Chronic Obstructive Lung Disease Grade Research Articles

Airway Mucus Plugs on Chest Computed Tomography Are Associated with Exacerbations in COPD.

Mucus plugs were visually-identified on baseline chest computed tomography (CT) scans from smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 2-4 COPD enrolled in two multicenter cohort studies: Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) and COPDGene. Associations between ordinal mucus plug score categories (0/1-2/≥3) and prospectively-ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate-to-severe) and/or ER/hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment. Among 3,250 participants in COPDGene (mean±SD age 63.7±8.4 years, FEV1 50.6%±17.8% predicted, 45.1% female) and 1,716 participants in ECLIPSE (age 63.3±7.1 years, FEV1 48.3%±15.8% predicted, 36.2% female), 44.4% and 46.0% had mucus plugs, respectively. The incidence rates of AEs were 61.0 (COPDGene) and 125.7 (ECLIPSE) per 100 person-years. Relative to those without mucus plugs, the presence of 1-2 and ≥3 mucus plugs was associated with increased risk (adjusted rate ratio, aRR [95%CI]=1.07[1.05-1.09] and 1.15[1.1-1.2] in COPDGene; aRR=1.06[1.02-1.09] and 1.12[1.04-1.2] in ECLIPSE, respectively) for prospective moderate-to-severe AEs. The presence of 1-2 and ≥3 mucus plugs was also associated with increased risk for severe AEs during follow-up (aRR=1.05[1.01-1.08] and 1.09[1.02-1.18] in COPDGene; aRR=1.17[1.07-1.27] and 1.37[1.15-1.62] in ECLIPSE, respectively). CT-based mucus plugs are associated with an increased risk for future COPD AEs.

Prevalence of and factors associated with cognitive frailty in elderly patients with chronic obstructive pulmonary disease: A cross-sectional study.

The status of cognitive frailty in elderly patients with chronic obstructive pulmonary disease (COPD) and its influencing factors in China remains unclear. This study aimed to investigate the prevalence of and factors associated with cognitive frailty in elderly patients with COPD. This cross-sectional study enrolled elderly patients with stable COPD between May and November 2022 from the Respiratory Department of the First Affiliated Hospital of Zhengzhou University and the Fifth Affiliated Hospital of Zhengzhou University. Convenience sampling method was adopted. Frailty Phenotype scale, Montreal Cognitive Assessment scale, Geriatric Depression Scale, and Clinical Dementia Rating scale were used to assess the prevalence of cognitive frailty in elderly patients with COPD. Multivariable logistic regression analysis was used to explore the associated factors. A total of 406 valid questionnaires were collected, and 173 patients (35.6%) had cognitive frailty. Binary logistic regression analysis showed that sex (odds ratio [OR] = 0.009; 95%CI: 0.001-0.770; P = .038), depression (OR = 17.780; 95%CI: 1.092-289.478; P = .043), modified Medical Research Council grade 1-3 (OR = 28.394-4095.683; 95%CI: 1.086-4,592,652.211; P < .05), global initiative for chronic obstructive lung disease grade 2 and 3 (OR = 32.508-282.072; 95%CI: 1.101-12,516.874; P < .05), and frequencies of acute exacerbations of COPD and hospitalizations within 1 year of 2 times (OR = 21.907; 95%CI: 4.587-104.622; P < .001) were independently associated with cognitive frailty. The prevalence of cognitive frailty in elderly patients with stable COPD was high. Female, depression, modified Medical Research Council grade, global initiative for chronic obstructive lung disease grade, and frequencies of acute exacerbations of COPD and hospitalizations within 1 year might be the factors independently associated with cognitive frailty, educational level might be a protective associated factor for cognitive frailty.

Quantifying the Length of Stay and Economic Impact of Albuterol and Levalbuterol in Hospitalized Patients With Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study.

