Analysis of clinical characteristics, prognosis and influencing factors in patients with bronchiectasis-chronic obstructive pulmonary disease overlap syndrome: A prospective study for more than five years.

Background: Considering the large population of bronchiectasis and chronic obstructive pulmonary disease (COPD) patients in China, we aimed to conduct a thorough analysis that investigates the clinical characteristics and prognosis of bronchiectasis-COPD overlap syndrome (BCOS). Further, we aimed to explore factors associated with acute exacerbation and death in BCOS, which may be of value in its early diagnosis and intervention. Methods: We recruited inpatients with COPD from the second Xiangya Hospital of Central South University in China in August 2016, with follow-up until March 2022. Patients in the BCOS group had to meet the criteria for diagnosing bronchiectasis. We used self-completion questionnaires, clinical records, and self-reported data as primary data collection methods. We used Kaplan-Meier survival analyses and Cox proportional hazard models to assess the risk of severe acute exacerbation and death for BCOS during the follow-up period. Results: A total of 875 patients were included and followed up. Patients in the BCOS group had more females, fewer smokers, lower discharge COPD assessment test (CAT) scores, lower forced vital capacity (FVC), a higher likelihood of co-occurring active tuberculosis, higher levels of eosinophils and inflammatory markers, and a higher rate of positive sputum cultures for Pseudomonas aeruginosa than patients in the COPD-only group. Patients in the acute exacerbation group (AE+) were found to have lower body mass index (BMI), more frequent acute exacerbations, higher modified Medical Research Council (mMRC) dyspnoea grade on admission, higher inflammatory markers, lower FVC, higher rates of using inhaled bronchodilators, and higher rates of both positive and Pseudomonas aeruginosa positive sputum cultures. Patients in the 'death' group were older, had a lower BMI, had spent longer time in the hospital, had higher mMRC dyspnoea grade and CAT scores upon admission and discharge, had higher levels of inflammatory markers, lower rates of using inhaled bronchodilators, were more likely to have a combination of pulmonary heart disease and obsolete pulmonary tuberculosis, as well as a higher rate of fungus-positive sputum cultures. Both erythrocyte sedimentation rate at baseline and Pseudomonas aeruginosa culture positivity were confirmed as independent predictors of severe acute exacerbation in multivariate analysis during the years of follow-up. Fungus culture positivity baseline blood urea nitrogen, baseline lymphocyte count, comorbidities with obsolete pulmonary tuberculosis and comorbidities with pulmonary heart disease were verified as independent predictors of death in multivariate analysis during the years of follow-up. Kaplan-Meier curves under survival analysis demonstrated no statistically significant difference in mortality between the COPD and the BCOS groups at the full one, two, and three years of follow-up. Conclusions: Patients with BCOS present with reduced lung function, increased susceptibility to different complications, elevated blood eosinophils and inflammatory markers, and elevated rates of positive Pseudomonas aeruginosa cultures. These distinctive markers are linked to a greater risk of severe acute exacerbations and mortality.

MiRNA-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via the Shh signaling pathway.

INTRODUCTION: The aim of the study is the regulatory effect of MicroRNA-210 (MiR-210) on cigarette smoke extract (CSE)-induced mouse lung epithelial type II cells (MLE-12) apoptosis and determine whether the MiR-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via Shh signaling pathway. METHODS: Expression of MiR-210 in CSE-induced MLE-12 was assessed by qRT-PCR. The emphysema mouse model and MiR-210 knockdown mice were each established by inhaling cigarette smoke or intratracheal lentiviral vector instillation. The Sonic hedgehog (Shh), Ptch1, Gli1, B-cell lymphoma-2 (Bcl-2), and Caspase 3 protein expressions were detected by Western blotting. mRNA expressions of MiR-210, Shh, Ptch1, and Gli1 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Apoptotic ratios in mice and CSE-induced HPVEC were assessed using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays and flow cytometry. RESULTS: Our results showed that MiR-210 mRNA levels were significantly down-regulated in the CSE-induced MLE 12. MLE 12 apoptosis with down-regulated Shh, Ptch1, Gli1, and Bcl-2 expression, increased Caspase 3 expression in the emphysema mouse model and CSE-induced MLE 12. Knockdown MiR-210 can facilitate cell apoptosis and emphysema via the Shh signaling pathway in mice. In vitro, MiR-210 can attenuate the apoptosis of CSE-exposed MLE 12. Moreover, MiR-210 regulated the Shh pathway and promoted its expression. CONCLUSIONS: MiRNA-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via the Shh signaling pathway. The present study reveals that MiRNA-210 may be a key regulator of cellular apoptosis and could be explored as a potential therapeutic target in the future.

