Disruption of parasympathetic pulmonary nerves, which release acetylcholine and trigger airway smooth muscle constriction, has been shown to improve lung function and alleviate symptoms in patients with chronic obstructive pulmonary disease (COPD). However, the current targeted lung denervation (TLD) mono-polar radiofrequency (RF) ablation system has the potential for structural improvement to enhance the generalizability and safety of the TLD procedure. To develop a novel TLD multi-polar RF ablation for COPD treatment and evaluate its feasibility, safety, and efficacy. In the preclinical study, we performed TLD in vitro (porcine lung and liver model) to validate its feasibility and in vivo (dogs and sheep) to ensure its safety and preliminary efficacy. Subsequently, we conducted a first-in-man study to evaluate TLD in patients with COPD forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (FEV1/FVC < 0.70; FEV1 20

OBJECTIVE:To investigate the prevalence and clinical characteristics of sleep apnea (SA) in patients with hypertrophic cardiomyopathy (HCM). METHODS:Eligible studies were screened and selected from four databases. The pooled prevalence of SA in HCM was calculated and presented as proportion with 95% confidence intervals (CI). Comparison of clinical characteristics between HCM patients with or without SA was then assessed and presented as mean difference (MD) or odds ratio (OR) with 95%CI. Sensitivity analyses, subgroup analyses and meta-regression were then applied for heterogeneity assessment. RESULTS:Eight studies with 3,922 HCM patients was included, revealing an SA prevalence of 53% (95% CI 39%, 67%). HCM patients with SA were associated with older age (MD 8.91, 95% CI 7.28, 10.54), male (OR 1.59, 95%CI 1.30, 1.95). elevated body mass index (MD 2.59, 95%CI 1.36, 3.81), smoking (OR 1.86, 95%CI 1.39, 2.49), hypertension (OR 2.54, 95%CI 2.06, 3.14), diabetes (OR 2.03, 95%CI 1.31, 3.13) and atrial fibrillation (OR 1.96, 95%CI 1.51, 2.54). Echocardiographic findings revealed that HCM with SA was associated with reduced interventricular septum thickness (MD -1.25, 95%CI -2.44, -0.06), increased left atrial diameter (MD 1.48, 95%CI 0.49, 2.47) and left ventricular end-diastolic diameter (MD 2.81, 95%CI 1.99, 3.62). Additionally, HCM patients with SA showed increased application of hypertensive drugs, and application of calcium channel blockers was identified as source of heterogeneity in meta-regression. CONCLUSION:SA is highly prevalent in HCM, and HCM patients with comorbid SA exhibit distinct baseline characteristics, cardiac structure and drug application.

Background:Although the link between smoking and various sleep disorders has been well-established, it is still unknown whether smoking increases the risk of restless legs syndrome (RLS). We investigated this association using a meta-analysis and explored the causality through Mendelian randomisation (MR). Methods:We searched six databases for studies reporting associations between smoking and RLS in overall adults, and the results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). We performed sensitivity, subgroup and meta-regression analyses to identify potential sources of heterogeneity. We obtained data used in MR analyses from the UK Biobank and the Genome-wide Association Studies Catalogue. We applied the inverse-variance weighted method, MR Egger, weighted median, simple mode and weighted mode for data analyses, and further conducted pleiotropy and heterogeneity tests, as well as leave-one-out analyses. Results:Based on 30 studies, we found that smoking was associated with increased risk of RLS (OR = 1.40; 95% CI = 1.17, 1.67, P < 0.001), with the risk significantly increased (P = 0.04) in pregnant women (OR = 2.41; 95% CI = 1.39, 4.16, P = 0.002) than in the non-pregnant adults (OR = 1.30, 95% CI = 1.09, 1.55, P = 0.004), and in current smokers compared with former smokers (OR = 1.09; 95% CI = 1.02, 1.16, P = 0.01). We identified multi-centre studies, diagnostic criteria for RLS and participants' age as potential sources of heterogeneity; however, MR results did not show any causal association between smoking and RLS (OR = 0.50; 95% CI = 0.16, 1.56, P = 0.23). Conclusions:Although the meta-analysis suggested that smoking increases the risk of RLS, MR analyses did not provide evidence for a causal relationship. Future studies are needed to elucidate the biological mechanisms underlying this association. Registration:PROSPERO: CRD420251048406.