Introduction Chronic obstructive pulmonary disease (COPD) affects millions in China and imposes a considerable economic burden on hospitalized patients who experience exacerbations. Nebulized short-acting beta-2 agonists (SABA) are recommended as initial therapy for exacerbation patients, but the optimal SABA remains uncertain. This study aimed to evaluate the impact of different SABAs, such as albuterol and levalbuterol, on the length of stay (LOS) and direct medical costs among hospitalized patients diagnosed with COPD. Methods This retrospective cohort study uses linked hospital administrative data from three hospitals in Chongqing. Patients with COPD, aged 40 years and older, who had been continuously treated with nebulized albuterol or levalbuterol during hospitalization, were eligible for the study. Patients were matched 1:1 by sex, age, and severity according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4. Patients were grouped according to the different SABA treatments they received. Demographic, economic, and clinical data were retrieved. LOS and direct healthcare costs were assessed. Results A total of 158 COPD patients were included, with 79 in each treatment group. Patients treated with levalbuterol had a significantly shorter median LOS (7.0 days vs. 8.0 days, P=0.003) and fewer direct healthcare median costs (total cost: ¥8,868.3 vs. ¥10,290.7, P=0.014; COPD-related western medicine fees: ¥383.8 vs. ¥505.3). Patients aged 60 or older were more likely to experience longer LOS and higher direct costs. Conclusion This retrospective cohort analysis supports that albuterol was associated with longer LOS and higher costs than levalbuterol.

Benefit-Harm Analysis of Earlier Initiation of Triple Therapy for Prevention of Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Reducing the risk of exacerbation is a fundamental goal in managing stable chronic obstructive pulmonary disease (COPD). Guidelines recommend triple therapy (inhaled corticosteroids, long-acting muscarinic antagonists, and long-acting β-agonists) only as a stepup from dual therapy (long-acting muscarinic antagonists and long-acting β-agonists) for patients at continued high risk of exacerbation, because of the trade-off of an increased risk of pneumonia associated with inhaled corticosteroid-containing therapies. However, there is little evidence on the optimum timing of initiating triple therapy. Objectives: To perform a benefit-harm analysis to evaluate the net benefit of earlier initiation of triple therapy for the prevention of acute exacerbations in patients with COPD compared with standard timing recommended in current guidelines. Methods: We used a validated whole-disease microsimulation model of COPD in the Canadian general population aged ⩾40 years to determine the benefit versus harm of earlier initiation of triple therapy over a 20-year time horizon compared with standard care. We assessed net change in quality-adjusted life-years (QALYs) from the reduction in risk of acute exacerbations and the increased risk of treatment-related pneumonia in subgroups of patients with COPD defined by exacerbation history, symptoms, and disease severity. Model parameters were determined from clinical trials and other published literature. Key parameters were varied in one-way sensitivity analysis. Results: In patients at high risk of acute exacerbation (54.7% female; mean age, 74.0 yr; 68% Global Initiative for Chronic Obstructive Lung Disease grades I and II), earlier initiation of triple therapy was associated with a net QALY gain of 4.8 per 100 patients with COPD over 20 years compared with standard care. The net QALY gain increased to 5.9 per 100 patients in the subgroup of patients with a high symptom burden (modified Medical Research Council dyspnea scale score, >1). Earlier initiation remained net beneficial in all subgroup and sensitivity analysis scenarios. Conclusions: Modeling suggests that earlier initiation of triple therapy is likely to be net beneficial for patients at high risk of acute exacerbation, with an even greater benefit to patients with a high symptom burden. Further clinical research is needed to verify these findings in empirical studies.

Feasibility and performance of the chronic obstructive pulmonary disease population screener and chronic obstructive pulmonary disease screening questionnaire in a Chinese physical examination center.

