This thesis consists of three parts. Part A describes in chapter 2 the complex diagnosis of asthma in the morbidly obese, and especially focuses on underdiagnosis and overdiagnosis of asthma in... Show moreThis thesis consists of three parts. Part A describes in chapter 2 the complex diagnosis of asthma in the morbidly obese, and especially focuses on underdiagnosis and overdiagnosis of asthma in this patient group. Part B investigates bronchial and systemic inflammation. It starts in chapter 3 with a review on the association between obesity and asthma, where the metabolic syndrome __ as state of systemic inflammation - is mentioned as possible explanation for the association between obesity and asthma. In chapter 4 systemic inflammation and the metabolic syndrome and impaired lung function in morbidly obese subjects are discussed. This is followed by chapter 5, in which the presence and possible relationship between bronchial and systemic inflammation in morbidly obese asthma subjects are discussed. Part C focuses on bariatric surgery, first pulmonary function testing and complications of bariatric surgery are discussed in chapter 6. In chapter 7 the effect of bariatric surgery on asthma is described. And finally, in chapter 8, a summary and general discussion of these studies is presented. Show less
In the last few decades, childhood allergy has alarmingly increased to epidemic levels in industrialized countries. Conversely, chronic helminth infections, which are highly prevalent in developing... Show moreIn the last few decades, childhood allergy has alarmingly increased to epidemic levels in industrialized countries. Conversely, chronic helminth infections, which are highly prevalent in developing countries, are negatively associated with allergic disorders. The work in this thesis revealed that, using B-cell IL-10-deficient mice, Schistosoma mansoni-mediated protection against experimental ovalbumin-induced allergic airway inflammation (AAI) was specifically dependent on splenic IL-10-producing CD1dhi regulatory B (Breg) cells. Furthermore, we demonstrated that another B cell subset, located in the lungs, provided protection against AAI, by showing a reduced capacity to initiate Th2 cytokine responses. Markedly, we found a similarly elevated population of IL-10-producing CD1dhi B cells in peripheral blood of Schistosoma haematobium-infected Gabonese children compared to uninfected children. We observed that schistosome-induced Breg cells reduced effector T-cell cytokines and induced more Treg cells. What is interesting in this aspect, is that we found that the Breg cell compartment of patients with allergic asthma is impairment in number and activity. Therefore, the identification of the mechanisms that underlying Breg cell induction by helminths, and the identification the helminth-derived molecules involved, may open novel avenues for the treatment of allergic disease disorders by driving potent Breg cells Show less
