Vermont Lung Center, University of Vermont, Burlington, Vermont, USA.
Respir Res. 2010 Feb 24;11(1):22. doi: 10.1186/1465-9921-11-22.
The relationship between airway structural changes (remodeling) and airways hyperresponsiveness (AHR) is unclear. Asthma guidelines suggest treating persistent asthma with inhaled corticosteroids and long acting beta-agonists (LABA). We examined the link between physiological function and structural changes following treatment fluticasone and salmeterol separately or in combination in a mouse model of allergic asthma.
BALB/c mice were sensitized to intraperitoneal ovalbumin (OVA) followed by six daily inhalation exposures. Treatments included 9 daily nebulized administrations of fluticasone alone (6 mg/ml), salmeterol (3 mg/ml), or the combination fluticasone and salmeterol. Lung impedance was measured following methacholine inhalation challenge. Airway inflammation, epithelial injury, mucus containing cells, and collagen content were assessed 48 hours after OVA challenge. Lungs were imaged using micro-CT.
Treatment of allergic airways disease with fluticasone alone or in combination with salmeterol reduced AHR to approximately naüve levels while salmeterol alone increased elastance by 39% compared to control. Fluticasone alone and fluticasone in combination with salmeterol both reduced inflammation to near naive levels. Mucin containing cells were also reduced with fluticasone and fluticasone in combination with salmeterol.
Fluticasone alone and in combination with salmeterol reduces airway inflammation and remodeling, but salmeterol alone worsens AHR: and these functional changes are consistent with the concomitant changes in mucus metaplasia.
气道结构变化（重塑）与气道高反应性（AHR）之间的关系尚不清楚。哮喘指南建议使用吸入性皮质类固醇和长效β-激动剂（LABA）治疗持续性哮喘。我们在一种过敏性哮喘的小鼠模型中分别或联合使用氟替卡松和沙美特罗治疗后，检查了生理功能与结构变化之间的联系。
BALB/c 小鼠经腹腔内卵清蛋白（OVA）致敏，随后进行 6 次每日吸入暴露。治疗包括 9 次每日雾化给予氟替卡松（6mg/ml）、沙美特罗（3mg/ml）或氟替卡松和沙美特罗联合治疗。在给予乙酰甲胆碱吸入挑战后测量肺阻抗。OVA 挑战后 48 小时评估气道炎症、上皮损伤、含粘液细胞和胶原含量。使用 micro-CT 对肺部进行成像。
单独使用氟替卡松或联合使用沙美特罗治疗过敏性气道疾病可将 AHR 降低至接近正常水平，而单独使用沙美特罗可使弹性增加 39%，与对照组相比。单独使用氟替卡松和氟替卡松联合沙美特罗均可使炎症降低至接近正常水平。粘液细胞也减少了氟替卡松和氟替卡松联合沙美特罗。
单独使用氟替卡松和联合使用沙美特罗可减少气道炎症和重塑，但单独使用沙美特罗会加重 AHR：这些功能变化与粘液化生的同时变化一致。
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