Genome-Wide DNA methylation profile analysis identifies differentially methylated loci associated with personal PM2.5 exposure in adults with asthma.

Particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) is a major environmental risk factor for acute asthma exacerbation, and the underlying mechanism is not completely understood. Studies have indicated that DNA methylation is a potential mechanism linking PM2.5 to its health effects. We conducted a panel study involving 24 adult patients with asthma in Beijing,China between 2017 and 2019. PM2.5 and other atmospheric pollutant exposure data were repeatedly measured. Blood samples were collected for genome-wide DNA methylation analysis. A linear mixed-effects (LME) model was conducted to identify differentially methylated probes (DMPs) associated with PM2.5 exposure. After filtering out probes that did not meet the criteria through quality control, 811,001 CpG sites were included in the LME model, and 36 DMPs were strongly associated with personal PM2.5 exposure at false discovery rate (FDR) < 0.05, of which 22 and 14 DMPs negatively and positively correlated with personal PM2.5 exposure, respectively. Functional analysis revealed that DMPs affected smooth muscle cell contraction and development, extracellular matrix synthesis and secretion, T cell activation and differentiation, and inflammatory factor production. This study provides evidence linking personal PM2.5 exposure to genome-wide DNA methylation in adult patients with asthma. Identifying enrichment pathways can provide biological insights into the acute health effects of PM2.5.

Portable spirometer-based pulmonary function test willingness in China: A nationwide cross-sectional study from the "Happy Breathing Program".

BACKGROUND: Understanding willingness to undergo pulmonary function tests (PFTs) and the factors associated with poor uptake of PFTs is crucial for improving early detection and treatment of chronic obstructive pulmonary disease (COPD). This study aimed to understand willingness to undergo PFTs among high-risk populations and identify any barriers that may contribute to low uptake of PFTs. METHODS: We collected data from participants in the "Happy Breathing Program" in China. Participants who did not follow physicians' recommendations to undergo PFTs were invited to complete a survey regarding their willingness to undergo PFTs and their reasons for not undergoing PFTs. We estimated the proportion of participants who were willing to undergo PFTs and examined the various reasons for participants to not undergo PFTs. We conducted univariable and multivariable logistic regressions to analyze the impact of individual-level factors on willingness to undergo PFTs. RESULTS: A total of 8475 participants who had completed the survey on willingness to undergo PFTs were included in this study. Out of these participants, 7660 (90.4%) were willing to undergo PFTs. Among those who were willing to undergo PFTs but actually did not, the main reasons for not doing so were geographical inaccessibility ( n  = 3304, 43.1%) and a lack of trust in primary healthcare institutions ( n  = 2809, 36.7%). Among the 815 participants who were unwilling to undergo PFTs, over half ( n  = 447, 54.8%) believed that they did not have health problems and would only consider PFTs when they felt unwell. In the multivariable regression, individuals who were ≤54 years old, residing in rural townships, with a secondary educational level, with medical reimbursement, still working, with occupational exposure to dust, and aware of the abbreviation "COPD" were more willing to undergo PFTs. CONCLUSIONS: Willingness to undergo PFTs was high among high-risk populations. Policymakers may consider implementing strategies such as providing financial incentives, promoting education, and establishing community-based programs to enhance the utilization of PFTs.

Associations Between Air Pollution and the Onset of Acute Exacerbations of COPD: A Time-Stratified Case-Crossover Study in China.

