Fen Dong

Background: Poor medication adherence is a critical impediment to effective chronic obstructive pulmonary disease (COPD) management and remains challenging to track in routine care. Digital therapeutic interventions may improve chronic disease management through remote monitoring and patient education. However, most existing digital interventions focus on individual components of disease management, and evidence from longer-term pragmatic randomized controlled trials evaluating integrated digital therapeutics in routine clinical practice remains limited. Objective: This study aimed to evaluate the effectiveness of a multicomponent digital therapeutic program combining electronic inhaler monitoring (EIM) with behavioral support in improving medication adherence and symptom-related outcomes among patients with COPD prescribed pressurized metered-dose inhalers, and to assess patient engagement and implementation in routine clinical practice. Methods: In this prospective, open-label, unblinded, randomized controlled trial, patients with COPD prescribed pressurized metered-dose inhalers were enrolled and randomized in a 2:1 ratio to either the intervention group or the control group. All participants received an EIM device to objectively record inhaler use throughout the 24-week study period. Patients in the intervention group also received personalized medication reminders from the EIM, adherence feedback, educational content, and clinician-supported follow-up through an integrated digital management platform based on EIM-derived data, whereas the control group received usual care. The primary outcome was medication adherence over 24 weeks. Secondary outcomes included exacerbations, COPD symptoms, quality of life, and lung function. Results: A total of 158 participants were randomized, including 106 in the intervention group and 52 in the control group. The median monitoring coverage was 161.5 (IQR 86.3‐168.0) days during the follow-up period. The self-reported adherence measured using the Test of Adherence to Inhalers showed no significant between-group differences at any follow-up time point. However, the electronically monitored adherence was significantly higher in the intervention group than in the control group (59.5% vs 33.1%, P =.009). Adherence declined over time in both groups, decreasing from 85.3% during weeks 0 to 4 to 43.0% during weeks 12 to 24 in the intervention group and from 76.8% to 11.9% in the control group over the same intervals, resulting in a progressively larger between-group difference over follow-up. No significant differences were observed in exacerbations, health-related quality of life, symptom burden, lung function, or mental health outcomes. In an exploratory analysis, a significantly greater proportion of participants in the intervention group achieved the minimal clinically important difference in the COPD Assessment Test score than in the control group (odds ratio 2.21, 95% CI 1.11‐4.41; P =.02). Conclusions: The multicomponent digital therapeutic program significantly improved objective medication adherence in patients with COPD over 24 weeks. While most clinical outcomes did not differ significantly between groups, the higher proportion of participants achieving a clinically meaningful improvement in the COPD Assessment Test score warrants further investigation.

Purpose: Chronic obstructive pulmonary disease (COPD) a major cause of morbidity, hospitalization, and healthcare burden worldwide and is increasingly recognized as a heterogeneous syndrome with diverse environmental and socioeconomic determinants. We aimed to identify phenotype-specific determinants of hospitalized exacerbations and annual total length of hospital stay (LHS) in smoking and non-smoking COPD. Patients and Methods: We analyzed 3,913 COPD patients from a nationwide multicenter prospective cohort in China, stratified by smoking status. Hospitalized exacerbations at baseline and during one-year follow-up, as well as LHS, were assessed. Multivariable logistic regression and ordinal logistic regression models were used to estimate adjusted odds ratios (ORs) for hospitalized exacerbations and annual total LHS within each subgroup. Results: Among 3,913 participants, 1,709 (43.7%) had non-smoking COPD and 2,204 (56.3%) had smoking-related COPD. During follow-up, 28.0% of non-smokers and 29.9% of smokers experienced hospitalized exacerbations. Rural residence, larger household size, and prior hospitalizations in the preceding year were consistently associated with hospitalized exacerbations and longer annual total LHS in both groups. Biomass exposure was independently associated with hospitalized exacerbations among non-smoking patients but not among smokers after full adjustment. Low body mass index (BMI) was associated with increased risk in non-smoking COPD. Findings were consistent across baseline and prospective analyses, as well as binary and ordinal outcome models. Conclusion: In China, rural residence, larger household size, and prior exacerbation history were common determinants of hospitalized exacerbations and longer annual total LHS in patients with COPD, while biomass exposure and low BMI exerted stronger effects in non-smoking COPD.

