The Nonlinear Relationship Between High-Density Lipoprotein and Changes in Pulmonary Structure Function and Pulmonary Function in COPD Patients in China.

Background: The previous findings on the correlation between spirometry and high-density lipoprotein (HDL) cholesterol are intriguing yet conflicting. The aim of this research is to evaluate the relationship between HDL levels and spirometry as well as imaging parameters in patients with chronic obstructive pulmonary disease (COPD) in China. Methods: This study encompasses a total of 907 COPD patients. Participants with complete data from questionnaire interviews, lipid profile examinations, spirometry testing, and computed tomography (CT) scans were included in the analysis. A generalized additive model was employed to identify the non-linear relationship between HDL levels and both spirometry and imaging parameters. In the presence of non-linear correlations, segmented linear regression model was applied to ascertain threshold effects. Results: After adjusting for various factors, we found a non-linear correlation between HDL levels and spirometry/imaging parameters, with an inflection point at 4.2 (66 mg/dL). When Ln (HDL) was below 4.2, each unit increase correlated significantly with reduced post-bronchodilator FEV1 (0.32L, 95% CI: 0.09-0.55), decreased predicted FEV1% (11.0%, 95% CI: 2.7-19.3), and lowered FEV1/FVC (8.0%, 95% CI: 4.0-12.0), along with notable increases in Ln (LAA-950) by 1.20 (95% CI: 0.60-1.79) and Ln (LAA-856) by 0.77 (95% CI: 0.37-1.17). However, no significant associations were observed when Ln (HDL) was greater than or equal to 4.2. Conclusion: A non-linear correlation existed between HDL levels with lung function and CT imaging in COPD patients. Prior to reaching 66 mg/dL, an elevation in HDL was significantly associated with impaired lung function, more severe gas trapping and emphysema.

Mechanism exploration of synergistic photo-immunotherapy strategy based on a novel exosome-like nanosystem for remodeling the immune microenvironment of HCC.

The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy. Thereafter, M1NVs can induce M1 repolarization of TAMs, resulting in increased infiltration of cytotoxic T lymphocytes within the tumor to promote tumor regression. This study investigated the effect of phototherapy on the immune environment of liver cancer using single-cell RNA sequencing (scRNA-seq) by comparing HCC tissues before and after MPDA/ICG@M1NVs + NIR treatment. The results showed significant shifts in cell composition and gene expression, with decreases in epithelial cells, B cells, and macrophages and increases in neutrophils and myeloid cells. Additionally, gene analysis indicated a reduction in pro-inflammatory signals and immunosuppressive functions, along with enhanced B-cell function and anti-tumor immunity, downregulation of the Gtsf1 gene in the epithelial cells of the MPDA/ICG @M1NVs + NIR group, and decreased expression of the lars2 gene in immune subpopulations. Eno3 expression is reduced in M1 macrophages, whereas Clec4a3 expression is downregulated in M2 macrophages. Notably, the B cell population decreased, whereas Pou2f2 expression increased. These genes regulate cell growth, death, metabolism, and tumor environment, indicating their key role in HCC progression. This study highlights the potential for understanding cellular and molecular dynamics to improve immunotherapy.

Clinical features and associated factors of impaired ventilatory efficiency: findings from the ECOPD study in China.

BACKGROUND: Impaired ventilatory efficiency during exercise is a predictor of mortality in chronic obstructive pulmonary disease. However, little is known about the clinical features and associated factors of impaired ventilatory efficiency in China. METHODS: We conducted a cross-sectional community-based study in China and collected demographic and clinical information, cardiopulmonary exercise testing, spirometry, and CT data. Impaired ventilatory efficiency was defined by a nadir ventilatory equivalent for CO2 production above the upper limit of normal. Multivariable linear and logistic regression models were used to explore the clinical features and associated factors of impaired ventilatory efficiency. RESULTS: The final analyses included 941 subjects, 702 (74.6%) of whom had normal ventilatory efficiency and 239 (25.4%) had impaired ventilatory efficiency. Participants with impaired ventilatory efficiency had more chronic respiratory symptoms, poorer lung function and exercise capacity, and more severe emphysema (natural logarithm transformation of the low-attenuation area of the lung with attenuation values below -950 Hounsfield units, logLAA-950: 0.19±0.65 vs -0.28±0.63, p<0.001) and air trapping (logLAA-856: 1.03±0.65 vs 0.68±0.70, p<0.001) than those with normal ventilatory efficiency. Older age (60-69 years, OR 3.10 (95% CI 1.33 to 7.21), p=0.009 and 70-80 years, OR 6.48 (95% CI 2.56 to 16.43), p<0.001 vs 40-49 years) and smoking (former, OR 3.19 (95% CI 1.29 to 7.86), p=0.012; current, OR 4.27 (95% CI 1.78 to 10.24), p=0.001 vs never) were identified as high risk factors of impaired ventilatory efficiency. CONCLUSIONS: Impaired ventilatory efficiency was associated with poorer respiratory characteristics. Longitudinal studies are warranted to explore the progression of individuals with impaired ventilatory efficiency.

