Apart from the deleterious effects on the lungs, chronic obstructive pulmonary disease (COPD) should be considered a complex, systemic disease involving several organs and systems. The nature and course of systemic inflammation in COPD is important since there is a potential for anti-inflammatory therapy. The objective of the current study was to assess biomarkers of systemic inflammation in stable and exacerbation phases of COPD patients as compared to healthy controls. We also investigated the course of these biomarkers after COPD exacerbation to evaluate their usefulness for disease monitoring. Eighty-three stable patients with moderate to very severe COPD, 20 patients in exacerbation phase, and 30 subjects with normal pulmonary function were included. Serum tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) levels were measured once in stable COPD patients and controls and three times in the COPD exacerbation group during follow-up. TNF-alpha and IL-6 levels were higher than in controls in both stable and exacerbation groups. Although NO was not higher in the stable COPD group than in controls, it was higher in the exacerbation group. In follow-up after the exacerbation period, significant alteration was not detected in cytokine or NO levels compared to admission. Raised serum levels of TNF-alpha and IL-6 support their use as biomarkers of the systemic inflammatory response in stable COPD patients. However, the circulating biomarkers we have studied are not found to be useful either as indicators of COPD exacerbation or for monitoring recovery after exacerbation.

The present study showed that ED is frequent and more severe in COPD patients than age-matched controls. Chronic systemic inflammation is likely to play a role in ED in COPD; the role of TNF-alpha should be evaluated further. Patients with COPD need comprehensive management including a detailed sexual evaluation.

Non-thyroidal illness syndrome (NTIS) is frequently detected in chronic, systemic diseases. The objectives of the current study is to assess the alterations of thyroid hormones during exacerbation period, recovery of exacerbation and stable phase of chronic obstructive pulmonary disease (COPD) and correlates of these hormonal alterations. A total of 83 stable COPD patients, 20 patients with acute exacerbation and 30 control subjects were evaluated. TT3, fT3, TT3/TT4 levels of both stable and exacerbation COPD groups were lower than control subjects. TSH was also decreased during exacerbation period. In follow-up of COPD exacerbation group, TSH, TT3, fT3 and TT3/TT4 were found to be increased in measurements on the day of discharge from hospital and after 1 month, compared to baseline values. TT3 and TT3/TT4 were lower in severe COPD; whereas TSH, fT3, TT3 and TT3/TT4 were lower in patients with severe hypoxemia. IL-6 and TNF-alpha were higher in both stable and exacerbation phase COPD groups and IL-6 was correlated to TT3 in stable COPD. As a result, there are significant alterations in thyroid hormones of stable COPD patients, which are related to severity of disease and hypoxemia. The hormonal changes are more significant during exacerbation and partially regress after 1 month when the disease is stabilized. We conclude that COPD patients should not be evaluated for thyroid disease during exacerbation of the disease, and thyroid function alterations during stable phase of the disease should be considered cautiously, since thyroid function abnormalities in non-thyroid illness may mimic or mask biochemical abnormalities observed in true thyroid disease.

In COPD, the systemic effects of the disease reflect the structural and/or biochemical alterations occurring in the structures or organs other than the lungs in relation to the characteristics of the primary disease. The disorders of endothelial structures due to COPD may lead vascular pathologies, such as ischemic heart disease, stroke, to occur more commonly in those with COPD. On consideration of the fact that the vascular endothelium is a major site in which the systemic effect of the inflammation occurs, should von Willebrand Factor, a clotting factor of endothelium origin, and the plasma level of fibrinogen vary with the severity of the disease in COPD, the variability of arterial blood gas values, and the stability or exacerbation of the disease? Considering the fact that microalbuminuria is an indirect manifestation of the renal endothelial permeability and/or renal perfusion; should there be an association between microalbuminuria and the severity of COPD? Therefore, in order to assess the effect of the systemic inflammation in COPD on the vascular endothelium, we compared the levels of the plasma vWF, fibrinogen, 24-h urine microalbuminuria of those with stable COPD (33 patients) and exacerbation of COPD (26 patients) with those of the controls (16 healthy subjects). The mean age was 63.42 -/+ 10.29, 68.00 -/+ 9.77 and 59.63 -/+ 14.10 years in SCOPD, COPDAE, and CG, respectively. The level of microalbuminuria was found to increase significantly in COPDAE group, compared to that of the controls (P = 0.004). When we investigated the relation between smoking burden and microalbuminuria, vWF, fibrinogen levels, the amount of consumption and positive relationship were found significant. (r = 0.336, P = 0.003 between smoking pack-years and vWF, r = 0.403, P = 0.001 between smoking pack-years and fibrinogen, and r = 0.262, P = 0.02 between smoking pack-years and microalbuminuria). The levels of vWF and fibrinogen are AECOPD > SCOPD > CG, with the highest being in AECOPD, and the difference among the groups was statistically significant. The relationship between the level of hypoxemia and microalbuminuria, fibrinogen and vWF was found to be significant (r = -0.360, P = 0.005 between oxygen saturation and microalbuminuria, r = -0.359, P = 0.005 between the level of PaO(2) and fibrinogen, and r = -0.336, P = 0.009 between PaO(2) and vWF). In conclusion, the levels of plasma vWF, fibrinogen, and microalbuminuria may be helpful in grading the severity of COPD exacerbation. The related increase in these markers may represent a possible pathophysiological mechanism behind the increased vascular morbidity of patients with COPD and detecting indirectly the endothelial dysfunction as a manifestation of systemic outcomes due to COPD and in detecting earlier the cases in which the risk for developing the associated complications are higher. We suggest that further studies are necessary to investigate the impact of antithrombotic treatment on microalbuminuria, plasma vWF and fibrinogen as markers of endothelial dysfunction...

Summary Objective:  Decreased anabolic hormone levels are described in chronic obstructive pulmonary disease (COPD), leading to important clinical consequences. The aim of this study was to evaluate the alterations in sex hormone levels in men with COPD to compare with age‐matched control subjects, the determinants of these alterations, the relationship between hypogonadism and markers of systemic inflammation [interleukin‐6 (IL‐6) and tumour necrosis factor alpha (TNF‐α)] and the androgen status during an acute exacerbation of COPD. Methods:  A total of 103 COPD patients and 30 control subjects were admitted to the study. 83 stable COPD patients and 30 control subjects were evaluated as outpatients. 20 patients with COPD exacerbation were hospitalised and evaluated before discharge and after 1 month. Results:  Testosterone and dehydroepiandrosteronesulphate (DHEAS) levels of both COPD groups were lower than that of the control group. Luteinizing hormone (LH), follicle stimulating hormone (FSH) levels were increased during exacerbation. Testosterone and DHEAS levels increased and LH decreased in follow‐up measurements of COPD exacerbation group. Testosterone and DHEAS levels were lower in severe COPD [forced expiratory volume in 1 s (FEV1) < 50%], in patients with severe hypoxaemia (PaO2 < 60 mmHg) and in hypercapnic patients. Circulating IL‐6 and TNF‐α concentrations were higher in both stable and exacerbation phase COPD groups than controls. There was no correlation between sex hormones and TNF‐α or IL‐6. Conclusion:  The alterations in sex hormone levels in COPD are particularly related to FEV1, hypoxaemia and hypercapnia. There are significant differences in hormone levels during stable and exacerbation phases of COPD; the hormonal changes are marked during exacerbation and partially regress after 1 month when the disease is stabilised.