Clinical Chronic Obstructive Pulmonary Disease Research Articles

Predicting mixed venous oxygen saturation (SvO2) impairment in COPD patients using clinical-CT radiomics data: A preliminary study.

Chronic obstructive pulmonary disease (COPD) is one of the most common chronic airway diseases in the world. To predict the degree of mixed venous oxygen saturation (SvO2) impairment in patients with COPD by modeling using clinical-CT radiomics data and to provide reference for clinical decision-making. A total of 236 patients with COPD diagnosed by CT and clinical data at Xiangyang No. 1 People's Hospital (n= 157) and Xiangyang Central Hospital (n= 79) from June 2018 to September 2021 were retrospectively analyzed. The patients were divided into group A (SvO⩾2 62%, N= 107) and group B (SvO<2 62%, N= 129). We set up training set and test set at a ratio of 7/3 and time cutoff spot; In training set, Logistic regression was conducted to analyze the differences in general data (e.g. height, weight, systolic blood pressure), laboratory indicators (e.g. arterial oxygen saturation and pulmonary artery systolic pressure), and CT radiomics (radscore generated using chest CT texture parameters from 3D slicer software and LASSO regression) between these two groups. Further the risk factors screened by the above method were used to establish models for predicting the degree of hypoxia in COPD, conduct verification in test set and create a nomogram. Univariate analysis demonstrated that age, smoking history, drinking history, systemic systolic pressure, digestive symptoms, right ventricular diameter (RV), mean systolic pulmonary artery pressure (sPAP), cardiac index (CI), pulmonary vascular resistance (PVR), 6-min walking distance (6MWD), WHO functional classification of pulmonary hypertension (WHOPHFC), the ratio of forced expiratory volume in the first second to the forced vital capacity (FEV1%), and radscore in group B were all significantly different from those in group A (P< 0.05). Multivariate regression demonstrated that age, smoking history, digestive symptoms, 6MWD, and radscore were independent risk factors for SvO2 impairment. The combined model established based on the abovementioned indicators exhibited a good prediction effect [AUC: 0.903; 95%CI (0.858-0.937)], higher than the general clinical model [AUC: 0.760; 95%CI (0.701-0.813), P< 0.05] and laboratory examination-radiomics model [AUC: 0.868; 95%CI (0.818-0.908), P= 0.012]. The newly created nomogram may be helpful for clinical decision-making and benefit COPD patients. SvO2 is an important indicator of hypoxia in COPD, and it is highly related to age, 6MWD, and radscore. The combined model is helpful for early identification of SvO2 impairment and adjustment of COPD treatment strategies.

The role of serum chloride ion in the prognosis of COPD

BackgroundAs exacerbations of chronic obstructive pulmonary disease (COPD) are one of the leading causes of hospitalization and are associated with significant mortality, it is particularly important to accurately assess the risk of exacerbations in COPD. Most of the current clinical biomarkers are related to inflammation and few consider how ion levels affect COPD. Chloride ion, the second most abundant serum electrolyte, has been shown to be associated with poor prognoses in several diseases, but their relationship with COPD remains unclear. MethodsIn total, 105 patients with acute exacerbations of COPD were recruited. Data on clinical characteristics, lung function, blood count, blood biochemistry, relevant scales including the Clinical COPD Questionnaire (CCQ), BODE (BMI, airflow obstruction, dyspnea, exercise capacity) index and the St. George's Respiratory Questionnaire (SGRQ) were collected from all patients for statistical analysis. ResultThere were significant differences in lung function indicators and disease severity in the low chloride ion subgroup compared with the high chloride ion subgroup. On multiple logistic regression analysis, chloride ion was an independent factor affecting lung function in COPD patients (OR = 0.808, 95% CI: 0.708 - 0.922, p = 0.002). The sensitivity of chloride ion in predicting COPD severity was 78%, the specificity was 63%, and the area under the curve was 0.734 (p < 0.001). Subgroup analysis showed that chloride ion was a stronger predictor in male and smoking patients. ConclusionsChloride ion was a novel prognostic biomarker for COPD, and low levels of chloride ion were independently associated with exacerbations in COPD patients.

