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Background and objective: The availability of chest computed tomography (CT) imaging can help diagnose comorbidities associated with chronic obstructive pulmonary disease (COPD). Their systematic identification and relationship with all‐cause mortality have not been explored. Furthermore, whether their CT‐detected prevalence differs from clinical diagnosis is unknown. Methods: The prevalence of 10 CT‐assessed comorbidities was retrospectively determined at baseline in 379 patients (71% men) with mild to severe COPD attending pulmonary clinics. Anthropometrics, smoking history, dyspnoea, lung function, exercise capacity, BODE (BMI, Obstruction, Dyspnoea and Exercise capacity) index and exacerbations rate were recorded. The prevalence of CT‐determined comorbidities was compared with that recorded clinically. Over a median of 78 months of observation, the independent association with all‐cause mortality was analysed. A 'CT‐comorbidome' graphically expressed the strength of their association with mortality risk. Results: Coronary artery calcification, emphysema and bronchiectasis were the most prevalent comorbidities (79.8%, 62.7% and 33.9%, respectively). All were underdiagnosed before CT. Coronary artery calcium (hazard ratio [HR] 2.09; 95% CI 1.03–4.26, p = 0.042), bronchiectasis (HR 2.12; 95% CI 1.05–4.26, p = 0.036) and low psoas muscle density (HR 2.61; 95% CI 1.23–5.57, p = 0.010) were independently associated with all‐cause mortality and helped define the 'CT‐comorbidome'. Conclusion: This study of COPD patients shows that systematic detection of 10 CT‐diagnosed comorbidities, most of which were not detected clinically, provides information of potential use to patients and clinicians caring for them. This multicentric study shows that chest computed tomography (CT) to evaluate the presence of 10 comorbidities detects important pathologies not diagnosed in the clinical management of those patients. While emphysema, coronary artery calcification (CAC) and bronchiectasis were the most prevalent CT‐detected comorbidities, CAC, bronchiectasis and low Psoas muscle density were independently associated with all‐cause mortality. See relatedEditorial [ABSTRACT FROM AUTHOR]

Background: The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression.Research Question: What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression?Study Design and Methods: We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time.Results: The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039).Interpretation: Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function.Trial Registry: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background: Despite the existing evidence-based smoking cessation interventions, chances of achieving that goal in real life are still low among patients with COPD. We sought to evaluate the clinical consequences of changes in smoking habits in a large cohort of patients with COPD.Methods: CHAIN (COPD History Assessment in Spain) is a Spanish multicenter study carried out at pulmonary clinics including active and former smokers with COPD. Smoking status was certified by clinical history and co-oximetry. Clinical presentation and disease impact were recorded via validated questionnaires, including the London Chest Activity of Daily Living (LCADL) and the Hospital Anxiety and Depression Scale (HADS). No specific smoking cessation intervention was carried out. Factors associated with and clinical consequences of smoking cessation were analyzed by multivariate regression and decision tree analyses.Results: One thousand and eighty-one patients with COPD were included (male, 80.8%; age, 65.2 [SD 8.9] years; FEV1, 60.2 [20.5]%). During the 2-year follow-up time (visit 2, 906 patients; visit 3, 791 patients), the majority of patients maintained the same smoking habit. Decision tree analysis detected chronic expectoration as the most relevant variable to identify persistent quitters in the future, followed by an LCADL questionnaire (cutoff 9 points). Total anxiety HADS score was the most relevant clinical impact associated with giving up tobacco, followed by the LCADL questionnaire with a cutoff value of 10 points.Conclusions: In this real-life prospective COPD cohort with no specific antismoking intervention, the majority of patients did not change their smoking status. Our study also identifies baseline expectoration, anxiety, and dyspnea with daily activities as the major determinants of smoking status in COPD.Trial Registry: ClinicalTrials.gov; No. NCT01122758; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

The article discusses a research study conducted to assess the prognostic value of the chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ) scores, and to compare them with the modified Medical Research Council (mMRC) dyspnea. Topics covered include the "COPD History Assessment in Spain (CHAIN)" cohort study, the clinical and physiological characteristics of the evaluated patients with COPD, and the development of the CAT and CCQ.

ABSTRACT Background The Global Obstructive Lung Disease (GOLD) 2011 revision recommends the multidimensional assessment of COPD including comorbidities and has developed a disease categories system (ABCD) attempting to implement this strategy. The added value provided by quantifying comorbidities and integrating them to multidimensional indices has not been explored. Objective Compare the prognostic value of the GOLD ABCD categories versus the BMI, Obstruction, Dyspnea, Exercise (BODE) index, and explore the added prognostic value of comorbidities evaluation to this multidimensional assessment. Methods From the patients who have been enrolled in the BODE study, we selected the most recent ones who had the available information needed to classify them by the ABCD GOLD categories. Cox proportional hazards ratios for all-cause mortality were performed for GOLD categories and BODE index. The added value of the comorbidity Copd cO-morbidity TEst (COTE) index was also explored using receiver operating curves (ROC) values. Results 707 patients were followed for 50±30 months including all degrees of airway limitation and BODE index severity. ABCD GOLD predicted global mortality (HR: 1.47; 95% CI 1.28 to 1.70) as did the BODE index (HR: 2.02; 95% CI 1.76 to 2.31). Area under the curve (AUC) of ROC for ABCD GOLD was 0.68; (95% CI 0.64 to 0.73) while for the BODE index was 0.71 (95% CI 0.67 to 0.76). The C statistics value was significantly higher for the observed difference. Adding the COTE index to the BODE index improved its AUC to 0.81 (95% CI 0.77 to 0.85), (χ2=40.28, p<0.001). Conclusions In this population of COPD patients, the BODE index had a better survival prediction than the ABCD GOLD categories. Adding the COTE to the BODE index was complimentary and significantly improved outcome prediction. [ABSTRACT FROM AUTHOR]

Rationale: Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD). Objective: To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only. Methods: We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data. Results: At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722). Conclusions: In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index. [ABSTRACT FROM AUTHOR]

Background: The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair. Methods: We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF α) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association Results (OSCAR) plot]. Results: Levels of the inflammatory markers IL-6, TNF α were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs. 4). Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05). Conclusions: In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival. [ABSTRACT FROM AUTHOR]

Background: The 6-minute walk distance (6MWD) has been useful in the evaluation of men with COPD. Little is known about 6MWD in women with the disease. Objectives: Using healthy women as a reference, to evaluate the factors that help determine 6MWD in women with COPD. To explore if the 350 meters threshold differentiates survival in women as it does in men. Methods: Healthy women (n == 164) and with COPD (n == 223) were included in the study. Age, pack-years history, smoking status, comorbidities (Charlson Index), BMI, MRC dyspnea, spirometry and 6MWD were recorded in all participants and PaO2 and IC/TLC in COPD women. The patients were prospectively followed and deaths registered. Factors predicting 6MWD were determined by multiple regression analysis. ROC analysis was used to calculate the best threshold value for the 6MWD with mortality as gold standard. Kaplan-Meier curves compared survival of patients that walked more or less than 350 m by age categories. Results: The 6MWD is decreased in women with COPD. Values decrease with age and GOLD stages. Age, BMI, smoking status, comorbidities, MRC and FEV1%% are statistical significant predictors of 6MWD. A 350 m cut-off value has a good sensitivity and specificity to predict (73%% and 80%% respectively) and differentiate survival (p < 0.001 for log rank comparisons) in these patients. Conclusions: In women with COPD, the 6MWD decreases with age and GOLD stages. A 350 m distance is a valid threshold to differentiate survival. Further studies in different settings should confirm our findings. [ABSTRACT FROM AUTHOR]