Introduction: Chronic obstructive pulmonary disease (COPD) affects the ageing population worldwide. Exacerbations worsen health status and increase health resource use. Existing guidelines recommend disease management, but they are not fully implemented in a clinical setting. Evidence regarding best practice and real-world effectiveness is limited. Methods and analysis: A nationwide multicentre clinical effectiveness trial is being performed between 2023 and 2027, involving 99 secondary hospitals in urban and rural areas in China. It is an open-label, adjudicator and assessor-blinded, parallel group, cluster randomised pragmatic trial. Hospitals are randomly allocated to standardised management (SM) or usual care. A total number of 3456 stable patients with COPD who are symptomatic (individuals in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Group B) or have exacerbation risk (individuals with one moderate exacerbation history in Group A and individuals in Group E) using GOLD 2023 ABE classification will be enrolled. In the SM group, an integrated intervention comprising five components will be delivered using a physician and nurse model. These are: (1) long-term inhaled maintenance therapy, (2) periodic inhaler technique assessment and symptom monitoring, (3) annual pulmonary function testing, (4) COPD education session and (5) health behaviour adoption (smoking cessation, vaccination, pulmonary rehabilitation). In the control group, patients will receive routine care. The primary goal is to assess the real-world effectiveness of guideline-directed disease management on exacerbation prevention, with moderate-to-severe exacerbation as the primary outcome and hospital admission, mortality, health status and COPD self-management as secondary outcomes. It is the first pragmatic trial undertaken of this form in a developing country. It is anticipated that it will provide a feasible and effective COPD management model that can inform guidelines and be rolled out into secondary and primary care, with modification, to ensure standardised COPD care nationwide. Trial registration number: NCT04664491 .

Aim: To explore the association between COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) scores in patients with stable COPD with a change in maintenance treatment. Methods: Stable patients from the PATTERN study were investigated between 2021–2023. CAT and mMRC were assessed at baseline. Patients’ socio-economic level, clinical profile and step-up in inhaled therapy were recorded from baseline with a follow-up of 3 months. Results: This study included 797 patients. Mean (SD) age was 67.1 (8.2) years, 88.2% of patients were male, and 54.1% were from tertiary hospitals. Median (IQR) baseline CAT score was 13 (7, 20) and 51.1% of patients had mMRC score of ≤1. A total of 25.2% of patients had an exacerbation in the previous year. A step-up in treatment occurred in 7.7%, 10.1%, 11.4% and 15.4% of patients with CAT scores of ≤10, 11–20, 21–30 and ≥31, respectively. CAT score was positively associated with a step-up in treatment (odds ratio [OR] [95% CI]: 1.03, [1.00-1.06], P=0.049), but mMRC score was not (OR [95% CI: 1.11 [0.86-1.44], P=0.409). After adjusting for covariates, the association between CAT score and a step-up in treatment was P=0.055 (Figure). Conclusion: Step-up of maintenance therapy in patients with stable COPD was marginally related to symptom level. The key reason for treatment step-up in these patients remains unclear. Funding: GSK (213550) erj;64/suppl_68/PA4794/F1 F1 F1

