Background: The pathways linking short-term air pollution exposure to hospitalization outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remain poorly understood. This study aims to investigate the associations between air pollutants and both hospitalization risk and prolonged length of stay among patients with AECOPD in Kashgar, and to further explore the potential mediating pathways underlying these associations. Methods: Based on a registry study of patients with AECOPD in Kashgar, China from January 2020 to June 2024, a time-stratified case-crossover design with conditional logistic regression was employed to evaluate the associations between short-term exposure to six ambient air pollutants and the risk of AECOPD hospitalization. Unconditional logistic regression models and LOESS curves were used to examine the relationships between air pollution exposure and length of hospital stay. Furthermore, mediation analyses of twenty-seven blood biomarkers were conducted to explore the potential biological pathways linking air pollutant exposure to hospitalization outcomes. Findings: Ninety-nine percent of patients hospitalized for AECOPD in Kashgar were non-smokers. This study revealed that short-term exposure to NO2 and SO2 was observed significantly associated with an increased risk of AECOPD hospitalization. In particular, SO2 exposure at lag1-2 days showed the strongest association with hospitalization risk. Moreover, exposure to PM2.5, CO, SO2, and O3 was significantly associated with longer hospital stays after adjustment for potential confounders. Furthermore, mediation analysis suggested that hemoglobin, total cholesterol, and several immunological and metabolic biomarkers played important mediating roles in the associations between air pollutants and poor hospitalization outcomes. Interpretation: Short-term exposure to ambient air pollutants, especially NO2 and SO2, may worsen both the incidence and severity of AECOPD. These associations may be partly mediated by alterations in hematological, immunological, and metabolic biomarkers. These findings underscore the importance of reducing air pollution exposure and provide insights into potential biological mechanisms linking air pollution to adverse hospitalization outcomes in patients with AECOPD.

This prospective study aimed to compare the prognostic value of [18F]FAPI-42 (fibroblast activation protein inhibitor) and [18F]FDG PET/CT in patients with idiopathic pulmonary fibrosis (IPF). Fifty-two patients with IPF underwent dual-tracer PET/CT. Whole-lung total uptake (wlTU) was quantified for [18F]FAPI-42 and [18F]FDG. PET parameters were correlated with percent predicted forced vital capacity (FVC

BackgroundSmall airway dysfunction (SAD) and impaired diffusion capacity of the lungs for carbon monoxide (DLCO) are positively associated with a worse prognosis. Individuals with both dysfunctions have been identified in clinical practice and it is unknown whether they have worse health status or need management. We conducted this study to explore the association between SAD and impairedDLCO, and the difference between the groups with two dysfunctions, with either one dysfunction and with no dysfunction.MethodsThis study involved subjects partly from those who had returned for the third-year follow-up (up to December 2022) of the Early Chronic Obstructive Pulmonary Disease study and those who newly participated. We assessed diffusion capacity, questionnaire, exacerbations, spirometry, impulse oscillometry (IOS) and computed tomography (CT). ImpairedDLCOwas defined asDLCO<80% predicted. Spirometry-defined SAD was defined using the percent predicted values of maximal mid-expiratory flow, and forced expiratory flow at 50% and 75% of forced vital capacity, at least two of these three values being <65% predicted after the use of a bronchodilator. IOS-defined SAD was defined when the difference in resistance at 5 and 20 Hz was >0.07 kPa·L−1·s. CT-defined SAD was defined when the percentage of expiratory low-attenuation areas <−856 HU comprised ≥15% of the total lung volume. Covariate analyses and logistic regression were performed to assess the association between impairedDLCOand SAD.ResultsThis study involved 581 subjects. The occurrence of both spirometry- and CT-defined SAD was significantly higher in subjects with impairedDLCOthan normalDLCO. Subjects with two dysfunctions were associated with worse preceding year's exacerbations than controls.ConclusionsImpaired diffusion capacity is positively associated with SAD. Subjects with impaired diffusion capacity and SAD may have a worse health status and need additional management.