Chronic obstructive pulmonary disease (COPD) affects up to 13% of the Chinese population, though it is under diagnosed throughout China. Screening among asymptomatic individual as part of routine health checks in China can facilitate early diagnosis and intervention to prevent disease progress. The COPD Population Screener (COPD-PS) or COPD Screening Questionnaire (COPD-SQ) has yet to be applied in Chinese physical examination centers (PECs) for COPD screening, and their feasibility and effectiveness should be clarified before full-scale implementation. This study is the first to apply the COPD-PS and COPD-SQ in a public hospital PEC in China to assess their feasibility and effectiveness and to identify their optimal cutoff values. People aged ≥40 years who attended the Second Affiliated Hospital of Shantou University PECs from September 2021 to December 2022 were asked to complete the COPD-PS and COPD-SQ and to undergo spirometry. The optimal cutoff values of the two questionnaires at the maximal Youden index were found, and the sensitivity and specificity were calculated. Data from 198 participants were analyzed; mean [standard deviation (SD)] age of patients was 63.52 (10.94) years. Twenty-five participants (12.63%) were diagnosed with COPD. The number of COPD patients classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 to 4 were 8, 12, 4, and 1, respectively. The area under the curves (AUCs) of the COPD-PS and COPD-SQ were 0.730 and 0.738, respectively. The optimal COPD-PS cutoff value of 4 points corresponded to a sensitivity of 72.00% and a specificity of 60.10%. The COPD-SQ optimal cutoff value of 15 points corresponded to a sensitivity of 76.00% and a specificity of 63.60%. Applying the COPD-PS and COPD-SQ in Chinese PECs is feasible, cost-effective and effective. COPD-PS and COPD-SQ can facilitate the early diagnosis of COPD, and whether they can improve the participants' quality of life would benefit a further study. It is recommended that the COPD-PS or COPD-SQ questionnaires be added to the screening of the physical examination program in PECs as part of health checks for people over 40 years old.

Cumulative occupational exposure to gases and fumes is associated with impairment in lung function and disease-related quality of life in a German COPD patient cohort

ObjectivesThe impact of occupational exposures on lung function impairments and quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD) was analysed and compared with that of smoking.MethodsData...

Comparative study on physical activity and its influencing factors in patients with chronic pulmonary obstructive disease between China and the United Kingdom

Objective: To compare physical activity and its influencing factors in patients with chronic obstructive pulmonary disease (COPD) between China and the United Kingdom. Methods: We analyzed baseline data from China Kadoorie Biobank and the United Kingdom Biobank among COPD patients who were diagnosed with a one-second rate (FEV1/FVC) less than 70%. Physical activity level was calculated as metabolic equivalent (MET) and divided into three levels: low, medium, and high, according to tertiles stratified by gender and age. Multiple logistic regression was used to estimate ORs and 95%CIs for COPD and Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade about physical activity level, and subgroup analysis was conducted. Results: A total of 506 073 Chinese adults and 231 884 British adults were included. After adjusting for potential confounders, COPD was associated with lower physical activity levels in both Chinese and British COPD patients, with OR (95%CI) of 1.07(1.03-1.10) and 1.03(1.01-1.06) compared with non COPD patients, respectively. The GOLD grade was inversely correlated with physical activity level, particularly in a dose-response manner in the CKB population (trend test P<0.001). The negative relationship was stronger among the elderly, people with less education and lower economic status, and those with a smoking or chronic disease history. Chinese rural COPD patients were at high risk of decline of physical activity. Conclusions: Physical activity is inversely related to COPD, with a dose-response connection to GOLD grade. Therefore, physical activity maintenance and improvement should be encouraged and promoted in COPD patients, especially in high-risk groups.

The clinical characteristics and treatment response of patients with chronic obstructive pulmonary disease with low body mass index.

Background: This study aimed to analyze the clinical characteristics and treatment response of patients with chronic obstructive pulmonary disease (COPD) with low body mass index (BMI). Methods: In this cross-sectional study, we enrolled patients with stable COPD from the database setup by the Second Xiangya Hospital of Central South University. We classified the patients into three groups based on BMI: low-BMI (<18.5kg/m2), normal-BMI (≥18.5 and <24.0kg/m2), and high-BMI (≥24kg/m2) groups. We defined clinically important deterioration (CID) as a COPD Assessment Test (CAT) score increase of ≥2 and minimum clinically important difference (MCID) as a CAT score decrease of ≥2 during 6months of follow-up. We recorded the number of exacerbations and mortality during 1year of follow-up. Results: A total of 910 COPD patients were included with 144 (15.8%) patients in low-BMI, 475 (52.2%) in normal-BMI, and 291 (32.0%) in high-BMI groups. Patients with low BMI had worse pulmonary function, higher symptom scores, and exacerbations in the past year compared with normal- and high-BMI groups (p < 0.05). Logistic regression analysis revealed that age, Global Initiative for Chronic Obstructive Lung Disease grades 3 and 4, and hospitalizations in the past year were independent risk factors for patients with low BMI (p < 0.05). After 1year of follow-up, patients with low BMI had higher mortality and number of hospitalizations. Patients with low BMI were more likely to attain CID and less likely to attain MCID compared with patients with high BMI (p < 0.05). In addition, patients with low BMI treated with long-acting β2-agonist (LABA)+long-acting muscarinic antagonist (LAMA) and LABA+LAMA+inhaled corticosteroid (ICS) were more likely to attain MCID than those treated with LABA+ICS and LAMA (p < 0.05). Conclusion: COPD patients with low BMI had worse pulmonary function, higher symptom scores, and higher risk of future hospitalizations and mortality and were less likely to attain MCID and more likely to attain CID. It is worth noting that patients with low BMI treated with LABA+LAMA and LABA+LAMA+ICS were more likely to attain MCID than those treated with LABA+ICS and LAMA.