BACKGROUND: Associations between air pollution and the acute exacerbations (AEs) of COPD have been established primarily in time-series studies in which exposure and case data were at the aggregate level, limiting the identification of susceptible populations. RESEARCH QUESTION: Are air pollutants associated with the onset of AEs of COPD in China? Who is more susceptible to the effects of air pollutants? STUDY DESIGN AND METHODS: Data regarding AEs of COPD were obtained from the Acute Exacerbation of Chronic Obstructive Pulmonary Disease Registry study, and air pollution data were assigned to individuals based on their residential address. We adopted a time-stratified case-crossover study design combined with conditional logistic regression models to estimate the associations between six air pollutants and AEs of COPD. Stratified analyses were performed by individual characteristics, disease severity, COPD types, and the season of exacerbations. RESULTS: A total of 5,746 patients were included. At a 2-day lag, for each interquartile range increase in fine particulate matter (PM2.5) and inhalable particulate matter (PM10) concentrations, ORs for AEs of COPD were 1.054 (95% CI, 1.012-1.097) and 1.050 (95% CI, 1.009-1.092), respectively. The associations were more pronounced in participants who were younger than 65 years, had experienced at least one severe AE of COPD in the past year, received a diagnosis of COPD between 20 and 50 years of age, and experienced AEs of COPD in the cool seasons. By contrast, significant associations for nitrogen dioxide, sulfur dioxide, and carbon monoxide lost significance when excluding patients collected before 2020 or with larger distance from the monitoring station, and no significant association was observed for ozone. INTERPRETATION: This study provides robust evidence that short-term exposure to PM2.5 and PM10 was associated with higher odds of AEs of COPD onset. Individuals who are young, have severe COPD, or whose first diagnosis of COPD was made when they were between 20 and 50 years of age and experience an exacerbation during the cooler seasons may be particularly susceptible. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT2657525; URL: www. CLINICALTRIALS: gov.

Developing and validating prediction models for severe exacerbations and readmissions in patients hospitalised for COPD exacerbation (SERCO) in China: a prospective observational study.

BACKGROUND: There is a lack of individualised prediction models for patients hospitalised with chronic obstructive pulmonary disease (COPD) for clinical practice. We developed and validated prediction models of severe exacerbations and readmissions in patients hospitalised for COPD exacerbation (SERCO). METHODS: Data were obtained from the Acute Exacerbations of Chronic Obstructive Pulmonary Disease Inpatient Registry study (NCT02657525) in China. Cause-specific hazard models were used to estimate coefficients. C-statistic was used to evaluate the discrimination. Slope and intercept were used to evaluate the calibration and used for model adjustment. Models were validated internally by 10-fold cross-validation and externally using data from different regions. Risk-stratified scoring scales and nomograms were provided. The discrimination ability of the SERCO model was compared with the exacerbation history in the previous year. RESULTS: Two sets with 2196 and 1869 patients from different geographical regions were used for model development and external validation. The 12-month severe exacerbations cumulative incidence rates were 11.55% (95% CI 10.06% to 13.16%) in development cohorts and 12.30% (95% CI 10.67% to 14.05%) in validation cohorts. The COPD-specific readmission incidence rates were 11.31% (95% CI 9.83% to 12.91%) and 12.26% (95% CI 10.63% to 14.02%), respectively. Demographic characteristics, medical history, comorbidities, drug usage, Global Initiative for Chronic Obstructive Lung Disease stage and interactions were included as predictors. C-indexes for severe exacerbations were 77.3 (95% CI 70.7 to 83.9), 76.5 (95% CI 72.6 to 80.4) and 74.7 (95% CI 71.2 to 78.2) at 1, 6 and 12 months. The corresponding values for readmissions were 77.1 (95% CI 70.1 to 84.0), 76.3 (95% CI 72.3 to 80.4) and 74.5 (95% CI 71.0 to 78.0). The SERCO model was consistently discriminative and accurate with C-indexes in the derivation and internal validation groups. In external validation, the C-indexes were relatively lower at 60-70 levels. The SERCO model discriminated outcomes better than prior severe exacerbation history. The slope and intercept after adjustment showed close agreement between predicted and observed risks. However, in external validation, the models may overestimate the risk in higher-risk groups. The model-driven risk groups showed significant disparities in prognosis. CONCLUSION: The SERCO model provides individual predictions for severe exacerbation and COPD-specific readmission risk, which enables identifying high-risk patients and implementing personalised preventive intervention for patients with COPD.

Abnormal heart rate responses to exercise in non-severe COPD: relationship with pulmonary vascular volume and ventilatory efficiency.

