Zheng L, Walters E H, Wang N, Whitford H, Orsida B, Levvey B, Bailey Michael, Williams T J, Snell G I
Department of Respiratory Medicine, Alfred Hospital and Monash University Medical School, Melbourne, Australia.
J Heart Lung Transplant. 2004 Apr;23(4):446-55. doi: 10.1016/S1053-2498(03)00199-2.
Inhaled fluticasone propionate (FP) therapy decreases inflammation and sub-basement membrane thickness in asthmatic airways. Bronchiolitis obliterans syndrome (BOS) in lung transplant recipients (LTRs) involves progressive airway fibrosis and obliteration. Therefore, augmented immunosuppression may be of some benefit in treating BOS. In this study, we examined the effect of 3 months of treatment with high-dose inhaled FP on the concentrations of 2 fibrogenic factors, transforming growth factor (TGF)-beta(1) and beta fibrogenic growth factor (bFGF) in bronchoalveolar lavage (BAL) fluid from clinically stable LTRs.
We conducted a randomized, double-blind, placebo-controlled, parallel group study with inhaled FP (750 microg, twice/day for 3 months) in 28 LTRs (15 FP and 13 placebo). We recruited 23 healthy controls. We performed spirometry, bronchoscopy, and bronchoalveolar lavage procedures before treatment and after 3 months of treatment. We used commercially available enzyme-linked immunosorbent assay kits to measure BAL fluid TGF-beta(1) and bFGF concentrations.
In LTRs before treatment, BAL TGF-beta(1) concentrations (but not bFGF concentrations), total cell counts, and neutrophil percentage increased compared with controls (p < 0.05). We found no significant differences between FP and placebo groups at baseline measurements. After treatment, BAL TGF-beta(1) concentrations significantly increased in the FP group (p = 0.03), but we found no difference between FP and placebo groups; BAL bFGF concentrations increased during treatment in both groups compared with controls (p < 0.05), but not significantly within either patient group (p > 0.05). We found a reverse correlation between forced expiratory volume in 1 second (FEV(1)) and BAL TGF-beta(1) concentration in the FP group (r = -0.53, p = 0.04), and between FEV(1) and BAL TGF-beta(1) concentration in the placebo group (r = -0.74, p = 0.004). Multivariable analysis indicated no significant independent effects of inhaled FP in either BAL TGF-beta(1) or bFGF concentrations.
Bronchoalveolar fluid TGF-beta(1) concentrations increased in LTRs after transplantation and may correlate with the decrease in lung function. Inhaled FP added to conventional immunosuppression had no effect on TGF-beta(1) or bFGF production in BAL fluid.
吸入丙酸氟替卡松（FP）治疗可减轻哮喘气道的炎症并降低基底膜下厚度。肺移植受者（LTRs）的闭塞性细支气管炎综合征（BOS）涉及进行性气道纤维化和闭塞。因此，增强免疫抑制可能对治疗BOS有益。在本研究中，我们检测了高剂量吸入FP治疗3个月对临床稳定的LTRs支气管肺泡灌洗（BAL）液中两种致纤维化因子，即转化生长因子（TGF）-β1和β纤维原细胞生长因子（bFGF）浓度的影响。
我们进行了一项随机、双盲、安慰剂对照的平行组研究，对28例LTRs（15例使用FP，13例使用安慰剂）吸入FP（750微克，每日2次，共3个月）。我们招募了23名健康对照者。在治疗前和治疗3个月后进行肺量计检查、支气管镜检查和支气管肺泡灌洗操作。我们使用市售的酶联免疫吸附测定试剂盒测量BAL液中TGF-β1和bFGF的浓度。
在治疗前的LTRs中，与对照组相比，BAL液中TGF-β1浓度（而非bFGF浓度）、总细胞计数和中性粒细胞百分比增加（p < 0.05）。在基线测量时，FP组和安慰剂组之间未发现显著差异。治疗后，FP组BAL液中TGF-β1浓度显著增加（p = 0.03），但FP组和安慰剂组之间未发现差异；与对照组相比，两组治疗期间BAL液中bFGF浓度均增加（p < 0.05），但在任何一组患者中均无显著增加（p > 0.05）。在FP组中，1秒用力呼气量（FEV1）与BAL液中TGF-β1浓度呈负相关（r = -0.53，p = 0.04），在安慰剂组中，FEV1与BAL液中TGF-β1浓度也呈负相关（r = -0.74，p = 0.004）。多变量分析表明，吸入FP对BAL液中TGF-β1或bFGF浓度均无显著独立影响。
移植后LTRs的支气管肺泡液中TGF-β1浓度增加，可能与肺功能下降相关。在传统免疫抑制基础上加用吸入FP对BAL液中TGF-β1或bFGF的产生无影响。
