Bacterial interactome disturbance in chronic obstructive pulmonary disease clinical stability and exacerbations.

RATIONALE: Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome. OBJECTIVES: To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes. METHODS: We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data. RESULTS: Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota. CONCLUSIONS: Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment.

Associations between mixed exposure to phthalates and latent tuberculosis infection among the general U.S. population from NHANES 2011-2012.

Background: People are constantly exposed to phthalates, but few reliable studies have focused on the connection between phthalate exposure and latent tuberculosis infection (LTBI). Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database (2011-2012). The LTBI was assessed by QuantiFERON®-TB Gold-In-Tube (QFT) or tuberculin skin testing (TST). The odds ratios (ORs) and 95% confidence intervals (CIs) per log10 unit change in the concentration of phthalate metabolites were calculated using crude and adjusted logistic regression models. The relationships between mixed phthalate concentrations and LTBI were assessed using Bayesian kernel machine regression (BKMR) models. Results: According to the results of the multivariable logistic regression, in a fully adjusted model, only monobenzyl phthalate (MBZP) was negatively associated with LTBI in Q3 (OR (95% CI): 0.485 (0.286,0.823), P = 0.007). According to the restricted cubic spline (RCS) model, there was a linear dose‒response association between all 11 phthalate metabolites and LTBI (p for nonlinearity >0.05). We found a significant positive correlation between mixed phthalate metabolites and LTBI by using fully adjusted BKMR model. Conclusions: Our analysis demonstrated that LTBI in the general U.S. population is linearly linked with exposure to single or combined phthalates.

Mediating Effect of Tobacco Dependence on the Association Between Maternal Smoking During Pregnancy and Chronic Obstructive Pulmonary Disease: Case-Control Study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. OBJECTIVE: This study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). METHODS: This case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the "bootstrap" method. RESULTS: The study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (ß=.097; P<.001). There was an association between MSDP and TD (ß=.074; P<.001) as well as between TD and COPD (ß=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: ß=.094; P<.001 and indirect: ß=.004; P=.03). The indirect effect remains present in the smoking population (direct: ß=.120; P<.001 and indirect: ß=.002; P=.03). CONCLUSIONS: This study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

Research progress of mitochondria in chronic obstructive pulmonary disease: a bibliometric analysis based on the Web of Science Core Collection.

Background: Due to its high morbidity and mortality, chronic obstructive pulmonary disease (COPD) has become a major global healthcare issue. Although there is abundant research regarding COPD, a bibliometric analysis of the literature related to mitochondria and COPD is lacking. Thus this study aimed to summarize the research status, research direction, and research hotspots of the published articles concerning COPD and mitochondria. Methods: A literature search for included publications related to COPD and mitochondria was carried out on the Web of Science Core Collection from the date of database establishment to December 15, 2022. A subsequent bibliometric and visual analysis of the included publications was conducted via Microsoft Excel, R software, CiteSpace, and VOSviewer. Results: A total of 227 published articles on COPD and mitochondria from 139 journals were included. Over the study period, the annual publication number and citation frequency in this field both showed a trend of continuous growth. The United States had the highest centrality and was the most productive country. The frequently occurring keywords were "oxidative stress", "obstructive pulmonary disease", "dysfunction", "mitochondria", "inflammation", and "cigarette smoke", among others. Recent research hotspots included autophagy, model, mitochondria, health, and extracellular vesicles (EVs). Despite an abundance and variety of research, there is still relatively little academic communications between scholars and institutions. Conclusions: This bibliometric study can help researchers gain a quick overview of the research into mitochondria and COPD and thus inform novel ideas and directions for future research in this field.

A simple and efficient clinical prediction scoring system to identify malignant pleural effusion.

