Department of Pediatrics and Child Neurology, Oita University, Oita, Japan.
Pediatr Allergy Immunol. 2010 May;21(3):489-92. doi: 10.1111/j.1399-3038.2009.00941.x.
To elucidate the mechanisms of intractable pediatric bronchial asthma and the indication of low-dose erythromycin (EM) therapy, the serum chemokine levels of and the angiogenic factor were evaluated in 55 pediatric patients with bronchial asthma; 7.4 +/- 3.5 yr old, who had been treated with inhaled steroid, leukotriene receptor antagonist, theophylline and others for more than a year. Both the levels of interleukin (IL) 8 (p = 0.036) and vascular endothelial growth factor (VEGF) (p = 0.005) were higher in patients with severe type than those of patients with the milder type, while other chemokine levels such as serum eotaxin and MCP1 did not show the correlation with the severity of bronchial asthma. Induction of therapy with low-dose EM induced improvement of the clinical symptoms in patients with severe type and decrease of their serum chemokine levels: IL8; from 736 +/- 88 to 75 +/- 85 pg/ml (p < 0.0005), and VEGF; from 352.0 +/- 160.5 to 132.2 +/- 59.9 pg/ml (p = 0.021) within the next 6 months. Moreover, low-dose EM resulted in a decreased daily peak-trough fluctuation rate of the serum theophylline concentration; (C(max )- C(min))/C(min), from 1.3 +/- 0.5 to 0.5 +/- 0.3, which led to the maintenance of effective serum levels. These results indicated that IL8 and VEGF affect the severity of standard therapies resistance intractable bronchial asthma. Through the suppression of these chemokines and maintenance of effective theophylline levels, low-dose EM therapy improves the symptoms of bronchial asthma.
为了阐明难治性小儿支气管哮喘的机制和低剂量红霉素(EM)治疗的适应证,评估了 55 例支气管哮喘患儿的血清趋化因子水平和血管生成因子;7.4 +/- 3.5 岁,已接受吸入性类固醇、白三烯受体拮抗剂、茶碱等治疗超过一年。重度患儿的白细胞介素(IL)8(p = 0.036)和血管内皮生长因子(VEGF)(p = 0.005)水平均高于轻度患儿,而其他趋化因子水平如血清嗜酸性粒细胞趋化因子和 MCP1 与支气管哮喘的严重程度无相关性。低剂量 EM 诱导治疗可改善重度患儿的临床症状,并降低其血清趋化因子水平:IL8;从 736 +/- 88 降至 75 +/- 85 pg/ml(p < 0.0005),VEGF;从 352.0 +/- 160.5 降至 132.2 +/- 59.9 pg/ml(p = 0.021),在接下来的 6 个月内。此外,低剂量 EM 导致血清茶碱浓度的日峰-谷波动率(C(max )- C(min))/C(min)从 1.3 +/- 0.5 降至 0.5 +/- 0.3,从而维持有效的血清水平。这些结果表明,IL8 和 VEGF 影响标准治疗耐药性难治性支气管哮喘的严重程度。通过抑制这些趋化因子和维持有效的茶碱水平,低剂量 EM 治疗可改善支气管哮喘症状。