BACKGROUND: Despite being a prognostic predictor, cardiac autonomic dysfunction (AD) has not been well investigated in chronic obstructive pulmonary disease (COPD). We aimed to characterise computed tomography (CT), spirometry, and cardiopulmonary exercise test (CPET) features of COPD patients with cardiac AD and the association of AD with CT-derived vascular and CPET-derived ventilatory efficiency metrics. METHODS: This observational cohort study included stable, non-severe COPD patients. They underwent clinical evaluation, spirometry, CPET, and CT. Cardiac AD was determined based on abnormal heart rate responses to exercise, including chronotropic incompetence (CI) or delayed heart rate recovery (HRR) during CPET. RESULTS: We included 49 patients with FEV1 of 1.2-5.0 L (51.1-129.7%), 24 (49%) had CI, and 15 (31%) had delayed HRR. According to multivariate analyses, CI was independently related to reduced vascular volume (VV; VV ≤ median; OR [95% CI], 7.26 [1.56-33.91]) and low ventilatory efficiency (nadir VE/VCO2 ≥ median; OR [95% CI], 10.67 [2.23-51.05]). Similar results were observed for delayed HRR (VV ≤ median; OR [95% CI], 11.46 [2.03-64.89], nadir VE/VCO2 ≥ median; OR [95% CI], 6.36 [1.18-34.42]). CONCLUSIONS: Cardiac AD is associated with impaired pulmonary vascular volume and ventilatory efficiency. This suggests that lung blood perfusion abnormalities may occur in these patients. Further confirmation is required in a large population-based cohort.

Efficacy and safety of a music-therapy facilitated pulmonary telerehabilitation program in COPD patients: the COPDMELODY study protocol.

Despite considerable evidence for the benefit in chronic obstructive pulmonary disease (COPD), the implementation of pulmonary rehabilitation (PR) is insufficient. However, music therapy may help address this gap due to its unique benefits. Therefore, we aimed to develop a music-therapy facilitated pulmonary telerehabilitation program based on rhythm-guided walking, singing, and objective telemonitoring. A supervised, parallel-group, single-blinded, randomized controlled clinical trial will be conducted, including 75 patients with COPD anticipated to be randomized in a 1:1:1 ratio into three groups. The intervention groups will receive a 12-week remotely monitored rehabilitation program, while the usual care group will not receive any rehabilitation interventions. Of the two intervention groups, the multi-module music therapy group will contain rhythm-guided walking and singing training, while the rhythm-guided walking group will only include music tempo-guided walking. The primary outcome is the distance of the incremental shuttle walking test. Secondary outcomes include respiratory muscle function, spirometry, lower extremity function, symptoms, quality of life, anxiety and depression levels, physical activity level, training adherence, and safety measurements. The results of this study can contribute to develop and evaluate a home-based music-facilitated rehabilitation program, which has the potential to act as a supplement and/or substitute (according to the needs) for traditional center-based PR in patients with stable COPD. Clinical trial registration: https://classic.clinicaltrials.gov/, NCT05832814.

Sociodemographic correlates with prevalence of comorbidities in patients with chronic obstructive pulmonary disease: a study from a Chinese National Survey.

Background: An increase in the prevalence of comorbidities has been reported in patients with chronic obstructive pulmonary disease (COPD). However, contemporary estimates of the overall prevalence of the sociodemographic correlates of COPD comorbidities are scarce and inconsistent in China. This study aimed to investigate the prevalence of sociodemographic correlates of comorbidities in patients with COPD across China. Methods: This was a cross-sectional study. We used data from the Enjoying Breathing Program between May 2020 and April 2022. Participants with COPD from 17 provinces (or equivalent) were included. Comorbidity clusters were stratified based on the number of comorbidities per person. Univariable and multivariable analyses were used to determine the sociodemographic associations of patients with COPD with specific clusters of comorbidities after adjusting for age, sex, and other prespecified covariates. Tetrachoric correlation analyses were performed to determine the associations between specific comorbidities. Findings: A total of 3913 participants with COPD were included, of whom 1744 (44.7%) had at least one comorbidity; 25.4% had one comorbid disease, 12.9% had two, and 6.4% had three or more concurrent diseases. The most common comorbidities were hypertension (17.8%), asthma (9.9%), bronchiectasis (8.2%), diabetes (8.2%), and coronary artery disease (7.7%). In the logistic regression models adjusted for a broad set of factors, patients with COPD residing in the east region of China and having health insurance experienced a decreased likelihood of comorbidities (from OR = 0.70 [95% confidence interval [CI], 0.53-0.93] to OR = 0.50 [95% CI, 0.25-0.99]). However, patients over 80 years had increased risk (OR 1.43 [95% CI 1.01-2.03]), as did those in all Modified Medical Research Council (mMRC) grade categories (grade 1: OR = 1.30 [95% CI, 1.02-1.65]; grade 2: OR = 1.39 [95% CI, 1.07-1.8]; grade 3: OR = 1.67 [95% CI, 1.23-2.26]; and grade 4: OR = 1.81 [95% CI, 1.00-3.28]) and in Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 classification (OR = 1.30 [95% CI, 1.03-1.65]) relative to their respective references. The associations observed in these subgroups were consistent regardless of the number of comorbidities per person. Tetrachoric correlations demonstrated negative associations in pairwise comparisons of the top five comorbidities, ranging from -0.03 to -0.31 (p < 0.001 in all groups). Interpretation: In China, comorbidities are highly prevalent among patients with COPD, with older age, higher mMRC grade, and lung function decline being the major risk factors. Studies with larger sample sizes are required to elucidate the complex mechanisms underlying COPD comorbidities. Funding: This study was funded by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-049 and 2022-I2M-C&T-B-107).

