engleski

Biomarkers of DNA damage in COPD patients undergoing pulmonary rehabilitation: Integrating clinical parameters with genomic profiling

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 nonresponders and in those patients receiving oxygen therapy. The overall variation of %TI during treatment significantly correlated with the level of pCO2 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.

Chronic obstructive pulmonary disease (COPD) ; Pulmonary rehabilitation ; DNA damage ; Comet assay ; Personalized medicine

This work is partially derived from the sabbatical stay of Emilio Rojas at the IRCCS San Raffaele, Rome and was realized with the support of PASPA-DGAPA-UNAM. Support was provided by the Italian Ministry of Health (grant for Institutional Research 2017-2018) and by the Associazione Italiana per la Ricerca sul Cancro (grant IG2015/ 17564IO).