Elevated Airway Purines in COPD
Elevated Airway Purines in COPD
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DOI：
10.1378/chest.10-2471
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发表时间：
2011-10-01
期刊：
影响因子：
9.6
通讯作者：
Boucher, Richard C.
中科院分区：
文献类型：
--
作者：
Esther, Charles R., Jr.;Lazaar, Aili L.;Boucher, Richard C.
背景资料：腺苷和相关嘌呤在炎症中的作用已经确定，并且在COPD患者中预测气道浓度升高。然而，在采集典型呼吸道样本过程中，由于嘌呤释放的刺激，准确的气道表面嘌呤测量可能会受到干扰。从36名健康的非吸烟者中无创性地收集呼吸道样本作为呼出气冷凝液（EBC 28名健康吸烟者（S组）和89名COPD受试者（29例GOLD [慢性阻塞性肺疾病全球倡议] II期，29例GOLD III期，31例GOLD IV期），并用质谱法分析腺苷、腺苷一磷酸（AMP）和苯丙氨酸，加上尿素作为稀释标记物。使用与尿素的比例控制EBC中气道分泌物的可变稀释度，并使用EBC与血清尿素基稀释因子计算气道表面浓度。EBC腺苷/尿素比值在NS中相似（0.20 ± 0.21）和S组（0.22 ± 0.20），但COPD组升高（0.32 ± 0.30，P <0.01 vs NS）。腺苷/尿素比值在病情最严重的队列中最高（GOLD IV，0.35 +/- 0.34，P <0.01 vs NS），与FEV（1）呈负相关（r =-0.27，P <0.01）。在COPD组中也观察到AMP与尿素的比值升高（0.58 +/- 0.97 COPD，0.29 +/- 0.35 NS，P <0.02），但苯丙氨酸与尿素的比值在所有组中相似。在COPD患者（n = 28）的一个亚组中计算的气道表面腺苷浓度为3.2 ± 2.7 μ M，而NS组为1.7 ± 1.5 μ M结论：气道嘌呤以生理学上显著的浓度存在于气道表面，在COPD中升高，并且与COPD严重程度的标志物相关。嘌呤能信号通路是COPD潜在的治疗靶点，EBC嘌呤是潜在的非侵入性生物标志物。胸部2011; 140（4）：954-960
Background: Adenosine and related purines have established roles in inflammation, and elevated airway concentrations are predicted in patients with COPD. However, accurate airway surface purine measurements can be confounded by stimulation of purine release during collection of typical respiratory samples.Methods: Airway samples were collected noninvasively as exhaled breath condensate (EBC) from 36 healthy nonsmokers (NS group), 28 healthy smokers (S group), and 89 subjects with COPD (29 with GOLD [Global Initiative for Chronic Obstructive Lung Disease] stage II, 29 with GOLD stage III, and 31 with GOLD stage IV) and analyzed with mass spectrometry for adenosine, adenosine monophosphate (AMP), and phenylalanine, plus urea as a dilution marker. Variable dilution of airway secretions in EBC was controlled using ratios to urea, and airway surface concentrations were calculated using EBC to serum urea-based dilution factors.Results: EBC adenosine to urea ratios were similar in NS (0.20 +/- 0.21) and S (0.22 +/- 0.20) groups but elevated in those with COPD (0.32 +/- 0.30, P < .01 vs NS). Adenosine to urea ratios were highest in the most severely affected cohort (GOLD IV, 0.35 +/- 0.34, P < .01 vs NS) and negatively correlated with FEV(1) (r = -0.27, P < .01). Elevated AMP to urea ratios were also observed in the COPD group (0.58 +/- 0.97 COPD, 0.29 +/- 0.35 NS, P < .02), but phenylalanine to urea ratios were similar in all groups. Airway surface adenosine concentrations calculated in a subset of subjects were 3.2 +/- 2.7 mu M in those with COPD (n = 28) relative to 1.7 +/- 1.5 mu M in the NS group (n = 16, P < .05).Conclusions: Airway purines are present on airway surfaces at physiologically significant concentrations, are elevated in COPD, and correlate with markers of COPD severity. Purinergic signaling pathways are potential therapeutic targets in COPD, and EBC purines are potential noninvasive biomarkers. CHEST 2011; 140(4):954-960