Pirfenidone and nintedanib exert additive antifibrotic effects by the SPP1-AKT pathway in macrophages and fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease with high mortality rates. It has been shown that pirfenidone (PFD) and nintedanib (Ofev) can slow down the decline in lung function of IPF patients, but their efficacy remains suboptimal. Some studies have suggested that the combination of PFD and Ofev may yield promising results. However, there is a lack of research on the combined application of these two medications in the treatment of IPF. A mouse model of bleomycin-induced (BLM) pulmonary fibrosis was established to investigate the impact of combination therapy on pulmonary fibrosis of mice. The findings demonstrated a significant reduction in lung tissue damage in mice treated with the combination therapy. Subsequent transcriptome analysis identified the differential gene secreted phosphoprotein 1 (SPP1), which was found to be associated with macrophages and fibroblasts based on multiple immunofluorescence staining results. Analysis of a phosphorylated protein microarray indicated that SPP1 plays a regulatory role in macrophages and fibroblasts via the AKT pathway. Consequently, the regulation of macrophages and fibroblasts in pulmonary fibrosis by the combination of PFD and Ofev is mediated by SPP1 through the AKT pathway, potentially offering a novel therapeutic option for IPF patients. Further investigation into the targeting of SPP1 for the treatment of pulmonary fibrosis is warranted.

Mediating Effect of Tobacco Dependence on the Association Between Maternal Smoking During Pregnancy and Chronic Obstructive Pulmonary Disease: Case-Control Study.

BACKGROUND: Maternal smoking during pregnancy (MSDP) is a known risk factor for offspring developing chronic obstructive pulmonary disease (COPD), but the underlying mechanism remains unclear. OBJECTIVE: This study aimed to explore whether the increased COPD risk associated with MSDP could be attributed to tobacco dependence (TD). METHODS: This case-control study used data from the nationwide cross-sectional China Pulmonary Health study, with controls matched for age, sex, and smoking status. TD was defined as smoking within 30 minutes of waking, and the severity of TD was assessed using the Fagerstrom Test for Nicotine Dependence. COPD was diagnosed when the ratio of forced expiratory volume in 1 second to forced vital capacity was <0.7 in a postbronchodilator pulmonary function test according to the 2017 Global Initiative for Chronic Obstructive Lung Disease criteria. Logistic regression was used to examine the correlation between MSDP and COPD, adjusting for age, sex, BMI, educational attainment, place of residence, ethnic background, occupation, childhood passive smoking, residential fine particulate matter, history of childhood pneumonia or bronchitis, average annual household income, and medical history (coronary heart disease, hypertension, and diabetes). Mediation analysis examined TD as a potential mediator in the link between MSDP and COPD risk. The significance of the indirect effect was assessed through 1000 iterations of the "bootstrap" method. RESULTS: The study included 5943 participants (2991 with COPD and 2952 controls). Mothers of the COPD group had higher pregnancy smoking rates (COPD: n=305, 10.20%; controls: n=211, 7.10%; P<.001). TD was more prevalent in the COPD group (COPD: n=582, 40.40%; controls: n=478, 33.90%; P<.001). After adjusting for covariates, MSDP had a significant effect on COPD (ß=.097; P<.001). There was an association between MSDP and TD (ß=.074; P<.001) as well as between TD and COPD (ß=.048; P=.007). Mediation analysis of TD in the MSDP-COPD association showed significant direct and indirect effects (direct: ß=.094; P<.001 and indirect: ß=.004; P=.03). The indirect effect remains present in the smoking population (direct: ß=.120; P<.001 and indirect: ß=.002; P=.03). CONCLUSIONS: This study highlighted the potential association between MSDP and the risk of COPD in offspring, revealing the mediating role of TD in this association. These findings contribute to a deeper understanding of the impact of prenatal tobacco exposure on lung health, laying the groundwork for the development of relevant prevention and treatment strategies.

Heterogeneities and impact profiles of early chronic obstructive pulmonary disease status: findings from the China Pulmonary Health Study.