Constitutively expressed small heat shock protein LsHsp21.5 not only enhances heat tolerance but also helps to maintain reproduction in female Laodelphax striatellus.

Coping with stressful conditions and maintaining reproduction are two key biological processes that affect insect population dynamics. Small heat shock proteins (sHSPs) are involved in the stress response and the development of insects. The sHsp gene Laodelphax striatellus (Hemiptera: Delphacidae) sHsp 21.5 (LsHsp21.5) showed constitutive, stage- and organ-specific expression in L. striatellus, a pest that damages cultivated rice in east Asia. The expression of LsHsp21.5 was highest in the ovary, with 43.60, 12.99 and 1.45 time higher expression here than in the head, gut and female fat bodies, respectively. The expression of this gene was weakly affected by heat or cold shock. The gene provided in vitro protection against heat damage to malate dehydrogenase and in vivo protection against heat stress in Escherichia coli (Enterobacteriales: Enterobacteriaceae) BL21(DE3) and L. striatellus. Moreover, L. striatellus reproduction decreased by 1.85 times when the expression of LsHsp21.5 was inhibited by RNA interference. The expression of some genes related to reproduction, such as the homologous gene of chorion protein, also declined. These results suggest that LsHsp21.5 expression not only protects other proteins against stress but also helps maintain the stable expression of some reproduction-related genes under non-stressful conditions, with impacts on L. striatellus fecundity.

Associations of medication regimen complexity with medication adherence and clinical outcomes in patients with chronic obstructive pulmonary disease: a prospective study.

BACKGROUND: High medication burdens are common in patients with chronic obstructive pulmonary disease (COPD). This study aimed to explore the associations of medication regimen complexity index (MRCI) with medication adherence and clinical outcomes among patients with acute exacerbations of COPD (AECOPD) after hospital discharge. METHODS: Data were obtained from a nationwide cohort study of inpatients with AECOPD in China. MRCI scores were calculated using the medication list 30 days after discharge and separated into COPD-specific and non-COPD MRCI scores. Medication adherence was measured by the withdrawal rate of COPD or inhaled long-acting bronchodilators 6 months after discharge. Clinical outcomes included re-exacerbations and COPD-related readmissions during the 30-day to 6-month follow-up period. The associations of MRCI with medication withdrawal and clinical outcomes were evaluated using univariate and multivariate logistic regressions. Potential covariates included sociodemographic factors, year of COPD diagnosis, post-bronchodilator percentage predicted forced expiratory volume in 1 s, mMRC score, CAT score, and comorbidities. RESULTS: Among the 2853 patients included, the median total MRCI score was 7 [interquartile range (IQR), 7-13]. A high MRCI score (>7) was presented in 1316 patients (46.1%). Of the MRCI score, 91% were COPD specific. The withdrawal rates of the COPD and inhaled long-acting bronchodilators were 24.2% and 24.4%, respectively. Re-exacerbation and COPD-related readmission rates were 10.2% and 7.5%, respectively. After adjusting for covariates, patients with high total MRCI scores were less likely to discontinue COPD drugs [odds ratio (OR), 0.62; 95% confidence interval (CI), 0.52-0.74] and inhaled long-acting bronchodilators (OR, 0.68; 95%CI, 0.57-0.81); conversely, these patients were more likely to experience re-exacerbation (OR, 1.64; 95% CI, 1.27-2.11) and readmission (OR, 1.57; 95% CI, 1.17-2.10). CONCLUSION: MRCI scores were relatively low among post-hospitalized patients with AECOPD in China. Higher MRCI scores were positively associated with adherence to COPD or inhaled medications, and risk of re-exacerbation and readmission. REGISTRATION: ClinicalTrials.gov identifier: NCT02657525.