BACKGROUND: Early diagnosis of malignant pleural effusion (MPE) is of great significance. Current prediction models are not simple enough to be widely used in heavy clinical work. OBJECTIVES: We aimed to develop a simple and efficient clinical prediction scoring system to distinguish MPE from benign pleural effusion (BPE). DESIGN: This retrospective study involved patients with MPE or BPE who were admitted in West China Hospital from December 2010 to September 2016. METHODS: Patients were divided into training, testing, and validation set. Prediction model was developed from training set and modified to a scoring system. The diagnostic efficacy and clinical benefits of the scoring system were estimated in all three sets. RESULTS: Finally, 598 cases of MPE and 1094 cases of BPE were included. Serum neuron-specific enolase, serum cytokeratin 19 fragment (CYFRA21-1), pleural carcinoembryonic antigen (CEA), and ratio of pleural CEA to serum CEA were selected to establish the prediction models in training set, which were modified to the scoring system with scores of 6, 8, 10, and 9 points, respectively. Patients with scores >12 points have high MPE risk while ⩽12 points have low MPE risk. The scoring system has a high predictive value and good clinical benefits to differentiate MPE from BPE or lung-specific MPE from BPE. CONCLUSION: This study developed a simple clinical prediction scoring system and was proven to have good clinical benefits, and it may help clinicians to separate MPE from BPE.

Single-cell RNA sequencing reveals immune microenvironment of small cell lung cancer-associated malignant pleural effusion.

We used 10 × genomics single-cell transcriptome sequencing technology to reveal the tumor immune microenvironment characteristics of small cell lung cancer (SCLC) in a patient with malignant pleural effusion (MPE). A total of 8008 high-quality cells were finally obtained for subsequent bioinformatic analysis, which were divided into 10 cell clusters further identified as B cells, T cells, myeloid cells, NK cells, and cancer cells. Such SCLC related genes as NOTCH1, MYC, TSC22D1, SOX4, BLNK, YBX3, VIM, CD8A, CD8B, and KLF6 were expressed in different degrees during differentiation of T and B cells. Different ligands and receptors between T, B and tumor cells almost interact through MHC II, IL-16, galectin, and APP signaling pathway.

Causal role of immune cells in chronic obstructive pulmonary disease: Mendelian randomization study.

OBJECTIVES: Innate and adaptive immunity play different roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, previous studies on the relationship between immune cells and COPD reported inconsistent results. METHODS: The causal connection between 731 immune cells and COPD was established using a two-sample Mendelian randomization (MR) analysis through publicly accessible genetic data. The heterogeneity and horizontal pleiotropism of the findings were confirmed using sensitivity analysis. RESULTS: In the B-cell panel, B-cell activating factor receptor (BAFF-R) on CD20- and CD20 on IgD-CD38bright (OR (95% CI): 0.93 (0.88, 0.99) and 0.97 (0.95, 0.98), respectively) were discovered to be protective. In the cDC panel, CD62L- plasmacytoid DC AC, CD80 on monocytes and CD11c on myeloid DCs (OR (95% CI): 0.94 (0.92, 0.97), 0.97 (0.94, 0.99) and (0.97 (0.95, 0.98), respectively) exerted protective effects. However, unswitched memory AC (OR (95%CI): 1.08 (1.01,1.15)) and CD 19 on IgD- CD 27- (OR (95%CI): 1.06 (1.02,1.10)) were hazardous in the B-cell panel. However, among the 731 immune cell phenotypes, no causal relationship was found for COPD on immune cells. CONCLUSION: This study found a potential causal relationship between immune cells in COPD, ruling out reverse causation. This study provides new avenues for studying the mechanisms of COPD.

Association between depression and COPD: results from the NHANES 2013-2018 and a bidirectional Mendelian randomization analysis.

BACKGROUND: Observational studies showed a bidirectional association between depression and chronic obstructive pulmonary disease (COPD). However, it is unclear whether the observed association is causal. Thus we estimated the relationship using observational studies combined with bidirectional Mendelian randomization [MR]. MATERIALS AND METHODS: The study included 9977 participants from the 2013-2018 National Health and Nutrition Examination Survey and used weighted logistic regression analysis to assess the association between depression and COPD, followed by a bidirectional Mendelian randomization analysis to verify their causality. RESULTS: Adjusted-weighted logistic regression in observational studies showed a significant association between COPD and mild depression (OR (95% CI): 1.81 (1.30, 2.52), P = 0.002) and COPD and depression (OR (95% CI): 1.93 (1.49, 2.50), P < 0.001). MR suggested depression may play a causal role in COPD risk (OR (95% CI): 1.45 (1.32, 1.60), P < 0.001), but more evidence for reverse causation is lacking (reverse MR OR (95% CI): 1.03 (0.99, 1.07), P = 0.151). CONCLUSION: In conclusion, our study found depression may play a potential causal role in the morbidity of COPD suggesting depression might be the etiology of COPD. This finding needs to be validated in further prospective cohort studies with large sample sizes and adequate follow-up time.

