Role of serum interleukin-6 in detecting disease severity in chronic obstructive pulmonary disease patients

Introduction: Little is known about protease, anti-protease markers in chronic obstructive pulmonary disease (COPD) patients. Objectives: The objective of present study was to identify and try to correlate serum markers of protease and anti-protease with pulmonary functions in different stages of patients with COPD and to determine the ratio of neutrophil elastase/alpha-1-antitrypsin in different stages of COPD patients. Methods: This prospective observational study was carried out in patients with stable COPD. Activities of serum alpha-1-antitrypsin and neutrophil elastase were measured in 220 stable COPD patients and in 60 healthy controls by ELISA method. 220 COPD patients were divided into 4 stages according to severity: stage I, II, III and IV. Results: An increase in serum neutrophil elastase and neutrophil elastase/alpha-1-antitrypsin ratio was observed in COPD patients with the advancement of the stage. In contrast to that, decreased activity of alpha-1-antitrypsin in serum was observed in different stages of COPD and is correlated positively with lung function parameters. Conclusion: From these findings we conclude that as the severity increases there is decrease in alpha-1-antitrypsin resulting in concomitant increase in neutrophil elastase activity causing imbalance between protease-antiprotease in COPD patients and this imbalance is associated with impairment of lung function. The neutrophil elastase/ α-1-antitrypsin ratio can tell us the severity of the chronic obstructive pulmonary disease it may be in terms of increased fibrosis of the lung. Though the magnitude of neutrophil elatase/alpha-1-antitrypsin ratio is minute, still it can be a good marker of pulmonary function in term of severity of the COPD.


 
 
 Background and aims: Recently a multidimensional grading system based on the body mass index (B), degree of airflow obstruction (O), dyspnea (D) and exercise capacity (E) - the BODE index - has begun to be used increasingly for the evaluation of chronic obstructive pulmonary disease (COPD) patients. The aim of our study was to investigate the relation- ship between the BODE index and disease duration, annual exacerbation and hospitalization rates, health related quality of life and systemic inflammatory markers like C-reactive protein (CRP), tumor necrosis factor (TNF)-α and interleukin (IL)-8.
 Materials and methods: In 88 stable COPD patients we evalu- ated the body-mass index, pulmonary function tests, Modified Medical Research Council dyspnea scale and six- minute walk test (6MWT). BODE scores were determined. Disease duration, number of exacerbations and hospitaliza- tion in the previous year were recorded. We also performed arterial blood gases analysis, administered the St. George’s Respiratory Questionnaire (SGRQ) and measured serum lev- els of CRP, TNF-α, IL-8.
 Results: According to BODE score 52% of patients were BODE 1, 21% BODE 2, 15% BODE 3 and 12% were BODE 4. There was a significant relationship between BODE index and COPD stage as classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (p < 0.001). Correlations between BODE score and disease duration (p = 0.011), number of exacerbations (p < 0.001) and hospitaliza- tions (p < 0.001) in the last year were also observed. SGRQ symptom, activity, emotion scores and total scores were found to be significantly correlated to BODE (p < 0.001). Serum CRP levels and BODE were also correlated (p = 0.014); however, no correlation was found between serum levels of TNF-α and IL-8 and BODE.
 
 
 Conclusions: As the BODE index shows a strong correlation with various prognostic and follow up parameters of COPD and systemic inflammation, its use should be considered for the evaluation of COPD patients.
 
 

Background and aimsRecently a multidimensional grading system based on the body mass index (B), degree of airflow obstruction (O), dyspnea (D) and exercise capacity (E) - the BODE index - has begun to be used increasingly for the evaluation of chronic obstructive pulmonary disease (COPD) patients. The aim of our study was to investigate the relationship between the BODE index and disease duration, annual exacerbation and hospitalization rates, health related quality of life and systemic inflammatory markers like C-reactive protein (CRP), tumor necrosis factor (TNF)-α and interleukin (IL)-8.Materials and methodsIn 88 stable COPD patients we evaluated the body-mass index, pulmonary function tests, Modified Medical Research Council dyspnea scale and six-minute walk test (6 MWT). BODE scores were determined. Disease duration, number of exacerbations and hospitalization in the previous year were recorded. We also performed arterial blood gases analysis, administered the St. George's Respiratory Questionnaire (SGRQ) and measured serum levels of CRP, TNF-α, IL-8.ResultsAccording to BODE score 52% of patients were BODE 1, 21% BODE 2, 15% BODE 3 and 12% were BODE 4. There was a significant relationship between BODE index and COPD stage as classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) (p < 0.001). Correlations between BODE score and disease duration (p = 0.011), number of exacerbations (p < 0.001) and hospitalizations (p < 0.001) in the last year were also observed. SGRQ symptom, activity, emotion scores and total scores were found to be significantly correlated to BODE (p < 0.001). Serum CRP levels and BODE were also correlated (p = 0.014); however, no correlation was found between serum levels of TNF-α and IL-8 and BODE.ConclusionsAs the BODE index shows a strong correlation with various prognostic and follow up parameters of COPD and systemic inflammation, its use should be considered for the evaluation of COPD patients.

