Chronic Obstructive Lung Disease Stage Research Articles

Are interstitial lung abnormalities associated with COPD? A nested case-control study.

PurposeIn this study, we tested the association between COPD and interstitial lung abnormality (ILA), notably in relation to the presence of computed tomography (CT) signs of lung fibrosis.Patients and methodsCOPD cases were selected from participants undergoing lung cancer screening (Multicentric Italian Lung Detection trial) for airflow obstruction (n=311/2,303, 13.5%) and 146 consecutive patients with clinical COPD. In all, 457 COPD cases were selected and classified according to the stages of Global Initiative for Chronic Obstructive Lung Disease. A nested matching (case:control = 1:2) according to age, sex, and smoking history was operated between each COPD case and two control subjects from Multicentric Italian Lung Detection trial without airflow obstruction. Low-dose CT scans of COPD cases and controls were reviewed for the presence of ILA, which were classified into definite or indeterminate according to the presence of signs of lung fibrosis.ResultsThe frequency of definite ILA was similar between COPD cases and controls (P=0.2), independent of the presence of signs of lung fibrosis (P=0.07). Combined definite and indeterminate ILA was homogeneously distributed across Global Initiative for Chronic Obstructive Lung Disease stages (P=0.6). Definite ILA was directly associated with current smoker status (odds ratio [OR] 4.05, 95% confidence interval [CI]: 2.2–7.4) and increasing pack-years (OR 1.01, 95% CI: 1–1.02). Subjects with any fibrotic ILA were more likely to be older (OR 1.17, 95% CI: 1.10–1.25) and male (OR 8.58, 95% CI: 1.58–68.9).ConclusionThere was no association between COPD and definite ILA. However, low-dose CT signs of lung fibrosis were also observed in COPD, and their clinical relevance is yet to be determined.

CT-derived Biomechanical Metrics Improve Agreement Between Spirometry and Emphysema

Many patients with chronic obstructive pulmonary disease (COPD) have marked discordance between forced expiratory volume in 1 second (FEV1) and degree of emphysema on computed tomography (CT). Biomechanical differences between these patients have not been studied. We aimed to identify reasons for the discordance between CT and spirometry in some patients with COPD. Subjects with Global initiative for chronic Obstructive Lung Disease stages I-IV from a large multicenter study (The Genetic Epidemiology of COPD) were arranged by percentiles of %predicted FEV1 and emphysema on CT. Three categories were created using differences in percentiles: Catspir with predominant airflow obstruction/minimal emphysema, CatCT with predominant emphysema/minimal airflow obstruction, and Catmatched with matched FEV1 and emphysema. Image registration was used to derive Jacobian determinants, a measure of lung elasticity, anisotropy, and strain tensors, to assess biomechanical differences between groups. Regression models were created with the previously mentioned categories as outcome variable, adjusting for demographics, scanner type, quantitative CT-derived emphysema, gas trapping, and airway thickness (model 1), and after adding biomechanical CT metrics (model 2). Jacobian determinants, anisotropy, and strain tensors were strongly associated with FEV1. With Catmatched as control, model 2 predicted Catspir and CatCT better than model 1 (Akaike information criterion 255.8 vs. 320.8). In addition to demographics, the strongest independent predictors of FEV1 were Jacobian mean (β = 1.60,95%confidence intervals [CI] = 1.16 to 1.98; P < 0.001), coefficient of variation (CV) of Jacobian (β = 1.45,95%CI = 0.86 to 2.03; P < 0.001), and CV of strain (β = 1.82,95%CI = 0.68 to 2.95; P = 0.001). CVs of Jacobian and strain are both potential markers of biomechanical lung heterogeneity. CT-derived measures of lung mechanics improve the link between quantitative CT and spirometry, offering the potential for new insights into the linkage between regional parenchymal destruction and global decrement in lung function in patients with COPD.

Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality; however, the role of inflammatory mediators in its pathobiology remains unclear. The aim of this study was to investigate the influence of gender in COPD on lipid mediator levels.Bronchoalveolar lavage fluid (BALF) and serum were obtained from healthy never-smokers, smokers and COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage I-II/A-B) (n=114). 94 lipid mediators derived from the cytochrome-P450, lipoxygenase, and cyclooxygenase pathways were analysed by liquid chromatography-mass spectrometry.Multivariate modelling identified a 9-lipid panel in BALF that classified female smokers with COPD from healthy female smokers (p=6×10(-6)). No differences were observed for the corresponding male population (p=1.0). These findings were replicated in an independent cohort with 92% accuracy (p=0.005). The strongest drivers were the cytochrome P450-derived epoxide products of linoleic acid (leukotoxins) and their corresponding soluble epoxide hydrolase (sEH)-derived products (leukotoxin-diols). These species correlated with lung function (r=0.87; p=0.0009) and mRNA levels of enzymes putatively involved in their biosynthesis (r=0.96; p=0.003). Leukotoxin levels correlated with goblet cell abundance (r=0.72; p=0.028).These findings suggest a mechanism by which goblet cell-associated cytochrome-P450 and sEH activity produce elevated leukotoxin-diol levels, which play a putative role in the clinical manifestations of COPD in a female-dominated disease sub-phenotype.

Corticosteroid modulation of immunoglobulin expression and B-cell function in COPD.

We investigated changes in gene expression that occur in chronic obstructive pulmonary disease (COPD) after corticosteroid treatment and sought to identify the mechanisms that regulate these changes. Biopsy samples were taken from patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage I to II) before and after treatment with fluticasone propionate (FP)/salmeterol (SM) (50/500, 4 wk). Gene expression was measured by microarray and was confirmed by real-time reverse transcription-quantitative PCR (RT-qPCR). The effect of FP on IgG expression and B-cell proliferation in the presence of oxidative stress was also studied. FP/SM significantly increased the expression of 180 genes while repressing 343 genes. The top 5 down-regulated genes were associated with immunoglobulin production, whereas the immunomodulatory FK506 binding protein (FK506BP) was up-regulated. Genes including IL6, IL8, and TBET-encoding TBX21 were unaffected. FP reduced IgG protein and mRNA expression and proliferation of human B cells through the dephosphorylation of ERK-1/2 via increased DUSP1 (dual-specificity protein phosphatase 1) expression. Consistent with in vivo data, oxidative stress did not prevent FP-induced suppression of IgG expression in human B cells in vitro Changes in expression were validated by RT-qPCR and by gene set enrichment analysis in distinct COPD cohorts. FP may reduce the adaptive immune response in COPD and may be more effective in patients with an increased B-cell/antibody response indicated by high autoantibody titers.-Lee, J., Machin, M., Russell, K. E., Pavlidis, S., Zhu, J., Barnes, P. J., Chung, K. F., Adcock, I. M., Durham, A. L. Corticosteroid modulation of immunoglobulin expression and B-cell function in COPD.

The patients with severe Chronic Obstructive Pulmonary Disease and chronic respiratory insufficiency

Caring for patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages III and IV with chronic respiratory failure is difficult independent of whether the target is survival or quality of life (QOL). The role of inhaled drug therapy in this specific set of very severe COPD patients has not previously been assessed. The only drug able to prolong survival in these patients is long term oxygen therapy, whereas there is little evidence to indicate long-term domiciliary mechanical ventilation in the routine management of stable hypercapnic patients. Supplemental oxygen during exercise reduces exercise breathlessness and improves exercise capacity of the hypoxaemic patient. Pulmonary rehabilitation including nutritional supplementation is a significant component of therapy, even in these severe patients. Relief of dyspnoea with drugs such as morphine should not be denied to severely disabled patients who share poor QOL with cancer patients. Non-invasive ventilation has been used as a palliative treatment to reduce dyspnoea. Lung Volume Reduction Surgery may improve mortality, exercise capacity, and QOL in selected patients, but is associated with significant morbidity and an early mortality rate in the most severe patients. Lung transplantation is a final step in end-stage patients, but short- and long-term outcomes remain significantly inferior in relation to other "solid" organs recipients.

