Adipokines and systemic inflammation in weight-losing lung cancer patients.

BACKGROUND: Cancer cachexia is a devastating condition leading to loss of function and independence, decreased performance status, decreased quality of life, and poor prognosis. Adipokines play a role in a wide variety of physiological or pathological processes, including immunity and inflammation, in addition to having significant effects on metabolism and lipogenesis. The objective of the present study was to investigate the relationship of adipokines and systemic inflammation in weight-losing advanced-stage non-small-cell lung cancer (NSCLC) patients. METHODS: Sixty-three male NSCLC patients (stages III and IV) and 25 age- and sex-matched controls were included. NSCLC patients were further divided into subgroups as those with a>5% weight loss in last 6 months and those who did not. Serum leptin, adiponectin, and TNF-α concentrations were measured by ELISA using commercially available kits. RESULTS: The positive acute-phase reactants (APR) CRP, leukocyte, ferritin, thrombocyte, and fibrinogen were higher in the NSCLC group. Serum albumin level (which is a negative APR) was lower in the cancer group, whereas there was no difference in transferrin level between the groups. TNF-α and leptin concentrations were similar in the cancer group and the control group, whereas adiponectin was lower in the cancer group. There was a difference in thrombocyte and transferrin levels between patients with and without weight loss, whereas CRP, TNF-α, and adiponectin levels were similar. Leptin was lower in weight-losing cancer patients. However, there was no correlation between adipokines and markers of systemic inflammation. CONCLUSION: These results revealed a lack of association between adipokine levels and systemic inflammation with cancer cachexia.

Osteopontin as a marker of weight loss in lung cancer.

Although the role of osteopontin (OPN) in tumorigenesis and invasiveness is well-known, its role in systemic consequences of lung cancer has not been studied yet. The objective of the current study was to assess the value of osteopontin as a marker of weight loss in relation to systemic inflammation in non-small cell lung cancer (NSCLC) patients. A total of 63 male NSCLC patients (stage III and IV) and 25 age and sex-matched controls were included. The NSCLC patients were further divided into subgroups depending on whether they had > 5% weight loss in the last 6 months or not. Serum OPN and TNF-α concentrations were measured by ELISA using commercially available kits. Serum C-reactive protein (CRP) concentration was measured by the turbidimetric method. OPN (p = 0.001) and CRP (p < 0.001) concentrations were significantly higher in lung cancer patients compared to controls whereas TNF-α concentrations were similar in cancer and control groups (p = 0.063). There were 33 NSCLC patients (52.4%) with weight loss. Serum OPN concentration was found to be higher in this weight-losing group (p = 0.042). CRP concentration was also higher in the weight-losing group but the difference was not statistically significant (p = 0.246). TNF-α concentrations were similar in both subgroups (p = 0.094). In correlation tests, there was a positive correlation between OPN and CRP (r = 0.299, p = 0.044), but no correlation was detected between OPN and TNF-α (r = − 0.009, p = 0.930). A negative correlation was detected between OPN and BMI (r = − 0.246, p = 0.048). In addition to being an indicator of systemic inflammation in lung cancer patients, osteopontin may also be an indicator of weight loss.

Biomarkers of systemic inflammation in stable and exacerbation phases of COPD.

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 value of C-reactive protein as a marker of systemic inflammation in stable chronic obstructive pulmonary disease.