Background: The prevalence, epidemiological and clinical heterogeneities, and impact profiles of individuals with preserved ratio impaired spirometry (PRISm), pre-COPD, young COPD, and mild COPD in general Chinese population were not known yet. Methods: Data were obtained from the China Pulmonary Health study (2012-2015), a nationally representative cross-sectional survey that recruited 50,991 adults aged 20 years or older. Definitions of the four early disease status were consistent with the latest publications and the Global Initiative for Chronic Obstructive Lung Disease criteria. Findings: The age-standardised prevalences of PRISm, pre-COPD, young COPD, and mild COPD were 5.5% (95% confidence interval, 4.3-6.9), 7.2% (5.9-8.8), 1.1% (0.7-1.8), and 3.1% (2.5-3.8), respectively. In summary, mild COPD was under more direct or established impact factor exposures, such as older age, male gender, lower education level, lower family income, biomass use, air pollution, and more accumulative cigarette exposures; young COPD and pre-COPD experienced more personal and parents' events in earlier lives, such as history of bronchitis or pneumonia in childhood, frequent chronic cough in childhood, parental history of respiratory diseases, passive smoke exposure in childhood, and mother exposed to passive smoke while pregnant; pre-COPD coexisted with heavier symptoms and comorbidities burdens; young COPD exhibited worse airway obstruction; and most of the four early disease status harbored small airway dysfunction. Overall, older age, male gender, lower education level, living in the urban area, occupational exposure, frequent chronic cough in childhood, more accumulated cigarette exposure, comorbid with cardiovascular disease and gastroesophageal reflux disease were all associated with increased presence of the four early COPD status; different impact profiles were additionally observed with distinct entities. Over the four categories, less than 10% had ever taken pulmonary function test; less than 1% reported a previously diagnosed COPD; and no more than 13% had received pharmaceutical treatment. Interpretation: Significant heterogeneities in prevalence, epidemiological and clinical features, and impact profiles were noted under varied defining criteria of early COPD; a unified and validated definition for an early disease stage is warranted. Closer attention, better management, and further research need to be administrated to these population. Funding: Chinese Academy of Medical Sciences Institute of Respiratory Medicine Grant for Young Scholars (No. 2023-ZF-9); China International Medical Foundation (No. Z-2017-24-2301); Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (No. 2021-I2M-1-049); National High Level Hospital Clinical Research Funding (No. 2022-NHLHCRF-LX-01); Major Program of National Natural Science Foundation of China (No. 82090011).

Combined effect of ozone and household air pollution on COPD in people aged less than 50 years old.

OBJECTIVES: Air pollution has been suggested as an important risk factor for chronic obstructive pulmonary disease (COPD); however, evidence of interactive effects on COPD between different factors was sparse, especially for young adults. We aimed to assess the combined effects of ambient ozone (O3) and household air pollution on COPD in young individuals. METHODS: We conducted a population-based study of residents aged 15-50 years in the low-income and middle-income regions of western China. We used multivariable logistic regression models to examine the associations between long-term ozone exposure and COPD in young individuals. RESULTS: A total of 6537 young cases were identified among the participants, with a COPD prevalence rate of 7.8 (95% CI 7.2% to 8.5%), and most young COPD individuals were asymptomatic. Exposure to household air pollution was associated with COPD in young patients after adjustment for other confounding factors (OR 1.82, 95% CI 1.41 to 2.37). We also found positive associations of COPD with O3 per IQR increase of 20 ppb (OR 1.92, 95% CI 1.59 to 2.32). The individual effects of household air pollution and O3 were 1.68 (95% CI 1.18 to 2.46) and 1.55 (95% CI 0.99 to 2.43), respectively, while their joint effect was 3.28 (95% CI 2.35 to 4.69) with the relative excess risk due to interaction of 1.05 (95% CI 0.33 to 1.78). CONCLUSIONS: This study concludes that exposure to ambient O3 and household air pollution might be important risk factors for COPD among young adults, and simultaneous exposure to high levels of the two pollutants may intensify their individual effects.

Ambient particulate matter associates with asthma in high altitude region: A population-based study.

