Chetta Alfredo, Zanini Andrea, Foresi Antonio, Del Donno Mario, Castagnaro Antonio, D'Ippolito Raffaele, Baraldo Simonetta, Testi Renato, Saetta Marina, Olivieri Dario
Department of Clinical Sciences, Section of Respiratory Diseases, University of Parma, Parma, Italy.
Am J Respir Crit Care Med. 2003 Mar 1;167(5):751-7. doi: 10.1164/rccm.200207-710OC. Epub 2002 Dec 4.
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.
我们进行了一项随机、双盲、平行组研究,以评估低剂量(每日两次,每次100微克)或高剂量(每日两次,每次500微克)吸入丙酸氟替卡松(FP)治疗6周对30例轻至中度哮喘患者气道重塑血管成分的影响。我们还研究了其对炎症细胞和基底膜厚度的影响,并将哮喘患者的支气管活检结果与8名对照受试者的结果进行了比较。在治疗前后测量了对乙酰甲胆碱的支气管反应性和哮喘症状评分。低剂量FP组的8例患者和高剂量FP组的8例患者完成了研究。在基线时,与对照受试者相比,哮喘患者的血管数量和血管面积增加。在哮喘患者中,血管数量与血管面积相关(p < 0.01),与肥大细胞数量相关(p < 0.01)。低剂量和高剂量FP治疗后,对乙酰甲胆碱的支气管反应性、哮喘症状评分和炎症细胞均显著降低(p < 0.05)。然而,仅在高剂量FP治疗后血管数量、血管面积和基底膜厚度才降低(p < 0.05)。总之,本研究表明,在轻至中度哮喘患者中,6周给予高剂量吸入FP可通过减少黏膜下血管生成和基底膜厚度来显著影响气道重塑。