Relationships between Airway Infection, Exacerbations and Severity of Cardiovascular Risk in COPD

Chronic obstructive pulmonary disease (COPD) is a common lung condition and the modern term for emphysema and/or chronic bronchitis. It is most often caused by smoking. Many patients suffer from repeated flare-ups of COPD caused by chest infections.
People with COPD also have an increased risk of heart attack and stroke. This seems to be more than just due to smoking, and something to do with COPD itself. We would like to establish whether those patients with the most frequent flare-ups of COPD are at the most risk of heart attack and stroke.
Some patients with COPD have bacteria and/or viruses living in their airways even when they are well. We are also planning to investigate whether this group are at greater risk of heart attack and stroke.
One virus in particular called ?RSV? appears to be present in the lungs of around a quarter of COPD patients. Using laboratory experiments, we will investigate a possible link between the way the body reacts to this virus and a higher risk of heart attack and stroke

Chronic obstructive pulmonary disease (COPD) is characterised by recurrent acute exacerbations usually caused by airway infection. It has been shown that bacteria and to a lesser extent respiratory syncytial virus (RSV) colonise the lower respiratory tract of COPD patients.
There is excessive cardiovascular risk in COPD patients beyond smoking, however, the mechanism remains unclear.
We hypothesise that the severity of cardiovascular co-morbidity in COPD relates to the frequency of COPD exacerbations, and that cardiovascular risk may be modulated by the presence of airway infection both in the stable state and at exacerbation.
Key questions:
? Are those COPD patients suffering frequent exacerbations more at risk of cardiovascular disease?
? Is the magnitude of cardiovascular risk in stable COPD related to the presence of airway bacteria and/or viruses?
? Are there further changes in cardiovascular risk during exacerbations, and does the magnitude of this change relate to exacerbation aetiology?
? Do patients with airway RSV in the stable state have altered systemic inflammatory responses to exacerbation stimuli? Is there a link between airway colonisation, exacerbations, systemic inflammation and cardiovascular risk?
Using the MRC-funded London COPD Cohort, we can access patients for cardiovascular risk and airway infection assessment in the stable state, at exacerbation and at two weeks post-exacerbation.
Cardiovascular risk will be assessed by measuring carotid-femoral aortic pulse wave velocity, gold-standard non-invasive test. 12-lead ECGs will be scored using the Cardiac Infarction and Injury Scale. Blood markers sampled will include NT-proBNP, troponin, HbA1c, fasting glucose and lipids, fibrinogen and urine microalbuminuria.
Spontaneous or induced sputum will be collected in order to identify airway bacteria and viruses. Bacterial work, already funded by the MRC will be undertaken at UCL, using quantitative PCR, 16S rDNA amplification and sequencing, and genotyping of dominant species.
Quantitative RT-PCR for rhinovirus and qualitative RT-PCR multiplex for other viruses will be performed at UCL. Respiratory syncytial virus (RSV) RT-PCR and genotyping will be performed at Imperial College. 15 patients identified as RSV-colonised, and 15 non-colonised subjects will be studied further. We will investigate the inflammatory responses of peripheral blood leukocytes to exacerbation stimuli (rhinovirus, RSV, LPS and controls) employing colour flow cytometry (FACS).
This study will enable us to elucidate the role of airway infection and inflammation in the increased cardiovascular risk among COPD patients. If an aetiological link is shown, further studies ought to be undertaken to eradicate airway infection aimed at decreasing cardiovascular morbidity and mortality