Clinical and molecular phenotyping of asthma and COPD

This thesis presents studies on clinical and molecular phenotyping of asthma and COPD. The clinical studies show that dysfunction of the small airways, i.e. airways with a diameter < 2 mm, is associated with respiratory symptoms and a decreased lung function. Asthma is generally treated with inhaled corticosteroids (ICS) with non-extrafine particles that do not reach the small airways. We studied additionally extrafine-particle ICS and conclude that extrafine-particle ICS are not more effective than non-extrafine ICS when treating smokers and ex-smokers with asthma. Furthermore, we showed that bronchial provocation tests with adenosine, which are used to demonstrate airway hyperresponsiveness, can be improved by using adenosine as a dry powder instead of a nebulized formulation. The molecular studies investigated gene expression profiles in the nose and lower airways of patients with asthma and COPD, and explored the effects of ICS on gene expression. Studies of the lower airways require a bronchoscopy, a not-so-patient-friendly procedure. We showed that COPD patients have a distinct gene expression profile in the nose compared to healthy controls. Furthermore, ICS appear to change the gene expression profile in the nose in asthma. Both COPD- and ICS-related gene expression changes in the nose had considerable overlap with the gene expression changes in the lower airways. This implies that nasal gene expression can potentially be used as a non-invasive biomarker. Finally, we investigated molecular changes in the lower airways of subjects with remission of asthma and showed that microRNAs and other noncoding RNAs likely contribute to obtain asthma remission