Outcomes of CT-Guided Deeper Localization Technique for Superficial Pulmonary Nodules.

BACKGROUND: The possibility of coil dislocation in computed tomography (CT)-guided microcoil localization of superficial pulmonary nodules is relatively high. The aim of the study is to investigate the outcomes of deeper localization technique during CT-guided microcoil localization of superficial pulmonary nodules before video-assisted thoracoscopic surgery (VATS). METHODS: Fifty-seven identified superficial pulmonary nodules (nodule-pleural distance ≤ 1 cm on CT image) from 51 consecutive patients underwent CT-guided microcoil localization, and subsequent VATSs were included. The rate of technical success, complications, and excised lung volume were compared between deeper localization technique group and conventional localization technique group. RESULTS: The technical success rate of the localization procedure was 100% (25/25) in the deeper localization group and 81.3% (26/32) in the conventional localization group (p = 0.030). Excluding one case of lobectomy, the excised lung volume in the deeper localization group and the conventional localization group was 39.3 ± 23.5 and 37.2 ± 16.2 cm3, respectively (p = 0.684). The incidence of pneumothorax was similar between the deeper localization group and the conventional localization group (24.0 vs. 21.9%, respectively, p = 0.850). The incidence of intrapulmonary hemorrhage in the deeper localization group was higher (16.0%) than that in the conventional localization group (6.3%), but the difference was not statistically significant (p = 0.388). CONCLUSION: CT-guided microcoil localization of superficial pulmonary nodules prior to VATS using a deeper localization technique is feasible. Deeper localization technique reduced the occurrence of dislocation but did not increase excised lung volume.

Pathogens are an important driving force for the rapid spread of symbionts in an insect host.

One of the biggest challenges for pathogens invading hosts is microbial symbionts but the role of pathogens in symbionts in nature is unknown. By tracking the dynamics of the entomopathogenic fungal Cordyceps javanica and symbionts in natural populations of the whitefly Bemisia tabaci from 2016 to 2021 across China, we reveal that Rickettsia, a newly invaded symbiont, is positively correlated with the pathogen in both frequency and density. We confirm that applying pathogen pressure can selectively drive Rickettsia to sudden fixation in whiteflies both in the laboratory and in the field. Furthermore, the driving force is elucidated by the Rickettsia-conferred suppression of pathogen infection quantity, proliferation and sporulation, acting as a potential barrier of onward transmission of the pathogen. These results show that pathogens are an important driving force for rapid shifts in host symbionts in the natural niche.

Influenza and pneumococcal vaccination coverage and associated factors in patients hospitalized with acute exacerbations of COPD in China: Findings from the real-world data.

