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Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study.

Lapperre TS, Sont JK, van Schadewijk A, Gosman MM, Postma DS, Bajema IM, Timens W, Mauad T, Hiemstra PS, GLUCOLD Study Gro - Respir. Res. (2007)

Bottom Line: Epithelial features were not different between short-term quitters (<3.5 years) and current smokers.Long-term quitters (> or =3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).NCT00158847.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept. of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands. t.s.lapperre@lumc.nl

ABSTRACT

Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.

Methods: 114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 +/- 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 +/- 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.

Results: Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters (<3.5 years) and current smokers. Long-term quitters (> or =3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).

Conclusion: Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).

Trial registration: NCT00158847.

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Related in: MedlinePlus

Epithelial phenotype in smokers (S) and ex-smokers with COPD. Individual values of: (A) % PAS/AB+ area of intact epithelium, (B) Ki-67+ cells (/mm basement membrane = BSM) in intact epithelium, (C) % squamous cell metaplasia (SCM) of intact epithelium (note: in a large % of patients no SCM was observed), (D) % EGFR+ area of intact epithelium. Data are grouped by COPD smokers (S), COPD ex-smokers who quit < 3.5 years ago (<3.5 yr), and who quit ≥3.5 years ago (≥3.5 yr). Horizontal bars represent median values, * p < 0.05.
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Figure 1: Epithelial phenotype in smokers (S) and ex-smokers with COPD. Individual values of: (A) % PAS/AB+ area of intact epithelium, (B) Ki-67+ cells (/mm basement membrane = BSM) in intact epithelium, (C) % squamous cell metaplasia (SCM) of intact epithelium (note: in a large % of patients no SCM was observed), (D) % EGFR+ area of intact epithelium. Data are grouped by COPD smokers (S), COPD ex-smokers who quit < 3.5 years ago (<3.5 yr), and who quit ≥3.5 years ago (≥3.5 yr). Horizontal bars represent median values, * p < 0.05.

Mentions: Ki-67+ cell numbers, the presence of squamous cell metaplasia, and the % PAS/AB+ area, were different between current smokers, ex-smokers who quit <3.5 years ago, and ex-smokers who quit ≥3.5 years ago (Kruskal Wallis: p = 0.011, p < 0.001, p = 0.049; respectively, Table 2, Figure 1). Percentage squamous cell metaplasia and EGFR+ areas and intensities were not significantly different between these three groups (Table 2, Figure 1). There were no differences between current smokers and those who quit <3.5 years ago for any of the epithelial features. In contrast, those who quit ≥3.5 years ago had significantly less Ki-67+ cell numbers, presence of squamous cell metaplasia, and % PAS/AB+ area than current smokers (p < 0.001, p = 0.029, p = 0.005, respectively; Table 2, Figure 1). The differences in PAS/AB and Ki-67 remained significant when adjusting for age and pack-year differences between both groups. Moreover, the % PAS/AB+ area was also lower in long-term quitters than those who quit <3.5 years ago (p = 0.008), and tended to be lower for Ki-67+ cell numbers (p = 0.050). When adjusting for differences in age, PAS/AB significance was lost (p = 0.061).


Smoking cessation and bronchial epithelial remodelling in COPD: a cross-sectional study.

Lapperre TS, Sont JK, van Schadewijk A, Gosman MM, Postma DS, Bajema IM, Timens W, Mauad T, Hiemstra PS, GLUCOLD Study Gro - Respir. Res. (2007)

Epithelial phenotype in smokers (S) and ex-smokers with COPD. Individual values of: (A) % PAS/AB+ area of intact epithelium, (B) Ki-67+ cells (/mm basement membrane = BSM) in intact epithelium, (C) % squamous cell metaplasia (SCM) of intact epithelium (note: in a large % of patients no SCM was observed), (D) % EGFR+ area of intact epithelium. Data are grouped by COPD smokers (S), COPD ex-smokers who quit < 3.5 years ago (<3.5 yr), and who quit ≥3.5 years ago (≥3.5 yr). Horizontal bars represent median values, * p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2214729&req=5

