Bronchoscopic evaluation of severe asthma - Persistent inflammation associated with high dose glucocorticoids
Bronchoscopic evaluation of severe asthma - Persistent inflammation associated with high dose glucocorticoids
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DOI：
10.1164/ajrccm.156.3.9610046
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发表时间：
1997-09-01
影响因子：
24.7
通讯作者：
Martin, RJ
中科院分区：
文献类型：
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作者：
Wenzel, SE;Szefler, SJ;Martin, RJ
炎症在长期使用高剂量糖皮质激素治疗的严重哮喘发病机制中的作用尚不清楚。尽管如此，治疗的目的是推进免疫调节剂和免疫调节剂治疗。本研究旨在评估严重哮喘患者气道炎症的存在和类型。一项前瞻性支气管镜研究评价了14例重度、大剂量口服糖皮质激素依赖性哮喘患者。分析支气管肺泡灌洗液的细胞学和炎症介质。在选定的患者中进行支气管内和经支气管活检，以进行巨噬细胞/单核细胞、中性粒细胞、嗜酸性粒细胞和淋巴细胞的形态学评价。这些结果与正常对照组和中度哮喘患者的灌洗、支气管内和经支气管活检研究进行了比较。支气管肺泡灌洗液中嗜酸性粒细胞浓度在未使用糖皮质激素的中度哮喘患者中最高，正常对照组和重度哮喘患者之间差异很小（组间差异显著，p = 0.007）。相比之下，重度哮喘患者的灌洗液中中性粒细胞浓度是轻中度哮喘患者或正常对照组的两倍（各组间p = 0.032，重度哮喘患者和两组对照组间p < 0.05）。在支气管内和经支气管活检标本中获得了类似的结果，这些结果一致显示重度哮喘患者的中性粒细胞数量显著高于对照组。类花生酸介质血栓素和白三烯B-4在重度哮喘组中也最高（组间差异分别为p = 0.019和p = 0.023）。这些发现表明，尽管用高剂量糖皮质激素治疗，炎症仍然存在于严重症状性哮喘患者中，这可能是由于疾病的严重程度、糖皮质激素治疗或其他尚未确定的因素。
The role of inflammation in the pathogenesis of severe asthma chronically treated with high doses of glucocorticoids is poorly understood. Despite this, treatment has been aimed at advancing antiinflammatory and immunomodulator therapy. This study was designed to evaluate both the presence and type of airway inflammation in patients with severe asthma. A prospective bronchoscopic study evaluated 14 severe, high-dose oral glucocorticoid dependent asthmatics. Bronchoalveolar lavage fluid was analyzed for cytology and inflammatory mediators. Endobronchial and transbronchial biopsies were performed in selected patients for morphometric evaluation of macrophage/monocytes, neutrophils, eosinophils and lymphocytes. These results were compared with lavage and endo- and transbronchial biopsy studies in normal controls and patients with moderate asthma. The concentration of eosinophils in bronchoalveolar lavage fluid was highest in the moderate asthmatics not on glucocorticoids, with very little difference between normal controls and severe asthmatics (significant difference among the groups, p = 0.007). In contrast, the severe asthmatics demonstrated a twofold higher concentration of neutrophils in lavage than either the mild-moderate asthmatics, or the normal controls (p = 0.032 among the groups, p < 0.05 between the severe asthmatics and both controls). Similar results were obtained in the endobronchial and transbronchial biopsy specimens, which consistently showed significantly higher numbers of neutrophils in the severe asthmatics than in the control groups. The eicosanoid mediators, thromboxane and leukotriene B-4, were also highest in the severe asthma group (differences among the groups, p = 0.019 and p = 0.023, respectively). These findings suggest that inflammation remains in severe symptomatic asthmatics despite treatment with high dose glucocorticoids which may be due to the severity of disease, glucocorticoid treatment, or other as yet undefined factors.