Airway responsiveness and exhaled nitric oxide : Studies in asthma and Sjögren's syndrome

Sammanfattning: In this thesis, four different types of provocation agents: methacholine, adenosine, cold air and mannitol were used to study different aspects of the airway responsiveness profile in asthma and Sjögren's syndrome. Exhaled nitric oxide (NO) and markers of eosinophil activation, serum eosinophil peroxidase (S-EPO) and eosinophil cationic protein (S-ECP) were measured.The main findings of this research are that atopic patients with asthma were significantly more hyperresponsive to adenosine than non-atopic asthmatic subjects and patients with Sjögren's syndrome. In atopic subjects with asthma, the airway responsiveness to adenosine was correlated to markers of eosinophil activation, S-EPO and S-ECP. Furthermore, hyperresponsiveness to cold air was more common in atopic asthmatics compared with patients with Sjögren's syndrome.Exhaled NO was almost twice as high in patients with Sjögren's syndrome and atopic asthmatics compared to healthy controls. In atopic asthmatics exhaled NO was significantly correlated with airway responsiveness to methacholine and was due to an increased NO flux from the airways but not the alveoli. After inhalation of dry powder mannitol the levels of exhaled NO decreased in asthmatics, but increased in healthy individuals. In conclusion, atopic and non-atopic subjects with asthma and patients with Sjögren'ssyndrome have different airway responsiveness profiles for adenosine and cold air. Exhaled NO is elevated in patients with Sjögren's syndrome and in atopic asthmatic subjects while non-atopic asthmatics have normal levels. Using a new bronchial provocation test with dry powder mannitol we show that healthy subjects can release NO after mannitol provocation, wheras asthmatics can not. More than one type of bronchial provocation may be required to detect different aspects of the airway hyperresponsiveness profile.