Direct Health Care Costs Associated With a Multicomponent COPD Exacerbation Intervention.

BACKGROUND: Health care costs attributed to COPD have been estimated at $4.7 trillion globally in the next 30 years. With the global burden of COPD rising, identification of interventions that might lead to health care cost savings is an imperative. Although many studies report the effect of COPD self-management interventions on subject outcomes and health care utilization, few data describe their effect on health care costs. METHODS: Using data linkage and established case-costing methods with provincial Canadian health databases, we established public health care costs (acute and community) for 12 months following randomization for the 462 participants enrolled in our randomized controlled trial of the Program of Integrated Care for Patients with COPD and Multiple Comorbidities. RESULTS: Total median (interquartile range) in-hospital costs in the 12 months follow-up for all (intervention and control) 462 trial participants were CAD $4,769 ($417-16,834) (equivalent to US $3,566 [$312-12,588]). Total costs incurred in the community were higher at CAD $8,011 ($4,749-13,831) (equivalent to US $5,990 [$3,551-10,342]). Controlling for sex, income quintile, Johns Hopkins Aggregated Diagnosis Groups score, and living in an urban locality, we found lower community health care costs but no differences in acute care costs for participants receiving our multicomponent COPD exacerbation prevention management intervention compared to usual care. CONCLUSIONS: Controlling for important confounders, we found lower public community health care costs but no difference in acute health care costs with our multicomponent COPD exacerbation prevention management intervention compared to usual care. Community health care costs were almost double those incurred compared to acute health care costs. Given this finding, although most COPD exacerbation management interventions generally focus on reducing the use of acute care, interventions that enable health care cost savings in the community require further exploration.

Exploring the Role of Gut-Lung Interactions in COPD Pathogenesis: A Comprehensive Review on Microbiota Characteristics and Inflammation Modulation.

Chronic obstructive pulmonary disease (COPD) is a paramount contributor to global morbidity and mortality. Over the past decade, the concept of the "gut-lung axis" has emerged, offering a lens through which to examine the intricate interplay between the host, microbiome, and respiratory diseases, including COPD. An expanding body of evidence underscores that the composition of both the gastrointestinal and respiratory microbiome deviates in COPD patients compared to healthy individuals, leading to distinct host immune responses and clinical manifestations. The objective of this review is to provide a concise overview of the role of both gut and respiratory microbiome plays in the development of COPD. This will be accomplished by compiling current literature on the microbiome profile in stable and exacerbated cases of COPD, as well as exploring the biological mechanisms through a discussion of relevant experiments conducted on murine models. Hallmark characteristics of the microbial profile in COPD encompass reduced Prevotella spp. in the respiratory microbiome, culminating in a loss of anti-inflammatory protection, and diminished Bacteroidetes in the gut microbiome, leading to a decrease in protective short-chain fatty acids (SCFAs). The proliferation of Proteobacteria, particularly Haemophilus spp., Moraxella spp. and Pseudomonas spp. contributes to COPD pathologies via recognition of proinflammatory lipopolysaccharide (LPS) via Toll-like receptors (TLRs). As a consequence, deteriorated pulmonary function, enhanced severity, increased onset of exacerbations and elevated mortality were observed.

sRAGE levels are decreased in plasma and sputum of COPD secondary to biomass-burning smoke and tobacco smoking: Differences according to the rs3134940 AGER variant.

The receptor for advanced glycation end products (RAGE) and its gene (AGER) have been related to lung injury and inflammatory diseases, including chronic obstructive pulmonary disease (COPD). We aimed to evaluate the association of rs2071288, rs3134940, rs184003, and rs2070600 AGER single-nucleotide variants and the soluble-RAGE plasma and sputum levels with COPD secondary to biomass-burning smoke (BBS) and tobacco smoking. Four groups, including 2189 subjects, were analyzed: COPD secondary to BBS exposure (COPD-BBS, n = 342), BBS-exposed subjects without COPD (BBES, n = 774), tobacco smoking-induced COPD (COPD-TS, n = 434), and smokers without COPD (SWOC, n = 639). Allelic discrimination assays determined the AGER variants. The sRAGE was quantified in plasma (n = 240) and induced-sputum (n = 72) samples from a subgroup of patients using the ELISA technique. In addition, a meta-analysis was performed for the association of rs2070600 with COPD susceptibility. None of the studied genetic variants were found to be associated with COPD-BBS or COPD-TS. A marginal association was observed for the rs3134940 with COPD-BBS (p = 0.066). The results from the meta-analysis, including six case-control studies (n = 4149 subjects), showed a lack of association of rs2070600 with COPD susceptibility (p = 0.681), probably due to interethnic differences. The sRAGE plasma levels were lower in COPD-BBS compared to BBS and in COPD-TS compared to SWOC. The sRAGE levels were also lower in sputum samples from COPD-BBS than BBES. Subjects with rs3134940-TC genotypes exhibit lower sRAGE plasma levels than TT subjects, mainly from the COPD-BBS and SWOC groups. The AGER variants were not associated with COPD-BBS nor COPD-TS, but the sRAGE plasma and sputum levels are related to both COPD-BBS and COPD-TS and are influenced by the rs3134940 variant.