Can CT-Based Arterial and Venous Morphological Markers of Chronic Obstructive Pulmonary Disease Explain Pulmonary Vascular Remodeling?

We analyzed changes in quantitative pulmonary artery and vein parameters to investigate pulmonary vascular remodeling characteristics in chronic obstructive pulmonary disease (COPD) patients. This retrospective study recruited healthy volunteers and COPD patients. Participants undergoing standard-of-care pulmonary function testing (PFT) and computed tomography (CT) evaluations were classified into five groups: normal and Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4. Artery and vein analyses (volumes, numbers, densities, and fractions) were performed using artificial intelligence. Among 139 subjects (136 men; mean age, 64years±8 [SD]) with GOLD grade 1 (n=13), grade 2 (n=49), grade 3 (n=42), grade 4 (n=17) and control subjects (n=18) enrolled, differences in arterial volumes (BV5-10, BV10+, pulmonary arterial volume) and venous densities (BV5 density, BV10+ density, pulmonary venous density, pulmonary venous branch density) among control and GOLD grades 1-4 were statistically significant (P<.05). Higher pulmonary arterial volumes and lower number were observed with more advanced COPD. The number and volumes of pulmonary veins were lower in GOLD grades 2 and 3 than in GOLD grade 1 but higher in GOLD grade 4 than in GOLD grade 3. The numbers and volumes of pulmonary arteries and veins showed varying positive correlations (γ=0.18-0.96, P<.05). Pulmonary vascular densities were mildly to moderately correlated with PFT results (γ=0.236-0.495, P<.05) and were moderately negatively correlated with the emphysema percentage (γ=-0.591 to -0.315, P<.05). Patients with COPD exhibited pulmonary vascular remodeling, which occurred in the arteries at the early grade of COPD and in the veins at the late grade. CT-based quantitative analysis of pulmonary vasculature may become an imaging marker for early diagnosis and assessment of COPD severity.

Clinical factors linked to the type of respiratory medication in COPD: results from the COSYCONET cohort.

The use of maintenance medication in patients with chronic obstructive pulmonary disease (COPD) in real life is known to deviate from recommendations in guidelines, which are largely based on randomized controlled trials and selected populations. We used the COSYCONET (COPD and Systemic Consequences - Comorbidities Network) cohort to analyze factors linked to the use of COPD drugs under non-interventional circumstances. COSYCONET is an ongoing, multi-center, non-interventional cohort of patients with COPD. Patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 0-4 participating in visits 1-5 were included. Data covered the period from 2010 to 2018. Generalized linear models were used to examine the relation of COPD characteristics to different types of respiratory medication. A total of 1043 patients were included. The duration of observation was 4.5 years. Use of respiratory medication depended on GOLD grades 0-4 and groups A-D. Long-acting muscarinic antagonist therapy increased over time, and was associated with low carbon monoxide (CO) diffusing capacity, while inhaled corticosteroid (ICS) use decreased. Active smoking was associated with less maintenance therapy in general, and female sex with less ICS use. From the eight items of the COPD Assessment Test, only hill and stair climbing were consistently linked to treatment. Using data from a large, close to real-life observational cohort, we identified factors linked to the use of various types of respiratory COPD medication. Overall, use was consistent with GOLD recommendations. Beyond this, we identified other correlates of medication use that may help us to understand and improve therapy decisions in clinical practice. ClinicalTrials.gov NCT01245933.

