scholarly journals New frontiers in the treatment of comorbid cardiovascular disease in chronic obstructive pulmonary disease

2019 ◽  
Vol 133 (7) ◽  
pp. 885-904 ◽  
Author(s):  
Kurt Brassington ◽  
Stavros Selemidis ◽  
Steven Bozinovski ◽  
Ross Vlahos

Abstract Chronic obstructive pulmonary disease (COPD) is a disease characterised by persistent airflow limitation that is not fully reversible and is currently the fourth leading cause of death globally. It is now well established that cardiovascular-related comorbidities contribute to morbidity and mortality in COPD, with approximately 50% of deaths in COPD patients attributed to a cardiovascular event (e.g. myocardial infarction). Cardiovascular disease (CVD) and COPD share various risk factors including hypertension, sedentarism, smoking and poor diet but the underlying mechanisms have not been fully established. However, there is emerging and compelling experimental and clinical evidence to show that increased oxidative stress causes pulmonary inflammation and that the spill over of pro-inflammatory mediators from the lungs into the systemic circulation drives a persistent systemic inflammatory response that alters blood vessel structure, through vascular remodelling and arterial stiffness resulting in atherosclerosis. In addition, regulation of endothelial-derived vasoactive substances (e.g. nitric oxide (NO)), which control blood vessel tone are altered by oxidative damage of vascular endothelial cells, thus promoting vascular dysfunction, a key driver of CVD. In this review, the detrimental role of oxidative stress in COPD and comorbid CVD are discussed and we propose that targeting oxidant-dependent mechanisms represents a novel strategy in the treatment of COPD-associated CVD.

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Elisabetta Zinellu ◽  
Angelo Zinellu ◽  
Alessandro G. Fois ◽  
Sara S. Fois ◽  
Barbara Piras ◽  
...  

Introduction. Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by airflow limitation that is not fully reversible after inhaled bronchodilator use associated with an abnormal inflammatory condition. The biggest risk factor for COPD is cigarette smoking. The exposure to noxious chemicals contained within tobacco smoke is known to cause airway epithelial injury through oxidative stress, which in turn has the ability to elicit an inflammatory response. In fact, the disruption of the delicate balance between oxidant and antioxidant defenses leads to an oxidative burden that has long been held responsible to play a pivotal role in the pathogenesis of COPD. There are currently several biomarkers of oxidative stress in COPD that have been evaluated in a variety of biological samples. The aim of this review is to identify the best studied molecules by summarizing the key literature findings, thus shedding some light on the subject. Methods. We searched for relevant case-control studies examining oxidative stress biomarkers in stable COPD, taking into account the analytical method of detection as an influence factor. Results. Many oxidative stress biomarkers have been evaluated in several biological matrices, mostly in the blood. Some of them consistently differ between the cases and controls even when allowing different analytical methods of detection. Conclusions. The present review provides an overview of the oxidative stress biomarkers that have been evaluated in patients with COPD, bringing focus on those molecules whose reliability has been confirmed by the use of different analytical methods.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaole Wang ◽  
Chuqiao Shen ◽  
Jie Zhu ◽  
Guoming Shen ◽  
Zegeng Li ◽  
...  

Oxidative stress takes responsibility for various diseases, such as chronic obstructive pulmonary disease (COPD), Alzheimer’s disease (AD), and cardiovascular disease; nevertheless, there is still a lack of specific biomarkers for the guidance of diagnosis and treatment of oxidative stress-related diseases. In recent years, growing studies have documented that oxidative stress has crucial correlations with long noncoding RNAs (lncRNAs), which have been identified as important transcriptions involving the process of oxidative stress, inflammation, etc. and been regarded as the potential specific biomarkers. In this paper, we review links between oxidative stress and lncRNAs, highlight lncRNAs that refer to oxidative stress, and conclude that lncRNAs have played a negative or positive role in the oxidation/antioxidant system, which may be helpful for the further investigation of specific biomarkers of oxidative stress-related diseases.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Mariana A. Antunes ◽  
Miquéias Lopes-Pacheco ◽  
Patricia R. M. Rocco

Chronic obstructive pulmonary disease (COPD) is a progressive and disabling disorder marked by airflow limitation and extensive destruction of lung parenchyma. Cigarette smoke is the major risk factor for COPD development and has been associated with increased oxidant burden on multiple cell types in the lungs. Elevated levels of reactive oxygen species (ROS) may significantly affect expression of biological molecules, signaling pathways, and function of antioxidant defenses. Although inflammatory cells, such as neutrophils and macrophages, contribute to the release of large quantities of ROS, mitochondrial dysfunction plays a critical role in ROS production due to oxidative phosphorylation. Although mitochondria are dynamic organelles, excess oxidative stress is able to alter mitochondrial function, morphology, and RNA and protein content. Indeed, mitochondria may change their shape by undergoing fusion (regulated by mitofusin 1, mitofusin 2, and optic atrophy 1 proteins) and fission (regulated by dynamin-related protein 1), which are essential processes to maintain a healthy and functional mitochondrial network. Cigarette smoke can induce mitochondrial hyperfusion, thus reducing mitochondrial quality control and cellular stress resistance. Furthermore, diminished levels of enzymes involved in the mitophagy process, such as Parkin (a ubiquitin ligase E3) and the PTEN-induced putative kinase 1 (PINK1), are commonly observed in COPD and correlate directly with faulty removal of dysfunctional mitochondria and consequent cell senescence in this disorder. In this review, we highlight the main mechanisms for the regulation of mitochondrial quality and how they are affected by oxidative stress during COPD development and progression.


Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1153
Author(s):  
Shih-Lung Cheng ◽  
Ching-Hsiung Lin

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease that is associated with significant morbidity and mortality, giving rise to an enormous social and economic burden. The Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) report is one of the most frequently used documents for managing COPD patients worldwide. A survey was conducted across country-level members of Asia-Pacific Society of Respiratory (APSR) for collecting an updated version of local COPD guidelines, which were implemented in each country. This is the first report to summarize the similarities and differences among the COPD guidelines across the Asia-Pacific region. The degree of airflow limitation, assessment of COPD severity, management, and pharmacologic therapy of stable COPD will be reviewed in this report.


Thorax ◽  
2001 ◽  
Vol 56 (9) ◽  
pp. 713-720
Author(s):  
J Hadcroft ◽  
P M A Calverley

BACKGROUNDBronchodilator reversibility testing is recommended in all patients with chronic obstructive pulmonary disease (COPD) but does not predict improvements in breathlessness or exercise performance. Two alternative ways of assessing lung mechanics—measurement of end expiratory lung volume (EELV) using the inspiratory capacity manoeuvre and application of negative expiratory pressure (NEP) during tidal breathing to detect tidal airflow limitation—do relate to the degree of breathlessness in COPD. Their usefulness as end points in bronchodilator reversibility testing has not been examined.METHODSWe studied 20 patients with clinically stable COPD (mean age 69.9 (1.5) years, 15 men, forced expiratory volume in one second (FEV1) 29.5 (1.6)% predicted) with tidal flow limitation as assessed by their maximum flow-volume loop. Spirometric parameters, slow vital capacity (SVC), inspiratory capacity (IC), and NEP were measured seated, before and after nebulised saline, and at intervals after 5 mg nebulised salbutamol and 500 μg nebulised ipratropium bromide. The patients attended twice and the treatment order was randomised.RESULTSMean FEV1, FVC, SVC, and IC were unchanged after saline but the degree of tidal flow limitation varied. FEV1 improved significantly after salbutamol and ipratropium (0.11 (0.02) l and 0.09 (0.02) l, respectively) as did the other lung volumes with further significant increases after the combination. Tidal volume and mean expiratory flow increased significantly after all bronchodilators but breathlessness fell significantly only after the combination treatment. The initial NEP score was unrelated to subsequent changes in lung volume.CONCLUSIONSNEP is not an appropriate measurement of acute bronchodilator responsiveness. Changes in IC were significantly larger than those in FEV1and may be more easily detected. However, our data showed no evidence for separation of “reversible” and “irreversible” groups whatever outcome measure was adopted.


2009 ◽  
Vol 106 (6) ◽  
pp. 1902-1908 ◽  
Author(s):  
Roberto Rodríguez-Roisin ◽  
Mitra Drakulovic ◽  
Diego A. Rodríguez ◽  
Josep Roca ◽  
Joan Albert Barberà ◽  
...  

Chronic obstructive pulmonary disease (COPD) is characterized by a decline in forced expiratory volume in 1 s (FEV1) and, in many advanced patients, by arterial hypoxemia with or without hypercapnia. Spirometric and gas exchange abnormalities have not been found to relate closely, but this may reflect a narrow range of severity in patients studied. Therefore, we assessed the relationship between pulmonary gas exchange and airflow limitation in patients with COPD across the severity spectrum. Ventilation-perfusion (V̇A/Q̇) mismatch was measured using the multiple inert gas elimination technique in 150 patients from previous studies. The distribution of patients according to the GOLD stage of COPD was: 15 with stage 1; 40 with stage 2; 32 with stage 3; and 63 with stage 4. In GOLD stage 1, AaPo2 and V̇A/Q̇ mismatch were clearly abnormal; thereafter, hypoxemia, AaPo2, and V̇A/Q̇ imbalance increased, but the changes from GOLD stages 1–4 were modest. Postbronchodilator FEV1 was related to PaO2 ( r = 0.62) and PaCO2 ( r = −0.59) and to overall V̇A/Q̇ heterogeneity ( r = −0.48) ( P < 0.001 each). Pulmonary gas exchange abnormalities in COPD are related to FEV1 across the spectrum of severity. V̇A/Q̇ imbalance, predominantly perfusion heterogeneity, is disproportionately greater than airflow limitation in GOLD stage 1, suggesting that COPD initially involves the smallest airways, parenchyma, and pulmonary vessels with minimal spirometric disturbances. That progression of V̇A/Q̇ inequality with spirometric severity is modest may reflect pathogenic processes that reduce both local ventilation and blood flow in the same regions through airway and alveolar disease and capillary involvement.


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