COPD characteristics and socioeconomic burden in Hellenic correctional institutions.

BackgroundThe high prevalence of smoking (80%) in Greek correctional institutions is anticipated to result in high prevalence of COPD in such settings.AimThe aim of the Greek obstructive luNg disease epidemiOlogy and health economics Study In corrective institutionS (GNOSIS) is to determine the prevalence of smoking and COPD among inmates and to assess the health-related quality of life.MethodsGNOSIS, a cross-sectional epidemiological study, was conducted between March 2011 and December 2011 in seven correctional institutions in Greece.ResultsA total of 552 participants, 91.3% male, median age of 43.0 years (interquartile range: 35–53), were enrolled. COPD prevalence was 6.0% and was found to increase with age (18.6% among those ≥60 years), length of prison stay, and length of sentence. Of the participants diagnosed with COPD, 36.4% were diagnosed with Global initiative for chronic Obstructive Lung Disease (GOLD) stage I and 51.5% were diagnosed with stage II. Dyspnea severity was assessed as grades 0–1 on the medical research council dyspnea scale for 88.3%, while 31% reported ≥2 COPD exacerbations in the past year. Seventy-nine percent of the total number of the participants were smokers, with a median smoking of 20.0 cigarettes per day, while 42.9% were assessed as having a strong addiction to nicotine. The median EuroQol visual analog scale score was 70.0 (interquartile range: 60.0–90.0). Problems in the dimension of anxiety/depression were reported by 82.8%.ConclusionThe results of the study support the notion that the prevalence of COPD among inmates of Greek correctional institutions may increase in the following years. The findings underscore the importance of taking actions to limit COPD prevalence and its risk factors in the Greek correctional system.

Oxidative and Nitrosative Stress and Histone Deacetylase-2 Activity in Exacerbations of COPD

BackgroundRespiratory virus infections are commonly associated with COPD exacerbations, but little is known about the mechanisms linking virus infection to exacerbations. Pathogenic mechanisms in stable COPD include oxidative and nitrosative stress and reduced activity of histone deacetylase-2 (HDAC2), but their roles in COPD exacerbations is unknown. We investigated oxidative and nitrosative stress (O&NS) and HDAC2 in COPD exacerbations using experimental rhinovirus infection.MethodsNine subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II), 10 smokers, and 11 nonsmokers were successfully infected with rhinovirus. Markers of O&NS-associated cellular damage, and inflammatory mediators and proteases were measured in sputum, and HDAC2 activity was measured in sputum and bronchoalveolar macrophages. In an in vitro model, monocyte-derived THP-1 cells were infected with rhinovirus and nitrosylation and activity of HDAC2 was measured.ResultsRhinovirus infection induced significant increases in airways inflammation and markers of O&NS in subjects with COPD. O&NS markers correlated with virus load and inflammatory markers. Macrophage HDAC2 activity was reduced during exacerbation and correlated inversely with virus load, inflammatory markers, and nitrosative stress. Sputum macrophage HDAC2 activity pre-infection was inversely associated with sputum virus load and inflammatory markers during exacerbation. Rhinovirus infection of monocytes induced nitrosylation of HDAC2 and reduced HDAC2 activity; inhibition of O&NS inhibited rhinovirus-induced inflammatory cytokines.ConclusionsO&NS, airways inflammation, and impaired HDAC2 may be important mechanisms of virus-induced COPD exacerbations. Therapies targeting these mechanisms offer potential new treatments for COPD exacerbations.

Risk Factors for Venous Thromboembolism in Chronic Obstructive Pulmonary Disease.