Clinical Characteristics and 2-Year Outcomes of Chronic Obstructive Pulmonary Disease Patients With High Blood Eosinophil Counts: A Population-based Prospective Cohort Study in China.

BACKGROUND: High blood eosinophil count (BEC) is a useful biomarker for guiding inhaled corticosteroid therapy in patients with chronic obstructive pulmonary disease (COPD), yet its implications in a community setting remain underexplored. This study aimed to elucidate the clinical characteristics and outcomes of COPD patients with high BEC within the Chinese community. METHODS: We obtained baseline and 2-year follow-up data from COPD patients (post-bronchodilator forced expiratory volume in 1 second/forced vital capacity <0.70) in the early COPD study. Patients with a BEC ≥300cells/µL were classified as the high BEC group. We assessed differences in the clinical characteristics and outcomes between high and low BEC patients. Subgroup analyses were conducted on COPD patients without a history of corticosteroid use or asthma. RESULTS: Of the 897 COPD patients, 205 (22.9%) had high BEC. At baseline, high BEC patients exhibited a higher proportion of chronic respiratory symptoms, lower lung function, and more severe small airway dysfunction than low BEC patients. Over the 2-year period, high BEC patients experienced a significantly higher risk of acute exacerbations (relative risk: 1.28, 95% confidence interval: 1.09-1.49; P=0.002), even after adjusting for confounders. No significant difference was observed in lung function decline rates. The subgroup analysis yielded consistent results. CONCLUSIONS: COPD patients with high BEC in a Chinese community exhibited poorer health status, more severe small airway dysfunction, and a higher risk of exacerbations. Future research should explore the pathological mechanisms underlying the poorer prognosis in patients with high BEC.

Current therapy in amyotrophic lateral sclerosis (ALS): A review on past and future therapeutic strategies.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the first and second motoneurons (MNs), associated with muscle weakness, paralysis and finally death. The exact etiology of the disease still remains unclear. Currently, efforts to develop novel ALS treatments which target specific pathomechanisms are being studied. The mechanisms of ALS pathogenesis involve multiple factors, such as protein aggregation, glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, apoptosis, inflammation etc. Unfortunately, to date, there are only two FDA-approved drugs for ALS, riluzole and edavarone, without curative treatment for ALS. Herein, we give an overview of the many pathways and review the recent discovery and preclinical characterization of neuroprotective compounds. Meanwhile, drug combination and other therapeutic approaches are also reviewed. In the last part, we analyze the reasons of clinical failure and propose perspective on the treatment of ALS in the future.

Clinical features and 1-year outcomes of variable obstruction in participants with preserved spirometry: results from the ECOPD study in China.

BACKGROUND: There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes. METHODS: Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC <0.70) were compared with those without variable obstruction (prebronchodilator FEV1/FVC ≥0.70). We performed subgroup analyses in never smokers, former and current smokers, and different variable obstruction types (postbronchodilator FVC