Pulmonary function testing (PFT) is a critical diagnostic and management tool for respiratory diseases, yet its implementation in China, particularly within primary hospitals, remains suboptimal. To investigate the current application status of PFTs specifically in western China, a cross-sectional survey based on an online questionnaire was conducted. Physicians from various hospitals completed this questionnaire, designed according to Chinese PFT Guidelines, during 2023-2024, and the analysis focused on the final valid responses. The study ultimately included data from 488 hospitals. A total of 97.13% were public institutions. A total of 38.32% had established independent respiratory departments. The overall PFT availability was 56.76%, 100.00% in tertiary hospitals, and only 25.00% in primary hospitals. A total of 42.24% of the hospitals had a daily workload of less than 5 people. The primary tests included pulmonary ventilation tests (100.00%), pulmonary volume tests (73.65%), and bronchial dilation tests (72.92%). Instrument calibration was performed in 83.03% of the hospitals, and 68.59% of the hospitals considered filter resistance. Over 60.00% of hospitals used estimated values provided by instruments as sources for PFT. A total of 65.70% of hospitals had a limited number of operators. In conclusion, the application of PFT in western China is characterized by a low implementation rate, imbalanced distribution, limited test variety, and insufficient personnel, especially in primary hospitals. It is essential to promote the widespread implementation and standardization of PFTs in western China.

BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a condition with high prevalence and mortality, causing a substantial disease burden. Airway mucus hypersecretion (AMH) is clinically associated with impaired pulmonary function, diminished quality of life, and increased mortality in COPD patients. The purpose of this bibliometric research was to identify research developments and emerging hotspots within the field of AMH and COPD by providing a comprehensive overview of the current research landscape. METHODS:The Web of Science core (WOSCC) database was searched for publications addressing COPD and AMH from January 1, 1994, to December 31, 2024. A total of 1,405 publications were retrieved and subjected to bibliometric and visual analyses using CiteSpace, VOSviewer, and R software. RESULTS:From 1994 to 2024, both publication output and citation frequency in this field demonstrated a sustained upward trajectory. The United States of America (USA) occupies a prominent position in this domain, characterized by substantial collaborative networks and research productivity. While extensive inter-country and inter-institutional collaborations were evident, researcher-level collaborations remained relatively fragmented. Notably, Boucher, Richard C. received substantial recognition owing to his exceptional research productivity and citation impact. Keywords including exacerbations, autophagy, and mucus plugs exhibited the strongest citation bursts during 2023--2024. Conclusions:This research illustrates the present landscape, focal points, and future directions in the fields of COPD and AMH. Researchers may benefit from obtaining a rapid synopsis, along with citations and innovative concepts, to facilitate and inform subsequent investigations.

Purpose:The clinical significance of pectoralis muscle depletion during acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains unclear. This study investigated the independent prognostic value of computed tomography (CT)-derived pectoralis muscle metrics for in-hospital mortality and invasive mechanical ventilation (IMV) in AECOPD. Patients and Methods:This retrospective study included 464 consecutive AECOPD patients who underwent chest CT within 48 hours of admission. Pectoralis muscle area and muscle density (PMD) were quantified from CT. The pectoralis muscle index (PMI) was calculated by normalizing muscle area to height squared. Multivariable Cox regression models evaluated associations between these indices and adverse outcomes. The incremental predictive value of adding muscle indices to DECAF and BAP-65 scores was assessed using the area under the curve (AUC). Results:Among 464 patients, 44 (9.5%) died and 86 (18.5%) required IMV during hospitalization. Both PMI and PMD were significantly lower in non-survivors and IMV patients (all P<0.001). In fully adjusted models, each 1 cm2/m2 increase in PMI was associated with reduced risks of in-hospital mortality (HR 0.68, 95% CI 0.58-0.78) and IMV (HR 0.72, 95% CI 0.64-0.81). Each 5 HU increase in PMD independently predicted lower in-hospital mortality (HR 0.77, 95% CI 0.66-0.90) and IMV (HR 0.59, 95% CI 0.50-0.70). Incorporation of both PMI and PMD into the DECAF and BAP-65 scores substantially increased the predictive AUCs for in-hospital mortality (AUC: 0.70 to 0.89 for DECAF; 0.71 to 0.89 for BAP-65) and for IMV (AUC: 0.61 to 0.78 for DECAF; 0.69 to 0.81 for BAP-65). Conclusion:CT-derived pectoralis muscle mass and quality are independent and incremental predictors of in-hospital mortality and IMV in AECOPD. Opportunistic muscle assessment from routine chest CT may enhance early risk stratification and inform clinical decision-making.