COPD patients are at increased risk for venous thromboembolism (VTE). VTE however remains under-diagnosed in this population and the clinical profile of VTE in COPD is unclear. Global initiative for chronic Obstructive Lung Disease (GOLD) stages II-IV participants in the COPD Genetic Epidemiology (COPDGene) study were divided into 2 groups: VTE+, those who reported a history of VTE by questionnaire, and VTE-, those who did not. We compared variables in these 2 groups with either t-test or chi-squared test for continuous and categorical variables, respectively. We performed a univariate logistic regression for VTE, and then a multivariate logistic regression using the significant predictors of interest in the univariate analysis to ascertain the determinants of VTE. The VTE+ group was older, more likely to be Caucasian, had a higher body mass index (BMI), smoking history, used oxygen, had a lower 6-minute walk distance, worse quality of life scores, and more dyspnea and respiratory exacerbations than the VTE- group. Lung function was not different between groups. A greater percentage of the VTE+ group described multiple medical comorbidities. On multivariate analysis, BMI, 6-minute walk distance, pneumothorax, peripheral vascular disease, and congestive heart failure significantly increased the odds for VTE by history. BMI, exercise capacity, and medical comorbidities were significantly associated with VTE in moderate to severe COPD. Clinicians should suspect VTE in patients who present with dyspnea and should consider possibilities other than infection as causes of COPD exacerbation.

Co-morbidities in 99 COPD patients: A case series from Syria.

ObjectivesTo assess the most frequent co-morbidities in chronic obstructive pulmonary disease (COPD) patients.Patients and MethodsWe studied 99 patients, including 72 males and 67 smokers, presented to our University Hospital in Lattakia, Syria in 2012, with a mean age of 63 years.ResultsOverall, there were 61% hypertension, 37% ischemic heart disease, 25% diabetes, 45% anemia, and 47% pulmonary hypertension. Other diseases were less significant. Patients who had more severe Global Initiative for Chronic Obstructive Lung Disease stage had a greater number of co-morbidities.ConclusionsWe recommend as a general practice, to assess cardiac co-morbidities, hypertension, and other co-morbidities in all COPD patients and vice versa. We also recommend performing spirometry in smokers complaining of chronic cough, sputum, or dyspnea for early diagnosis of COPD.

Prevalence of chronic obstructive pulmonary disease in asymptomatic smokers.

BackgroundPhysicians do not routinely recommend smokers to undergo spirometry unless they are symptomatic.ObjectiveTo test the hypothesis that there are a significant number of asymptomatic smokers with chronic obstructive pulmonary disease (COPD), we estimated the prevalence of COPD in a group of asymptomatic smokers.MethodsTwo thousand nine hundred and sixty-one smokers with a cumulative consumption history of at least 10 pack-years, either smokers with symptoms or smokers without symptoms (WOS) were invited to perform a spirometry and complete a symptom questionnaire.ResultsSix hundred and thirty-seven (21.5%) smokers had no symptoms, whereas 2,324 (78.5%) had at least one symptom. The prevalence of COPD in subjects WOS was 1.5% when considering the whole group of smokers (45/2,961) and 7% when considering only the group WOS (45/637). From 329 smokers with COPD, 13.7% were WOS. Subjects WOS were younger, had better lung function and lower cumulative consumption of cigarettes, estimated as both cigarettes per day and pack-years. According to severity of airflow limitation, 69% vs 87% of subjects were classified as Global Initiative for Chronic Obstructive Lung Disease stages I–II in the WOS and smokers with symptoms groups, respectively (P<0.001). A multivariate analysis showed that forced expiratory volume in 1 second (mL) was the only predictive factor for COPD in asymptomatic smokers.ConclusionPrevalence of COPD in asymptomatic smokers is 1.5%. This number of asymptomatic smokers may be excluded from the benefit of an “early” intervention, not just pharmacological but also from smoking cessation counseling. The higher forced expiratory volume in 1 second may contribute to prevent early diagnosis.