Rationale: Little is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD). Hypothesis: There are differences in serum biomarker levels between women and men with COPD. Objective: Explore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD. Methods: We measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without COPD (40 males, 40 females) and 152 stable COPD patients (76 males, 76 females) with similar airflow obstruction. We determined anthropometrics, smoking history, lung function, exercise tolerance, body composition, BODE index, co-morbidities and quality of life. We then explored associations between plasma biomarkers levels and the clinical characteristics of the patients and also with the clinical and physiological variables known to predict outcome in COPD. Results: The plasma biomarkers level explored were similar in men and women without COPD. In contrast, in patients with COPD the median value in pg/mL of IL-6 (6.26 vs 8.0, p = 0.03), IL-16 (390 vs 321, p = 0.009) and VEGF (50 vs 87, p = 0.02) differed between women and men. Adjusted for smoking history, gender was independently associated with IL-16, PARC and VEGF levels. There were also gender differences in the associations between IL-6, IL-16 and VEGF and physiologic variables that predict outcomes. Conclusions: In stable COPD patients with similar airflow obstruction, there are gender differences in plasma biomarker levels and in the association between biomarker levels and important clinical or physiological variables. Further studies should confirm our findings. [ABSTRACT FROM AUTHOR]

The article presents a study on the health benefits of the 6-minute walk test (6MWT) on chronic obstructive pulmonary disease (COPD). The study involves the participation and observation of 576 stable COPD outpatients in Spain and U.S. for three years. During the 6MWT, body mass index, Charlson comorbidity score, and 6-minute walk distance (6MWD) were measured using pulse oximetry. The research shows that the test was a good predictor of all-cause and respiratory mortality of patients.

Objectives: Evaluate gender differences in respiratory factors associated with dyspnea in COPD patients. Methods: In a FEV1 % matched population of 100 men and women with COPD we measured: age, MMRC, FEV1, FVC, TLC, IC/TLC, PaO2, PaCO2, DLCO, Pimax, P0.1, Ti/Ttot, BMI, ffmi, 6MWD and VAS scale before and after the test, the Charlson score and the SGRQ. We estimated the association between these parameters and MMRC scores. Multivariate analysis determined the independent strength of those associations. Results: MMRC correlated with: BMI (men:-0.29, p = 0.04; women:-0.28, p = 0.05), ffmi (men:- 0.39, p = 0.01), FEV1 % (men:-0.64, p < 0.001; women:-0.29, p = 0.04), FVC % (men:-0.45, p = 0.001; women:-0.33, p = 0.02), IC/TLC (men:-0.52, p < 0.001; women: -0.27, p = 0.05), PaO2 (men:-0.59, p < 0.001), PaCO2 (men:0.27, p = 0.05), DLCO (men:-0.54, p < 0.001), P0.1/Pimax (men:0.46, p = 0.002; women:0.47, p = 0.005), dyspnea measured with the Visual Analog Scale before (men:0.37, p = 0.04; women:0.52, p = 0.004) and after 6MWD (men:0.52, p = 0.002; women:0.48, p = 0.004) and SGRQ total (men:0.50, p < 0.001; women:0.59, p < 0.001). Regression analysis showed that P0.1/Pimax in women (r2 = 0.30) and BMI, DLCO, PaO2 and P0.1/Pimax in men (r2 = 0.81) were the strongest predictors of MMRC scores. Conclusion: In mild to severe COPD patients attending a pulmonary clinic, P0.1/Pimax was the unique predictor of MMRC scores only in women. Respiratory factors explain most of the variations of MMRC scores in men but not in women. Factors other than the respiratory ones should be included in the evaluation of dyspnea in women with COPD. [ABSTRACT FROM AUTHOR]

Background: The influence of gender on the expression of COPD has received limited attention. Quality of Life (QoL) has become an important outcome in COPD patients. The aim of our study was to explore factors contributing to gender differences in Quality of Life of COPD patients. Methods: In 146 men and women with COPD from a pulmonary clinic we measured: Saint George's Respiratory Questionnaire (SGRQ), age, smoking history, PaO2, PaCO2, FEV1, FVC, IC/TLC, FRC, body mass index (BMI), 6 minute walk distance (6MWD), dyspnea (modified MRC), degree of comorbidity (Charlson index) and exacerbations in the previous year. We explored differences between genders using Mann-Whitney U-rank test. To investigate the main determinants of QoL, a multiple lineal regression analysis was performed using backward Wald's criteria, with those variables that significantly correlated with SGRQ total scores. Results: Compared with men, women had worse scores in all domains of the SGRQ (total 38 vs 26, p = 0.01, symptoms 48 vs 39, p = 0.03, activity 53 vs 37, p = 0.02, impact 28 vs 15, p = 0.01). SGRQ total scores correlated in men with: FEV1% (-0.378, p < 0.001), IC/TLC (-0.368, p = 0.002), PaO2 (-0.379, p = 0.001), PaCO2 (0.256, p = 0.05), 6MWD (-0.327, p = 0.005), exacerbations (0.366, p = 0.001), Charlson index (0.380, p = 0.001) and MMRC (0.654, p < 0.001). In women, the scores correlated only with FEV1% (-0.293, p = 0.013) PaO2 (-0.315, p = 0.007), exacerbations (0.290, p = 0.013) and MMRC (0.628, p < 0.001). Regression analysis (B, 95% CI) showed that exercise capacity (0.05, 0.02 to 0.09), dyspnea (17.6, 13.4 to 21.8), IC/TLC (-51.1, -98.9 to -3.2) and comorbidity (1.7, 0.84 to 2.53) for men and dyspnea (9.7, 7.3 to 12.4) and oxygenation (-0.3, -0.6 to -0.01) for women manifested the highest independent associations with SGRQ scores. Conclusion: In moderate to severe COPD patients attending a pulmonary clinic, there are gender differences in health status scores. In turn, the clinical and physiological variables independently associated with those scores differed in men and women. Attention should be paid to the determinants of QoL scores in women with COPD. [ABSTRACT FROM AUTHOR]

This article presents information on a study which compares gender differences in the clinical expression of COPD patients attending a pulmonary clinic. The influence of gender on the expression of COPD has received limited attention. Gender differences in airway behavior and in the clinical manifestations of airway disease occur throughout life and are thought to be related to biological as well as sociocultural factors. The lack of information regarding gender and COPD is surprising because according to COPD disease surveillance in the United States, there was a fivefold increase in the mortality rate due to COPD in women between 1971 and 2000.

