Systemic Inflammation In COPD Research Articles

Unraveling the Pathogenesis of Asthma and Chronic Obstructive Pulmonary Disease Overlap: Focusing on Epigenetic Mechanisms.

Asthma and COPD overlap (ACO) is characterized by patients presenting with persistent airflow limitation and features of both asthma and COPD. It is associated with a higher frequency and severity of exacerbations, a faster lung function decline, and a higher healthcare cost. Systemic inflammation in COPD and asthma is driven by type 1 T helper (Th1) and Th2 immune responses, respectively, both of which may contribute to airway remodeling in ACO. ACO-related biomarkers can be classified into four categories: neutrophil-mediated inflammation, Th2 cell responses, arachidonic acid-eicosanoids pathway, and metabolites. Gene–environment interactions are key contributors to the complexity of ACO and are regulated by epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNAs. Thus, this review focuses on the link between epigenetics and ACO, and outlines the following: (I) inheriting epigenotypes without change with environmental stimuli, or epigenetic changes in response to long-term exposure to inhaled particles plus intermittent exposure to specific allergens; (II) epigenetic markers distinguishing ACO from COPD and asthma; (III) potential epigenetic drugs that can reverse oxidative stress, glucocorticoid insensitivity, and cell injury. Improved understanding of the epigenetic regulations holds great value to give deeper insight into the mechanisms, and clarify their implications for biomedical research in ACO.

C-reactive protein as a biomarker of response to inhaled corticosteroids among patients with COPD

AimsC-reactive protein (CRP) is an important biomarker in systemic inflammation in COPD; reports have suggested inhaled corticosteroids (ICS) attenuate CRP levels. We evaluated the risk of moderate-to-severe exacerbations, severe exacerbations and all-cause mortality among patients with COPD currently exposed to Inhaled corticosteroids (ICS) stratified by CRP levels compared to never ICS users with low CRP levels. MethodsWe included subjects age 40 or more who had a diagnosis of COPD from January 1, 2005 to January 31, 2014 from the UK Clinical Practice Research Datalink (CPRD). ICS exposure was determined time-dependently, as current, recent, past or never users. We evaluated the risk of moderate-to-severe exacerbations, severe exacerbations and all-cause mortality among ICS users stratified by CRP levels. Results17,722 subjects diagnosed with COPD met the inclusion criteria. Among current or never ICS with elevated CRP levels we found, no significantly reduced risk of moderate-to-severe or severe exacerbations. For patients currently exposed ICS with CRP levels ≥8 mg/L there was no reduced risk of moderate-to-severe exacerbations (adjusted hazard ratio [adj. HR] 0.99; 95% confidence interval [CI] 0.76–1.31) or severe exacerbations (adj.HR 1.52; 95% CI 0.71–3.27). However, we found an increased risk of all-cause mortality among COPD patients with CRP levels ≥8 mg/L irrespective of ICS exposure. ConclusionWe did not find a reduced risk of moderate and/or severe COPD exacerbations among COPD patients with varying CRP levels currently exposed to ICS. However, low-grade systemic inflammation was associated with all-cause mortality among COPD patients.

Evaluation of lung parenchyma, blood vessels, and peripheral blood lymphocytes as a potential source of acute phase reactants in patients with COPD.

Background: Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments.Methods: Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry.Results: A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, P=0.015 and P<0.001, respectively; 8-fold higher for SAA2, P<0.001) and peripheral blood leukocytes (16-fold higher for SAA1, 439-fold higher for SAA2, and 5-fold higher for SAA4; P<0.001). No correlation between plasma levels of inflammatory markers and their expression in the lung and peripheral blood leukocytes was observed.Conclusions: The expression of SAA in lung parenchyma is higher than in pulmonary artery and peripheral blood leukocytes. Notably, no associations were noted between lung expression of APRs and their circulating plasma levels, making the leakage of inflammatory proteins from the lung to the bloodstream unlikely. Based on these results, other potential sources of systemic inflammation in COPD (eg, the liver) need further scrutiny.

Psychological co-morbidities in COPD: Targeting systemic inflammation, a benefit for both?