BACKGROUND: Influenza and pneumococcal vaccination are a priority in patients with chronic obstructive pulmonary disease (COPD). However, limited information is available on vaccination coverage among patients with acute exacerbations of COPD (AECOPD) in China. This study aimed to determine the rates and associated factors of influenza and pneumococcal vaccination in patients hospitalized with AECOPD. METHODS: Baseline data from a national, multicenter, hospital-based study that included adult inpatients with AECOPD between 2017 and 2021 were analyzed. The outcomes of interest were the influenza vaccination in the past year and the pneumococcal vaccination in the past 5 years. To ensure national representativeness, rates were weighted according to the distribution of hospital levels and types enrolled in this study. Multivariable Poisson regression based on mixed-effects models were used to determine the associated factors. The independent variables included the region and hospital features where the participants were located, sociodemographic characteristics (age, sex, rural/urban residence, education, etc.), and clinical indicators (COPD disease history, lung function parameters, comorbidities, etc.). The treatment profiles of the vaccinated and unvaccinated participants were compared. RESULTS: Of 6949 eligible participants, the weighted rates of influenza/pneumococcal, influenza, and pneumococcal vaccination were 2.72% (95% confidence interval [CI]: 2.34-3.10%), 2.09% (95% CI: 1.76-2.43%), and 1.25% (95% CI: 0.99-1.51%), respectively. In multivariable models, age ≥60 years (60-69 years, odds ratio [OR]: 1.90, 95% CI: 1.11-3.25; ≥80 years, OR: 2.00, 95% CI: 1.06-3.78), geographical regions (Northern China relative to Eastern China, OR: 5.09, 95% CI: 1.96-13.21), urban residence (OR: 1.69, 95% CI: 1.07-2.66), a higher education level (junior high school, OR: 1.77, 95% CI: 1.21-2.58; senior high school or above, OR: 2.61, 95% CI: 1.69-4.03), former smoking (OR: 1.79, 95% CI: 1.15-2.79), and regular inhaled medication treatment (OR: 3.28, 95% CI: 2.29-4.70) were positively associated with vaccination. Patients who had experienced severe exacerbations in the past year were less likely to be vaccinated (OR: 0.65, 95% CI: 0.45-0.96). Compared with unvaccinated participants, vaccinated participants adhered better to pharmacological and non-pharmacological treatment. CONCLUSIONS: Influenza and pneumococcal vaccination coverage are extremely low. Urgent measures are necessary to increase vaccination coverage among inpatients with AECOPD in China.

Influence of Human Behavior on COVID-19 Dynamics Based on a Reaction-Diffusion Model.

To investigate the influence of human behavior on the spread of COVID-19, we propose a reaction-diffusion model that incorporates contact rate functions related to human behavior. The basic reproduction number R0 is derived and a threshold-type result on its global dynamics in terms of R0 is established. More precisely, we show that the disease-free equilibrium is globally asymptotically stable if R0≤1; while there exists a positive stationary solution and the disease is uniformly persistent if R0>1. By the numerical simulations of the analytic results, we find that human behavior changes may lower infection levels and reduce the number of exposed and infected humans.

Association between long-term exposure to ambient particulate matter and pulmonary function among men and women in typical areas of South and North China.

Background: Studies comparing the effects of different sizes and concentrations of ambient particulate matter (PM) on pulmonary function in different regions and sexes remain sparse. Objectives: To investigate the associations of different sizes and levels of long-term ambient PM exposure with pulmonary function among people of different sexes in typical areas of South and North China. Methods: In 2021, a total of 1,592 participants aged 20-73 years were recruited to participate in the pulmonary function test from the baseline survey of the Diverse Life-Course Cohort (DLCC) in typical areas of Guangdong Province and Hebei Province. The three-year (2018-2020) average ambient PM concentrations were assessed from the ChinaHighPM1 dataset, ChinaHighPM2.5 dataset and ChinaHighPM10 dataset. Mean differences in pulmonary function were used in multilevel models for different regions and sexes. Results: We discovered significant associations of ambient PM exposure with reduced forced vital capacity (FVC) and increased forced expiratory volume in 1 s/forced vital capacity ratio (FEV1/FVC) among men and lower levels of FEV1 and FVC among women, such that a 5-µg/m3 concentration increase in PM1, PM2.5, and PM10 was associated with decreases in FVC of 122.1 ml (95% confidence interval (CI): 30.8, 213.4), 54.6 ml (95% CI: 15.8, 93.3) and 42.9 ml (95% CI: 12.7, 73.1) and increases in FEV1/FVC of 2.2% (95% CI: 0.6, 3.9), 1.1% (95% CI: 0.4, 1.9) and 0.9% (95% CI: 0.3, 1.5) among men and decreases in FEV1 of 51.1 ml (95% CI: 9.7, 92.4), 21.6 ml (95% CI: 4.3, 38.9) and 16.7 ml (95% CI: 3.3, 30.1) and in FVC of 77.8 ml (95% CI: 10.0, 145.6), 38.7 ml (95% CI: 9.0, 68.5) and 31.1 ml (95% CI: 8.1, 54.1) among women in Hebei Province. There was no association between ambient PM and pulmonary function in Guangdong Province. Conclusion: Long-term exposure to different sizes and concentrations of ambient PM were associated with FEV1 and FVC among men and women differently. The impact of ambient PM on FVC should be of greater concerned.