COPD: Iron Deficiency and Clinical Characteristics in Patients With and Without Chronic Respiratory Failure.

Background: The prevalence of iron deficiency in patients with COPD varies in previous studies. We aimed to assess its prevalence according to three well-known criteria for iron deficiency, its associations with clinical characteristics of COPD and mortality. Methods: In a cohort study consisting of 84 COPD patients, of which 21 had chronic respiratory failure, and 59 non-COPD controls, ferritin, TSat and mortality across 6.5 years were assessed. Associations between clinical characteristics and iron deficiency were examined by logistic regression, while associations with mortality were assessed in mixed effects Cox regression analyses. Results: The prevalence of iron deficiency in the study population was 10-43% according to diagnostic criteria, and was consistently higher in COPD, peaking at 71% in participants with chronic respiratory failure. Ferritin < cutoff was significantly associated with FEV1 (OR 0.33 per liter increase), smoking (OR 3.2) and cardiovascular disease (OR 4.7). TSat < 20% was associated with BMI (OR 1.1 per kg/m2 increase) and hemoglobin (OR 0.65 per g/dL increase). The combined criterion of low ferritin and TSat was only associated with FEV1 (OR 0.39 per liter increase). Mortality was not significantly associated with iron deficiency (HR 1.2-1.8) in adjusted analyses. Conclusion: The prevalence of iron deficiency in the study population increased with increasing severity of COPD. Iron deficiency, defined by ferritin < cutoff, was associated with bronchial obstruction, current smoking and cardiovascular disease, while TSat < 20% was associated with reduced level of hemoglobin and increased BMI. Iron deficiency was not associated with increased mortality.

Pulmonary volumes and signs of chronic airflow limitation in quantitative computed tomography.

BACKGROUND: Computed tomography (CT) offers pulmonary volumetric quantification but is not commonly used in healthy individuals due to radiation concerns. Chronic airflow limitation (CAL) is one of the diagnostic criteria for chronic obstructive pulmonary disease (COPD), where early diagnosis is important. Our aim was to present reference values for chest CT volumetric and radiodensity measurements and explore their potential in detecting early signs of CAL. METHODS: From the population-based Swedish CArdioPulmonarybioImage Study (SCAPIS), 294 participants aged 50-64, were categorized into non-CAL (n = 258) and CAL (n = 36) groups based on spirometry. From inspiratory and expiratory CT images we compared lung volumes, mean lung density (MLD), percentage of low attenuation volume (LAV%) and LAV cluster volume between groups, and against reference values from static pulmonary function test (PFT). RESULTS: The CAL group exhibited larger lung volumes, higher LAV%, increased LAV cluster volume and lower MLD compared to the non-CAL group. Lung volumes significantly deviated from PFT values. Expiratory measurements yielded more reliable results for identifying CAL compared to inspiratory. Using a cut-off value of 0.6 for expiratory LAV%, we achieved sensitivity, specificity and positive/negative predictive values of 72%, 85% and 40%/96%, respectively. CONCLUSION: We present volumetric reference values from inspiratory and expiratory chest CT images for a middle-aged healthy cohort. These results are not directly comparable to those from PFTs. Measures of MLD and LAV can be valuable in the evaluation of suspected CAL. Further validation and refinement are necessary to demonstrate its potential as a decision support tool for early detection of COPD.