Vasoactive Intestinal Peptide for Diagnosing Exacerbation in Chronic Obstructive Pulmonary Disease

Background: Vasoactive intestinal peptide (VIP) is the most abundant neuropeptide in the lung. VIP has been linked to pulmonary arterial hypertension and hypoxia. Objectives: We aimed to assess circulating VIP levels at exacerbation and at stable chronic obstructive pulmonary disease (COPD) and to evaluate the diagnostic performance in a well-characterized cohort of COPD patients. Methods: The nested cohort study included patients with Global Initiative for Chronic Obstructive Lung Disease stage II-IV. Patients were examined at stable state and at acute exacerbation of COPD (AE-COPD), and dedicated serum was collected at both conditions. Serum VIP levels were determined by enzyme-linked immunosorbent assay. Diagnostic accuracy was analyzed by receiver operating characteristic curve and area under the curve (AUC). Results: Patients with acute exacerbation (n = 120) and stable COPD (n = 163) had similar characteristics at baseline. Serum VIP levels did not correlate with oxygen saturation at rest (p = 0.722) or at exercise (p = 0.168). Serum VIP levels were significantly higher at AE-COPD (130.25 pg/ml, 95% CI 112.19-151.83) as compared to stable COPD (40.07 pg/ml, 95% CI 37.13-43.96, p < 0.001). The association of increased serum VIP with AE-COPD remained significant after propensity score matching (p < 0.001). Analysis of the Youden index indicated the optimal serum VIP cutoff value as 56.6 pg/ml. The probability of AE-COPD was very low if serum VIP was ≤35 pg/ml (sensitivity >90%) and very high if serum VIP was ≥88 pg/ml (specificity >90%). Serum VIP levels presented a robust performance to diagnose AE-COPD (AUC 0.849, 95% CI 0.779-0.899). Conclusions: Increased serum VIP levels are associated with AE-COPD.

Role of oxidative stress and serum lipid levels in stable chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) has been associated with increased oxidative stress or reduced antioxidant resources. The main goal of this study was to evaluate the levels of serum ischemia-modified albumin (IMA), oxidized low-density lipoprotein (ox-LDL), total oxidant status (TOS), and total antioxidant status in patients with stable COPD, compared with a control group. MethodsThis study was performed on 51 patients with stable COPD (42 men and 9 women; mean age 56.92 ± 3.0 years) and 45 healthy control participants (32 men and 13 women; 54.8 ± 3.8 years). The levels of serum lipids, IMA, total antioxidant status, TOS, and ox-LDL were measured in all participants. ResultsThe levels of serum IMA, ox-LDL, and TOS were significantly higher in patients with COPD than those in control individuals. There was no difference between the levels of serum total antioxidant status, triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C) of patients with COPD and those of control individuals. Serum high-density lipoprotein cholesterol levels were significantly lower in patients with COPD than in control individuals. ConclusionOur study indicated that serum IMA, ox-LDL, and TOS may be increased as a result of chronic hypoxia, inflammation, and oxidative stress in patients with severe and very severe stable COPD. Our findings also revealed that IMA is higher in patients with Global Initiative for Chronic Obstructive Lung Disease Stages II, III, and IV, while TOS and ox-LDL are higher in patients with Global Initiative for Chronic Obstructive Lung Disease Stage IV. Measurements of serum IMA, TOS, and ox-LDL levels may be useful markers in the evaluation of stable COPD.

