Siddiqui Salman, Sutcliffe Amanda, Shikotra Aarti, Woodman Lucy, Doe Camille, McKenna Sue, Wardlaw Andrew, Bradding Peter, Pavord Ian, Brightling Christopher
Institute of Lung Health, University of Leicester, Leicester, United Kingdom.
J Allergy Clin Immunol. 2007 Oct;120(4):813-9. doi: 10.1016/j.jaci.2007.05.028. Epub 2007 Jul 5.
Increased vascularity and expression of vascular endothelial growth factor (VEGF) are recognized features of the asthmatic airway. The association of vascular remodeling with airway hyperresponsiveness (AHR) is unclear.
To assess vascular remodeling and sputum VEGF concentration in subjects with asthma, subjects with nonasthmatic eosinophilic bronchitis (EB), and healthy controls.
In cohort 1, 19 patients with asthma (Global Initiative for Asthma [GINA] 1-2, n = 9; GINA 3-5, n = 10), 10 patients with EB, and 11 healthy matched controls were recruited. Expression of the endothelial marker EN4 was assessed in bronchial biopsy samples. Vessels were counted using the validated mean Chalkley count by a blind observer. For cohort 2, a second independent cohort of 31 patients with asthma (GINA 1-2, n = 11; GINA 3-5, n = 20), 14 patients with EB, and 15 matched controls was recruited. Induced sputum supernatant VEGF was measured by ELISA.
The mean chalkley count was significantly greater in GINA 3-5 asthma (5.2 [0.4]) and EB (4.8 [0.3]) compared with controls (3.5 [0.5]) and demonstrated a significant inverse correlation with the postbronchodilator FEV(1)% predicted in patients with asthma (R(2) = 0.28; P = .02). Sputum VEGF concentration was also increased in GINA 3-5 asthma (2365 [1361-4110] pg/g) and EB (4699 [2818-7834] pg/g) compared with controls (1094 [676-1774] pg/g) and was inversely related to postbronchodilator FEV(1)% predicted in asthma (R(2) = 0.2; P = .01).
Vascular remodeling is a feature of asthma, and EB and is inversely associated with the postbronchodilator FEV(1) in asthma, suggesting that vascular remodeling is associated with airflow obstruction but not AHR.
Vascular remodeling is dissociated from AHR in asthma and associated with airflow limitation.
血管生成增加以及血管内皮生长因子(VEGF)表达增加是哮喘气道的公认特征。血管重塑与气道高反应性(AHR)之间的关联尚不清楚。
评估哮喘患者、非哮喘性嗜酸性支气管炎(EB)患者和健康对照者的血管重塑及痰液VEGF浓度。
在队列1中,招募了19例哮喘患者(全球哮喘防治创议[GINA]1 - 2级,n = 9;GINA 3 - 5级,n = 10)、10例EB患者和11名健康对照者。在支气管活检样本中评估内皮标志物EN4的表达。由一名盲法观察者使用经过验证的平均Chalkley计数法对血管进行计数。对于队列2,招募了另一个独立队列,包括31例哮喘患者(GINA 1 - 2级,n = 11;GINA 3 - 5级,n = 20)、14例EB患者和15名对照者。通过ELISA法检测诱导痰液上清液中的VEGF。
与对照组(3.5 [0.5])相比,GINA 3 - 5级哮喘患者(5.2 [0.4])和EB患者(4.8 [0.3])的平均Chalkley计数显著更高,并且与哮喘患者支气管扩张剂后预测的FEV(1)%呈显著负相关(R(2)=0.28;P = 0.02)。与对照组(1094 [676 - 1774] pg/g)相比,GINA 3 - 5级哮喘患者(2365 [1361 - 4110] pg/g)和EB患者(4699 [2818 - 7834] pg/g)的痰液VEGF浓度也升高,并且与哮喘患者支气管扩张剂后预测的FEV(1)%呈负相关(R(2)=0.2;P = 0.01)。
血管重塑是哮喘和EB的一个特征,并且在哮喘中与支气管扩张剂后FEV(1)呈负相关,提示血管重塑与气流受限相关,但与AHR无关。
在哮喘中,血管重塑与AHR分离,与气流受限相关。