First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small-cell lung cancer in China (AK105-302): a multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial.

BACKGROUND: Penpulimab is a novel programmed death (PD)-1 inhibitor. This study aimed to establish the efficacy and safety of first line penpulimab plus chemotherapy for advanced squamous non-small-cell lung cancer. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial enrolled patients with locally advanced or metastatic squamous non-small-cell lung cancer from 74 hospitals in China. Eligible participants were aged 18-75 years, had histologically or cytologically confirmed locally advanced (stage IIIb or IIIc) or metastatic (stage IV) squamous non-small-cell lung cancer, were ineligible to complete surgical resection and concurrent or sequential chemoradiotherapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, did not have previous systemic chemotherapy for locally advanced or metastatic non-small-cell lung cancer, and had one or more measurable lesions according to RECIST (version 1.1). Participants were randomly assigned (1:1) to receive intravenous penpulimab 200 mg or placebo (excipient of penpulimab injection), plus paclitaxel 175 mg/m2 and carboplatin AUC of 5 intravenously on day 1 every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy. Stratification was done according to the PD-L1 tumour proportion score (<1% vs 1-49% vs ≥50%) and sex (male vs female). The participants, investigators, and other research staff were masked to group assignment. The primary outcome was progression-free survival assessed by the masked Independent Radiology Review Committee in the intention-to-treat population and patients with a PD-L1 tumour proportion score of 1% or more (PD-L1-positive subgroup). The primary analysis was based on the intention-to-treat analysis set (ie, all randomly assigned participants) and the PD-L1-positive subgroup. The safety analysis included all participants who received at least one dose of study drug after enrolment. This trial was registered with ClinicalTrials.gov (NCT03866993). FINDINGS: Between Dec 20, 2018, and Oct 10, 2020, 485 patients were screened, and 350 participants were randomly assigned (175 in the penpulimab group and 175 in the placebo group). Of 350 participants, 324 (93%) were male and 26 (7%) were female, and 347 (99%) were of Han ethnicity. In the final analysis (June 1, 2022; median follow-up, 24·7 months [IQR 0-41·4]), the penpulimab group showed an improved progression-free survival compared with the placebo group, both in the intention-to-treat population (median 7·6 months, 95% CI 6·8--9·6 vs 4·2 months, 95% CI 4·2-4·3; HR 0·43, 95% CI 0·33-0·56; p<0·0001) and in the PD-L1-positive subgroup (8·1 months, 5·7-9·7 vs 4·2 months, 4·1-4·3; HR 0·37, 0·27-0·52, p<0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 120 (69%) 173 patients in the penpulimab group and 119 (68%) of 175 in the placebo group. INTERPRETATION: Penpulimab plus chemotherapy significantly improved progression-free survival in patients with advanced squamous non-small-cell lung cancer compared with chemotherapy alone. The treatment was safe and tolerable. Penpulimab combined with paclitaxel and carboplatin is a new option for first-line treatment in patients with this advanced disease. FUNDING: The National Natural Science Foundation of China, Shanghai Municipal Health Commission, Chia Tai Tianqing Pharmaceutical, Akeso.

Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

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.

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.

Incidence and prognostic role of pleural effusion in patients with acute pancreatitis: a meta-analysis.

BACKGROUND: Pleural effusion (PE) is reported as a common complication in acute pancreatitis (AP), while the incidence of PE in AP varies widely among studies, and the association between PE and mortality is not clear. This study aimed to comprehensively analyze the pooled incidence of PE in patients with AP and to evaluate the influence of PE on mortality through a meta-analysis. METHOD: Six databases (PubMed, Web of Science, EMBASE, Cochrane, Scopus, and OVID) were searched thoroughly for relevant studies. Data were extracted, and Stata SE 16.0 software was applied to compute the pooled incidence of PE and assess the association between PE and mortality, taking the risk ratio (RR) as the effect size. RESULTS: Thirty-five articles involving 7,675 patients with AP were eventually included in this meta-analysis. The pooled incidence of PE was 34% (95% CI: 28%-39%), with significant heterogeneity among studies (I2=96.7%). Further analysis revealed that the pooled incidence of unilateral and small PE occupied 49% (95% CI: 21%-77%) and 59% (95% CI: 38%-81%) of AP patients complicated by PE, respectively. The subgroup analysis revealed that "region" and "examination method" may contribute to heterogeneity. PE may be associated with increased mortality in AP patients (RR 3.99, 95% CI: 1.73-9.2). CONCLUSION: This study suggested that PE is a common complication with high pooled incidence and that PE may be associated with increased mortality in AP patients. More studies should be performed to validate our findings.

