血管通透性增加先于细胞炎症预示哮喘控制的恶化
2010/02/23
背景：哮喘患者气道微血管存在异常，但血管变化在哮喘恶化中的作用仍不明确。我们希望通过吸入性糖皮质激素（ICS）剂量递减模型评估血管变化伴随的哮喘恶化。
目的：评价由气道ICS 反滴定诱导的哮喘恶化中的血管分布、血管通透性和血管内皮生长因子（VEGF）表达。
方法：纳入20例接受低-中等剂量ICS治疗的伴轻-中度持续性症状的哮喘患者。使用大剂量丙酸氟替卡松（1000 μg/天）连续治疗4周控制症状，然后在4～8周内剂量逐步减少至研究前剂量的一半，直至出现哮喘症状，并获取以上两个治疗期后的支气管组织和支气管肺泡灌洗液（BAL）样本。
结果：随着ICS剂量的降低，通过血管数量和大小测量的血管分布和VEGF的表达无变化。即使是给予高剂量ICS，哮喘患者血管周围白蛋白染色和BAL中微白蛋白水平（两者作为血管通透性的标志）与正常受试者相比仍然增加，且随着ICS剂量递减，两者进一步显著增加。血管渗漏与哮喘临床恶化显著相关。气道白蛋白增加与先前报告的气道壁T淋巴细胞浸润相关。
结论：我们的结果显示，气道血管渗漏是哮喘早期恶化的主要病理生理学特征，其出现早于细胞炎症复发。
（刘国梁 审校）
Clin Exp Allergy. 2009 Nov;39(11):1659-1667.
Increased vascular permeability precedes cellular inflammation as asthma control deteriorates.
Khor YH, Teoh AK, Lam SM, Mo DC, Weston S, Reid DW, Walters EH.
BACKGROUND: Airway microcirculation is abnormal in asthma but the role of vascular changes in asthma deteriorations remains poorly defined. We prospectively assessed the vascular changes accompanying worsening of asthma control by using an inhaled corticosteroid (ICS) dose-reduction model.
OBJECTIVES: To evaluate airway vascularity, vascular permeability and expression of vascular endothelial growth factor (VEGF) in early asthma deterioration induced by ICS back-titration.
METHODS: Twenty mild-to-moderate persistent symptomatic asthmatics on low-to-moderate ICS were recruited and treated with 4 weeks of high-dose fluticasone propionate (1000 microg/day) to achieve symptom control. This was followed by dose reduction to half of the pre-study doses for 4-8 weeks until the symptoms began to return. Endobronchial biopsy and bronchoalveolar lavage (BAL) samples were obtained after both treatment periods.
RESULTS: Vascularity as measured by the number and size of blood vessels, as well as VEGF expression did not change following ICS reduction. Even on high-dose ICS, perivascular albumin staining and BAL microalbumin levels in asthmatic subjects, as markers of permeability, were elevated when compared with normal subjects and both further increased significantly after ICS reduction. There was a significant association between changes in vascular leakiness and clinical deterioration. Increases in airway albumin correlated with previously reported increases in airway wall infiltration with T lymphocytes.
CONCLUSIONS: Our results suggest that airway vascular leakage is a major pathophysiologic feature of early asthma deterioration, occurring before recrudescence of cellular inflammation.
Khor YH, Teoh AK, Lam SM, et al. Clin Exp Allergy. 2009 Nov;39(11):1659-67.
目的：评价由气道ICS 反滴定诱导的哮喘恶化中的血管分布、血管通透性和血管内皮生长因子（VEGF）表达。
方法：纳入20例接受低-中等剂量ICS治疗的伴轻-中度持续性症状的哮喘患者。使用大剂量丙酸氟替卡松（1000 μg/天）连续治疗4周控制症状，然后在4～8周内剂量逐步减少至研究前剂量的一半，直至出现哮喘症状，并获取以上两个治疗期后的支气管组织和支气管肺泡灌洗液（BAL）样本。
结果：随着ICS剂量的降低，通过血管数量和大小测量的血管分布和VEGF的表达无变化。即使是给予高剂量ICS，哮喘患者血管周围白蛋白染色和BAL中微白蛋白水平（两者作为血管通透性的标志）与正常受试者相比仍然增加，且随着ICS剂量递减，两者进一步显著增加。血管渗漏与哮喘临床恶化显著相关。气道白蛋白增加与先前报告的气道壁T淋巴细胞浸润相关。
结论：我们的结果显示，气道血管渗漏是哮喘早期恶化的主要病理生理学特征，其出现早于细胞炎症复发。
（刘国梁 审校）
Clin Exp Allergy. 2009 Nov;39(11):1659-1667.
Increased vascular permeability precedes cellular inflammation as asthma control deteriorates.
Khor YH, Teoh AK, Lam SM, Mo DC, Weston S, Reid DW, Walters EH.
BACKGROUND: Airway microcirculation is abnormal in asthma but the role of vascular changes in asthma deteriorations remains poorly defined. We prospectively assessed the vascular changes accompanying worsening of asthma control by using an inhaled corticosteroid (ICS) dose-reduction model.
OBJECTIVES: To evaluate airway vascularity, vascular permeability and expression of vascular endothelial growth factor (VEGF) in early asthma deterioration induced by ICS back-titration.
METHODS: Twenty mild-to-moderate persistent symptomatic asthmatics on low-to-moderate ICS were recruited and treated with 4 weeks of high-dose fluticasone propionate (1000 microg/day) to achieve symptom control. This was followed by dose reduction to half of the pre-study doses for 4-8 weeks until the symptoms began to return. Endobronchial biopsy and bronchoalveolar lavage (BAL) samples were obtained after both treatment periods.
RESULTS: Vascularity as measured by the number and size of blood vessels, as well as VEGF expression did not change following ICS reduction. Even on high-dose ICS, perivascular albumin staining and BAL microalbumin levels in asthmatic subjects, as markers of permeability, were elevated when compared with normal subjects and both further increased significantly after ICS reduction. There was a significant association between changes in vascular leakiness and clinical deterioration. Increases in airway albumin correlated with previously reported increases in airway wall infiltration with T lymphocytes.
CONCLUSIONS: Our results suggest that airway vascular leakage is a major pathophysiologic feature of early asthma deterioration, occurring before recrudescence of cellular inflammation.
Khor YH, Teoh AK, Lam SM, et al. Clin Exp Allergy. 2009 Nov;39(11):1659-67.
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分析间隔对呼出气一氧化氮多导呼出气流分段技术的影响
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甘露醇激发试验在评价哮喘患者气道反应性、气道炎症及炎症表型中的作用