The cuproptosis-related gene glutaminase promotes alveolar macrophage copper ion accumulation in chronic obstructive pulmonary disease

Cuproptosis, a novel mode of cell death, is strongly associated with a variety of diseases. However, the contribution of cuproptosis to the onset or progression of chronic obstructive pulmonary disease (COPD), the third most common chronic cause of mortality, is not yet clear. To investigate the potential role of cuproptosis in COPD, raw datasets from multiple public clinical COPD databases (including RNA-seq, phenotype, and lung function data) were used. For further validation, mice exposed to cigarette smoke for three months were used as in vivo models, and iBMDMs (immortalized bone marrow-derived macrophages) and RAW264.7 cells stimulated with cigarette smoke extract were used as in vitro models. For the first time, the expression of the cuproptosis-related gene glutaminase (GLS) was found to be decreased in COPD, and the low expression of GLS was significantly associated with the grade of pulmonary function. In vivo experiments confirmed the decreased expression of GLS in COPD, particularly in alveolar macrophages. Furthermore, in vitro studies revealed that copper ions accumulated in alveolar macrophages, leading to a substantially decreased amount of cell activity of macrophages when stimulated with cigarette extract. In summary, we demonstrate the high potential of GLS as an avenue for diagnosis and therapy in COPD.

Nurse and Social Worker Palliative Telecare Team and Quality of Life in Patients With COPD, Heart Failure, or Interstitial Lung Disease

Many patients with chronic obstructive pulmonary disease (COPD), heart failure (HF), and interstitial lung disease (ILD) endure poor quality of life despite conventional therapy. Palliative care approaches may benefit this population prior to end of life. Determine the effect of a nurse and social worker palliative telecare team on quality of life in outpatients with COPD, HF, or ILD compared with usual care. Single-blind, 2-group, multisite randomized clinical trial with accrual between October 27, 2016, and April 2, 2020, in 2 Veterans Administration health care systems (Colorado and Washington), and including community-based outpatient clinics. Outpatients with COPD, HF, or ILD at high risk of hospitalization or death who reported poor quality of life participated. The intervention involved 6 phone calls with a nurse to help with symptom management and 6 phone calls with a social worker to provide psychosocial care. The nurse and social worker met weekly with a study primary care and palliative care physician and as needed, a pulmonologist, and cardiologist. Usual care included an educational handout developed for the study that outlined self-care for COPD, ILD, or HF. Patients in both groups received care at the discretion of their clinicians, which could include care from nurses and social workers, and specialists in cardiology, pulmonology, palliative care, and mental health. The primary outcome was difference in change in quality of life from baseline to 6 months between the intervention and usual care groups (FACT-G score range, 0-100, with higher scores indicating better quality of life, clinically meaningful change ≥4 points). Secondary quality-of-life outcomes at 6 months included disease-specific health status (Clinical COPD Questionnaire; Kansas City Cardiomyopathy Questionnaire-12), depression (Patient Health Questionnaire-8) and anxiety (Generalized Anxiety Disorder-7) symptoms. Among 306 randomized patients (mean [SD] age, 68.9 [7.7] years; 276 male [90.2%], 30 female [9.8%]; 245 White [80.1%]), 177 (57.8%) had COPD, 67 (21.9%) HF, 49 (16%) both COPD and HF, and 13 (4.2%) ILD. Baseline FACT-G scores were similar (intervention, 52.9; usual care, 52.7). FACT-G completion was 76% (intervention, 117 of 154; usual care, 116 of 152) at 6 months for both groups. Mean (SD) length of intervention was 115.1 (33.4) days and included a mean of 10.4 (3.3) intervention calls per patient. In the intervention group, 112 of 154 (73%) patients received the intervention as randomized. At 6 months, mean FACT-G score improved 6.0 points in the intervention group and 1.4 points in the usual care group (difference, 4.6 points [95% CI, 1.8-7.4]; P = .001; standardized mean difference, 0.41). The intervention also improved COPD health status (standardized mean difference, 0.44; P = .04), HF health status (standardized mean difference, 0.41; P = .01), depression (standardized mean difference, -0.50; P < .001), and anxiety (standardized mean difference, -0.51; P < .001) at 6 months. For adults with COPD, HF, or ILD who were at high risk of death and had poor quality of life, a nurse and social worker palliative telecare team produced clinically meaningful improvements in quality of life at 6 months compared with usual care. ClinicalTrials.gov Identifier: NCT02713347.

