Sputum hyaluronan and versican in severe eosinophilic asthma.

Sputum hyaluronan and versican in severe eosinophilic asthma.
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DOI:
10.1159/000343031
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发表时间:
2013
影响因子:
2.8
通讯作者:
Nair P
Nair P
中科院分区:
医学3区
文献类型:
--
作者:
Ayars AG;Altman LC;Potter-Perigo S;Radford K;Wight TN;Nair P

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我们检测了服用甲波利单抗(抗IL-5单抗)与安慰剂治疗的哮喘患者痰中透明质酸(一种基质糖胺聚糖)和维西康(一种基质蛋白多糖)的水平,以评估这些测量作为哮喘控制和气道重塑的可能生物标志物的有效性。严重的泼尼松依赖型哮喘患者接受甲波利单抗或安慰剂治疗,如先前发表的一项随机、双盲、安慰剂对照研究所述。我们用酶联免疫吸附试验(ELISA)检测治疗前和治疗16周后收集的痰中透明质酸和万西康的水平。如果患者病情没有恶化,患者将接受预先定义的泼尼松逐渐减少计划,并监测痰嗜酸粒细胞百分比、哮喘控制问卷(ACQ)和肺活量测定。在甲波利单抗治疗和泼尼松逐渐减少6个月后,安慰剂组的痰透明质酸显著高于基线(P=0.003)。相比之下,与安慰剂组相比,积极治疗组痰中透明质酸显著降低(P=0.007),这与FEV1%(P=0.001)和ACQ评分(P=0.009)的改善以及痰中嗜酸粒细胞的减少(P=0.02)有关。安慰剂组的痰通西肯增加不明显(P=0.16),美波利单抗组的痰通西肯减少(P=0.13),痰通西卡减少与FEV1%改善呈显著负相关(P=0.03)。用美波利单抗治疗后,痰中透明质酸值降低,并与临床和肺活量测定值的改善相关,提示这项测量可作为哮喘控制的非侵入性生物标志物。
We examined levels of hyaluronan, a matrix glycosaminoglycan and versican, a matrix proteoglycan, in the sputum of asthmatics treated with mepolizumab (anti-IL-5 mAb) versus placebo to evaluate the utility of these measurements as possible biomarkers of asthma control and airway remodeling. Severe, prednisone-dependent asthmatics received either mepolizumab or placebo as described in a previously published randomized, double blind, placebo controlled study. We measured hyaluronan and versican levels by enzyme-linked immunosorbent assay (ELISA) in sputum collected before and after the 16-week treatment phase. Patients underwent a predefined prednisone tapering schedule if they remained exacerbation free and sputum eosinophil percentage, asthma control questionnaire (ACQ) and spirometry were monitored. After 6 months of mepolizumab therapy and prednisone tapering there was a significant increase in sputum hyaluronan in the placebo group compared with baseline (P=0.003). In contrast, there was a significant decrease in sputum hyaluronan in the active treatment group compared with placebo (P=0.007) which correlated with improvements in FEV1% (P=0.001) and ACQ scores (P=0.009) as well as a decrease in sputum eosinophils (P=0.02). There was a non-significant increase in sputum versican in the placebo group (P=0.16), a decrease in the mepolizumab group (P=0.13) and a significant inverse correlation between versican reduction and FEV1% improvement (P=0.03). Sputum hyaluronan values are reduced with mepolizumab therapy and correlate with improved clinical and spirometry values suggesting this measurement may serve as a non-invasive biomarker of asthma control.
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