On 2016 May 02, Riccardo Polosa commented:

Evidence that activation of the haemo-coagulative system occurs in COPD is accumulating with potential implications for cardiovascular disease (CVD)(1,2). Maclay and colleagues(3) have recently reported a significant but small increase in platelet activity by flow cytometric analysis of circulating platelet-monocyte aggregates in COPD patients. This does not seem to be strongly supportive of this view as the observed changes are well within test repeatability and mainly due to a handful of outliers. Moreover, no changes were reported for the well characterised platelet activation marker, P-selectin.

Although small sample size, co-morbidities and medications may have contributed to these largely negative findings, an important factor to be considered is smoking. Of note, the authors excluded active smokers from COPD patients and included a control group of smoking habit- (i.e. ≥10 pack/yrs; at least 6 months tobacco abstinence) and age-matched ex-smokers with no respiratory symptoms. However, as for several biomarkers of systemic inflammation (e.g. C-reactive protein)(4), airway inflammation (e.g. sputum neutrophilia)(5), and clotting activation (e.g. D-Dimer and prothrombin fragment 1+2)(6), elevation in markers of platelet activation may persist for many years after smoking cessation, reflecting that the underlying damage caused by smoking takes a protracted time to recover. Thus, the baseline level of platelet activation in the control group may not be truly representative. Future studies should recruit either lifetime non-smokers or ex-smokers who have been abstinent for 3-5 years as controls.

Assuming that platelet activation is significant in COPD, it is highly speculative to suggest that such mechanisms are associated with increased risk of CVD in COPD. Firstly, measurements of platelet activation in smoking-related conditions may not be that efficient in predicting cardiovascular mortality and morbidity. Secondly, platelet activation is not disease specific (can occur in degenerative, inflammatory and smoking-related diseases) and may be due to immobilization during hospitalization. A control group for this confounder was not included in the exacerbation study. Thirdly, although systemic inflammation may be responsible for platelet activation, we cannot discount a role for the underlying tissue/cellular injury that persists for many years after smoking cessation(4-6). Specifically, the source of systemic inflammation (± platelet activation) in COPD may not necessarily be associated with activation/injury of the airway epithelium. Alternatively, direct spill-over of pro-inflammatory mediators and potent platelet activators in the bloodstream can be traced to the vascular endothelium, which are metabolically activated on smoke exposure(7,8). Lastly, it is unclear whether the low-grade systemic inflammation reported in COPD has an independent causal role in cardiovascular co-morbidities(9). CVD is known to occur long before the onset of COPD and is known to be strongly associated with cigarette smoking. Conclusive evidence of systemic inflammation contributing to greater risk of CVD requires large well-controlled long-term prospective studies normalized for intensity and duration of smoking.

References

1. Wedzicha JA, Syndercombe-Court D, Tan KC. Increased platelet aggregate formation in patients with chronic airflow obstruction and hypoxaemia. Thorax. 1991;46(7):504-7.
2. Polosa R, Malerba M, Cacciola RR, Morjaria JB, Maugeri C, Prosperini G, et al. Effect of acute exacerbations on circulating endothelial, clotting and fibrinolytic markers in COPD patients. Intern Emerg Med. 2011. Epub 2011/06/11.
3. Maclay JD, McAllister DA, Johnston S, Raftis J, McGuinnes C, Deans A, et al. Increased platelet activation in patients with stable and acute exacerbation of COPD. Thorax. 2011;66(9):769-74.
4. Yanbaeva DG, Dentener MA, Creutzberg EC, Wesseling G, Wouters EF. Systemic effects of smoking. Chest. 2007;131(5):1557-66.
5. Willemse BW, ten Hacken NH, Rutgers B, Lesman-Leegte IG, Postma DS, Timens W. Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers. Eur Respir J. 2005;26(5):835-45.
6. Caponnetto P, Russo C, Di Maria A, Morjaria JB, Barton S, Guarino F, et al. Circulating endothelial-coagulative activation markers after smoking cessation: a 12-month observational study. Eur J Clin Invest. 2011;41(6):616-26.
7. Cacciola RR, Guarino F, Polosa R. Relevance of endothelial-haemostatic dysfunction in cigarette smoking. Curr Med Chem. 2007;14(17):1887-92.
8. Guarino F, Cantarella G, Caruso M, Russo C, Mancuso S, Arcidiacono G, et al. Endothelial activation and injury by cigarette smoke exposure. J Biol Regul Homeost Agents. 2011;25(2):259-68.
9. Morjaria JB, Polosa, R. The holistic perspective of chronic obstructive pulmonary disease: doubt some more. Ther Adv Chronic Dis. 2010;1(2):37-41.