Development of a prediction model to identify undiagnosed chronic obstructive pulmonary disease patients in primary care settings in China.

BACKGROUND: At present, a large number of chronic obstructive pulmonary disease (COPD) patients are undiagnosed in China. Thus, this study aimed to develop a simple prediction model as a screening tool to identify patients at risk for COPD. METHODS: The study was based on the data of 22,943 subjects aged 30 to 79 years and enrolled in the second resurvey of China Kadoorie Biobank during 2012 and 2013 in China. We stepwisely selected the predictors using logistic regression model. Then we tested the model validity through P-P graph, area under the receiver operating characteristic curve (AUROC), ten-fold cross validation and an external validation in a sample of 3492 individuals from the Enjoying Breathing Program in China. RESULTS: The final prediction model involved 14 independent variables, including age, sex, location (urban/rural), region, educational background, smoking status, smoking amount (pack-years), years of exposure to air pollution by cooking fuel, family history of COPD, history of tuberculosis, body mass index, shortness of breath, sputum and wheeze. The model showed an area under curve (AUC) of 0.72 (95% confidence interval [CI]: 0.72-0.73) for detecting undiagnosed COPD patients, with the cutoff of predicted probability of COPD=0.22, presenting a sensitivity of 70.13% and a specificity of 62.25%. The AUROC value for screening undiagnosed patients with clinically significant COPD was 0.68 (95% CI: 0.66-0.69). Moreover, the ten-fold cross validation reported an AUC of 0.72 (95% CI: 0.71-0.73), and the external validation presented an AUC of 0.69 (95% CI: 0.68-0.71). CONCLUSION: This prediction model can serve as a first-stage screening tool for undiagnosed COPD patients in primary care settings.

Outdoor particulate matter exposure affects metabolome in chronic obstructive pulmonary disease: Preliminary study.

Introduction: The metabolomic changes caused by airborne fine particulate matter (PM2.5) exposure in patients with chronic obstructive pulmonary disease (COPD) remain unclear. The aim of this study was to determine whether it is possible to predict PM2.5-induced acute exacerbation of COPD (AECOPD) using metabolic markers. Methods: Thirty-eight patients with COPD diagnosed by the 2018 Global Initiative for Obstructive Lung Disease were selected and divided into high exposure and low exposure groups. Questionnaire data, clinical data, and peripheral blood data were collected from the patients. Targeted metabolomics using liquid chromatography-tandem mass spectrometry was performed on the plasma samples to investigate the metabolic differences between the two groups and its correlation with the risk of acute exacerbation. Results: Metabolomic analysis identified 311 metabolites in the plasma of patients with COPD, among which 21 metabolites showed significant changes between the two groups, involving seven pathways, including glycerophospholipid, alanine, aspartate, and glutamate metabolism. Among the 21 metabolites, arginine and glycochenodeoxycholic acid were positively associated with AECOPD during the three months of follow-up, with an area under the curve of 72.50% and 67.14%, respectively. Discussion: PM2.5 exposure can lead to changes in multiple metabolic pathways that contribute to the development of AECOPD, and arginine is a bridge between PM2.5 exposure and AECOPD.

The national COPD screening programme in China: rationale and design.

Background: COPD is the most prevalent chronic respiratory disease in China. It is estimated that there is a large, as-yet undetected, high-risk population who will develop in COPD in future. Methods and design: In this context, a nationwide COPD screening programme was launched on 9 October 2021. This multistage sequential screening programme incorporates a previously validated questionnaire (i.e. COPD Screening Questionnaire) and pre- and post-bronchodilator spirometry to target the COPD high-risk population. The programme plans to recruit 800 000 participants (eligible age 35-75 years) from 160 districts or counties of 31 provinces, autonomous regions or municipalities across China. The filtered COPD high-risk population and early-detected COPD patients will receive integrated management and be followed-up for ≥1 year. Discussion: This is the first large-scale prospective study to determine the net benefit of mass screening for COPD in China. Whether the smoking cessation rate, morbidity, mortality and health status of individuals at high risk of COPD could be improved along with this systematic screening programme will be observed and validated. Moreover, the diagnostic accuracy, cost-effectiveness and superiority of the screening programme will also be assessed and discussed. The programme marks a remarkable achievement in the management of chronic respiratory disease in China.