Background: Exposure to particulate matter (PM) has been a major public health threat, but the potentially differential effects on asthma of PM remain largely unknown in high altitude settings. We evaluated the effects of ambient PM on asthma in high altitude settings. Methods: The study recruited a representative sample from high altitude settings using a multistage stratified sampling procedure. Asthma was defined by a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. The annual mean PM2.5 and PM10 concentrations were calculated for each grid cell at 1-km spatial resolution based on the geographical coordinates. Results: We analyzed data for participants (mean age 39.1 years, 51.4% female) and 183 (3.7%, 95% confidence interval (CI): 3.2-4.2) of the participants had asthma. Prevalence was higher in women (4.3%, 95% CI 3.5-5.1) than in men (3.1%, 2.4-3.8) and increasing with higher concentration of PM exposures. For an interquartile range (IQR) difference (8.77 µg/m3) in PM2.5 exposure, the adjusted odds ratio (OR) was 1.64 (95% CI 1.46-1.83, P < 0.001) for risk of asthma. For PM10, there was evidence for an association with risk of asthma (OR 2.34, 95% CI: 1.75-3.15, P < 0.001 per IQR of 43.26 µg/m3). Further analyses showed that household mold or damp exposure may aggravate PM exposure associated risks of asthma. Conclusions: This study identified that PM exposure could be a dominate environmental risk factor for asthma but largely unconsidered in the high-altitude areas. The association between PM exposure and asthma should be of interest for planners of national policies and encourage programs for prevention of asthma in residents living at high altitudes.

HNRNPD is a prognostic biomarker in non-small cell lung cancer and affects tumor growth and metastasis via the PI3K-AKT pathway.

Heterogeneous nuclear ribonucleoprotein D (HNRNPD) can regulate expression of key proteins in various cancers. However, the prognostic predictive value and biology function of HNRNPD in non-small cell lung cancer (NSCLC) is unknown. First, we used the TCGA and GEO datasets to determine that HNRNPD predicts the prognosis of NSCLC patients. Following that, we knocked down HNRNPD in NSCLC cell lines in vitro and validated its biological function using CCK-8, transwell assays, wound healing tests, and Western blotting. Finally, we constructed tissue microarrays (TMAs) from 174 NSCLC patients and verified our findings using immunohistochemistry staining for HNRNPD from public databases. In both the public datasets, NSCLC tissues with elevated HNRNPD expression had shorter overall survival (OS). In addition, HNRNPD knockdown NSCLC cell lines showed significantly reduced proliferation, invasion, and metastatic capacity via the PI3K-AKT pathway. Finally, elevated HNRNPD expression in NSCLC TMAs was linked to a poorer prognosis and decreased PD-L1 expression levels. HNRNPD is associated with a poorer prognosis in NSCLC and affects tumor growth and metastasis via the PI3K-AKT pathway.

Airflow obstruction and small airway dysfunction following pulmonary tuberculosis: a cross-sectional survey.

OBJECTIVES: Pulmonary function impairment and chronic respiratory symptoms after tuberculosis are relatively common in low-income and middle-income countries. We aimed to estimate the impact of post-tuberculosis (post-TB) on pulmonary function. METHODS: This large cross-sectional, population-based study included subjects aged 15 years or older with technically acceptable postbronchodilator spirometry measurements. Post-TB was diagnosed on the basis of radiological evidence and/or medical history. Airflow obstruction was defined as a postbronchodilator forced expiratory volume in 1 s/forced vital capacity ratio below the lower limit of normal of Global Lung Function Initiative (GLI) lung function equations. Small airway dysfunction was diagnosed if at least two of the following indicators were less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50% or FEF 75%. RESULTS: In this population sample (N=8680, mean age: 40.1 years), 610 (7.0% (95% CI 6.5 to 7.6) participants were post-TB. Post-TB subjects had more frequent respiratory symptoms (46.8% vs 28.3%). Among post-TB subjects, 130 (21.3% (95% CI 18.1 to 24.8)) had airflow obstruction; OR of airflow obstruction was significantly associated with post-TB after adjustment for other confounding factors (OR 1.31, 95% CI 1.05 to 1.62). Post-TB was also associated with small airway dysfunction (OR 1.28, 95% CI1.07 to 1.53), which was present in 297 (48.9% (95% CI 33.9 to 53.0)) post-TB subjects. CONCLUSIONS: Our findings support existing knowledge that post-TB is positively associated with pulmonary function impairment and make for frequent respiratory symptoms. Post-TB should be considered as a potentially important cause of airflow obstruction and respiratory symptoms in patients originating from countries with a high burden of tuberculosis.

Prevalence and burden of chronic cough in China: a national cross-sectional study.

