COPD and stroke: are systemic inflammation and oxidative stress the missing links?

Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and loss of lung function, and is currently the third largest cause of death in the world. It is now well established that cardiovascular-related comorbidities such as stroke contribute to morbidity and mortality in COPD. The mechanisms linking COPD and stroke remain to be fully defined but are likely to be interconnected. The association between COPD and stroke may be largely dependent on shared risk factors such as aging and smoking, or the association of COPD with traditional stroke risk factors. In addition, we propose that COPD-related systemic inflammation and oxidative stress may play important roles by promoting cerebral vascular dysfunction and platelet hyperactivity. In this review, we briefly discuss the pathogenesis of COPD, acute exacerbations of COPD (AECOPD) and cardiovascular comorbidities associated with COPD, in particular stroke. We also highlight and discuss the potential mechanisms underpinning the link between COPD and stroke, with a particular focus on the roles of systemic inflammation and oxidative stress.

Prevalence and influence of chronic obstructive pulmonary disease on stroke outcomes in hospitalized stroke patients

“…First, patients with COPD have associated comorbid conditions (17) that have been associated with increased mortality in stroke patients including depression ( 18, 19, 20), and kidney disease (21). Second, patients with stroke are at increased risk of dysphagia, aspiration, and pneumonia all of which are worsened by the COPD status (22), third patients with severe COPD are hypoxemic and hypercapnic at baseline which may increase their susceptibility to brain injury and increase their risk of death, finally COPD especially during exacerbation is associated with pulmonary inflammation which can lead to systemic inflammation and increased oxidative stress leading to unstable plaques and prothrombotic events all of which could be associated with higher stroke burden (23, 24)…”

Modelling COPD co‐morbidities in preclinical models

“…Thus, these studies highlight that chronic exposure to cigarette smoke causes systemic features that closely resemble extrapulmonary manifestations observed in COPD patients, and that these murine models are a useful tool in exploring therapeutics aimed at treating skeletal muscle wasting and dysfunction observed in human COPD. While skeletal muscle wasting and dysfunction is the best developed COPD co‐morbidity in mice, we and others are developing clinically relevant animal models to investigate the link between COPD and cardiovascular, cognitive and metabolic co‐morbidities . A current limitation is that the smoke exposure mouse models do not cause severe COPD, where a complementary genetic susceptibility strategy may be required to develop a more severe model of COPD co‐morbidities.…”

Oxygen therapy improves cerebral oxygen delivery and neurovascular function in hypoxaemic chronic obstructive pulmonary disease patients

“…This indicates that the lack of responsiveness to O 2 normalization in COPD is not representative of normal cerebrovascular function. To interpret this notion judiciously, it is important to consider that differences between healthy individuals and COPD patients in response to O 2 normalization might be the result of differences in systemic inflammation, oxidative stress, age or medications and their potential influences on vascular control (Austin, Crack, Bozinovski, Miller, & Vlahos, ; Barnes, ; Hoffman, Albrecht, & Miletich, ). Importantly, this abnormal response (i.e.…”