OBJECTIVE:To examine the seasonal distribution of AECOPD hospitalizations in Shijiazhuang (2020-2024), the lag associations of air pollutants (PM2.5, PM10, NO2, O3, SO2, CO) and meteorological factors (mean temperature, diurnal temperature range) across seasons, and to explore the season-specific models for high-incidence admission days as an exploratory environmental-surveillance analysis rather than a ready-to-deploy clinical early-warning system. METHODS:This city-wide retrospective time-series study analyzed 22,468 AECOPD admissions in Shijiazhuang from January 1, 2020 to December 31, 2024, using hospitalization front-page records covering all tertiary, secondary, and community hospitals in the city, obtained from the municipal medical insurance database (inpatient admissions only; ED discharges without admission were not included). Each year was divided by solar terms into spring (3/7-6/7), summer (6/8-9/7), autumn (9/8-12/7), and winter (12/8-3/6), with daily air pollution and meteorological data matched to admissions. Univariate and multivariate Poisson generalized linear regression (GLM) assessed single-day lag associations (lags 0-7 as eight separate lags); multivariable models and prediction features used the 7-day mean of lags 0-6 (admission day + preceding 6 days), not an 8-day lag0-7 average. Using each factor's 7-day cumulative window as input, we built logistic regression, random forest, and gradient boosting models and evaluated high-incidence-day prediction via fivefold time-series cross-validation, treating the many lag × pollutant × season tests as exploratory. Sensitivity analyses added during revision included collinearity diagnostics (VIF/correlation matrix), quasi-Poisson models with smooth time, a distributed-lag nonlinear temperature model (DLNM), COVID-period analyses, humidity/heating checks, alternative lag windows, and a near-term exposure prediction re-run. RESULTS:AECOPD admissions peaked in winter and were the lowest in summer (winter 6,009; spring 5,854; autumn 5,554; summer 5,051); the male-to-female ratio was ∼3.7:1 and mean age 71.7 ± 9.1 years. After multivariate adjustment, each 10 µg/m³ rise in winter PM10 and NO2 was associated with a 6.9% (IRR 1.069, 95%CI 1.052-1.085) and 8.9% (1.089, 1.050-1.129) higher admission rate, respectively. A 1 °C fall in mean temperature corresponded to a 4.4% increase (IRR 0.958, 0.947-0.969) and a 1 °C wider diurnal range to a 5.5% increase (1.055, 1.034-1.077). O3 was positively associated in summer and autumn (1.035, 1.015-1.056; 1.022, 1.005-1.039). Apparent protective multipollutant IRRs (e.g., winter PM2.5) were interpreted cautiously given collinearity. Prediction discrimination was the modest even when above chance: winter random forest fivefold CV AUC of 0.653 ± 0.112; other seasons ranged 0.50-0.62. Overall, environmental exposures were weak predictors of high-incidence days. Diagnostic re-analyses (Section 3.4), after reconciling the panel to the locked 22,468-admission cohort, showed acceptable collinearity (all VIF < 5, addressed with single-pollutant models), overdispersion handled by quasi-Poisson, and nonlinear temperature effects by DLNM (cold-induced excess, heat-related reduction), alongside a 2022 admission trough (∼50-54% of 2020/2024) and a near-term exposure re-run (same-day and lags 1-3 features) that reproduced the modest winter discrimination (AUC ≈0.66); against a calendar-only baseline the incremental value of the environmental block was small (overall ΔAUC ≈ +0.02 to +0.045), indicating the exposures are primarily explanatory rather than operationally predictive. CONCLUSION:AECOPD admissions show high winter incidence, with PM10, NO2, CO, low temperature, and a wide diurnal range as the main winter associated factors, and summer-autumn O3 exposure warranting attention. The 7-day cumulative-exposure model showed only the modest discrimination in winter (AUC ≈0.65) and is best viewed as an exploratory, hypothesis-generating surveillance analysis rather than a preliminary operational early-warning tool.
