Chronic Obstructive Pulmonary Disease Subgroups Research Articles

Components of the Chronic Obstructive Pulmonary Disease Assessment Test Associated with the Exacerbation of Severe Chronic Obstructive Pulmonary Disease Patients

Introduction: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) score is widely used for evaluating the health status of patients diagnosed with COPD. The aim of this study was to identify which components of the CAT are associated with exacerbations in severe COPD patients. Methods: Using data from the Korean COPD Subgroup Study (KOCOSS), we identified 3,440 COPD patients, among which 1,027 patients are classified as having severe COPD based on spirometry results. The CAT scores on 8 items were evaluated and classified into respiratory and non-respiratory categories. We analyzed the association between CAT item scores and moderate-to-severe exacerbations during study enrollment and the following years. Results: Patients with a history of moderate-to-severe exacerbations had higher scores on non-respiratory CAT components. Longitudinal CAT scores on all items after enrollment were higher in the moderate-to-severe exacerbation group. Additionally, the frequency of severe exacerbations was associated with specific CAT components related to limited activities, confidence leaving home, sleeplessness, and energy. Conclusions: This study revealed that the non-respiratory CAT component scores were statistically significant factors for predicting the moderate-to-severe exacerbation of severe COPD patients. Non-respiratory symptoms and functional limitations should be considered in patients with severe COPD. Interventions, such as pulmonary rehabilitation, may be needed to improve patients’ overall well-being and prevent exacerbations.

Natural Killer Cells as a Further Insight into the Course of Chronic Obstructive Pulmonary Disease.

The role of natural killer (NK) cells in chronic obstructive pulmonary disease (COPD) pathogenesis has been discussed but is not yet clearly understood. This current study aimed to evaluate the associations between immunophenotypes, degrees of maturity, and the expression level of functional receptors of NK cells in the lung environment present in bronchoalveolar lavage fluid (BALF), and an attempt was made to determine their relationship in the course and progression of COPD. A total of 15 COPD patients and 14 healthy smokers were included. The clinical parameters of COPD were evaluated. In both groups, NK cells using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry were assessed in the peripheral blood. Additionally, NK cells using the same method were assessed in BALF in the COPD subgroup. The blood's NK cells differed from the estimated group's maturity and receptor expression. Functional receptors CD158b+, CD314+, and CD336+ expressed by NK cells were significantly interlinked with age, RV, TLC, 6MWT, smoking, and the number of exacerbations. These results confirm the essential role of NK cells in COPD pathogenesis. Additionally, the relationship between clinical parameters and NK cell expression may indicate its participation in the disease progression and exacerbation and allow for a better understanding of NK cell biology in COPD.

Factors Associated with the Discrepancy between Exercise Capacity and Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease.

Exercise capacity is associated with lung function decline in chronic obstructive pulmonary disease (COPD) patients, but a discrepancy between exercise capacity and airflow limitation exists. This study aimed to explore factors contributing to this discrepancy in COPD patients. Data for this prospective study were obtained from the Korean COPD Subgroup Study. The exercise capacity and airflow limitation were assessed using the 6-minute walk distance (6-MWD; m) and forced expiratory volume in 1 second (FEV1). Participants were divided into four groups: FEV1 >50%+6-MWD >350, FEV1 >50%+6- MWD ≤350, FEV1 ≤50%+6-MWD >350, and FEV1 ≤50%+6-MWD ≤350 and their clinical characteristics were compared. A total of 883 patients (male:female, 822:61; mean age, 68.3±7.97 years) were enrolled. Among 591 patients with FEV1 >50%, 242 were in the 6-MWD ≤350 group, and among 292 patients with FEV1 ≤50%, 185 were in the 6-MWD >350 group. The multiple regression analyses revealed that male sex (odds ratio [OR], 8.779; 95% confidence interval [CI], 1.539 to 50.087; p=0.014), current smoking status (OR, 0.355; 95% CI, 0.178 to 0.709; p=0.003), and hemoglobin levels (OR, 1.332; 95% CI, 1.077 to 1.648; p=0.008) were significantly associated with discrepancies in exercise capacity and airflow limitation in patients with FEV1 >50%. Meanwhile, in patients with FEV1 ≤50%, diffusion capacity of carbon monoxide (OR, 0.945; 95% CI, 0.912 to 0.979; p=0.002) was significantly associated with discrepancies between exercise capacity and airflow limitation. The exercise capacity of COPD patients may be influenced by factors other than airflow limitation, so these aspects should be considered when assessing and treating patients.

