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重度肺动脉高压患者呼出气冷凝物中挥发性化合物的分析

Analysis of volatile compounds in exhaled breath condensate in patients with severe pulmonary arterial hypertension.

作者信息

Mansoor J K, Schelegle Edward S, Davis Cristina E, Walby William F, Zhao Weixiang, Aksenov Alexander A, Pasamontes Alberto, Figueroa Jennifer, Allen Roblee

机构信息

Department of Physical Therapy, University of the Pacific, Stockton, California, United States of America.

Department of Anatomy, Physiology and Cell Biology, University of California Davis, Davis, California, United States of America.

出版信息

PLoS One. 2014 Apr 18;9(4):e95331. doi: 10.1371/journal.pone.0095331. eCollection 2014.

Abstract

BACKGROUND

An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH.

METHODOLGY AND FINDINGS

Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients.

CONCLUSIONS

These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH.

摘要

背景

肺动脉高压(PAH)诊断和治疗面临的一项重大挑战是早期发现隐匿性肺血管病变。症状常与其他疾病实体相混淆,导致不适当的干预,并使疾病进展至晚期。迫切需要开发用于PAH早期疾病检测和管理的新标志物。

方法与结果

比较了30名年龄匹配的正常健康个体与27名纽约心脏协会功能分级为III级和IV级的特发性肺动脉高压(IPAH)患者(PAH的一个亚组)的呼出气冷凝物(EBC)样本。使用气相色谱/质谱联用仪(GC/MS)分析EBC样本中的挥发性有机化合物(VOC)。在两组中均鉴定出GC图谱中的各个峰,并将其与IPAH组的肺血流动力学和临床终点相关联。此外,使用自回归随后进行偏最小二乘回归(AR/PLSR)分析对GC/MS数据进行分析,以区分IPAH组和对照组。校正药物因素后,对照组中有62种独特化合物,IPAH组中有32种独特化合物,两组间有14种共同化合物。对IPAH组EBC样本的GC图谱进行逐峰分析,鉴定出6种与IPAH诊断中重要的肺血流动力学变量显著相关的化合物。对GC/MS数据进行AR/PLSR分析,得出了IPAH患者独特且可识别的代谢特征。

结论

这些发现表明EBC中VOC分析在区分重度IPAH与健康人群方面具有实用性;此外,我们鉴定出了与IPAH肺血流动力学变量相关的潜在新型生物标志物,这些标志物可能在筛查较轻形式的IPAH中具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b02a/3991617/3a16dfd43a91/pone.0095331.g001.jpg

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