Mendelian randomization analysis identifies druggable genes and drugs repurposing for chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a prevalent condition that significantly impacts public health. Unfortunately, there are few effective treatment options available. Mendelian randomization (MR) has been utilized to repurpose existing drugs and identify new therapeutic targets. The objective of this study is to identify novel therapeutic targets for COPD. Methods: Cis-expression quantitative trait loci (cis-eQTL) were extracted for 4,317 identified druggable genes from genomics and proteomics data of whole blood (eQTLGen) and lung tissue (GTEx Consortium). Genome-wide association studies (GWAS) data for doctor-diagnosed COPD, spirometry-defined COPD (Forced Expiratory Volume in one second [FEV1]/Forced Vital Capacity [FVC] <0.7), and FEV1 were obtained from the cohort of FinnGen, UK Biobank and SpiroMeta consortium. We employed Summary-data-based Mendelian Randomization (SMR), HEIDI test, and colocalization analysis to assess the causal effects of druggable gene expression on COPD and lung function. The reliability of these druggable genes was confirmed by eQTL two-sample MR and protein quantitative trait loci (pQTL) SMR, respectively. The potential effects of druggable genes were assessed through the phenome-wide association study (PheWAS). Information on drug repurposing for COPD was collected from multiple databases. Results: A total of 31 potential druggable genes associated with doctor-diagnosed COPD, spirometry-defined COPD, and FEV1 were identified through SMR, HEIDI test, and colocalization analysis. Among them, 22 genes (e.g., MMP15, PSMA4, ERBB3, and LMCD1) were further confirmed by eQTL two-sample MR and protein SMR analyses. Gene-level PheWAS revealed that ERBB3 expression might reduce inflammation, while GP9 and MRC2 were associated with other traits. The drugs Montelukast (targeting the MMP15 gene) and MARIZOMIB (targeting the PSMA4 gene) may reduce the risk of spirometry-defined COPD. Additionally, an existing small molecule inhibitor of the APH1A gene has the potential to increase FEV1. Conclusions: Our findings identified 22 potential drug targets for COPD and lung function. Prioritizing clinical trials that target these identified druggable genes with existing drugs or novel medications will be beneficial for the development of COPD treatments.

Discovery, Structure-Based Modification, In Vitro, In Vivo, and In Silico Exploration of m-Sulfamoyl Benzoamide Derivatives as Selective Butyrylcholinesterase Inhibitors for Treating Alzheimer's Disease.

For the potential therapy of Alzheimer's disease (AD), butyrylcholinesterase (BChE) has gradually gained worldwide interest in the progression of AD. This study used a pharmacophore-based virtual screening (VS) approach to identify Z32439948 as a new BChE inhibitor. Aiding by molecular docking and molecular dynamics, essential binding information was disclosed. Specifically, a subpocket was found and structure-guided design of a series of novel compounds was conducted. Derivatives were evaluated in vitro for cholinesterase inhibition and physicochemical properties (BBB, log P, and solubility). The investigation involved docking, molecular dynamics, enzyme kinetics, and surface plasmon resonance as well. The study highlighted compounds 27a (hBChE IC50 = 0.078 ± 0.03 µM) and (R)-37a (hBChE IC50 = 0.005 ± 0.001 µM) as the top-ranked BChE inhibitors. These compounds showed anti-inflammatory activity and no apparent cytotoxicity against the human neuroblastoma (SH-SY5Y) and mouse microglia (BV2) cell lines. The most active compounds exhibited the ability to improve cognition in both scopolamine- and Aß1-42 peptide-induced cognitive deficit models. They can be promising lead compounds with potential implications for treating the late stage of AD.

Clinical characterization and outcomes of impulse oscillometry-defined bronchodilator response: an ECOPD cohort-based study.

BACKGROUND: The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR. METHODS: Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ - 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ - 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model. RESULTS: This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up. CONCLUSIONS: The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

Butyrylcholinesterase-Activated Near-Infrared Fluorogenic Probe for In Vivo Theranostics of Alzheimer's Disease.

Butyrylcholinesterase (BChE) is a promising biomarker and effective therapeutic target for Alzheimer's disease (AD). Herein, we designed a BChE-activated near-infrared (NIR) probe, DTNP, which could be activated by BChE and inhibit its enzymatic activity. DTNP is composed of a cyclopropane moiety as the recognition unit, a NIR fluorophore hemicyanine as the NIR reporter, and a BChE inhibitor as the therapeutic unit. DTNP specifically binds BChE with high sensitivity and exhibits strong "turn-on" NIR fluorescence as well as nerve cell protection. In vivo imaging shows DTNP has favorable blood-brain barrier permeability and long-term tracking ability with preliminary competence in AD diagnosis. DTNP can significantly inhibit BChE activity, promote the release of ACh, and rescue learning deficits and cognitive impairment. Therefore, DTNP, the first reported and partially validated theranostic probe for the detection of BChE in AD, may provide a foundation and inspiration for imaging and therapy in AD.

Association between long-term ozone exposure and readmission for chronic obstructive pulmonary disease exacerbation.