Clinical Characteristics and Frequency of Chronic Obstructive Pulmonary Disease Exacerbations in Korean Patients: Findings From the KOCOSS Cohort 2012-2021.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) exert a substantial burden on patients and healthcare systems; however, data related to the frequency of AECOPD in the Korean population are limited. Therefore, this study aimed to describe the frequency of severe, and moderate or severe AECOPD, as well as clinical and demographic characteristics of patients with chronic obstructive pulmonary disease (COPD) in South Korea. Data from patients aged > 40 years with post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity ≤ 70% of the normal predicted value from the Korea COPD Subgroup Study database were analyzed (April 2012 to 2021). The protocol was based on the EXAcerbations of COPD and their OutcomeS International study. Data were collected retrospectively for year 0 (0-12 months before study enrollment) based on patient recall, and prospectively during years 1, 2, and 3 (0-12, 13-24, and 25-36 months after study enrollment, respectively). The data were summarized using descriptive statistics. Data from 3,477 Korean patients (mean age, 68.5 years) with COPD were analyzed. Overall, most patients were male (92.3%), former or current smokers (90.8%), had a modified Medical Research Council dyspnea scale score ≥ 1 (83.3%), and had moderate airflow limitation (54.4%). The mean body mass index (BMI) of the study population was 23.1 kg/m², and 27.6% were obese or overweight. Hypertension was the most common comorbidity (37.6%). The mean blood eosinophil count was 226.8 cells/μL, with 21.9% of patients having ≥ 300 cells/μL. A clinically insignificant change in FEV1 (+1.4%) was observed a year after enrollment. Overall, patients experienced a mean of 0.2 severe annual AECOPD and approximately 1.1 mean moderate or severe AECOPD. Notably, the rates of severe AECOPD remained generally consistent over time. Compared with patients with no exacerbations, patients who experienced severe exacerbations had a lower mean BMI (21.7 vs. 23.1 kg/m²; P < 0.001) and lower lung function parameters (all P values < 0.001), but reported high rates of depression (25.5% vs. 15.1%; P = 0.044) and anxiety (37.3% vs. 16.7%; P < 0.001) as a comorbidity. Findings from this Korean cohort of patients with COPD indicated a high exacerbation burden, which may be attributable to the unique characteristics of the study population and suboptimal disease management. This highlights the need to align clinical practices with the latest treatment recommendations to alleviate AECOPD burden in Korea. ClinicalTrials.gov Identifier: NCT05750810.

Development of a daily predictive model for the exacerbation of chronic obstructive pulmonary disease

Acute exacerbation (AE) of chronic obstructive pulmonary disease (COPD) compromises health status; it increases disease progression and the risk of future exacerbations. We aimed to develop a model to predict COPD exacerbation. We merged the Korean COPD subgroup study (KOCOSS) dataset with nationwide medical claims data, information regarding weather, air pollution, and epidemic respiratory virus data. The Korean National Health and Nutrition Examination Survey (KNHANES) dataset was used for validation. Several machine learning methods were employed to increase the predictive power. The development dataset consisted of 590 COPD patients enrolled in the KOCOSS cohort; these were randomly divided into training and internal validation subsets on the basis of the individual claims data. We selected demographic and spirometry data, medications for COPD and hospital visit for AE, air pollution data and meteorological data, and influenza virus data as contributing factors for the final model. Six machine learning and logistic regression tools were used to evaluate the performance of the model. A light gradient boosted machine (LGBM) afforded the best predictive power with an area under the curve (AUC) of 0.935 and an F1 score of 0.653. Similar favorable predictive performance was observed for the 2151 individuals in the external validation dataset. Daily prediction of the COPD exacerbation risk may help patients to rapidly assess their risk of exacerbation and will guide them to take appropriate intervention in advance. This might lead to reduction of the personal and socioeconomic burdens associated with exacerbation.

