MacRedmond Ruth E, Singhera Gurpreet K, Wadsworth Samuel J, Attridge Susan, Bahzad Mohammed, Williams Kristy, Coxson Harvey O, White Steven R, Dorscheid Delbert R
Centre for Heart Lung Innovation, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
Department of Medicine, University of Chicago, Chicago, Illinois, USA.
J Steroids Horm Sci. 2014 Jun 11;5(2). doi: 10.4172/2157-7536.1000134.
The airway epithelium has a number of roles pivotal to the pathogenesis of asthma, including provision of a physical and immune barrier to the inhaled environment. Dysregulated injury and repair responses in asthma result in loss of airway epithelial integrity. Inhaled corticosteroids are a corner stone of asthma treatment. While effective in controlling asthma symptoms, they fail to prevent airway remodeling. Direct cytopathic effects on the airway epithelium may contribute to this.
This study examined the effects of a 4-week treatment regimen of inhaled fluticasone 500 μg twice daily in healthy human subjects. Induced sputum was collected for cell counts and markers of inflammation. Barrier function was examined by diethylenetriaminepentacetic acid (DTPA) clearance measured by nuclear scintillation scan, and albumin concentration in induced sputum.
Steroid exposure resulted in epithelial injury as measured by a significant increase in the number of airway epithelial cells in induced sputum. There was no change in airway inflammation by induced sputum inflammatory cell counts or cytokine levels. Epithelial shedding was associated with an increase in barrier function, as measured by both a decrease in DTPA clearance and decreased albumin in induced sputum. This likely reflects the normal repair response.
Inhaled corticosteroids cause injury to normal airway epithelium. These effects warrant further evaluation in asthma, where the dysregulated repair response may contribute to airway remodeling.
气道上皮在哮喘发病机制中具有许多关键作用，包括为吸入环境提供物理和免疫屏障。哮喘中损伤和修复反应失调导致气道上皮完整性丧失。吸入性糖皮质激素是哮喘治疗的基石。虽然它们能有效控制哮喘症状，但无法预防气道重塑。对气道上皮的直接细胞病变效应可能对此有影响。
本研究检测了健康人体受试者每日两次吸入500μg氟替卡松，为期4周的治疗方案的效果。收集诱导痰进行细胞计数和炎症标志物检测。通过核闪烁扫描测量二乙三胺五乙酸（DTPA）清除率以及诱导痰中的白蛋白浓度来检测屏障功能。
通过诱导痰中气道上皮细胞数量显著增加来衡量，类固醇暴露导致上皮损伤。诱导痰炎症细胞计数或细胞因子水平检测显示气道炎症无变化。通过DTPA清除率降低和诱导痰中白蛋白减少来衡量，上皮脱落与屏障功能增加相关。这可能反映了正常的修复反应。
吸入性糖皮质激素会对正常气道上皮造成损伤。这些效应在哮喘中值得进一步评估，因为失调的修复反应可能导致气道重塑。