Background: Chronic cough is a common complaint, but there are no population-based data on its burden in China. We determined the prevalence of chronic cough and its impact on health status in adults stratified by sex, age and the diagnosis of COPD or the presence of small airway dysfunction (SAD). Methods: A representative sample of 57 779 Chinese adults aged 20 years or older was recruited and pulmonary function test was measured. Chronic cough was defined as cough lasting for >3 months in each year. Quality of life was assessed by the 12-item Short Form Health Survey (SF-12), and self-reported history of hospital visits was recorded. Results: Chronic cough was found in 3.6% (95% CI 3.1-4.1) of Chinese adults, 2.4% (95% CI 1.9-3.1) of those aged 20-49 years and 6.0% (95% CI 5.3-6.8) of those aged 50 years or older. Individuals with chronic cough had an impaired physical component summary (PCS) score of the SF-12 (p<0.0001) and more emergency visits (p=0.0042) and hospital admissions (p=0.0002). Furthermore, the impact of chronic cough on PCS score was more significant in those aged 50 years or older, or with COPD (p=0.0018 or 0.0002, respectively), with the impact on hospital admission being more significant in those with COPD or with SAD (p=0.0026 or 0.0065, respectively). Conclusions: Chronic cough is prevalent in China and is associated with a poorer health status, especially in individuals aged 50 years or older and those with the diagnosis of COPD or SAD.

Ginsenoside Rb1 Alleviates Bleomycin-Induced Pulmonary Inflammation and Fibrosis by Suppressing Central Nucleotide-Binding Oligomerization-, Leucine-Rich Repeat-, and Pyrin Domains-Containing Protein Three Inflammasome Activation and the NF-κB Pathway.

Purpose: Idiopathic pulmonary fibrosis is a chronic and irreversible fibrotic interstitial pneumonia of unknown etiology and therapeutic strategies are limited. Emerging evidence suggests that the continuous activation of the central nucleotide-binding oligomerization-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is involved in the pathogenesis of pulmonary fibrosis. Ginsenoside Rb1 (G-Rb1) is the most abundant component in the traditional Chinese herb ginseng and has anti-inflammatory and anti-fibrotic activities. The purpose of this study was to explore whether G-Rb1 exerts anti-inflammatory and anti-fibrotic activities in vivo and in vitro by suppressing the activation of the NLRP3 inflammasome and NF-κB pathway. Methods: Forty-eight male C57BL/6 mice were randomly divided into four groups (n=12/group) as follows: control, bleomycin (BLM), BLM/G-Rb1, and G-Rb1. A pulmonary fibrosis model was developed via an intratracheal injection of BLM. Six mice from each group were euthanized on days 3 and 21. The degree of pulmonary fibrosis was examined by histological evaluation and assessing α-smooth muscle actin levels. THP-1 cells were differentiated into macrophages, and stimulated by lipopolysaccharide and adenosine triphosphate. Activation of the NLRP3 inflammasome and NF-κB pathway was determined by Western blotting. Interleukin-1 beta and interleukin-18 levels were measured by ELISA. MRC-5 cells were cultured in the conditioned medium of the treated macrophages, after which markers of myofibroblasts were determined by Western blotting. Results: G-Rb1 ameliorated BLM-induced pulmonary inflammation and fibrosis in mice, and suppressed NLRP3 inflammasome activation and the NF-κB pathway in lung tissues. Moreover, interleukin-1 beta secreted after NLRP3 inflammasome activation in macrophages promoted fibroblast differentiation. G-Rb1 inhibited lipopolysaccharide- and adenosine triphosphate-induced NLRP3 inflammasome activation in macrophages and disturbed the crosstalk between macrophages and fibroblasts. Conclusion: G-Rb1 ameliorates BLM-induced pulmonary inflammation and fibrosis by suppressing NLRP3 inflammasome activation and the NF-κB pathway. Hence, G-Rb1 is a potential novel therapeutic drug for idiopathic pulmonary fibrosis.

Chronic Obstructive Pulmonary Disease With Asthma-Like Features in the General Population in China.