Does the 2017 global initiative for chronic obstructive lung disease revision really improve the assessment of Chinese chronic obstructive pulmonary disease patients? A multicenter prospective study for more than 5 years.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 proposed a new classification that reclassified many chronic obstructive pulmonary disease (COPD) patients from group D to B. However, there is a paucity of data related to the comparison between reclassified and non-reclassified COPD patients in terms of long-term prognosis. This study aimed to investigate long-term outcomes of them and determine whether the GOLD 2017 revision improved the assessment of COPD patients. METHODS: This observational, multicenter, prospective study recruited outpatients at 12 tertiary hospitals in China from November 2016 to February 2018 and followed them up until February 2022. All enrolled patients were classified into groups A to D based on GOLD 2017, and the subjects in group B included patients reclassified from group D to B (group DB) and those remaining in group B (group BB). Incidence rates and hazard ratios (HRs) were calculated for the exacerbation of COPD and hospitalization in each group. RESULTS: We included and followed up 845 patients. During the first year of follow-up, the GOLD 2017 classification had a better discrimination ability for different risks of COPD exacerbation and hospitalization than GOLD 2013. Group DB was associated with a higher risk of moderate-to-severe exacerbation (HR = 1.88, 95% confidence interval [CI] = 1.37-2.59, P  <0.001) and hospitalization for COPD exacerbation (HR = 2.23, 95% CI = 1.29-3.85, P  = 0.004) than group BB. However, during the last year of follow-up, the differences in the risks of frequent exacerbations and hospitalizations between group DB and BB were not statistically significant (frequent exacerbations: HR = 1.02, 95% CI = 0.51-2.03, P  = 0.955; frequent hospitalizations: HR = 1.66, 95% CI = 0.58-4.78, P  = 0.348). The mortality rates of the two groups were both approximately 9.0% during the entire follow-up period. CONCLUSIONS: The long-term prognosis of patients reclassified into group B and of those remaining in group B was similar, although patients reclassified from group D to group B had worse short-term outcomes. The GOLD 2017 revision could improve the assessment of Chinese COPD patients in terms of long-term prognosis.

Long noncoding RNA HOTAIR facilitates pulmonary vascular endothelial cell apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in COPD.