OBJECTIVES:The diagnosis of connective tissue disease-associated interstitial lung disease (CTD-ILD) primarily relies on high-resolution computed tomography or lung biopsy, while several challenges persist in the clinical application of these modalities. This study aims to investigate the performance of lung ultrasound (LUS) in diagnosis of ILD in patients with CTD. METHODS:Records from five electronic databases were screened and selected for eligible studies. Quality assessment of eligible studies was performed via Quality Assessment of Diagnostic Accuracy Studies-2. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and area under the curve (AUC) of LUS was calculated. Sensitivity analyses, subgroup analyses and meta-regression were applied to identify sources of heterogeneity. RESULTS:Twenty-eight eligible studies were selected from 417 records, with a total of 2,196 participants (1,117 with CTD-ILD and 1,079 CTD patients without ILD). All studies reached moderate to high quality. LUS has shown good diagnostic performance in detecting CTD-ILD, with a sensitivity of 0.92, a specificity of 0.88 and an AUC of 0.96. Further stratified analyses suggested that good performance of LUS was also observed in diagnosing rheumatoid arthritis-associated ILD (sensitivity: 0.91, specificity: 0.90, AUC: 0.96) and systemic sclerosis-associated ILD (sensitivity: 0.96, specificity: 0.78, AUC: 0.94). Significant heterogeneity and publication bias was observed. CONCLUSIONS:Although LUS has shown good performance in diagnosing CTD-ILD, this approach does not yet justify routine application due to heterogeneity and publication bias. Further studies may focus on performance of LUS in other subtypes of CTD-ILD.

OBJECTIVES:Current guidelines recommend influenza and pneumococcal vaccination in the majority of patients with rheumatic diseases. This study aimed to summarize the coverage of influenza and pneumococcal vaccines among these patients. METHODS:A literature search was conducted in PubMed, Embase, Web of Science and Scopus for eligible studies. Vaccination rate was presented as a percentage with 95% CI. Clinical characteristics of the vaccinated patients were shown as the mean difference or odds ratio with 95% CI. Sensitivity analyses, subgroup analyses and meta-regression were performed to identify sources of heterogeneity. RESULTS:A total of 51 studies were identified. The pooled vaccination rates of influenza vaccine in patients with RA, SLE, SpA and PsA were 50%, 42%, 43% and 53%, respectively. The corresponding rates of pneumococcal vaccination in patients were 37%, 30%, 39% and 41%, respectively. Compared with unvaccinated RA patients, vaccinated RA patients were associated with older age and an increased prevalence of comorbidities. Geographical location and use of DMARDs were two significant factors affecting the heterogeneity of the study results. A larger proportion of patients received vaccine education from rheumatologists rather than general practitioners, and the two major reasons for not receiving vaccination were 'lack of awareness' and 'not offered by doctors'. CONCLUSION:Influenza and pneumococcal vaccine coverage was still suboptimal in patients with rheumatic diseases. Enhancing vaccine education from physicians and improving awareness of patients may become two important approaches to improve vaccination rates.