Exploring Histologic Emphysema in a Rural Lobectomy Cohort: Insights and a Review Correlations of Histologic Emphysema

Exposure to cigarette smoking is extensive in rural Appalachia where one in four adults’ smokes. The clinical implications of this habit are evident among patients with some of the highest national rates for chronic obstructive pulmonary disease (COPD), lung cancer, and pulmonary fibrosis. Individuals undergoing surgical lung resection for suspicious lung nodules or masses at a major rural academic center in the area demonstrated an excessive burden of histologic emphysema (73.5%). This destructive process of the alveoli was linked to a significant burden of comorbid conditions, various radiologic patterns of interstitial lung diseases and interstitial lung abnormalities, histologic fibrosis, inflammatory processes (respiratory bronchitis, desquamative interstitial pneumonia, peribronchiolar metaplasia), anthracosis, and lung cancer. Physiologically, this combination of injuries imposed substantial limitations. Findings presented may enhance the understanding of concurrent changes occurring in the smoker. The complex inter-relationships and disparities between clinical COPD, radiologic and histologic emphysema are defined. While emphysema remains an irreversible pathology, associated inflammatory and fibrotic conditions are possibly amenable to earlier smoking cessation strategies and available disease-modifying therapies.

Adherence to the Canadian Thoracic Society Chronic Obstructive Pulmonary Disease Pharmacotherapy Guidelines in a real-world hospital setting

RATIONALE The Canadian Thoracic Society (CTS) publishes chronic obstructive pulmonary disease (COPD) guidelines with recommendations regarding which inhaled pharmacotherapy to prescribe. A minimal amount is known about the implementation of these guidelines in routine clinical practice. OBJECTIVES The main goals of this review were to assess the adherence to the CTS COPD pharmacotherapy guidelines in a real-world setting of patients with a severe exacerbation, to determine predictors of increased guidelines adoption, and to review if subjects leaving the hospital without recommended inhaled therapy had a higher rate of readmission for COPD within 30 days. METHODS Patients treated in 2022 at Montfort Hospital for a COPD exacerbation (hospitalization or emergency department) were reviewed. Medication lists at the time of presentation and discharge were charted in addition to patient clinical characteristics and COPD admissions up to 30 days after the initial assessment. A comparison of COPD patients with and without recommended inhaled therapy optimization was performed. MEASUREMENTS AND MAIN RESULTS A total of 214 patients were admitted for a COPD exacerbation. From this sample, 111 were candidates for review of their inhaled therapy as per the CTS guidelines; however, only 22 (20%) received recommended optimization. Subjects who were admitted to inpatient units and those with spirometry results on file were more likely to receive appropriate pharmacotherapy at discharge (both p = 0.02). Patients not optimized as per the guidelines were at higher risk of readmission for a COPD exacerbation within 30 days (p = 0.02). CONCLUSIONS Adherence to the CTS COPD pharmacotherapy guidelines was low in a real-world hospital setting. Interventions that would help increase their adoption would result in improved patient outcomes.

Identifying critical inhalation technique errors in Dry Powder Inhaler use in patients with COPD based on the association with health status and exacerbations: findings from the multi-country cross-sectional observational PIFotal study