Effect of acetazolamide on pulmonary vascular haemodynamics in patients with COPD going to altitude: a randomised, placebo-controlled, double-blind trial.

COPD may predispose to symptomatic pulmonary hypertension at high altitude. We investigated haemodynamic changes in lowlanders with COPD ascending to 3100 m and evaluated whether preventive acetazolamide treatment would attenuate the altitude-induced increase in pulmonary artery pressure (PAP). In this randomised, placebo-controlled, double-blind, parallel-group trial, patients with COPD Global Initiative for Chronic Obstructive Lung Disease grades 2-3 who were living <800 m and had peripheral oxygen saturation (S pO2 ) >92% and arterial carbon dioxide tension <6 kPa were randomised to receive either acetazolamide (125-250 mg·day-1) or placebo capsules, starting 24 h before ascent from 760 m and during a 2-day stay at 3100 m. Echocardiography, pulse oximetry and clinical assessments were performed at 760 m and after the first night at 3100 m. Primary outcome was PAP assessed by tricuspid regurgitation pressure gradient (TRPG). 112 patients (68% men, mean±sd age 59±8 years, forced expiratory volume in 1 s (FEV1) 61±12% pred, S pO2 95±2%) were included. Mean±sd TRPG increased from 22±7 to 30±10 mmHg in 54 patients allocated to placebo and from 20±5 to 24±7 mmHg in 58 patients allocated to acetazolamide (both p<0.05) resulting in a mean (95% CI) treatment effect of -5 (-9 to -1) mmHg (p=0.015). In patients assigned to placebo at 760/3100 m, mean±sd S pO2 was 95±2%/88±3%; in the acetazolamide group, the respective values were 94±2%/90±3% (both p<0.05), resulting in a treatment effect of +2 (1 to 3)% (p=0.001). In lowlanders with COPD travelling to 3100 m, preventive acetazolamide treatment attenuated the altitude-induced rise in PAP and improved oxygenation.

Prevalence of Metabolic Syndrome in Chronic Obstructive Pulmonary Disease and its Correlation with Body Mass Index, Airflow Obstruction, Dyspnea, and Exercise Index and C-Reactive Protein

Context: Chronic obstructive pulmonary disease (COPD) is a widespread reason of disease and death in developing countries like India, although it is preventable, controllable, and treatable. Objectives: We studied the occurrence of metabolic syndrome (MetS) among cases of stable COPD and determined the correlation between stable COPD with MetS and body mass index, airflow obstruction, dyspnea, and exercise (BODE index) and C-reactive protein (CRP) titer. Methods: The study was a case–control analysis conducted on 90 patients from November 2019 to August 2020. Results: Seventy percentage of our case population belonged to Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade 1 and 2. A significant correlation between forced expiratory volume 1 s (FEV1) with body mass index (BMI), triglycerides (TGs), high-density lipoproteins (HDL), systolic blood pressure (SBP), and fasting blood sugar (FBS) was found. The higher the GOLD grade (lower FEV1), the higher the values of BMI, TG, HDL, SBP, and FBS. A negative association with MetS is related to small study population. Conclusion: Patients with MetS had significantly lower FEV1, higher mean SI, higher mean waist circumference, higher mean BMI, higher mean SBP and diastolic blood pressure, higher FBS, and higher HDL and TG. Patients with MetS showed higher BODE index and CRP titer compared to ones without it. Apart from routine vaccination, assessment of systemic comorbidities for early detection of MetS plays a pivotal role to provide best possible quality of life and utmost care to COPD patients and helps reduce mortality and morbidities of COPD.

Detection of COPD in the SUMMIT Study lung cancer screening cohort using symptoms and spirometry.