Assesses the efficacy of nocturnal noninvasive positive pressure ventilation (NPPV) versus conventional standard treatment in patients with severe chronic obstructive pulmonary disease. Effects of NPPV on dyspnea, arterial blood gases, pulmonary function and neuropsychological parameters.

Rationale and Objective: Patients with chronic obstructive pulmonary disease (COPD), usually diagnosed after the 6th decade, frequently suffer from comorbidities. Whether COPD patients 50 years or younger (Young COPD) have similar comorbidities with the same frequency and mortality impact as aged-matched controls or older COPD patients is unknown.Methods: We compared comorbidity number, prevalence and type in 3 groups of individuals with ≥ 10 pack-years of smoking: A Young (≤ 50 years) COPD group (n = 160), an age-balanced control group without airflow obstruction (n = 125), and Old (> 50 years) COPD group (n = 1860). We also compared survival between the young COPD and control subjects. Using Cox proportional model, we determined the comorbidities associated with mortality risk and generated Comorbidomes for the "Young" and "Old" COPD groups.Results: The severity distribution by GOLD spirometric stages and BODE quartiles were similar between Young and Old COPD groups. After adjusting for age, sex, and pack-years, the prevalence of subjects with at least one comorbidity was 31% for controls, 77% for the Young, and 86% for older COPD patients. Compared to controls, "Young" COPDs' had a nine-fold increased mortality risk (p < 0.0001). "Comorbidomes" differed between Young and Old COPD groups, with tuberculosis, substance use, and bipolar disorders being distinct comorbidities associated with increased mortality risk in the Young COPD group.Conclusions: Young COPD patients carry a higher comorbidity prevalence and mortality risk compared to non-obstructed control subjects. Young COPD differed from older COPD patients by the behavioral-related comorbidities that increase their risk of premature death. [ABSTRACT FROM AUTHOR]

Background: Plasma metabolomics profile (PMP) in COPD has been associated with clinical characteristics, but PMP's relationship to survival has not been reported. We determined PMP differences between patients with COPD who died an average of 2 years after enrollment (Non-survivors, NS) compared to those who survived (S) and also with age matched controls (C).Methods: We studied prospectively 90 patients with severe COPD and 30 controls. NS were divided in discovery and validation cohorts (30 patients each) and the results compared to the PMP of 30 S and C. All participants completed lung function tests, dyspnea scores, quality of life, exercise capacity, BODE index, and plasma metabolomics by liquid and gas chromatography / mass spectometry (LC/MS, LC/MS2, GC/MS). Statistically, we used Random Forest Analysis (RFA) and Support Vector Machine (SVM) to determine metabolites that differentiated the 3 groups and compared the ability of metabolites vs. clinical characteristics to classify patients into survivors and non-survivors.Results: There were 79 metabolites statistically different between S and NS [p < 0.05 and false discovery rate (q value) < 0.1]. RFA and SVM classification of COPD survivors and non-survivors had a predicted accuracy of 74 and 85% respectively. Elevation of tricyclic acid cycle intermediates branched amino acids depletion and increase in lactate, fructose and xylonate showed the most relevant differences between S vs. NS suggesting alteration in mitochondrial oxidative energy generation. PMP had similar predictive power for risk of death as information provided by clinical characteristics.Conclusions: A plasma metabolomic profile characterized by an oxidative energy production difference between survivors and non-survivors was observed in COPD patients 2 years before death. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a previously published article related to therapy in patients with chronic respiratory insufficiency.

Lung cancer (LC) is the most common cause of cancer death, with 75% of cases being diagnosed in late stages. This study aimed to determine potential miRNAs as biomarkers for the early detection of LC in chronic obstructive pulmonary disease (COPD) cases. Ninety-nine patients were included, with registered clinical and lung function parameters followed for 6 years. miRNAs were determined in 16 serum samples from COPD patients (four with LC and four controls) by next generation sequencing (NGS) at LC diagnosis and 3 years before. The validation by qPCR was performed in 33 COPD-LC patients and 66 controls at the two time points. Over 170 miRNAs (≥10 TPM) were identified; among these, miR-224-5p, miR-206, miR-194-5p, and miR-1246 were significantly dysregulated (p < 0.001) in COPD-LC 3 years before LC diagnosis when compared to the controls. The validation showed that miR-1246 and miR-206 were differentially expressed in COPD patients who developed LC three years before (p = 0.035 and p = 0.028, respectively). The in silico enrichment analysis showed miR-1246 and miR-206 to be linked to gene mediators in various signaling pathways related to cancer. Our study demonstrated that miR-1246 and miR-206 have potential value as non-invasive biomarkers of early LC detection in COPD patients who could benefit from screening programs. [ABSTRACT FROM AUTHOR]

Background: The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair.Methods: We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF α) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association Results (OSCAR) plot].Results: Levels of the inflammatory markers IL-6, TNF α were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs. 4). Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05).Conclusions: In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival. [ABSTRACT FROM AUTHOR]

Mitokines (Humanin (HN), GDF15 and FGF21) are produced as a result of mitochondrial dysfunction and may have major roles in chronic inflammation, malnutrition and exercise capacity in people with COPD. Except for GDF15, studies on this subject are lacking. A total of 165 patients with stable COPD and 49 smokers without COPD were enrolled. We assessed their serum mitokine levels and clinical characteristics at baseline. We recorded moderate and severe exacerbation for the next 12 months. Baseline serum HN (p = 0.037) and GDF-15 (p = 0.013) levels were higher in the COPD group. High HN levels were independently associated with a high risk of exacerbation (HRE) (OR 2.798, 95% CI 1.266–6.187, p = 0.011), malnutrition (OR 6.645, 95% CI 1.859–23.749, p = 0.004), and 6MWD (OR 0.995, 95% CI 0.991–0.999, p = 0.008), and future moderate (HR 1.826, 95% CI 1.181–2.822, p = 0.007) and severe exacerbations (HR 3.445, 95% CI 1.357–8.740, p = 0.009). High GDF15 levels were associated with HRE (OR 3.028, 95% CI 1.134–8.083, p = 0.027), 6MWD (OR 0.995, 95% CI 0.990–0.999, p = 0.017) and predicted desaturation in 6MWT (OR 3.999, 95% CI 1.487–10.757, p = 0.006). High FGF21 levels were associated with HRE (OR 2.144, 95% CI 1.000–4.600, p = 0.05), and predicted future severe exacerbation (HR 4.217, 95% CI 1.459–12.193, p = 0.008). The mitokine levels were higher in patients with COPD than smokers without COPD, and were associated with important clinical outcomes such as exercise capacity and COPD exacerbation. Among the mitokines, HN showed the strongest association with COPD and may serve as a future risk biomarker in this disease. Trial registation NCT04449419. [ABSTRACT FROM AUTHOR]