BackgroundCorrect inhaler use depends on a complex interplay of factors, including device preparation and generating sufficient inspiratory flow. It is currently unknown which inhalation technique errors can be considered critical in Chronic Obstructive Pulmonary Disease (COPD) patients on Dry Powder Inhaler (DPI) maintenance therapy.ObjectiveTo investigate the association between inhalation technique errors and health status or exacerbations in patients with COPD. Additionally, the association between the number of errors and COPD outcomes was determined.MethodsThe PIFotal study is a cross-sectional multi-country observational study in a primary care setting, including 1434 COPD patients aged ≥ 40 years (50.1% female; mean age 69.2 yrs) using a DPI for their maintenance therapy. Inhalation technique was video recorded and scored by two independent researchers using inhaler-specific checklists. Health status was assessed with two questionnaires; the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT). The number of moderate and severe exacerbations in the past 12 months was recorded. Critical errors were identified based on their association with health status or exacerbations through multi-level prediction models adjusted for identified confounding.ResultsErrors in inhalation technique steps ‘Breathe in’, ‘Hold breath’, and ‘Breathe out calmly after inhalation’ were significantly associated with poorer CCQ and CAT outcomes and thus deemed critical. None of the errors were significantly associated with moderate exacerbations. Patients with errors ‘Preparation’, ‘Hold inhaler in correct position during inhalation’, and ‘Breathe in’ had significantly more severe exacerbations, and therefore these errors were also deemed critical. 81.3% of patients with COPD made at least one critical error. Specific combinations of errors were associated with worse outcomes. The more inhalation technique errors identified, the poorer the health status and the higher the exacerbation rate.ConclusionIn this study, we identified multiple critical inhalation technique errors in COPD patients using DPIs each associated with poorer outcomes. Explorative analysis revealed that specific combinations of errors may be of clinical relevance, especially those related to the inhalation manoeuvre. COPD outcomes worsened with increasing error count. These results warrant further prospective longitudinal studies to establish the effect of correcting these errors on COPD control.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04532853 (31/08/2020)

The effectiveness of an unsupervised home-based pulmonary rehabilitation with self-management program in patients with chronic obstructive pulmonary disease.

To assess the effectiveness of an unsupervised home-based pulmonary rehabilitation with self-management program in patients with chronic obstructive pulmonary disease (COPD). A few recent studies have shown that unsupervised home-based pulmonary rehabilitation can improve the clinical outcome of patients with COPD. More studies are needed to prove its benefits. This study used a quasi-experimental design. Seventy-two admitted COPD patients were assigned to experimental group or control group through purposeful sampling. Data were collected from March 2016 to November 2017 in the Thoracic Intensive Care Unit of a Medical Center in Taiwan. The Medical Research Council dyspnea scale, the COPD Self-Efficacy Scale and the Clinical COPD Questionnaire were measured before education and at the first, second and third months after discharge. The Medical Research Council dyspnea scale and COPD Self-Efficacy Scale results in the experimental group were significantly improved compared with the control group in the third month after discharge. The Clinical COPD Questionnaire score continued to improve in both groups in the third month after discharge, and there was no difference between the two groups. A short-term unsupervised home-based pulmonary rehabilitation with self- management program had significant benefits for patients with COPD. The long-term effects need to be confirmed.

Assessment of health status and its correlation with lung function in patients with chronic obstructive pulmonary disease: a study from a tertiary care center in north India.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 recommends a comprehensive multidimensional assessment for patients with chronic obstructive pulmonary disease (COPD) and stresses the need for evaluation of their health status and quality of life (QOL). The COPD assessment test (CAT), clinical COPD questionnaire (CCQ), and St. George respiratory questionnaire (SGRQ) are recommended by GOLD for such assessments. However, their correlation with spirometry in the Indian population is not known. Other similar questionnaires like the COPD and sleep impact scale (CASIS), functional performance inventory-short form (FPI-SF), and COPD and asthma fatigue scale (CAFS), though used internationally as a research tool, are still in the offspring stage and have never been used in India. A cross-sectional study was hence conducted in the Department of Pulmonary Medicine, Government Medical College, Patiala, Punjab, India, on 100 COPD patients. Patients were assessed for health status and QOL by CAT, CCQ, SGRQ, CASIS, FPI-SF, and CAFS. The relationship between these questionnaires and airflow limitations was investigated. The majority of the patients were males (n=97), >50 years of age (n=83), illiterate (n=72), had moderate/severe COPD, and belonged to group B (n=66). The mean value of forced expiratory volume in one second (FeV1) decreased with a deterioration in CAT and CCQ score grouping (p<0.001). Patients with poorer CAT and CCQ scores belonged to higher GOLD grades (k=0.33, p<0.001). The correlation of health-related quality of life (HRQL) questionnaires among each other, with FEV1 predicted and with GOLD grade, was strong to very strong in most of the comparisons (p<0.01 in the majority). On comparison of GOLD grade with mean scores of HRQL questionnaires, it was seen that with the increase in GOLD grading from 1 to 4, the mean values of CAT, CCQ, SGRQ, CASIS, FPI-SF, and CAFS also deteriorated (p<0.001, p<0.001, p<0.001, p<0.005, p<0.001 and p<0.001, respectively). Various easy-to-use HRQL scores should be routinely used in outpatient departments for a comprehensive assessment of COPD patients. These questionnaires, in combination with clinical features, can help in providing a rough estimate of the severity of the disease in places where lung function assessments are not readily available.