The relationship between long-term ozone (O3) exposure and readmission for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains elusive. In this study, we collected individual-level information on AECOPD hospitalizations from a standardized electronic database in Guangzhou from January 1, 2014, to December 31, 2015. We calculated the annual mean O3 concentration prior to the dates of the index hospitalization for AECOPD using patients' residential addresses. Employing Cox proportional hazards models, we assessed the association between long-term O3 concentration and the risk of AECOPD readmission across several time frames (30 days, 90 days, 180 days, and 365 days). We estimated the disease and economic burden of AECOPD readmissions attributable to O3 using a counterfactual approach. Of the 4574 patients included in the study, 1398 (30.6%) were readmitted during the study period, with 262 (5.7%) readmitted within 30 days. The annual mean O3 concentration was 90.3 µg/m3 (standard deviation [SD] = 8.2 µg/m3). A 10-µg/m3 increase in long-term O3 concentration resulted in a hazard ratio (HR) for AECOPD readmission within 30 days of 1.28 (95% confidence interval [CI], 1.09 to 1.49), with similar results for readmission within 90, 180, and 365 days. Older patients (aged 75 years or above) and males were more susceptible (HR, 1.33; 95% CI, 1.10-1.61 and HR, 1.29; 95% CI, 1.09-1.53, respectively). The population attributable fraction for 30-day readmission due to O3 exposure was 29.0% (95% CI, 28.4%-30.0%), and the attributable mean cost per participant was 362.3 USD (354.5-370.2). Long-term exposure to elevated O3 concentrations is associated with an increased risk of AECOPD readmission, contributing to a significant disease and economic burden.

Sono-Immunotherapy Mediated Controllable Composite Nano Fluorescent Probes Reprogram the Immune Microenvironment of Hepatocellular Carcinoma.

Background: Despite the clinical efficacy of immunotherapy in treating malignant tumors, its effectiveness is often hampered by the immunosuppressive nature of the tumor microenvironment (TME). In this study, we propose the design of a nanoscale ultrasound contrast agent capable of triggering macrophage polarization and immunogenic cell death (ICD) for the treatment of hepatocellular carcinoma (HCC) through sonodynamic treatment (SDT) and immunotherapy. Methods: The re-educator (designated as ICG@C3F8-R848 NBs) is composed of the Toll-like receptor agonist resiquimod (R848) and the sonosensitizer Indocyanine green (ICG), utilizing nanobubbles (NBs) as carriers. The technique known as ultrasound-targeted nanobubble destruction (UTND) employs nanosized microbubbles and low-frequency ultrasound (LFUS) to ensure accurate drug delivery and enhance safety. Results: Following intravenous delivery, ICG@C3F8-R848 NBs have the potential to selectively target and treat primary tumors using SDT in conjunction with ultrasonography. Importantly, R848 can enhance antitumor immunity by inducing the polarization of macrophages from an M2 to an M1 phenotype. Conclusion: The SDT-initiated immunotherapy utilizing ICG@C3F8-R848 NBs demonstrates significant tumor suppression effects with minimal risk of systemic toxicity. The utilization of this self-delivery re-education technique would contribute to advancing the development of nanomedicine for the treatment of hepatocellular carcinoma.

Characteristics of inflammatory phenotypes in patients with chronic obstructive pulmonary disease: a cross-sectional study.

BACKGROUND: The relationship between airway inflammation in chronic obstructive pulmonary disease (COPD) and clinical characteristics remains unclear. This study aimed to investigate the airway inflammatory phenotypes in COPD and their association with clinical characteristics. METHODS: 895 patients with COPD were recruited from Guangdong Province, China in this study. Each patient underwent questionnaire interviews, spirometry testing, CT scans and induced sputum examination. Classification of airway inflammation phenotypes was based on sputum inflammatory cell counts. Covariance analysis was applied to assess associations with airway inflammation phenotypes. RESULTS: In this study, we found that neutrophilic phenotype (NP, 58.0%) was the most common airway inflammation phenotype in patients with COPD, followed by mixed granulocytic phenotype (MGP, 32.6%), eosinophilic phenotype (EP, 5.4%) and paucigranulocytic phenotype (PP, 4.0%). Compared with NP patients, those with MGP exhibited more frequent chronic respiratory symptoms, and a higher proportion of individuals classified under Global Initiative for Chronic Obstructive Lung Disease stages 3 and 4. After adjusting for confounding factors, MGP patients had lower lung function, and more severe emphysema and air trapping. On the contrary, patients with PP had the best pulmonary function and less emphysema and air trapping. CONCLUSIONS: NP was the most common airway inflammation phenotype in patients with COPD. Patients with MGP had more respiratory symptoms, greater loss of lung function, and more severe emphysema and gas trapping compared with those with NP. Meanwhile, PP may be a phenotype of mild damage to lung structure in patients with COPD.

