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

被引:86
作者
Lapperre, Therese S. [1 ]
Sont, Jacob K. [2 ]
van Schadewijk, Annemarie [1 ]
Gosman, Margot M. E. [5 ]
Postma, Dirkje S. [5 ]
Bajema, Ingeborg M. [3 ]
Timens, Wim [6 ]
Mauad, Thais [1 ,4 ]
Hiemstra, Pieter S. [1 ]
Kauffman, H. F. [8 ]
de Reus, D. [8 ]
Boezen, H. M. [9 ]
Jansen, D. F. [9 ]
Vonk, J. [9 ]
Barentsen, M. D. W. [10 ]
Timens, W. [10 ]
Zeinstra-Smit, M. [10 ]
Luteijn, A. J. [11 ]
van der Molen, T. [11 ]
ter Veen, G. [11 ]
Gosman, M. M. E. [12 ]
ten Hacken, N. H. T. [12 ]
Kerstjens, H. A. M. [12 ]
van Maaren, M. S. [12 ]
Postma, D. S. [12 ]
Veltman, C. A. [12 ]
Verbokkem, A. [12 ]
Verhage, I. [12 ]
Vink-Kloosters, H. K. [12 ]
Snoeck-Stroband, J. B. [13 ]
Thiadens, H. [13 ]
Sont, J. K. [14 ]
Bajema, I. [15 ]
Gast-Strookman, J. [16 ]
Hiemstra, P. S. [16 ]
Janssen, K. [16 ]
Lapperre, T. S. [16 ]
Rabe, K. F. [16 ]
van Schadewijk, A. [16 ]
Schrumpf, J. A. [16 ]
Smit-Bakker, J. [16 ]
Stolk, J. [16 ]
Tire, A. C. J. A. [16 ]
van der Veen, H. [16 ]
Wijffels, M. M. E. [16 ]
Willems, L. N. A. [16 ]
Sterk, P. J. [17 ]
Mauad, T. [18 ]
机构
[1] Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Med Decis Making, Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands
[4] Univ Sao Paulo, Dept Pathol, Sao Paulo, Brazil
[5] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, Groningen, Netherlands
[6] Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands
[7] Groningen Leiden Univ, Leiden, Netherlands
[8] Univ Med Ctr Groningen, Dept Allergol, Groningen, Netherlands
[9] Univ Med Ctr Groningen, Dept Epidemiol & Stat, Groningen, Netherlands
[10] Univ Med Ctr Groningen, Dept Pathol, Groningen, Netherlands
[11] Univ Med Ctr Groningen, Dept Gen Practice, Groningen, Netherlands
[12] Univ Med Ctr Groningen, Dept Pulmonol, Groningen, Netherlands
[13] Leiden Univ, Med Ctr, Dept Gen Practice, Leiden, Netherlands
[14] Leiden Univ, Med Ctr, Dept Med Decis Making, Leiden, Netherlands
[15] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands
[16] Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands
[17] Univ Amsterdam, Acad Med Ctr, Dept Pulmonol, NL-1012 WX Amsterdam, Netherlands
[18] Univ Sao Paulo, Sao Paulo, Brazil
关键词
GROWTH-FACTOR RECEPTOR; OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC MUCUS HYPERSECRETION; HUMAN NEUTROPHIL DEFENSINS; AIRWAY INFLAMMATION; PERIPHERAL AIRWAYS; CURRENT SMOKERS; EXPRESSION; INTERVENTION; BRONCHODILATOR;
D O I
10.1186/1465-9921-8-85
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
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 FEV 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 (= 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).
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