How Important is Spirometry for Identifying Patients with COPD Appropriate for Palliative Care?

Providing palliative care to patients with chronic obstructive pulmonary disease (COPD) is a priority. Spirometry demonstrating airflow limitation is a diagnostic test for COPD and a common inclusion criterion for palliative care research. However, requiring spirometry with airflow limitation may exclude appropriate patients unable to complete spirometry, or patients with preserved-ratio impaired spirometry and symptoms or imaging consistent with COPD. To determine differences in quality of life (QOL) and symptoms between patients with COPD identified based on International Classification of Diseases (ICD) codes and spirometry with airflow limitation compared to ICD codes only. Patients with COPD enrolled in a palliative care trial were included. Patients were at high risk of hospitalization and death and reported poor QOL. Baseline measures of QOL (Functional Assessment of Cancer Therapy-General (FACT-G), the Clinical COPD Questionnaire, and Quality of Life at the End of Life), and symptoms (Patient Health Questionnaire-8, Generalized Anxiety Disorder-7, fatigue, Insomnia Severity Index) were compared. Two hundred eight patients with COPD were predominantly male, White, and average age was 68.4. Between patients with ICD codes and spirometry with airflow limitation compared to patients with ICD codes only, there were no significant differences in FACT-G (59.0 vs. 55.0, P=0.33), other measures of QOL, or symptoms between groups. These results imply that spirometry may not need to be a requirement for inclusion into palliative care research or clinical care for patients with poor quality of life and at high risk for adverse outcomes.

A Preliminary Investigation of Mobile Respiratory Function Testing in Western Australian Communities

Although underutilized, spirometry is essential in the diagnosis and management of chronic obstructive pulmonary disease (COPD) and asthma. This study aimed to investigate a mobile (i.e., transportable) lung function testing (LFT) services in two metropolitan and two rural clinics in Western Australia. Individuals attending a mobile LFT clinic in 2021 were invited to complete questionnaires at baseline and after 6–8 weeks. Questionnaires were completed by 59/74 (79.7%) respondents (mean age 62.5 ± 14.2 years); most were female (35/59; 59.3%). A history of asthma was reported in 50.9% (30/59) and COPD in 18.6% (11/59) of respondents [13.6% (8/59) reported both]. At baseline, most (22/30; 73.3%) had asthma control test scores ≤19 (mean 16.6; range 8.0–25.0); at follow-up, 16/31 (51.6%) had scores ≤19 (mean score 18.0; range 6.0–25.0). Of the 11 diagnosed with COPD at baseline, the mean Clinical COPD Questionnaire and COPD assessment test scores were greater at follow-up (1.9 vs. 2.3; and: 10.3 vs. 14.7 respectively), reflecting worsening disease. Most participants (57/59; 96.6%) were satisfied with the LFT experience. The role of mobile LFT services to optimize the diagnosis and management of chronic lung disease and to minimize patient burden requires further investigation to improve short term patient outcomes.

Improvements in health status with revefenacin, a once-daily, nebulized, long-acting muscarinic antagonist for chronic obstructive pulmonary disease

BackgroundReplicate, 12-week, phase 3 trials (0126 and 0127) of once-daily nebulized revefenacin 175 μg vs placebo demonstrated significant bronchodilation and improvements in health status in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). This post hoc analysis evaluated improvement in patient-reported outcomes (PROs), including the St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and Clinical COPD Questionnaire (CCQ) in both women and men. MethodsParticipants were pooled from the two 12-week studies (411 [51%] women and 401 [49%] men). Changes in PROs were assessed overall and separately in men and women. ResultsRevefenacin improved SGRQ and CAT total scores from baseline in both studies; improvement in CCQ total score reached significance only in 0126. In pooled data, a greater proportion of patients achieved clinically meaningful response in SGRQ score (≥4-unit decrease from baseline) with revefenacin vs placebo (odds ratio, 1.5; 95% confidence interval, 1.1–2.1; P = 0.012). Clinically meaningful responses were also seen in CAT (≥2-unit decrease from baseline) and CCQ (≥0.4-unit decrease from baseline) scores with revefenacin vs placebo. When stratified by sex, improvements from baseline in SGRQ, CAT, and CCQ scores following revefenacin vs placebo reached statistical significance only in women. ConclusionsMaintenance treatment with revefenacin improved health status in patients with moderate to very severe COPD; however, the effect was more pronounced for women than men. Clinicaltrials.govNCT02459080; NCT02512510.