Background: The COPD-Lung Cancer Screening Score (COPD-LUCSS) is a tool designed to help identify patients with COPD with the highest risk of developing lung cancer (LC). The COPD-LUCSS includes the determination of radiological emphysema, a potential limitation for its implementation in clinical practice. The diffusing capacity for carbon monoxide (DLCO) is a surrogate marker of emphysema and correlates well with CT-determined emphysema.Objective: To explore the use of the COPD-LUCSS using the DLCO instead of radiological emphysema, as a tool to identify patients with COPD at higher risk of LC death.Methods: The Body Mass Index, Airflow Obstruction, Dyspnea, Exercise Performance international cohort database was analyzed. By logistic regression analysis, we confirmed that the other parameters included in the COPD-LUCSS (age > 60, pack-years > 60, BMI < 25) were independently associated with LC death. We selected the best cutoff value for DLCO that independently predicted LC death. We then integrated the new COPD-LUCSS-DLCO assigning points to each parameter according to its hazard ratio value in the Cox regression model. The score ranges from 0 to 8 points.Results: By regression analysis, age > 60, BMI <25 kg/m(2), pack-year history > 60, and DLCO < 60% were independently associated with LC diagnosis. Two COPD-LUCSS-DLCO risk categories were identified: low risk (scores 0-3) and high risk (scores 3.5-8). In comparison to patients at low risk, risk of death from LC increased 2.4-fold (95% CI, 2.0-2.7) in the high-risk category.Conclusions: The COPD-LUCSS using DLCO instead of CT-determined emphysema is a useful tool to identify patients with COPD at risk of LC death and may help in its implementation in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Blood eosinophils are considered a biomarker for the treatment of chronic obstructive pulmonary disease (COPD). Population-based studies are needed to better understand the determinants of the blood eosinophil count (BEC) in individuals with and without COPD.Methods: EPISCAN II is a multicentre, cross-sectional, population-based epidemiological study aimed at investigating the prevalence and determinants of COPD in Spain. Study subjects were randomly selected from the general population, and COPD was defined by a post-bronchodilator FEV1/FVC < 0.7. For the pre-specified outcomes related to BEC, the first 35 COPD and 35 non-COPD subjects were consecutively recruited in 12 of the participating centres with the objective of analysing 400 individuals in each group. Baseline BEC and its association with demographic, clinical and functional variables were analysed.Results: A total of 326 COPD and 399 non-COPD subjects were included in the analysis. The mean age (standard deviation [SD]) was 63.2 years (11.0), 46.3% were male, and 27.6% were active smokers. BEC was significantly higher in individuals with COPD [192 cells/μL (SD: 125) vs. 160 cells/μL (SD: 114); p = 0.0003]. In a stepwise multivariate model, being male, active smoker and having a previous diagnosis of asthma were independently associated with having a higher BEC.Conclusions: This population-based study estimated the distribution of eosinophils in the healthy adult population and concluded that COPD patients have a significantly higher BEC. Male sex, active smoking and concomitant asthma were significantly associated with a higher BEC. [ABSTRACT FROM AUTHOR]

The article examines the correlation between serum levels of C-reactive protein (CRP) and survival in patients with moderate to severe chronic obstructive pulmonary disease (COPD) and compares this with other parameters for the prognosis of the disease. Research findings show that there is no association between CRP levels and survival compared to other prognostic clinical tools for COPD.

Background: Data suggest that women are more susceptible to develop airway obstruction compared to men for the same number of cigarettes smoked. Objectives: To compare the prevalence of chronic obstructive lung disease (COPD) and the effect of smoking on the risk of developing COPD according to gender, in a population of high-risk smokers. Methods: In 795 smokers, spirometry was performed using the criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) to determine airflow obstruction. COPD prevalence was determined in smokers grouped according to the number of cigarettes smoked per year [<20 (I), 20–40 (II), 40–60 (III) and >60 pack-years (IV)] and age. Results: Men were older, smoked more and for a longer period. Age at smoking initiation and the number of packs smoked per day did not differ. COPD was diagnosed in 26% of the subjects (30.5% men and 22.3% women, p < 0.001) with similar degree of obstruction (forced expiratory volume in 1 s: 78% of predicted in men vs. 75% in women). COPD prevalence was lower in women in all categories irrespective of the pack-year history (I: 9 vs. 19%; II: 16 vs. 28%; III: 28 vs. 39%, and IV: 25 vs. 42%, respectively, p < 0.001). In those older than 50 years, 34% men and 17% women (p < .001) had COPD. Conclusions: Using the GOLD criteria, the prevalence of COPD in smokers was higher than previous reports. In this self-selected sample of high-risk smokers having the same smoking history, prevalence was lower in women than in men, suggesting a lower susceptibility for the development of airway obstruction. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The Global Initiative for Obstructive Lung Disease (GOLD) does not promote diffusing capacity for carbon monoxide (Dlco) values in the evaluation of COPD. In GOLD spirometric stage I COPD patients, the clinical and prognostic impact of a low Dlco has not been explored.Research Question: Could a Dlco threshold help define an increased risk of death and a different clinical presentation in these patients?Study Design and Methods: GOLD stage I COPD patients (n = 360) were enrolled and followed over 109 ± 50 months. Age, sex, pack-years' history, BMI, dyspnea, lung function measurements, exercise capacity, BODE index, and history of exacerbations were recorded. A cutoff value for Dlco was identified for all-cause mortality and the clinical and physiological characteristics of patients above and below the threshold compared. Cox regression analysis explored the predictive power of that cutoff value for all-cause mortality.Results: A Dlco cutoff value of <60% predicted was associated with all-cause mortality (Dlco ≥ 60%: 9% vs Dlco < 60%: 23%, P = .01). At a same FEV1% predicted and Charlson score, patients with Dlco < 60% had lower BMI, more dyspnea, lower inspiratory capacity (IC)/total lung capacity (TLC) ratio, lower 6-min walk distance (6MWD), and higher BODE. Cox multiple regression analysis confirmed that after adjusting for age, sex, pack-years history, smoking status, and BMI, a Dlco < 60% is associated with all-cause mortality (hazard ratio [HR], 95% CI = 3.37, 1.35-8.39; P = .009) INTERPRETATION: In GOLD I COPD patients, a Dlco < 60% predicted is associated with increased risk of death and worse clinical presentation. What the cause(s) of this association are and whether they can be treated need to be determined. [ABSTRACT FROM AUTHOR]