COPD is a major comorbidity in lung cancer screening (LCS) cohorts, with a high prevalence of undiagnosed COPD. Combining symptom assessment with spirometry in this setting may enable earlier diagnosis of clinically significant COPD and facilitate increased understanding of lung cancer risk in COPD. In this study, we wished to understand the prevalence, severity, clinical phenotype and lung cancer risk of individuals with symptomatic undiagnosed COPD in a LCS cohort. 16 010 current or former smokers aged 55-77 years attended a lung health check as part of the SUMMIT Study. A respiratory consultation and spirometry were performed alongside LCS eligibility assessment. Those with symptoms, no previous COPD diagnosis and airflow obstruction were labelled as undiagnosed COPD. Baseline low-dose computed tomography (LDCT) was performed in those at high risk of lung cancer (PLCOm2012 score ≥1.3% and/or meeting USPSTF 2013 criteria). Nearly one in five (19.7%) met criteria for undiagnosed COPD. Compared with those previously diagnosed, those undiagnosed were more likely to be male (59.1% versus 53.2%; p<0.001), currently smoking (54.9% versus 47.6%; p<0.001) and from an ethnic minority group (p<0.001). Undiagnosed COPD was associated with less forced expiratory volume in 1 s impairment (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 and 2: 85.3% versus 68.4%; p<0.001) and lower symptom/exacerbation burden (GOLD A and B groups: 95.6% versus 77.9%; p<0.001) than those with known COPD. Multivariate analysis demonstrated that airflow obstruction was an independent risk factor for lung cancer risk on baseline LDCT (adjusted OR 2.74, 95% CI 1.73-4.34; p<0.001), with a high risk seen in those with undiagnosed COPD (adjusted OR 2.79, 95% CI 1.67-4.64; p<0.001). Targeted case-finding within LCS detects high rates of undiagnosed symptomatic COPD in those most at risk. Individuals with undiagnosed COPD are at high risk for lung cancer.

COPD identification and grading based on deep learning of lung parenchyma and bronchial wall in chest CT images.

Chest CT can display the main pathogenic factors of chronic obstructive pulmonary disease (COPD), emphysema and airway wall remodeling. This study aims to establish deep convolutional neural network (CNN) models using these two imaging markers to diagnose and grade COPD. Subjects who underwent chest CT and pulmonary function test (PFT) from one hospital (n = 373) were retrospectively included as the training cohort, and subjects from another hospital (n = 226) were used as the external test cohort. According to the PFT results, all subjects were labeled as Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grade 1, 2, 3, 4 or normal. Two DenseNet-201 CNNs were trained using CT images of lung parenchyma and bronchial wall to generate two corresponding confidence levels to indicate the possibility of COPD, then combined with logistic regression analysis. Quantitative CT was used for comparison. In the test cohort, CNN achieved an area under the curve of 0.899 (95%CI: 0.853-0.935) to determine the existence of COPD, and an accuracy of 81.7% (76.2-86.7%), which was significantly higher than the accuracy 68.1% (61.6%-74.2%) using quantitative CT method (p < 0.05). For three-way (normal, GOLD 1-2, and GOLD 3-4) and five-way (normal, GOLD 1, 2, 3, and 4) classifications, CNN reached accuracies of 77.4 and 67.9%, respectively. CNN can identify emphysema and airway wall remodeling on CT images to infer lung function and determine the existence and severity of COPD. It provides an alternative way to detect COPD using the extensively available chest CT. CNN can identify the main pathological changes of COPD (emphysema and airway wall remodeling) based on CT images, to infer lung function and determine the existence and severity of COPD. CNN reached an area under the curve of 0.853 to determine the existence of COPD in the external test cohort. The CNN approach provides an alternative and effective way for early detection of COPD using extensively used chest CT, as an important alternative to pulmonary function test.

A polygenic risk score and age of diagnosis of COPD.

