Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma
Effects of budesonide and formoterol on allergen-induced airway responses, inflammation, and airway remodeling in asthma
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DOI：
10.1016/j.jaci.2009.09.011
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发表时间：
2010-02-01
影响因子：
14.2
通讯作者：
O'Byrne, Paul M.
中科院分区：
文献类型：
--
作者：
Kelly, Margaret M.;O'Connor, Terence M.;O'Byrne, Paul M.
背景资料：联合吸入性皮质类固醇与长效β 2受体激动剂;与单独吸入性皮质类固醇相比，可改善哮喘症状控制，减少哮喘急性发作。然而，关于这些有益作用是否是由于增强的抗炎作用或这种联合治疗是否影响哮喘患者的气道重塑的数据有限。目的：我们试图确定吸入布地奈德/福莫特罗联合治疗与吸入布地奈德单独或吸入安慰剂对过敏原诱导的气道反应、气道炎症和气道重塑的影响。方法：14名吸入变应原后出现双重应答的哮喘受试者被纳入这项前瞻性、随机、双盲、3阶段交叉研究。结果包括早期和晚期哮喘反应，气道反应性的变化，痰嗜酸性粒细胞测定之前和之后过敏原的挑战，气道粘膜下肌成纤维细胞的数量，和平滑肌面积测量之前和之后的研究treatment.Results：过敏原诱导的痰嗜酸性粒细胞增多症显着减少联合治疗在更大程度上比单独布地奈德。变应原吸入导致粘膜下组织肌成纤维细胞数量显著增加，平滑肌面积百分比显著降低。联合治疗，但不是布地奈德单药治疗，显着衰减这些变化的肌成纤维细胞的数量和smooth muscle area.Conclusions：在痰嗜酸性粒细胞，气道肌成纤维细胞的数量，和平滑肌的过敏原诱导的变化的影响与联合治疗表明，这种治疗的好处可能与气道炎症和重塑的影响。通过联合治疗减弱早期哮喘反应和气道高反应性可能是由于福莫特罗的已知功能性拮抗作用。（J Allergy Clin Immunol 2010;125：349-56.）
Background: Combining inhaled corticosteroids with long-acting beta(2)-agonists; results in improved asthma symptom control and fewer asthma exacerbations compared with those seen after inhaled corticosteroids alone. However, there are limited data as to whether these beneficial effects are due to enhanced anti-inflammatory actions or whether such combination therapies affect airway remodeling in patients with asthma.Objective: We sought to determine the effects of inhaled budesonide/formoterol combination therapy versus inhaled budesonide alone or inhaled placebo on allergen-induced airway responses, airway inflammation, and airway remodeling.Methods: Fourteen asthmatic subjects with dual responses after allergen inhalation were included in this prospective, randomized, double-blind, 3-period crossover study. Outcomes included early and late asthmatic responses, changes in airway responsiveness, sputum eosinophilia measured before and after allergen challenge, numbers of airway submucosal myofibroblasts, and smooth muscle area measured before and after study treatment.Results: Allergen-induced sputum eosinophilia was significantly reduced by combination treatment to a greater extent than by budesonide alone. Allergen inhalation resulted in a significant increase in submucosal tissue myofibroblast numbers and produced a significant decrease in percentage smooth muscle farea. Combination therapy, but not budesonide monotherapy, significantly attenuated these changes in myofibroblast numbers and smooth muscle area.Conclusions: The effects on allergen-induced changes in sputum eosinophils, airway myofibroblast numbers, and smooth muscle seen with combination therapy suggest that the benefits associated with this treatment might relate to effects on airway inflammation and remodeling. The attenuation of early asthmatic responses and airway hyperresponsiveness by combination treatment was likely due to the known functional antagonistic effect of formoterol. (J Allergy Clin Immunol 2010;125:349-56.)