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Background: Eosinophils are involved in the development of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroid responsiveness. We evaluated clinical predictors of high sputum eosinophil levels in a COPD cohort in China. Methods: We conducted an observational, prospective, population-based, cross-sectional study. Participants were tested for COPD and underwent spirometry, computed tomography scans, and a blood test. Participants also produced induced sputum and responded to an information-gathering questionnaire. High sputum eosinophils were defined as ≥3.0%. Multivariate logistic regression was used to identify predictors of high sputum eosinophil levels. Results: We recruited 895 patients with complete and quality control data. The median percentage of sputum eosinophil abundance was 2.00% (interquartile range: 0.75–5.00) and the prevalence of COPD with high sputum eosinophils was 38.0%. Covariance analysis indicated that the high sputum eosinophil group had lower lung function, more severe emphysema, and air trapping. Multivariate logistic regression indicated that high blood eosinophil levels, severe respiratory symptoms, being a former smoker, and a family history of respiratory diseases were associated with high sputum eosinophil levels. Conclusion: High blood eosinophil levels, severe respiratory symptoms, being a former smoker, and a family history of respiratory diseases may be predictors of high sputum eosinophil levels in Chinese COPD patients. High sputum eosinophils were associated with lower lung function, more emphysema, and gas trapping.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and its clinically relevant subtypes are not well understood. Which clinical characteristics are more likely to be present among individuals who develop COPD remains to be studied in depth. Therefore, we designed a prospective observational cohort study, entitled the Early Chronic Obstructive Pulmonary Disease (ECOPD) study, to fill this evidence gap. The ECOPD study has four specific aims: (I) identification of characteristics, parameters, and biomarkers that may predict the development of airflow obstruction and annual decline in lung function with normal spirometry; (II) identification of clinically relevant early COPD subtypes; (III) identification of characteristics, parameters, and biomarkers that may predict disease progression in these early COPD subtypes; (IV) development and validation of machine learning models to predict development of airflow obstruction and disease progression. METHODS: We will recruit approximately 2,000 participants aged 40–80 years, including approximately 1,000 with COPD [post-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC)

Background: Airway abnormalities assessed by impulse oscillometry (IOS) were common in patients with chronic obstructive pulmonary disease (COPD). However, most studies only used difference from R5 to R20 (R5-R20) > 0.7kPa/L/s to diagnose airway abnormalities, which may ignore the value of other IOS indicators in the diagnosis of airway abnormalities. Our study aimed to comprehensively assess clinical symptoms and radiologic features of airway abnormalities in COPD patients in China. Methods: We enrolled 805 COPD patients from a part of ECOPD cohort, they underwent questionnaires, symptom scores, lung function, IOS and HRCT. The criteria of airway abnormalities were based on standardized IOS reference values. Logistic regression was used to analyze risk factors of airway abnormalities. The associations between acute exacerbation of COPD (AECOPD) in the previous year and airway abnormalities were assessed by Poisson regression. Logistic regression was used to assess the associations between CT imaging and airway abnormalities. Results: The proportion of airway abnormalities evaluated by other indicators increased gradually with COPD severity except for R20. Multivariate logistic analysis showed dyspnea, low FEV1% predicted and airway obstruction were associated with risk of airway abnormalities. Compared with normal airway group, airway abnormalities group had more clinical symptoms (wheeze and dyspnea) and higher mMRC and CAT scores. Airway abnormalities assessed by X5 and AX had more emphysema, gas trapping and higher risk of AECOPD in the previous year. Conclusions: Reactance (X5, AX) assessment of airway abnormalities had more clinical symptoms, emphysema, gas trapping and higher risk of AECOPD in the previous year.

BackgroundThe inter-relationships among neutrophilic airway inflammation, air trapping and future exacerbation in chronic obstructive pulmonary disease (COPD) remain unclear.ObjectiveTo evaluate the associations between sputum neutrophil proportions and future exacerbation in COPD and to determine whether these associations are modified by significant air trapping.MethodsParticipants 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.ResultsThere 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.ConclusionsWe 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.

BackgroundEvidence 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.MethodsWe 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.ResultsNOCB 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 pConclusionsNever-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.

