STEROID-RESISTANT ASTHMA - IMMUNOLOGICAL AND PHARMACOLOGICAL FEATURES
STEROID-RESISTANT ASTHMA - IMMUNOLOGICAL AND PHARMACOLOGICAL FEATURES
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DOI：
10.1016/0091-6749(92)90379-g
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发表时间：
1992-03-01
影响因子：
14.2
通讯作者：
SZEFLER, SJ
中科院分区：
文献类型：
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作者：
ALVAREZ, J;SURS, W;SZEFLER, SJ
糖皮质激素在哮喘治疗中发挥着重要作用；然而，一部分患者反应不佳。 我们评估了 17 名年龄在 16 岁至 69 岁（平均年龄 29 岁）之间的类固醇抵抗 (SR) 哮喘患者（6 名男性和 11 名女性患者）的免疫学和药理学特征。 SR 哮喘被定义为在口服泼尼松（平均剂量，45 毫克/天）2 周疗程后未能改善早晨支气管扩张剂前 FEV1 > 预测值的 60%。 这些患者与 24 名年龄 5 至 70 岁的类固醇敏感 (SS) 患者（平均年龄 17 岁；17 名男性和 7 名女性患者）以及 47 名年龄 20 至 40 岁的健康对照受试者进行比较。 SS 患者的平均泼尼松剂量为 25 毫克/天。 在 6 名 SR 哮喘患者中评估了类固醇药代动力学。 所有研究均在正常范围内。 所有受试者的外周血单核细胞（PBMC）均用10μg/ml的植物血凝素刺激，并与10（-5）至10（-9）mol/L的甲泼尼龙（Mpn）一起孵育72小时。 SR 哮喘患者的 PBMC 的 Mpn 剂量反应曲线表明，与 SS 患者和正常受试者相比，在 Mpn 存在的情况下，与植物血凝素刺激的 PBMC 相比，DNA 合成显着增加（p < 0.05），即 T 细胞增殖更多。 这种 DNA 合成的增强在体外用 10-mu-g/ml 醋竹桃霉素可逆。 我们得出结论，SR 哮喘患者的 PBMC 在 T 细胞有丝分裂原存在的情况下表现出对 Mpn 的反应改变。 尽管接受糖皮质激素治疗，这种细胞反应异常可能会导致 SR 哮喘患者持续出现气道炎症。 此外，这种免疫异常似乎是可逆的。
Glucocorticoids play an important role in asthma therapy; however, a subset of patients are poorly responsive. We evaluated immunologic and pharmacologic features of 17 patients with steroid-resistant (SR) asthma (six male and 11 female patients) between the ages of 16 and 69 years (mean age, 29 years). SR asthma was defined as failure to improve morning prebronchodilator FEV1 > 60% predicted after a 2-week course of oral prednisone (mean dose, 45 mg/day). These patients were compared to 24 steroid-sensitive (SS) patients, aged 5 to 70 years (mean age, 17 years; 17 male and seven female patients), and 47 healthy control subjects, aged 20 to 40 years. Mean prednisone dose in SS patients was 25 mg/day. Steroid pharmacokinetics were evaluated in six patients with SR asthma. All studies were within normal limits. Peripheral blood mononuclear cells (PBMCs) from all subjects were stimulated with 10-mu-g/ml of phytohemagglutinin and incubated for 72 hours with 10(-5) to 10(-9) mol/L of methylprednisolone (Mpn). The Mpn dose-response curve for PBMCs from patients with SR asthma demonstrated a significant (p < 0.05) increase in DNA synthesis, that is, more T cell proliferation than PBMCs stimulated with phytohemagglutinin in the presence of Mpn, as compared to SS patients and normal subjects. This augmentation of DNA synthesis was reversible with 10-mu-g/ml of troleandomycin in vitro. We conclude that PBMCs from patients with SR asthma demonstrate altered response to Mpn in the presence of a T cell mitogen. This abnormality in cellular response may contribute to persistent airway inflammation in patients with SR asthma despite glucocorticoid therapy. Furthermore, this immunologic abnormality appears to be reversible.