Objective: Given the established impact of exercise in reducing arterial stiffness and the potential for intermittent hypoxia to induce its elevation, this study aims to understand how oxygen desaturation during exercise affects arterial stiffness in individuals with COPD. Methods: We enrolled patients with stable COPD from China-Japan Friendship Hospital from November 2022 to June 2023. The 6-minute walk test (6-MWT) was performed with continuous blood oxygen saturation (SpO₂) monitoring in these patients. The patients were classified into three groups: non-exercise induced desaturation (EID), mild-EID and severe-EID, according to the changes in SpO₂ during the 6-MWT. The Cardio-Ankle Vascular Index (CAVI) and the change in CAVI (ΔCAVI, calculated as CAVI before 6MWT minus CAVI after the 6MWT) were measured before and immediately after the 6MWT to assess the acute effects of exercise on arterial stiffness. GOLD Stage, pulmonary function, and other functional outcomes were also measured in this study. Results: A total of 37 patients with stable COPD underwent evaluation for changes in CAVI (ΔCAVI) before and after the 6-MWT. Stratification based on revealed three subgroups: non-EID (n=12), mild-EID (n=15), and severe-EID (n=10). The ΔCAVI values was − 0.53 (− 0.95 to − 0.31) in non-EID group, − 0.20 (− 1.45 to 0.50) in mild-EID group, 0.6 (0.08 to 0.73) in severe-EID group. Parametric tests indicated significant differences in ΔCAVI among EID groups (p = 0.005). Pairwise comparisons demonstrated significant distinctions between mild-EID and severe-EID groups, as well as between non-EID and severe-EID groups (p = 0.048 and p = 0.003, respectively). Multivariable analysis, adjusting for age, sex, GOLD stage, diffusion capacity, and blood pressure, identified severe-EID as an independent factor associated with ΔCAVI (B = 1.118, p = 0.038). Conclusion: Patients with COPD and severe-EID may experience worsening arterial stiffness even during short periods of exercise.

Introduction ST-segment elevation myocardial infarction (STEMI) with high thrombus burden is associated with a poor prognosis. Manual aspiration thrombectomy reduces coronary vessel distal embolisation, improves microvascular perfusion and reduces cardiovascular deaths, but it promotes more strokes and transient ischaemic attacks in the subgroup with high thrombus burden. Intrathrombus thrombolysis (ie, the local delivery of thrombolytics into the coronary thrombus) is a recently proposed treatment approach that theoretically reduces thrombus volume and the risk of microvascular dysfunction. However, the safety and efficacy of intrathrombus thrombolysis lack sufficient clinical evidence. Methods and analysis The intrAThrombus Thrombolysis versus aspiRAtion thrombeCTomy during prImary percutaneous coronary interVEntion trial is a multicentre, prospective, open-label, randomised controlled trial with the blinded assessment of outcomes. A total of 2500 STEMI patients with high thrombus burden who undergo primary percutaneous coronary intervention will be randomised 1:1 to intrathrombus thrombolysis with a pierced balloon or upfront routine manual aspiration thrombectomy. The primary outcome will be the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, heart failure readmission, stent thrombosis and target-vessel revascularisation up to 180 days. Ethics and dissemination The trial was approved by Ethics Committees of China-Japan Friendship Hospital (2022-KY-013) and all other participating study centres. The results of this trial will be published in peer-reviewed journals. Trial registration number NCT05554588.

Objective To compare the clinical features and outcomes in patients with pre-chronic obstructive pulmonary disease (COPD) and COPD hospitalised for confirmed or suspected acute exacerbation of COPD (AECOPD). Design A multicentre, longitudinal observational cohort study. Setting Data were obtained from the AECOPD Inpatient Registry Study in China. Participants 5896 patients hospitalised for AECOPD between 2017 and 2021. Outcomes Patients were divided into the COPD (n=5201) and pre-COPD (n=695) groups according to the lung function test results. The outcomes of interest included all-cause, respiratory disease-related and cardiovascular disease-related deaths as well as readmissions within 30 days and 12 months after discharge. Cumulative incidence functions were used to estimate the risk of cause-specific mortality and readmission. Multivariate hazard function models were used to determine the association between lung function and outcomes. Results There were significant between-group differences in the symptoms at admission and medication use during hospitalisation. However, there was no significant between-group difference in the 30-day all-cause mortality (0.00 vs 2.23/1000 person-month (pm), p=0.6110) and readmission (33.52 vs 30.64/1000 pm, p=0.7175). Likewise, the 30-day and 12-month cause-specific outcomes were not significantly different between groups (30-day readmission with acute exacerbation (AE): 26.07 vs 25.11/1000 pm; 12-month all-cause mortality: 0.20 vs 0.93/1000 pm; all-cause readmission: 11.49 vs 13.75/1000 pm; readmission with AE: 9.15 vs 11.64/1000 pm, p>0.05 for all comparisons). Cumulative incidence curves revealed no significant between-group differences in the 30-day and 12-month prognosis (p>0.05). Multivariate analysis revealed no significant association of lung function categories with 30-day and 12-month mortality or readmission (p>0.05 for all effect estimations). Conclusions Patients with pre-COPD have mild symptoms and similar risks for mortality and readmission during follow-up as patients with COPD. Patients with pre-COPD should receive optimal therapies before the occurrence of irreversible damage.