COPD is a chronic lung disease characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities. Furthermore, COPD is often characterized by extrapulmonary manifestations and comorbidities worsening COPD progression and quality of life. A neglected comorbidity in COPD management is mental health impairment defined by anxiety, depression and cognitive problems. This paper summarizes the evidence for impaired mental health in COPD and focuses on current pharmacological intervention strategies. In addition, possible mechanisms in impaired mental health in COPD are discussed with a central role for inflammation.Many comorbidities are associated with multi-organ-associated systemic inflammation in COPD. Considering the accumulative evidence for a major role of systemic inflammation in the development of neurological disorders, it can be hypothesized that COPD-associated systemic inflammation also affects the function of the brain and is an interesting therapeutic target for nutra- and pharmaceuticals.

Acute and chronic effects of treatment with mesenchymal stromal cells on LPS-induced pulmonary inflammation, emphysema and atherosclerosis development.

BackgroundCOPD is a pulmonary disorder often accompanied by cardiovascular disease (CVD), and current treatment of this comorbidity is suboptimal. Systemic inflammation in COPD triggered by smoke and microbial exposure is suggested to link COPD and CVD. Mesenchymal stromal cells (MSC) possess anti-inflammatory capacities and MSC treatment is considered an attractive treatment option for various chronic inflammatory diseases. Therefore, we investigated the immunomodulatory properties of MSC in an acute and chronic model of lipopolysaccharide (LPS)-induced inflammation, emphysema and atherosclerosis development in APOE*3-Leiden (E3L) mice.MethodsHyperlipidemic E3L mice were intranasally instilled with 10 μg LPS or vehicle twice in an acute 4-day study, or twice weekly during 20 weeks Western-type diet feeding in a chronic study. Mice received 0.5x106 MSC or vehicle intravenously twice after the first LPS instillation (acute study) or in week 14, 16, 18 and 20 (chronic study). Inflammatory parameters were measured in bronchoalveolar lavage (BAL) and lung tissue. Emphysema, pulmonary inflammation and atherosclerosis were assessed in the chronic study.ResultsIn the acute study, intranasal LPS administration induced a marked systemic IL-6 response on day 3, which was inhibited after MSC treatment. Furthermore, MSC treatment reduced LPS-induced total cell count in BAL due to reduced neutrophil numbers. In the chronic study, LPS increased emphysema but did not aggravate atherosclerosis. Emphysema and atherosclerosis development were unaffected after MSC treatment.ConclusionThese data show that MSC inhibit LPS-induced pulmonary and systemic inflammation in the acute study, whereas MSC treatment had no effect on inflammation, emphysema and atherosclerosis development in the chronic study.

Systemic inflammation in COPD is not influenced by pulmonary rehabilitation

Purpose: Pulmonary rehabilitation is known to lead to improvements in exercise tolerance, health-related quality of life and help reduce symptoms. Exercise, one of the largest components of such an intervention, although of great benefit, can increase the inflammatory response related to chronic obstructive pulmonary disease, depending on intensity and duration. Through this study, the effects of a 12week, high-intensity PR programme on COPD inflammatory-related markers were investigated.Materials and methods: This study is a longitudinal, observational type of study. Sixty COPD patients were enrolled, 49 of which completed the programme. A 2-h high-intensity PR programme was delivered, twice weekly for 12 weeks. The following markers were assessed at baseline, 4, 8 and 12 weeks through rehabilitation – C-reactive protein, erythrocyte sedimentation rate, neutrophil, eosinophil counts, complete blood count, six-minute walk test and St. George’s Respiratory Questionnaire. Serum amyloid A levels were assessed at baseline, week 8 and 12 and exhaled NO at baseline and upon completion of the programme.Results: This 12-week PR programme resulted in no changes in the inflammatory markers but resulted in significant improvements in both the 6MW distance and health quality of life.Conclusions: Beneficial effects on functional and HRQoL measures resulted, which, however, appear unrelated to changes in the systemic inflammatory markers.

