Oxidative stress and the inflammatory nature of asthma exacerbations

Linsey E. S. de Groot

Research output: ThesisThesis: Research University of Amsterdam, graduation University of Amsterdam

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.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • University of Amsterdam, Netherlands
Supervisors/Advisors
  • Lutter, Rene, Supervisor
  • Hamann, Jörg, Co-supervisor
  • Melgert, Barbro N., Co-supervisor, External person
Award date12 Feb 2021
Print ISBNs9789464162844
Publication statusPublished - 2021

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