Background: Patients with features of both asthma and chronic obstructive pulmonary disease (COPD) are seen commonly in the clinic but less is known in the general population. We investigated the prevalence and the heterogeneity of COPD with concomitant features of asthma in Chinese adult population. Methods: COPD was defined as post-bronchodilator ratio of forced expiratory volume in 1s (FEV1) to forced vital capacity of less than the lower limits of normal. COPD with concomitant features of asthma was defined as either COPD with asthma diagnosed by self-reported physician-diagnosis or by presence of current wheeze, or as COPD with high bronchodilator response (HBR) defined as an increase in FEV1 >15% and >400 ml after bronchodilator. Results: COPD with concomitant features of asthma was found in 1.62% (95% CI 1.31-2.00) of adults (≥20 years) or in 15.2% (95% CI 13.0-17.7) of COPD patients. Compared with COPD with HBR, COPD with asthma diagnosis or wheeze were older (61.8 ± 1.1 years vs. 47.4 ± 2.8 years, P < 0.001), and with a lower post-bronchodilator FEV1%pred (68.2 ± 2.3 vs. 96.6 ± 3.4, P < 0.001). Age, smoking status, biomass use and allergic rhinitis were associated with increasing prevalence of COPD with asthma diagnosis or wheeze, and had greater impaired health status, more comorbidities and more acute exacerbations in the preceding 12 months. Conclusions: COPD with concomitant features of asthma is common in people with COPD and those with COPD with asthma diagnosis or wheeze experience worse clinical severity than COPD with HBR. These findings will help toward the definition of the asthma-COPD overlap condition.

Development and Validation of a Screening Questionnaire of COPD from a Large Epidemiological Study in China.

OBJECTIVE: We aimed to establish an easy-to-use screening questionnaire with risk factors and suspected symptoms of COPD for primary health care settings. METHODS: Based on a nationwide epidemiological study of pulmonary health among adults in mainland China (China Pulmonary Health, CPH study) between 2012 and 2015, participants ≥40 years who completed the questionnaire and spirometry tests were recruited and randomly divided into development set and validation set by the ratio of 2:1. Parameters including sex, age, BMI, residence, education, smoking status, smoking pack-years, biomass exposure, parental history of respiratory diseases and daily respiratory symptoms were initially selected for the development of scoring system. Receiver operating characteristic (ROC) curve, area under curve (AUC), positive and negative predictive values were calculated in development set and validation set. RESULTS: After random split by 2:1 ratio, 22443 individuals were assigned to development set and 11221 to validation set. Ten variables were significantly associated with COPD independently in development set after a stepwise selection by multivariable logistic model and used to develop scoring system. The scoring system yielded good discrimination, as measured by AUC of 0.7737, and in the validation set, the AUC was 0.7711. When applying a cutoff point of ≥16, the sensitivity in development set was 0.69 (0.67 - 0.71); specificity 0.72 (0.71 - 0.73), PPV 0.25 (0.24 - 0.26) and NPV 0.94 (0.94 - 0.95). CONCLUSION: We developed and validated a comprehensive screening questionnaire, COPD-CPHS, with good discrimination. The score system still needs to be validated by large cohort in the future.Supplemental data for this article is available online at https://doi.org/10.1080/15412555.2022.2042504 .

Role of Pyroptosis in Respiratory Diseases and its Therapeutic Potential.

Pyroptosis is an inflammatory type of regulated cell death that is dependent on inflammasome activation and downstream proteases such as caspase-1 or caspase 4/5/11. The main executors are gasdermins, which have an inherent pore-forming function on the membrane and release inflammatory cytokines, such as interleukin (IL)-1ß, IL-18 and high mobility group box 1. Emerging evidence demonstrates that pyroptosis is involved in the pathogenesis of various pulmonary diseases. In this review, we mainly discuss the biological mechanisms of pyroptosis, explore the relationship between pyroptosis and respiratory diseases, and discuss emerging therapeutic strategies for respiratory diseases.

Management of acute exacerbation of chronic obstructive pulmonary disease under a tiered medical system in China.