Background: Control in COPD is a dynamic concept that can reflect changes in patients' clinical status that may have prognostic implications, but there is no information about changes in control status and its long-term consequences.Methods: We classified 798 patients with COPD from the CHAIN cohort as controlled/uncontrolled at baseline and over 5 years. We describe the changes in control status in patients over long-term follow-up and analyze the factors that were associated with longitudinal control patterns and related survival using the Cox hazard analysis.Results: 134 patients (16.8%) were considered persistently controlled, 248 (31.1%) persistently uncontrolled and 416 (52.1%) changed control status during follow-up. The variables significantly associated with persistent control were not requiring triple therapy at baseline and having a better quality of life. Annual changes in outcomes (health status, psychological status, airflow limitation) did not differ in patients, regardless of clinical control status. All-cause mortality was lower in persistently controlled patients (5.5% versus 19.1%, p = 0.001). The hazard ratio for all-cause mortality was 2.274 (95% CI 1.394-3.708; p = 0.001). Regarding pharmacological treatment, triple inhaled therapy was the most common option in persistently uncontrolled patients (72.2%). Patients with persistent disease control more frequently used bronchodilators for monotherapy (53%) at recruitment, although by the end of the follow-up period, 20% had scaled up their treatment, with triple therapy being the most frequent therapeutic pattern.Conclusions: The evaluation of COPD control status provides relevant prognostic information on survival. There is important variability in clinical control status and only a small proportion of the patients had persistently good control. Changes in the treatment pattern may be relevant in the longitudinal pattern of COPD clinical control. Further studies in other populations should validate our results.Trial Registration: Clinical Trials.gov: identifier NCT01122758. [ABSTRACT FROM AUTHOR]

The CODEX index was developed and validated in patients hospitalized for COPD exacerbation to predict the risk of death and readmission within one year after discharge. Our study aimed to validate the CODEX index in a large external population of COPD patients with variable durations of follow-up. Additionally, we aimed to recalculate the thresholds of the CODEX index using the cutoffs of variables previously suggested in the 3CIA study (mCODEX). Individual data on 2,755 patients included in the COPD Cohorts Collaborative International Assessment Plus (3CIA+) were explored. A further two cohorts (ESMI AND EGARPOC-2) were added. To validate the CODEX index, the relationship between mortality and the CODEX index was assessed using cumulative/dynamic ROC curves at different follow-up periods, ranging from 3 months up to 10 years. Calibration was performed using univariate and multivariate Cox proportional hazard models and Hosmer-Lemeshow test. A total of 3,321 (87.8% males) patients were included with a mean ± SD age of 66.9 ± 10.5 years, and a median follow-up of 1,064 days (IQR 25–75% 426–1643), totaling 11,190 person-years. The CODEX index was statistically associated with mortality in the short- (≤3 months), medium- (≤1 year) and long-term (10 years), with an area under the curve of 0.72, 0.70 and 0.76, respectively. The mCODEX index performed better in the medium-term (<1 year) than the original CODEX, and similarly in the long-term. In conclusion, CODEX and mCODEX index are good predictors of mortality in patients with COPD, regardless of disease severity or duration of follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome‐wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco‐induced non‐small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n = 3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (pcombined = 5.66 × 10−5; ORcombined = 2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (pcombined = 1.02 × 10−4; ORcombined = 2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early‐stage NSCLC. PDE10A and ATP10DmRNA expressions correlated with survival in 821 stage I–II NSCLC patients (p = 0.01 and p < 0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I–II NSCLC (p = 0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco‐induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco‐induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC. [ABSTRACT FROM AUTHOR]

Abstract: Background and objective: Cluster analysis has been utilized to explore phenotypic heterogeneity in chronic obstructive pulmonary disease (COPD). To date, little is known about the longitudinal variability of clusters in COPD patients. We aimed to evaluate the 2‐year cluster variability in stable COPD patients. Methods: We evaluated the following variables in COPD patients at baseline and 2 years later: age, gender, pack‐year history, body mass index (BMI), modified Medical Research Council (MMRC) scale, 6‐min walking distance (6MWD), spirometry and COPD Assessment Test (CAT). Patient classification was performed using cluster analysis at baseline and 2 years later. Each patient’s cluster variability after 2 years and its parameters associated with cluster change were explored. Results: A total of 521 smokers with COPD were evaluated at baseline and 2 years later. Three different clusters were consistently identified at both evaluation times: cluster A (of younger age, mild airway limitation, few symptoms), cluster B (intermediate) and cluster C (of older age, severe airway limitation and highly symptomatic). Two years later, 70% of patients were unchanged, whereas 30% changed from one cluster to another: 20% from A to B; 15% from B to A; 15% from B to C; 42% from C to B and 8% from C to A. 6MWD, forced expiratory volume in 1 s (FEV1) % and CAT were the principal parameters responsible for this change. Conclusion: After 2 years of follow‐up, most of the COPD patients maintained their cluster assignment. Exercise tolerance, lung function and quality of life were the main driving parameters in those who change their cluster assignment. [ABSTRACT FROM AUTHOR]

Rationale: Pulmonary artery enlargement (PAE) is associated with exacerbations in Chronic Obstructive Pulmonary Disease (COPD) and with survival in moderate to severe patients. The potential role of PAE in survival prediction has not been compared with other clinical and physiological prognostic markers. Methods: In 188 patients with COPD, PA diameter was measured on a chest CT and the following clinical and physiological parameters registered: age, gender, smoking status, pack-years history, dyspnea, lung function, exercise capacity, Body Mass Index, BODE index and history of exacerbations in year prior to enrolment. Proportional Cox regression analysis determined the best predictor of all cause survival. Results: During 83 months (±42), 43 patients died. Age, pack-years history, smoking status, BMI, FEV1%, six minute walking distance, Modified Medical Research Council dyspnea scale, BODE index, exacerbation rate prior to enrollment, PA diameter and PAE (diameter≥30mm) were associated with survival. In the multivariable analysis, age (HR: 1.08; 95%CI: 1.03–1.12, p<0.001) and PAE (HR: 2.78; 95%CI: 1.35–5.75, p = 0.006) were the most powerful parameters associated with all-cause mortality. Conclusions: In this prospective observational study of COPD patients with mild to moderate airflow limitation, PAE was the best predictor of long-term survival along with age. [ABSTRACT FROM AUTHOR]

Background: Aging is an important risk factor for most chronic diseases. Patients with COPD develop more comorbidities than non-COPD subjects. We hypothesized that the development of comorbidities characteristically affecting the elderly occur at an earlier age in subjects with the diagnosis of COPD. Methods and findings: We included all subjects carrying the diagnosis of COPD (n = 27,617), and a similar number of age and sex matched individuals without the diagnosis, extracted from the 727,241 records of individuals 40 years and older included in the EpiChron Cohort (Aragon, Spain). We compared the cumulative number of comorbidities, their prevalence and the mortality risk between both groups. Using network analysis, we explored the connectivity between comorbidities and the most influential comorbidities in both groups. We divided the groups into 5 incremental age categories and compared their comorbidity networks. We then selected those comorbidities known to affect primarily the elderly and compared their prevalence across the 5 age groups. In addition, we replicated the analysis in the smokers’ subgroup to correct for the confounding effect of cigarette smoking. Subjects with COPD had more comorbidities and died at a younger age compared to controls. Comparison of both cohorts across 5 incremental age groups showed that the number of comorbidities, the prevalence of diseases characteristic of aging and network’s density for the COPD group aged 56–65 were similar to those of non-COPD 15 to 20 years older. The findings persisted after adjusting for smoking. Conclusion: Multimorbidity increases with age but in patients carrying the diagnosis of COPD, these comorbidities are seen at an earlier age. [ABSTRACT FROM AUTHOR]

