CD8+ T cells characterize early smoking-related airway pathology in patients with asthma

被引:29
|
作者
Ravensberg, A. Janneke [1 ]
Slats, Annelies M. [1 ]
van Wetering, Sandra [1 ]
Janssen, Kirsten [1 ]
van Wijngaarden, Simone [1 ]
de Jeu, Ronald [1 ]
Rabe, Klaus F. [1 ,2 ]
Sterk, Peter J. [1 ,3 ]
Hiemstra, Pieter S. [1 ]
机构
[1] Leiden Univ, Dept Pulmonol, Med Ctr, Leiden, Netherlands
[2] Grosshansdorf Hosp, Ctr Pneumonol, Grosshansdorf, Germany
[3] Univ Amsterdam, Acad Med Ctr, Dept Resp Med, NL-1105 AZ Amsterdam, Netherlands
关键词
Asthma; Smoking; Airway inflammation; CD8(+) T lymphocyte; Airway epithelium; LUNG-FUNCTION DECLINE; CIGARETTE-SMOKING; INHALED CORTICOSTEROIDS; BRONCHIAL BIOPSIES; INFLAMMATION; SMOKERS; MILD; EPITHELIUM; COPD; STANDARDIZATION;
D O I
10.1016/j.rmed.2013.03.018
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Smoking in asthma occurs frequently and is associated with increased symptom severity, an impaired response to corticosteroids, and accelerated lung function decline. Airway pathology in smoking asthmatics is characterized by neutrophilia and epithelial changes such as goblet cell hyperplasia and increased proliferation. Bronchial CD8(+) T cells are implicated in lung function decline in asthma and COPD. We hypothesized that smoking modifies airway inflammation in asthma by increasing the number of CD8(+) T cells at an early stage. Objectives & methods: To study effects of smoking on airway pathology in bronchial biopsies from atopic patients with controlled intermittent or mild persistent asthma (12 smokers, 9.7 py and 11 never-smokers, 0.0 py; 20-50 yrs; FEV1 > 70% predicted; PC(20)MCh <8 mg/mL, no ICS) using immunohistochemistry. Results: Smoking asthmatics showed higher numbers of bronchial CD8(+) T cells (55.8 vs 23.9 cells/0.1 mm(2); p = 0.001) and CD68(+) macrophages (7.5 vs 4.6 cells/0.1 mm(2), p = 0.012), and a lower CD4(+)/CD8(+) cell ratio (0.16 vs 0.40; p = 0.007) compared with non-smoking asthmatics, but no difference in neutrophils. Furthermore, the % intact epithelium was higher in smoking asthmatics (49.3 vs 23.3, p = 0.001). Conclusion: Smoking asthmatics with a limited smoking history show a distinct pattern of airway pathology characterized by a bronchial infiltrate of CD8(+) T cells and CD68(+) macrophages, and epithelial remodelling resembling COPD-like features. This raises the hypothesis that early presence of CD8(+) T cells contributes to disease progression in smoking asthmatics. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:959 / 966
页数:8
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