Efficacy of online cognitive behavioral therapy for nonorganic erectile dysfunction in reproductive-age males during the COVID-19 pandemic: a randomized wait list-controlled trial.

BACKGROUND: Previous research has documented the impact of the COVID-19 pandemic on male sexual and mental health. However, no prior study has evaluated the efficacy of online cognitive behavioral therapy (CBT) during the COVID-19 pandemic for treating nonorganic erectile dysfunction (ED) by improving negative emotions and self-esteem. AIM: To test the efficacy of online CBT for nonorganic ED during the COVID-19 pandemic in Shanghai, China. METHODS: A randomized controlled trial was conducted during the COVID-19 pandemic. Paired t-tests and 1-way analysis of variance were used to analyze and compare erectile functioning, self-esteem, and emotional state between and within groups. OUTCOMES: The main outcome measures included scores on the 5-item International Index of Erectile Function, Rosenberg Self-esteem Scale, 9-item Patient Health Questionnaire, and 7-item Generalized Anxiety Disorder scale to evaluate erectile functioning, self-esteem, depression, and anxiety, respectively. RESULTS: In the CBT group, erectile functioning, intercourse satisfaction, orgasmic functioning, sexual desire, and overall satisfaction were significantly improved at posttreatment as compared with pretreatment (P < .05). After treatment, group differences in emotional state and self-esteem were observed between the CBT group and the control group. Results revealed that the CBT group had significantly better scores than the control group at posttreatment on the Rosenberg Self-esteem Scale (mean ± SD, 30.43 ± 6.51 vs 22.67 ± 10.74), Patient Health Questionnaire (7.07 ± 2.74 vs 11.07 ± 4.41), and Generalized Anxiety Disorder scale (8.36 ± 1.97 vs 11.13 ± 3.94; P < .05). CLINICAL IMPLICATIONS: This study represents an important advance in understanding of the efficacy of online CBT for treating nonorganic ED in reproductive-age males during the COVID-19 pandemic. STRENGTHS AND LIMITATIONS: The study participants, treatment modality, and COVID-19 pandemic background of this study are innovative and therefore strengths. However, our study has several limitations-namely, its sample size and use of self-report data to measure erectile functioning due to the pandemic. Further studies should incorporate sexual functioning-monitoring instruments as well as self-report data to measure erectile function. CONCLUSION: Online CBT clearly improved the emotional state and self-esteem of patients with ED during the COVID-19 pandemic.

Clinical features and 1-year outcomes of chronic bronchitis in participants with normal spirometry: results from the ECOPD study in China.

BACKGROUND: Evidence regarding clinical features and outcomes of individuals with non-obstructive chronic bronchitis (NOCB) remains scarce, especially in never-smokers. We aimed to investigate the clinical features and 1-year outcomes of individuals with NOCB in the Chinese population. METHODS: We obtained data on participants in the Early Chronic Obstructive Pulmonary Disease Study who had normal spirometry (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ≥0.70). NOCB was defined as chronic cough and sputum production for at least 3 months for two consecutive years or more at baseline in participants with normal spirometry. We assessed the differences in demographics, risk factors, lung function, impulse oscillometry, CT imaging and frequency of acute respiratory events between participants with and without NOCB. RESULTS: NOCB was present in 13.1% (149/1140) of participants with normal spirometry at baseline. Compared with participants without NOCB, those with NOCB had a higher proportion of men and participants with smoke exposure, occupational exposure, family history of respiratory diseases and worse respiratory symptoms (all p<0.05), but there was no significant difference in lung function. Never-smokers with NOCB had higher rates of emphysema than those without NOCB, but airway resistance was similar. Ever-smokers with NOCB had greater airway resistance than those without NOCB, but emphysema rates were similar. During 1-year follow-up, participants with NOCB had a significantly increased risk of acute respiratory events compared with participants who did not have NOCB, after adjustment for confounders (risk ratio 2.10, 95% CI 1.32 to 3.33; p=0.002). These results were robust in never-smokers and ever-smokers. CONCLUSIONS: Never-smokers and ever-smokers with NOCB had more chronic obstructive pulmonary disease-related risk factors, evidence of airway disease and greater risk of acute respiratory events than those without NOCB. Our findings support expanding the criteria defining pre-COPD to include NOCB.