Protein N-glycosylation in the bronchoalveolar space differs between never-smokers and long-term smokers with and without COPD.

Chronic obstructive pulmonary disease (COPD) kills millions of people annually and patients suffering from exacerbations of this disorder display high morbidity and mortality. The clinical course of COPD is associated with dysbiosis and infections, but the underlying mechanisms are poorly understood. Glycosylation of proteins play roles in regulating interactions between microbes and immune cells, and knowledge on airway glycans therefore contribute to the understanding of infections. Furthermore, glycans have biomarker potential for identifying smokers with enhanced risk for developing COPD as well as COPD subgroups. Here, we characterized the N-glycosylation in the lower airways of healthy never-smokers (HNS, n=5) and long-term smokers (LTS) with (LTS+, n=4) and without COPD (LTS-, n=8). Using mass spectrometry, we identified 57 highly confident N-glycan structures whereof 38 oligomannose, complex, and paucimannose type glycans were common to BAL samples from HNS, LTS- and LTS+ groups. Hybrid type N-glycans were identified only in the LTS+ group. Qualitatively and quantitatively, HNS had lower inter-individual variation between samples compared to LTS- or LTS+. Cluster analysis of BAL N-glycosylation distinguished LTS from HNS. Correlation analysis with clinical parameters revealed that complex N-glycans were associated with health and absence of smoking whereas oligomannose N-glycans were associated with smoking and disease. The N-glycan profile from monocyte-derived macrophages differed from the BAL N-glycan profiles. In conclusion, long-term smokers display substantial alterations of N-glycosylation in the bronchoalveolar space, and the hybrid N-glycans identified only in long-term smokers with COPD deserve to be further studied as potential biomarkers.

Clinical significance of normalized airflow obstruction in patients with chronic obstructive pulmonary disease

BackgroundThere is ongoing debate regarding the diagnostic criteria for chronic obstructive pulmonary disease (COPD); recent studies have focused on the early COPD detection and management. Here, we compared clinical features and prognosis in patients with FEV1/FVC<0.70 at baseline, according to normalized airflow obstruction status during follow-up. MethodsWe used the Korea COPD Subgroup Study (KOCOSS) cohort database, a prospective nationwide observational COPD study. Normalized obstruction (NO) was defined as FEV1/FVC ≥0.7 in the 2-year follow-up period, whereas fixed obstruction (FO) was defined as FEV1/FVC <0.7. Demographic and clinical data, 1-year exacerbation risk and difference in FEV1 decline over 2 years were compared between NO and FO groups. ResultsAmong the 670 COPD patients with post-bronchodilator FEV1/FVC <0.7 in this study, 95 (14.2%) displayed NO. Compared with the FO group, the NO group had higher FEV1, and DLCO, body mass index, as well as lower Saint George Respiratory Questionnaire, Beck Depression Index, and Beck Anxiety Index. Blood eosinophil count, IgE level, and FeNO did not significantly differ between two groups. There was no significant difference in exacerbation frequency between the two groups, but the NO group had a significant increase in FEV1 compared with the FO group during follow-up. ConclusionTransient airflow obstruction in the NO group may represent a clinical manifestation of early COPD; close monitoring is needed for such patients.

Breathlessness and exercise performance to predict mortality in long-term oxygen therapy – The population-based DISCOVERY study

BackgroundPatients with chronic respiratory failure treated with long-term oxygen therapy (LTOT) often have severe breathlessness, impaired exercise performance, and high but variable mortality that is difficult to predict. We aimed to evaluate breathlessness and exercise performance upon starting LTOT as predictors of overall and short-term mortality. MethodsThis was a longitudinal, population-based study of patients who initiated LTOT between 2015 and 2018 in Sweden. Breathlessness was measured using the Dyspnea Exertion Scale, and exercise performance using the 30s-Sit-To-Stand test. Associations with overall and three-month mortality were analyzed using Cox-regression. Subgroup analyses were performed for patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) respectively. The predictive capacity of models was assessed using a C-statistic. ResultsA total of 441 patients (57.6% female, aged 75.4 ± 8.3 years) were analyzed, of whom 141 (32%) died during a median follow-up of 260 (IQR 75–460) days. Both breathlessness and exercise performance were independently associated with overall mortality in the crude models, but only exercise performance remained independently associated with overall mortality when models were adjusted for other predictors, when short-term mortality was analyzed, or when breathlessness and exercise capacity were analyzed concurrently. The multivariable model including exercise performance but not breathlessness provided a relatively high predictive capacity for overall mortality, C-statistic 0.756 (95% CI 0.702–0.810). Similar results were seen in the COPD and ILD subgroups. ConclusionExercise performance as measured by the 30s-STS may be useful to identify patients with higher mortality on LTOT for optimized management and follow-up.

