Carpagnano G E, Lacedonia D, Carone M, Soccio P, Cotugno G, Palmiotti G A, Scioscia G, Foschino Barbaro M P
Department of Medical and Surgical Sciences, Institute of Respiratory Diseases, University of Foggia, Foggia, Italy.
J Breath Res. 2016 Apr 11;10(2):026005. doi: 10.1088/1752-7155/10/2/026005.
Mitochondrial DNA (MtDNA) has been studied as an expression of oxidative stress in asthma, COPD, lung cancer and obstructive sleep apnea, but it has been mainly investigated systemically, although the pathogenetic mechanisms begin in the airways and only later progress to systemic circulation. The aim of this study was to investigate the MtDNA alterations in the exhaled breath condensate (EBC) of patients with asthma, COPD and asthma-COPD overlap syndrome (ACOS). In order to analyze better what happens to mitochondria, both locally and systemically, we compared MtDNA/nDNA in blood and EBC of paired patients. Thirteen (13) COPD patients, 14 asthmatics, 23 ACOS (10 according to Spanish guidelines, 13 in line with GINA guidelines) and 12 healthy subjects were enrolled. Patients underwent clinical and functional diagnostic tests as foreseen by the guidelines. They underwent blood and EBC collection. Content of MtDNA and nuclear DNA (nDNA) was measured in the blood cells and EBC of patients by Real Time PCR. The ratio between MtDNA/nDNA was calculated. For the first time we were able to detect MtDNA/nDNA in the EBC. We found higher exhaled MtDNA/nDNA in COPD, asthmatic and ACOS patients respectively compared to healthy subjects (21.9 ± 4.9 versus 6.51 ± 0.21, p < 0.05; 7.9 ± 2.5 versus 6.51 ± 0.21, p = 0.06; 18.3 ± 3.4 versus 6.51 ± 0.21, p < 0.05). The level of exhaled MtDNA/nDNA was positively correlated with the plasmatic one. The levels of MtDNA/nDNA in the EBC, as expression of oxidative stress, are increased in COPD, asthmatic and ACOS patients compared to healthy subjects. These are preliminary results in a small number of well characterized patients that requires confirmation on a larger population. We support new studies directed toward the analysis of exhaled MtDNA/nDNA as a new exhaled non-invasive marker in other inflammatory/oxidative airways diseases.
线粒体DNA（MtDNA）已被作为哮喘、慢性阻塞性肺疾病（COPD）、肺癌和阻塞性睡眠呼吸暂停中氧化应激的一种表现进行研究，但主要是全身性研究，尽管其发病机制始于气道，随后才进展到体循环。本研究的目的是调查哮喘、COPD和哮喘-COPD重叠综合征（ACOS）患者呼出气冷凝液（EBC）中的MtDNA改变。为了更好地分析线粒体在局部和全身发生了什么变化，我们比较了配对患者血液和EBC中的MtDNA/核DNA（nDNA）。纳入了13例COPD患者、14例哮喘患者、23例ACOS患者（10例符合西班牙指南，13例符合全球哮喘防治创议（GINA）指南）和12例健康受试者。患者按照指南进行了临床和功能诊断测试。他们进行了血液和EBC采集。通过实时荧光定量PCR测量患者血细胞和EBC中MtDNA和核DNA（nDNA）的含量。计算MtDNA/nDNA的比值。我们首次在EBC中检测到MtDNA/nDNA。我们发现，与健康受试者相比，COPD、哮喘和ACOS患者呼出的MtDNA/nDNA分别更高（21.9±4.9对6.51±0.21，p<0.05；7.9±2.5对6.51±0.21，p=0.06；18.3±3.4对6.51±0.21，p<0.05）。呼出的MtDNA/nDNA水平与血浆中的水平呈正相关。与健康受试者相比，COPD、哮喘和ACOS患者EBC中作为氧化应激表现的MtDNA/nDNA水平升高。这些是在少数特征明确的患者中得到的初步结果，需要在更大规模人群中进行验证。我们支持开展新的研究，将呼出MtDNA/nDNA分析作为其他炎症/氧化性气道疾病新的呼出无创标志物。