Inter-relationships among neutrophilic inflammation, air trapping and future exacerbation in COPD: an analysis of ECOPD study.

BACKGROUND: The inter-relationships among neutrophilic airway inflammation, air trapping and future exacerbation in chronic obstructive pulmonary disease (COPD) remain unclear. OBJECTIVE: To evaluate the associations between sputum neutrophil proportions and future exacerbation in COPD and to determine whether these associations are modified by significant air trapping. METHODS: Participants with completed data were included and followed up to the first year in the Early Chronic Obstructive Pulmonary Disease study (n=582). Sputum neutrophil proportions and high-resolution CT-related markers were measured at baseline. Sputum neutrophil proportions were dichotomised based on their median (86.2%) to low and high levels. In addition, subjects were divided into the air trapping or non-air trapping group. Outcomes of interest included COPD exacerbation (separately any, severe and frequent exacerbation, occurring in the first year of follow-up). Multivariable logistic regressions were performed to examine the risk of severe exacerbation and frequent exacerbation with either neutrophilic airway inflammation groups or air trapping groups. RESULTS: There was no significant difference between high and low levels of sputum neutrophil proportions in the exacerbation in the preceding year. After the first year of follow-up, subjects with high sputum neutrophil proportions had increased risks of severe exacerbation (OR=1.68, 95% CI: 1.09 to 2.62, p=0.020). Subjects with high sputum neutrophil proportions and significant air trapping had increased odds of having frequent exacerbation (OR=3.29, 95% CI: 1.30 to 9.37, p=0.017) and having severe exacerbation (OR=2.72, 95% CI: 1.42 to 5.43, p=0.003) when compared with those who had low sputum neutrophil proportions and non-air trapping. CONCLUSIONS: We found that subjects with high sputum neutrophil proportions and significant air trapping are prone to future exacerbation of COPD. It may be a helpful predictor of future exacerbation.

The Short-term Efficacy of Contrast-enhanced Ultrasound (CEUS) and Gd-EOB-DTPA-enhanced Magnetic Resonance Imaging (MRI) Fusion Imaging-guided Radiofrequency Ablation (RFA) for Colorectal Liver Metastasis (CRLM).

OBJECTIVE: This study is to explore the efficacy of contrast-enhanced ultrasound (CEUS) / Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) fusion imaging-guided（fusion group）radiofrequency ablation (RFA) versus conventional ultrasound imaging-guided (conventional group) RFA for colorectal cancer liver metastases (CRLM) in a short-term. METHODS: From December 2020 to December 2021, patients who underwent imaging-guided RFA of CRLM at our hospital with available CT/MRI images were enrolled consecutively. 22 patients with 46 lesions had undergone conventional group RFA whereas 29 patients with 63 lesions had undergone fusion group RFA. The lesion detection rate, technical success, local tumor progression (LTP) and complications were calculated. RESULT: In this retrospective study, 51 patients with 130 lesions were diagnosed with CRLM. However, there were 12 lesions and 9 lesions invisible in the conventional group and fusion group, respectively. The lesion detection rate on the fusion imaging was significantly higher than on the US or CEUS in the fusion group (P＜0.05). There were no significant differences of the detection rate between the conventional group and the fusion group (P=0.207). In both groups, the technical success rate was 100%. For local tumor progression (LTP), there were no significant differences between the two groups (P＞0.05). The complications after ablation had no significant differences between the two groups (P=0.97). CONCLUSION: CEUS/ Gd-EOB-DTPA-enhanced MRI fusion imaging is a safe and effective method for RFA in the management of CRLM patients, and it may improve the therapeutic effect by detecting small lesions early.

Impaired exercise capacity in individuals with non-obstructive small airway dysfunction.