Chronic obstructive pulmonary disease (COPD) has a profound impact on daily life, yet remains underdiagnosed and undertreated. This study aims to discover potential protein biomarkers for diagnosis and classification of COPD. Fifty-seven COPD patients and 40 controls were divided into a training set (30 COPD patients, 20 healthy controls) and a test set (27 COPD patients, 20 healthy controls). Serum proteomic profiles were measured using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). A classification tree was established using Biomarker Pattern Software (BPS). Next we screened distinct proteins present in patients with acute exacerbations of COPD (AECOPD), stable COPD and healthy controls, in order to establish diagnostic models for classification of COPD. Twenty peaks showed statistically significant differences between COPD patients and healthy controls (P < 0.05). Two proteomic peaks (3167 and 5477 m/z) were chosen by BPS to establish a classification tree in the training set. The sensitivity and specificity of this classification tree were 92.59% and 90.00% respectively in the testing set. Furthermore, differently expressed proteins were detected among the patients with AECOPD, stable COPD, and healthy controls. Two protein profiles (3167 and 4645 m/z) could distinguish between stable COPD patients and healthy controls. Three protein profiles (3167, 2963 and 2973 m/z) could distinguish between AECOPD patients and healthy controls. Three protein profiles (5476, 14039 and 2831 m/z) could distinguish between stable COPD patients and AECOPD patients. SELDI-TOF-MS Proteinchip technology is a quick, easy and practical, high throughput analytic method. It shows the diagnostic models established by distinguished proteomic peaks can discriminate COPD patients from healthy control and can identify different stages of COPD. It will provide a highly accurate approach for diagnosis and clinical staging of COPD.

Maintenance pharmacotherapy of mild and moderate COPD: What is the Evidence?

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a number of different comorbidities. Cardiovascular diseases (CVD) are the most frequent comorbidities in COPD. The economic burden associated with cardiovascular comorbidity (CVC) in this population of patients is considerable. The COPD patients are related to the increased systemic inflammation, reduced capacity for physical activity, and airflow obstruction. AIM: The aim of our investigation was to evaluate the dyspnea as a disabling symptom in COPD patients with cardiovascular comorbidity (CVC) especially heart failure. The main aim of this study is to evaluate its intensity in patients with COPD in stages II according to GOLD. METHODS: The investigation was conducted from December 2019 to January 2020, on pulmonology and allergology clinic and cardiology clinic of medical faculty in Skopje. We investigated 65 outpatients with COPD, 44 with different type of CVD, Group I, and 21 without CVD, Group II. All patients were with partial chronic respiratory failure (In type 1 respiratory failure hypoxemic). Patients, according GOLD initiative, were in COPD stadium II, 70% &lt; forced expiratory volume in 1 s (FEV1)&gt;50%. Heart condition was diagnosed on the basis of clinical examination, electrocardiography, and echocardiography of the heart. Included patients with CVD were with ejection fraction (EF) &lt;65%. Dyspnea was measured with modified MRC (mMRC) dyspnea scale. RESULTS: The forced vital capacity and forced expiratory volume in 1 s were statically significantly higher in Group II with CVD. Dyspnea measured with Modified Medical Research Council (MRC) dyspnea scale showed statistically significantly higher values in Group I COPD patients with CVC (2.9 ± 1.4) versus Group II without CVC (1.7 ± 1.4), (p &lt; 0.05). The perception of the higher dyspnea in Group I was associated with increased COPD assessment test-scores, in Group I: Group I (19.8 ± 9.1) versus Group II: (9.8 ± 9.1), (p &lt; 0.001). The number of exacerbations and what is more important the number of severe exacerbation leading to hospitalizations was statistically higher in patients of Group I with CVC than in Group II without CVC (3.0 ± 1.1 vs. 1.0 ± 2.1), (p &lt; 0.001) and the number of hospitalizations (1.0 ± 1.1 vs. 0.3 ± 2.1) (p &lt; 0.001). CONCLUSION: We can conclude that patients with COPD who have CVC have an increased risk of high symptoms, which mean poor quality of life and increased morbidity.