Cuiqiong Dai,* Zihui Wang,* Zhishan Deng, Fan Wu, Huajing Yang, Shan Xiao, Xiang Wen, Youlan Zheng, Jianwu Xu, Lifei Lu, Ningning Zhao, Peiyu Huang, Yumin Zhou, Pixin Ran State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pixin Ran; Yumin Zhou, The State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, No. 195 Dongfeng Xi Road, Guangzhou, 510000, People’s Republic of China, Tel +86-020 83205187, Fax +86-020 81340482, Email pxran@gzhmu.edu.cn; zhouyumin410@126.comBackground: Serum total bilirubin has been reported to have antioxidant properties against chronic respiratory diseases. The objective of our study is to evaluate the association of total bilirubin (TB) with annual lung function decline in COPD patients with different GOLD stages.Methods: This study used pooled data from two observational and prospective cohorts of 612 COPD patients whose TB levels were measured at baseline. The associations between TB and postbronchodilator FEV1, FEV1pred, FVC, FVCpred, FEV1/FVC, and the rate of their decline were all determined using linear regression models in the total population and strata of GOLD stages.Results: Serum TB was positively related to FEV1 and FVC in the total group (β 0.02, 95% CI 0.001∼ 0.02, P = 0.025 and β 0.02, 95% CI 0.002∼ 0.03, P = 0.022, respectively). Additionally, TB was inversely associated with the annual decline in FEV1 and FEV1pred (β 4.91, 95% CI 1.68∼ 8.14, P = 0.025 and β 0.21, 95% CI 0.06∼ 0.36, P = 0.022, respectively) when adjusted for multivariables. After stratification, the significant associations merely persisted in COPD patients with GOLD 2 and GOLD 3– 4.Conclusion: Increased TB level was related to less annual decline in FEV1 as well as FEV1pred in moderate-to-severe COPD but not mild COPD, which indicated the different status of TB in different COPD severity and the possible role as potential biomarker merely in moderate-to-severe COPD. Future researches to determine whether TB could be served as biomarker for COPD and the mechanisms should be focused on some target patients with a certain disease severity.Keywords: total bilirubin, COPD, lung function, GOLD stage, decline

Background Aging has been evidenced to bring about some structural and functional lung changes, especially in COPD. However, whether aging affects SAD, a possible precursor of COPD, has not been well characterized. Objective We aimed to comprehensively assess the relationship between aging and SAD from computed tomography, impulse oscillometry, and spirometry perspectives in Chinese. Methods We included 1859 participants from ECOPD, and used a linear-by-linear association test for evaluating the prevalence of SAD across various age subgroups, multivariate regression models for determining impact of age on the risk and extent of SAD. We then repeated the analyses in these subjects stratified by airflow limitation. Results The prevalence of SAD increases over aging regardless of definitional methods. After adjustment for other confounding factors, per 10-yrs increase in age was significantly associated with the risk of CT-defined SAD (OR = 2.57, 95% CI: 2.13 to 3.10) and the increase in the extent of air trapping (β: 2.09, 95% CI: -0.06 to 4.25 for LAA− 856), airway reactance (β: -0.02, 95%CI: -0.04 to -0.01 for X5; β: 0.30, 95%CI: 0.13 to 0.47 for AX; β: 1.75, 95% CI: 0.85 to 2.66 for Fres), as well as the decrease in expiratory flow rates (β: -3.95, 95% CI: -6.19 to -1.71 for MMEF%predicted; β: -5.42, 95% CI: -7.88 to -2.95 for FEF50%predicted) for SAD. All these associations were generally maintained in SAD defined by IOS or spirometry. After stratification of airflow limitation, we further found that the effect of age on LAA− 856 was the most significant among almost all the subgroups . Conclusions Aging is independently associated with the prevalence, risk, as well as worse extent of SAD. CT may be a more optimal measure to assess aging-related SAD. The molecular mechanisms for the role of aging in SAD need to be explored in the future. Trial registration : Chinese Clinical Trial Registry ChiCTR1900024643. Registered on 19 July 2019.