High risks adverse events associated with usage of aspirin in chronic obstructive pulmonary disease.

BACKGROUND: Despite potential benefits and widespread prescription of aspirin among chronic obstructive pulmonary disease (COPD) patients, limited research has investigated its adverse effects (AEs) in COPD population. METHODS: We conducted a retrospective analysis of adverse drug events (ADEs) reported in the US Food and Drug Administration Adverse Event Reporting System (FAERS) between Q1 2013 and Q2 2022. COPD patients were categorized into two groups based on aspirin use. ADEs related to aspirin use were identified using combined reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC) methods. RESULTS: A total of 56,660 ADEs reports associated with COPD patients were included in the study. Among these reports, 144 adverse events were linked to aspirin use in COPD patients, including fatigue (4.12%), diarrhea (3.13%), dyspnea exertional (2.03%), rhinorrhea (1.99%), weight increased (1.89%) and vomiting (1.84%), muscle spasms (1.79%), cardiac disorder (1.74%), heart rate increased (1.69%) and peripheral swelling (1.59%). Subgroup analysis indicates that age and gender might affect the AEs frequency in COPD patients using aspirin. CONCLUSIONS: Our findings identify 10 most frequently reported ADEs associated with aspirin use in COPD patients, thus offer valuable insights into the AEs of aspirin for safer clinical utilization in COPD management.

Mitochondrial damage-associated molecular patterns in chronic obstructive pulmonary disease: Pathogenetic mechanism and therapeutic target.

Chronic obstructive pulmonary disease (COPD) is a common inflammatory airway disease characterized by enhanced inflammation. Recent studies suggest that mitochondrial damage-associated molecular patterns (DAMPs) may play an important role in the regulation of inflammation and are involved in a serial of inflammatory diseases, and they may also be involved in COPD. This review highlights the potential role of mitochondrial DAMPs during COPD pathogenesis and discusses the therapeutic potential of targeting mitochondrial DAMPs and their related signaling pathways and receptors for COPD. Research progress on mitochondrial DAMPs may enhance our understanding of COPD inflammation and provide novel therapeutic targets.

Prevalence and clinical characteristics of sleep disorders in chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: Sleep disorders, including obstructive sleep apnea (OSA), restless leg syndrome (RLS) and insomnia, are present in chronic obstructive pulmonary disease (COPD) with varied prevalence. The aim of this systematic review and meta-analysis was to investigate prevalence of OSA, RLS and insomnia in patients with COPD and summarize their clinical characteristics. METHODS: We searched PubMed, Web of Science and Scopus for eligible articles reporting the prevalence of OSA, RLS, and insomnia in COPD patients. The Newcastle‒Ottawa scale was applied for quality assessment. Odds ratios or mean differences with 95 % confidence intervals (CIs) were applied for the overall prevalence calculation and clinical characteristics assessment. Sensitivity analysis, subgroup analysis and meta-regression were conducted to evaluate the heterogeneity of the results. RESULTS: Sixty articles reporting the prevalence of sleep disorders in patients with COPD were included, and the prevalence of OSA, RLS, and insomnia reached 29.1 %(95%CI 27.2%-30.9 %), 21.6 %(95%CI 11.8%-33.3 %) and 29.5 %(95%CI 16.9%-44.0 %), respectively. COPD patients with OSA were characterized by male sex (OR 1.631 95 % CI: 1.231-2.161), obesity(kg/m2) (MD 4.435, 95 % CI 3.218-5.652), higher Epworth Sleepiness Scale (MD: 3.741, 95 % CI: 0.655-6.828, p = 0.018), better pulmonary function (MD 5.66, 95 % CI 3.546-7.774) and higher risks of hypertension (OR 1.933 95 % CI 1.382-2.70) and diabetes (OR 1.898 95 % CI 1.264-2.849). COPD patients with RLS were associated with a higher Epworth sleepiness scale (ESS) score (MD 3.444, 95 % CI 1.880-5.008) and a longer COPD duration(year) (MD: 3.656, 95 % CI: 2.209-5.103). COPD patients with insomnia were characterized by female sex(OR 0.556, 95%CI 0.545,0.567, p < 0.001). CONCLUSION: Our study suggests that OSA, RLS and insomnia are common in COPD patients with specific clinical characteristics. Further studies are needed to explore the interactions between COPD and sleep disorders.