Correlation of serum vascular adhesion protein-1 with airflow limitation and quality of life in stable chronic obstructive pulmonary disease.

Objective To value different stages of chronic obstructive pulmonary disease (COPD) patients with the detection of the levels of serum thymic stromal lymphopoietin (TSLP), serum amyloid A (SAA), and C-reactive protein (CRP). Methods A total of 33 patients with COPD during and after hospitalization and 16 healthy controls were enrolled in the study from the 3rd affiliated hospital of SYSU. Differences and correlations of the level of serum TSLP, SAA and CRP were analyzed to value the veracity of those factors in different stages of COPD. Results The levels of CRP and SAA were higher in acute exacerbation of COPD (AECOPD) group than stable COPD group, TSLP was lower in the AECOPD group than the healthy control group (P<0.05). CRP had a positive correlation with SAA (correlation r=0.546, P=0.000), CRP [area under curve (AUC) =0.797] and SAA (AUC=0.815), and they were statistically significant in identity of different stages of COPD (P<0.05). Conclusions Serum TSLP level is decreased in acute exacerbation phase of COPD. CRP and SAA are increased in AECOPD. SAA is more confident in identity of different phases of COPD. Key words: Lymphopoiesis; Thymus gland/CY/ME; Serum amyloid A protein/ME; C-reactive protein/ME; Pulmonary disease, chronic obstructive/ME

BackgroundThe burden of symptoms and risk of exacerbations are the main drivers of the overall assessment of the Chronic Obstructive Pulmonary Disease (COPD) and the adequate treatment approaches per current Global Initiative for Chronic Obstructive Lung Disease (GOLD). Physical activity has emerged as both functional outcome and non-pharmacological intervention in COPD patients, despite the lack of standardized measures or guidelines in clinical practice. This study aimed to explore in more depth the 24-h respiratory symptoms, the physical activity level (PAL) and the relationship between these two determinants in stable COPD patients.MethodsThis was a multinational, multicenter, observational, cross-sectional study conducted in ten European countries and Israel. Dedicated questionnaires for each part of the day (morning, daytime, night) were used to assess respiratory symptoms. PAL was evaluated with self- and interview-reported tools [EVS (exercise as vital sign) and YPAS (Yale Physical Activity Survey)], and physician’s judgement. Patients were stratified in ABCD groups by 2013 and 2017 GOLD editions using the questionnaires currently recommended: modified Medical Research Council dyspnea scale and COPD Assessment Test.ResultsThe study enrolled 2190 patients (mean age: 66.9 years; male: 70.0%; mean % predicted FEV1: 52.6; GOLD groups II-III: 84.5%; any COPD treatment: 98.9%). Most patients (> 90%) reported symptoms in any part of the 24-h day, irrespective of COPD severity. PAL evaluations showed discordant results between patients and physicians: 32.9% of patients considered themselves completely inactive, while physicians judged 11.9% patients as inactive. By YPAS, the overall study population spent an average of 21.0 h/week performing physical activity, and 68.4% of patients were identified as sedentary. In any GOLD ABCD group, the percentage of inactive patients was high. Our study found negative, weak correlations between respiratory symptoms and self-reported PAL (p < 0.001).ConclusionsDespite regular treatment, the majority of stable COPD patients with moderate to severe disease experienced daily variable symptoms. Physical activity level was low in this COPD cohort, and yet overestimated by physicians. With evidence indicating the negative consequences of inactivity, its adequate screening, a more active promotion and regular assessment of physical activity are urgently needed in COPD patients for better outcomes.Trial registrationNCT03031769, retrospectively registered, 23 Jan 2017.