Cuiqiong Dai,1,* Zihui Wang,1,* Huajing Yang,1,* Shan Xiao,1 Jianwu Xu,1 Zhishan Deng,1 Fan Wu,1,2 Xiang Wen,1 Youlan Zheng,1 Lifei Lu,1 Ningning Zhao,1 Peiyu Huang,1 Yumin Zhou,1,2 Pixin Ran1,2 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou Laboratory, Bio-Island, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pixin Ran; Yumin Zhou, Tel +86-20 3710 3616, Fax +86-20 81340482, Email pxran@gzhmu.edu.cn; zhouyumin410@126.comBackground: The potential protective role of serum total bilirubin (TB) for chronic obstructive pulmonary disease (COPD) is controversial. We aimed to investigate whether serum TB could prevent airflow limitation (reduce the risk of COPD) and whether these associations were causal or reversely causal.Methods: We conducted a multi-center and cross-sectional study including 3069 participants. Logistic regression model (LRM) with restricted cubic spline (RCS) and priori defined quintile categories were used to assess the associations of TB with COPD. Besides, ordinary least squares (OLS) regression model with RCS curves were applied to assess the dose-response relationship between serum TB and airflow limitation (FEV1/FVC). To verify the causal direction between TB and COPD, a bidirectional Mendelian randomization analysis was carried out with GWAS data from European ancestry.Results: In the cross-sectional study, the relationship between levels of TB and COPD risk was U shaped (P=0.001), and the low and high concentrations of TB apparently increasing the risk of COPD (OR 1.40, 95% CI 1.07 to 1.82 for less than 9 μmol/L; OR 1.36, 95% CI 1.06 to 1.76 for 9.01– 1 0.88 μmol/L; OR 1.50, 95% CI 1.16 to 1.95 for more than 13 μmol/L). There was a significant non-linear relationship between TB and FEV1/FVC (non-linear p=0.004). Furthermore, results of bidirectional Mendelian randomization analysis (OR 1.000; 95% CI 0.983 to 1.017 for MR and OR 0.998; 95% CI 0.976 to 1.020 for reversal MR) did not support the causal effects between serum TB and FEV1/FVC after controlling the effect of potential confounders and revised causality.Conclusion: Our study reveals that there was non-linear does-response pattern between serum TB and COPD. However, there was little evidence for the linear causal associations of serum TB with airflow limitation. The relationship of TB with COPD needs further study and careful interpretation.Keywords: total bilirubin, COPD, airflow limitation, Mendelian randomization analysis

In this article, we study the secure beamforming design for a two-way cognitive radio (CR) Internet of Things (IoT) network aided with the simultaneous wireless information and power transfer (SWIPT). Located at the center of secondary network, the IoT controller helps to provide relay assistance and cooperative physical layer security (PLS) for two primary users (PUs) against an eavesdropper, while transmitting information and power to the other IoT devices (IoDs) with primary spectrum. To enhance the information security, we aim to maximize the secrecy sum rate (SSR) for PUs by jointly designing the beamforming matrix and vectors at the central controller. To efficiently solve the nonconvex problem, we first propose the branch-reduce-and-bound (BRB)-based algorithm to obtain an upper bound for the SSR and offer a feasible solution by Gaussian randomization, which demands two-level iteration and thus has high complexity. To strike a balance between the complexity and the performance, we then propose iterative algorithm based on constrained-convex-concave programming (CCCP) and a zero forcing (ZF)-based noniterative algorithm, the latter of which with lowest complexity is suitable for the central controller with limited-power supply. The simulation results are provided to demonstrate the effectiveness of our proposed optimization algorithms in comparison to the traditional schemes.