Dynamic analysis of gene signatures in the progression of COPD.

Aims: Oxidative stress is an important amplifying mechanism in COPD; however, it is unclear how oxidative stress changes and what its exact amplification mechanism is in the pathological process. We aimed to dynamically analyse the progression of COPD and further elucidate the characteristics of each developmental stage and unveil the underlying mechanisms. Methods: We performed a holistic analysis by integrating Gene Expression Omnibus microarray datasets related to smoking, emphysema and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification based on the concept of gene, environment and time (GET). Gene ontology (GO), protein-protein interaction (PPI) networks and gene set enrichment analysis (GSEA) were used to explore the changing characteristics and potential mechanisms. Lentivirus was used to promote HIF3A overexpression. Results: In smokers versus nonsmokers, the GO term mainly enriched in "negative regulation of apoptotic process". In later transitions between stages, the main enriched terms were continuous progression of "oxidation-reduction process" and "cellular response to hydrogen peroxide". Logistic regression showed that these core differentially expressed genes (DEGs) had diagnostic accuracy in test (area under the curve (AUC)=0.828) and validation (AUC=0.750) sets. GSEA and PPI networks showed that one of the core DEGs, HIF3A, strongly interacted with the ubiquitin-mediated proteolysis pathway. Overexpression of HIF3A restored superoxide dismutase levels and alleviated the reactive oxygen species accumulation caused by cigarette smoke extract treatment. Conclusion: Oxidative stress was continuously intensified from mild emphysema to GOLD 4; thus, special attention should be paid to the identification of emphysema. Furthermore, the downregulated HIF3A may play an important role in the intensified oxidative stress in COPD.

CT-guided microcoil localization for scapula-blocked pulmonary nodules using penetrating lung puncture before video-assisted thoracic surgery.

PURPOSE: To retrospectively analyze the effectiveness and safety of computed tomography (CT)-guided microcoil localization for scapula-blocked pulmonary nodules using penetrating lung puncture prior to video-assisted thoracic surgery (VATS). METHODS: One hundred thirty-eight patients with 138 pulmonary nodules were included in this single-center retrospective study. Among them, 110 patients who underwent CT-guided microcoil localization using the routine puncture technique formed the routine group; the other 28 patients who underwent the CT-guided microcoil localization using the penetrating lung puncture technique formed the penetrating lung group. The main outcomes were the success rate and complication rate of the two groups. RESULTS: The localization success rate was 95.5% (105/110) in the routine group and 89.3% (25/28) in the penetrating lung group (P = 0.205). There was no statistical difference in any of the complications (pneumothorax, intrapulmonary hemorrhage, or moderate and severe chest pain) in both groups (P = 0.178, P = 0.204, P = 0.709, respectively). Localization procedure time was significantly increased in the penetrating lung group compared with the routine group (31.0 ± 3.0 min vs. 21.2 ± 2.8 min, P < 0.001). CONCLUSION: CT-guided microcoil localization for scapula-blocked pulmonary nodules using penetrating lung puncture prior to VATS resection is effective and safe. However, the deployment of the microcoil using penetrating lung puncture required more time than the routine puncture method.

Pulmonary rehabilitation restores limb muscle mitochondria and improves the intramuscular metabolic profile.

BACKGROUND: Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated. METHODS: Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n  = 8), non-COPD/exercise ( n  = 7), COPD/rest ( n  = 7), COPD/medium exercise ( n  = 10), and COPD/intensive exercise ( n  = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). RESULTS: At the end of 90 days, COPD rats' weight gain was smaller than control by 59.48 ±â€Š15.33 g ( P  = 0.0005). The oxidative muscle fibers proportion was lower ( P  < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P  = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P  = 0.0093), myofibrils diameter (Δ0.06 µm, 95% CI: 0.02-0.10 µm, P  = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P  = 0.0434), mitochondria oxidative phosphorylate capacity ( P  < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. CONCLUSION: COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.