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

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

Training and asymmetrical transfer effects of working memory and inhibitory control in primary school children.

Working memory (WM) and inhibitory control (IC) are two fundamental and supportive components of executive function (EF) that are critical for school-age children. However, the direct comparison of the training and transfer effects of WM and IC training in school-age children still needs to be improved. This study adopted a "pre-, post-, and delayed posttest" design to compare the training, near-transfer, and far-transfer effects of WM and IC in school-age children. A total of 60 children aged 8 to 10 years were randomly assigned to the WM training group, IC training group, or control group. Children in the WM and IC training groups completed 12 sessions of multiple adaptive training tasks tapping different subcomponents of WM (visual-spatial and verbal WM) and IC (interference control and response inhibition) separately. In the pretraining, posttraining, and 6-month follow-up stages, we used WM and IC tasks to evaluate training and near-transfer effects and used analogical reasoning tasks to evaluate far-transfer effects. Results showed significant training effects on visual-spatial and verbal WM, near-transfer effects on response inhibition, and far-transfer effects on analogical reasoning for WM training in the posttraining stage. The improvements in verbal WM and analogical reasoning were maintained for 6 months, whereas for IC training only the training effects on response inhibition and the far-transfer effects on analogical reasoning were observed in the posttraining stage and only the training effects on response inhibition were maintained for 6 months. Results suggested positive training and asymmetrical transfer effects of WM and IC training, which provide new evidence for the effectiveness of WM and IC training in school-age children.

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

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

Association between chronic obstructive pulmonary disease and 28-day mortality in patients with sepsis: a retrospective study based on the MIMIC-III database.

BACKGROUND: Sepsis is a common cause of mortality in critically ill patients, and chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in septic patients. However, the impact of COPD on patients with sepsis remained unclear. Therefore, the purpose of this study aimed to assess the effect of COPD on the prognosis of septic patients based on Medical Information Mart for Intensive Care (MIMIC-III) database. METHODS: In this retrospective study based on the (MIMIC)-III database version 1.4 (v1.4), we collected clinical data and 28-day all-cause mortality from patients with sepsis in intensive care unit (ICU) and these patients met the diagnostic criteria of Sepsis 3 on ICU admission between 2008 and 2012. International Classification of Diseases (ICD-9) (4660, 490, 4910, 4911, 49120, 49121, 4918, 4919, 4920, 4928, 494, 4940, 4941, 496) was used to identified COPD. We applied Kaplan-Meier analysis to compare difference of 28-day all-cause mortality between septic patients with and without COPD. Cox proportional-hazards model was applied to explore the risk factor associated with 28-day all-cause mortality in patients with sepsis. RESULTS: Six thousand two hundred fifty seven patients with sepsis were included in this study, including 955 (15.3%) patients with COPD and 5302 patients without COPD (84.7%). Compared with patients without COPD, patients with COPD were older (median: 73.5 [64.4, 82.0] vs 65.8 [52.9, 79.1], P < 0.001), had higher simplified acute physiology score II (SAPSII) (median: 40.0 [33.0, 49.0] vs 38.0 [29.0,47.0], P < 0.001) and greater proportion of mechanical ventilatory support (MV) (55.0% vs 48.9%, P = 0.001). In our study, septic patients with COPD had higher 28-day all-cause mortality (23.6% vs 16.4%, P < 0.001) than patients without COPD. After adjusting for covariates, the results showed that COPD was an independent risk factor for the 28-day all-cause mortality of patients with sepsis (HR 1.30, 95%CI: 1.12-1.50, P = 0.001). CONCLUSIONS: COPD was an independent risk factor of 28-day all-cause mortality in septic patients. Clinically, septic patients with COPD should be given additional care.

The association between small airway dysfunction and aging: a cross-sectional analysis from the ECOPD cohort.

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, and multivariate regression models for determining the impact of age on the risk and severity 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 severity of air trapping (ß 2.09, 95% CI - 0.06 to 4.25 for LAA-856), airway reactance (ß - 0.02, 95% CI - 0.04 to - 0.01 for X5; ß 0.30, 95% CI 0.13 to 0.47 for AX; ß 1.75, 95% CI 0.85 to 2.66 for Fres), as well as the decrease in expiratory flow rates (ß - 3.95, 95% CI - 6.19 to - 1.71 for MMEF%predicted; ß - 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 subgroups. CONCLUSIONS: Aging is significantly associated with the prevalence, increased risk, as well as worse severity 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.

Preserved ratio impaired spirometry is associated with small airway dysfunction and reduced total lung capacity.