BACKGROUND: The Chinese government has promoted the 'tiered medical services' policy in which diseases are classified by severity, mode of onset and difficulty of treatment since 2015 to optimize medical resources. We evaluated the diagnosis and treatment of acute exacerbation (AE) of chronic obstructive pulmonary disease (AECOPD) under the tiered system. METHODS: We conducted a cross-sectional study. COPD characteristics and treatments were compared among hospitals in different tiers. Associations were examined by univariate and multivariable logistic regression analysis. In addition, multivariate logistic regression was performed to identify the possible influencing factors of antibiotics, glucocorticoids and anticoagulant usages. RESULTS: Eligible COPD patients (n = 432) were consecutively recruited from eight hospitals in different tiers in China. Patients in the countryside preferred the community hospitals, whereas patients in cities preferred second-tier and teaching hospitals when they suffer from AECOPD. It indicates most COPD patients are likely to treat their disease locally. The severity of COPD AE increased with tiers of hospitals (p < 0.001). However, our results clearly show that most community hospitals can only deal with mild exacerbation of COPD. Approximately 90% of AE patients received antibiotics. We speculated that antibiotics abuse might exist in the three tiers of hospitals. Multivariate analysis demonstrated that long-term antibiotics usage (⩾14 days) was associated with moderate exacerbation [odds ratio (OR): 5.295, 95% confidence intervals (CI) 2.248-12.473, p < 0.001], radiographic progression (OR: 2.176, 95% CI: 1.047-4.522, p = 0.037), positive sputum etiology (OR: 3.073, 95% CI: 1.477-6.394, p = 0.003) and increased white blood cells (OR: 2.470, 95% CI: 1.190-5.126, p = 0.015). The proportion of glucocorticoids increased with the hospital hierarchy (18.6% versus 45.6% versus 69.2%, p < 0.001). The proportions of severe cases in the second-tier hospitals were 26.9%; however, non-invasive positive pressure ventilation (NPPV) rate was only 14.7%. Anticoagulant is not commonly used in AECOPD, and the community hospitals had the lowest proportion of anticoagulation regimen (1.7% versus 14.3% versus 20.5%, p = 0.002). CONCLUSIONS: The 'tiered medical services' policy in AECOPD management has been unsatisfactory in the past years. Irrational treatment strategies in different hospitals were still found when comparing with international guideline. Further reform of the policy is still needed to optimize the management of AECOPD in China.

Associations of residential greenness with lung function and chronic obstructive pulmonary disease in China.

BACKGROUND: Studies on the association of greenness with respiratory health are scarce in developing countries, and previous studies in China have focused on only one or two indicators of lung function. OBJECTIVE: The study aims to evaluate the associations of residential greenness with full-spectrum lung function indicators and prevalence of chronic obstructive pulmonary disease (COPD). METHODS: This nationwide cross-sectional survey included 50,991 participants from the China Pulmonary Health study. Lung function indicators included four categories: indicators of obstructive ventilatory dysfunction (FEV1, FVC and FEV1/FVC); an indicator of large-airway dysfunction (PEF); indicators of small-airway dysfunction (FEF25-75% and FEV3/FEV6); and other indicators. Residential greenness was assessed by the Normalized Difference Vegetation Index (NDVI). Multivariable linear regression models and logistic regression models were used to analyze associations of greenness with lung function and COPD prevalence. RESULTS: Within the 500 m buffer, an interquartile range (IQR) increase in NDVI was associated with higher FEV1 (24.76 mL), FVC (16.52 mL), FEV1/FVC (0.38), FEF50% (56.34 mL/s), FEF75% (33.43 mL/s), FEF25-75% (60.73 mL/s), FEV3 (18.59 mL), and FEV6 (21.85 mL). However, NDVI was associated with lower PEF. In addition, NDVI was significantly associated with 10% lower odds of COPD. The stratified analyses found that the associations were only significant in middle-young people, females, and nonsmokers. The associations were influenced by geographic regions. CONCLUSIONS: Residential greenness was associated with better lung function and lower odds of COPD in China. These findings provide a scientific basis for healthy community planning.

Stable Chronic Obstructive Pulmonary Disease (COPD) Management Under a Tiered Medical System in China.