Larger proportions of chronic obstructive pulmonary disease (COPD) patients are currently overweight or with obesity than underweight, and the combination of COPD and obesity is increasing. The purpose of this study was to investigate differences in the body composition, pulmonary function tests, exercise capacity, and health-related quality of life among normal weight, overweight, and obese patients with COPD. A total of 514 patients with COPD were included in the study. According to the World Health Organization criteria for body mass index, the patients were classified as normal weight, overweight, and obese. Evaluations included fat-free mass, fat-free mass index, phase angle, pulmonary function tests, and 6-minute walk test. Dyspnea was assessed using the modified Medical Research Council dyspnea scale, and the health-related quality of life was evaluated using COPD Assessment Test and St. George's Respiratory Questionnaire. Values were compared among the three groups. There were 315 male and 199 female patients, with a mean age of 66.7 ± 8.4years. Fat-free mass, fat-free mass index, and phase angle values were significantly higher in COPD patients with obesity than in other patients (P < .001, P < .001, P < .001). Forced expiratory volume in 1 s, forced expiratory volume in 1 s/forced vital capacity, and diffusing capacity of lung for carbon monoxide value in pulmonary function tests were significantly higher in COPD patients with obesity than in other patients (P = .046, P < .001, P < .001), while the forced vital capacity values were similar in all groups. Exercise capacity (6-min walk test distance), dyspnea symptoms (modified Medical Research Council scale), and health-related quality of life (COPD Assessment Test and St. George's Respiratory Questionnaire) did not differ significantly between groups. According to our study, obesity has no negative effect on pulmonary function tests, dyspnea perception, exercise capacity, and health-related quality of life.

Background: The association between low body mass index (BMI) and poor prognosis of patients with chronic obstructive pulmonary disease (COPD) is a common clinical observation and it varies with different stages of COPD. Aims: To find out any correlation between BMI and severity of obstruction (Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging) of COPD patients. Settings and Design: We conducted a cross-sectional, observational study among 101 male patients of COPD, attending the chest medicine department in our medical college during the period from March 2011 to February 2012. Materials and Methods: We classify the severity of obstruction in COPD patients according to GOLD staging through spirometry. BMI of all the patients was measured. Correlation between BMI and severity of obstruction (post bronchodilator forced expiratory volume in 1 st second (FEV 1 ) % predicted) in COPD patients was determined. Statistical Analysis: Analysis was carried out using Statistical Package for Social Sciences (SPSS) 20.0 software for windows. Pearson correlation, one way analysis of variance (ANOVA) analysis and post hoc Turkey test were used to determine the relationship between BMI and post bronchodilator FEV 1 %predicted. Results: Mean age of the study subject was 58.18 ± 9.29 years. Commonest age group was 50-59 years (40%). Mean BMI of stage 1 COPD subjects was 26.21, stage 2 was 22.91, stage 3 was 20.78, and stage 4 was 15.71. One-way ANOVA showed that BMI of the patients were decreasing with increasing severity of the disease (GOLD) and it was statistically significant (P < 0.05). The post hoc Turkey test also indicated that there were significant differences present in different GOLD stages of COPD in respect to BMI. Conclusion: There was positive correlation between severity of airway obstruction and BMI in COPD patients.

IntroductionChemokine (C-C motif) ligand 18 (CCL-18) has been shown to be elevated in chronic obstructive pulmonary disease (COPD) patients. This study primarily aimed to evaluate whether the serum CCL-18 level differentiates the frequent exacerbator COPD phenotype from infrequent exacerbators. The secondary aim was to investigate whether serum CCL-18 level is a risk factor for exacerbations requiring hospitalization.Materials and methodsClinically stable COPD patients and participants with smoking history but normal spirometry (NSp) were recruited for the study. Modified Medical Research Council Dyspnea Scale, COPD Assessment Test, spirometry, and 6-min walking test were performed. Serum CCL-18 levels were measured with a commercial ELISA Kit.ResultsSixty COPD patients and 20 NSp patients were recruited. Serum CCL-18 levels were higher in COPD patients than those in NSp patients (169 vs 94 ng/mL, P<0.0001). CCL-18 level was significantly correlated with the number of exacerbations (r=0.30, P=0.026), although a difference in CCL-18 values between infrequent and frequent exacerbator COPD (168 vs 196 ng/mL) subgroups did not achieve statistical significance (P=0.09). Serum CCL-18 levels were significantly higher in COPD patients who had experienced at least one exacerbation during the previous 12 months. Overall, ROC analysis revealed that a serum CCL-18 level of 181.71 ng/mL could differentiate COPD patients with hospitalized exacerbations from those who were not hospitalized with a 88% sensitivity and 88.2% specificity (area under curve: 0.92). Serum CCL-18 level had a strong correlation with the frequency of exacerbations requiring hospitalization (r=0.68, P<0.0001) and was found to be an independent risk factor for hospitalized exacerbations in the multivariable analysis.ConclusionCCL-18 is a promising biomarker in COPD, as it is associated with frequency of exacerbations, particularly with severe COPD exacerbations requiring hospitalization, as well as with functional parameters and symptom scores.