Stratification of COPD patients towards personalized medicine: reproduction and formation of clusters

The global initiative for chronic obstructive lung disease (GOLD) 2020 emphasizes that there is only a weak correlation between FEV1, symptoms and impairment of the health status of patients with chronic obstructive pulmonary disease (COPD). Various studies aimed to identify COPD phenotypes by cluster analyses, but behavioral aspects besides smoking were rarely included. The aims of the study were to investigate whether (i) clustering analyses are in line with the classification into GOLD ABCD groups; (ii) clustering according to Burgel et al. (Eur Respir J. 36(3):531-9, 2010) can be reproduced in a real-world COPD cohort; and (iii) addition of new behavioral variables alters the clustering outcome. Principal component and hierarchical cluster analyses were applied to real-world clinical data of COPD patients newly referred to secondary care (n = 155). We investigated if the obtained clusters paralleled GOLD ABCD subgroups and determined the impact of adding several variables, including quality of life (QOL), fatigue, satisfaction relationship, air trapping, steps per day and activities of daily living, on clustering. Using the appropriate corresponding variables, we identified clusters that largely reflected the GOLD ABCD groups, but we could not reproduce Burgel's clinical phenotypes. Adding six new variables resulted in the formation of four new clusters that mainly differed from each other in the following parameters: number of steps per day, activities of daily living and QOL. We could not reproduce previously identified clinical COPD phenotypes in an independent population of COPD patients. Our findings therefore indicate that COPD phenotypes based on cluster analysis may not be a suitable basis for treatment strategies for individual patients.

The Effectiveness and Tolerability of Glycopyrronium for Patients with Chronic Obstructive Pulmonary Disease in a Clinical Setting: GLARE-Taiwan.

Glycopyrronium (GLY) is a pharmacological maintenance treatment for chronic obstructive pulmonary disease (COPD). However, its effectiveness and tolerability for COPD patients in routine clinical practice have not been well-investigated. This study aimed to assess the effectiveness of GLY on health-related quality of life and its safety in patients with COPD in a routine clinical care setting. This multi-center, prospective, six-month observational study recruited patients diagnosed with COPD and treated with GLY at three medical centers in central Taiwan. The full analysis set (n = 102) had a significant improvement in the Clinical COPD Questionnaire total (mean ± SD = −0.39 ± 0.90, p = 0.002), symptoms (mean ± SD = −0.61 ± 0.90, p < 0.001) and mental state scores (mean ± SD = −0.54 ± 1.72, p = 0.021) but not the functional state score (mean ± SD = −0.10 ± 1.15, p = 0.529). During the observational period, 58 patients (52.73%) experienced adverse events; only one adverse event (dizziness) was suspected to be related to the study drug. Three patients (2.73%) discontinued the study and GLY treatment because of an adverse event. One patient (0.91%) died during the study period because of a cerebral infarction, which was judged to be not associated with GLY treatment. In conclusion, GLY could be effective in improving the health status and is safe for patients with COPD in a real-life setting.

Muscle function and functional performance after pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a prospective observational study

This study aimed to measure changes in different properties of skeletal muscles and evaluate their contribution and relationship to changes in functional performance after pulmonary rehabilitation (PR) in patients with chronic obstructive pulmonary disease (COPD). COPD outpatients attending 5 weeks of conventional PR were recruited. Functional performance [5-repetitions sit-to-stand (5STS), and 4-m gait speed (4mGS)], and muscle function (maximal isometric strength, power, force control, and relative concentric and eccentric activation during 5STS) were assessed after PR and 3 months of follow-up. Twenty patients (71 years; 52% of predicted FEV1) completed the study. 4mGS and relative concentric activation during 5STS decreased respectively by 7.7% and 26% between the beginning of PR and follow-up. Quadriceps strength, power, and force control improved by 10.4%, 27.3%, and 15.2%, respectively, from the beginning of PR to follow-up the relative eccentric activation during 5STS explained 31% of the variance in 4mGS changes. In conclusion, functional performance appeared to decline after conventional PR, whereas several properties of skeletal muscles were maintained at follow-up in COPD outpatients. Of note, eccentric contractions might play a role in the improvement of functional performance. Therefore, future studies with interventional design should include eccentric training in PR programs during clinical COPD practice.