BACKGROUND:People with COPD are more likely to be sedentary, a behaviour associated with reduced life expectancy. COPD is also associated with social isolation and socioeconomic deprivation. Therefore, this study aimed to examine the relationship between these determinants and sedentary time. METHODS:This study analysed 23,559 UK Biobank participants with COPD (recruited 2006-2010), with a follow-up accelerometer assessment (2013-2015). Primary analyses were performed on accelerometer participants (n = 1,558) with complete covariate and accelerometer data. Associations between sedentary time, social isolation, and deprivation were explored using multivariable linear regression, stratified by COPD severity (GOLD stages). RESULTS:Sedentary time rose stepwise with disease severity (p < 0.001); with GOLD 4 individuals spending 19% more of their day sedentary than GOLD 1. Social isolation interacted with severity (p = 0.033), predicting an extra 1.5 h of daily sedentary time in GOLD 3-4 (95% CI, 0.49-2.47; p = 0.004). Deprivation had the greatest impact on sedentary time in mild disease. CONCLUSIONS:This large observational study suggests sedentary behaviour is associated with social isolation in severe COPD and socioeconomic deprivation in mild disease severity. This highlights the need to consider individual social and environmental factors alongside a clinical focus to reduce sedentary behaviour.
This study aimed to investigate the impact of adherence to non-invasive ventilation (NIV) on the prognosis of patients with overlap syndrome (OS). This retrospective cohort study included 115 hospitalised patients with OS who initiated home NIV therapy and were followed up for 12 months. Adherence was classified as good (≥4 h/d) or poor (<4 h/d). Outcomes included annual exacerbation frequency, time to first exacerbation, severity of exacerbations, and St. George's Respiratory Questionnaire (SGRQ) scores. Initiating NIV treatment during hospitalisation was associated with a higher rate of NIV acceptance at home (33.99% vs. 11.34%, p < 0.001); however, there was no control group for treatment initiated on an outpatient basis. Good adherence significantly delayed the first acute exacerbation (log-rank test = 13.032, p < 0.001) and reduced the annual exacerbation rate (0.89 ± 0.86 vs. 1.24 ± 0.98, p = 0.041), but did not affect the severity of exacerbations. SGRQ scores at 6 and 12 months were better in the good adherence group (p < 0.05). There were no differences between groups in eosinophil counts or the use of benzodiazepines and opioids. This study demonstrates that good adherence to home NIV therapy following AECOPD significantly delays time to first exacerbation and reduces annual exacerbation frequency in patients with OS, while improving health-related quality of life. Additionally, in-hospital NIV initiation was associated with higher rates of home NIV acceptance compared to outpatient initiation, though this secondary finding requires prospective validation with appropriate comparator groups. These findings support the implementation of systematic screening and early intervention strategies for OS patients hospitalised for AECOPD.
BACKGROUND:Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) drive disease progression and morbidity. Early prediction could enable timely intervention and thereby potentially limit the severity of the AECOPD and shorten its course. Smart inhalers measure inhalation parameters that may detect physiological changes preceding AECOPDs. OBJECTIVE:To explore whether changes in inhalation parameters (inhalation duration, Peak Inspiratory Flow (PIF), inhalation volume) as measured by a smart inhaler (RS01XTM) can identify clinical worsening leading up to an exacerbation within 14 days preceding an AECOPD. METHODS:This single-centre observational pilot study included nine COPD patients using maintenance therapy (LAMA/LABA ± ICS) with the RS01XTM inhaler for six months. AECOPD were defined based on daily symptom diary data. Trends in inhalation parameters during the 14-day pre-AECOPD window were compared with 14-day control periods without AECOPD using descriptive statistics, visual inspection, slope calculations, and exploratory generalised estimating equations (GEE). RESULTS:During the follow-up period, five AECOPDs occurred in three patients. While PIF (p = .007) showed a clear decline preceding AECOPD, inhalation duration (p = .712) and volume (p = .215) remained stable prior to an AECOPD. CONCLUSION:Inhalation parameters, particularly PIF, appear promising and may reflect physiological changes associated with AECOPD. However, their use as a standalone predictor is still too early. The heterogeneity of COPD and the explorative design of this study limit their current predictive utility within a 14-day window. Nevertheless, these findings suggest potential for future research, particularly when combined with clinical and contextual data to improve predictive accuracy.