Guideline on treating community-acquired pneumonia with Chinese patent medicines.

Community-acquired pneumonia (CAP) is one of the most common infectious diseases, and its morbidity and mortality increase with age. Resistance and mutations development make the use of anti-infective therapy challenging. Chinese patent medicines (CPMs) are often used to treat CAP in China and well tolerable. However, currently there are no evidence-based guideline for the treatment of CAP with CPMs, and the misuse of CPMs is common. Therefore, we established a guideline panel to develop this guideline. We identified six clinical questions through two rounds of survey, and we then systematically searched relevant evidence and performed meta-analyses, evidence summaries and GRADE decision tables to draft recommendations, which were then voted on by a consensus panel using the Delphi method. Finally, we developed ten recommendations based on evidence synthesis and expert consensus. For the treatment of severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Xuebijing injection, Shenfu injection, and Shenmai injection respectively. For the treatment of non-severe CAP in adults, we recommend Tanreqing injection, Reduning injection, Lianhua Qingwen capsule/granule, Qingfei Xiaoyan Pill and Shufeng Jiedu capsule respectively. CPMs have great potential to help in the fight against CAP worldwide, but more high-quality studies are still needed to strengthen the evidence.

Incorporation of a Toll-like receptor 2/6 agonist potentiates mRNA vaccines against cancer and infectious diseases.

mRNA vaccines have emerged rapidly in recent years as a prophylactic and therapeutic agent against various diseases including cancer and infectious diseases. Improvements of mRNA vaccines have been underway, among which boosting of efficacy is of great importance. Pam2Cys, a simple synthetic metabolizable lipoamino acid that signals through Toll-like receptor (TLR) 2/6 pathway, eliciting both humoral and cellular adaptive immune responses, is an interesting candidate adjuvant. To investigate the enhancement of the efficacies of mRNA vaccines by Pam2Cys, the adjuvant was incorporated into mRNA-lipid nanoparticles (LNPs) to achieve co-delivery with mRNA. Immunization with the resulting mRNA-LNPs (Pam2Cys) shaped up the immune milieu in the draining lymph nodes (dLNs) through the induction of IL-12 and IL-17, among other cytokines. Antigen presentation was carried out mainly by migratory and dLN-resident conventional type 2 DCs (cDC2s) and significantly more potent antitumor responses were triggered in both prophylactic and therapeutic tumor models in a CD4+ and CD8+ T cell-dependent fashion. Accompanying memory antitumor immunity was also established. Moreover, the vaccine also stimulated much more robust humoral and cellular immunity in a surrogate COVID-19 prophylactic model. Last but not the least, the new vaccines exhibited good preliminary safety profiles in murine models. These facts warrant future development of Pam2Cys-incorporated mRNA vaccines or relevant mRNA therapeutics for clinical application.

Inherent differences of small airway contraction and Ca2+ oscillations in airway smooth muscle cells between BALB/c and C57BL/6 mouse strains.