Fan Wu,1,2,&ast; Changbin Jiang,1,&ast; Yumin Zhou,1,2,&ast; Youlan Zheng,1,&ast; Heshen Tian,1 Haiqing Li,1 Zhishan Deng,1 Ningning Zhao,1 Huai Chen,3 Pixin Ran1,2 1National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou Laboratory, Bio-island, Guangzhou, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pixin RanNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaTel +86 20 83205187Fax +86 20-81340482Email pxran@gzhmu.edu.cnBackground: It has been found that the degree of terminal bronchiole destruction is associated with the severity of COPD. However, total airway count (TAC) of CT-visible and its relationship with COPD lung function severity and pulmonary function decline remains controversial. The present study aimed to determine whether TAC is significantly reduced in early-stage COPD (GOLD stage I–II) compared with healthy control subjects and whether TAC is associated with annual decline in pulmonary function in Chinese patients with early-stage COPD.Methods: A total of 176 participants were enrolled in this study, of which 139 participants had undergone at least two spirometry measurements within 7 years (average 5.5 [standard deviation 0.8] years) after baseline data acquisition. CT-visible TAC was measured by summing all airway segments using semi-automated software. Average lumen diameter, average inner area, emphysema index, air trapping, and inspiratory Pi10 were also measured. Multivariable linear analysis was performed to evaluate variables that were significantly related to pulmonary function parameters and to evaluate the correlation between TAC and annual decline in longitudinal pulmonary function.Results: Compared with healthy control subjects, CT-visible TAC was significantly reduced by 51% in GOLD II and by 31% in GOLD I after adjustment. TAC had the greatest impact on pre-bronchodilator FEV1, pre-bronchodilator FVC, post-bronchodilator FEV1, and post-bronchodilator FEV1/FVC (both p< 0.001) among all CT indicators measured. TAC has the best correlation with inspiratory Pi10 (ρ=− 0.751, p< 0.001), an evaluation indicator of the degree of airway remodeling. TAC was independently associated with annual decline in pre-bronchodilator FEV1 (p=0.023), post-bronchodilator FEV1 (p=0.018), and post-bronchodilator FEV1/FVC (p< 0.001).Conclusion: This finding suggests that CT-visible TAC may be an evaluation indicator of the degree of airway remodeling, and was diminished in greater COPD lung function severity, and independently associated with disease progression. Early-stage COPD patients have already occurred lung structural changes and early intervention may be needed to ameliorate the progression of disease.Clinical Trial Registration: ChiCTR-OO-14004264.Keywords: chronic obstructive pulmonary disease, COPD, computed tomography, total airway count, TAC

Small airway dysfunction (SAD) is an early lesion of chronic respiratory disease that is best detected using impulse oscillometry (IOS). Few studies have investigated risk factors for IOS-defined SAD (IOS-SAD) in a large population. We aimed to explore the clinical features of and risk factors for IOS-SAD in a community-based population.We divided subjects into IOS-SAD and non-SAD groups based on a cutoff of0.07 kPa/L/s in the difference between the resistance at 5 Hz versus the resistance at 20 Hz (R5-R20). All participants underwent spirometry, IOS, and completed a questionnaire; some participants underwent computed tomography (CT). We analyzed the risk factors for SAD based on binary logistic regression.The total cohort comprised 1327 subjects. The prevalence of IOS-SAD was 32.9% (437/1327). Compared with the non-SAD group, the IOS-SAD group was older (64.0 ± 7.8 vs. 59.6 ± 7.8 years, p 0.001), included less never-smokers (30.2% vs. 35.8%, p 0.001), had greater airway resistance and worse lung function, indicated by a larger R5-R20 (0.15 ± 0.08 vs. 0.03 ± 0.02 kPa/L/s, p 0.001) and smaller forced expiratory volume in 1 s to forced vital capacity after bronchodilation (60.2 ± 14.4% vs. 72.6 ± 10.0%, p 0.001); on CT, the IOS-SAD group had higher prevalences of emphysema and gas trapping. Risk factors for SAD were older age, high BMI, smoking, childhood cough, and asthma.Subjects with IOS-SAD had increased airway resistance and visible CT changes. Individuals with smoking exposure, advanced age, high BMI, childhood cough, and asthma were more prone to SAD.ChiCTR1900024643.