Assessment of reduced mineral bone density in COPD

BackgroundChronic obstructive pulmonary disease (COPD) is responsible for reduced bone mineral density (BMD).AimThe aim of this study was to explore and assess the association of low BMDwith systemic inflammation in patients with COPD.Patients and methodsA total of 10 healthy normal control individuals and 30 patients with clinically stable COPD (Global Initiative for Chronic Obstructive Lung Disease stages I–III) were included in the study and divided into four groups. All patients underwent chest radiography; computed tomographic scan of the chest; spirometry; dual-energy X-ray absorptiometry for measurement of BMD of the lumbar (L) spines, forearm, and femur; and blood sampling for measurement of C-reactive protein (CRP) and total and ionized serum calcium.Statistical analysisDescriptive data are expressed as mean±SD. Pearson’s correlation analysis was used for drawing correlations.ResultsOsteoporosis in the spine was detected in 20% of both mild and moderate COPD cases and 100% of severe COPD cases, with statistical significant difference between patients with severe COPD and control group (P=0.027). Osteoporosis in the femur bone was shown in 30, 50, and 90% of mild, moderate, and severe COPD cases, respectively, whereas 20% of moderate and 30% of severe COPD cases had osteoporosis in the forearm. T-scores of BMD were different among the four studied groups (P=0.0001). BMD correlated positively with BMI and forced expiratory volume at timed interval 1 s (%) predicted. CRP values differed significantly between the four studied groups (P=0.0001). CRP correlated negatively with forced expiratory volume at timed interval 1 s (%) predicted and BMD.ConclusionCRP is seen in high levels with low BMD in severe COPD, indicating the association of low BMD with systemic inflammation in COPD.

Sarcopenia correlates with systemic inflammation in COPD.

BackgroundMuscle wasting and chronic inflammation are predominant features of patients with COPD. Systemic inflammation is associated with an accelerated decline in lung function. In this study, the prevalence of sarcopenia and the relationships between sarcopenia and systemic inflammations in patients with stable COPD were investigated.Materials and methodsIn a cross-sectional design, muscle strength and muscle mass were measured by handgrip strength (HGS) and bioelectrical impedance analysis in 80 patients with stable COPD. Patients (≥40 years old) diagnosed with COPD were recruited from outpatient clinics, and then COPD stages were classified. Sarcopenia was defined as the presence of both low muscle strength (by HGS) and low muscle mass (skeletal muscle mass index [SMMI]). Levels of circulating inflammatory biomarkers (IL-6 and high-sensitivity TNFα [hsTNFα]) were measured.ResultsSarcopenia was prevalent in 20 (25%) patients. Patients with sarcopenia were older, had lower body mass index, and a higher percentage of cardiovascular diseases. In addition, they had significantly higher modified Medical Research Council scores and lower 6-minute walk distance than those without sarcopenia. HGS was significantly correlated with age, modified Medical Research Council score, and COPD Assessment Test scores. Both HGS and SMMI had associations with IL-6 and hsTNFα (HGS, r=−0.35, P=0.002; SMMI, r=−0.246, P=0.044) level. In multivariate analysis, old age, lower body mass index, presence of cardiovascular comorbidities, and higher hsTNFα levels were significant determinants for sarcopenia in patients with stable COPD.ConclusionSarcopenia is very common in patients with stable COPD, and is associated with more severe dyspnea-scale scores and lower exercise tolerance. Systemic inflammation could be an important contributor to sarcopenia in the stable COPD population.

SMOKING’S ROLE IN THE PATHOGENESIS OF BRONCHIAL AND SYSTEMIC INFLAMMATION AT THE INITIAL STAGE COPD

COPD is characterized by a pathological inflammatory response in the lungs. Inflammation is qualitatively and quantitatively different from that of smokers and persons without nicotine addiction. There is evidence for the presence of systemic inflammation in COPD, which probably originates in the lungs. Immune system was investigated on the basis of blood cytotoxic lymphocytes such as cytotoxic T — lymphocytes and NK — cells in patients with COPD 2 tbsp. The study included 42 patients with COPD severity according to 2 g (22) GOLD 2014 criteria. 22 patients with COPD 2 tbsp had smoking index of at least 20 pack \ years and 20 patients who had never smoked. In all patients, there were no data on atopy and asthma history. All surveyed patients received inhaled M-holinolitik — tiotropium bromide monohydrate 18 micrograms, and on-demand short-acting bronchodilators for 2 breaths. Age of patients was 1 group (smokers) from 50 to 62 years (mean age 54,1±1,3 years) .2 The second group — 58-75 years (58,21±0,7 years). By indirect immunofluorescence were determined relative and absolute content in peripheral blood lymphocytes, ekspresiruyuschie antigens CD3, CD4, CD16, CD20, CD23, CD25, CD54, CD71, CD72, HLA-DR, CD95, membrane immunoglobulin mIgM and mIgG. As a result of the study it was found that patients in the early stages of COPD 2 tbsp. there was a significant change in blood levels of cytotoxic lymphocytes, regardless of the addiction to smoking. But when smoking signs “oxidative stress” are more pronounced, resulting in a more rapid and possibly further more severe course of the disease. Thus, COPD is characterized by the development of systemic inflammation, however, the underlying mechanisms, as well as the desirability and feasibility of the suppression of inflammatory processes require further study.