Background: Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for cardiovascular (CV) disease, one of the most frequent causes of death in COPD patients. The goal of the present study was to evaluate the prognostic value of non-invasive CV risk markers in COPD patients.Methods: CV risk was prospectively evaluated in 287 COPD patients using non-invasive markers including the Framingham score, the Systematic Coronary Risk Evaluation (SCORE) charts, coronary arterial calcium (CAC), epicardial adipose tissue (EAT), as well as clinical, biochemical and physiological variables. The predictive power of each parameter was explored using CV events as the main outcome.Results: During a median follow up of 65 months (ICR: 36-100), 44 CV events were recorded, 12 acute myocardial infarctions (27.3%), 10 ischemic heart disease/angina (22.7%), 12 peripheral artery disease events requiring surgery (27.3%) and 10 strokes (22.7%). A total of 35 CV deaths occurred during that period. Univariable analysis determined that age, hypertension, CRP, total Cholesterol, LDL-Cholesterol, Framingham score and CAC were independently associated with CV events. Multivariable analysis identified CAC as the best predictor of CV events (HR; 95%CI: 1.32; 1.19-1.46, p < 001).Conclusions: In COPD patients attending pulmonary clinics, CAC was the best independent non-invasive predictor of CV events. This tool may help evaluate the risk for a CV event in patients with COPD. Larger studies should reproduce and validate these findings. [ABSTRACT FROM AUTHOR]

Background: Chronic Obstructive Pulmonary Disease (COPD) may be associated with accelerated aging. Telomere shortening is a biomarker of aging. Cross-sectional studies describe shorter telomeres in COPD compared with matched controls. No studies have described telomere length trajectory and its relationship with COPD progression. We investigated telomere shortening over time and its relationship to clinical and lung function parameters in a COPD cohort and smoker controls without COPD.Methods: At baseline leukocyte telomere length was measured by qPCR in 121 smokers with COPD and 121 without COPD matched by age (T/S0). The measurements were repeated in 70 of those patients with COPD and 73 non-COPD smokers after 3 years of follow up (T/S3).Results: At initial measurement, telomeres were shorter in COPD patients when compared to smoker controls (T/S = 0.68 ± 0.25 vs. 0.88 ± 0.52, p = 0.003) independent from age and sex. During the follow-up period, we observed an accelerated telomere shortening in individuals with COPD in contrast to smoker controls (T/S0 = 0.66 ± 0.21 vs. T/S3 = 0.46 ± 0.16, p < 0.001, for the patients with COPD and T/S0 = 0.83 ± 0.56 vs. T/S3 = 0.74 ± 0.52, p = 0.023 for controls; GLIM, p = 0.001). This shortening was inversely related to the baseline telomere length (r = -0.49, p < 0.001). No significant relationship was found between the rate of change in telomere length and change in lung function in the patients with COPD (p > 0.05).Conclusions: Compared with smokers, patients with COPD have accelerated telomere shortening and this rate of attrition depends on baseline telomere length. Furthermore, the telomere length and its rate of shortening did not relate to clinical and lung function parameters changes over 3 years of follow-up. [ABSTRACT FROM AUTHOR]

Volcanic eruptions emit gases and particulate matter into the atmosphere which, if inhaled, can have an impact on health. The eruption of the volcano situated in the Cumbre Vieja Nature Reserve (La Palma, Canary Islands, Spain) affords a unique opportunity to study the effect of such a phenomenon on health. The aim of the proposed study is to assess the short-, medium- and long-term respiratory health effects of exposure to volcanic emissions from the eruption in three different population groups. We propose to undertake a multidesign study: an ambispective cohort study to analyze the effect of the eruption on the general population, the highly exposed population, and the childhood population; and a pre-post quasi-experimental study on subjects with previously diagnosed respiratory diseases. The information will be collected using a personal interview, biologic specimens, air pollution data, data from medical records, respiratory tests and imaging tests. The study has an envisaged follow-up of five years, to run from the date of initial recruitment, with annual data-collection. This study has been approved by the Santa Cruz de Tenerife Provincial Research Ethics Committee (Canary Island Health Service) on March 10, 2022. This study will make it possible to advance our knowledge of the effect a volcano eruption has on population health, both short- and long-term, and to assess the potential respiratory injury attributable to volcanic eruptions. It may serve as a model for future studies of new volcanic eruptions in the coming years. • There are uncertainties about the medium and long-term effect of volcanic eruptions on the health of the population. • Characteristics of La Palma eruption afford an unique opportunity to assess its possible effects on health. • This study will be the most ambitious to date and will use data from different sources. [ABSTRACT FROM AUTHOR]

Hypoxia is involved in the development of chronic inflammatory processes. Under hypoxic conditions HIF1A, VEGF and VEGFR2 are expressed and mediate the course of the resultant disease. The aim of the present study was to define the associations between tSNPs in these genes and COPD susceptibility and progression in a Spanish cohort. The T alleles in rs3025020 and rs833070 SNPs (VEGFA gene) were less frequent in the group of COPD cases and were associated with a lower risk of developing the disease (OR = 0.60; 95% CI = 0. 39–0.93; p = 0.023 and OR = 0.60; 95% CI = 0.38–0.96; p = 0.034, respectively) under a dominant model of inheritance. The haplotype in which both SNPs presented the T allele confirmed the association found (OR = 0.02; 95% CI = 0.00 to 0.66; p = 0.03). Moreover, patients with COPD carrying the T allele in homozygosis in rs3025020 SNP showed higher lung function values and this association remained constant during 3 years of follow-up. In conclusion, T allele in rs833070 and rs3025020 may confer a protective effect to COPD susceptibility in a Spanish population and the association of the SNP rs3025020 with lung function may be suggesting a role for VEGF in the progression of the disease. [ABSTRACT FROM AUTHOR]

Background: The Global Initiative for Obstructive Lung Diseases (GOLD) defines COPD as a disease that is usually progressive. GOLD also provides a spirometric classification of airflow limitation. However, little is known about the long-term changes of patients in different GOLD grades. Objective: Explore the proportion and characteristics of COPD patients that change their spirometric GOLD grade over long-term follow-up. Methods: Patients alive for at least 8 years since recruitment and those who died with at least 4 years of repeated spirometric measurements were selected from the BODE cohort database. We purposely included the group of non survivors to avoid a “survival selection” bias. The proportion of patients that had a change (improvement or worsening) in their spirometric GOLD grading was calculated and their characteristics compared with those that remained in the same grade. Results: A total of 318 patients were included in the survivor and 217 in the non-survivor groups. Nine percent of survivors and 11% of non survivors had an improvement of at least one GOLD grade. Seventy one percent of survivors and non-survivors remained in the same GOLD grade. Those that improved had a greater degree of airway obstruction at baseline. Conclusions: In this selected population of COPD patients, a high proportion of patients remained in the same spirometric GOLD grade or improved in a long-term follow-up. These findings suggest that once diagnosed, COPD is usually a non-progressive disease. [ABSTRACT FROM AUTHOR]