Genetic susceptibility may be associated with earlier onset of chronic obstructive pulmonary disease (COPD). We hypothesised that a polygenic risk score (PRS) for COPD would be associated with earlier age of diagnosis of COPD. In 6647 non-Hispanic White (NHW) and 2464 African American (AA) participants from COPDGene, and 6812 participants from the Framingham Heart Study (FHS), we tested the relationship of the PRS and age of COPD diagnosis. Age at diagnosis was determined by: 1) self-reported age at COPD diagnosis or 2) age at visits when moderate-to-severe airflow limitation (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 2-4) was observed on spirometry. We used Cox regression to examine the overall and time-dependent effects of the PRS on incident COPD. In the COPDGene study, we also examined the PRS's predictive value for COPD at age <50 years (COPD50) using logistic regression and area under the curve (AUC) analyses, with and without the addition of other risk factors present at early life (e.g. childhood asthma). In Cox models, the PRS demonstrated age-dependent associations with incident COPD, with larger effects at younger ages in both cohorts. The PRS was associated with COPD50 (OR 1.55 (95% CI 1.41-1.71) for NHW, OR 1.23 (95% CI 1.05-1.43) for AA and OR 2.47 (95% CI 2.12-2.88) for FHS participants). In COPDGene, adding the PRS to known early-life risk factors improved prediction of COPD50 in NHW (AUC 0.69 versus 0.74; p<0.0001) and AA (AUC 0.61 versus 0.64; p=0.04) participants. A COPD PRS is associated with earlier age of diagnosis of COPD and retains predictive value when added to known early-life risk factors.

Significant Spirometric Transitions and Preserved Ratio Impaired Spirometry Among Ever Smokers

Emerging data from longitudinal studies suggest that preserved ratio impaired spirometry (PRISm), defined by proportionate reductions in FEV1 and FVC, is a heterogeneous population with frequent transitions to other lung function categories relative to individuals with normal and obstructive spirometry. Controversy regarding the clinical significance of these transitions exists (eg, whether transitions merely reflect measurement variability or noise). Are individuals with PRISm enriched for transitions associated with substantial changes in lung function? Current and former smokers enrolled in the Genetic Epidemiology of COPD (COPDGene) study with spirometry available in phases 1 through 3 (enrollment, 5-year follow-up, and 10-year follow-up) were analyzed. Postbronchodilator lung function categories were as follows: PRISm (FEV1< 80%predicted with FEV1/FVC ratio≥ 0.7), Global Initiative for Chronic Obstructive Lung Disease grade 0 (FEV1≥ 80%predicted and FEV1/FVC≥ 0.7), and obstruction (FEV1/FVC< 0.7). Significant transition status was affirmative if a subject belonged to two or more spirometric categories and had > 10%change in FEV1 %predicted and/or FVC %predicted between consecutive visits. Ever-PRISm was present if a subject had PRISm at any visit. Logistic regression examined the association between significant transitions and ever-PRISm status, adjusted for age, sex, race, FEV1 %predicted, current smoking, pack-years, BMI, and ever-positive bronchodilator response. Among subjects with complete data (N= 1,775) over 10.1 ± 0.4 years of follow-up, the prevalence of PRISm remained consistent (10.4%-11.3%) between phases 1 through 3, but nearly one-half of subjects with PRISm transitioned into or out of PRISm at each visit. Among all subjects, 19.7%had a significant transition; ever-PRISm was a significant predictor of significant transitions (unadjusted OR, 10.3; 95%CI, 7.9-13.5; adjusted OR, 14.9; 95%CI, 10.9-20.7). Results were similar with additional adjustment for radiographic emphysema and gas trapping, when lower limit of normal criteria were used to define lung function categories, and when FEV1 alone (regardless of change in FVC %predicted) was used to define significant transitions. PRISm is an unstable group, with frequent significant transitions to both obstruction and normal spirometry over time. ClinicalTrials.gov; No.: NCT000608764; URL: www. gov.

Imaging phenotypes of chronic obstructive pulmonary disease based on biphasic quantitative CT features

Quantitative analysis was performed on the biphasic CT of 40 patients [43-80 (66.1±9.0) years old, including 37 males] with stable chronic obstructive pulmonary disease (COPD) to measure the percentage of emphysema (Emph%); the percentage of small airway disease (SAD%) and the square root of the wall area of hypothetical airway with internal perimeter of 10 mm (Pi10). Based on the cluster analysis of Emph%, SAD% and Pi10, the patients were divided into five imaging phenotypes including no obvious imaging abnormality type (n=11), small airway disease-dominant type (n=9), bronchial wall thickening-dominant type (n=8), emphysema-dominant type (n=6) and mixed type (n=6). Patients with the same Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade had similar degree of airflow limitation, but the lesion components were not identical. Being different from the traditional imaging classification, even in the cases of mild emphysema, they can be further divided into small airway disease-dominant type and bronchial wall thickening-dominant type according to the difference of airway disease.

