Airway pathology in COPD : smoking cessation and pharmacological treatment intervention. Results from the GLUCOLD study

Abstract

This thesis comprises data from the GLUCOLD study (Groningen Leiden Universities and Corticosteroids in Obstructive Lung Disease), a prospective study in COPD. In chapter 2 is shown that airflow limitation, asthma-like components, exhaled nitric oxide and sputum inflammatory cell counts offer separate and additive information about the pathophysiological condition of COPD. Chapter 3 shows that uneven distribution of ventilation and airway closure in stable COPD are associated with neutrophilic inflammation in bronchial biopsies and bronchoalveolar lavage fluid. Chapter 4 and 5 show that ex-smokers with COPD have higher bronchial CD4+ and plasma cell numbers, and less bronchial epithelial mucin stores, proliferating cells, and squamous cell metaplasia than current smokers, whereas neutrophil, macrophage, and CD8+ cell numbers are not different between both groups. Bronchial inflammation and epithelial changes are associated with duration of smoking cessation. Chapter 6 shows that long-term treatment with inhaled corticosteroids in COPD reduces bronchial T-lymphocyte and mast cell numbers, whilst increasing bronchial epithelial integrity and bronchial eosinophil numbers. This is accompanied by a reduced FEV1 decline and improved airway hyperresponsiveness, dyspnea and quality of life. Discontinuation of inhaled corticosteroids at 6 months leads to a relapse of bronchial inflammation and clinical outcome.