Background Although the postbronchodilator FEV 1 /FVC is the gold standard for diagnosing COPD, it is not easily obtainable due to various reasons. This study aims to investigate whether FEV 1 /FEV 6 may serve as an easily accessible surrogate for FEV 1 /FVC in detecting airway obstruction and COPD. Methods Eligible articles were screened from PubMed, Web of Science and Scopus. The Quality Assessment of Diagnostic Accuracy Studies-2 was applied for quality assessment. The pooled sensitivity, specificity, and area under the curve (AUC) of the summary receiver operating curve were calculated to evaluate the diagnostic performance of FEV 1 /FEV 6 in detecting airway obstruction and COPD and to determine the optimal cutoff value. Sensitivity analyses, subgroup analyses and meta-regression were performed to explore the source of heterogeneity. Results With 28 eligible articles and 65,744 subjects, the FEV 1 /FEV 6 ratio showed good diagnostic performance in detecting both airway obstruction (sensitivity: 0.87, specificity: 0.94, AUC 0.95) and COPD (sensitivity: 0.83, specificity: 0.88, AUC 0.91). Further analyses of the optimal cutoff value suggested that an FEV 1 /FEV 6 <0.72 was the best criterion for detecting airway obstruction (sensitivity: 0.84, specificity: 0.97, AUC 0.96), whereas an FEV 1 /FEV 6 <0.74 was the best criterion for detecting COPD (sensitivity: 0.87, specificity: 0.89, AUC 0.93). The results of subgroup analyses and meta-regression suggested that study design and geographical location may affect the heterogeneity of both sensitivity and specificity in detecting airway obstruction and COPD. Conclusion The FEV 1 /FEV 6 may serve as an easily accessible alternative in detecting airway obstruction and COPD. However, application of FEV 1 /FEV 6 may also be constrained by availability and affordability of devices. Further studies are required to determine the best-suited population for FEV 1 /FEV 6 application.

OBJECTIVES:To explore and compare the diagnostic performance of multiple case-finding approaches in screening for chronic obstructive pulmonary disease (COPD). STUDY DESIGN:Systematic review and network meta-analysis. METHODS:Records from PubMed, Embase, Web of Science and Scopus were screened to identify eligible studies. A direct meta-analysis was performed to evaluate the pooled sensitivity, specificity and area under curve (AUC) of each questionnaire. An additional network meta-analysis was subsequently conducted to perform network comparisons. The surface under the cumulative ranking (SUCRA) was also conducted to rank all screening methods according to sensitivity and specificity, respectively. RESULTS:A total of 31 studies with 70,693 participants covering 11 screening approaches were included in this meta-analysis. The COPD diagnostic questionnaire (CDQ) reached the highest sensitivity (0.78, 95%CI 0.70, 0.84) and AUC (0.76, 95%CI 0.72, 0.79) among all approaches in the direct meta-analysis. In the network meta-analysis, the sensitivity rankings of all screening approaches based on SUCRA were: CDQ (83.9) > CAPTURE (62.3) > IPAG (58.0) > PUMA (52.8) > COPD-PS + PEF (52.3) > COPD-PS (49.1) > COPD-SQ (41.1) > COPD-SQ + PEF (33.6) > LFQ (33.5) > CAPTURE + PEF (24.9) > COLA-6 (8.6). The specificity rankings were: COLA-6 (75.8) > COPD-SQ + PEF (75.3) > PUMA (56.7) > CAPTURE + PEF (55.6) > COPD-PS (47.9) > LFQ (42.7) > COPD-PS + PEF (41.7) > COPD-SQ (38.3) > IPAG (33.0) > CDQ (25.7) > CAPTURE (7.3). CONCLUSIONS:CDQ, CAPTURE, and IPAG ranked the three highest in terms of sensitivity, whereas COLA-6, COPD-SQ combined with PEF, and PUMA ranked the three highest in terms of specificity. Further studies are still needed to explore effective COPD screening strategies in different settings.