Undersampled Diffusion-Weighted 129Xe MRI Morphometry of Airspace Enlargement: Feasibility in Chronic Obstructive Pulmonary Disease

Multi-b diffusion-weighted hyperpolarized gas MRI measures pulmonary airspace enlargement using apparent diffusion coefficients (ADC) and mean linear intercepts (Lm). Rapid single-breath acquisitions may facilitate clinical translation, and, hence, we aimed to develop single-breath three-dimensional multi-b diffusion-weighted 129Xe MRI using k-space undersampling. We evaluated multi-b (0, 12, 20, 30 s/cm2) diffusion-weighted 129Xe ADC/morphometry estimates using a fully sampled and retrospectively undersampled k-space with two acceleration-factors (AF = 2 and 3) in never-smokers and ex-smokers with chronic obstructive pulmonary disease (COPD) or alpha-one anti-trypsin deficiency (AATD). For the three sampling cases, mean ADC/Lm values were not significantly different (all p > 0.5); ADC/Lm values were significantly different for the COPD subgroup (0.08 cm2s-1/580 µm, AF = 3; all p < 0.001) as compared to never-smokers (0.05 cm2s-1/300 µm, AF = 3). For never-smokers, mean differences of 7%/7% and 10%/7% were observed between fully sampled and retrospectively undersampled (AF = 2/AF = 3) ADC and Lm values, respectively. For the COPD subgroup, mean differences of 3%/4% and 11%/10% were observed between fully sampled and retrospectively undersampled (AF = 2/AF = 3) ADC and Lm, respectively. There was no relationship between acceleration factor with ADC or Lm (p = 0.9); voxel-wise ADC/Lm measured using AF = 2 and AF = 3 were significantly and strongly related to fully-sampled values (all p < 0.0001). Multi-b diffusion-weighted 129Xe MRI is feasible using two different acceleration methods to measure pulmonary airspace enlargement using Lm and ADC in COPD participants and never-smokers.

Safety and pulmonary function impact of surgical mask usage in stable COPD patients during the COVID-19 pandemic

There are hesitations about the use of surgical face masks, which are the main tools in protection from the COVID-19 pandemic, one of the biggest disasters of our age, in chronic airway diseases. The purpose of the study was to examine how stable patients with chronic obstructive pulmonary disease (COPD) responded to short-term surgical mask use in terms of in-mask air quality, oxygen saturation, and pulmonary function. Forty-one patients with stable COPD, by clinical presentation and pulmonary function tests (PFTs), were included in a quasi-experimental study. Stable COPD patients' PFTs, in-mask air quality, and pollution measures were collected before and after wearing surgical masks for two hours at rest. The findings of simultaneous tests of peripheral-blood-oxygen saturation were also recorded. The mean age of participants was 67.1 years and 87.8% were male. The pre- and post-mask PFTs parameters for GOLD (A+B) group were FEV1 (ml), FEV1 (%), FVC (ml), FVC (%), FEV1/FVC (%) and DLCO (%) (p=0.067, p=0. 065, p=0.062, p=0.083, p=0.083, p=0.269, p=0.956, respectively), whereas in GOLD (C+D) group (p=0.340, p=0.538, p=0.728, p=0.044, p=0.105, p=0.054, respectively). In post-mask measurements, the respiratory function was not impaired in GOLD-2022 (A-B-C-D) COPD subgroups. Oxygen and carbon-monoxide concentrations in exhaled air and oxygen saturation decreased after surgical mask use. The difference was statistically significant, but the difference was unimportant in terms of clinical implications. Surgical masks don’t appear to have a negative effect on pulmonary function and clinical parameters in stable COPD. This study may help provide evidence-based data to overcome hesitations in use of surgical masks in chronic airway diseases.