BACKGROUND: Systemic aspects of chronic obstructive pulmonary disease (COPD) include oxidative stress and altered circulating levels of inflammatory mediators and acute-phase proteins. C-reactive protein (CRP) reflects total systemic burden of inflammation in several disorders and has been shown to upregulate the production of proinflammatory cytokines. The aim of this study was to evaluate circulating CRP levels to determine the value of CRP as a biomarker of systemic inflammation and as an indicator of malnutrition or severity of COPD in stable COPD patients in comparison to the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). METHODS: Thirty-five male patients with stable COPD and 30 age- and sex-matched subjects with normal pulmonary function were admitted to the study. Serum CRP levels were measured using a commercially available kit with the turbidimetric method. Serum TNF-alpha and IL-6 concentrations were measured with ELISA kits. RESULTS: Sixty percent of the patients had severe or very severe and 40% moderate COPD. Serum CRP was significantly higher in stable COPD patients than in control subjects (p<0.001), while TNF-alpha and IL-6 concentrations were not statistically different. Serum TNF-alpha was higher in severe or very severe COPD patients (p=0.046). When the COPD patients with a low BMI were compared to those with a normal-to-high BMI, there was a significant difference in CRP (p=0.034) and TNF-alpha (p=0.037). CONCLUSION: The present study confirms that circulating CRP levels are higher in stable COPD patients and may thus be regarded as a valid biomarker of low-grade systemic inflammation. In addition, CRP is significantly higher in COPD patients with a low BMI and thus, together with TNF-alpha, may be considered an indicator of malnutrition in COPD patients.

Correlates of non-thyroidal illness syndrome in chronic obstructive pulmonary disease.

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.

Correlates of erectile dysfunction in moderate-to-severe chronic obstructive pulmonary disease patients.

OBJECTIVE AND BACKGROUND: Erectile dysfunction (ED) has important negative effects on male quality of life and self-esteem. The aim of this study was to acquire an insight into the sexual status of COPD patients. METHODS: Ninety-five male patients aged 48-75 years, with moderate-to-severe stable COPD, and 30 age-matched subjects with normal pulmonary function were included. After clinical evaluation and measurement of serum sex hormones and TNF-alpha concentration, subjects were asked to answer the International Index of Erectile Function (IIEF) questionnaire as a method to diagnose and classify ED. RESULTS: Varying degrees of ED were detected in 87% of COPD patients and 83% of controls. Although the total percentages of subjects with various severities of ED seemed similar, moderate and severe ED was 57% in COPD group and 20% in control subjects, suggesting a more severe course of ED in COPD patients. ED score of COPD patients was not correlated with age, smoking burden, duration of COPD, FEV1%, PaO2, PaCO2, serum dehydroepiandrosterone-sulphate, testosterone or estradiol levels. When patients were subgrouped according to severity of ED, serum TNF-alpha concentration, used as a marker of systemic inflammatory status in COPD, was significantly higher in patients with moderate-to-severe ED compared with mild-moderate ED. CONCLUSION: 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.

Determinants of BMI in patients with COPD.

OBJECTIVE: COPD is characterized by significant chronic inflammation that is evident not only in the pulmonary compartment but also in the circulation. Peripheral blood features of COPD include markers of oxidative stress and altered circulating levels of inflammatory mediators and acute-phase proteins. The presence of a systemic inflammatory response may influence quality of life by giving rise to weight loss, muscle wasting and tissue depletion. The aim of the present study was to evaluate the determinants of body mass and the value of serum tumour necrosis factor alpha (TNF-alpha) as a marker of weight loss in COPD patients, and to correlate this with the burden of oxidative stress as measured by serum malonyldialdehyde (MDA) levels. METHODOLOGY: Fifty-two male COPD patients (mean age 62.55 +/- 6.81 years) were studied. After anthropometric measurements and standard spirometry, serum TNF-alpha concentration was measured by enzyme-linked immunosorbent assay using an hTNF-alpha kit, and MDA was studied spectrophotometrically using the Yoshioka-Kawada method. RESULTS: The mean BMI was 24.82 +/- 3.46. BMI was lower than normal (< 19) in six patients. Mean serum TNF-alpha concentration was 14.99 +/- 8.98 pg/mL and MDA was 0.93 +/- 0.13 nmol/L. There was no significant correlation between serum MDA and TNF concentrations (P = 0.140). Serum TNF-alpha and MDA concentrations were not correlated with severity of airflow obstruction or degree of hypoxaemia (P > 0.05 for all). BMI was negatively correlated with burden of smoking (pack-years) (r = -0.392, P= 0.004); but not with pulmonary function, degree of hypoxaemia, serum TNF-alpha or MDA levels. BMI was significantly lower in current smokers than ex-smokers (P = 0.041); however, serum MDA and TNF levels were similar in both groups. CONCLUSION: The results of this study indicate that body mass is related to smoking status (both pack-years and continuance of smoking) in COPD; however, serum TNF-alpha concentration does not seem to be a good marker of weight loss in these patients.

