Patient characteristics at baseline.

<p>Patient characteristics for current smokers and ex-smokers with COPD and groups treated with placebo and fluticasone (only compliant patients). Bronchial biopsies were available at baseline of 64 (elastic fibers), 56 (versican), 61 (decorin), 61 (collagen I) and 64 (collagen III) patients. After 30 months, bronchial biopsies of 32 compliant patients were available, tissue from 29 (elastic fibers), 26 (versican), 27 (decorin), 28 (collagen I) and 28 (collagen III) patients had sufficient surface area for analysis (≥0.09 mm²) (fluticasone and placebo groups combined). Data are presented as mean (SD) or median (IQR), unless otherwise stated. Methacholine PC₂₀: provocative concentration of methacholine that causes a 20% decrease in FEV₁, expressed as mean doubling doses. Part of the data have been published previously <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063430#pone.0063430-Lapperre1" target="_blank">[17]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063430#pone.0063430-Lapperre2" target="_blank">[22]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063430#pone.0063430-Kunz1" target="_blank">[27]</a>.</p>*<p>p<0.05 compared to current smokers (two tailed unpaired t-tests).</p

Correlation between percentage collagen type I at baseline and lung function parameters.

<p>Panel A presents post-bronchodilator FEV₁ (% predicted) and panel B shows PC₂₀ (in doubling dose).</p

Percentage and density of stained area at baseline of ex-smokers and smokers with COPD.

<p>Percentage (upper panel) and density (lower panel) of stained area in bronchial biopsies is presented. Ex-smokers are presented as open circles, current smokers as closed circles. Horizontal bars represent medians. No significant differences were found for all studied extracellular matrix proteins (both percentage stained area and density).</p

Examples of (immuno)histochemical stainings.

<p>The same bronchial biopsy section is shown for the histochemical staining for elastic fibers (A) and the immunohistochemical stainings for versican (B), decorin (C), collagen type I (D) and collagen type III (E). Original magnification 200×.</p

Inhaled Steroids Modulate Extracellular Matrix Composition in Bronchial Biopsies of COPD Patients:A Randomized, Controlled Trial

<p>Rationale: 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.</p><p>Objective: 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 exsmokers with COPD.</p><p>Methods: 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.</p><p>Results: 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.</p><p>Conclusions: 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.</p>