Diagnostic accuracy of interleukin-2 receptor in sarcoidosis: a systematic review and meta-analysis.

INTRODUCTION: Soluble interleukin-2 receptor (sIL-2 R), a valuable diagnostic biomarker for sarcoidosis, has been reported with variable results. Based on the literatures currently accessible, a systematic review and meta-analysis of the diagnostic performance of serum sIL-2 R for sarcoidosis were performed. METHODS: Relevant studies investigating sIL-2 R for sarcoidosis diagnosis in several databases were searched and data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled by STATA 16.0 software. Overall test performance was assessed using summary receiver operating characteristic curves and the area under the curve (AUC). Potential publication bias was assessed by Deeks test. RESULTS: We included eleven studies involving 1,424 subjects, with 1,099 cases of sarcoidosis and 325 of non-sarcoidosis. The pooled parameters of sIL-2 R in diagnosing sarcoidosis were summarized as follows: sensitivity, 0.85 (95% CI: 0.72-0.93); specificity, 0.88 (95% CI: 0.72-0.96); PLR, 7.3 (95% CI: 2.7-20.1); NLR, 0.17 (95% CI:0.08-0.36); DOR, 44 (95% CI: 8-231); and the AUC, 0.93 (95% CI: 0.90-0.95). No publication bias was identified (P = 0.64). CONCLUSIONS: Evidence suggests sIL-2 R performs well in diagnosing sarcoidosis. Nevertheless, results of sIL-2 R assay should be interpreted with other diagnostic examinations.

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.

Gabapentin for chronic refractory cough: A system review and meta-analysis.

Objective: To evaluate the efficacy and safety of gabapentin in the treatment of chronic refractory cough by Meta-Analysis. Methods: Literatures were retrieved from PubMed, Embase (OvidIP), Cochrane Library, CNKI, VIP, Wanfang Database and China Biomedical Management System and eligible prospective studies were screened. Data were extracted and analyzed by using RevMan 5.4.1 software. Results: Six articles (2 RCTs and 4 prospective studies) with 536 participants were finally included. Meta-analysis showed that gabapentin was better than placebo in cough-specific quality of life (LCQ score, MD = 4.02, 95%CI [3.26,4,78], Z = 10.34, P < 0.00001), cough severity (VAS score, MD = -29.36, 95% CI (-39.46, -19.26), Z = 5.7, P < 0.00001), cough frequency (MD = -29.87, 95% CI [- 43.84, -15.91], Z = 4.19, P < 0.0001) and therapeutic efficacy (RR = 1.37,95%CI [1.13,1.65], Z = 3.27, P = 0.001), and equal in safety (RR = 1.32,95%CI [0.47,3.7], Z = 0.53, P = 0.59). Gabapentin was similar to other neuromodulators in therapeutic efficacy (RR = 1.07,95%CI [0.87,1.32], Z = 0.64, P = 0.52), but its safety was better. Conclusion: Gabapentin is effective in the treatment of chronic refractory cough in both subjective and objective evaluations, and its safety is better than other neuromodulators.

Incidence and Prognostic Role of Pleural Effusion in Patients with Pulmonary Embolism: A Systematic Review and Meta-Analysis.

BACKGROUND: Pleural effusion is a common pulmonary embolism (PE) complication, which has been documented to increase the risk of death in PE and relate to disease progression. However, the incidence of pleural effusion varies among studies and its association with PE outcome is still unclear. This study sought to determine the pooled incidence and prognostic value of pleural effusion events in patients with PE. METHODS: We systematically searched the PubMed, EMBASE, SCOPE, Web of Science, Cochrane, LILACS, CINAHL, EBSCO, AMED, and OVID databases from the inception of each database to 7 September 2022 with a restriction on human studies, to identify studies assessing the association between pleural effusion and PE including all prospective and retrospective clinical studies. An exploratory meta-analysis was performed using a random-effects model. We evaluated the heterogeneity and performed subgroup analyses. RESULTS: The final meta-analysis included 29 studies involving 13,430 PE patients. The pooled incidence of pleural effusion in PE patients was 41.2% (95% CI: 35.7-46.6%), which tended to be unilateral (pooled incidence: 60.8%, 95% CI: 45.7-75.8%) and small (pooled incidence: 85.9%, 95% CI: 82.6-89.1%). Pooled analysis using a random-effects model (I2 = 53.2%) showed that pleural effusion was associated with an increased risk of 30-day mortality (RR 2.19, 95% CI: 1.53-3.15, p < 0.001, I2 = 67.1%) and in-hospital mortality (RR 2.39, 95% CI: 1.85-3.09, p < 0.001, I2 = 37.1%) in patients with PE. CONCLUSIONS: Our meta-analysis found that PE patients had a high incidence of pleural effusion, which was usually unilateral and small. Pleural effusion generally increases 30-day and in-hospital mortality in patients with PE, and it is recommended that physicians be aware of the risk of death from PE, especially when patients have pleural effusion. Further investigations focusing on PE with pleural effusion are warranted.