Dual long-acting bronchodilators are a standard treatment in chronic obstructive pulmonary disease (COPD), aimed at alleviating dyspnea, improving exercise tolerance, and preventing exacerbations. Metronome-paced tachypnea (MPT) offers a feasible alternative to exercise testing for the evaluation of dynamic hyperinflation (DH) in COPD. Because MPT can be performed during MRI, its combination with single-slice phase-resolved functional lung (PREFUL) MRI provides a promising approach to investigate changes in regional ventilation dynamics induced by DH. This approach was evaluated in a randomized, investigator-blinded, placebo-controlled, single-dose (SD) crossover trial with a two-week extension of once daily dual bronchodilator medication, in which patients with stable COPD underwent PREFUL MRI during resting tidal breathing (RTB) and during MPT. During RTB, no significant improvements in MRI-derived parameters were observed after SD treatment compared with placebo. During MPT, however, regional ventilation, flow-volume loop correlation, its defect percentage, and end-expiratory lung area improved significantly after SD treatment compared to the placebo scan (all p < 0.02). After multi-dose treatment, five out of six measured parameters improved during MPT, when compared to the baseline scan without bronchodilator treatment (all p < 0.03). In contrast to RTB, PREFUL MRI during MPT was able to detect changes in COPD patients already after SD treatment. The combination of MPT and PREFUL MRI represents a promising method to evaluate the effects of dual bronchodilators on regional ventilation dynamics and hyperinflation.
Background Swallowing dysfunction (dysphagia) is increasingly recognised in chronic obstructive pulmonary disease (COPD) and has been associated with aspiration, exacerbations, and impaired health status. However, longitudinal data on dysphagia in COPD are limited.Aim To investigate the 2-year stability of self-perceived dysphagia in a COPD cohort and to identify factors associated with persistent dysphagia.Methods This prospective cohort study included 438 patients with spirometry-confirmed COPD from the Swedish Tools for Identifying Exacerbations (TIE) study. Self-reported swallowing symptoms were assessed at baseline and at 2-year follow-up using three questions. Dysphagia was defined as the presence of at least one symptom. Clinical assessments included lung function, dyspnoea (mMRC), health status (CAT), physical performance, body mass index (BMI), and exacerbation history. Dysphagia trajectories over time were analysed.Results The prevalence of patient-reported dysphagia remained stable over the 2-year period (32% at baseline vs. 33% at follow-up). Four dysphagia trajectories were identified: no dysphagia (59%), incident dysphagia (8%), remission (8%), and persistent dysphagia (25%). Participants with dysphagia at follow-up had higher dyspnoea and CAT scores, poorer physical performance, higher BMI, and more frequent exacerbations. Persistent dysphagia was associated with a consistently higher symptom burden and poorer functional outcomes over time. In multivariate analysis, CAT ≥10 remained independently associated with dysphagia.Conclusion Self-perceived dysphagia affects approximately one-third of individuals with COPD and remains stable over two years. Persistent dysphagia may identifiy a more symptomatic COPD phenotype and warrants clinical attention. These findings support the inclusion of simple swallowing screening in routine COPD follow-up.
BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a leading global cause of death and disability, with a disproportionate burden in low- and middle-income countries. Secondhand smoke (SHS) contributes substantially to the COPD burden through toxic mechanisms. Current evidence on the COPD burden attributable to SHS remains limited. METHODS:Disability-adjusted life years (DALYs) were estimated using data from the Global Burden of Disease (GBD) 2021 study (1990-2021) by age, sex, and Socio-Demographic Index (SDI). Temporal trends were assessed using estimated annual percentage change, health inequality analyses were conducted across SDI groups, and projections were performed with Bayesian age-period-cohort models. RESULTS:In 2021, 7.09% of global COPD DALYs were attributable to SHS, highest in Oceania and South Asia, lowest in Latin America and high-income Asia. From 1990 to 2021, the age-standardized DALY rate of COPD attributable to SHS declined in Europe, North America, Sub-Saharan Africa, and the Middle East, with pronounced reductions in both sexes. In Asia, Latin America, and the Caribbean, declines slowed, projected to rise after 2021. DALYs showed age- and sex-specific patterns, males higher in high- and low-SDI regions, females in others, peak burden at 70-74, varying across SDI levels. DALYs were negatively associated with SDI, with regional variations and persistent health inequalities, increasingly concentrated in higher-SDI regions. CONCLUSION:The global COPD-SHS burden varies by socioeconomic status, geography, age, and sex. Despite overall declines, it remains high in Asia and North Africa, disproportionately affecting older adults and economically underdeveloped regions, highlighting the need for targeted interventions.
Background Long non-coding RNA MIR31HG (lncRNA MIR31HG) plays a well-defined role in tumor progression. However, its roles in chronic obstructive pulmonary disease (COPD) progression remain elusive. This study aimed to investigate the expression level and the physiological role of lncRNA MIR31HG in COPD, and further examine the relationship of the lncRNA MIR31HG and miR-342-3p with disease severity, clinical features, and inflammation levels.Methods Serum levels of lncRNA MIR31HG and miR-342-3p were measured by RT‑qPCR in healthy controls (HC), patients with stable COPD, and those with acute exacerbation COPD (AECOPD). An in vitro model simulating COPD was created through treatment of Beas-2B cells with 2% cigarette smoke extract (CSE). Cell proliferation and inflammatory cytokines were detected by CCK-8 method and ELISA respectively. The relationship between lncRNA MIR31HG and miR-342-3p was examined using dual luciferase reporter and rescue assays.Results The expression of lncRNA MIR31HG was up-regulated in COPD patients and CSE-exposed Beas-2B cells. LncRNA MIR31HG positively regulated COPD-related malignant characteristics. The silencing of lncRNA MIR31HG alleviated the slow cell proliferation and inflammation caused by CSE exposure. The expression level of miR-342-3p was more attenuated in COPD patients compared with HC. Assays confirmed that lncRNA MIR31HG participates in cell proliferation and inflammatory response by targeting miR-342-3p.Conclusion The lncRNA MIR31HG expression was increased in patients with COPD. Its level was positively correlated with disease severity and inflammation but negatively associated with miR-342-3p. LncRNA MIR31HG might be an effective target for COPD distinction and treatment.
OBJECTIVE:To review the literature relating to patient barriers and facilitators to self-management in chronic obstructive pulmonary disease. METHODS:This review involved a systematic search and narrative synthesis. MEDLINE, CINAHL complete, PsycINFO and the Cochrane database of systematic reviews were systematically searched in March 2025. Search terms related to chronic obstructive pulmonary disease, self-management and potential barriers and facilitators to patient engagement or self-care. We reported according to PRISMA and analysis involved narrative synthesis. FINDINGS:Sixty-three papers were included. Barriers and facilitators to self-management were grouped across the following themes: i) healthcare systems (including time in appointments, treatment use and financial gateways), ii) emotions (incorporating stigma or emotional distress, positive outlook and acceptance of diagnosis or treatment), iii) communication with healthcare professionals (comprising understanding and perceived sufficiency of information, smoking habits, health behaviours and memory, tailoring needs and trust and person-centred care), iv) social factors (including support from family or friends and cultural or social norms) and v) environment (concerning environmental triggers and socioeconomic factors). Within these, challenges and enablers of self-management were encountered. Challenges included a lack of time in appointments, emotional distress and insufficient information from healthcare professionals. Enablers included positive outlook, support from family and friends and person-centred care. CONCLUSIONS:This review has identified multiple patient barriers and facilitators to self-management in chronic obstructive pulmonary disease. Future interventions should be tailored to address the barriers whilst building upon the facilitators identified in this review.