OBJECTIVE:To investigate the prevalence of depression and anxiety in interstitial lung disease (ILD) and reveal whether ILD is causally associated with depression and anxiety via Mendelian randomization (MR). METHODS:Eligible studies were identified and selected from Web of Science, PubMed and Scopus. The pooled prevalence of depression and anxiety in ILD, as well as the clinical characteristics of ILD with depression or anxiety, were assessed. Sensitivity analyses, subgroup analyses and meta-regression were applied for heterogeneity assessments. Data of MR analysis were derived from the UK biobank and Finngen cohort, and the inverse variance weighting approach was selected as the main approach for causality evaluation. RESULTS:A total of 35 studies were included in this meta-analysis, with 34 studies reporting depression in ILD and 21 reporting anxiety in ILD. The pooled prevalence of depression and anxiety in ILD were 22% (95% CI 17%, 26%, I2 = 97%) and 25% (95% CI 18%, 32%, I2 = 98%), respectively. There was no significant difference in the prevalence of depression (p = 0.41) or anxiety (p = 0.39) across various subtypes of ILD. ILD patients with depression had a lower BMI (MD -2.11, 95% CI -3.82, -0.41, p = 0.02). Results of MR analysis revealed no causal associations for either the ILD-depression (OR 1.000, 95% CI 0.997, 1.003; p = 0.962) or the ILD-anxiety (OR 1.000, 95% CI 0.998, 1.002; p = 0.888) relationships. CONCLUSION:Although the prevalence of depression and anxiety were high in patients with ILD, no causal relationship was observed. Future studies are needed to investigate the intricate association between ILD and mental health.

Objective: Reducing the length of hospital stay (LOS) is a core objective in the management of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). This study aimed to develop an interpretable and clinically applicable machine learning tool for predicting prolonged LOS in this population. Methods: This retrospective three-center study enrolled 1342 patients, who were randomly allocated to a training set (70%) and a test set (30%). Candidate predictors were screened using least absolute shrinkage and selection operator (LASSO) regression, and six machine learning models were developed and compared: logistic regression, random forest, gradient boosting machine, CatBoost, support vector machine, and neural network. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis. Model interpretability was achieved through SHapley Additive exPlanations (SHAP) and subgroup analyses. Results: Prolonged LOS, defined as >10 days (the median LOS in the training set), occurred in 42.0% of patients. Nine predictors were identified, including daily inhaled medication use, sputum microbiological examination, antibiotic administration, corticosteroid therapy, diuretic use, ICU admission, oxygenation index, platelet count, and neutrophil count. The random forest model demonstrated superior and consistent discriminative performance, achieving an AUC of 0.778 (95% CI: 0.748-0.807) in the training set and 0.721 (95% CI: 0.672-0.771) in the test set. SHAP analysis ranked diuretic use, daily inhaled medication use, corticosteroid therapy, sputum microbiological examination, and antibiotic administration as the five most influential features, revealing treatment-related variables associated with prolonged LOS. Subgroup analyses indicated better predictive performance in lower-risk patients (age ≤ 65 years with eGFR 1-2 stage). Conclusions: Random Forest may enable to promptly identify prolonged LOS high-risk patients, enhancing clinical vigilance and optimizing healthcare resource allocation in AECOPD patients.

BACKGROUND:Differentiating pleural effusion remains a challenge in clinical practice. Serum and effusion chemistries help pulmonologists assess the risk of underlying causes and select further diagnostic procedures. Amino acids (AAs) in body fluids are promising tools for estimating the probability of underlying causes. This proof-of-concept study aimed to investigate the accessibility of serum and pleural fluid AAs in distinguishing the four major etiologies of pleural effusions: malignancy, heart failure, tuberculosis, and pneumonia. METHODS:This study prospectively enrolled 153 patients with pleural effusion and unknown causes on admission. The concentrations of 11 AAs in both pleural fluid and serum were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Logistic regression was used to investigate the potential of the AAs panel. The receiver operating characteristic (ROC) curve was used to assess the performance of the AAs panel. Decision curve analysis (DCA) was used to evaluate the net benefit of the panel for patients with pleural effusion. RESULTS:Our study included pleural effusions caused by heart failure (n = 23, 15%), malignancy (n = 66, 43%), pneumonia (n = 32, 21%), tuberculosis pleurisy (n = 20, 13%), and other causes (n = 8, 5%). Significant differences were observed among various AAs, including alanine and phenylalanine. The areas under the curves (AUCs) for the 11-AA panel in serum to identify four different causes were all ≥0.75. Among them, the AUC for heart failure-related pleural effusion was 0.90 (95% CI: 0.83-0.97). Furthermore, the decision curves for the AAs panels were consistently above the reference lines. CONCLUSIONS:This proof-of-concept study finds that AAs detection in pleural effusion and serum is possible and feasible, but currently has a minor to moderate added diagnostic role.

