Leiden University Scholarly Publications

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Kunz, L.I.Z. (2016)

Effects of inhaled corticosteroids on clinical and pathological outcomes in COPD - Insights from the GLUCOLD study

Doctoral Thesis
This thesis focuses on the relationship between smoking and macrophages in chronic obstructive pulmonary disease (COPD), and on treatment with inhaled corticosteroids (ICS). Macrophages play an important role in COPD, and constitute a heterogeneous population with pro- (Mf1) and anti-inflammatory (Mf2) cells. This thesis evaluated YKL-40 and CD163 as markers for Mf1 and Mf2, respectively. Peripheral airways contained more CD163-positive Mf2 compared to central airways. Smoking cessation skewed the macrophage phenotype towards Mf2 in the peripheral airways, but did not influence YKL-40 levels in sputum. Whereas smoking can induce structural alterations in extracellular matrix (ECM) components in the airways, no differences in ECM components in bronchial biopsies were found between current and ex-smokers with COPD.
ICS treatment attenuates lung function decline and decreases airway inflammation in a subgroup of COPD patients. However, long-term ICS treatment did not change...Show more This thesis focuses on the relationship between smoking and macrophages in chronic obstructive pulmonary disease (COPD), and on treatment with inhaled corticosteroids (ICS). Macrophages play an important role in COPD, and constitute a heterogeneous population with pro- (Mf1) and anti-inflammatory (Mf2) cells. This thesis evaluated YKL-40 and CD163 as markers for Mf1 and Mf2, respectively. Peripheral airways contained more CD163-positive Mf2 compared to central airways. Smoking cessation skewed the macrophage phenotype towards Mf2 in the peripheral airways, but did not influence YKL-40 levels in sputum. Whereas smoking can induce structural alterations in extracellular matrix (ECM) components in the airways, no differences in ECM components in bronchial biopsies were found between current and ex-smokers with COPD.
ICS treatment attenuates lung function decline and decreases airway inflammation in a subgroup of COPD patients. However, long-term ICS treatment did not change YKL-40 levels in sputum and serum. ICS increased deposition of several ECM proteins in the airways, which was correlated with improved lung function, suggesting prevention of airway collapse. Withdrawal of ICS after long-term treatment induced a relapse in lung function decline and increased airway inflammation in bronchial biopsies and sputum, suggesting that benefits of ICS do not persist after discontinuation of ICS.Show less
COPD
Airway inflammation
Macrophages
Remodeling
Inhaled corticosteroids
All authors
Kunz, L.I.Z.
Supervisor
Hiemstra, P.S.; Sterk, P.J.; Postma, D.S.
Committee
Taube, C.; Wouters, E.F.M.; Heijdra, Y.F.; Grünberg, K.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2016-11-30
ISBN (print)
9789462334366

Funding

Sponsorship
Netherlands Organization for Scientific Reaearch (NWO), Netherlands Lung Foundation (Longfonds), GlaxoSmithKline The Netherlands, Leiden University Medical Center, Groningen University Medical Center