In patients with moderate-to-severe COPD, airway mucus-occlusions correlate with airflow limitation, exacerbation and mortality-risk. However, the clinical relevance of mucus-plugs in milder COPD is not well-understood. We evaluated pulmonary function, six-minute-walk-distance (6MWD), emphysema and airway mucus-plugs at baseline and 31 ± 7 months later (follow-up), in ex-smokers with COPD, and those at risk of COPD, but with normal spirometry. Ninety-three ex-smokers with (n = 54) and without COPD (n = 39) underwent spirometry, plethysmography, the six-minute-walk-test (6MWT),129Xe MRI, and CT at a baseline visit and 31 ± 7 months later. Baseline and follow-up FEV1, FVC, RV/TLC, DLCO, mucus-score, -count, -volume, -length, airway wall-thickness%, total-airway-count (TAC), relative-area-of-lung-with-attenuation ≤-950 Hounsfield Units (RA950), and 129Xe MRI ventilation-defect-percent (VDP) were measured. A Sankey plot was generated to follow mucus-plug dynamics at follow-up. At follow-up, there was significantly worse 6MWD, RV/TLC (COPD, p ≤ 0.04), VDP, CT RA950, airway WT% and TAC in participants with (p ≤ 0.002) and without COPD (p ≤ 0.03), but there was no change in FEV1, mucus-score, count, volume or length (all p > 0.07). At baseline, there were 289 plugs in 58 participants; at FU, 94/289 (33%) mucus-plugs persisted and there were 193 new plugs for a total of 287 mucus-plugs (Δmucus-score = 0, p = 0.7; Δmucus-count = -2, p = 0.5). In COPD and participants at-risk for COPD, there was significantly worse airway remodelling, emphysema, gas-trapping, exercise capacity, and ventilation defects. While two thirds of plugs resolved, new plugs, in new locations were observed at follow-up; mucus-count and score did not change. The temporal dynamics of mucus-plugs should be considered when evaluating their clinical relevance in COPD patients.Clinical Trial Registration: www.clinicaltrials.gov NCT02279329.
People living with COPD are frequently inadequately treated due to underdiagnosis or misdiagnosis. The aim of this study was to evaluate the real-world performance of the beclomethasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) fixed triple combination formulated in a dry powder inhaler (DPI) in improving symptoms, lung function, and adherence in moderate to severe COPD patients uncontrolled on dual therapies. We conducted a non-interventional, open-label, single-arm, multicenter, prospective study across 19 outpatient centers in Slovenia. The primary objective was to measure symptom improvement with the COPD Assessment Tool (CAT). A total of 359 patients with moderate to severe COPD (97% classified as GOLD E, frequent exacerbators) were followed for 24 weeks. There was a significant 6-point reduction in the CAT score after switching from dual therapies to BDP/FF/G inhalation powder (95% CI: -7.0 to -5.5; p < 0.0001). FEV1 increased by 110 mL (95% CI: 90-130; p < 0.0001) and FVC by 95 mL (95% CI: 65-120; p < 0.0001), reaching a statistically significant improvement of 2.5 percentage points in the FEV1/FVC quotient. The net improvement in dyspnea severity was 50.9% (95% CI 44.7%-57.2%), as assessed using the modified Medical Research Council (mMRC) Scale. Treatment adherence improved significantly after 6 months of triple therapy. In our cohort, switching uncontrolled moderate-to-severe COPD patients from dual therapy to BDP/FF/G fixed triple inhalation powder led to significant improvements in symptoms, lung function, dyspnea, sleep quality, and treatment adherence.