A Harmonised Approach to Curating Research-Ready Datasets for Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) in England, Wales and Scotland Using Clinical Practice Research Datalink (CPRD), Secure Anonymised Information Linkage (SAIL) Databank and DataLoch.

Background: Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations. Methods and Results: We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons. Conclusion: Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.

The application of impulse oscillometry system based on machine learning algorithm in the diagnosis of chronic obstructive pulmonary disease.

OBJECTIVE: Diagnosing chronic obstructive pulmonary disease (COPD) using Impulse Oscillometry (IOS) is challenging due to the high level of clinical expertise it demands from doctors , which limits the clinical application of IOS in screening. The primary aim of this study is to develop a COPD diagnostic model based on machine learning algorithms using IOS test results. Approach:Feature selection was conducted to identify the optimal subset of features from the original feature set, which significantly enhanced the classifier's performance. Additionally, secondary features area of reactance (AX) were derived from the original features based on clinical theory, further enhancing the performance of the classifier. The performance of the model was analyzed and validated using various classifiers and hyperparameter settings to identify the optimal classifier. We collected 528 clinical data examples from the China-Japan Friendship Hospital for training and validating the model. Main results:The proposed model achieved reasonably accurate diagnostic results in the clinical data (accuracy=0.920, specificity=0.941, precision=0.875, recall=0.875). Significance:The results of this study demonstrate that the proposed classifier model, feature selection method, and derived secondary feature AX provide significant auxiliary support in reducing the requirement for clinical experience in COPD diagnosis using IOS. .

Pulmonary Rehabilitation: A Look Back, a Look Forward.

Pulmonary rehabilitation (PR) is a comprehensive approach to the management of patients with chronic lung disease that encompasses exercise, education, and psychosocial support. The development of PR programs began in the mid-20th century with the appreciation that exercise provided real benefit in chronic lung disease and that effective disease management involved patient education focused on medications, lifestyle changes, and lifelong regular exercise. Initially PR was primarily facility-based, but today PR is extending into the home with telemedicine, and this is encouraging a real partnership of patients and professionals supporting self-management. The evidence base supporting PR as a safe and effective modality has grown exponentially over the last 4 decades, and PR is strongly endorsed by virtually all the major professional societies. Importantly, PR has also clearly been shown to be cost-effective. Challenges remain, however. Access is still very limited for a variety of reason (logistics, financial, patient motivation) that need to be addressed. More focused and personalized exercise programs and monitoring strategies that encourage a patient's lifetime commitment to the principles of PR need to be developed and refined. The opportunity to really impact important clinical outcomes exists with PR, and this needs to be exploited.

Prevalence and predictors of restless legs syndrome among patients having stable chronic obstructive pulmonary disease.

BACKGROUND: Patients having COPD share some factors, e.g., chronic hypoxemia, anemia of chronic disease and nicotine use, which are also the risk factors for RLS hence predispose them to experience RLS in higher then general population. There are limited studies with methodological constraints evaluating the prevalence and/or correlates of RLS among patients with COPD. METHODS: Consecutive adult patients of either gender, having stable COPD as per GOLD guidelines 2021, were assessed for RLS using IRLSSG (2014) criteria (excluding RLS mimics) and the severity of RLS was determined in participants having RLS. Phenomenology of RLS, past medical history and laboratory parameters were gathered. Insomnia and depression were assessed using the insomnia severity index and PHQ-9, respectively. RESULTS: Participants' (N = 210) mean age was 63.02 ± 8.19 years, and 83.8% of subjects were men. 12.9% of participants were found to have RLS. Among those having RLS, nearly half (51.9%) had moderate symptoms, and 18.5% experienced severe symptoms. RLS was more prevalent among younger, females, those having severe COPD, participants having exacerbation of COPD in the previous year, lower post-bronchodilator FEV1, higher dyspnea and COPD assessment test score. Multivariate analysis showed that younger age, female gender, lower post-bronchodilator FEV1, lower FEV1/FVC ratio and higher serum creatinine increased the odds of having RLS. Depressive symptoms were more frequent in participants having RLS. CONCLUSIONS: The present study found that the prevalence of RLS among patients with stable COPD was higher than the general population. Female gender, younger age, higher airflow limitation and higher serum creatinine (though in the physiological range) increase the odds of having RLS. Stable patients with COPD having these characteristics must be screened for RLS.

Association between dietary inflammation index and asthma COPD overlap.