BACKGROUND: Preserved ratio impaired spirometry (PRISm) refers to decreased forced expiratory volume in 1 s (FEV1) in the setting of preserved ratio. Little is known about the role of PRISm and its complex relation with small airway dysfunction (SAD) and lung volume. Therefore, we aimed to investigate the associations between PRISm and SAD and lung volume. METHODS: We conducted a cross-sectional community-dwelling study in China. Demographic data, standard respiratory epidemiology questionnaire, spirometry, impulse oscillometry (IOS) and computed tomography (CT) data were collected. PRISm was defined as post-bronchodilator FEV1/FVC ≥ 0.70 and FEV1 < 80% predicted. Spirometry-defined SAD was defined as at least two of three of the post-bronchodilator maximal mid-expiratory flow (MMEF), forced expiratory flow 50% (FEF50), and forced expiratory flow 75% (FEF75) less than 65% of predicted. IOS-defined SAD and CT-defined gas trapping were defined by the fact that the cutoff value of peripheral airway resistance R5-R20 > 0.07 kPa/L/s and LAA- 856>20%, respectively. Analysis of covariance and logistic regression were used to determine associations between PRISm and SAD and lung volume. We then repeated the analysis with a lower limit of normal definition of spirometry criteria and FVC definition of PRISm. Moreover, we also performed subgroup analyses in ever smoker, never smoker, subjects without airway reversibility or self-reported diagnosed asthma, and subjects with CT-measured total lung capacity ≥70% of predicted. RESULTS: The final analysis included 1439 subjects. PRISm had higher odds and more severity in spirometry-defined SAD (pre-bronchodilator: odds ratio [OR]: 5.99, 95% confidence interval [95%CI]: 3.87-9.27, P < 0.001; post-bronchodilator: OR: 14.05, 95%CI: 8.88-22.24, P < 0.001), IOS-defined SAD (OR: 2.89, 95%CI: 1.82-4.58, P < 0.001), and CT-air trapping (OR: 2.01, 95%CI: 1.08-3.72, P = 0.027) compared with healthy control after adjustment for confounding factors. CT-measured total lung capacity in PRISm was lower than that in healthy controls (4.15 ± 0.98 vs. 4.78 ± 1.05 L, P < 0.05), after adjustment. These results were robust in repeating analyses and subgroup analyses. CONCLUSION: Our finding revealed that PRISm was associated with SAD and reduced total lung capacity. Future studies to identify the underlying mechanisms and longitudinal progression of PRISm are warranted.

Validity of a portable spirometer in the communities of China.

BACKGROUND: The lack of simple and affordable spirometry has led to the missed and delayed diagnoses of chronic respiratory diseases in communities. The PUS201P is a portable spirometry developed to solve this problem. OBJECTIVE: We aimed to verify the consistency of the PUS201P spirometer with conventional Jaeger spirometer. METHODS: In this cross-sectional study, we randomly recruited 202 subjects aged > 40 years. Testing with the portable spirometry and conventional spirometry were performed on all participants. We compared forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC measured by the PUS201P device with the conventional spirometer. Pearson correlation coefficient and Interclass Correlation Coefficient (ICC) were assessed to confirm the consistency of the measures from two instruments. Bland-Altman graph was created to assess the agreement of the measures from two devices. RESULTS: 202 participants were included in this study. The ICC on FEV1, FVC, FEV1/FVC measured by the portable spirometer and the conventional spirometer were 0.95 (95% confidence interval [CI]: 0.94-0.96), 0.92 (95% CI: 0.90-0.94], 0.93 (95% CI: 0.91-0.95), respectively. The Bland-Altman plots showed that the mean difference between the measures from two spirometers are always located in the 95% limits of agreement. CONCLUSIONS: Our results support that the measures from the portable spirometer and the conventional spirometer have a good agreement and reproducibility. And the portable spirometer is a reliable tool to screen and diagnose chronic airway diseases in the primary care settings.

Associations Between Estimated Pulse Wave Velocity and Five-Year All-Cause Mortality in Patients with Atherosclerotic Cardiovascular Disease with and without Standard Modifiable Risk Factors: Evidence From NHANES 1999-2016.

