Russo Patrizia, Lamonaca Palma, Milic Mirta, Rojas Emilio, Prinzi Giulia, Cardaci Vittorio, Vitiello Laura, Proietti Stefania, Santoro Alessia, Tomino Carlo, Fini Massimo, Bonassi Stefano
Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Roma, Italy.
Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Mutat Res Genet Toxicol Environ Mutagen. 2019 Jul;843:111-117. doi: 10.1016/j.mrgentox.2019.04.003. Epub 2019 Apr 12.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by severe respiratory symptoms. COPD shows several hallmarks of aging, and an increased oxidative stress, which is responsible for different clinical and molecular COPD features, including an increased frequency of DNA damage. The current pharmacological treatment options for COPD are mostly symptomatic, and generally do not influence disease progression and survival. In this framework, pulmonary rehabilitation is the most effective therapeutic strategy to improve physical performance, reducing hospital readmissions and mortality. Response to rehabilitation may greatly differ among patients calling for a personalized treatment. In this paper we will investigate in a group of COPD patients those variables that may predict the response to a program of pulmonary rehabilitation, integrating clinical parameters with cellular and molecular measurements, offering the potential for more effective and individualized treatment options. A group of 89 consecutive COPD patients admitted to a 3-weeks Pulmonary Rehabilitation (PR) program were evaluated for clinical and biological parameters at baseline and after completion of PR. DNA fragmentation in cryopreserved lymphocytes was compared by visual scoring and using the Comet Assay IV analysis system. The comparison of DNA damage before and after PR showed a highly significant increase from 19.6 ± 7.3 at admission to 21.8 ± 7.2 after three weeks of treatment, with a significant increase of 2.46 points (p < 0.001). Higher levels of DNA damage were observed in the group of non- responders and in those patients receiving oxygen therapy. The overall variation of %TI during treatment significantly correlated with the level of pCO at admission and negatively with the level of IL-6 at admission. Measuring the frequency of DNA damage in COPD patients undergoing pulmonary rehabilitation may provide a meaningful biological marker of response and should be considered as additional diagnostic and prognostic criterion for personalized rehabilitation programs.
慢性阻塞性肺疾病（COPD）是一种以严重呼吸道症状为特征的进行性肺部疾病。COPD呈现出衰老的几个特征，以及氧化应激增加，氧化应激是导致不同临床和分子COPD特征的原因，包括DNA损伤频率增加。目前COPD的药物治疗选择大多是对症治疗，通常不会影响疾病进展和生存率。在此背景下，肺康复是改善身体机能、减少住院再入院率和死亡率的最有效治疗策略。患者对康复的反应可能差异很大，因此需要个性化治疗。在本文中，我们将在一组COPD患者中研究那些可能预测肺康复计划反应的变量，将临床参数与细胞和分子测量相结合，为更有效和个性化的治疗选择提供可能。对一组连续89例参加为期3周肺康复（PR）计划的COPD患者在基线和PR完成后进行临床和生物学参数评估。通过视觉评分和使用彗星试验IV分析系统比较冷冻保存淋巴细胞中的DNA片段化。PR前后DNA损伤的比较显示，从入院时的19.6±7.3显著增加到治疗3周后的21.8±7.2，显著增加了2.46分（p<0.001）。在无反应者组和接受氧疗的患者中观察到更高水平的DNA损伤。治疗期间%TI的总体变化与入院时pCO水平显著相关，与入院时IL-6水平呈负相关。测量接受肺康复的COPD患者的DNA损伤频率可能提供一个有意义的反应生物学标志物，应被视为个性化康复计划的额外诊断和预后标准。