Associations between depression and anxiety index and frequency of acute exacerbation in chronic obstructive pulmonary disease.

Comorbidities of chronic obstructive pulmonary disease (COPD) influence clinical characteristics and prognosis. This study compared the clinical characteristics and exacerbation rate of COPD according to the presence of depression or anxiety. This study used data from The Korea COPD Subgroup Study (KOCOSS) cohort, a nationwide prospective cohort from 54 medical centers, between April 2012 and 2019. Depression and anxiety were diagnosed with the Beck Depression Inventory and Beck Anxiety Inventory. Negative binomial regression analysis was performed to analyze the frequency of exacerbations in depressed patients and anxiety. Differences in lung function trajectory according to presence of depression/anxiety were analyzed using a linear mixed model. In all, 2147 patients were enrolled. Depressed patients or anxiety had lower lung function, higher modified Medical Research Council (mMRC) grade, St. George Respiratory Questionnaire (SGRQ) score, and COPD assessment test score, and higher rates of exacerbation in the past year than those without depression/anxiety. Depressed patients had a higher frequency of moderate to severe exacerbations [Incidence Rate Ratio (IRR): 1.57, CI: 1.17-2.11, p = 0.002] and those with anxiety had higher frequencies of moderate to severe (IRR: 1.52, CI: 1.03-2.27, p = 0.038) and severe exacerbations (IRR: 2.13, CI: 1.09-4.15, p = 0.025) during 1-year follow-up compared to those without these comorbidities. The differences in the change in annual forced expiratory volume in 1 seconds (FEV1) over 3 years according to the presence of depression or anxiety were not statistically significant. Depressed and anxious patients showed increased respiratory symptoms and exacerbation rate as well as reduced health-related quality of life, whereas there were no significant differences in changes in lung function between groups with and without depression/anxiety.

Heterogeneity of asthma-chronic obstructive pulmonary disease (COPD) overlap from a cohort of patients with severe asthma and COPD.

A considerable proportion of patients have features of both asthma and chronic obstructive pulmonary disease (COPD) simultaneously, called asthma-COPD overlap (ACO). The aim of this study was to identify heterogeneity of ACO from a cohort of patients with severe asthma and COPD using the same diagnostic criteria. We used the International Severe Asthma Registry (ISAR) and the Korean COPD Subgroup Study (KOCOSS) to evaluate clinical characteristics of ACO from each cohort. We classified subjects into four groups: (1) pure severe asthma, (2) ACO from the severe asthma cohort, (3) ACO from the COPD cohort, and (4) pure COPD. ACO was defined by satisfying extreme bronchodilator response (BDR) >15% and 400 ml and/or blood eosinophil count ⩾300 /µL in patients aged 40 years or older and post-BD forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7. The ACO group had 25 (23%) of 111 in the ISAR cohort and 403 (23%) of 1781 in the KOCOSS cohort. The ACO from the COPD cohort was older with more males and more smokers, but had similar degree of airflow limitation compared with the ACO from the severe asthma cohort. ICS-containing inhaler treatment was prescribed for all severe asthma subjects, but only for 43.9% of ACO subjects from the COPD cohort. Compared with patients having pure severe asthma, the risk for exacerbation was comparable in ACO either from severe asthma or COPD cohort [adjusted odds ratio (aOR): 1.54, 95% CI: 0.22-10.95 or aOR: 2.15, 95% CI: 0.59-7.85]. The prevalence of ACO was similar in severe asthma and COPD cohorts applying identical diagnostic criteria. ACO from the severe asthma cohort was similar to ACO from the COPD cohort in terms of lung function and exacerbation risk.

Physical Activity and Symptom Burden in COPD: The Canadian Obstructive Lung Disease Study.

