International Journal of Chronic Obstructive Pulmonary Disease最新文献

Purpose: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major cause of hospital admissions and are associated with significant morbidity and mortality. Several scoring systems are available for early risk stratification, such as DECAF, BAP-65, and NEWS, each incorporating parameters from different clinical domains. This study aimed to validate and compare established risk scores for predicting in-hospital mortality in patients with AECOPD and to assess the accuracy of a novel composite model.

Patients and methods: The BAP-65 score, a modified version of the DECAF score (DECAFm), and the National Early Warning Score (NEWS) were calculated using admission data of patients hospitalized for AECOPD in a Swiss hospital in 2022 and 2023. Predictive power for in-hospital death was compared using receiver operating characteristic (ROC) curves and the respective area under the curve (AUC). A novel scoring system, AECOPD-COMBI, combining parameters used in the three scores, was validated in the same cohort.

Results: 314 patients (mean age 73 years (range 48-94), 47% female) were included, of whom 7 died during hospitalization (2.2%). Patients who died had significantly higher scores at admission across all validated tools. Among the established scores, the BAP-65 performed best in the prediction of in-hospital death (AUC 0.79), followed by DECAFm (AUC 0.72) and NEWS (0.64). The novel AECOPD-COMBI reached the highest AUC of 0.9 and, when setting the high-risk score threshold to S=18.5, it demonstrated strong classification accuracy (sensitivity 100%, specificity 81%, accuracy 81%).

Conclusion: The AECOPD-COMBI score showed promising potential in identifying patients at risk of in-hospital death, potentially outperforming established scores. While the cohort's low event rate may have influenced predictive estimates and performance differences were not statistically significant, these findings still highlight the score's potential value in clinical decision-making. Given the small sample size and preliminary nature of the study, these results should be interpreted with caution. Larger studies are needed to validate the score's applicapbility and assess its performance for other relevant outcomes.

Background: Chronic obstructive pulmonary disease (COPD) is an important risk factor for the development of, and death from, lung cancer.

Methods: We conducted a systematic review and meta-analysis assessing the risk of lung cancer incidence and mortality among adults with a COPD diagnosis in the United States (US) and exploring differences by subgroups. We searched MEDLINE, Embase, and PubMed from inception to July 2024 for observational studies that investigated the association between COPD and lung cancer incidence and mortality risk. We conducted a meta-analysis for overall risk and COPD assessment methods, and a systematic review for analyses within sex, race/ethnicity, smoking status.

Results: Twenty observational studies (n=638,610) were included in the systematic review and meta-analysis. US adults with COPD were found to have higher odds of developing (OR, 1.76; [1.53 to 1.99]) and higher hazards of dying (HR, 1.48; [1.06 to 1.89]) from lung cancer compared to those without COPD. Mixed results were observed when stratifying the impact of COPD on lung cancer risk by subgroups (ie, sex, race and ethnicity and smoking status). Generally, the same trend was observed where people in each subgroup with COPD were at higher risk of lung cancer incidence and mortality compared to those in the same subgroups without the disease. Individuals assessed by self-reported COPD and spirometry showed greater incidence risk but not mortality risk.

Conclusion: US adults with COPD, including those with a smoking history, are at an increased risk for lung cancer incidence and mortality compared to those without COPD regardless of sex and race and ethnicity.

Background: Higher blood eosinophil counts in COPD patients are associated with a greater response to inhaled corticosteroid (ICS) treatment, with type 2 (T2) inflammation being the target for ICS in COPD. Current smokers have reduced responses to ICS treatment. We have investigated whether current smoking modulates the levels of T2 mediators in the airways, thereby influencing ICS responsiveness.

Methods: Induced sputum samples were collected from 73 COPD patients, including 41 ex-smokers. Twenty-six patients donated a second sputum sample, approximately 6 months after the initial sample. Sputum cell gene expressions of IL13, CLCA1, CCL26 and CST1 were assessed by quantitative RT-PCR. Differential cell counts were performed.

Results: Expression levels of all four genes significantly correlated with sputum eosinophil percentages. IL13 and CCL26 gene expression levels were significantly lower in COPD current versus ex-smokers (IL13 p<0.0001; CCL26 p=0.005); there were no differences for CLCA1 or CST1. In repeat samples, IL13, CCL26 and CST1 expression showed good or very good consistency, while CLCA1 levels were more variable.