Adenosine deaminase-based measurement in the differential diagnosis of pleural effusion: a multicenter retrospective study.

INTRODUCTION: The differential diagnosis of pleural effusion is difficult, and studies have reported on the potential role of adenosine deaminase (ADA) in the differential diagnosis of undiagnosed pleural effusion. This retrospective study aimed to investigate the diagnostic role of ADA in pleural effusion. METHODS: 266 patients with pleural effusion from three centers were enrolled. The concentrations of ADA and lactate dehydrogenase (LDH) were measured in pleural fluids and serum samples of the patients. The diagnostic performance of ADA-based measurement for tuberculous pleural effusion (TPE), malignant pleural effusion (MPE), and parapneumonic effusion (PPE) was examined by receiver operating characteristic (ROC) curve analysis. RESULTS: An area under the ROC curve (AUC) value of 0.909 was obtained using the pleural ADA values as the indicator for TPE identification (sensitivity: 87.50%, specificity: 87.82%). The ratio of serum LDH to pleural ADA (cancer ratio) provided the predictive capacity with an AUC of 0.879 for MPE diagnosis (sensitivity: 95.04%, specificity: 67.06%). At a cut-off value of 14.29, the pleural ADA/LDH ratio showed a sensitivity and specificity of 81.13% and 83.67%, respectively, and a high AUC value of 0.888 for the differential diagnosis of PPE from TPE. CONCLUSION: ADA-based measurement is helpful for the differential diagnosis of pleural effusion. Further studies should be performed to validate these results.

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.

Incidence of complications from indwelling pleural catheter for pleural effusion: A meta-analysis.

Indwelling pleural catheter (IPC) is widely used in patients with pleural effusion (PE). This meta-analysis aimed to comprehensively summarize the clinical complication from IPC. We searched four large electronic databases (PubMed, EMBASE, MEDLINE, and Cochrane Library) for potentially relevant studies and assessed the included studies' quality using the methodological index for nonrandomized studies' criteria. Extracted data were used to pool rates, and to conduct subgroup and meta-regression analyses. Forty-one studies involving a cumulative 4983 patients with 5650 IPCs were included in this meta-analysis. The overall incidence of IPC complications was 20.3% (95% confidence interval [CI]: 15.0-26.3). The top four complications were: overall infection incidence 5.7% (95% CI: 0.7-2.4); overall catheter abnormality incidence 4.4% (95% CI: 2.8-6.3); pain incidence 1.2% (95% CI: 0.4-2.4); and overall loculation incidence 0.9% (95% CI: 0.1-2.1). Subgroup and meta-regression analyses for overall complications and infections by country, PE site, and PE type demonstrated these factors did not contribute significantly to heterogeneity. Further subgroup analyses for infection of benign PE showed that the overall infection incidence (12.6% [95% CI: 8.1-17.8] vs 0.7% [95% CI: 0.0-4.5]) and empyema incidence (9.1% [95% CI: 5.3-13.8] vs 0.0% [95% CI: 0.0-2.3]) of patients with liver-related PE were significantly higher than that of patients with heart-related PE. Our meta-analysis showed reliable pooled incidences of IPC-related complications, with infection being the most common. These results serve to remind clinicians about the incidence of IPC-related complications and emphasize the importance of taking corresponding preventive and therapeutic steps.

Impact of sleep disordered breathing on postoperative atrial fibrillation in patients who underwent cardiac surgery: a meta-analysis.