Should chronic obstructive pulmonary disease outpatients be routinely evaluated for trace elements?

We searched for serum concentrations of trace elements and correlated them to malondialdehyde (MDA), which is an indirect marker of oxidative stress, in order to clarify if routine evaluation is necessary in chronic obstructive pulmonary disease (COPD) outpatients. Serum concentrations of copper (Cu), zinc (Zn), and magnesium (Mg) were determined by atomic absorption spectrophotometry and iron (Fe) by a ILLab 1800 autoanalyzer with ILLab test kits. Serum MDA concentrations were detected in terms of TBARS (thiobarbituric acid reactive substances) spectrophotometrically. Serum Cu, Zn, Mg, Fe, and MDA concentrations in patient and control groups were all in the normal reference range. The results respectively were as follows: Cu:123 +/- 29.2 and 122.2 +/- 23.4 microg/dL; Zn: 87.8 +/- 17.8 and 96.9 +/- 12.9 microg/dL; Mg: 2.3 +/- 0,5 and 2.04 +/- 0.28 mg/dL; Fe: 73.8 +/-35.5 and 80.7+/-51.2 microg/dL; MDA: 1.09+/-0.11 and 0.95+/-0.06 nmol/L. MDA was not correlated to Cu, Zn, Mg, or Fe (p>0.05 for all). The serum Zn concentration of COPD group was lower than the control group (p=0.042), whereas the Mg concentration was higher (p=0.021). There was no statistical difference in other study parameters. Oxidative stress was not increased in clinically stable, regularly treated COPD patients. Although there was no deficiency in trace elements (Cu, Fe, Mg, and Zn), serum Zn was close to the lower limit of the reference value. There is no need for routine evaluation of trace elements in clinically stable, regularly treated COPD outpatients.

Erythrocyte fragility is not altered in stable chronic obstructive pulmonary disease with normal arterial pH.

The aim of this study is to investigate if erythrocyte fragility is altered in chronic obstructive pulmonary disease (COPD) due to oxidative stress. Fasting blood samples were collected into both plain tubes and tubes with K(3) EDTA and analyzed in two hours for hematologic indexes and erythrocyte osmotic fragility (EOF). Malondialdehyde (MDA) concentrations in serum were detected in terms of TBARS (thiobarbituric acid reactive substances), spectrophotometrically. Thirty-nine clinically stable male COPD patients with mean age 67+/-8 were prospectively studied. The control subjects consisted of healthy males with mean age 64+/-12. Pulmonary function tests of COPD patients revealed severe airway obstruction whereas they were normal for control group. Normal pH with mild hypoxemia and hypercapnia were detected in arterial blood gas analyses. Hemoglobin, haematocrit and mean corpuscular volume values of two groups were similar. Mean serum MDA concentration was 1.09+/-0.11 micromol/l in COPD patients and 0.95+/-0.06 micromol/l in the control group (p=0.336). EOF was 33.06+/-1.24% in COPD group and 33.17+/-1.55% in controls (p=0.453). There was no correlation between EOF and MDA concentrations of COPD patients (r=-0.18, p=0.924). EOF and MDA did not correlate with severity of COPD (p>0.05). We conclude that markers of oxidative stress are not increased and erythrocyte osmotic fragility is not altered in stable COPD patients with normal arterial pH.