Conclusion: Sputum gene expression of IL13 and CCL26 is affected by the smoking status of COPD patients and have stable expression over time. These findings implicate IL-13 and CCL26 as key components of T2 inflammation in COPD but also suggest that current smoking skews the immune response away from a T2 profile.

Purpose: This study aimed to explore factors affecting adherence to remote home-based pulmonary rehabilitation (PR) in patients with stable chronic obstructive pulmonary disease (COPD) and to develop a predictive model.

Patients and methods: This multicenter, cross-sectional survey study included 86 patients who underwent 12 weeks of health education-integrated, home-based PR with remote monitoring. Patients were stratified into high-completion (HC, ≥ 70%) and low-completion (LC, < 70%) groups. Demographic data, clinical features, and psychological parameters were analyzed. Receiver operating characteristic curve and area under the curve (AUC) analyses evaluated the predictive performance of key indicators. Binary logistic regression identified four predictors: Pulmonary Rehabilitation Adapted Index of Self-Efficacy (PRAISE), Outcome Expectations for Exercise Scale (OEE), Montreal Cognitive Assessment (MoCA), and Visual Analog Scale (VAS). These components formed an optimized predictive model with corresponding formula and cutoff values.

Results: A cross-sectional survey of 71 patients, 44 in the HC group and 27 in the LC group, revealed significantly higher scores in the HC group in the following domains of the 36-Item Short Form Health Survey (SF-36), including physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, mental health, and social functioning, as well as in the MoCA scores (all p-values < 0.05). Significant intergroup differences were also observed in PRAISE, OEE and VAS scores (all p < 0.001). PRAISE (AUC = 0.810), OEE (AUC = 0.784), MoCA (AUC = 0.719), and VAS (AUC = 0.801) demonstrated discriminatory power in assessing PR adherence. The combined predictive model achieved an AUC of 0.895 (95% confidence interval: 0.812-0.977, p < 0.05), with 77.8% sensitivity and 93.2% specificity.

Conclusion: Social cognitive theory (SCT) originated from social learning theory. It explains human behavior through a triadic, dynamic, and reciprocal model. This model posits continuous interaction among an individual's behavior, cognitive factors, and environmental context. The four-variable predictive model, based on SCT, effectively evaluates adherence to home-based PR under remote monitoring in patients with COPD. Among the indicators in the four-variable model, PRAISE shows potential as a target for intervention to enhance PR completion rates.

Purpose: The red blood cell distribution width-to-albumin ratio (RAR) is an emerging biomarker that reflects systemic inflammation and nutritional status. However, its prognostic value in patients with chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to evaluate the predictive value of RAR for 1-year all-cause mortality in patients with COPD and to explore its clinical relevance.

Patients and methods: We conducted a retrospective analysis using two independent cohorts: hospitalized COPD patients from the MIMIC-IV database (2008-2019, n = 2649) and community-dwelling individuals with COPD from the NHANES database (2003-2018, n = 2415). RAR levels were stratified into quartiles (Q1-Q4). Multivariable logistic regression models were used to examine the association between RAR and 1-year all-cause mortality. Generalized additive models (GAMs) assessed nonlinear relationships. Receiver operating characteristic (ROC) analysis evaluated the predictive performance of RAR compared with other markers such as NLR, PLR, and RDW.

Results: Higher RAR levels were independently associated with an increased risk of 1-year all-cause mortality in patients with COPD. In the MIMIC-IV cohort, the highest quartile (Q4) had an OR of 7.90 (95% CI: 6.05-10.32; P < 0.001) compared to Q1. In the NHANES cohort, the OR for Q4 was 11.16 (95% CI: 4.42-28.18; P < 0.001). ROC analysis revealed that RAR achieved a higher area under the curve (AUC) (0.801 in MIMIC-IV and 0.787 in NHANES) than other markers, indicating superior discriminatory ability.

Conclusion: RAR serves as an independent predictor of 1-year all-cause mortality in patients with COPD. By integrating indicators of systemic inflammation and nutritional status, RAR provides a reliable tool for clinical risk stratification.

Background: Non-invasive ventilation (NIV) improves outcomes in acute life-threatening hypercapnic respiratory failure due to exacerbations of COPD (ECOPD), but the benefits of long-term home NIV (LTH-NIV) for managing hypercapnic chronic respiratory failure (CRF) in COPD remain unclear.

Purpose: 1) To assess the long-term survival of severe COPD patients with hypercapnic CRF started on LTH-NIV and mortality related factors; 2) To evaluate the impact of LTH-NIV on ECOPD and hospital admissions at follow-up.