NT-proBNP predicts the need for ventilatory support in the patients with acute exacerbation of chronic obstructive pulmonary disease

Introduction. Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may need ventilatory support (VS) due to respiratory failure. Risk stratification on admission could identify patients at higher risk of deterioration. Cardiac biomarkers are associated with outcome in AECOPD but were not studied as predictors for VS. Objectives. The aim of this study was to evaluate association between admission NT- proBNP and ventilatory support (VS) in the patients with AECOPD. Methods. The prospective observational study included 139 patients with a clinical diagnosis of AECOPD and GlobalInitiative for Chronic Obstructive Lung Disease (GOLD) stages III-IV. NT-proBNP was determined from venous blood samples on patient admissions to the hospital with the use of a quantitative electrochemiluminescence assay on an Elecsys 2010 analyzer (Roche Diagnostics) according to established methods. The VS was defined as any form of invasive or noninvasive VS applied during index hospital stay. Results. Patients who did not require (no.:108) vs. those who required VS (no.:31) and patients with invasive (no.:15) vs. those with noninvasive VS (no.:16) were of similar age, gender and GOLD stage (p > 0.2 for all). NT-proBNP was higher in patients who required VSthen in those without VS (2407 ± 3431 vs. 1709 ± 4648 ng/L ; p < 0.05). Patients with noninvasive VS had higher NT-proBNP then those without VS (3213 ± 4389 vs.1709 ± 4648 ng/L ; p < 0.05). The difference between patients treated with noninvasive vs. invasive VS was not significant (3213 ± 4389 vs. 1534 ± 1753 ng/L ; p=NS). Patients receiving invasive VS had similar admission NT-proBNP as those without VS (1534 ± 1753 vs. 1709 ± 4648 ng/L ; p=NS). Conclusions. Admission NT-proBNP may predict need for noninvasive VS in patients with AECOPD.

Prognostic implications of heart failure with preserved ejection fraction in patients with an exacerbation of chronic obstructive pulmonary disease.

Diagnosing heart failure with preserved ejection fraction (HFpEF) in patients with chronic obstructive pulmonary disease (COPD) is difficult due to overlapping pathophysiological pathways, risk factors and clinical presentations. We investigated the prevalence and prognostic implications of coexisting HFpEF in patients hospitalized for acute exacerbation of COPD. A total of 116 consecutive patients with an acute exacerbation of COPD were evaluated for HFpEF and followed for an average period of 22±9months for the occurrence of death from any cause. HFpEF was diagnosed in 22 (19%) patients with COPD, who were older, and also had higher LV mass, left atrial size, and mitral E/Ea ratio than those without HFpEF (p<0.05 for all comparisons). HFpEF was not independently associated with all-cause mortality [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.44-2.62]. Global initiative for chronic Obstructive Lung Disease (GOLD) stage (IV vs. I-III, HR 2.37, CI 1.23-4.59) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels (HR 2.79, CI 1.12-6.98) were independent predictors of long-term survival. HFpEF is present in one-fifth of patients with exacerbated COPD. Non-invasively diagnosed HFpEF may not be an independent predictor of all-cause mortality. Elevated NT-proBNP levels and very severe COPD were independently associated with unfavorable overall survival.

B Cell-Activating Factor. An Orchestrator of Lymphoid Follicles in Severe Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) have increased pulmonary lymphoid follicle (LF) counts. B cell-activating factor of tumor necrosis factor family (BAFF) regulates B cells in health, but its role in COPD pathogenesis is unclear. To determine whether BAFF expression in pulmonary LFs correlates with COPD severity, LF size or number, and/or readouts of B-cell function in LFs. We correlated BAFF immunostaining in LFs in lung explants or biopsies from nonsmoking control subjects (NSC), smokers without COPD (SC), and patients with COPD with the number and size of LFs, and LF B-cell apoptosis, activation, and proliferation. We analyzed serum BAFF levels and BAFF expression in B cells in blood and bronchoalveolar lavage samples from the same subject groups. We assessed whether: (1) cigarette smoke extract (CSE) increases B-cell BAFF expression and (2) recombinant BAFF (rBAFF) rescues B cells from CSE-induced apoptosis by inhibiting activation of nuclear factor-κB (NF-κB). Patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD had increased numbers and larger pulmonary LFs than patients with GOLD stages I-II COPD and SC. We identified two main types of pulmonary LFs: (1) type A, the predominant type in GOLD stages I-II COPD and SC, characterized by abundant apoptotic but few BAFF-positive cells (mostly B cells); and (2) type B, the main type in GOLD stage IV COPD, characterized by abundant BAFF-positive cells but few apoptotic cells (mostly B cells). BAFF levels were also higher in blood and bronchoalveolar lavage B cells in patients with COPD versus NSC and SC. Surprisingly, rBAFF blocked CSE-induced B-cell apoptosis by inhibiting CSE-induced NF-κB activation. Our data support the hypothesis that B-cell BAFF expression creates a self-perpetuating loop contributing to COPD progression by promoting pulmonary B-cell survival and LF expansion.