PurposeNT-proBNP, a peptide biomarker synthesized and secreted by cardiomyocytes in response to cardiac load, has gained attention in recent years for its potential role in respiratory diseases. Chronic Obstructive Pulmonary Disease (COPD), a chronic and progressive inflammatory condition affecting the respiratory system, is frequently associated with comorbidities involving the cardiovascular system. Consequently, the aim of this systematic review and meta-analysis was to evaluate the variations in NT-proBNP levels across distinct patient groups with COPD and establish a foundation for future investigations into the precise clinical significance of NT-proBNP in COPD.MethodsThe search databases for this study were conducted in PubMed, Excerpt Medica database (Embase), Web of Science (WOS), and Cochrane Library databases. Databases were searched for studies on the predictive value of NT-proBNP in adult COPD patients.ResultsA total of 29 studies (8534 participants) were included. Patients with stable COPD exhibit elevated levels of NT-proBNP [standardized mean difference(SMD) [95CI%]=0.51 [0.13,0.89]; p=0.0092]. COPD patients with predicted forced expiratory volume in 1 s (FEV1) < 50% exhibit significantly elevated levels of NT-proBNP compared to those with FEV1 ⩾50%[SMD [95CI%]=0.17 [0.05,0.29]; p=0.0058]. NT-proBNP levels were significantly higher in acute exacerbations (AECOPD) compared to patients with stable COPD [SMD [95CI%]=1.18 [0.07,2.29]; p=0.037]. NT-proBNP levels was significantly higher in non-survivors than in survivors of hospitalised AECOPD patients [SMD [95CI%]=1.67 [0.47,2.88]; p=0.0063]. Both COPD patients with pulmonary hypertension(PH) [SMD [95CI%]=0.82 [0.69,0.96]; p<0.0001] and chronic heart failure(CHF) [SMD [95CI%]=1.49 [0.96,2.01]; p<0.0001] showed higher NT-proBNP level.ConclusionNT-proBNP, a biomarker commonly used in clinical practice to evaluate cardiovascular disease, demonstrates significant variations in different stages of COPD and during the progression of the disease. The fluctuations in NT-proBNP levels could be indicative of the severity of pulmonary hypoxia and inflammation and cardiovascular stress among COPD patients. Therefore, assessing NT-proBNP levels in COPD patients can aid in making informed clinical decisions.

Background Chronic obstructive pulmonary disease (COPD) is a respiratory conditionimpacting daily activities of susceptible individuals and increasing the risk of respiratory infections and cardiovascular disease. Body Mass Index, AirflowObstruction, Dyspnea, and Exercise Capacity (BODE) index is applied clinically to measure the survival of COPD patients. Inflammatory mediators, including cytokines and chemokines, significantly contribute to the COPD pathology. In this study, the association between the BODE index and systemic inflammatory mediators in stable COPD patients was evaluated. Methodology This was a cross-sectional observational study performed on 85 clinically stable COPD patients and the GOLD criteria were used for the diagnosis. The demographics and clinical history of the patients were documented. The clinical assessment comprising the Modified Medical Research Council (MMRC) dyspnea scale, COPD Assessment Test (CAT) and BODE index was measured. The serum levels of systemic inflammatory mediators, tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and interleukin-6 (IL-6) were measured. The association between the BODE index and inflammatory markers was analyzed using Pearson's correlation analysis. Results The majority of patients (61.2%) were in stage I BODE index and BODE index showed a significant correlation with GOLD stage severity (p=0.001). The CRP, TNF-α and IL-6 levels were increased in BODE stage IV when compared to stage III, II and I (p=0.001). The CRP (r=0.654; p=0.000), TNF-α (0.542; p=0.01) and IL-6 (r=0.498; p=0.02) showed significant correlation with BODE index. Conclusion The evaluation of the BODE index alongside systemic inflammatory markers is crucial for enhancing the management of COPD and subsequently improving patient outcomes.

Nutritional status and long-term mortality in hospitalised patients with chronic obstructive pulmonary disease (COPD)