Validation of Clinical COPD Phenotypes for Prognosis of Long-Term Mortality in Swedish and Dutch Cohorts

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease with variable mortality risk. The aim of our investigation was to validate a simple clinical algorithm for long-term mortality previously proposed by Burgel et al. in 2017. Subjects with COPD from two cohorts, the Swedish PRAXIS study (n = 784, mean age (standard deviation (SD)) 64.0 years (7.5), 42% males) and the Rotterdam Study (n = 735, mean age (SD) 72 years (9.2), 57% males), were included. Five clinical clusters were derived from baseline data on age, body mass index, dyspnoea grade, pulmonary function and comorbidity (cardiovascular disease/diabetes). Cox models were used to study associations with 9-year mortality. The distribution of clinical clusters (1–5) was 29%/45%/8%/6%/12% in the PRAXIS study and 23%/26%/36%/0%/15% in the Rotterdam Study. The cumulative proportion of deaths at the 9-year follow-up was highest in clusters 1 (65%) and 4 (72%), and lowest in cluster 5 (10%) in the PRAXIS study. In the Rotterdam Study, cluster 1 (44%) had the highest cumulative mortality and cluster 5 (5%) the lowest. Compared with cluster 5, the meta-analysed age- and sex-adjusted hazard ratio (95% confidence interval) for cluster 1 was 6.37 (3.94–10.32) and those for clusters 2 and 3 were 2.61 (1.58–4.32) and 3.06 (1.82–5.13), respectively. Burgel’s clinical clusters can be used to predict long-term mortality risk. Clusters 1 and 4 are associated with the poorest prognosis, cluster 5 with the best prognosis and clusters 2 and 3 with intermediate prognosis in two independent cohorts from Sweden and the Netherlands. Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2039608 .

Effectiveness of chronic obstructive pulmonary disease (COPD) treatment with a combination of tiotropium / olodaterol in Polish standard clinical practice as measured by the improvement of the Clinical COPD Questionnaire score: an observational study.

Health‑related quality of life in patients with chronic obstructive pulmonary disease (COPD) can be measured by the Clinical COPD Questionnaire (CCQ). In this study, the CCQ was used to assess the therapeutic success of a fixed‑dose tiotropium / olodaterol combination treatment in Polish COPD patients. We aimed to evaluate the changes in the CCQ score in Polish patients with COPD after 6 weeks of treatment with tiotropium / olodaterol and to assess the predictors of response to this treatment. Data of the Polish subgroup of the NIS‑CCQ observational study (NCT03663569) were extracted. COPD patients who had received a new tiotropium / olodaterol prescription were included. The primary end point was therapeutic success predefined as a 0.4‑point reduction in the CCQ score after 6 weeks of tiotropium / olodaterol treatment. Post‑hoc logistic regression analysis was performed to identify the predictors of response to the treatment. After 6 weeks of treatment, 72.4% of patients achieved therapeutic success. The therapy was successful in 83.4% of treatment‑naïve patients, as compared with 62.6% and 73.3% of those previously treated with long‑acting muscarinic antagonists or long‑acting β2 agonists in monotherapy and in combination with inhaled corticosteroids, respectively. Therapeutic success was achieved by at least 50% of patients regardless of the COPD severity and exacerbation history but it was more frequent in patients with more severe disease. The airflow limitation severity grades 2 to 4, modified Medical Research Council Dyspnea Scale classes 2 to 4, exacerbations within the last year before the study, and treatment‑naïve status predicted a better response to tiotropium / olodaterol. Tiotropium / olodaterol treatment improved clinical control in Polish COPD patients. Therapeutic success was the most pronounced in individuals with more severe COPD and in the treatment‑naïve group but occurred also in those with moderate disease and in previously treated participants.