Myeloid‑derived suppressor cells in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease.

INTRODUCTION Myeloid‑derived suppressor cells (MDSCs) have the potent ability to suppress T‑cell function, and are important in the regulation of chronic inflammation and carcinogenesis. MDSCs may influence local and systemic inflammation and carcinogenesis in COPD; however, their presence in bronchoalveolar lavage fluid (BALF) and peripheral blood (PB) or their relationship with clinical parameters in COPD has not been studied yet. OBJECTIVES The aim of the study was to assess MDSCs in BALF and PB and to analyze the relationship between MDSCs and clinical parameters in COPD. PATIENTS AND METHODS The study included 64 patients with stable COPD. The clinical parameters of the patients were studied, and MDSCs were assessed using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. RESULTS The percentage of MDSCs in BALF was lower than that in PB (0.63 ±0.90 vs 3.94 ±0.38). In BALF, MDSCs (% of mononuclear cells) correlated with forced expiratory volume in 1 second (rs = -0.30, P = 0.0185), residual volume/total lung capacity (rs = 0.32, P = 0.0148), PaO2 (rs = -0.45, P = 0.0002), arterial oxygen saturation (SaO2; rs = -0.41, P = 0.0008), and diffusion capacity of carbon dioxide (rs = -0.32, P = 0.0211). There was a significant negative correlation between MDSCs (% of all leukocytes) and arterial oxygen pressure (rs = -0.42, P = 0.0006) and SaO2 (rs = -0.37, P = 0.0027). No correlations were found in PB. CONCLUSIONS MDSCs are present in human lung microenvironment and may be involved in local inflammation in COPD. Future studies should focus on a detailed assessment of MDSCs in local and systemic inflammation in COPD.

Steroid resistance in COPD is associated with impaired molecular chaperone Hsp90 expression by pro-inflammatory lymphocytes.

BackgroundCorticosteroid resistance is a major barrier to effective treatment of COPD. We have shown that the resistance is associated with decreased expression of glucocorticoid receptor (GCR) by senescent CD28nullCD8+ pro-inflammatory lymphocytes in peripheral blood of COPD patients. GCR must be bound to molecular chaperones heat shock proteins (Hsp) 70 and Hsp90 to acquire a high-affinity steroid binding conformation, and traffic to the nucleus. We hypothesized a loss of Hsp70/90 from these lymphocytes may further contribute to steroid resistance in COPD.MethodsBlood was collected from COPD (n = 10) and aged-matched controls (n = 10). To assess response to steroids, cytotoxic mediators, intracellular pro-inflammatory cytokines, CD28, GCR, Hsp70 and Hsp90 were determined in T and NKT-like cells in the presence of ± 10 μM prednisolone and 2.5 ng/mL cyclosporine A (binds to GCR-Hsp70/90 complex) using flow cytometry, western blot and fluorescence microscopy.ResultsA loss of expression of Hsp90 and GCR from CD28null CD8+ T and NKT-like cells in COPD was noted (Hsp70 unchanged). Loss of Hsp90 expression correlated with the percentage of CD28null CD8+ T and NKT-like cells producing IFNγ or TNFα in all subjects (eg, COPD: R = −0.763, p = 0.007 for T-cell IFNγ). Up-regulation of Hsp90 and associated decrease in pro-inflammatory cytokine production was found in CD28nullCD8+ T and NKT-like cells in the presence of 10 μM prednisolone and 2.5 ng/mL cyclosporine A.ConclusionsLoss of Hsp90 from cytotoxic/pro-inflammatory CD28nullCD8+ T and NKT-like cells could contribute to steroid resistance in COPD. Combination prednisolone and low-dose cyclosporine A therapy inhibits these pro-inflammatory cells and may reduce systemic inflammation in COPD.