The relationship between symptom burden and physical activity (PA) in chronic obstructive pulmonary disease (COPD) remains poorly understood with limited data on undiagnosed individuals and those with mild to moderate disease. The primary objective was to evaluate the relationship between symptom burden and moderate-to-vigorous intensity PA (MVPA) in individuals from a random population-based sampling mirroring the population at large. Baseline participants of the Canadian Cohort Obstructive Lung Disease (n=1558) were selected for this cross-sectional sub-study. Participants with mild COPD (n=406) and moderate COPD (n=331), healthy individuals (n=347), and those at risk of developing COPD (n=474) were included. The Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire was used to estimate MVPA in terms of energy expenditure. High symptom burden was classified using the COPD Assessment Test ([CAT] ≥10). Significant associations were demonstrated between high symptom burden and lower MVPA levels in the overall COPD sample (β=-717.09; 95% confidence interval [CI]=-1079.78, -354.40; p<0.001) and in the moderate COPD subgroup (β=-694.1; 95% CI=-1206.54, -181.66; p=0.006). A total of 72% of the participants with COPD were previously undiagnosed. The undiagnosed participants had significantly higher MVPA than those with physician diagnosed COPD (β=-592.41 95% CI=-953.11, -231.71; p=0.001). MVPA was found to be inversely related to symptom burden in a large general population sample that included newly diagnosed individuals, most with mild to moderate COPD. Assessment of symptom burden may help identify patients with lower MVPA, especially for moderate COPD and for relatively inactive individuals with mild COPD.

STUDY OF LIPID PROFILE AND ATHEROGENIC INDEX IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Objectives: The present study’s design investigated the lipid parameters level and atherogenic index in atherosclerosis and cardiovascular disease risk development in chronic obstructive pulmonary disease patients. Methods: The study consists of 108 clinically diagnosed and confirmed spirometry-stable chronic obstructive pulmonary disease (COPD) patients (Mild, Moderate, and Severe), and the controls were 36 healthy individuals of the same age and sex. Blood samples were collected and the lipid profile was done. The atherogenic index of all COPD patients was calculated using the values of lipid parameters. Results: The observation revealed that as compared to the control group, total cholesterol, triglycerides, low-density lipoproteins (LDL), and very LDLs were significantly (p&lt;0.001) raised in all the COPD sub-groups, and high-density lipoproteins levels showed significantly (p&lt;0.001) decreasing levels in all COPD groups as compared to controls. The COPD sub-group has a higher atherogenic risk (p&lt;0.001) than controls. Conclusion: In COPD patients with dyslipidemia, there is an increased atherogenic risk, which predicts future cardiovascular risk.

Risk Factors of Rapid FEV1 Decline in a Real-World Chronic Obstructive Pulmonary Disease Cohort

Background: Rapid forced expiratory volume in 1 s (FEV₁) decliners have been considered a unique subgroup of patients with chronic obstructive pulmonary disease (COPD). Rapid FEV₁ decline manifests early and is associated with poor prognosis. This necessitates the pre-emptive identification of risk factors for rapid FEV₁ decline. Objectives: We aimed to determine the risk factors and clinical outcomes in patients with COPD. Methods: This longitudinal, observational study was based on the Korea COPD Subgroup Study cohort (NCT02800499) from January 2012 to December 2019 across 54 medical centers in South Korea. Eligible patients were followed up for 3 years with serial spirometric tests. We calculated the annualized percentage change in FEV₁ from baseline. Rapid decliners were defined as the quartile of patients with the highest annualized percentage FEV₁ decline. Results: Of the 518 patients, 130 were rapid decliners who lost 6.2%/year and 100 mL/year of FEV₁. The multivariable logistic regression identified male sex, current smoking, blood eosinophil count <150/µL, and high forced vital capacity as the independent risk factors for rapid FEV₁ decline. Among rapid decliners, the lung function deteriorated more rapidly in current smokers and patients with severe dyspnea, while triple combination therapy attenuated lung function decline in comparison with mono-bronchodilator therapy. Rapid decliners had a higher rate of severe exacerbation than nonrapid decliners (0.2/year vs. 0.1/year, p value = 0.032). Conclusions: We identified the independent risk factors for rapid FEV₁ decline. This information may assist physicians in the early detection and pertinent management of rapid decline among patients with COPD.

Relationships between Airway Remodeling and Clinical Characteristics in COPD Patients.

