- Author
-
L.E.S. de Groot
- Title
- Oxidative stress and the inflammatory nature of asthma exacerbations
- Supervisors
-
R. Lutter
- Co-supervisors
- Award date
- 12 February 2021
- Number of pages
- 187
- ISBN
- 9789464162844
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
Patients with asthma may suffer from periodic acute worsening of disease symptoms, called exacerbations or loss of control when milder, which are typically characterized by increased airway inflammation and oxidative stress. The actual contribution of inflammatory and oxidative stress events in (the development of) exacerbations is only poorly understood and represents the central theme of this thesis. We focused on three different effector cells with known respiratory burst activities; eosinophils, neutrophils, and macrophages.
In Part I, we described two different experimental loss of asthma control models in humans to investigate inflammatory and oxidative stress responses; the rhinovirus 16 (RV16) challenge model (combined with mepolizumab treatment) and the corticosteroid withdrawal model. We found that in steroid-naïve mild asthma eosinophils contribute to oxidative stress during virus-induced loss of control, but not at stable disease. We also found that the clinical effect upon corticosteroid withdrawal in mild to moderate asthma is not based on the classic respiratory burst activation of granulocytes, but possibly on (eosinophil) extracellular trap formation.
In Part II, we extensively characterized bronchoalveolar lavage macrophages from patients and healthy controls infected with RV16. Distinct macrophage clusters were detected before versus after RV16, but also between patients versus healthy controls, suggesting changes in overall phenotype. Moreover, we investigated the effects of farm-derived particulate matter (BioPM) on peripheral blood mononuclear cells from patients with asthma and healthy volunteers. BioPM elicited inflammatory cytokine responses, largely irrespective of the presence or state of disease. These events were mediated by reactive oxygen species, as evidenced by treatment with antioxidants. - Persistent Identifier
- https://hdl.handle.net/11245.1/ce794917-a799-4f56-abf2-56d2c314fbe8
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General introduction and thesis outline
Chapter 2: Do eosinophils contribute to oxidative stress in mild asthma?
Chapter 3: Corticosteroid withdrawal-induced loss of control in mild to moderate asthma is independent of classic granulocyte activation
Chapter 4: The different faces of the macrophage in asthma
Chapter 5: Oxidative stress and macrophages: Driving forces behind exacerbations of asthma and chronic obstructive pulmonary disease?
Chapter 6: Phenotypic comparison of human alveolar macrophages before and after in vivo rhinovirus 16 challenge
Chapter 7: Ex vivo innate responses to particulate matter from livestock farms in asthma patients and healthy individuals
Chapter 8: General discussion and summary
Nederlandse samenvatting; List of publications; PhD portfolio; Curriculum vitae; Dankwoord
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