Background Tiotropium improves lung function and ameliorates the annual decline in forced expiratory volume in 1 s (FEV1) after bronchodilator use in patients with mild to moderate chronic obstructive pulmonary disease (COPD). However, whether these benefits persist in patients with early-stage COPD after tiotropium discontinuation is unknown. Methods In this prospective cohort observational follow-up study, patients who had completed the Tiotropium in Early-Stage COPD (Tie-COPD) trial were followed for a maximum of 3 years, continuing or discontinuing treatment according to their willingness. The outcomes measured were spirometry parameters, COPD exacerbations, COPD Assessment Test (CAT) scores, Clinical COPD Questionnaire (CCQ) scores, modified Medical Research Council (mMRC) scores and the use of respiratory medications. Results Out of 376 patients, 262 (126 in the post-placebo group and 136 in the post-tiotropium group) completed the maximum 3-year follow-up after the study medication was withdrawn. After discontinuation, the decrease in FEV1 and forced vital capacity (FVC) did not differ significantly between the two groups, and neither did their annual decline. In addition, the frequency of acute COPD exacerbations and the mMRC scores were similar between the two groups after medication withdrawal. Both the mean CAT and CCQ scores were significantly lower in the post-tiotropium group than in the post-placebo group (p, Tiotropium improves lung function and ameliorates the annual decline in early-stage COPD patients. In order to maintain continuous improvement of the pulmonary function, continuous drug intervention is needed. http://ow.ly/ASNx30n4Kdo

BACKGROUND: Prior pulmonary tuberculosis (TB) can cause permanent changes in lung anatomy and is associated with lung function loss. However, it remains unclear whether pulmonary function impairment owing to TB is associated with airflow obstruction, the hallmark of chronic obstructive pulmonary disease (COPD). The aim of this systematic review and meta-analysis was to assess the association and quantify the magnitudes of association between pulmonary TB and COPD, and to evaluate the prevalence of COPD in patients with prior pulmonary TB. METHODS: We searched the PubMed, Embase, and Web of Science databases for studies published from inception to January 1, 2020. Pooled effect sizes were calculated according to a random effects model or fixed effect model depending on heterogeneity. Specific subgroups (different diagnostic criteria, smoking status, income level) were examined. RESULTS: A total of 23 articles were included in this study. Compared with controls, patients with pulmonary TB had an odds ratios (ORs) of 2.59 [95% confidence interval (CI): 2.12–3.15; P

Aims To assess possible effect of air quality improvements, we investigated the temporal change in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) associated with pollutant concentrations. Methods We collected daily concentrations of particulate matter (i.e., PM2.5, PM10 and PMcoarse), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and admissions for AECOPD for 21 cities in Guangdong from 2013 to 2017. We examined the association of air pollution with AECOPD admissions using two-stage time-series analysis, and estimated the annual attributable fractions, numbers, and direct hospitalization costs of AECOPD admissions with principal component analysis. Results From 2013–2017, mean daily concentrations of SO2, PM10 and PM2.5 declined by nearly 40%, 30%, and 26% respectively. As the average daily 8 h O3 concentration increased considerably, the number of days exceeding WHO target (i.e.,100 μg/m³) increased from 103 in 2015–152 in 2017. For each interquartile range increase in pollutant concentration, the relative risks of AECOPD admission at lag 0–3 were 1.093 (95% CI 1.06–1.13) for PM2.5, 1.092 (95% CI 1.08–1.11) for O3, and 1.092 (95% CI 1.05–1.14) for SO2. Attributable fractions of AECOPD admission advanced by air pollution declined from 9.5% in 2013 to 4.9% in 2016, then increased to 6.0% in 2017. A similar declining trend was observed for direct AECOPD hospitalization costs. Conclusion Declined attributable hospital admissions for AECOPD may be associated with the reduction in concentrations of PM2.5, PM10 and SO2 in Guangdong, while O3 has emerged as an important risk factor. Summarizes the main finding of the work： Reduction in PM may result in declined attributable hospitalizations for AECOPD, while O3 has emerged as an important risk factor following an intervention.

