation and coagulation in patients with mild allergic asthma after inhalation of house dust mite allergen and lipopolysaccharide.
The research described in this thesis showed that bronchial segmental challenge with single or multiple environmental agents is safe and well tolerated in healthy and asthmatic volunteers when carefully performed. Inhalation of carbon nanoparticles as part of traffic-related air pollution causes a dose-dependent increase in blood neutrophils while coagulation parameters were not altered. Challenge of patients with mild allergic asthma using inhalation corticosteroids, with house dust mite allergen and lipopolysaccharide caused an increase in eosinophilic inflammation. Pre-treatment with recombinant human activated protein C, reduced neutrophil recruitment and degranulation products in the alveolar space.
These results show a significant inflammatory response to environmental exposures, which warrants and directs future research. - Persistent Identifier
- https://hdl.handle.net/11245.1/71242cab-c72d-4114-b226-b4544af5bd3d
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