Background: Asthma-COPD overlap syndrome (ACOS) has been recently described by international guidelines. A stepwise approach to diagnosis using usual features of both diseases is recommended although its clinical application is difficult.Methods: To identify patients with ACOS, a cohort of well-characterized patients with COPD and up to 1 year of follow-up was analyzed. We evaluated the presence of specific characteristics associated with asthma in this COPD cohort, divided into major criteria (bronchodilator test > 400 mL and 15% and past medical history of asthma) and minor criteria (blood eosinophils > 5%, IgE > 100 IU/mL, or two separate bronchodilator tests > 200 mL and 12%). We defined ACOS by the presence of one major criterion or two minor criteria. Baseline characteristics, health status (COPD Assessment Test [CAT]), BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index, rate of exacerbations, and mortality up to 1 year of follow-up were compared between patients with and without criteria for ACOS.Results: Of 831 patients with COPD included,125 (15%) fulfilled the criteria for ACOS, and 98.4% of them sustained these criteria after 1 year. Patients with ACOS were predominantly male (81.6%), with symptomatic mild to moderate disease (67%), who were receiving inhaled corticosteroids (63.2%). There were no significant differences in baseline characteristics, and only survival was worse in patients with non-ACOS COPD after 1 year of follow-up (P < .05).Conclusions: The proposed ACOS criteria are present in 15% of a cohort of patients with COPD and these patients show better 1-year prognosis than clinically similar patients with COPD with no ACOS criteria.Trial Registry: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Background and objective: COPD is a leading cause of dead worldwide and tobacco smoking is its major risk factor. IL8 is a proinflammatory chemokine mainly involved in the acute inflammatory reaction. The aim of this study was to test the association of IL-8, CXCR1 and CXCR2 gene variants and COPD susceptibility as part of a replication study and explore the effect of these variations in disease progression. Methods: 9 tagSNPs were genotyped in 728 Caucasian individuals (196 COPD patients, 80 smokers and 452 non-smoking controls). Pulmonary compromise was evaluated using spirometry and clinical parameters at baseline and annually over a 2 years period. We also determined plasma levels of TNF-α, IL-6, IL-8 and IL-16 in COPD patients. Results: There was a lack of association between gene variants or haplotypes with predisposition to COPD. No correlation was observed between the polymorphisms and cytokines levels. Interestingly, significant associations were found between carriers of the rs4073A (OR = 3.53, CI 1.34-9.35, p = 0.01), rs2227306C (OR = 5.65, CI 1.75-18.88, p = 0.004) and rs2227307T (OR = 4.52, CI = 1.49-12.82, p = 0.007) alleles in the IL-8 gene and patients who scored higher in the BODE index and showed an important decrease in their FEV1 and FVC during the 2 years follow-up period ( p < 0.05). Conclusions: Despite no association was found between the studied genes and COPD susceptibility, three polymorphisms in the IL-8 gene appear to be involved in a worse progression of the disease, with an affectation beyond the pulmonary function and importantly, a reduction in lung function along the follow-up years. [ABSTRACT FROM AUTHOR]

Background: FEV1 is universally used as a measure of severity in COPD. Current thresholds are based on expert opinion and not on evidence. Objectives: We aimed to identify the best FEV1 (% predicted) and dyspnea (mMRC) thresholds to predict 5-yr survival in COPD patients. Design and Methods: We conducted a patient-based pooled analysis of eleven COPD Spanish cohorts (COCOMICS). Survival analysis, ROC curves, and C-statistics were used to identify and compare the best FEV1 (%) and mMRC scale thresholds that predict 5-yr survival. Results: A total of 3,633 patients (93% men), totaling 15,878 person-yrs. were included, with a mean age 66.4±9.7, and predicted FEV1 of 53.8% (±19.4%). Overall 975 (28.1%) patients died at 5 years. The best thresholds that spirometrically split the COPD population were: mild ≥70%, moderate 56–69%, severe 36–55%, and very severe ≤35%. Survival at 5 years was 0.89 for patients with FEV1≥70 vs. 0.46 in patients with FEV1 ≤35% (H.R: 6; 95% C.I.: 4.69–7.74). The new classification predicts mortality significantly better than dyspnea (mMRC) or FEV1 GOLD and BODE cutoffs (all p<0.001). Prognostic reliability is maintained at 1, 3, 5, and 10 years. In younger patients, survival was similar for FEV1 (%) values between 70% and 100%, whereas in the elderly the relationship between FEV1 (%) and mortality was inversely linear. Conclusions: The best thresholds for 5-yr survival were obtained stratifying FEV1 (%) by ≥70%, 56–69%, 36–55%, and ≤35%. These cutoffs significantly better predict mortality than mMRC or FEV1 (%) GOLD and BODE cutoffs. [ABSTRACT FROM AUTHOR]

The article presents a study to determine the distribution and prognostic validity of the new Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading system up to 10 years. The study involved 3,633 patients with chronic obstructive pulmonary disease (COPD) cohorts grouped into four categories from A (low risk, less symptoms) up to D (high risk, more symptoms). It finds that the new GOLD grading produces an uneven split of the COPD population, one-third each in Group A and D.

Rationale: The distance walked in the 6-min walk test (6MWT) predicts mortality in patients with severe COPD. Little is known about its prognostic value in patients with a wider range of COPD severity, living in different countries, and the potential additional impact of oxygen desaturation measured during the test.Methods: We enrolled 576 stable COPD outpatients in Spain and the United States and observed them for at least 3 years (median, 60 months). We measured FEV1, body mass index, Pao2, Charlson comorbidity score, 6-min walk distance (6MWD), and oxygen saturation by pulse oximetry (Spo2) during the 6MWT. Desaturation was defined as a fall in Spo2 > or = 4% or Spo2 < 90%. Regression analysis helped determine the association between these variables and all-cause and respiratory mortality.Results: The 6MWD was a good predictor of all-cause and respiratory mortality primarily in patients with FEV1 < 50% of predicted (p < 0.001) after adjusting for all covariates. Patients with desaturation during the 6MWT had a higher mortality rate than patients without desaturation (67% vs 38%, p < 0.001). Oxygen desaturation predicted mortality (relative risk, 2.63; 95% confidence interval, 1.53 to 4.51; p < 0.001) but with less power than Pao2 at rest.Conclusions: The 6MWD helps predict mortality primarily in patients with severe COPD. Although the oxygen desaturation profile during the 6MWT improves the predictive ability of the 6MWD, it appears to be of less relevance than in other lung diseases and than the resting Pao2. [ABSTRACT FROM AUTHOR]

