气道中的超细颗粒：慢性阻塞性肺疾病急性加重风险和炎症状态的一种新型标志物。
Ultrafine particles in airways: a novel marker of COPD exacerbation risk and inflammatory status.
作者信息
Fireman Klein Einat, Adir Yochai, Krencel Amir, Peri Regina, Vasserman Bella, Fireman Elizabeth, Kessel Aharon
机构信息
Pulmonary Division, Carmel Medical Center, Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel,
Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel.
出版信息
Int J Chron Obstruct Pulmon Dis. 2019 Mar 1;14:557-564. doi: 10.2147/COPD.S187560. eCollection 2019.
PURPOSE
Ultrafine particles (UFP) are toxic due to their small size and penetration into deeper lung compartments. We aimed to evaluate the exhaled breath condensate (EBC)-UFP content as a reflection of inflammation and oxidative stress status in COPD patients and as an exacerbation risk marker.
METHODS
EBC was collected by conventional methods. Particles were analyzed with NanoSight LM20. EBC carbonyl and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured using ELISA kits. Study population (58 COPD patients and 40 healthy smoker and non-smoker controls) underwent spirometry, diffusion capacity, EBC testing, and blood sampling.
RESULTS
Absolute eosinophil count, C-reactive protein (CRP), and lactate dehydrogenase in serum were elevated in the COPD group compared with the controls (224 U/L, 5 mg/L, and 391 U/L vs 154 U/L, 3 mg/L, and 330 U/L, =0.009, =0.05, and =0.004, respectively). COPD patients had lower UFP concentrations in EBC compared with controls (0.24 E8/mL vs 0.51 E8/mL, ≤0.001). A mirror image was detected in serum: COPD patients had higher UFP concentrations compared with controls (9.8 E8/mL vs 6.7 E8/mL, respectively, =0.03). EBC carbonyl and 8-OHdG levels were higher among COPD patients compared with controls (5.1 per 1 µg/mL protein and 0.036 ng/mL vs 0.41 per 1 µg/mL protein and 0.003 ng/mL, =0.001 and ≤0.001, respectively). EBC UFP concentrations were negatively correlated with pack years (=-0.44, ≤0.001) and positively correlated with FEV and diffusing lung capacity for carbon monoxide (=0.46, 0.23, ≤0.001 and =0.04, respectively). Low EBC UFP concentrations (≤0.18 E8/mL) and CRP levels ≥5 mg/L were independent predictors of the frequent exacerbator phenotype (OR 3.6; 95% CI: 1.06-7.97; =0.04 and OR 4.4; 95% CI: 1.24-10.2; =0.02, respectively).
CONCLUSION
UFP content in EBC reflects the inflammatory state of airways. Low UFP concentrations in EBC and high in serum of COPD patients support our hypothesis that increased epithelial permeability could be the mechanism behind those findings.
目的
超细颗粒物（UFP）因其体积小且能深入肺部更深区域而具有毒性。我们旨在评估呼出气冷凝物（EBC）中的UFP含量，以反映慢性阻塞性肺疾病（COPD）患者的炎症和氧化应激状态，并作为病情加重风险标志物。
方法
采用常规方法收集EBC。使用纳米视镜LM20分析颗粒。使用酶联免疫吸附测定试剂盒测量EBC中的羰基和8-羟基脱氧鸟苷（8-OHdG）水平。研究人群（58例COPD患者以及40名健康吸烟者和非吸烟者对照）接受了肺功能测定、弥散功能测定、EBC检测和血液采样。
结果
与对照组相比，COPD组血清中的绝对嗜酸性粒细胞计数、C反应蛋白（CRP）和乳酸脱氢酶升高（分别为224 U/L、5 mg/L和391 U/L，而对照组为154 U/L、3 mg/L和330 U/L，P = 0.009、P = 0.05和P = 0.004）。与对照组相比，COPD患者EBC中的UFP浓度较低（0.24×10⁸/mL对0.51×10⁸/mL，P≤0.001）。在血清中检测到相反的情况：与对照组相比，COPD患者的UFP浓度较高（分别为9.8×10⁸/mL对6.7×10⁸/mL，P = 0.03）。与对照组相比，COPD患者EBC中的羰基和8-OHdG水平较高（每1μg/mL蛋白质中分别为5.1和0.036 ng/mL，而对照组为每1μg/mL蛋白质中0.41和0.003 ng/mL，P = 0.001和P≤0.001）。EBC中的UFP浓度与吸烟包年数呈负相关（r = -0.44，P≤0.001），与第一秒用力呼气容积（FEV₁）和一氧化碳弥散量呈正相关（r分别为0.46、0.23，P≤0.001和P = 0.04）。低EBC UFP浓度（≤0.18×10⁸/mL）和CRP水平≥5 mg/L是频繁急性加重型表型的独立预测因素（分别为OR 3.6；95%置信区间：1.06 - 7.97；P = 0.04和OR 4.4；95%置信区间：1.24 - 10.2；P = 0.02）。
结论
EBC中的UFP含量反映气道的炎症状态。COPD患者EBC中UFP浓度低而血清中UFP浓度高，支持了我们的假设，即上皮通透性增加可能是这些发现背后的机制。
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