BACKGROUND: To study the regulatory effect of Long non-coding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) on pulmonary vascular endothelial cell (HPVEC) apoptosis and determine whether the HOTAIR facilitate HPVEC apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in chronic obstructive pulmonary disease (COPD). METHODS: LncRNA array was used to measure the differentially expressed lncRNAs in COPD and non-COPD lung tissues. Expression of HOTAIR in COPD patient lungs and cigarette smoke extract (CSE)-induced HPVEC was assessed by qRT-PCR. The location of HOTAIR was determined in COPD patient lungs and HPVEC by RNA in situ hybridization (RNA-ISH). The emphysema mouse model and HOTAIR knockdown mice were each established by inhaling cigarette smoke or intratracheal lentiviral vectors instillation. The dysregulation of DNA methyltransferase enzyme 1 (DNMT1), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and Cleaved-caspase 3 protein expression were detected by Western blotting. HOTAIR, DNMT1, Bcl-2 and Bax mRNA expression were measured by quantitative real-time polymerase chain reaction. TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays were used to assess apoptotic ratio in mice and CSE-induced HPVEC. Methylation-specific PCR (MSP) assay was conducted to observe the alterations in the methylation of the Bcl-2 promoter in specimens. RNA pull-down assay was used for analysis of the correlation between HOTAIR and DNMT1. RESULTS: The expression levels of the HOTAIR were up-regulated in COPD patient lungs and CSE-induced HPVEC. HPVEC apoptosis with down-regulated Bcl-2 expression, increased promoter methylation, DNMT1, Bax and Cleaved-caspase 3 expression was found in emphysema mouse model and CSE-induced HPVEC. Knockdown HOTAIR can attenuate cell apoptosis and emphysema via DNMT1 mediated hypermethylation of Bcl-2 promoter in mice. In vitro, HOTAIR can aggravate the apoptosis of CSE-exposed HPVEC. DNMT1 was a target of HOTAIR and had a positive correlation with HOTAIR. CONCLUSION: HOTAIR facilitates HPVEC apoptosis via DNMT1 mediated hypermethylation of Bcl-2 promoter in COPD, and attenuating the expression of HOTAIR may be a new therapy to prevent COPD.

Subgroup analysis reveals higher reliability of the new comprehensive evaluation of Global Initiative for Chronic Obstructive Lung Disease 2019.

To estimate the severity of the disease in outpatients with chronic obstructive pulmonary disease (COPD) in Hunan Province, China and use the subgroup analysis to evaluate the reliability of the new comprehensive evaluation of Global Initiative for Chronic Obstructive Lung Disease (GOLD). COPD outpatients from 12 medical centers in Hunan Province, China were stratified into groups A-D, and group D patients were further stratified into subgroups D1-D3 according to the GOLD 2016 and 2019 comprehensive assessment. Demography, clinical characteristics and medications were compared among groups. In 1017 COPD outpatients, the distribution from group A to D and subgroup D1 to D3 was 41 (4.0%), 249 (24.5%), 17 (1.7%), 710 (69.8%) and 214 (30.2%), 204 (28.7%), 292 (41.1%), according to GOLD 2016. In terms of demographic and clinical characteristics related to A-D groups, there was a significant difference in COPD assessment test (CAT), modified Medical British Research Council (mMRC), the clinical COPD questionnaire(CCQ), age, BMI, education level, smoking history, comorbidities, the course of chronic bronchitis/emphysema, number of exacerbations/hospitalisations in the previous year, treatment protocols, forced expiratory volume in one second (FEV1) % predicted, and FEV1/forced vital capacity (FVC) (p < 0.01). Furthermore, some patients in groups C-D regrouped to groups A-B were all C1 and D1 subgroups according to GOLD 2019. Comparing subgroup D1 with group B, subgroup D2 and subgroup D3, it was found that the demography, clinical characteristics and medications of subgroup D1 were the closest to group B, according to GOLD 2016 (p < 0.01). The disease severity of outpatients with COPD in Hunan Province was more pronounced in group B and D and patients in groups A-D had different demography, clinical characteristics and medications. Subgroup analysis can explain to a certain extent that GOLD2019's new comprehensive assessment is more reliable than GOLD 2016.

Analysis of diagnostic delay and its influencing factors in patients with chronic obstructive pulmonary disease: a cross-sectional study.

