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

Abstract

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 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.

• Authors: Patrizia Russo, Palma Lamonaca, Mirta Milic, Emilio Rojas, Giulia Prinzi, Vittorio Cardaci, Laura Vitiello, Stefania Proietti, Alessia Santoro, Carlo Tomino, Massimo Fini, Stefano Bonassi
• Journal: Mutation research. Genetic toxicology and environmental mutagenesis (Mutat Res Genet Toxicol Environ Mutagen) Vol. 843 Pg. 111-117 (Jul 2019) ISSN: 1879-3592 [Electronic] Netherlands
• PMID: 31421732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Adrenal Cortex Hormones
• Biomarkers
• Bronchodilator Agents
• IL6 protein, human
• Interleukin-6
• Muscarinic Antagonists
• C-Reactive Protein

Topics

• Adrenal Cortex Hormones (therapeutic use)
• Aged
• Aged, 80 and over
• Biomarkers
• Bronchodilator Agents (therapeutic use)
• C-Reactive Protein (analysis)
• Combined Modality Therapy
• Comet Assay
• DNA Breaks, Single-Stranded
• DNA Damage
• DNA Fragmentation
• Disease Progression
• Female
• Genomic Instability
• Humans
• Interleukin-6 (blood)
• Lymphocytes (chemistry)
• Male
• Muscarinic Antagonists (therapeutic use)
• Oxygen Inhalation Therapy
• Precision Medicine
• Pulmonary Disease, Chronic Obstructive (blood, genetics, rehabilitation, therapy)
• Respiratory Therapy
• Severity of Illness Index