Patients and methods: COPD patients who started LTH-NIV between January 2009 and December 2018 were included. Medical records and clinical outcomes were retrospectively reviewed.

Results: Forty-four COPD patients (mean [SD] age 66.5 [10.4] years, 81.8% men) with severe airflow obstruction (mean [SD] FEV₁ 36 [16] % of predicted), hypercapnic CRF (mean [SD] PaCO₂ 60.8 [9.2] mmHg) and exacerbator phenotype (mean [IQR] moderate-severe ECOPD 3 [3] in previous year) were included. Median survival from LTH-NIV was 100.3 months. Survival at one, three and five years was 86.4%, 72.7% and 68.2%, respectively. In a multivariate Cox regression model, patients with a significantly increased risk of death were those with older age, lower absolute FVC, more hospitalisations and especially those adapted to LTH-NIV in the acute phase (HR 3.67 (IC 1.04-13), p<0.05). LTH-NIV allowed an estimated mean reduction in ECOPD of 39.7% (65.2% in hospitalisations) at 12 months and 57.4% (81% in hospitalisations) at 24 months.

Conclusion: The survival rate of COPD patients with hypercapnic CRF on LTH-NIV is currently high (>50% at 5 years). Adaptation to LTH-NIV in the stable phase is the most important prognostic determinant and should be considered especially in patients with more hospitalisations and lower FVC values. Initiation of LTH-NIV reduces moderate to severe ECOPD at follow-up.

Purpose: Chronic obstructive pulmonary disease (COPD) suffers from high prevalence, disability and mortality rates and a heavy economic burden. miR-335-5p takes part in multiple respiratory diseases such as pulmonary fibrosis, whereas its study in COPD has not been reported. The aim of our research was to explore miR-335-5p in predicting elevated COPD susceptibility and in human bronchial epithelial cells injury.

Patients and methods: qRT-PCR was performed to examine miR-335-5p levels in serum and cells. ROC curve and logistic regression analyses were utilized to evaluate the predictive capacity of miR-335-5p for COPD susceptibility. Pearson correlation was used to assess the association of miR-335-5p with TNF-α, IL-6, FEV1, and FEV1/FVC. Human bronchial epithelial cells were exposed to cigarette smoke extract (CSE) conditions to simulate cell injury. Cell proliferation, apoptosis, inflammatory response and oxidative stress-related factors were assayed by CCK8, flow cytometry and ELISA, respectively.

Results: miR-335-5p is reduced on COPD patients. ROC curve recommended that miR-335-5p has high sensitivity (88.9%) and specificity (80.0%) to distinguish COPD from healthy individuals. Logistic regression showed that reduced miR-335-5p predicted elevated COPD susceptibility. Moreover, miR-335-5p was significantly negatively related to TNF-α and IL-6 and positively related to FEV1, and FEV1/FVC in COPD patients. Cellular experiments revealed that CSE treatment decreased miR-335-5p expression, repressed cell proliferation, facilitated apoptosis, raised TNF-α, IL-6, ROS, and MDA levels, and reduced SOD levels. miR-335-5p overexpression facilitated cell proliferation, suppressed apoptosis, diminished TNF-α, IL-6, ROS, and MDA levels, and elevated SOD levels, whereas knockdown of miR-335-5p reversed this trend.

Conclusion: Downregulation of miR-335-5p increased COPD susceptibility and negatively correlated with inflammatory factors. Overexpression of miR-335-5p alleviated CSE-induced injury to human bronchial epithelial cells, which suggested that miR-335-5p may be a potential target for COPD treatment.

Introduction: Assessment of blood eosinophil count (BEC) is recommended to guide the use of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD), with BEC ≥300 cells/μL predictive of patients most likely to benefit.

Objective: To compare outcomes between patients initiating dual bronchodilator therapy with tiotropium/olodaterol (TIO/OLO) versus triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in patients with COPD and BEC ≤300 cells/μL.

Methods: A retrospective cohort study using claims data from the Optum Research Database. Patients with COPD initiated on TIO/OLO or FF/UMEC/VI between 01 June 2015 and 30 November 2019, with a baseline BEC were included. TIO/OLO initiators were 1:1 propensity score matched with FF/UMEC/VI initiators. Time to first exacerbation and pneumonia diagnosis were assessed using Kaplan-Meier analysis. COPD exacerbations and COPD and/or pneumonia-related healthcare resource utilization (HRU) and cost outcomes were presented as population annualized averages.