Identification and validation of aging-related genes in COPD based on bioinformatics analysis.

Chronic obstructive pulmonary disease (COPD) is a serious chronic respiratory disorder. One of the major risk factors for COPD progression is aging. Therefore, we investigated aging-related genes in COPD using bioinformatic analyses. Firstly, the Aging Atlas database containing 500 aging-related genes and the Gene Expression Omnibus database (GSE38974) were utilized to screen candidates. A total of 24 candidate genes were identified related to both COPD and aging. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we found that this list of 24 genes was enriched in genes associated with cytokine activity, cell apoptosis, NF-κB and IL-17 signaling. Four of these genes (CDKN1A, HIF1A, MXD1 and SOD2) were determined to be significantly upregulated in clinical COPD samples and in cigarette smoke extract-exposed Beas-2B cells in vitro, and their expression was negatively correlated with predicted forced expiratory volume and forced vital capacity. In addition, the combination of expression levels of these four genes had a good discriminative ability for COPD patients (AUC = 0.794, 95% CI 0.743–0.845). All four were identified as target genes of hsa-miR-519d-3p, which was significantly down-regulated in COPD patients. The results from this study proposed that regulatory network of hsa-miR-519d-3p/CDKN1A, HIF1A, MXD1, and SOD2 closely associated with the progression of COPD, which provides a theoretical basis to link aging effectors with COPD progression, and may suggest new diagnostic and therapeutic targets of this disease.

Biomarkers, Clinical Course, and Individual Needs in COPD Patients in Primary Care: The Study Protocol of the Stockholm COPD Inflammation Cohort (SCOPIC).

BackgroundTo facilitate effective personalized medicine, primary health care needs better methods of assessing and monitoring chronic obstructive pulmonary disease (COPD).AimThis cohort study aims to investigate how biomarkers relate to clinical characteristics and COPD patients’ subjective needs over time.MethodsPatients (n=750) in different COPD severity according to the GOLD criteria and age- and sex-matched controls (n=750) will be recruited over a period of 5 years from 15 primary health care centers in Region Stockholm, Sweden, and followed for 10 years in the first instance. Data on patients’ subjective needs will be collected via telephone/email, data on clinical/physiological variables (eg, symptoms, exacerbations, comorbidities, medications, smoking habits, lung function) from existing databases that are based on medical records, and data on biomarkers via repeated blood sampling. Quantitative and qualitative methods will be used. Initial results are expected after 2 years (feasibility test), and a larger body of evidence after 5 years.DiscussionThe study is expected to provide definitive and clinically useful scientific evidence about how biomarkers relate to clinical variables and patients’ subjective needs. This new evidence will facilitate accurate, and personalized COPD management by the use of valid biomarkers. It will provide useful tools for primary care professionals and may facilitate optimal self-management.

Improved health status of severe COPD patients after being included in an integrated primary care service: A prospective cohort study

Background Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease. It is assumed that severe patients will receive better treatment in specialised care centres but the prevalence of severe COPD in primary care is high. Integrated primary care services combine input from several sources and advice from pulmonologists to provide general practitioners with support needed to improve diagnosis and treatment of patients with COPD. Objectives To evaluate patient-reported outcomes and costs of managing patients classified as GOLD D in an integrated primary care service over 12 months. Methods Patients were included in this 1-year prospective cohort study if they met the 2014 GOLD D criteria, were aged ≥ 40 years and gave written informed consent for this study. Recruitment took place through the patients’ general practitioners. The primary outcome was health status, assessed with the Clinical COPD Questionnaire (CCQ) and COPD Assessment Test (CAT). Secondary outcomes included self-reported exacerbations, quality-adjusted life years and health(care)-related costs. Results Forty-nine patients were included. At baseline, the mean CAT score was 15.9 and the median CCQ score was 1.7. After 12 months, scores had improved by 2.3 (95% confidence interval, 0.8–3.7) and 0.4 (95% confidence interval, 0.2–0.7), respectively. Percentage of patients with ≥2 exacerbations in the past 12 months also decreased from baseline (77.6%) to 12 months (16.7%). Changes in mean quarterly costs were small. Conclusion An integrated service for COPD based in primary care may improve the health status of patients with a large burden of disease while not increasing health care costs.