Asthma and COPD: Smoking, Atopy and Corticosteroid responsiveness

The aim of this thesis was to describe, investigate and compare the effects of smoking and atopy in asthma and COPD. A part of the research focused on asthmatic patients with ageing and smoking COPD phenotype, resulting in difficulties to discriminate between these two disorders. The following conclusions can be drawn: • Pathologists are able to differentiate between asthma and COPD, on condition they use a number of pathological criteria, and take the clinical setting into account, particularly the use of inhaled corticosteroids (ICS). • Prevalence of atopy is significantly higher in COPD patients who are males, have overweight and lower age. Atopy significantly associates with higher prevalence of respiratory symptoms and higher likelihood to lose cough upon treatment with busedonide.• Absence of atopy and non-ICS use contribute independently to higher numbers of IL-17 expressing cells. IL17-positive cells were found to be predominantly neutrophils. • CCL20 levels are higher in sputum of asthmatics who use ICS, whereas glucocorticoids increase the release of CCL20 by primary bronchial epithelial cells in vitro.• Smoking associates with higher epithelial HDAC-2 expression in airway biopsies from asthmatics, independent of ICS-use. • Increased Eosinophil Peroxidase (EPX) immunopositivity in airway biopsies from asthmatic subjects associates significantly with lower intact epithelium, particularly in uncontrolled asthma.In summary: heterogeneous populations of asthma and COPD patients determine the broad spectrum of obstructive airway diseases. Smoking and atopy may modulate the underlying inflammatory and clinical phenotype, and affect corticosteroid responsiveness. This heterogeneity should be taken into account when designing clinical studies