Results: The study population included 3867 individuals with a baseline BEC result. Among these, 3168 (81.9%) had BEC ≤300 cells/μL. After matching, 1098 matched pairs with BEC ≤300 cells/μL were retained. The follow-up annualized count of moderate/severe exacerbations was not significantly different between TIO/OLO and FF/UMEC/VI initiators (1.05 vs 0.99, p=0.535). Annualized counts of COPD and/or pneumonia-related HRU were not significantly different, except for emergency department visits, which were lower for TIO/OLO than FF/UMEC/VI (0.59 vs 0.83, p=0.018). Annualized COPD and/or pneumonia-related emergency department ($370 vs $538, p=0.034) and pharmacy costs ($4692 vs $6573, p<0.001) were lower for TIO/OLO versus FF/UMEC/VI initiators.

Conclusion: Eight in ten patients with COPD who initiated FF/UMEC/VI had BEC ≤300 cells/μL. TIO/OLO and FF/UMEC/VI users with BEC ≤300 cells/μL experienced similar rates of COPD exacerbations. TIO/OLO initiators incurred lower pharmacy costs related to COPD and/or pneumonia than FF/UMEC/VI initiators. These results support treatment recommendations of reserving inhaled corticosteroids for frequent exacerbators and patients with elevated eosinophil counts.

Objective: Neutrophilic inflammation, a key feature of chronic obstructive pulmonary disease (COPD), is associated with exacerbations and poor outcomes. Myeloperoxidase (MPO) is released from activated neutrophil granules. High or increasing MPO levels are associated with tissue damage, lung function decline and increased exacerbation risk in patients with COPD. We hypothesize that treatment with mitiperstat, a novel oral MPO inhibitor, may reduce lung oxidative stress, inflammation and exacerbations, thereby improving symptoms, lung function, and comorbidities in patients with COPD.

Patients and methods: CRESCENDO is a partially decentralized, Phase 2a, randomized, 24-week, double-blind study evaluating the efficacy and safety of mitiperstat versus placebo in patients (40-80 years, inclusive) with COPD at high risk of exacerbation (based on a documented history of ≥1 moderate or severe acute COPD exacerbation, frequent productive cough, or severe airflow limitation [forced expiratory volume in 1 second <50% predicted]). Patients recruited from approximately 100 sites across 14 countries, from primary or secondary care and community-based facilities, will be randomized 1:1 to receive mitiperstat 5 mg or placebo orally, once daily. The primary endpoint is the time to first CompEx event, a novel composite endpoint reflecting disease worsening, including changes in symptoms, reliever use, lung function, treatment for exacerbation, or study dropout. The study period is planned to take between 18 and 30 weeks for each patient.

Conclusion: CRESCENDO will assess efficacy and safety of mitiperstat using a novel, patient-centric trial design to enhance participant recruitment, partially via community-based facilities, helping to overcome restrictive trial designs and better reflect the real-world population with COPD, as well as reducing its environmental impact.

Objective: This study aimed to provide real-life data on COPD healthcare resource utilization (HCRU)-related costs in patients receiving triple therapy and to quantify the economic burden of uncontrolled COPD patients (ie, ≥1 severe or 2 moderate exacerbations within 12 months before inclusion and at least one exacerbation under treatment) versus controlled COPD patients and the general population.

Methods: Patients aged over 40 years receiving triple therapy in 2015 (ie, long-acting ß2-agonist, long-acting anticholinergic and inhaled corticosteroids) for at least 90 continuous days were included. The index date was defined as the 91st day of triple therapy exposure. Patients were followed for up to 5 years. HCRU-costs were computed by calendar year in controlled and uncontrolled COPD patients and in the general population. The association between costs and COPD has been estimated, for each calendar year, using GEE with a negative binomial distribution.

Results: Among the 186,963 patients included, 21.2% (N= 39,647) of patients were identified as uncontrolled. Among these, the average cost related to HCRU per patient was around 12,000€ by year. Hospitalizations, drugs and medical devices represented approximately 2/3 of expenses. Costs were in average 1.25 higher than in controlled COPD treated patients and 2.7 higher than the general population. Attributable costs to COPD in uncontrolled patients were estimated at approximately €7,600 per patient each year.

Conclusion: This study offers a robust representation of health care resource consumption and related costs of COPD patients receiving triple therapy in France over several years with a focus on uncontrolled patients.