To explore the status of diagnostic delay and to clarify its potentially influencing factors in patients with chronic obstructive pulmonary disease (COPD). A cross-sectional study was conducted in a Chinese tertiary hospital between July 2019 and February 2020. A total of 408 eligible outpatients with COPD were recruited, and relevant data were collected in the form of questionnaires. Diagnostic delay was compared among different characteristics using the Wilcoxon test and Kruskal-Wallis H test. Multivariable linear regression analysis was performed to determine the factors related to diagnostic delay. The median (interquartile range [IQR]) duration of diagnostic delay was 230 (50-720) days. The proportions of COPD patients who chose tertiary, secondary, and first-level hospitals for the first visit were 53.7%, 29.9%, and 16.4%, respectively. Additionally, the proportions of patients who underwent pulmonary function tests for the first visit in tertiary, secondary, and first-level hospitals were 74.0%, 24.6%, and 1.5% (p < 0.001), respectively. In terms of characteristics related to diagnostic delay, there was a significant difference in residence, resident manner, COPD assessment test (CAT) score, modified Medical British Research Council (mMRC) dyspnea scale, age, forced expiratory volume in one second (FEV1) % predicted, and years of education (all p < 0.01). Linear regression analysis showed that significant predictors of diagnostic delay included FEV1% predicted (p < 0.05), resident manner (p < 0.001), and years of education (p < 0.01). Our study indicates that varying degrees of diagnostic delay may exist in patients with COPD. Measures are needed to intervene in the potential factors associated with diagnostic delay.

The relationship between inflammation and neurocognitive dysfunction in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS), a state of sleep disorder, is characterized by repetitive apnea, chronic hypoxia, oxygen desaturation, and hypercapnia. Previous studies have revealed that intermittent hypoxia (IH) conditions in OSAS patients elicited neuron injury (especially in the hippocampus and cortex), leading to cognitive dysfunction, a significant and extraordinary complication of OSAS patients. The repeated courses of airway collapse and obstruction in OSAS patients resulted in apnea and arousal during sleep, leading to IH and excessive daytime sleepiness (EDS) and subsequently contributing to the development of inflammation. IH-mediated inflammation could further trigger various types of cognitive dysfunction. Many researchers have found that, besides continuous positive airway pressure (CPAP) treatment and surgery, anti-inflammatory substances might alleviate IH-induced neurocognitive dysfunction. Clarifying the role of inflammation in IH-mediated cognitive impairment is crucial for potentially valuable therapies and future research in the related domain. The objective of this article was to critically review the relationship between inflammation and cognitive deficits in OSAS.

Classification and treatment of chronic obstructive pulmonary disease outpatients in China according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017: comparison with GOLD 2014.

BACKGROUND: In 2017, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposed new classification criteria for patients with chronic obstructive pulmonary disease (COPD), which categorizes them into groups A-D based on risk of exacerbations and symptoms. The impact of the 2017 revisions on categorization and subsequent drug selection has been insufficiently studied in China. METHODS: This observational, multicenter, cross-sectional study recruited patients attending the outpatient clinics of 12 tertiary hospitals in China between April 2016 and July 2018. Patients were classified according to the GOLD 2014 and 2017 classification criteria and profiled based on categorization, demographics, clinical characteristics, and treatment regimens. RESULTS: In total, 1,278 COPD patients [mean age (±SD), 62.4±8.4 years; body mass index (BMI), 22.3±3.4 kg/m2] were included. According to the GOLD 2014 and 2017 classification criteria, the distribution in groups A-D was 58 (4.5%), 288 (22.5%), 28 (2.2%), 904 (70.7%) and 71 (5.6%), 573 (44.8%), 15 (1.2%), 619 (48.4%), respectively. Overall, 32% of patients in groups C-D were reclassified to groups A-B. Based on both GOLD 2014 and 2017, low BMI and education level were independent risk factors for high risk of exacerbation (i.e., being in groups C-D) (P<0.05). The patients who were reclassified from group D to B were younger and had fewer symptoms than those who remained in group D. The most frequently prescribed regimen was triple inhaled treatment (39.4%). Inhaled corticosteroids (ICS) were prescribed across all groups, and 205 (71.9%) of the 285 patients who were reclassified from group D to B were treated with ICS. CONCLUSIONS: GOLD 2017 reclassified COPD patients to low-risk groups. The risk of exacerbation increased with decreased BMI or education levels. Overtreatment was observed in many patients, and physicians should reexamine treatment patterns for patients reclassified into low-risk groups.