Figure 1: Epithelial phenotype in smokers (S) and ex-smokers with COPD. Individual values of: (A) % PAS/AB+ area of intact epithelium, (B) Ki-67+ cells (/mm basement membrane = BSM) in intact epithelium, (C) % squamous cell metaplasia (SCM) of intact epithelium (note: in a large % of patients no SCM was observed), (D) % EGFR+ area of intact epithelium. Data are grouped by COPD smokers (S), COPD ex-smokers who quit < 3.5 years ago (<3.5 yr), and who quit ≥3.5 years ago (≥3.5 yr). Horizontal bars represent median values, * p < 0.05.
Mentions: Ki-67+ cell numbers, the presence of squamous cell metaplasia, and the % PAS/AB+ area, were different between current smokers, ex-smokers who quit <3.5 years ago, and ex-smokers who quit ≥3.5 years ago (Kruskal Wallis: p = 0.011, p < 0.001, p = 0.049; respectively, Table 2, Figure 1). Percentage squamous cell metaplasia and EGFR+ areas and intensities were not significantly different between these three groups (Table 2, Figure 1). There were no differences between current smokers and those who quit <3.5 years ago for any of the epithelial features. In contrast, those who quit ≥3.5 years ago had significantly less Ki-67+ cell numbers, presence of squamous cell metaplasia, and % PAS/AB+ area than current smokers (p < 0.001, p = 0.029, p = 0.005, respectively; Table 2, Figure 1). The differences in PAS/AB and Ki-67 remained significant when adjusting for age and pack-year differences between both groups. Moreover, the % PAS/AB+ area was also lower in long-term quitters than those who quit <3.5 years ago (p = 0.008), and tended to be lower for Ki-67+ cell numbers (p = 0.050). When adjusting for differences in age, PAS/AB significance was lost (p = 0.061).

Bottom Line: Epithelial features were not different between short-term quitters (<3.5 years) and current smokers.Long-term quitters (> or =3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).NCT00158847.

View Article: PubMed Central - HTML - PubMed

Affiliation: Dept. of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands. t.s.lapperre@lumc.nl

ABSTRACT

Background: Chronic Obstructive Pulmonary Disease (COPD) is associated with bronchial epithelial changes, including squamous cell metaplasia and goblet cell hyperplasia. These features are partially attributed to activation of the epidermal growth factor receptor (EGFR). Whereas smoking cessation reduces respiratory symptoms and lung function decline in COPD, inflammation persists. We determined epithelial proliferation and composition in bronchial biopsies from current and ex-smokers with COPD, and its relation to duration of smoking cessation.

Methods: 114 COPD patients were studied cross-sectionally: 99 males/15 females, age 62 +/- 8 years, median 42 pack-years, no corticosteroids, current (n = 72) or ex-smokers (n = 42, median cessation duration 3.5 years), postbronchodilator FEV1 63 +/- 9% predicted. Squamous cell metaplasia (%), goblet cell (PAS/Alcian Blue+) area (%), proliferating (Ki-67+) cell numbers (/mm basement membrane), and EGFR expression (%) were measured in intact epithelium of bronchial biopsies.

Results: Ex-smokers with COPD had significantly less epithelial squamous cell metaplasia, proliferating cell numbers, and a trend towards reduced goblet cell area than current smokers with COPD (p = 0.025, p = 0.001, p = 0.081, respectively), but no significant difference in EGFR expression. Epithelial features were not different between short-term quitters (<3.5 years) and current smokers. Long-term quitters (> or =3.5 years) had less goblet cell area than both current smokers and short-term quitters (medians: 7.9% vs. 14.4%, p = 0.005; 7.9% vs. 13.5%, p = 0.008; respectively), and less proliferating cell numbers than current smokers (2.8% vs. 18.6%, p < 0.001).

Conclusion: Ex-smokers with COPD had less bronchial epithelial remodelling than current smokers, which was only observed after long-term smoking cessation (>3.5 years).

Trial registration: NCT00158847.

Show MeSH
Related in: MedlinePlus