Chronic Obstructive Pulmonary Disease (COPD) remains underdiagnosed and undertreated despite the availability of clinical guidelines. Variability in care delivery suggests that factors beyond clinical knowledge influence how care is implemented in practice. Understanding the barriers and facilitators shaping healthcare professionals’ behaviour is essential to improving COPD identification and management. This review aimed to synthesise evidence on the barriers and facilitators influencing healthcare professionals’ ability to identify and manage COPD. A systematic search of CINAHL, MEDLINE, PsycINFO, and the Cochrane Database of Systematic Reviews was conducted to identify studies published between 2015 and 2025. Studies examining healthcare professionals’ experiences of COPD identification and management were included. Data were extracted and analysed using narrative synthesis, with barriers and facilitators coded and grouped across stages of care. Sixty-one studies across 28 countries were included. Barriers were reported more frequently than facilitators and were shaped by interacting system, practitioner and patient-level factors. Key barriers included limited time, restricted access to diagnostic and treatment resources, unclear professional roles, and gaps in knowledge and confidence. Facilitators included access to training, supportive organisational structures, multidisciplinary collaboration and clear care pathways. Barriers were often interdependent, with system constraints influencing practitioner behaviour and patient engagement. Barriers to COPD care are multi-level and interconnected, suggesting that single-component interventions are unlikely to be effective. Improving care requires coordinated approaches that address system constraints, support practitioner confidence and role clarity, and strengthen patient engagement. These findings provide a framework for designing interventions responsive to the complexity of real-world COPD care.
Noninvasive ventilation (NIV) is increasingly used in acute and chronic hypercapnic respiratory failure (HRF), with BiPAP traditionally considered the standard mode. Average volume assured pressure support (AVAPS) adjusts inspiratory pressure to maintain target tidal volume, potentially improving CO2 clearance. Its comparative clinical effectiveness remains uncertain. We conducted a systematic review and meta-analysis per PRISMA 2020 guidelines (PROSPERO ID: CD1031775), searching MEDLINE, EMBASE, Cochrane CENTRAL, Scopus, Web of Science, and gray literature through March 2025. Eligible studies were RCTs or comparative cohort studies in adults (≥18 years) with acute HRF or equivalent emergency indications, directly comparing AVAPS and BiPAP. Primary outcomes were endotracheal intubation and short-term mortality; secondary outcomes included arterial blood gases (pH, pO2, pCO2) and hospital length of stay (LOS). Random-effects meta-analysis (Hartung-Knapp) and one-way ANOVA of arm-level means were applied, with evidence graded using GRADE. Eleven studies met inclusion criteria (n = 280 for intubation, n = 300 for mortality). AVAPS significantly reduced intubation risk compared with BiPAP (RR 0.43, 95% CI 0.23-0.79; p = 0.027; I2 = 0%), corresponding to a 57% relative and 4.7% absolute risk reduction (NNT ≈ 21). No significant difference in short-term mortality was observed (RR 0.87, 95% CI 0.38-2.00; p = 0.62; I2 = 31.8%), though exploratory NNT favored AVAPS (47). Physiological outcomes and LOS were similar between groups (all p > 0.63). In adults with acute HRF, AVAPS lowers intubation rates compared with BiPAP, without clear short-term survival benefit. Physiological outcomes and LOS appear equivalent. AVAPS may be preferred for selected patients, though larger, high-quality RCTs are needed to confirm the mortality effects.
Exacerbation of chronic obstructive pulmonary disease (ECOPD) frequently coexists with diabetes mellitus, creating competing priorities for respiratory stabilization and safe inpatient glycemic control. Evidence for an integrated, respiratory-endocrinology co-management pathway in this population remains limited. A total of 162 inpatients hospitalized with ECOPD and comorbid diabetes between January 1 and December 31, 2025 were randomly allocated to a respiratory-endocrinology multidisciplinary co-management pathway or usual care. The intervention comprised an ECOPD care bundle, protocolized glycemic management, pulmonary rehabilitation, and a structured discharge transition package. Primary outcomes were chronic airways assessment test (CAAT) and patient-day hyperglycemia/hypoglycemia. Secondary outcomes included length of stay, 30-day readmission, functional capacity assessed by the 1-min sit-to-stand (1-min STS) test (at discharge and 30 days), patient satisfaction (CSQ-8; at discharge and 30 days), and care-transition quality measured by the Care Transitions Measure-3 (CTM-3; at 7 and 30 days). Compared with usual care, co-management yielded clinically meaningful improvements in CAAT at discharge and at 30 days. Co-management reduced hyperglycemic patient-days (rate ratio 0.799) without an increase in mild, moderate or severe hypoglycemia. The intervention group also had a shorter length of stay, a lower 30-day readmission rate, higher CSQ-8 scores, higher CTM-3 scores, and greater 1-min sit-to-stand performance at discharge and 30 days. Findings were consistent in sensitivity analyses restricted to systemic corticosteroid recipients. A structured respiratory-endocrinology multidisciplinary co-management pathway improved ECOPD-related health status and inpatient glycemic safety while enhancing functional recovery, patient experience, and short-term utilization outcomes in hospitalized patients with ECOPD and diabetes.