Introduction The presence of increased oxidative stress and airway inflammation has been proven in subjects with chronic obstructive pulmonary disease (COPD). Several studies have demonstrated that drugs with antioxidant and anti-inflammatory properties such as N-acetylcysteine (NAC) can reduce the rate of exacerbations in patients with COPD. However, the beneficial effects of NAC in early-stage COPD are minimally discussed. We are investigating whether high-dose NAC has therapeutic effects in Chinese patients with early-stage COPD. Method and analysis A randomized, double-blinded, placebo-controlled, parallel-group, multicenter clinical trial is evaluating the efficacy and safety of NAC for the long-term treatment of patients with early-stage COPD at 24 centers in China. Subjects aged 40–80 years and recruited by physicians or researchers with special training will be randomized to either NAC 600 mg twice daily group or matching placebo group for 2 years. Measurements will include forced expiratory volume in 1 s (FEV1), the number of COPD exacerbations, health-related quality, and pharmacoeconomic analysis. Discussion Currently, there are no randomized controlled trials with high-dose N-acetylcysteine (600 mg twice daily) for patients with mild-to-moderate COPD (GOLD I–II). We designed this multicenter randomized controlled trial (RCT) to assess the effectiveness, safety, and cost-effectiveness of long-term treatment with high-dose N-acetylcysteine. The results of this trial may guide clinical practice and change the standard of early COPD management. Trial registration Chinese Clinical Trial Registry ChiCTR-IIR-17012604. Registered on 07 September 2017.

Background The association between diurnal temperature range (DTR) and hospitalization for exacerbation of chronic respiratory diseases (CRD) was rarely reported. Objectives To examine the association between DTR and daily hospital admissions for exacerbation of CRD and find out the potential effect of modifications on this association. Method Data on daily hospitalization for exacerbation of chronic obstructive pulmonary disease (COPD), asthma and bronchiectasis and meteorology measures from 2013 through 2017 were obtained from 21 cities in South China. After controlling the effects of daily mean temperature, relative humidity (RH), particulate matter 2.5) and other confounding factors, a standard generalized additive model (GAM) with a quasi-Poisson distribution was performed to evaluate the relationships between DTR and daily hospital admissions of CRD in a two-stage strategy. Subgroup analysis was performed to find potential modifications, including seasonality and population characteristics. Result Elevated risk of hospitalization for exacerbation of CRD (RR = 1.09 [95%CI: 1.08 to 1.11]) was associated with the increase in DTR (the 75th percentile versus the 25th percentile of DTR at lag0–6). The effects of DTR on hospital admissions for CRD were strong at low DTR in the hot season and high DTR in the cold season. The RR (the 75th percentile versus the 25th percentile of DTR at lag0–6) of hospitalization was 1.11 (95%CI: 1.08 to 1.12) for exacerbations of COPD and 1.09 (95%CI: 1.05 to 1.13) for asthma. The adverse effect of DTR on hospitalization for bronchiectasis was only observed in female patients (RR = 1.06 [95%CI: 1.03 to 1.10]). Conclusion Our study provided additional evidence for the association between DTR and daily hospitalization for exacerbation of CRD, and these associations are especially stronger in COPD patients and in the cold season than the hot season. Preventive measures to reduce the adverse impacts of DTR were needed for CRD patients.

Additional file 1.

Additional file 1. List of research centers.

Background Criteria of obstruction that establish a diagnosis of COPD have been debated in recent years. We carried out a follow-up study to assess the impact of the new LLN reference equation for Chinese on detecting COPD compared with the traditional 0.7fixed criteria. Methods We examined the prevalence and characteristics of airflow limitation for a non-child population using post-bronchodilator airflow with both age-dependent predicted lower limit of the normal value and fixed-ratio spirometric criterion. Questionnaires and spirometry were completed for all eligible subjects during the baseline examination. Participants with inconsistent diagnosis according to the two criteria, normal participants (controls) and COPD patients in stages I or II, were invited to take a cardiopulmonary exercise testing (CPET) examination and follow up for 2–4 years. Results A total of 5448 (mean age 50.51 ± 13.2 yr) study subjects with acceptable spirometry and complete questionnaire data were included in our final analyses. COPD detection based on LLN was consistent with the GOLD 0.7 fixed-ratio in general, as 51 subjects (0.9%) were underdiagnosed, and 61 subjects (1.1%) were overdiagnosed when using LLN as the reference diagnostic criterion. The underdiagnosed subjects were younger, had more symptoms, more exposure to biofuels and worse FEV1 than the normal group; they also demonstrated a damaged cardiopulmonary reserve capacity and significant FEV1 decline. Except for being older, the overdiagnosed subjects differed little from the normal group. Conclusions Individual-dependent LLN appears to better reveal impacts on detecting airflow limitation. Participants underdiagnosed by GOLD criterion should be paid more attention. Clinical Trial Registration ChiCTR-ECS-13004110