BALB/c and C57BL/6 mouse strains are widely used as animal model in studies of respiratory diseases, such as asthma. Asthma is characterized by airway hyperresponsiveness, which is eventually resulted from the excessive airway smooth muscle (ASM) contraction mediated by Ca2+ oscillations in ASM cells. It is reported that BALB/c mice have inherently higher airway responsiveness, but show no different contractive response of tracheal ring as compared to C57BL/6 mice. However, whether the different airway responsiveness is due to the different extents of small airway contraction, and what's underlying mechanism remains unknown. Here, we assess agonist-induced small airway contraction and Ca2+ oscillations in ASM cells between BALB/c and C57BL/6 mice by using precision-cut lung slices (PCLS). We found that BALB/c mice showed an intrinsically stronger extent of small airway narrowing and faster Ca2+ oscillations in ASM cells in response to agonists. These differences were associated with a higher magnitude of Ca2+ influx via store-operated Ca2+ entry (SOCE), as a result of increased expression of SOCE components (STIM1, Orai1) in the ASM cells of small airway of BALB/c mice. An established mathematical model and experimental results suggested that the increased SOC current could result in increased agonist-induced Ca2+ oscillations. Therefore, the inherently higher SOC underlies the increased Ca2+ oscillation frequency in ASM cells and stronger small airway contraction in BALB/c mice, thus higher airway responsiveness in BALB/c than C57BL/6 mouse strain.

REALizing and improving management of stable COPD in China: results of a multicentre, prospective, observational study (REAL).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) management in China is far from adequate; underdiagnosis and undertreatment are major barriers to optimal care and improved patient outcomes. OBJECTIVE: To generate reliable information on COPD management, outcomes, treatment patterns and adherence, and disease knowledge in China in a real-world setting. DESIGN: A 52-week multicentre, prospective, observational study. METHODS: Outpatients (⩾40 years old) diagnosed with COPD were enrolled from 50 secondary and tertiary hospitals across six geographical regions. Data were collected in routine clinical practice. RESULTS: Between June 2017 and January 2019, 5013 patients were enrolled and 4978 included in the analysis. Mean [standard deviation (SD)] age was 66.2 (8.9) years, 79.5% were male and 90% had moderate-to-very-severe airflow limitation. Annual rates of overall and severe exacerbation were 0.56 and 0.31, respectively. During 1 year, 1536 (30.8%) patients experienced ⩾1 exacerbation and 960 (19.3%) patients had ⩾1 exacerbation requiring hospitalization/emergency visit. Mean (SD) COPD assessment test score was 14.6 (7.6) at baseline and 10.6 (6.8) at follow-up; however, 42-55% of patients had persistent dyspnoea, chest tightness and wheezing at 1 year. The most prescribed treatments were inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA) (36.0%), ICS/LABA + long-acting muscarinic antagonist (LAMA) (17.7%) and LAMA monotherapy (15.3%). Among patients with high exacerbation risk (GOLD Groups C and D), 10.1% and 13.1%, respectively, did not receive any long-acting inhalers; only 53.8% and 63.6% of Group C and D patients with ⩾1 exacerbation during follow-up were prescribed ICS-containing therapy, respectively. Mean (SD) adherence for long-acting inhalers was 59.0% (34.3%). Mean (SD) score for the COPD questionnaire was 6.7 (2.4). CONCLUSION: These results indicate a high burden of severe exacerbations and symptoms in Chinese outpatients with COPD, and low adherence with treatment guidelines, highlighting the need for more effective management nationwide. REGISTRATION: The trial was registered on 20 March 2017 (ClinicalTrials.gov identifier: NCT03131362).

Use of CAPTURE to Identify Individuals Who May or May Not Require Treatment for Chronic Obstructive Pulmonary Disease.