Proteoglycan 4 is a diagnostic biomarker for COPD.

IntroductionThe measurement of C-reactive protein (CRP) to confirm the stability of COPD has been reported. However, CRP is a systemic inflammatory biomarker that is related to many other diseases.ObjectiveThe objective of this study is to discover a diagnostic biomarker for COPD.MethodsSixty-one subjects with COPD and 15 healthy controls (10 healthy non-smokers and 5 smokers) were recruited for a 1-year follow-up study. Data regarding the 1-year acute exacerbation frequency and changes in lung function were collected. CRP and the identified biomarkers were assessed in the validation COPD cohort patients and healthy subjects. Receiver operating characteristic values of CRP and the identified biomarkers were determined. A validation COPD cohort was used to reexamine the identified biomarker. Correlation of the biomarker with 1-year lung function decline was determined.ResultsProteoglycan 4 (PRG4) was identified as a biomarker in COPD. The serum concentrations of PRG4 in COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stages 1+2 and 3+4 were 10.29 ng/mL and 13.20 ng/mL, respectively; 4.99 ng/mL for healthy controls (P<0.05); and 4.49 ng/mL for healthy smokers (P<0.05). PRG4 was more sensitive and specific than CRP for confirming COPD severity and acute exacerbation frequency. There was no correlation between CRP and PRG4 levels, and PRG4 was negatively correlated with the 1-year change in predicted forced vital capacity percent (R2=0.91, P=0.013).ConclusionPRG4 may be a biomarker for identification of severity in COPD. It was related to the 1-year forced vital capacity decline in COPD patients.

β-Blockers are associated with a reduction in COPD exacerbations

BackgroundWhile some retrospective studies have suggested that β-blocker use in patients with COPD is associated with a reduction in the frequency of acute exacerbations and lower mortality, there is concern...

Comorbidities in obstructive lung disease in Korea: data from the fourth and fifth Korean National Health and Nutrition Examination Survey.

BackgroundComorbidities can occur frequently in patients with chronic obstructive pulmonary disease (COPD) and can influence mortality and morbidity independently. It is increasingly recognized that many patients with COPD have comorbidities that have a major impact on their quality of life and survival. Therefore, we investigated the prevalence of comorbidities in Korean COPD populations.MethodsWe used data obtained in the 6 years of the fourth and fifth Korean National Health and Nutrition Examination Survey (KNHANES) IV and V. Among 50,405 subjects, 16,151 subjects aged ≥40 years who performed spirometry adequately were included in this study. Airway obstruction was defined as forced expiratory volume in 1 second/forced vital capacity <0.7, and the Global Initiative For Chronic Obstructive Lung Disease stage was used to evaluate the severity of airway obstruction. Statistical analyses were performed using SAS 9.2.ResultsAmong the 16,151 subjects (43.2% male, 56.8% female; mean age: 57.1 years for men and 57.2 years for women), 13.1% had obstructive lung function; 11.3%, restrictive lung function; and 75.6%, normal lung function. Among individuals with obstructive lung function, 45.3%, 49.4%, and 5.3% had mild, moderate, and severe and very severe airflow limitation. The prevalence of hypertension, diabetes mellitus (DM), underweight, and hypertriglyceridemia was higher in the obstructive lung function group than in the normal lung function group (49.6% vs 35.2%; 16.8% vs 10.5%; 3.3% vs 1.3%; 19.7% vs 17.0%). According to the severity of airway obstruction, hypertension and underweight were more common as severity increased, although the prevalence of DM and hypertriglyceridemia was lower in subjects with severe airway obstruction. The prevalence of hypercholesterolemia, overweight, and osteoarthritis was lower in the obstructive lung function group, especially in the severe airway obstruction groups.ConclusionsOverall, our analysis is similar to research that was conducted earlier. Our study showed that hypertension and underweight are common comorbidities in COPD patients, and are higher as the severity of airflow obstruction increased in both men and women. DM, hypertriglyceridemia, and low high-density lipoprotein cholesterol are more common in subjects with airway obstruction, although their incidence is lower in the severe group.