On 2016 May 02, Riccardo Polosa commented:

Evidence that activation of the haemo-coagulative system occurs in COPD is accumulating with potential implications for cardiovascular disease (CVD)(1,2). Maclay and colleagues(3) have recently reported a significant but small increase in platelet activity by flow cytometric analysis of circulating platelet-monocyte aggregates in COPD patients. This does not seem to be strongly supportive of this view as the observed changes are well within test repeatability and mainly due to a handful of outliers. Moreover, no changes were reported for the well characterised platelet activation marker, P-selectin.

Although small sample size, co-morbidities and medications may have contributed to these largely negative findings, an important factor to be considered is smoking. Of note, the authors excluded active smokers from COPD patients and included a control group of smoking habit- (i.e. ≥10 pack/yrs; at least 6 months tobacco abstinence) and age-matched ex-smokers with no respiratory symptoms. However, as for several biomarkers of systemic inflammation (e.g. C-reactive protein)(4), airway inflammation (e.g. sputum neutrophilia)(5), and clotting activation (e.g. D-Dimer and prothrombin fragment 1+2)(6), elevation in markers of platelet activation may persist for many years after smoking cessation, reflecting that the underlying damage caused by smoking takes a protracted time to recover. Thus, the baseline level of platelet activation in the control group may not be truly representative. Future studies should recruit either lifetime non-smokers or ex-smokers who have been abstinent for 3-5 years as controls.

Assuming that platelet activation is significant in COPD, it is highly speculative to suggest that such mechanisms are associated with increased risk of CVD in COPD. Firstly, measurements of platelet activation in smoking-related conditions may not be that efficient in predicting cardiovascular mortality and morbidity. Secondly, platelet activation is not disease specific (can occur in degenerative, inflammatory and smoking-related diseases) and may be due to immobilization during hospitalization. A control group for this confounder was not included in the exacerbation study. Thirdly, although systemic inflammation may be responsible for platelet activation, we cannot discount a role for the underlying tissue/cellular injury that persists for many years after smoking cessation(4-6). Specifically, the source of systemic inflammation (± platelet activation) in COPD may not necessarily be associated with activation/injury of the airway epithelium. Alternatively, direct spill-over of pro-inflammatory mediators and potent platelet activators in the bloodstream can be traced to the vascular endothelium, which are metabolically activated on smoke exposure(7,8). Lastly, it is unclear whether the low-grade systemic inflammation reported in COPD has an independent causal role in cardiovascular co-morbidities(9). CVD is known to occur long before the onset of COPD and is known to be strongly associated with cigarette smoking. Conclusive evidence of systemic inflammation contributing to greater risk of CVD requires large well-controlled long-term prospective studies normalized for intensity and duration of smoking.

References

1. Wedzicha JA, Syndercombe-Court D, Tan KC. Increased platelet aggregate formation in patients with chronic airflow obstruction and hypoxaemia. Thorax. 1991;46(7):504-7.
2. Polosa R, Malerba M, Cacciola RR, Morjaria JB, Maugeri C, Prosperini G, et al. Effect of acute exacerbations on circulating endothelial, clotting and fibrinolytic markers in COPD patients. Intern Emerg Med. 2011. Epub 2011/06/11.
3. Maclay JD, McAllister DA, Johnston S, Raftis J, McGuinnes C, Deans A, et al. Increased platelet activation in patients with stable and acute exacerbation of COPD. Thorax. 2011;66(9):769-74.
4. Yanbaeva DG, Dentener MA, Creutzberg EC, Wesseling G, Wouters EF. Systemic effects of smoking. Chest. 2007;131(5):1557-66.
5. Willemse BW, ten Hacken NH, Rutgers B, Lesman-Leegte IG, Postma DS, Timens W. Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers. Eur Respir J. 2005;26(5):835-45.
6. Caponnetto P, Russo C, Di Maria A, Morjaria JB, Barton S, Guarino F, et al. Circulating endothelial-coagulative activation markers after smoking cessation: a 12-month observational study. Eur J Clin Invest. 2011;41(6):616-26.
7. Cacciola RR, Guarino F, Polosa R. Relevance of endothelial-haemostatic dysfunction in cigarette smoking. Curr Med Chem. 2007;14(17):1887-92.
8. Guarino F, Cantarella G, Caruso M, Russo C, Mancuso S, Arcidiacono G, et al. Endothelial activation and injury by cigarette smoke exposure. J Biol Regul Homeost Agents. 2011;25(2):259-68.
9. Morjaria JB, Polosa, R. The holistic perspective of chronic obstructive pulmonary disease: doubt some more. Ther Adv Chronic Dis. 2010;1(2):37-41.