Background: Airway remodeling is a cardinal feature of chronic obstructive pulmonary disease (COPD) pathology. However, inconsistent findings have been reported regarding the nature of proximal airway remodeling in COPD. This is likely due to the heterogeneity of COPD. This study investigated the histopathological features of airway remodeling in bronchial biopsies of COPD patients compared to smoking controls (S). We tested the hypothesis that histopathological features in bronchial biopsies relate to clinical characteristics in COPD patients, focusing on smoking status, symptom burden, lung function, exacerbation risk and inhaled corticosteroid (ICS) use. Methods: We recruited 24 COPD patients and 10 S. We focused on reticular basement membrane thickness (RBM), surface immunoglobulin A (IgA) expression, goblet cell numbers (periodic acid-Schiff [PAS]+), sub-mucosal remodeling markers including collagen 4, 6 and laminin expression, and inflammatory cell counts (CD45+). Results: RBM thickness was increased in frequent exacerbators, IgA expression was reduced in COPD patients with worse lung function, and goblet cell numbers were increased in COPD patients compared to S but with no difference between the COPD subgroups. Collagen 4 expression was associated with higher symptom burden and worse quality of life. Sub-mucosal inflammatory cell counts were increased in COPD non-inhaled corticosteroid (ICS) users compared to ICS users and S. Conclusion: We observed relationships between the histopathological features of airway remodeling and clinical characteristics in COPD patients. Our data highlight the influence of clinical heterogeneity on diverse patterns of airway remodeling in COPD patients.

Plasma Glycine Concentration but Not Whole Body Production Production Rate Is a Marker of Abdominal Obesity in Older Adults Independent of the Presence of a Chronic Disease

ObjectivesPreviously, in healthy older adults, the concentration of the plasma amino acid glycine was found to be negatively related to the amount of visceral adipose tissue (VAT). It remains unclear whether this is due to alterations in the whole body glycine production, and independent of the presence of a concomitant chronic disease in older adults (e.g., Chronic Obstructive Pulmonary Disease (COPD)).MethodsIn this study, 88 healthy older adults (40 males/48 females) and 122 older adults with stable moderate to severe COPD (58 males/64 females) were studied. In all subjects, body composition and VAT (by DXA) were assessed, as well as muscle function (respiratory strength by mouth pressure, hand- and leg peak strength and endurance by dynamometers) and Charlson Comorbidity index. We also measured plasma concentration and whole body production (WBP) of glycine using stable isotope techniques and analyzed them by LC-MS/MS. Statistics performed by ANCOVA included age, gender, and body mass index as covariates. Significance was set at p < 0.05 and results were expressed as means [95% CI].ResultsAlthough plasma glycine concentration was comparable between healthy and COPD older adults (p = 0.21), a negatively association was found with VAT area (p < 0.0002; Slope −0.08 [−0.07, −0.10] μM/cm2 VAT) in the total group as well as in the healthy and COPD subgroups. The ROC area was 0.8801 [0.8329, 0.9273] when separating VAT at 800 cm2. WBP of glycine was also not different between healthy older adults and those with COPD but no significant relationship was found with VAT area (p = 0.49). Also no association was found between VAT and any of the other measured parameters.ConclusionsIndependent of the presence of COPD, a lower plasma glycine concentration, but not the whole body glycine production, relates to a higher amount of visceral fat in older adults. We conclude that plasma glycine concentration is a marker of the amount of visceral adipose tissue in older adults independent of the presence of a chronic disease.Funding SourcesNone.

Non-respiratory symptom dominance is associated with depression in patients with chronic obstructive pulmonary disease