Background Chronic obstructive pulmonary disease (COPD) is associated with high mortality and morbidity, with a complex inflammatory mechanism. Previous studies have demonstrated that Bactericidal/Perme Ability-Increasing Fold-Containing Family B member 4 (BPIFB4) plays a significant role in maintaining inflammatory balance. This study aimed to explore the roles of BPIFB4, microRNA (miR)-181a, and long non-coding (lnc) RNA TUG1 in COPD inflammatory processes.Methods Induced sputum was collected from 20 COPD patients and 20 healthy controls. THP-1 cells were treated with cigarette smoke extract (CSE) to simulate an in vitro inflammatory response. Expression levels of BPIFB4, LncTUG1, and miR-181a were detected by qPCR and western blot. Bioinformatic prediction and dual luciferase assays were used to predict the targeting relationship. Flow cytometry and ELISA assays evaluated the content of macrophages and inflammatory cytokines, respectively.Results The expression levels of BPIFB4 and LncTUG1 were elevated in COPD patients, while miR-181a expression was downregulated. BPIFB4 and LncTUG1 were direct targets of miR-181a. Overexpression of BPIFB4 led to increased M2 macrophages and related anti-inflammatory cytokines. In contrast, silencing BPIFB4 resulted in elevated M1 macrophages and associated cytokines. Silencing LncTUG1 elevated miR-181a expression, reduced BPIFB4 expression, and increased M1-type macrophages and pro-inflammatory factors, while overexpression of LncTUG1 showed the opposite effects.Conclusions This study concludes that downregulation of LncTUG1 promotes inflammation by reducing BPIFB4 expression through miR-181a. Overexpression of BPIFB4 promotes macrophage polarization toward the M2 type, thereby alleviating the inflammatory response in COPD. These findings provide theoretical support and potential new targets for COPD treatment.
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and excessive mucin production. Two major gel-forming mucins, MUC5AC and MUC5B, correlate with worsened disease progression and pulmonary function. In COPD, neutrophils are important players in chronic inflammation that contribute to tissue damage through releasing reactive oxygen species (ROS). IL-1β, a pro-inflammatory cytokine, plays various roles in COPD disease progression. It is known to recruit and activate neutrophils and is also known to induce mucin production in bronchial epithelium. This study aimed to investigate whether IL-1β induces ROS production in neutrophils and whether neutrophil-derived ROS drives mucin secretion in bronchial epithelial cells. HL-60-derived neutrophils were treated with IL-1β or vehicle and neutrophil ROS production was assessed through flow cytometry. Using a co-culture system, human bronchial epithelial cells were exposed to IL-1β-treated neutrophils, and MUC5AC and MUC5B levels on these cells were evaluated at RNA and protein levels through RT-qPCR, immunofluorescence, and ELISAs. IL-1β induced neutrophil ROS production. The elevated ROS production in neutrophils induced MUC5AC and MUC5B production at mRNA and protein levels in bronchial epithelial cells. Inhibition of ROS production in neutrophils using a NOX2 inhibitor reduced MUC5AC and MUC5B secretion in bronchial epithelial cells. IL-1β-induced neutrophil-derived ROS is a key driver of mucin hypersecretion in bronchial epithelial cells, potentially contributing to COPD disease progression.Trial registration: Not applicable.