BACKGROUND: Early diagnosis and proper management of a large number of chronic obstructive pulmonary disease (COPD) patients are great challenges for the Chinese health care system. Although tiered medical services have been promoted by the Chinese government since 2015, they have not been ideally implemented for COPD diagnosis and management. PATIENTS AND METHODS: We designed a cross-sectional study. Eligible COPD patients (n = 648) and physicians (n = 161) were consecutively recruited from 8 hospitals in different tiers in China. COPD characteristics and treatments were compared among hospitals in different tiers. Multivariate logistic regression was performed to identify risk factors associated with airflow limitation, symptoms and acute exacerbation. RESULTS: The PFT rate at first diagnosis was 99%, 69.4% and 29.9% in teaching, second-tier and community hospitals (P < 0.001). Only approximately 10.9%, 1.7% and 9.6% and 21.8%, 6.9% and 32% of COPD patients received influenza or pneumococcal vaccines (P < 0.001). The proportion of patients who did not use inhaled drugs or had irregular inhalation was 2%, 24.6% and 78.8% (P < 0.001). Education level (RR-1 = -41.26%, P = 0.007), FEV1%pred (RR-1 = -2.76%, P < 0.001), and influenza vaccination in the last year (RR-1 = -64.53%, P = 0.006) were all negatively correlated with COPD acute exacerbation (AE). COPD duration (RR-1 = 131.73%, P = 0.009), AE (RR-1 = 151.39%, P < 0.001), and COPD Assessment Test (CAT) scores (RR-1 = 3.82%, P = 0.019) were all positively correlated with COPD airflow limitation severity. CONCLUSION: Differences exist in the diagnosis, treatment and management of COPD among different tiers of hospitals in China. Teaching hospitals can manage COPD patients relatively well. There are still some gaps compared with developed countries.

Long-Term Ozone Exposure and Small Airway Dysfunction: The China Pulmonary Health (CPH) Study.

Rationale: It remains unknown whether long-term ozone exposure can impair lung function. Objectives: To investigate the associations between long-term ozone exposure and adult lung function in China. Methods: Lung function results and diagnosis of small airway dysfunction (SAD) were collected from a cross-sectional study, the China Pulmonary Health Study (N = 50,991). We used multivariable linear and logistic regression models to examine the associations of long-term ozone exposure with lung function parameters and SAD, respectively, adjusting for demographic characteristics, individual risk factors, and longitudinal trends. We then performed a stratification analysis by chronic obstructive pulmonary disease (COPD). Measurements and Main Results: We observed that each 1 SD (4.9 ppb) increase in warm-season ozone concentrations was associated with a 14.2 ml/s (95% confidence interval [CI], 8.8-19.6 ml/s] decrease in forced expiratory flow at the 75th percentile of vital capacity and a 29.5 ml/s (95% CI, 19.6-39.5 ml/s) decrease in mean forced expiratory flow between the 25th and 75th percentile of vital capacity. The odds ratio of SAD was 1.09 (95% CI, 1.06-1.11) for a 1 SD increase in warm-season ozone concentrations. Meanwhile, we observed a significant association with decreased FEV1/FVC but not with FEV1 or FVC. The association estimates were greater in the COPD group than in the non-COPD group. Conclusions: We found independent associations of long-term ozone exposure with impaired small airway function and higher SAD risks, while the associations with airflow obstruction were weak. Patients with COPD appear to be more vulnerable.

Anxiety and Depression in Patients with Chronic Obstructive Pulmonary Disease in China: Results from the China Pulmonary Health [CPH] Study.

PURPOSE: Anxiety and depression are often underdiagnosed and affect the prognosis of patients with chronic obstructive pulmonary disease (COPD). We analyzed data from the China Pulmonary Health (CPH) study to assess the prevalence of anxiety and depression in COPD patients and their relationship with disease severity. PATIENTS AND METHODS: A total of 57,779 subjects aged 20 years or older were recruited in the CPH study. All participants were assessed using a standard questionnaire and underwent pulmonary function tests before and after the use of a bronchodilator in local health centers. The Hospital Anxiety and Depression Scale (HADS) questionnaire with a cutoff score of 8 was used to define anxiety and depression. The prevalence of anxiety and depression in patients of COPD were investigated. Multivariate logistic regression was used to investigate the effects of COPD and lung function on anxiety and depression. RESULTS: A total of 49,053 participants (20,661 men and 28,392 women) completed the questionnaire with reliable post-bronchodilator pulmonary function test results and were included in the final analysis, of which 4686 (9.55%) were diagnosed with COPD. Of the patients with COPD, 10.79% had anxiety, 13.65% had depression, and 7.08% had anxiety and depression concomitantly. In the multivariate logistic regression analysis, COPD was not significantly associated with anxiety, depression, or both. After adjusting for confounders in model 1, patients in the GOLD III-IV group had a significantly higher risk of anxiety, depression, and their coincidence. After further adjusting for respiratory symptoms in model 2, lung function impairment in the GOLD III-IV group was only significantly associated with a higher risk of depression or at least one of anxiety and depression. CONCLUSION: Anxiety and depression are prevalent in patients with COPD in China. More severe lung function impairment is significantly associated with a higher risk of depression.