IntroductionDepression is a common and important comorbidity in patients with chronic obstructive pulmonary disease (COPD). Depressive status is associated with a high COPD assessment test (CAT) total score, but it is difficult to distinguish patients with depression from those with severe symptomatic COPD. We hypothesized that a non-respiratory symptom-dominant elevation in CAT score is associated with depression in patients with COPD. MethodsA total of 226 patients in the KYOTO cohort in Japan and 924 patients in the Korea COPD Subgroup Study (KOCOSS) cohort in the Republic of Korea were analyzed. Depression was diagnosed based on a PHQ-9 (patient health questionnaire-9) ≥5 in the KYOTO cohort and a BDI-II (Beck Depression Inventory-II) ≥17 in the KOCOSS cohort. Sums of respiratory symptoms (Q1-Q4; Q1234) and non-respiratory symptoms (Q5-Q8; Q5678) from CAT items were analyzed. ResultsFifty-three (23.5%) patients in the KYOTO cohort and 111 (11.2%) patients in the KOCOSS cohort were identified as having depression. Fifty-five patients (24.3%) in the KYOTO cohort and 249 patients (26.9%) in the KOCOSS cohort showed non-respiratory symptom dominance (Q1234 ≤ Q5678), and they had a significantly higher prevalence of depression than did patients with respiratory symptom dominance (Q1234 > Q5678). Multivariable logistic regression analysis showed that both the CAT total score and Q1234 ≤ Q5678 were significantly associated with depression in both cohorts. Moreover, even in symptomatic patients (CAT total score ≥10), these significant associations were preserved. ConclusionNon-respiratory symptom dominance in CAT is a suspicious feature for depression in patients with COPD.

Clinical Characteristics of Non-Smoking Chronic Obstructive Pulmonary Disease Patients: Findings from the KOCOSS Cohort

ABSTRACT Chronic obstructive pulmonary disease (COPD) has been regarded as a disease of smokers, but the prevalence of non-smoking COPD patients have been reported to be considerable. We investigated differences in clinical characteristics between smoking and non-smoking COPD patients. We used data from the Korea COPD Subgroup Study (KOCOSS) database, which is a multicenter cohort that recruits patients from 54 medical centres in Korea. Comprehensive comparisons of smoking and non-smoking COPD patients were performed based on general characteristics, exacerbations, symptom scores, radiological findings, and lung-function tests. Of the 2477 patients included in the study, 8.1% were non-smokers and 91.9% were smokers. Non-smoking COPD patients were more likely to be female and to have a higher body mass index and lower level of education. Non-smoking COPD patients had more comorbidities, including hypertension, osteoporosis, and gastroesophageal reflux disease, and experienced more respiratory and allergic diseases. No significant differences in exacerbation rates, symptom scores, or exercise capacity scores were observed between the two groups. Smoking COPD patients had more emphysematous lung according to the radiological findings, and non-smoking patients had more tuberculosis-destroyed lung and bronchiectasis. Lung-function testing revealed no significant difference in the forced expiratory capacity in 1 sec between the two groups, but smokers had more rapid lung-function decline in the 5 years of follow-up data. We found differences in general characteristics and radiological findings between smoking and non-smoking COPD patients. No significant differences in exacerbation or symptom scores were observed, but decline in lung function was less steep in non-smoking patients. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2053088 .

Empagliflozin in patients with type 2 diabetes mellitus and chronic obstructive pulmonary disease

AimsType 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) often co-exist, yielding increased risk of cardiovascular (CV) complications including heart failure (HF). We assessed risk of cardiorenal outcomes, mortality and safety in patients with versus without COPD in the EMPA-REG OUTCOME trial. MethodsPatients (n = 7,020) with T2DM and CV disease (CVD) were treated with empagliflozin (10 mg or 25 mg) or placebo. Cox regression was used to assess COPD subgroup (placebo only) associations with, and treatment effects of empagliflozin versus placebo on first hospitalization for HF (HHF), CV death, all-cause mortality, incident/worsening nephropathy, and all-cause hospitalization. ResultsAt baseline, patients with COPD (n = 707) had more HF and used insulin more frequently than those without COPD. During follow-up in the placebo group, those with baseline COPD had increased risk of HHF (HR 2.15 [95% CI 1.32, 3.49]), HHF/CV death (1.60 [1.10, 2.33]), incident/worsening nephropathy (1.68 [1.26, 2.24]), all-cause hospitalization (1.44 [1.19, 1.74]) and all-cause death (1.60 [1.09, 2.35]) compared to those without COPD. Empagliflozin consistently reduced all clinical outcomes, irrespective of COPD status (interaction p-values 0.14 to 0.96), with a confirmed safety profile. ConclusionsIn patients with T2DM and CVD, COPD increased the risk of mortality and cardiorenal outcomes, including HF. Empagliflozin consistently reduced these outcomes versus placebo regardless of COPD, suggesting that empagliflozin’s benefits in patients with T2DM and CVD are not mitigated by the presence of COPD.