There are few studies on the relationship between dietary habits and asthma-COPD overlap (ACO). In this study, we aimed to investigate the association between dietary inflammation index (DII) score and ACO. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020. The DII score was first calculated and the demographic characteristics of the grouping based on the DII quartile were assessed. The weighted logistic regression model was used to study the relationship between DII and ACO. Subgroup analysis was used to further explore the differences in different subgroups. Restricted cubic spline (RCS) plot was used to show the general trend of DII score and disease risk, and threshold effect analysis was used to determine the inflection point. In a comparison of baseline characteristics, the highest ACO prevalence was found in the fourth quartile array of people in DII. An adjusted weighted logistic regression model showed that DII was positively correlated with the incidence of ACO. Subgroup analysis showed that the association was more pronounced in women, non-Hispanics, people with cardiovascular disease, and people without diabetes. The RCS graph shows that overall, the risk of ACO increases with the increase of DII score. Threshold effect analysis showed that the inflection point was 3.779, and the risk was more significant after the DII score was greater than the inflection point value (OR 2.001, 95% CI 1.334-3.001, P < 0.001). Higher DII scores were positively associated with ACO risk. These results further support diet as an intervention strategy for ACO prevention and treatment.

A mRNA panel for differentiation between acute exacerbation or pneumonia in COPD patients.

Introduction: Patients suffering from chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations (AECOPD) or community acquired pneumonia (CAP), both posing severe risk of morbidity and mortality. There is no available biomarker that correctly separates AECOPD from COPD. However, because CAP and AECOPD differ in aetiology, treatment and prognosis, their discrimination would be important. Methods: This study analysed the ability of selected candidate transcripts from peripheral blood mononuclear cells (PBMCs) to differentiate between patients with AECOPD, COPD & CAP, and CAP without pre-existing COPD. Results: In a previous study, we identified differentially regulated genes between CAP and AECOPD in PBMCs. In the present new cohort, we tested the potential of selected candidate PBMC transcripts to differentiate at early time points AECOPD, CAP+COPD, and CAP without pre-existing COPD. Expression of YWHAG, E2F1 and TDRD9 held predictive power: This gene set predicted diseases markedly better (model accuracy up to 100%) than classical clinical markers like CRP, lymphocyte count and neutrophil count (model accuracy up to 82%). Discussion: In summary, in our cohort expression levels of YWHAG, E2F1 and TDRD9 differentiated with high accuracy between COPD patients suffering from acute exacerbation or CAP.

Outcomes of coronary artery bypass grafting (CABG) in patients with OSA-COPD overlap syndrome versus COPD alone: an analysis of US Nationwide Inpatient Sample.

BACKGROUND: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are associated with unfavorable outcomes following coronary artery bypass grafting (CABG). The purpose of this study was to compare in-hospital outcomes of patients with COPD alone versus OSA-COPD overlap after CABG. METHODS: Data of adults ≥ 18 years old with COPD who received elective CABG between 2005 and 2018 were extracted from the US Nationwide Inpatient Sample (NIS). Patients were divided into two groups: with OSA-COPD overlap and COPD alone. Propensity score matching (PSM) was employed to balance the between-group characteristics. Logistic and linear regression analyses determined the associations between study variables and inpatient outcomes. RESULTS: After PSM, data of 2,439 patients with OSA-COPD overlap and 9,756 with COPD alone were analyzed. After adjustment, OSA-COPD overlap was associated with a significantly increased risk of overall postoperative complications (adjusted odd ratio [aOR] = 1.12, 95% confidence interval [CI]: 95% CI: 1.01-1.24), respiratory failure/prolonged mechanical ventilation (aOR = 1.27, 95%CI: 1.14-1.41), and non-routine discharge (aOR = 1.16, 95%CI: 1.03-1.29), and AKI (aOR = 1.14, 95% CI: 1.00-1.29). Patients with OSA-COPD overlap had a lower risk of in-hospital mortality (adjusted odd ratio [aOR] = 0.53, 95% CI: 0.35-0.81) than those with COPD only. Pneumonia or postoperative atrial fibrillation (AF) risks were not significantly different between the 2 groups. Stratified analyses revealed that, compared to COPD alone, OSA-COPD overlap was associated with increased respiratory failure/prolonged mechanical ventilation risks among patients ≥ 60 years, and both obese and non-obese subgroups. In addition, OSA-COPD overlap was associated with increased risk of AKI among the older and obese subgroups. CONCLUSION: In US adults who undergo CABG, compared to COPD alone, those with OSA-COPD are at higher risks of non-routine discharge, AKI, and respiratory failure/prolonged mechanical ventilation, but a lower in-hospital mortality. No increased risk of AF was noted.