This survey aimed to investigate the availability of drugs for stable chronic obstructive pulmonary disease (COPD) treatment in Chinese hospitals and to determine whether drug availability significantly varied among hospitals with different characteristics. A well-constructed questionnaire was designed according to the Chinese Guidelines for the Diagnosis and Management of COPD (revised version 2021). Both inhaled drugs (monotherapy, double therapy and triple therapy) and oral drugs (expectorants, theophylline, antibiotics, and bacterial lysates) were included in this survey. Doctors from different hospitals completed the survey via WeChat. The availability of each category and kind of drug was analyzed based on final valid responses. Subgroup analyses were also conducted to reveal drug availability in hospitals with different characteristics. A total of 1018 hospitals with different characteristics were enrolled in this survey, with 53.73

OBJECTIVE:To investigate whether chronic obstructive pulmonary disease (COPD) and asthma increase the risk of gallstones based on the National Health and Nutrition Examination Survey (NHANES) and Mendelian randomization (MR). METHODS:Data from the NHANES 2017-2023 were included in the cross-sectional study. Diagnoses of COPD, asthma and gallstones were obtained from self-report questionnaires. Multivariate logistic regression, subgroup analyses and interaction tests were applied to explore these associations. Data for MR analysis were obtained from the Finnish cohort and the Integrative Epidemiology Unit (IEU). The inverse variance weighting (IVW) estimate was applied as the main approach to determine the causality of associations. RESULTS:A total of 8,728 participants were enrolled in the cross-sectional study. Both COPD (OR 1,842, 95% CI 1.144, 2.968, p = 0.015) and asthma (OR 1.434, 95% CI 1.093, 1.883, p = 0.012) were associated with increased gallstone risk before and after covariate adjustments, and diabetes history may interact with the COPD-gallstone association (p = 0.020). In MR analysis, although a causal association was observed between COPD and gallstones (OR 1.216, 95% CI 1.023, 1.445; p = 0.026), leave-one-out analysis suggested that the causal association disappeared without serpin family A member 1 (SERPINA1). No causal association was observed between asthma and gallstones (OR 1.016, 95% CI 0.932, 1.108; p = 0.718). CONCLUSIONS:Although both COPD and asthma were positively associated with gallstones based on NHANES, the COPD-gallstone association was largely driven by SERPINA1, and no causality was observed in asthma-gallstone association. The available evidence provided limited support for causal associations between obstructive lung diseases and gallstones.

BACKGROUND:The coexisting prevalence and causal associations between obstructive sleep apnea (OSA) and pulmonary hypertension (PH) warranted further investigations. OBJECTIVES:To investigate the prevalence of PH in patients with OSA and OSA in patients with PH and reveal the bidirectional causal association between OSA and PH via Mendelian randomization (MR). METHODS:Eligible records were selected from PubMed, Web of Science and Scopus. The pooled prevalence of PH in OSA patients and OSA in PH patients, as well as the clinical characteristics of patients with PH-OSA overlap were evaluated. MR data were obtained from the Integrative Epidemiology Unit and the Finngen cohort. The inverse variance weighted mode was applied as the main approach in the MR analysis. MR‒Egger regression, leave-one-out analysis and the Cochrane Q test were also conducted. RESULTS:Thirteen studies with 1792 participants were included. The pooled prevalence of PH in OSA and OSA in PH reached 36 % and 34 %, respectively. Patients with OSA-PH overlap were associated with a lower FEV1/FVC (%) compared with OSA patients without PH, and were associated with male sex, older age (year), greater body mass index (kg/m2) and greater apnea‒hypopnea index (n/h) compared with PH patients without OSA. The MR suggested that OSA has a causal effect on PH, whereas PH has no causal effect on OSA. CONCLUSION:OSA and PH are highly prevalent mutual comorbidities. OSA appears to be causally linked to PH. However, further prospective and mechanistic studies are required to confirm this directionality and determine the clinical impact.

