Vascular Component of Airway Remodeling in Asthma Is Reduced by High Dose of Fluticasone

Abstract

We conducted a randomized, double-blind, parallel-group study to assess the effect of 6 weeks treatment with low-dose (100 microg twice a day) or high-dose (500 microg twice a day) inhaled fluticasone propionate (FP) on the vascular component of airway remodeling in 30 patients with mild to moderate asthma. We also studied the effect on the inflammatory cells and the basement membrane thickness, and we compared findings from bronchial biopsies taken in patients with asthma with those in eight control subjects. Bronchial responsiveness to methacholine and asthma symptom score were measured before and after treatments. Eight patients in the low-dose FP group and eight patients in high-dose FP group completed the study. At baseline, patients with asthma showed an increase in the number of vessels and in vascular area as compared with control subjects. In the subjects with asthma, number of vessels correlated with vascular area (p < 0.01) and with number of mast cells (p < 0.01). Bronchial responsiveness to methacholine, asthma symptom score, and inflammatory cells decreased significantly after both low- and high-dose FP (p < 0.05). However, the number of vessels, the vascular area, and the basement membrane thickness decreased only after high-dose FP (p < 0.05). In conclusion, this study shows that in patients with mild to moderate asthma, high dose of inhaled FP given over 6 weeks can significantly affect airway remodeling by reducing both submucosal vascularity and basement membrane thickness.

Expression and Functions of the Vascular Endothelial Growth Factors and Their Receptors in Human Basophils

“…Preincubation of basophils with high concentrations of the agonist is known to cause desensitization to a subsequent challenge with the same stimulus (23,27). We examined the relationship between VEGF-A 165 and eotaxin or Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) by evaluating the effects of heterologous desensitization between these stimuli on basophil chemotaxis. Purified basophils were preincubated with buffer or with VEGF-A 165 (500 ng/ml) or eotaxin (100 ng/ml) or Hp (2-20) (500 nM) in P-EDTA for 1 h at 37°C.…”

“…Angiogenesis is critical for such chronic inflammatory disorders as rheumatoid arthritis (3), bronchial asthma (4,5), and tumor growth (6). Vascular endothelial growth factor (VEGF) 3 is the most potent proangiogenic mediator known so far.…”

“…Increasing evidence implicates angiogenesis not only in tumor growth but also in several chronic inflammatory disorders (3)(4)(5). Peripheral blood basophils express the tetrameric (␣␤␥ 2 ) structure of the FcRI and synthesize proinflammatory mediators and a restricted Th2-like cytokine profile (IL-4 and IL-13) (20).…”

Inhaled corticosteroids reduce asthma-associated airway hyperperfusion through genomic and nongenomic mechanisms

“…In a cross-sectional study, therapy with high doses (≥ 800 µg/day) of beclomethasone dipropionate was associated with a reduced vascular area of the lamina propria [38]. In interventional studies, beclomethasone dipropionate (800 µg/day) therapy for 6 months reduced the number of blood vessels and the vascular area [39], whereas a 6-week treatment with fluticasone propionate was effective at 1000 µg/day inhaled dose in reducing the number of blood vessels and the vascular area [29].…”

“…A number of studies have also demonstrated increased vascularity (i.e. size and number of vessels, or cross-sectional vascular area) of the bronchial mucosa in patients with asthma compared with healthy controls [28,29].…”