Spirometry is the standard for assessing airflow obstruction but can be challenging and/or time-consuming for patients. Oscillometry offers an effort-independent alternative. This study assessed the consistency between oscillometry and spirometry in Chinese patients with suspected or confirmed chronic obstructive pulmonary disease (COPD) or asthma. This prospective study enrolled patients from 46 Chinese hospitals. All underwent oscillometry with the Ambulatory Lung Diagnosis System followed by spirometry, both before and after salbutamol. The primary outcome was prebronchodilator (pre-BD) test consistency (normal vs. abnormal), evaluated using Cohen's Kappa. Secondary outcomes included the number of attempts to complete each test, post-BD consistency in the COPD group, and BD test consistency overall. From February 8 and August 30, 2024, 801 patients were enrolled; 788 completed both tests and were analyzed (COPD: 197 suspected, 194 confirmed; asthma: 200 suspected, 197 confirmed). Pre-BD results showed moderate test consistency (kappa = 0.4188, 95% CI: 0.3556-0.4820; overall agreement = 70.9%). Overall BD test had only fair agreement (kappa = 0.2722, 95% CI: 0.1870-0.3575; overall agreement = 80.3%) between tests. Post-BD results in the COPD group showed moderate consistency between tests (kappa = 0.4662, 95% CI: 0.3803-0.5521; overall agreement = 73.6%), with a high positive predictive value (87.4%) of abnormal oscillometry for spirometrydefined COPD. For satisfactory results, oscillometry required significantly fewer attempts than spirometry (mean: 8.5 vs. 11.0, p < 0.0001). While oscillometry showed only moderate consistency with spirometry, its high positive predictive value suggests potential as a rule-in test for COPD diagnosis when spirometry is not feasible. An alternative oscillometry-based diagnostic pathway may help improve COPD diagnosis under such circumstances. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov (NCT06172777).
Individuals with Chronic Obstructive Pulmonary Disease (COPD) constitute a high-risk population for Cardiovascular Disease (CVD). There is growing concern that standard risk assessment tools like the Framingham Risk Score (FRS) may be subject to underestimation of CVD risk in COPD patients. Therefore, the potential of combining lung function parameters with the FRS to improve risk prediction warrants further exploration. To determine whether the integration of lung function parameters with the Framingham Risk Score enhances the prediction of prevalent cardiovascular disease among individuals with COPD. We performed a cross-sectional analysis of adults with COPD from the 2007-2012 NHANES cycles. COPD was defined as a post-bronchodilator FEV1/FVC < 0.70 or a self-reported physician diagnosis of emphysema or chronic bronchitis. Cardiovascular disease (CVD) was defined as a self-reported history of coronary heart disease, congestive heart failure, heart attack, or angina. The primary predictors were the Framingham Risk Score (FRS) and multiple spirometric parameters, including FEV1, FVC, FEV1%pred, FVC%pred and FEV1/FVC. The FRS, which estimates an individual's 10-year risk of developing CVD, was calculated using the established algorithm that incorporates sex, age, total and high-density lipoprotein (HDL) cholesterol levels, systolic blood pressure, antihypertensive medication use, smoking status, and diabetes status. We used multivariable logistic regression to assess their association with prevalent CVD. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC), and the incremental value of adding lung function parameters to the FRS was formally tested with DeLong's test. Subgroup analyses were conducted to test the consistency of the main findings across different demographic and clinical strata. The integration of lung function parameters with the Framingham Risk Score (FRS) improved predictive discrimination. The AUC for the FRS-alone model was 0.646. This increased to 0.681 for FRS + FEV1%pred, 0.702 for FRS + FVC%pred, and 0.724 for FRS + FEV1/FVC. The addition of each spirometric measure provided statistically significant incremental value over the FRS alone (all *p* < 0.01 by DeLong's test), with the greatest improvement observed for the FEV1/FVC.