The value of coronary artery calcium score in the early diagnosis of coronary artery disease in patients with stable chronic obstructive pulmonary disease.

Objective:Our aim was to assess the value of coronary artery calcium score (CACS) in the early diagnosis of coronary artery disease in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II chronic obstructive pulmonary disease (COPD) patients and to identify high-risk patients.Methods:Forty-two patients with GOLD stage II COPD and 31 healthy control subjects were enrolled in the study. This study was designed as a prospective observational cross-sectional study. Pearson’s correlation coefficient was used for comparisons between groups. Criteria for stage II COPD diagnosis were forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of <70% and 50%≤FEV1<80%. Excluded from the study were individuals who had a previous diagnosis of coronary artery disease, GOLD stage I-III-IV COPD, or left ventricular systolic dysfunction.Results:As compared with the control group, CACS values were significantly higher in the patient group (p=0.030 and 0.001, respectively). CACS was significantly higher in male patients with a positive family history, physical inactivity, long duration of disease, and low FEV1 (0.027, 0.008; 0.001 and 0.001; 0.001, respectively). Logistical regression analysis of sex, age, diabetes mellitus, hypertension, cigarette smoking, family history, physical inactivity, and FEV1 values showed that physical inactivity was independently correlated with high CACS [odds ratio (OR): 7; confidence interval (CI): 3–20; p=0.001].Conclusion:The value of CACS is high in stage II COPD patients. Male stage II COPD patients with a disease duration of 10 years, physical inactivity, and/or a positive family history should be monitored for early stage coronary artery disease and coronary events, regardless of risk factors such as diabetes, hypertension, and hyperlipidemia.

Non-anaemic iron deficiency impairs response to pulmonary rehabilitation in COPD.

Non-anaemic iron deficiency (NAID) might alter the oxygen pathway in health and disease. The current study aims at assessing the impact of NAID on aerobic capacity in patients with chronic obstructive pulmonary disease (COPD). A prospective sample of 70 non-anaemic COPD patients candidate to participate in an 8-week pulmonary rehabilitation (PR) programme was studied. Incremental cycling exercise to peak oxygen uptake (V'O2peak ) and constant work-rate exercise at 80% V'O2peak to exhaustion were assessed pre- and post-PR. Training-induced increase of endurance time (ET) ≥33%, which represented the minimal clinically important difference, classified patients as responders to exercise training. The prevalence of NAID was 48% (n = 34) showing no relationship with the Global Initiative for Chronic Obstructive Lung Disease stages (P = 0.209). Patients with NAID showed lower pre-training ET (P = 0.033) and V'O2peak (P = 0.007) than normal iron status (NIS) patients after adjustment for potential covariates. Significant training-induced physiological changes were seen in the NIS group (ΔV'O2peak 68(132) mL/min; P = 0.009), but not in the NAID group (ΔV'O2peak 26 (126) mL/min; P = 0.269). The NAID group showed lower percentage of responders to training (56%) than the NIS group (78%) (P = 0.041). COPD patients with NAID showed lower pre-training aerobic capacity and reduced training-induced response than NIS patients after adjusting for potential confounding variables.