Asthma exacerbations after glucocorticoid withdrawal reflects T cell recruitment to the airway
Asthma exacerbations after glucocorticoid withdrawal reflects T cell recruitment to the airway
复制标题
DOI：
10.1164/rccm.200208-960oc
复制
发表时间：
2004-04-01
影响因子：
24.7
通讯作者：
Holtzman, MJ
中科院分区：
文献类型：
--
作者：
Castro, M;Bloch, SR;Holtzman, MJ
我们推断，对哮喘患者糖皮质激素戒断的前瞻性评估将提供对疾病发作基础的深入了解。因此，我们招募了25名中度持续性哮喘受试者，用吸入性丙酸氟替卡松（1，760 μ g/天）治疗30天，然后停药，直至呼气峰气流下降25%，FEV 1下降15%或6周。糖皮质激素停药后，25例受试者中有13例达到目标，而12例未达到目标。两组患者停用糖皮质激素后，支气管活检中嗜酸性粒细胞的数量均增加，但仅在急性发作患者中发现气道T细胞增加。T细胞蓄积反映了CD 4（+）和CD 8（+）T细胞的相似增加，并伴随着气道上皮中趋化因子CCL 5（活化后调节，正常T细胞表达和分泌）的表达增加，而不激活转录因子核因子-κ B。在哮喘急性发作期间糖皮质激素敏感性炎症的模式更像是抗病毒反应，而不是嗜酸性粒细胞为主的过敏原反应，这意味着气道T细胞在介导哮喘发作和确定糖皮质激素治疗这种疾病的疗效中发挥独立作用。
We reasoned that a prospective assessment of glucocorticoid withdrawal in subjects with asthma would provide insight into the basis for flares of the disease. We therefore enrolled 25 subjects with moderate persistent asthma and treated them for 30 days with inhaled fluticasone propionate (1,760 mug/day) followed by a withdrawal period that lasted until peak expiratory airflow decreased by 25% and FEV1 by 15% or 6 weeks elapsed. After glucocorticoid withdrawal, 13 of 25 subjects reached the target, whereas 12 subjects did not. The number of eosinophils in bronchial biopsies was increased by glucocorticoid withdrawal in both groups, but increases in airway T cells were found in only those with exacerbation. T-cell accumulation was a reflection of similar increases in both CD4(+) and CD8(+) T cells and was accompanied by increased expression of chemokine CCL5 (regulated upon activation, normal T cell expressed and secreted) in the airway epithelium without activation of the transcription factor nuclear factor-kappaB. The pattern of glucocorticoid-sensitive inflammation during an asthma exacerbation is more reminiscent of an antiviral response than an eosinophil-predominant response to allergen and implies an independent role for airway T cells in mediating asthma flares and in determining glucocorticoid efficacy in the treatment of this disease.