Rationale: The CAPTURE tool (Chronic Obstructive Pulmonary Disease [COPD] Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk) was developed to identify patients with undiagnosed COPD with an FEV1 <60% predicted or risk of exacerbation as treatment criteria. Objectives: To test the ability of CAPTURE to identify patients requiring treatment because of symptoms or risk of exacerbation or hospitalization. Methods: Data were from COMPASS (Clinical, Radiological and Biological Factors Associated with Disease Progression, Phenotypes and Endotypes of COPD in China), a prospective study of COPD, chronic bronchitis without airflow limitation (postbronchodilator FEV1/FVC ratio ≥0.70), and healthy never-smokers. CAPTURE was tested as questions alone and with peak expiratory flow measurement. Sensitivity, specificity, and positive and negative predicted values (PPV and NPV) were calculated for COPD Assessment Test (CAT) scores ⩾10 versus <10, modified Medical Research Council (mMRC) scores ⩾2 versus <2, and at least one moderate exacerbation or hospitalization in the previous year versus none. Measurements and Main Results: Patients with COPD (n = 1,696) had a mean age of 65 ± 7.5 years, and 90% were male, with a postbronchodilator FEV1 of 66.5 ± 20.1% predicted. Control participants (n = 307) had a mean age of 60.2 ± 7.0 years, and 65% were male, with an FEV1/FVC ratio of 0.78 ± 0.04. CAPTURE using peak expiratory flow showed the best combination of sensitivity and specificity. Sensitivity and specificity were 68.5% and 64.0%, respectively, to detect a CAT score ⩾10; 85.6% and 61.0% to detect an mMRC score ⩾2; 63.5% and 55.6% to detect at least one moderate exacerbation; and 70.2% and 59.4% to detect at least one hospitalization. PPVs ranged from 15.6% (moderate exacerbations) to 47.8% (CAT score). NPVs ranged from 80.8% (CAT score) to 95.6% (mMRC score). Conclusions: CAPTURE has good sensitivity to identify patients with COPD who may require treatment because of increased symptoms or risk of exacerbations or hospitalization, including those with an FEV1 >60% predicted. High NPV values show that CAPTURE can also exclude those who may not require treatment. Clinical trial registered with www.clinicaltrials.gov (NCT04853225).

Diagnostic and prognostic value of Ang-2 in ARDS: a systemic review and meta-analysis.

BACKGROUND: To investigate the diagnostic and prognostic value of angiopoietin-2 (Ang-2) for acute respiratory distress syndrome (ARDS). METHODS: Seven databases (4 English and 3 Chinese databases) were searched, the quality was evaluated by QUADAS-2 and GRADE profile. The bivariate model was employed to combine area under the curve (AUC), pooled sensitivity (pSEN) and pooled specificity (pSPE), the Fagan's nomogram was employed for evaluating clinical utility. This study was registered in PROSPERO (NO.CRD42022371488). RESULTS: 18 eligible studies comprising 27 datasets (12 diagnostic and 15 prognostic datasets) were included for meta-analysis. For diagnostic analysis, Ang-2 yielded an AUC of 0.82, with a pSEN of 0.78 and a pSPE of 0.74; in clinical utility analysis, a pretest probability of 50% regulated the post probability positive (PPP) of 75% and the post probability negative (PPN) of 23%. In prognostic analysis, Ang-2 yielded an AUC of 0.83, with a pSEN of 0.69, a pSPE of 0.81, and good clinical utility (a pretest probability of 50% regulated the PPP of 79% and the PPN of 28%). Heterogeneity existed in both diagnostic and prognostic analysis. CONCLUSIONS: Ang-2 demonstrates promising diagnostic and prognostic capabilities as a noninvasive circulating biomarker for ARDS, especially in the Chinese population. It is advisable to dynamically monitor Ang-2 in critically ill patients both suspected and with confirmed ARDS.

Treatment patterns in patients with stable COPD in China: analysis of a prospective, 52-week, nationwide, observational cohort study (REAL).