Objective: An increasing number of studies suggest that sleep disordered breathing (SDB) may be associated with postoperative atrial fibrillation (POAF), but these studies present discrepant results. Thus, this meta-analysis aimed to synthesize the data associating SDB with POAF in patients who underwent cardiac surgery.Methods: A literature search was performed in the Scopus, PubMed, Web of Science, EMBASE, CENTRAL, Weipu, Wanfang Data, and China National Knowledge Infrastructure databases before August 2022. Data were extracted, and the strength of the relationship between SDB and the risk of POAF was evaluated using odds ratio (OR) and 95% confidence intervals (CIs). All statistical analysis was carried out using the Stata 12.0 software.Results: A total of 24 studies with 660,685 subjects were included in current meta-analysis. SDB was significantly associated with the risk of POAF in the patients who underwent cardiac surgery (OR = 1.49; 95% CI, 1.30-1.70; p < .001). Next subgroup analysis revealed that such association may be increased in the group with medical equipment-measured SDB (OR = 2.27; 95% CI, 1.59-3.23; p < .001), prospective studies (OR = 2.17; 95% CI, 1.55-3.03; p < .001), patients without a previous history of atrial fibrillation (OR = 2.04; 95% CI, 1.47-2.82; p < .001), and patients who received a coronary artery bypass graft (OR = 2.10; 95% CI, 1.45-3.05; p < .001). No publication bias was identified.Conclusion: The results of meta-analysis support that SDB may be associated with an increased risk of POAF in patients who had undergone cardiac surgery, and these results should be confirmed in more rigorously designed studies.KEY MESSAGESPatients with SDB who underwent cardiac surgery showed increased risk of POAF.The relationship between SDB and POAF should be explained with caution with the consideration of various covariate.The effect of pre-treatment of SDB on POAF should be examined in future.

The effect of N-acetylcysteine in patients with non-cystic fibrosis bronchiectasis (NINCFB): study protocol for a multicentre, double-blind, randomised, placebo-controlled trial.

BACKGROUND: N-acetylcysteine (NAC), which is specifically involved in airway mucus clearance and antioxidation, is recommended by the treatment guideline for non-cystic fibrosis bronchiectasis (NCFB). However, there is little clinical evidence of its long-term efficacy concerning quality of life (QoL) and exacerbation in patients with NCFB. In addition, the influences of NAC on airway bacterial colonization, chronic inflammation and oxidative stress in NCFB are also unclear. METHODS: NINCFB is a prospective, multicentre, double-blind, randomised, placebo-controlled trial that will recruit 119 patients with NCFB and randomly divide them into an NAC group (n = 79) and a control group (n = 40). Participants in the NAC group will receive 600 mg oral NAC twice daily for 52 weeks, while patients in the control group will receive 600 mg placebo twice daily for 52 weeks. The information at baseline will be collected once participants are enrolled. The primary endpoints are the changes in St George's Respiratory Questionnaire scores and the number of exacerbations in 52 weeks. The secondary endpoints are the 16S rRNA of sputum and the levels of inflammatory factors and oxidative stressors in sputum and serum. Other data related to radiography, lung function tests, number of oral and/or intravenous antibiotic therapies and adverse events (AEs) will also be analysed. Further subgroup analysis distinguished by the severity of disease, severity of lung function, airway bacterial colonization and exacerbation frequency will be performed. DISCUSSION: The objective of this study is to determine the long-term efficacy of NAC on QoL and exacerbation of NCFB and to explore the effectiveness of NAC for antibiosis, anti-inflammation and antioxidation in NCFB. The study results will provide high-quality clinical proof for the revision and optimization of treatment guidelines and for expert consensus on NCFB treatment. TRIAL REGISTRATION: The trial was registered on the Chinese Clinical Trial Register at April 11, 2020 ( chictr.org.cn , ChiCTR2000031817).

Performance of Serum Angiotensin-Converting Enzyme in Diagnosing Sarcoidosis and Predicting the Active Status of Sarcoidosis: A Meta-Analysis.

The usefulness of serum angiotensin-converting enzyme (sACE) for diagnosing sarcoidosis and determining the active status of sarcoidosis has been reported with varying outcomes. On the basis of the majority of published data, we conducted a meta-analysis to calculate the overall predictive accuracy of sACE in sarcoidosis disease and the active status of sarcoidosis. The inclusion of related research listed in Web of Science, PubMed, Scopus, and other literature databases was assessed. SROC curves were generated to characterize the overall test results after data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were combined. Publication bias was identified using Deeks' funnel plot. Thirty-five publications with 8645 subjects met the inclusion criteria. The following are summary estimates of sACE diagnostic performance for sarcoidosis: sensitivity, 60% (95% confidence interval (CI), 52-68%); specificity, 93% (95% CI, 88-96%); PLR, 8.4 (95% CI, 5.3-13.3); NLR, 0.43 (95% CI, 0.36-0.52); and DOR, 19 (95% CI, 12-31). The area under the SROC curve (AUC) was 0.84 (95% CI, 0.80-0.87). Summary estimates for predicting the active status of sarcoidosis were as follows: sensitivity, 0.76 (95% CI, 0.61-0.87); specificity, 0.80 (95% CI, 0.64-0.90); PLR, 3.9 (95% CI, 2.1-7.3); NLR, 0.29 (95% CI, 0.17-0.49); and DOR, 13 (95% CI, 6-31). The AUC was 0.85 (95% CI, 0.82-0.88). There was no evidence of publication bias. Our meta-analysis suggests that measuring the sACE may assist in the diagnosis of sarcoidosis and predicting the active status of sarcoidosis, but the interpretation of the sACE results should be with caution. Future studies should validate our results.

