Author(s): Siddiqui S, Sutcliffe A, Shikotra A, Woodman L, Doe C
RATIONALE: 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.
OBJECTIVE: To assess vascular remodeling and sputum VEGF concentration in subjects with asthma, subjects with nonasthmatic eosinophilic bronchitis (EB), and healthy controls.
METHODS: 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.
RESULTS: 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).
CONCLUSION: 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.
CLINICAL IMPLICATIONS: Vascular remodeling is dissociated from AHR in asthma and associated with airflow limitation.Journal of Allergy & Therapy