Rational:Asthma severity assessment is essential for asthma management. Transcriptomics contributes substantially to asthma pathogenesis. Then, this study aimed to explore asthma severity-associated transcriptomics profile and promising biomarkers for asthma severity prediction. Methods:In discovery cohort, induced sputum cells from 3 non-severe and 3 severe asthma patients were collected and analyzed using RNA-seq. Multivariate analysis was performed to explore asthma severity-associated transcriptomics profile and differential expressed genes (DEGs). The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used for pathway enrichment analysis. Subsequently, based on the previous study and clinical experience, the mRNA expressions of 6 overlapped asthma severity-associated DEGs and C3 in induced sputum cells and serum C3 were verified in validation cohort. Results:Distinct asthma severity-associated transcriptomics profile was identified in induced sputum cells in discovery cohort. Then, 345 DEGs were found, of which 38 terms and 32 pathways were enriched using GO and KEGG, respectively. In validation cohort, the mRNA expressions of ZNF331, CD163, MACC1, ADAMTS2, and C3 were increased, and RYR1 and NRXN3 were decreased in induced sputum cells in severe asthma. Meanwhile, the AUC of ROC was 0.890 for serum C3 in asthma severity prediction, with the best cut-off of 1.272 g/L. Conclusion:Collectively, this study provides the first identification of the association between induced sputum cells transcriptomics profile and asthma severity, indicating the potential value of transcriptomics for asthma management. The study also reveals the promising value of serum C3 for predicting asthma severity in clinical practice.

Autism is a prevalent neurodevelopmental disorder characterized by social deficits. Environmental factors, such as prenatal exposure to valproic acid (VPA), are major risk factors for the development of autism in offspring. Environmental epigenetics investigates how environmental factors influence gene expression and function. Exosomal miRNAs carry epigenetic information, but their role in autism remains unknown. Here, we found that prenatal VPA exposure reduced the majority of exosomal miRNA expressions in male newborn amygdala tissue, with exosomal miR-215-5p showing the highest decline. Reduced exosomal miR-215-5p increased neuronal lncRNA NEAT1 expression. Overexpressed neuronal NEAT1 increased the recruitment of the HSP90AB1-MAPK1-CRMP2 complex, which elevated phosphorylated CRMP2 (p-CRMP2) levels. Enhanced p-CRMP2 acted as an "eat me" signal to microglia, resulting in excessive synaptic pruning and aberrant synaptic maturation. Increasing neuronal p-CRMP2 levels via phosphorylation virus T514E or overexpression of MAPK1 promoted microglial synaptic pruning, leading to synaptic defects and social dysfunction. Furthermore, NEAT1 silencing or MAPK1 inhibition reversed the elevated p-CRMP2 levels in VPA-exposed offspring, hence preventing excessive synaptic pruning and social dysfunction. These findings suggested that prenatal VPA exposure reduced exosomal miR-215-5p and activated NEAT1/MAPK1/p-CRMP2 pathway, which resulted in abnormal synaptic development and social interaction disorders.

This study aims to discover drug targeted genes and explore the potential epigenetics mechanisms in bronchiectasis. Cis-expression quantitative trait locus (eQTL) was obtained as exposure, and bronchiectasis from the FinnGen cohort was used as outcome. Mendelian Randomization (MR) was performed to identify therapeutic targets associated with bronchiectasis. Colocalization and summary-data-based MR (SMR) analyses were carried out to further confirm the causal roles of candidate genes in bronchiectasis. The value of these drug targets was validated via drug prediction and molecular docking. Finally, we used mediation analysis to identify the DNA methylation QTLs to bronchiectasis mediated by candidate genes. Ten drug targets were significantly associated with bronchiectasis. Strong evidence for the colocalization of ACVR2A and VRK2 with bronchiectasis was found (PP.H4 > 0.75). SMR analysis revealed that higher expressions of DDR1 and VRK2 were linked to a higher risk of bronchiectasis, and higher expressions of SCD5, TNFRSF4 and XCL2 were linked to a lower risk of bronchiectasis. Finally, mediation analysis revealed potential causality effect of the DNA methylation site cg21568453 to bronchiectasis risk via VRK2. The increased expression of VRK2 regulated by DNA methylation at cg21568453 may promote the occurrence of bronchiectasis.