BACKGROUND: Underdiagnosis and undertreatment pose major barriers to optimal management of chronic obstructive pulmonary disease (COPD) in China. OBJECTIVE: The REAL trial was performed to generate reliable information on real-world COPD management, outcomes and risk factors among Chinese patients. Here, we present study outcomes related to COPD management. DESIGN: It is a 52-week, prospective, observational, multicentre study. METHODS: Outpatients (aged ⩾40 years) enrolled from 50 secondary and tertiary hospitals across six geographic regions of China were followed up for 12 months, with two onsite visits and by telephone every 3 months following baseline. RESULTS: Between June 2017 and January 2019, 5013 patients were enrolled and 4978 included in the analysis. Mean [standard deviation (SD)] age was 66.2 (8.9) years, the majority of patients were male (79.5%) and mean (SD) time since COPD diagnosis was 3.8 (6.2) years. The most common treatments at each study visit were inhaled corticosteroids/long-acting beta-agonists (ICSs/LABAs; 28.3-36.0%), long-acting muscarinic antagonists (LAMAs; 13.0-16.2%) and ICS/LABA + LAMA (17.5-18.7%), but up to 15.8% of patients at each visit received neither ICS nor long-acting bronchodilators. The use of ICS/LABA, LAMA and ICS/LABA + LAMA differed across regions and hospital tiers; up to fivefold, more patients received neither ICS nor long-acting bronchodilators in secondary (17.3-25.4%) versus tertiary hospitals (5.0-5.3%). Overall, rates of nonpharmacological management were low. Direct treatment costs increased with disease severity, but the proportion of direct treatment costs incurred due to maintenance treatment decreased with disease severity. CONCLUSION: ICS/LABA, LAMA and ICS/LABA + LAMA were the most frequently prescribed maintenance treatments for patients with stable COPD in China, although their use differed between region and hospital tier. There is a clear need for improved COPD management across China, particularly in secondary hospitals. REGISTRATION: The trial was registered on 20 March 2017 (ClinicalTrials.gov identifier: NCT03131362; https://clinicaltrials.gov/ct2/show/NCT03131362). PLAIN LANGUAGE SUMMARY: Treatment patterns in patients with COPD in ChinaBackground: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by progressive and irreversible airflow limitation. In China, many patients with this disease do not receive a diagnosis or appropriate treatment.Objective: This study aimed to generate reliable information on the treatment patterns among patients with COPD in China to help inform future management strategies.Study design and methods: Patients (aged ⩾40 years) were enrolled from 50 hospitals across 6 regions of China and physicians collected data over the course of 1 year during routine outpatient visits.Results: The majority of patients were receiving long-acting inhaled treatments, which are recommended to prevent worsening of the disease. Up to 16% of patients in this study, however, did not receive any of these recommended treatments. The proportion of patients who received long-acting inhaled treatments differed across regions and hospital tiers; there were about five times more patients in secondary hospitals (about 25%) who did not receive these treatments compared with those in tertiary hospitals (about 5%). Guidelines recommend that pharmacological treatment should be complemented by nondrug treatment, but this was only received by a minority of patients in this study. Patients with higher disease severity incurred greater direct treatment costs compared with those with milder disease. Maintenance treatment costs made up a smaller proportion of overall direct costs for patients with higher disease severity (60-76%) compared with patients with milder disease (81-94%).Conclusion: Long-acting inhaled treatments were the most frequently prescribed maintenance treatments among patients with COPD in China, but their use differed between region and hospital tier. There is a clear need to improve disease management across China, especially in secondary hospitals.