Study objectives: The potential benefits of noninvasive positive pressure ventilation (NIPPV) for patients with COPD remains inconclusive, as most studies have included only a small number of patients. We therefore undertook a meta-analysis of randomized controlled trials (RCTs) that compared nocturnal NIPPV with conventional management in patients with COPD and stable respiratory failure. Design: RCTs were identified from several sources, such as MEDLINE, EMBASE, and CINAHL. In addition, records were identified through hand searching of abstracts from meetings of the American Thoracic Society, the American College of Chest Physicians, and the European Respiratory Society. Patients: Patients with COPD according to the definition of the American Thoracic Society. Interventions: NIPPV applied via a nasal or facemask for at least 5 h/d for at least 3 weeks. Patients in the actively treated group continued to receive the usual management for COPD. The control group received the same management as the study group but did not receive NIPPV. Measurements and results: PaCO[sub 2], PaO[sub 2], 6-min walking distance (6MWD), respiratory muscle function, FEV[sub 1], vital capacity, and sleep efficiency (time asleep as a percentage of total time in bed) were used as outcome measures. The publications were reduced to 10 potentially eligible articles from 164 publications retrieved from computer searches and 8 further abstracts. Four trials were finally included in the meta-analysis. The only outcome for which the confidence intervals excluded zero was maximal inspiratory pressure (PImax). The confidence intervals for the other outcomes included zero. The mean treatment effects for FEV[sub 1] and PImax were small, whereas it was moderate for the 6MWD. Small negative effects were found for the outcomes of vital capacity, PaCO[sub 2], and sleep efficiency. Conclusions: This meta-analysis of 3 months of NIPPV in patients with stable COPD showed that ventilatory support did not... [ABSTRACT FROM AUTHOR]

Background: Pulmonary artery enlargement (PAE) detected using chest computed tomography (CT) is associated with poor outcomes in chronic obstructive pulmonary disease (COPD). It is unknown whether nocturnal hypoxemia occurring in smokers, with or without COPD, obstructive sleep apnoea (OSA) or their overlap, may be associated with PAE assessed by chest CT. Methods: We analysed data from two prospective cohort studies that enrolled 284 smokers in lung cancer screening programs and completing baseline home sleep studies and chest CT scans. Main pulmonary artery diameter (PAD) and the ratio of the PAD to that of the aorta (PA:Ao ratio) were measured. PAE was defined as a PAD ≥ 29 mm in men and ≥27 mm in women or as a PA:Ao ratio > 0.9. We evaluated the association of PAE with baseline characteristics using multivariate logistic models. Results: PAE prevalence was 27% as defined by PAD measurements and 11.6% by the PA:Ao ratio. A body mass index ≥ 30 kg/m2 (OR 2.01; 95%CI 1.06–3.78), lower % predicted of forced expiratory volume in one second (FEV1) (OR 1.03; 95%CI 1.02–1.05) and higher % of sleep time with O2 saturation < 90% (T90) (OR 1.02; 95%CI 1.00–1.03), were associated with PAE as determined by PAD. However, only T90 remained significantly associated with PAE as defined by the PA:Ao ratio (OR 1.02; 95%CI 1.01–1.03). In the subset group without OSA, only T90 remains associated with PAE, whether defined by PAD measurement (OR 1.02; 95%CI 1.01–1.03) or PA:Ao ratio (OR 1.04; 95%CI 1.01–1.07). Conclusions: In smokers with or without COPD, nocturnal hypoxemia was associated with PAE independently of OSA coexistence. [ABSTRACT FROM AUTHOR]

Background: External validations and comparisons of prognostic models or scores are a prerequisite for their use in routine clinical care but are lacking in most medical fields including chronic obstructive pulmonary disease (COPD). Our aim was to externally validate and concurrently compare prognostic scores for 3-year all-cause mortality in mostly multimorbid patients with COPD.Methods: We relied on 24 cohort studies of the COPD Cohorts Collaborative International Assessment consortium, corresponding to primary, secondary, and tertiary care in Europe, the Americas, and Japan. These studies include globally 15,762 patients with COPD (1871 deaths and 42,203 person years of follow-up). We used network meta-analysis adapted to multiple score comparison (MSC), following a frequentist two-stage approach; thus, we were able to compare all scores in a single analytical framework accounting for correlations among scores within cohorts. We assessed transitivity, heterogeneity, and inconsistency and provided a performance ranking of the prognostic scores.Results: Depending on data availability, between two and nine prognostic scores could be calculated for each cohort. The BODE score (body mass index, airflow obstruction, dyspnea, and exercise capacity) had a median area under the curve (AUC) of 0.679 [1st quartile-3rd quartile = 0.655-0.733] across cohorts. The ADO score (age, dyspnea, and airflow obstruction) showed the best performance for predicting mortality (difference AUCADO - AUCBODE = 0.015 [95% confidence interval (CI) = -0.002 to 0.032]; p = 0.08) followed by the updated BODE (AUCBODE updated - AUCBODE = 0.008 [95% CI = -0.005 to +0.022]; p = 0.23). The assumption of transitivity was not violated. Heterogeneity across direct comparisons was small, and we did not identify any local or global inconsistency.Conclusions: Our analyses showed best discriminatory performance for the ADO and updated BODE scores in patients with COPD. A limitation to be addressed in future studies is the extension of MSC network meta-analysis to measures of calibration. MSC network meta-analysis can be applied to prognostic scores in any medical field to identify the best scores, possibly paving the way for stratified medicine, public health, and research. [ABSTRACT FROM AUTHOR]

Background Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. Methods After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. Main outcomes Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. Findings A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. Conclusions The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed. [ABSTRACT FROM AUTHOR]

A correction to the article "Telomere shortening and accelerated aging in COPD: findings from the BODE cohort" in the previous issue is presented.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by an incompletely reversible limitation in airflow. A physiological variable — the forced expiratory volume in one second (FEV1) — is often used to grade the severity of COPD. However, patients with COPD have systemic manifestations that are not reflected by the FEV1. We hypothesized that a multidimensional grading system that assessed the respiratory and systemic expressions of COPD would better categorize and predict outcome in these patients. Methods: We first evaluated 207 patients and found that four factors predicted the risk of death in this cohort: the body-mass index (B), the degree of airflow obstruction (O) and dyspnea (D), and exercise capacity (E), measured by the six-minute–walk test. We used these variables to construct the BODE index, a multidimensional 10-point scale in which higher scores indicate a higher risk of death. We then prospectively validated the index in a cohort of 625 patients, with death from any cause and from respiratory causes as the outcome variables. Results: There were 25 deaths among the first 207 patients and 162 deaths (26 percent) in the validation cohort. Sixty-one percent of the deaths in the validation cohort were due to respiratory insufficiency, 14 percent to myocardial infarction, 12 percent to lung cancer, and 13 percent to other causes. Patients with higher BODE scores were at higher risk for death; the hazard ratio for death from any cause per one-point increase in the BODE score was 1.34 (95 percent confidence interval, 1.26 to 1.42; P<0.001), and the hazard ratio for death from respiratory causes was 1.62 (95 percent confidence interval, 1.48 to 1.77; P<0.001). The C statistic for the ability of the BODE index to predict the risk of death was larger than that for the FEV1 (0.74 vs. 0.65). Conclusions: The BODE index, a simple multidimensional grading system, is better than the FEV1 at predicting the risk of death from any cause and from respiratory causes among patients with COPD. N Engl J Med 2004;350:1005-12. [ABSTRACT FROM AUTHOR]