Around 5-10% of patients with asthma do not respond adequately to inhaled steroids and long-acting bronchodilators and become difficult-to-treat; they remain symptomatic, have recurrent... Show moreAround 5-10% of patients with asthma do not respond adequately to inhaled steroids and long-acting bronchodilators and become difficult-to-treat; they remain symptomatic, have recurrent exacerbations or persistent airflow limitation. This thesis focuses on the mechanisms that may explain why these patients become difficult-to-treat and investigate biomarkers that can predict the development of specific asthma phenotypes. The different studies describe the possible role of alpha- antitrypsin in the development of persistent airflow limitation, the relationship between severity of asthma and the degree of peripheral airway inflammation and dysfunction, the clinical and inflammatory characteristics of obese patients with difficult-to-treat asthma, risk factors of lung function decline and the consistency of the eosinophilic phenotype Show less
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... Show moreThis 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. Show less
