Mass spectrometric analysis of biomarkers and dilution markers in exhaled breath condensate reveals elevated purines in asthma and cystic fibrosis
Mass spectrometric analysis of biomarkers and dilution markers in exhaled breath condensate reveals elevated purines in asthma and cystic fibrosis
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DOI：
10.1152/ajplung.90512.2008
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发表时间：
2009-06-01
影响因子：
4.9
通讯作者：
Boucher, Richard C.
中科院分区：
文献类型：
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作者：
Esther, Charles R., Jr.;Boysen, Gunnar;Boucher, Richard C.
Esther CR Jr, Boysen G, Olsen BM, Collins LB, Ghio AJ, Swenberg JW, Boucher RC。呼气冷凝物中生物标记物和稀释标记物的质谱分析显示哮喘和囊性纤维化中嘌呤升高。[J] .中国生物医学工程学报，2009,31(6):987- 993。首次发表于2009年3月20日；doi: 10.1152 / ajplung.90512.2008。呼气冷凝物（EBC）分析有望成为一种简单且无创的方法来测量气道生物标志物，但在方法上存在相当大的挑战。在两项研究中，我们利用质谱法测量EBC嘌呤生物标志物腺苷和AMP加尿素，以控制稀释变异性：1)对28名健康儿童、40名囊性纤维化（CF）儿童和11名哮喘儿童进行横断面分析；2)对26例CF患儿肺加重治疗前后的纵向分析。EBC的腺苷、AMP和尿素很容易通过质谱法检测和定量，分析表明稀释变异性显著。使用生物标记物与尿素比率作为稀释对照，CF患者的EBC amp与尿素比率高于对照组（中位数为1.3，四分位间距（IQR） 0.7-2.3）（中位数为0.75，IQR为0.3-1.4,P < 0.05），哮喘患者的腺苷与尿素比率高于对照组（中位数为1.5，IQR为0.9-2.9）（中位数为0.4，IQR为0.2-1.6,P < 0.05）。CF加重治疗后EBC嘌呤-尿素比值的变化与1 s内预测用力呼气量百分比（FEV(1)）的变化相关（r = -0.53 AMP/尿素，r = -0.55腺苷/尿素；两者P < 0.01）。使用血清与EBC尿素比或EBC电解质计算的稀释因子观察到类似的结果，CF和对照组EBC电解质与尿素的可比比率（中位数为3.2，IQR为1.6-6.0 CF；中位数为5.5，IQR为1.4-7.7对照组）验证了气道尿素作为EBC稀释标记物的使用。这些结果表明，质谱分析可以应用于EBC中嘌呤的测量，并证明EBC中腺苷与尿素和amp与尿素的比率是气道疾病的潜在无创生物标志物。
Esther CR Jr, Boysen G, Olsen BM, Collins LB, Ghio AJ, Swenberg JW, Boucher RC. Mass spectrometric analysis of biomarkers and dilution markers in exhaled breath condensate reveals elevated purines in asthma and cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 296: L987-L993, 2009. First published March 20, 2009; doi: 10.1152/ajplung.90512.2008.-Exhaled breath condensate (EBC) analyses promise simple and noninvasive methods to measure airway biomarkers but pose considerable methodological challenges. We utilized mass spectrometry to measure EBC purine biomarkers adenosine and AMP plus urea to control for dilutional variability in two studies: 1) a cross-sectional analysis of 28 healthy, 40 cystic fibrosis (CF), and 11 asthmatic children; and 2) a longitudinal analysis of 26 CF children before and after treatment of a pulmonary exacerbation. EBC adenosine, AMP, and urea were readily detected and quantified by mass spectrometry, and analysis suggested significant dilutional variability. Using biomarker-to-urea ratios to control for dilution, the EBC AMP-to-urea ratio was elevated in CF [median 1.3, interquartile range (IQR) 0.7-2.3] vs. control (median 0.75, IQR 0.3-1.4; P < 0.05), and the adenosine-to-urea ratio was elevated in asthma (median 1.5, IQR 0.9-2.9) vs. control (median 0.4, IQR 0.2-1.6; P < 0.05). Changes in EBC purine-to-urea ratios correlated with changes in percent predicted forced expiratory volume in 1 s (FEV(1)) (r = -0.53 AMP/urea, r = -0.55 adenosine/ urea; P < 0.01 for both) after CF exacerbation treatment. Similar results were observed using dilution factors calculated from serum-to-EBC urea ratios or EBC electrolytes, and the comparable ratios of EBC electrolytes to urea in CF and control (median 3.2, IQR 1.6-6.0 CF; median 5.5, IQR 1.4-7.7 control) validated use of airway urea as an EBC dilution marker. These results show that mass spectrometric analyses can be applied to measurement of purines in EBC and demonstrate that EBC adenosine-to-urea and AMP-to-urea ratios are potential noninvasive biomarkers of airways disease.