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血浆和尿脱氧木糖作为慢性阻塞性肺疾病生物标志物的临床有效性。

Clinical validity of plasma and urinary desmosine as biomarkers for chronic obstructive pulmonary disease.

机构信息

Translational Medicine Research Collaboration, Dundee, UK.

出版信息

Thorax. 2012 Jun;67(6):502-8. doi: 10.1136/thoraxjnl-2011-200279. Epub 2012 Jan 16.

Abstract

BACKGROUND

Although an increased concentration of degraded elastin products in patients with chronic obstructive pulmonary disease (COPD) has been reported for many years, its clinical validity and utility remain uncertain due to technical difficulties, small study groups and the unknown relationship between exacerbation and elastin degradation. The objectives of this study were to determine the validity of urinary and blood total desmosine/isodesmosine in patients with COPD and asthma and to evaluate their relationship to exacerbation status and lung function.

METHODS

Urinary and blood desmosine levels were measured using validated isotopic dilution liquid chromatography-tandem mass spectrometry methods.

RESULTS

390 study participants were recruited from the following groups: healthy volunteers, stable asthma, stable and 'during an exacerbation' COPD. Compared with healthy non-smokers, we found increased urinary or blood desmosine levels in patients with COPD, but no differences in patients with asthma or healthy smokers. The elevation of urinary desmosine levels was associated with the exacerbation status in patients with COPD. Approximately 40% of patients with stable and 'during an exacerbation' COPD showed elevated blood desmosine levels. Blood desmosine levels were strongly associated with age and were negatively correlated with lung diffusing capacity for carbon monoxide.

CONCLUSION

The results suggest that urinary desmosine levels are raised by exacerbations of COPD whereas blood desmosine levels are elevated in a subgroup of patients with stable COPD and reduced lung diffusing capacity. The authors speculate that a raised blood desmosine level may identify patients with increased elastin degradation suitable for targeted therapy. Future prospective studies are required to investigate this hypothesis.

摘要

背景

尽管多年来一直有报道称慢性阻塞性肺疾病(COPD)患者体内降解的弹性蛋白产物浓度升高,但由于技术困难、研究小组规模较小以及加重与弹性蛋白降解之间的未知关系,其临床有效性和实用性仍不确定。本研究的目的是确定 COPD 和哮喘患者尿液和血液总脱氧异戊烯素/异脱氧异戊烯素的有效性,并评估其与加重状态和肺功能的关系。

方法

使用经过验证的同位素稀释液相色谱-串联质谱法测量尿液和血液脱氧异戊烯素水平。

结果

从以下组别的 390 名研究参与者中招募了研究对象:健康志愿者、稳定型哮喘、稳定型和“在加重期”COPD。与健康不吸烟者相比,我们发现 COPD 患者的尿液或血液脱氧异戊烯素水平升高,但哮喘患者或健康吸烟者的差异无统计学意义。尿液脱氧异戊烯素水平升高与 COPD 患者的加重状态相关。大约 40%的稳定型和“在加重期”COPD 患者的血液脱氧异戊烯素水平升高。血液脱氧异戊烯素水平与年龄密切相关,与肺一氧化碳弥散量呈负相关。

结论

结果表明,COPD 加重时尿液脱氧异戊烯素水平升高,而稳定型 COPD 患者中存在血液脱氧异戊烯素水平升高且肺弥散量降低的亚组患者。作者推测,血液脱氧异戊烯素水平升高可能会识别出弹性蛋白降解增加的患者,适合进行靶向治疗。需要进一步的前瞻性研究来验证这一假说。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9744/3358730/b82901d5f34c/thoraxjnl-2011-200279fig1.jpg

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