Inhaled steroids modulate extracellular matrix composition in bronchial biopsies of COPD patients: a randomized, controlled trial

Smoking and inflammation contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), which involves changes in extracellular matrix. This is thought to contribute to airway remodeling and airflow obstruction. We have previously observed that long-term treatment with inhaled corti...

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Bibliographic Details
Published in:PloS one 2013-05, Vol.8 (5), p.e63430-e63430
Main Authors: Kunz, Lisette I Z, Strebus, Jolanda, Budulac, Simona E, Lapperre, Therese S, Sterk, Peter J, Postma, Dirkje S, Mauad, Thais, Timens, Wim, Hiemstra, Pieter S
Format: Article
Language:English
Subjects:
Administration, Inhalation
Adult
Air flow
Analysis
Androstadienes - administration & dosage
Androstadienes - pharmacology
Androstadienes - therapeutic use
Asthma
Biology
Biopsy
Bronchi - drug effects
Bronchi - pathology
Bronchi - physiopathology
Bronchodilators
Chronic obstructive lung disease
Chronic obstructive pulmonary disease
Cigarettes
Clinical trials
Collagen
Collagen (type I)
Collagen (type III)
Collagen Type I - metabolism
Collagens
Corticoids
Corticosteroid drugs
Corticosteroids
Decorin
Digital imaging
Extracellular matrix
Extracellular Matrix - drug effects
Extracellular Matrix - pathology
Extracellular Matrix Proteins - metabolism
Female
Fibroblasts
Fluticasone
Forced Expiratory Volume
Gene expression
Histochemistry
Humans
Image analysis
Image processing
Immunohistochemistry
Inflammation
Lung diseases
Male
Medicine
Middle Aged
Obstructive lung disease
Pathogenesis
Patients
Placebos
Predictive control
Proteins
Proteoglycans
Pulmonary Disease, Chronic Obstructive - drug therapy
Pulmonary Disease, Chronic Obstructive - pathology
Pulmonary Disease, Chronic Obstructive - physiopathology
Randomization
Remodeling
Respiratory function
Respiratory system agents
Respiratory therapy
Respiratory tract
Smoking
Smoking - adverse effects
Smoking cessation
Steroid hormones
Steroids
Steroids - administration & dosage
Steroids - pharmacology
Steroids - therapeutic use
Studies
Task forces
Versican
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Summary:Smoking and inflammation contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), which involves changes in extracellular matrix. This is thought to contribute to airway remodeling and airflow obstruction. We have previously observed that long-term treatment with inhaled corticosteroids can not only reduce bronchial inflammation, but can also attenuate lung function decline in moderate-severe COPD. We hypothesized that inhaled corticosteroids and current smoking modulate bronchial extracellular matrix components in COPD. To compare major extracellular matrix components (elastic fibers; proteoglycans [versican, decorin]; collagens type I and III) in bronchial biopsies 1) after 30-months inhaled steroids treatment or placebo; and 2) between current and ex-smokers with COPD. We included 64 moderate-severe, steroid-naive COPD patients (24/40 (ex)-smokers, 62±7 years, 46 (31-54) packyears, post-bronchodilator forced expiratory volume in one second (FEV1) 62±9% predicted) at baseline in this randomized, controlled trial. 19 and 13 patients received 30-months treatment with fluticasone or placebo, respectively. Bronchial biopsies collected at baseline and after 30 months were studied using (immuno)histochemistry to evaluate extracellular matrix content. Percentage and density of stained area were calculated by digital image analysis. 30-Months inhaled steroids increased the percentage stained area of versican (9.6% [CI 0.9 to 18.3%]; p = 0.03) and collagen III (20.6% [CI 3.8 to 37.4%]; p = 0.02) compared to placebo. Increased collagen I staining density correlated with increased post-bronchodilator FEV1 after inhaled steroids treatment (Rs = 0.45, p = 0.04). There were no differences between smokers and ex-smokers with COPD in percentages and densities for all extracellular matrix proteins. These data show that long-term inhaled corticosteroids treatment partially changes the composition of extracellular matrix in moderate-severe COPD. This is associated with increased lung function, suggesting that long-term inhaled steroids modulate airway remodeling thereby potentially preventing airway collapse in COPD. Smoking status is not associated with bronchial extracellular matrix proteins. ClinicalTrials.gov NCT00158847.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0063430