Aim: The study aimed to analyze the associations between estimated pulse wave velocity (ePWV) and 5-year mortality in atherosclerotic cardiovascular disease (ASCVD) patients with and without standard modifiable risk factors (SMuRFs), which included smoking status, hypertension, diabetes, and hypercholesterolemia. Methods: The present retrospective cohort study utilized data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2016. Patients with ASCVD who completed both the questionnaire survey and serum testing were included. Patients were categorized into the ≥1 SMuRF group if they had at least one SMuRF, while those without any SMuRFs were classified into the SMuRF-less group. The ePWV, which was calculated using the age and mean blood pressure, was evenly divided into three categories: low (Q1), medium (Q2), and high (Q3). Multivariable weighted Cox proportional-hazard regression analyses were utilized to explore the risk factors associated with 5-year mortality in patients with and without SMuRFs. And restricted cubic spline curve (RCS) was used to assess their nonlinear correlation. Results: A total of 1901 patients with ASCVD were included in the study. For the patients in ≥1 SMuRF group, the Q3 group included patients who were older, with a higher proportion of males, more comorbidities, and a lower body mass index than the Q1 group (P<0.05). The Cox proportional-hazard regression model results revealed, the Q3 group had a higher risk of 5-year mortality than the Q1 group [hazard ratio (HR) 4.30, 95% confidence interval (CI) (2.66, 6.95), P<0.001]. RCS demonstrated a linear trend between high level of ePWV and decreased risks of mortality. Similar results were observed in the SMuRF-less group [HR 10.62, 95% CI (1.22, 92.06), P=0.032]. Conclusion: A high level of ePWV signified a higher risk of 5-year mortality in ASCVD patients with and without SMuRFs.

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

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

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

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

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

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

Replication of Porcine Astrovirus Type 1-Infected PK-15 Cells In Vitro Affected by RIG-I and MDA5 Signaling Pathways.

The interferon (IFN) system is an extremely powerful antiviral response in animal cells. The subsequent effects caused by porcine astrovirus type 1 (PAstV1) IFN activation are important for the host's response to viral infections. Here, we show that this virus, which causes mild diarrhea, growth retardation, and damage of the villi of the small intestinal mucosa in piglets, induces an IFN response upon infection of PK-15 cells. Although IFN-ß mRNA was detected within infected cells, this response usually occurs during the middle stages of infection, after genome replication has taken place. Treatment of PAstV1-infected cells with the interferon regulatory factor 3 (IRF3) inhibitor BX795 decreased IFN-ß expression, whereas the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) inhibitor BAY11-7082 did not. These findings indicate that PAstV induced the production of IFN-ß via IRF3-mediated rather than NF-κB-mediated signaling pathways in PK-15 cells. Moreover, PAstV1 increased the protein expression levels of retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) in PK-15 cells. The knockdown of RIG-I and MDA5 decreased the expression levels of IFN-ß and the viral loads and increased the infectivity of PAstV1. In conclusion, PAstV1 induced the production of IFN-ß via the RIG-I and MDA5 signaling pathways, and the IFN-ß produced during PAstV1 infection inhibited viral replication. These results will help provide new evidence that PAstV1-induced IFNs may protect against PAstV replication and pathogenesis. IMPORTANCE Astroviruses (AstVs) are widespread and can infect multiple species. Porcine astroviruses produce mainly gastroenteritis and neurological diseases in pigs. However, astrovirus-host interactions are less well studied, particularly with respect to their antagonism of IFN. Here, we report that PAstV1 acts via IRF3 transcription pathway activation of IFN-ß. In addition, the knockdown of RIG-I and MDA5 attenuated the production of IFN-ß induced by PAstV1 in PK-15 cells and increased efficient viral replication in vitro. We believe that these findings will help us to better understand the mechanism of how AstVs affect the host IFN response.

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

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

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

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

In Situ Synthesis Mechanism and Photocatalytic Performance of Cyano-Bridged Cu (I)/Cu (II) Ultrathin Nanosheets.

In situ synthesis of cyano-bridged Cu (I)/Cu (II) complexes usually requires organometallic catalysts or is carried out under high-temperature and high-pressure conditions. Herein, the cyano-bridged two-dimensional Cu (I)/Cu (II) photocatalyst, [Cu2 (Py)3(CN)3]n (1), is synthesized in situ at room temperature. The in situ synthesis mechanism of 1 shows that the partial Cu (II) complex catalyzed the C-C bond cleavage of 1,3-isophthalonitrile (L) to introduce -CN and generate Cu (I)/Cu (II). Its ultrathin nanosheets can be obtained by adding sodium dodecyl benzene sulfonate and performing ultrasonic synthesis in the process of synthesis 1. The ultrathin nanosheets of 1 have a lattice distance of about 0.31 nm, and it can rapidly decompose methylene blue (MB) (K = 0.25 mg L-1 min-1 at pH = 3). This research work is beneficial for in situ synthesis of cyano-bridged Cu (I)/Cu (II) complexes at room temperature and explores their synthesis and photocatalytic mechanism.