Rosuvastatin, lycopene and omega-3 fatty acids: A potential treatment for systemic inflammation in COPD; a pilot study

Background/AimsChronic Obstructive Pulmonary Disease (COPD) is characterized by airway inflammation, in which contributes to loss of lung function. Systemic inflammation is also a feature of COPD contributing to many associated co-morbidities. Statins, omega-3 fatty acids (docosahexanoic acid, DHA and eicosapentanoic acid, EPA) and lycopene have been shown to decrease systemic inflammation; however their combined effects have not been investigated. This study aims to identify changes in systemic and airway inflammation induced by statins alone or in combination with DHA, EPA and lycopene in COPD. MethodsCOPD patients (n = 11) received rosuvastatin (20 mg/day) for 4 weeks, then a combination of rosuvastatin (20 mg/day), DHA and EPA (1.5 g/day) and lycopene (45 mg/day) for 8 weeks. Blood and sputum were collected and lung function measured by spirometry at baseline, week 4 and 12. Plasma fatty acids were measured using gas chromatography, while plasma carotenoids were analysed using high-performance liquid chromatography. Plasma CRP and IL-6 concentrations were measured using ELISA; and peripheral blood gene expression was measured using the nCounter™ GX Human Inflammation Kit 2. ResultsFollowing the interventions, clinical characteristics and plasma IL-6 and CRP were unchanged. Sputum neutrophil proportion and absolute count was increased and macrophage proportion decreased by rosuvastatin (P = 0.020 and P = 0.015; respectively). Rosuvastatin increased LTB4R and decreased CXCL10 and AGER gene expression in white blood cells. The addition of lycopene and omega-3 fatty acids decreased LTB4R and increased CXCL10 to basal levels, whilst combined use of interventions increased ALOX15 blood gene expression. ConclusionThis study shows that rosuvastatin, omega-3 fatty acids and lycopene have some anti-inflammatory effects systemically, but rosuvastatin may increase airway neutrophils, which would be undesirable in COPD patients, warranting further investigation.

Rosuvastatin, lycopene and omega-3 fatty acids: A potential treatment for systemic inflammation in COPD

Rosuvastatin, lycopene and omega-3 fatty acids: A potential treatment for systemic inflammation in COPD

Lymphocyte senescence in COPD is associated with decreased histone deacetylase 2 expression by pro-inflammatory lymphocytes.

BackgroundHistone acetyltransferases (HAT) and histone deacetylases (HDAC) are enzymes that upregulate and down-regulate pro-inflammatory gene transcription respectively. HDAC2 is required by corticosteroids to switch off activated inflammatory genes and is reduced in lung macrophages in COPD. We have shown that COPD patients have increased steroid resistant CD28null (senescent) pro-inflammatory T and NKT-like peripheral blood cells (particularly CD8+ subsets) and we hypothesized that these changes would be associated with a loss of HDAC2 from these senescent pro-inflammatory lymphocytes.MethodsBlood was collected from 10 COPD and 10 aged-matched controls. Intracellular pro-inflammatory cytokines, IFNγ and TNFα, and expression of CD28, HDAC2 and HAT, were determined in lymphocyte subsets in the presence of ± 5 mg/ml theophylline (HDAC2 activator), 10 μM prednisolone and 2.5 ng/ml cyclosporine A (immunosuppressant), using flow cytometry.ResultsThere was a loss of HDAC2 from CD28null CD8+ T and NKT-like cells in COPD. There was a significant negative correlation between HDAC2 expression and the percentage of CD28null CD8+ T and NKT-like cells producing IFNγ or TNFα in all subjects (eg, COPD: R = −.763, p < 0.001 for T-cell IFNγ). There was a synergistic upregulation of HDAC2 and associated decrease in pro-inflammatory cytokine production in CD28nullCD8+ T and NKT-like cells in the presence of 5 mg/L theophylline + 10−6 M prednisolone or 2.5 ng/mL cyclosporine A (CsA).ConclusionsLymphocyte senescence in COPD is associated with loss of HDAC2 in CD28nullCD8+ T and NKT-like cells. Alternative treatment options such as combined theophylline with low-dose CsA, that inhibit these pro-inflammatory cells, may reduce systemic inflammation in COPD.