Clinical Indicators for Asthma-COPD Overlap: A Systematic Review and Meta-Analysis.

Background: Some clinical indicators have been reported to be useful in differentiating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) from pure asthma/COPD, but the results were inconsistent. This study aims to evaluate the diagnostic value of these indicators for ACO. Methods: Databases of PubMed, EMBASE, Ovid and Web of Science were retrieved. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated in random-effects models. Results: 48 eligible studies were included. The pooled results indicated, compared with pure asthma, ACO patients had lower levels of forced expiratory volume in the first second (FEV1)% predicted (pred) (SMD=-1.09, 95% CI -1.3 to -0.87), diffusion lung capacity for carbon monoxide (DLCO)% pred (SMD=-0.83, 95% CI -1.24 to -0.42), fractional exhaled nitric oxide (FeNO) (SMD=-0.23, 95% CI -0.36 to -0.11), and higher levels of induced sputum neutrophil (SMD = 0.51, 95% CI 0.21 to 0.81), circulating YKL-40 (SMD = 0.96, 95% CI 0.27 to 1.64). However, relative to COPD alone, ACO patients had higher levels of FEV1% pred (SMD = 0.15, 95% CI 0.05 to 0.26), DLCO% pred (SMD = 0.38, 95% CI 0.16 to 0.6), FeNO (SMD = 0.59, 95% CI 0.40 to 0.78), serum total immunoglobulin (Ig)E (SMD = 0.42, 95% CI 0.1 to 0.75), blood eosinophil (SMD = 0.44, 95% CI 0.29 to 0.59), induced sputum eosinophil (SMD = 0.62, 95% CI 0.42 to 0.83), and lower levels of induced sputum neutrophil (SMD=-0.48, 95% CI -0.7 to -0.27), circulating YKL-40 (SMD=-1.09, 95% CI -1.92 to -0.26). Conclusion: Compared with pure asthma/COPD, ACO patients have different levels of FEV1% pred, DLCO% pred, FeNO, serum total IgE, blood eosinophil, induced sputum eosinophil/neutrophil, and circulating YKL-40, which could be helpful to establish a clinical diagnosis of ACO.

DNA Methylation Profiling in a Cigarette Smoke-Exposed Mouse Model of Airway Inflammation.

Purpose: DNA methylation, a major epigenetic modification, has been documented to play an important role in chronic obstructive pulmonary disease (COPD). In this study, we aimed to profile the DNA methylation patterns in a mouse model of airway inflammation induced by cigarette smoke (CS), a foremost risk factor of COPD. Material and Methods: To establish a model of airway inflammation, wild-type mice were exposed to mainstream CS or room air for 2 hours twice daily, 6 days per week for consecutive 4 weeks. Lung tissues of the mice were collected for genome-wide DNA methylation analysis by liquid hybridization capture-based bisulfite sequencing, which were used for intersection analysis with gene expression by cDNA microarray to identify candidate methylated genes. Then, functional enrichment analyses with protein-protein interaction (PPI) network regarding these genes were conducted to explore the potential mechanisms. Results: After 4-week CS exposure, the level of DNA methylation accompanied by a subacute airway inflammation was markedly enhanced, and 2002 differentially methylated genes (DMGs) were annotated, including 565 DMGs contained methylations in gene promoters, which were used for intersection with the differentially expressed genes. Then, 135 candidate methylated genes were further selected by the intersection, among which 58 genes with functional methylated modification were finally identified. Further analyses revealed candidate methylated genes were significantly enriched in a complicated network of signals and processes, including interleukins, toll-like receptors, T-cells differentiation, oxidative stress, mast cells activation, stem cells proliferation, etc., as well as the 58 functional methylated genes were partially located at key positions in PPI network, especially CXCL1, DDX58 and JAK3. Conclusion: This study suggests CS exposure significantly enhances DNA methylated level, and the potential functional methylated genes are closely related to complicated inflammatory-immune responses, which may provide some new experimental evidence in understanding the epigenetic mechanisms of CS-induced airway inflammation in COPD.