Validity of regional network systems on reperfusion therapy in diabetes mellitus and non-diabetes mellitus patients with ST-segment elevation myocardial infarction.

Background: Patients with ST-segment elevation myocardial infarction (STEMI) with diabetes mellitus (DM) had higher mortality and poorer prognosis than those without DM. Previous studies had demonstrated the effectiveness of regional network systems (RNS) for reperfusion therapy in patients with STEMI. However, the differences in nursing care with RNS in subgroups of patients with DM with STEMI were unclear. Our study aimed to evaluate the validity of RNS in reperfusion therapy in patients with STEMI with or without DM. Methods: We retrospectively enrolled patients with STEMI who received reperfusion therapy at the chest pain center of the 920th Hospital in Kunming City, Yunnan Province from 2019 to 2021. Personal information and hospitalization information for patients with STEMI were collected through the chest pain center registration system. Univariate and multivariate logistic regression were used to analyze factors associated with outcomes in patients with STEMI who received RNS. Wilcoxon rank-sum test and chi-squared test were used to analyze the differences in reperfusion therapy times and clinical outcomes between RNS and non-RNS in patients with STEMI with or without DM. Results: This study enrolled 1,054 patients with STEMI, including 148 patients with DM and 906 patients without DM. Logistic regression analysis indicated that DM was associated with patients with STEMI who received RNS [OR 1.590 95% CI (1.034-2.446), P = 0.035]. RNS may decrease the reperfusion therapy time in patients with STEMI and patients without DM with STEMI, including the first medical contact (FMC) to door, FMC to wire and FMC to catheterization laboratory activity (all P < 0.05). However, we found no significant difference in reperfusion therapy times with and without RNS in patients with DM (all P > 0.05). Conclusion: Regional network systems may decrease the reperfusion therapy time in patients without DM with STEMI, but no decrease was found in patients with DM with STEMI.

Association Between Serum Total Bilirubin Level and Lung Function Decline in Patients with COPD: Results from a Pooled Study.

Background: 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 (ß 0.02, 95% CI 0.001~0.02, P = 0.025 and ß 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 (ß 4.91, 95% CI 1.68~8.14, P = 0.025 and ß 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.

Discordant Spirometry and Impulse Oscillometry Assessments in the Diagnosis of Small Airway Dysfunction.

Background and objective: Spirometry is commonly used to assess small airway dysfunction (SAD). Impulse oscillometry (IOS) can complement spirometry. However, discordant spirometry and IOS in the diagnosis of SAD were not uncommon. We examined the association between spirometry and IOS within a large cohort of subjects to identify variables that may explain discordant spirometry and IOS findings. Methods: 1,836 subjects from the ECOPD cohort underwent questionnaires, symptom scores, spirometry, and IOS, and 1,318 subjects were examined by CT. We assessed SAD with R5-R20 > the upper limit of normal (ULN) by IOS and two of the three spirometry indexes (maximal mid-expiratory flow (MMEF), forced expiratory flow (FEF)50%, and FEF75%) < 65% predicted. Multivariate regression analysis was used to analyze factors associated with SAD diagnosed by only spirometry but not IOS (spirometry-only SAD) and only IOS but not spirometry (IOS-only SAD), and line regression was used to assess CT imaging differences. Results: There was a slight agreement between spirometry and IOS in the diagnosis of SAD (kappa 0.322, p < 0.001). Smoking status, phlegm, drug treatment, and family history of respiratory disease were factors leading to spirometry-only SAD. Spirometry-only SAD had more severe emphysema and gas-trapping than IOS-only SAD in abnormal lung function. However, in normal lung function subjects, there was no statistical difference in emphysema and gas-trapping between discordant groups. The number of IOS-only SAD was nearly twice than that of spirometry. Conclusion: IOS may be more sensitive than spirometry in the diagnosis of SAD in normal lung function subjects. But in patients with abnormal lung function, spirometry may be more sensitive than IOS to detect SAD patients with clinical symptoms and CT lesions.

Association Between Serum Total Bilirubin and COPD: Results from a Cross-Sectional Study and a Bidirectional Mendelian Randomization Analysis.

Background: 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.

Corrigendum: Discordant spirometry and impulse oscillometry assessments in the diagnosis of small airway dysfunction.

[This corrects the article DOI: 10.3389/fphys.2022.892448.].