Wenzel S E, Szefler S J, Leung D Y, Sloan S I, Rex M D, Martin R J
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA.
Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):737-43. doi: 10.1164/ajrccm.156.3.9610046.
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 anti-inflammatory 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 B4, 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.
高剂量糖皮质激素长期治疗的重度哮喘发病机制中炎症的作用尚不清楚。尽管如此，治疗一直致力于推进抗炎和免疫调节治疗。本研究旨在评估重度哮喘患者气道炎症的存在情况和类型。一项前瞻性支气管镜研究评估了14名重度、高剂量口服糖皮质激素依赖型哮喘患者。对支气管肺泡灌洗液进行细胞学和炎症介质分析。对部分患者进行支气管内和经支气管活检，以对巨噬细胞/单核细胞、中性粒细胞、嗜酸性粒细胞和淋巴细胞进行形态计量学评估。将这些结果与正常对照和中度哮喘患者的灌洗及支气管内和经支气管活检研究结果进行比较。未使用糖皮质激素的中度哮喘患者支气管肺泡灌洗液中嗜酸性粒细胞浓度最高，正常对照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，重度哮喘患者灌洗液中中性粒细胞浓度比轻度至中度哮喘患者或正常对照者高出两倍（组间p = 0.032，重度哮喘患者与两个对照组之间p < 0.05）。支气管内和经支气管活检标本也得到了类似结果，重度哮喘患者的中性粒细胞数量始终显著高于对照组。类花生酸介质血栓素和白三烯B4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，尽管使用了高剂量糖皮质激素治疗，但重度症状性哮喘患者仍存在炎症，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明确的因素所致。