Evaluation of serum interleukin-1 beta as an inflammatory marker in COPD patients

BackgroundCOPD is a chronic disease of the lungs characterized by increased obstruction to airflow that does not change markedly over periods of several months. Low-grade systemic inflammation is considered a hallmark of COPD that potentially links COPD to increased rate of systemic manifestations of the disease. Evaluation of systemic inflammation in COPD particularly when the disease is severe and during exacerbation can be measured either as increased circulating cytokines, chemokines and acute phase proteins, or as abnormalities in the circulating cells and markers. One of these inflammatory mediators is IL-1B which demonstrated recent reports in significantly high levels of IL-1β in serum of the COPD patients as compared to the healthy controls. Aim of the studyTo assess the level of serum IL-1B in chronic obstructive pulmonary disease patients during acute exacerbation and in stable conditions and also, to determine if the changes in its level correlated with changes in the ventilatory functions. Methods80 cases were included in this study: 60 COPD patients and 20 healthy subjects as a control. There were 48 males and 12 females in COPD groups and 17 males and 3 females in the control group. Their age ranged from 41 to 79years with a mean age of 59years. The subjects were classified into 3 groups. Group I includes (30) patients with acute exacerbation of COPD. Group II includes (30) patients with stable controlled COPD. Group III includes (20) healthy persons as a control. ResultsThere was a highly statistically significant difference in serum IL-1B (pg/ml) between studied groups, which indicates that IL-1B plays a role in systemic inflammatory process. There was a highly statistically significant difference in serum IL-1B concentration (pg/ml) and severity of COPD cases. ConclusionsIL-1β correlated with clinical aspects of disease severity, suggesting that IL-1β may play a critical role in COPD.

Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study.

BackgroundModerate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients.MethodsTo investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines.ResultsPatients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months. Patients in the control group had no improvement. Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline. IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group. The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group.ConclusionsA mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients. Decreased systemic inflammation may contribute to these clinical benefits. (Clinical trial registration No.: NCT01631019)

A possible link between increased metabolic activity of fat tissue and aortic wall inflammation in subjects with COPD. A retrospective 18F-FDG-PET/CT pilot study

Fat tissue, and particularly visceral fat, is known to play a role in low grade systemic inflammation in COPD, and is likely to contribute to the excess cardiovascular comorbidity in COPD. Therefore, we aimed to study (18)FDG-PET-assessed inflammation of the aorta and the (visceral) fat, and evaluate its interrelations and differences in subjects with and without COPD. We retrospectively identified 42 patients (71% male, 48% current smokers, mean age 66.6 ± 8.3 years, mean BMI 25.1 ± 4.3 kg/m(2)), who underwent (18)F-FDG-PET/CT for suspected early stage bronchus carcinoma. COPD-diagnosis was based on spirometry and defined as FEV1/FVC < lower limit of normal. Inflammatory status of aortic and fat regions was defined as the average of obtained maximum target-to-background ratios (meanTBRmax). The TBR is the standardized uptake value (SUV) normalized to (18)F-FDG blood pool activity. Compared to controls, patients with COPD (n = 19; 45%) had increased meanTBRmax of both the abdominal aorta (1.31 ± 0.14 vs. 1.49 ± 0.31; p = 0.02) and the abdominal visceral fat (0.28 ± 0.09 vs. 0.38 ± 0.18; p = 0.047), while inflammatory activity of the abdominal subcutaneous fat failed to show statistically significant differences (0.21 ± 0.09 vs. 0.24 ± 0.09; p = 0.345). In all patients, meanTBRmax of abdominal visceral fat was correlated with meanTBRmax of the abdominal aorta, independently of age and BMI (β = 0.590, p = 0.002). Metabolic activity of the abdominal aorta and visceral fat is increased in COPD patients compared to peers. The degree of visceral fat metabolic activity is associated with aortic inflammation. More prospective research is warranted concerning the role of visceral fat in the development of vascular comorbidity in COPD.