Purpose: To identify clinical features and outcomes associated with pulmonary heart disease among patients with chronic obstructive pulmonary disease exacerbation (COPD), which may help reduce economic burden accrued over hospital stay and shorten length of stay (LOS). Patients and Methods: Totally, 4386 patients with acute exacerbation of COPD (AECOPD) classified into pulmonary heart disease (PHD) group and non-pulmonary heart disease group, were included from the ACURE registry, a prospective multicenter patient registry study. Clinical features and outcomes were compared between groups. Results: PHD patients had a more severe profile, including having higher scores of COPD assessment test and modified British Medical Research Council, worse lung function, more patients hospitalized more than once in the past year due to acute exacerbation of COPD, and more comorbidities. Furthermore, drug cost was higher and length of stay was longer in AECOPD patients with PHD. Conclusion: AECOPD patients with PHD had a more severe profile and worse clinical outcomes, including higher drug cost and longer LOS. PHD is an independent risk factor of drug cost and LOS. Complicated with PHD in COPD/AECOPD patients with PHD means heavier disease burden and worse prognosis. It merits further study to focus on PHD management in COPD/AECOPD patients.

Objectives: To identify factors associated with length of stay (LOS) in chronic obstructive pulmonary disease (COPD) hospitalised patients, which may help shorten LOS and reduce economic burden accrued over hospital stay.Design: A retrospective cohort study.Setting: This study was performed in a tertiary hospital in China.Participants: Patients with COPD who were aged ≥40 years and newly admitted between 2016 and 2017.Primary and secondary outcome measures: LOS at initial admission was the primary outcome and health expenditures were the secondary outcome. To identify factors associated with LOS, we collected information at index hospitalisation and constructed a conceptual model using directed acyclic graph. Potential factors were classified into five groups: demographic information, disease severity, comorbidities, hospital admission and environmental factors. Negative binomial regression model was fitted for each block of factors and a parsimonious analysis was performed.Results: In total, we analysed 565 patients with COPD. The mean age was 69±11 years old and 69.4% were men. The median LOS was 10 (interquartile range 8–14) days. LOS was significantly longer in patients with venous thromboembolism (VTE) (16 vs 10 days, p=0.0002) or with osteoporosis (15 vs 10 days, p=0.0228). VTE ((rate ratio) RR 1.38, 95% CI 1.07 to 1.76), hypoxic–hypercarbic encephalopathy (RR 1.53, 95% CI 1.06 to 2.20), respiratory infection (RR 1.12, 95% CI 1.01 to 1.24), osteoporosis (RR 1.45, 95% CI 1.07 to 1.96) and emergence admission (RR 1.08, 95% CI 1.01 to 1.16) were associated with longer LOS. In parsimonious analysis, all these factors remained significant except emergency admission, highlighting the important role of concomitant morbidities in patients’ hospital stay. Total hospitalisation cost and patients’ out-of-pocket cost increased monotonically with LOS (both p_trend <0.0001).Conclusion: Patients’ concomitant morbidities predicted excessive LOS in patients with COPD. Healthcare cost increased over the LOS. Quality improvement initiatives may need to identify patients at high risk for lengthy stay and implement early interventions to reduce COPD economic burden.