Association of fine particulate matter air pollution and its constituents with lung function: The China Pulmonary Health study.

The associations of long-term exposure to various constituents of fine particulate matter (≤2.5 µm in aerodynamic diameter, PM2.5) air pollution with lung function were not clearly elucidated in developing countries. The aim was to evaluate the associations of long-term exposure to main constituents of PM2.5 with lung function in China. This is a nationwide, cross-sectional analysis among 50,991 study participants from the China Pulmonary Health study. Multivariable linear regression models were used to obtain differences of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow (PEF), and forced expiratory flow at 25-75% of exhaled FVC (FEF25-75%) associated with an interquartile range (IQR) change of PM2.5 or its constituents. Residential annual PM2.5 levels varied from 26 µg/m3 to 92 µg/m3 (average: 53 µg/m3). An IQR increase of PM2.5 concentrations was associated with lower FEV1 (19.82 mL, 95% CI: 11.30-28.33), FVC (17.45 mL, 95% CI: 7.16-27.74), PEF (86.64 mL/s, 95% CI: 59.77-113.52), and FEF25-75% (31.93 mL/s, 95% CI: 16.64-47.22). Black carbon, organic matter, ammonium, sulfate, and nitrate were negatively associated with most lung function indicators, with organic matter and nitrate showing consistently larger magnitude of associations than PM2.5 mass. This large-scale study provides first-hand epidemiological evidence that long-term exposure to ambient PM2.5 and some constituents, especially organic matter and nitrate, were associated with lower large- and small- airway function.

Liproxstatin-1 alleviates bleomycin-induced alveolar epithelial cells injury and mice pulmonary fibrosis via attenuating inflammation, reshaping redox equilibrium, and suppressing ROS/p53/α-SMA pathway.

With undetermined etiology and limited treatment option, idiopathic pulmonary fibrosis (IPF) an age related disease is extremely lethal. Persistent injury of epithelial cells, abnormal activation of fibroblasts/myofibroblasts, and superabundant deposition of extracellular matrix protein pathologically characterize IPF. Redox imbalance is reported to play a vital role in both IPF development and senescence. This study aim to investigate whether and how Liproxstatin-1 (Lip-1), a strong lipid autoxidation inhibitor, regulates bleomycin (BLM) induced pulmonary fibrosis both in vivo and in vitro. It's demonstrated that Lip-1 exerted a potent anti-fibrotic function in BLM-induced mice pulmonary fibrosis via alleviating inflammatory, reshaping redox equilibrium, and ameliorating collagen deposition. Lip-1 reduced the level of reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA), promoted the expression of glutathione (GSH), catalase (CAT), and total superoxide dismutase (T-SOD) after BLM treatment. Moreover, in vitro experiments verified that Lip-1 protected A549 cells from BLM-induced injury and fibrosis. Lip-1 seemed to attenuate BLM-induced fibrosis by targeting ROS/p53/α-SMA signaling both in vivo and in vitro. In summary, this study demonstrates that Lip-1 administration performs a protective role in against pulmonary fibrosis and lights up the potential of Lip-1 treatment for patient with IPF in future.

Pulmonary emphysema, bullae, and pneumothorax in COVID-19 pneumonia.

In this paper, we described 2 cases with COVID-19 pneumonia, who developed pulmonary emphysema, bullae, and pneumothorax during therapy. In a 48-year-old man with mechanical ventilation, parts of ground glass opacities and consolidations transformed into emphysema and giant bulla, and bilateral pneumothorax were also observed. In a 35-year-old man, localized emphysema and pulmonary bullae were seen in subpleural area in bilateral upper lobes, where no previous lesions were presented. In conclusion, pulmonary emphysema, bullae, and pneumothorax could be complications of COVID-19. On one hand, surgical emphysema in ventilated COVID-19 patients was observed as in SARS patients. On the other hand, more serious destruction of lung parenchyma was found in COVID-19 patients.