Daily Step Count Is Associated With Plasma C-Reactive Protein and IL-6 in a US Cohort With COPD

Physical activity is an important clinical marker of disease status in COPD. COPD is also characterized by low-grade systemic inflammation. However, the relationship between physical activity and systemic inflammation in COPD is unclear. We monitored daily step count, a directly measured physical activity, using the StepWatch Activity Monitor, an ankle-worn accelerometer, in 171 people with stable COPD. Exercise capacity was assessed with the 6-min walk test (6MWT). We measured plasma C-reactive protein (CRP) and IL-6 levels. Linear regression models examined the cross-sectional associations of daily step count and 6MWT distance with CRP and IL-6 levels. Subjects had a mean age 72±8 years and mean FEV1 1.5±0.57 L (54±20% predicted). Median daily step count was 5,203 (interquartile range [IQR], 3,627-7,024], CRP level was 2.4 mg/L (IQR, 1.2-5.0), and IL-6 level was 2.9 pg/mL (IQR, 2.0-5.1). Each 1,000-step increase in daily step count was associated with a 0.94 mg/L and 0.96 pg/mL decrease in CRP (P=.020) and IL-6 (P=.044) levels, respectively, adjusting for age, FEV1 % predicted, pack-years smoked, cardiac disease, current statin use, history of acute exacerbations, and season. There was a significant linear trend of increasing daily step count by quartiles and decreasing CRP (P=.0007) and IL-6 (P=.023) levels. Higher 6MWT distance was also significantly associated with lower CRP and IL-6 values. People with COPD who walked the most had the lowest plasma CRP and IL-6 levels. These results provide the conceptual basis to study whether an intervention to promote walking will reduce systemic inflammation in people with COPD.

Increased circulating obestatin in patients with chronic obstructive pulmonary disease

Background: Some peptides, which regulate the metabolic balance, are thought to play important roles in nutritional disorders and systemic inflammation in COPD. Treatment of rats with obestatin decreased body-weight gain. Obestatin was also found to be correlated with inflammation in rheumatoid arthritis. The aims of this study were to investigate the level of circulating obestatin in COPD and to analyze the relationship among obestatin and nutritional status, and systemic inflammation.&#x0D; Methods: 32 COPD patients with BMI less than 20 kg/m2 and 22 normal controls were included. Body composition was estimated using “foot-to-foot” BIA technology. Circulating obestatin was determined with enzyme-linked immunosorbent assay. Pulmonary function, TNF-α and C reactive protein were also measured.&#x0D; Results: The level of circulating obestatin was higher in COPD with underweight than that in normal control (5562.75 ± 3435.43 pg/ml in COPD, 3663.90 ± 2313.95 pg/ml in controls, p = 0.028). BMI, Waist circumference, hip circumference, bodyFAT and FAT% in COPD group were lower than those in normal control. Positive correlation was found among circulating C reactive protein, TNF-α and obestatin. There was no significant correlation among BMI, pulmonary function and obestatin.&#x0D; Conclusions: This study shows that circulating obestatin is higher in underweight COPD patients, and positively correlated to systemic inflammation, but not to nutritional status.

Increased circulating obestatin in patients with chronic obstructive pulmonary disease

BackgroundSome peptides, which regulate the metabolic balance, are thought to play important roles in nutritional disorders and systemic inflammation in COPD. Treatment of rats with obestatin decreased body-weight gain. Obestatin was also found to be correlated with inflammation in rheumatoid arthritis. The aims of this study were to investigate the level of circulating obestatin in COPD and to analyze the relationship among obestatin and nutritional status, and systemic inflammation.Methods32 COPD patients with BMI less than 20 kg/m2 and 22 normal controls were included. Body composition was estimated using “foot-to-foot” BIA technology. Circulating obestatin was determined with enzyme-linked immunosorbent assay. Pulmonary function, TNF-α and C reactive protein were also measured.ResultsThe level of circulating obestatin was higher in COPD with underweight than that in normal control (5562.75 ± 3435.43 pg/ml in COPD, 3663.90 ± 2313.95 pg/ml in controls, p = 0.028). BMI, Waist circumference, hip circumference, bodyFAT and FAT% in COPD group were lower than those in normal control. Positive correlation was found among circulating C reactive protein, TNF-α and obestatin. There was no significant correlation among BMI, pulmonary function and obestatin.ConclusionsThis study shows that circulating obestatin is higher in underweight COPD patients, and positively correlated to systemic inflammation, but not to nutritional status.