Exacerbation in patients with stable COPD in China: analysis of a prospective, 52-week, nationwide, observational cohort study (REAL).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) management in China is inadequate and there is a need to improve care and outcomes for patients nationwide. OBJECTIVES: The REAL study was designed to generate reliable information on COPD management from a representative sample of Chinese patients with COPD. Here, we present study outcomes related to acute exacerbations. DESIGN: A 52-week, multicentre, prospective, observational study. METHODS: Outpatients (aged ⩾ 40 years) enrolled from 25 tertiary and 25 secondary hospitals across six geographic regions in China were followed for 12 months. Risk factors for COPD exacerbation and disease severity by exacerbation were assessed using multivariate Poisson and ordinal logistic regression models, respectively. RESULTS: Between June 2017 and January 2019, 5013 patients were enrolled, with 4978 included in the analysis. Mean (standard deviation) age was 66.2 (8.9) years. More patients presented with exacerbations in secondary versus tertiary hospitals (59.4% versus 40.2%) and in rural versus urban areas (53.2% versus 46.3%). Overall exacerbation rates differed across regions (range: 0.27-0.84). Patients from secondary versus tertiary hospitals had higher rates of overall exacerbation (0.66 versus 0.47), severe exacerbation (0.44 versus 0.18) and exacerbation that resulted in hospitalisation (0.41 versus 0.16). Across regions and hospital tiers, the rates of overall exacerbation and exacerbations that resulted in hospitalisation were highest in patients with very severe COPD (based on the severity of airflow limitation or GOLD 2017 combined assessment). Strong predictors of exacerbation included demographic and clinical characteristics, modified Medical Research Council scores, mucus purulence, exacerbation history and the use of maintenance mucolytic treatment. CONCLUSION: COPD exacerbation rates varied across regions and were higher in secondary compared with tertiary hospitals in China. Understanding the factors associated with COPD exacerbation may facilitate improved management of COPD exacerbations in China. REGISTRATION: The trial was registered on 20 March 2017 (ClinicalTrials.gov: NCT03131362; https://clinicaltrials.gov/ct2/show/NCT03131362). PLAIN LANGUAGE SUMMARY: Exacerbations in patients with chronic obstructive pulmonary disease in ChinaBackground: Chronic obstructive pulmonary disease (COPD) causes progressive and irreversible airflow limitation. As the disease progresses, patients often experience a flare up of symptoms referred to as an exacerbation. There is inadequate management of COPD in China and, therefore, there is a need to improve care and outcomes for patients across the country.Objective: This study aimed to generate reliable information on exacerbations among Chinese patients with COPD to help inform future management strategies.Study design and methods: Patients (aged ⩾ 40 years) were enrolled from 25 secondary and 25 tertiary hospitals across six regions of China. Physicians collected data over 1 year during routine outpatient visits.Results: There were more patients who experienced an exacerbation in secondary versus tertiary hospitals (59% versus 40%) and in rural versus urban areas (53% versus 46%). Patients in different geographic regions experienced varying frequencies of exacerbations over 1 year. Compared with patients from tertiary hospitals, patients from secondary hospitals experienced exacerbations (including exacerbations that were severe and those that resulted in hospitalisation) at a higher frequency over 1 year. Patients with very severe disease experienced exacerbations (including exacerbations that resulted in hospitalisation) at the highest frequency over 1 year, regardless of the patient's geographic region or hospital tier. Patients who had certain characteristics and symptoms, had exacerbation(s) over the previous year, or received medication that aids in the clearance of mucus were more likely to experience exacerbations.Conclusion: The frequency of exacerbations among Chinese patients with COPD varied between patients living in different geographic regions and between patients presenting to different hospital tiers. Understanding the factors related to the occurrence of an exacerbation may help physicians better manage the disease.

Efficacy and safety of tiotropium bromide inhalation in symptomatic patients with chronic obstructive pulmonary disease: A multicenter, prospective, and observational study.

OBJECTIVES: Treatment guidelines have recommended tiotropium bromide inhalation (TBI), a long-acting muscarinic antagonist, for chronic obstructive pulmonary disease (COPD); however, its efficacy in symptomatic Chinese patients with COPD remains uninvestigated. METHODS: This multicenter, prospective, observational study enrolled patients with COPD assessment test (CAT) scores exceeding 10 points from 19 hospitals spread across China. All patients received TBI and underwent follow-up for 3 months. The demographic and clinical information were assessed. RESULTS: The final analysis included 378 patients. The forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) of all participants improved markedly after 3 months of treatment (FEV1: mean 1.33 L versus 1.61 L, P < 0.001; FEV1/FVC: mean 0.53 versus 0.62, P < 0.001). The mean CAT scores decreased from 26.56 to 16.28 (P < 0.001). Patients classified into group D based on the Global Initiative for COPD guidelines showed greater improvement in FEV1 and FEV1/FVC than that in patients in group B. The proportion of patients with acute exacerbations also declined from 28.6% in the first month to 4.2% in the third month. CONCLUSION: TBI for 3 months could effectively and safely attenuate symptoms and airflow obstruction in symptomatic Chinese patients with COPD.