DACH1 Attenuates Airway Inflammation in COPD by Activating NRF2 Signaling.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways, it is characterized by impaired lung function induced by cigarette smoke (CS). Reduced DACH1 expression has a detrimental role in numerous disorders. However, its role in COPD remains understudied. This study aims to elucidate the role and underlying mechanism of DACH1 in airway inflammation of COPD. DACH1 expression was measured in lung tissues of patients with COPD. Airway epithelium-specific DACH1 knockdown mice and AAV-transfected DACH1 overexpressed mice were used to investigate its role and potential for therapeutic targeting in experimental COPD caused by CS. Furthermore, we discovered a potential mechanism of DACH1 in inflammation induced by cigarette smoke extract simulation (CSE) in vitro. Compared to non-smokers and smokers without COPD, COPD patients had reduced DACH1 expression, especially in the airway epithelium. Airway epithelium-specific DACH1 knockdown aggravated mice airway inflammation and lung function decline caused by CS, whereas DACH1 overexpression protected mice from airway inflammation and lung function decline. DACH1 knockdown and overexpression promoted and inhibited IL-6 and IL-8 secretion in 16 HBE cells after CSE simulation, respectively. Nuclear factor erythroid 2-related factor 2 (NRF2) was discovered to be a novel downstream target of DACH1, which binds directly to its promoter. By activating NRF2 signaling, DACH1 induction reduced inflammation. DACH1 levels are lower in smokers and nonsmoking COPD patients when compared to nonsmokers. DACH1 has protective effects against inflammation induced by CS by activating NRF2 signaling pathway. Targeting DACH1 is a potentially viable therapeutic approach for COPD treatment.

A feeling of not being alone - Patients' with COPD experiences of a group-based self-management education with a digital website: A qualitative study.

AIM: To describe patients' with chronic obstructive pulmonary disease (COPD) experiences of group-based self-management education with a digital website. DESIGN: A qualitative approach with a phenomenologicalmethod. Patients participating in an earlier study, with self-experience of COPD as a special competence, were involved as research partners at the design of this study. METHODS: Eleven individual and two group interviews with five participants in each group were conducted. RESULTS: Group-based self-management education with a digital website supports learning. Sharing experiences with others in similar situations creates security and reduces the feeling of being alone. Based on questions and discussion in the group, and through self-reflection, general information is transformed into useful knowledge and understanding of one's own situation. COPD information on the website provides an opportunity to gain knowledge continuously based on needs that contributes to learning. This research has demonstrated that adapting learning activities to individual learning styles increases sustainability of learning. Sharing experiences reduces feelings of loneliness. It is therefore important to create spaces for sharing experiences and in-depth reflection that support learning over time.

Explicate molecular landscape of combined pulmonary fibrosis and emphysema through explainable artificial intelligence: a comprehensive analysis of ILD and COPD interactions using RNA from whole lung homogenates.

Combined pulmonary fibrosis and emphysema (CPFE) presents a unique challenge in respiratory disorders, merging features of interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). Using the random forest algorithm, our study thoroughly examines the molecular details of CPFE. Analyzing gene expression datasets from GSE47460 (ILD: 254, COPD: 220, control: 108), we identify key genes namely ADRB2, CDH3, IRS2, MATN3, CD38, PDIA4, VEGFC, and among twenty others, crucial in airway regulation, lung function, and apoptosis, shaping the complex pathogenesis of CPFE. Additionally, miRNAs (hsa-mir-101-3p, hsa-mir-1343-3p, hsa-mir-27a-3p, and miR-16-5p) showcase regulatory impacts on CPFE-related molecular pathways. Our machine learning model unveils these intricate interactions, offering a comprehensive insight into CPFE's molecular mechanisms. This research not only pinpoints potential therapeutic targets and biomarkers but also opens avenues for innovative approaches in managing CPFE, linking ILD and COPD within this complex respiratory condition.