Investigation of the Clinical, Radiological and Biological Factors Associated with Disease Progression, Phenotypes and Endotypes of COPD in China (COMPASS): study design, protocol and rationale.

COPD is heterogeneous, and its presentation varies between countries. The major COPD cohort studies have only been performed in Western populations; the disease is not well characterised in other regions. The COMPASS (Investigation of the Clinical, Radiological and Biological Factors, Humanistic and Healthcare Utilisation Burden Associated with Disease Progression, Phenotypes and Endotypes of COPD in China; NCT04853225) is a prospective, 2.5-year-long, multi-centre, longitudinal, observational study with three aims: 1) to characterise stable and exacerbation phenotypes/endotypes in terms of clinical characteristics, blood and sputum biomarkers, lung microbiome and lung imaging; 2) to understand the relevance of markers of COPD disease progression identified in Western cohorts to Chinese patients; and 3) to characterise treatment pathways and healthcare resource utilisation. COMPASS will recruit 2000 participants, of which 1700 will be in Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grades I–IV (n=700, 700, 200 and 100, respectively), 180 participants with chronic bronchitis without airflow limitation and 120 never-smoker healthy controls. Study visits will be at baseline, 6, 18 and 30 months and at exacerbation. Assessments include lung function, exacerbation frequency, health status, blood biomarkers and, in a sub-cohort of 400 patients, chest high-resolution computed tomography, additional blood and sputum biomarkers, airway micro-, viral- and myco-biome, and physical activity. COMPASS will establish a unique clinical and biological dataset in a well-characterised cohort of individuals with COPD in China, with a particular focus on milder patients. As the first study of its kind attempting to understand the disease in an Asian setting, it will provide valuable insights into regional and ethnic differences in COPD.

TOLERABILITY, SAFETY, AND LUNG FUNCTION RESPONSE OF REVEFENACIN AND FORMOTEROL VIA NEBULIZATION IN PATIENTS WITH MODERATE TO VERY SEVERE COPD: A SUBGROUP ANALYSIS OF A PHASE 3 TRIAL

TOLERABILITY, SAFETY, AND LUNG FUNCTION RESPONSE OF REVEFENACIN AND FORMOTEROL VIA NEBULIZATION IN PATIENTS WITH MODERATE TO VERY SEVERE COPD: A SUBGROUP ANALYSIS OF A PHASE 3 TRIAL

Current symptom-based risk scores for stable coronary artery disease evaluation are not applicable in COPD patients.

BackgroundCardiovascular diseases are arguably the most important comorbidity in patients with COPD. Despite an increased prevalence of coronary artery disease (CAD) in COPD patients, there are no dedicated diagnostic recommendations.ObjectivesWe investigated whether COPD patients receive adequate primary evaluation of CAD despite overlapping symptoms.MethodsIn total, 302 patients with COPD who underwent invasive coronary angiography (ICA) were retrospectively matched (for age, body mass index and cardiovascular risk factors) with 302 patients without functional lung diseases. Quality and onset of symptoms prior to ICA were documented, and individual patients’ pretest probabilities according to European Society of Cardiology (ESC) guidelines were calculated. Endpoints were delay of ICA referral after symptom onset and clinical outcome, defined as subsequent revascularisation.ResultsMean delay between symptom onset and ICA was 19.9±22.0 months in COPD patients compared to 8.3±12.7 months in the control group (p<0.0001). COPD patients had a lower rate of typical chest pain (25.2% versus 38.1%, p=0.0009), and dyspnoea only (18.2% versus 26.8%, p=0.015). Sub-analysis of Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades revealed an incremental delay with increasing COPD severity: GOLD 1: 16.1±17.3 months; GOLD 2: 17.6±22.1 months; GOLD 3: 20.1±21.3 months; and GOLD 4: 24.2±23.4 months. Overall significant CAD prevalence (>70% stenosis) was 35.3%; the revascularisation rate increased with higher pretest probability for the control group but decreased for patients with COPD GOLD 1–4.ConclusionPatients with COPD are insufficiently evaluated for CAD due to overlapping symptoms. Current CAD risk scores for stable chest pain appear inappropriate for patients with COPD.