Background: Whether individuals with non-obstructive spirometry-defined small airway dysfunction (SAD) have impaired exercise capacity is unclear, particularly in never-smokers. This study clarifies the degree of impaired exercise capacity and its potential cause in individuals with non-obstructive SAD. Methods: This community-based, multiyear cross-sectional study analyzed data collected in Guangdong, China from 2012-2019 by the National Science and Technology Support Plan Program. Measurements of exercise capacity [peak work rate and peak oxygen uptake ( V ˙ O 2peak )] in participants with non-obstructive spirometry-defined SAD (n=157) were compared with those in controls (n=85) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) I patients (n=239). Subgroup analyses were performed by smoking status. Results: The risk of impaired exercise capacity was significantly higher in participants with non-obstructive SAD [ V ˙ O 2peak <84%predicted, adjusted odds ratio (aOR) =2.53; 95% confidence interval (CI): 1.42-4.52] than in controls but was not significantly different from that in GOLD I patients. Results were consistent within subgroups of smoking status (ever-smokers: non-obstructive SAD vs. controls, aOR =2.44; 95% CI: 1.08-5.51; never-smokers: non-obstructive SAD vs. controls, aOR =2.38, 95% CI: 1.02-5.58). Participants with non-obstructive SAD had a significantly lower peak work rate (ß=-10.5; 95% CI: -16.3 to -4.7) and V ˙ O 2peak (%predicted, ß=-4.0; 95% CI: -7.7 to -0.2) and tended to have higher ventilatory equivalents for carbon dioxide at the ventilatory threshold ( V ˙ E / V ˙ CO 2AT , ß=1.1; 95% CI: -0.1 to 2.3) when compared with controls. Both peak work rate and V ˙ O 2peak were negatively correlated with V ˙ E / V ˙ CO 2AT . Conclusions: Although not meeting the current criteria for chronic obstructive pulmonary disease, individuals with non-obstructive SAD have impaired exercise capacity that may be associated with ventilatory inefficiency regardless of smoking status.

Clinical characteristics of airway impairment assessed by impulse oscillometry in patients with chronic obstructive pulmonary disease: findings from the ECOPD study in China.

BACKGROUND: The role of airway impairment assessed by impulse oscillometry (IOS) in patients with chronic obstructive pulmonary disease (COPD) remains unclear. Therefore, this study aimed to analyze the proportion and clinical characteristics of airway impairment assessed by IOS across COPD severities, and explore whether airway impairment is a subtype of COPD. METHODS: This study was based on cross-sectional data from the ECOPD cohort in Guangdong, China. Subjects were consecutively recruited from July 2019 to August 2021. They filled out questionnaires and underwent lung function tests, IOS and computed tomography (CT). COPD was defined as post-bronchodilator forced expiratory volume in one second/forced vital capacity < lower limit of normal (LLN). Meanwhile, airway impairment was defined as IOS parameters > upper limit of normal or < LLN. On the one hand, Poisson regression was employed to analyze the associations between acute exacerbations of COPD (AECOPD) in the previous year and airway impairment. On the other hand, logistic regression was used to assess differences in CT imaging between patients with IOS parameters' abnormalities and patients with normal IOS parameters. RESULTS: 768 COPD subjects were finally enrolled in the study. The proportion of airway impairment assessed by R5, R20, R5-R20, X5, AX, and Fres was 59.8%, 29.7%, 62.5%, 52.9%, 60.9% and 67.3%, respectively. Airway impairment assessed by IOS parameters (R5, R5-R20, X5, AX, and Fres) in patients with COPD was present across all severities of COPD, particularly in GOLD 3-4 patients. Compared with patients with normal IOS parameters, patients with IOS parameters' abnormalities had more respiratory symptoms, more severe airway obstruction and imaging structural abnormalities. Patients with IOS parameters' abnormalities assessed by R5 [risk ratio (RR): 1.58, 95% confidential interval (CI): 1.13-2.19, P = 0.007], R5-R20 [RR: 1.73, 95%CI: 1.22-2.45, P = 0.002], X5 [RR: 2.11, 95%CI: 1.51-2.95, P < 0.001], AX [RR: 2.20, 95%CI: 1.53-3.16, P < 0.001], and Fres [RR: 2.13, 95%CI: 1.44-3.15, P < 0.001] had a higher risk of AECOPD in the previous year than patients with normal IOS parameters. CONCLUSIONS: Airway impairment assessed by IOS may be a subtype of COPD. Future studies are warranted to identify the underlying mechanisms and longitudinal progression of airway impairment.