Vascular component of airway remodeling in asthma is reduced by high dose of fluticasone

被引:139
作者
Chetta, A
Zanini, A
Foresi, A
Del Donno, M
Castagnaro, A
D'Ippolito, R
Baraldo, S
Testi, R
Saetta, M
Olivieri, D
机构
[1] Univ Parma, Sect Resp Dis, Dept Clin Sci, I-43100 Parma, Italy
[2] IRCCS, Rehabil Inst Tradate, Salvatore Maugeri Fdn, Div Pneumol, Tradate, Italy
[3] Sesto S Giovanni Hosp, Resp Pathophysiol Lab, Sesto San Giovanni, Italy
[4] Univ Padua, Sect Resp Dis, Dept Clin & Expt Med, Padua, Italy
[5] GSK, Res & Dev Unit, Verona, Italy
关键词
asthma; airway inflammation; inhaled steroids; bronchial biopsy;
D O I
10.1164/rccm.200207-710OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
We conducted a randomized, double-blind, parallel-group study to assess the effect of 6 weeks treatment with low-dose (100 mug twice a day) or high-dose (500 mug 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 FIR 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 FIR given over 6 weeks can significantly affect airway remodeling by reducing both submucosal vascularity and basement membrane thickness.
引用
收藏
页码:751 / 757
页数:7
相关论文
共 38 条
[1]  
[Anonymous], 1987, AM REV RESPIR DIS, V136, P225
[2]   MAST-CELL HEPARIN STIMULATES MIGRATION OF CAPILLARY ENDOTHELIAL-CELLS INVITRO [J].
AZIZKHAN, RG ;
AZIZKHAN, JC ;
ZETTER, BR ;
FOLKMAN, J .
JOURNAL OF EXPERIMENTAL MEDICINE, 1980, 152 (04) :931-944
[3]   Mast cells can secrete vascular permeability factor vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of Fcε receptor I expression [J].
Boesiger, J ;
Tsai, M ;
Maurer, M ;
Yamaguchi, M ;
Brown, LF ;
Claffey, KP ;
Dvorak, HF ;
Galli, SJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (06) :1135-1145
[4]   EFFECT OF HIGH-DOSE INHALED FLUTICASONE PROPIONATE ON AIRWAY INFLAMMATION IN ASTHMA [J].
BOOTH, H ;
RICHMOND, I ;
WARD, C ;
GARDINER, PV ;
HARKAWAT, R ;
WALTERS, EH .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 1995, 152 (01) :45-52
[5]   IMMUNOHISTOCHEMISTRY ON RESIN SECTIONS - A COMPARISON OF RESIN EMBEDDING TECHNIQUES FOR SMALL MUCOSAL BIOPSIES [J].
BRITTEN, KM ;
HOWARTH, PH ;
ROCHE, WR .
BIOTECHNIC & HISTOCHEMISTRY, 1993, 68 (05) :271-280
[6]   THE STRUCTURE OF LARGE AND SMALL AIRWAYS IN NONFATAL AND FATAL ASTHMA [J].
CARROLL, N ;
ELLIOT, J ;
MORTON, A ;
JAMES, A .
AMERICAN REVIEW OF RESPIRATORY DISEASE, 1993, 147 (02) :405-410
[7]   EFFECT OF HISTAMINE ON TRACHEAL MUCOSAL PERFUSION, WATER-CONTENT AND AIRWAY SMOOTH-MUSCLE IN SHEEP [J].
CHEDIAK, AD ;
ELSASSER, S ;
CSETE, ME ;
GAZEROGLU, H ;
WANNER, A .
RESPIRATION PHYSIOLOGY, 1991, 84 (02) :231-243
[8]   Airways remodeling is a distinctive feature of asthma and is related to severity of disease [J].
Chetta, A ;
Foresi, A ;
DelDonno, M ;
Bertorelli, G ;
Pesci, A ;
Olivieri, D .
CHEST, 1997, 111 (04) :852-857
[9]  
CRAPO RO, 1981, AM REV RESPIR DIS, V123, P659
[10]  
DAMORE PA, 1992, AM J RESP CELL MOL, V6, P1