The relation of acute fluctuations of air pollution to hospital admission for bronchiectasis remained uncertain, and large-scale studies were needed. We collected daily concentrations of particulate matter (PM), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and daily hospitalizations for bronchiectasis for 21 cities across Guangdong Province from 2013 through 2017. We examined their association using two-stage time-series analysis. Our analysis was stratified by specific sub-diagnosis, sex and age group to assess potential effect modifications. Relative risks of hospitalization for bronchiectasis were 1.060 (95%CI 1.014-1.108) for PM10 at lag0-6, 1.067 (95%CI 1.020-1.116) for PM2.5 at lag0-6, 1.038 (95%CI 1.005-1.073) for PMcoarse at lag0-6, 1.058 (95%CI 1.015-1.103) for SO2 at lag0-4, 1.057 (95%CI 1.030-1.084) for NO2 at lag0 and 1.055 (95%CI 1.025-1.085) for CO at lag0-6 per interquartile range increase of air pollution. Specifically, acute fluctuations of air pollution might be a risk factor for bronchiectasis patients with lower respiratory infection but not with hemoptysis. Patients aged ≥65 years, and female patients appeared to be particularly susceptible to air pollution. Acute fluctuations of air pollution, particularly PM may increase the risk of hospital admission for bronchiectasis exacerbations, especially for the patients complicated with lower respiratory infection. This study strengthens the importance of reducing adverse impact on respiratory health of air pollution to protect vulnerable populations.

Criteria of obstruction that establish a diagnosis of COPD have been debated in recent years. We carried out a follow-up study to assess the impact of the new LLN reference equation for Chinese on detecting COPD compared with the traditional 0.7fixed criteria.We examined the prevalence and characteristics of airflow limitation for a non-child population using post-bronchodilator airflow with both age-dependent predicted lower limit of the normal value and fixed-ratio spirometric criterion. Questionnaires and spirometry were completed for all eligible subjects during the baseline examination. Participants with inconsistent diagnosis according to the two criteria, normal participants (controls) and COPD patients in stages I or II, were invited to take a cardiopulmonary exercise testing (CPET) examination and follow up for 2-4 years.A total of 5448 (mean age 50.51 ± 13.2 yr) study subjects with acceptable spirometry and complete questionnaire data were included in our final analyses. COPD detection based on LLN was consistent with the GOLD 0.7 fixed-ratio in general, as 51 subjects (0.9%) were underdiagnosed, and 61 subjects (1.1%) were overdiagnosed when using LLN as the reference diagnostic criterion. The underdiagnosed subjects were younger, had more symptoms, more exposure to biofuels and worse FEVIndividual-dependent LLN appears to better reveal impacts on detecting airflow limitation. Participants underdiagnosed by GOLD criterion should be paid more attention.ChiCTR-ECS-13004110.

Background: Tiotropium improves lung function and ameliorates the annual decline in the forced expiratory volume in 1 second (FEV1) after bronchodilator use in patients with mild to moderate chronic obstructive pulmonary disease (COPD). However, whether these benefits persist in patients with early-stage COPD after tiotropium discontinuation is unknown. Methods: In this prospective cohort observational follow-up study, patients who had completed the tiotropium in early-stage COPD (Tie-COPD) trial were followed for a maximum of 3 years, continuing or discontinuing treatment according to their willingness. The outcomes measured were spirometry parameters, COPD exacerbations, COPD Assessment Test (CAT) scores, Clinical COPD Questionnaire (CCQ) scores, modified British Medical Research Council (mMRC) scores and the use of respiratory medications. Results: Of 353 patients, 262 (126 in post-placebo group and 136 in post-tiotropium group) completed the maximum 3-year follow-up after the study medication was withdrawn. After discontinuation, both the FEV1 and forced vital capacity decreased, with no significant difference between the two groups. The frequency of acute COPD exacerbations and the mMRC scores were also similar between the two groups after medication withdrawal. Both the mean CAT and CCQ scores were significantly lower in the post-tiotropium group than in the post-placebo group (P