BACKGROUND:Preserved ratio impaired spirometry (PRISm) is regarded as a COPD precursor, but whether this varies by smoking status remains unclear. RESEARCH QUESTION:Are annual lung function decline and the risk of developing airflow limitation different among PRISm subtypes by smoking status? STUDY DESIGN AND METHODS:A total of 2,850 participants from a 15-year population-based prospective cohort were included in this analysis. Participants were categorized into 3 groups: patients with normal spirometry who do not smoke (normal control), patients with PRISm who do not smoke (NS-PRISm), and patients with PRISm who have ever smoked (ES-PRISm). We compared annual lung function decline and the risk of developing airflow limitation among the 3 groups. RESULTS:Participants in the normal control group exhibited the fastest decline in annual lung function, followed by the ES-PRISm group, with the NS-PRISm group showing the slowest decline. Participants in the ES-PRISm group had significantly faster annual lung function decline than the NS-PRISm group. Participants in the ES-PRISm group had a significantly increased risk of developing airflow limitation than the NS-PRISm group (95 of 256 [37.1%] vs 69 of 470 [14.7%]; adjusted hazard ratio [HR], 1.90; 95% CI, 1.31-2.77; P = .001) and normal control group (95 of 256 [37.1%] vs 193 of 2,124 [9.1%]; adjusted HR, 2.69; 95% CI, 1.96-3.69; P < .001). Participants in the NS-PRISm group also exhibited a higher risk of developing airflow limitation than those in the normal control group (69 of 470 [14.7%] vs 193 of 2,124 [9.1%]; adjusted HR, 1.41; 95% CI, 1.07-1.87; P = .016). When the ES-PRISm group was further divided into participants with PRISm who currently smoke and those who formerly smoked, both of these PRISm subtypes showed a faster annual lung function decline and a similarly higher risk of airflow limitation than the NS-PRISm group. INTERPRETATION:These findings suggest that both NS-PRISm and ES-PRISm may be potential precursors to COPD and indicate that PRISm should not be restricted to evaluating individuals with a history of smoking alone.

Fibrosing mediastinitis (FM) can block pulmonary vessels and airways, hindering treatment efficacy. Pulmonary artery (PA) stenting might provide a solution in such cases. This study involved 30 patients who had 49 PA stenting procedures for FM. Data on baseline characteristics, CT pulmonary angiography images, stent patency, and hemodynamics were collected. Patients with FM often had a history of chronic obstructive pulmonary disease (15/30), tuberculosis (12/30), and pneumoconiosis (11/30). Patients exhibited typical symptoms such as dyspnea, exercise intolerance, and cough. FM appeared as multiple bilateral shadows with enlarged hilar and mediastinal lymph nodes. Our study found that the PA involvement alone was predominantly in the left and right lower basilar trunk, with the left lower pulmonary arteries (LLPA) involved in 80% of cases and the right lower pulmonary arteries (RLPA) in 100%. Moreover, over 2/3 of patients showed involvement of both PA and pulmonary vein (PV), mainly in the bilateral upper lung lobes, then in the right middle lobe and left lingual lobe. After PA stent implantation, patients showed enhanced tricuspid annular plane systolic excursion (20.6 vs. 18.5, p < 0.001) and reduced right atrial diameter (35.5 vs. 37.3, p = 0.042), along with significant gains in 6-min walk distance (465.2 vs. 392.7, p = 0.002) and improved World Health Organization functional class (p < 0.001). Hemodynamic parameters improved after PA stent placement with significant reductions in systolic pulmonary artery pressure (PAP) (51.1 vs. 64.2, p < 0.001), mean PAP (28.4 vs. 35.2, p < 0.001), pulmonary vascular resistance (4.7 vs. 5.9, p = 0.004), and stent gradient (11.2 vs. 33.4, p < 0.001), along with increased patency (84.8% vs. 28%, p < 0.001), and fractional flow reserve (0.84 vs. 0.44, p < 0.001). Over a median follow-up of 331 days (range 45-980), no significant stent stenosis occurred (p = 0.287). Mild adverse events like cough and mild hemoptysis were noted during the procedure. Secondary intervention was needed for 5 of 49 stents. PA stents placement, especially the LLPA and RLPA, improved pulmonary vascular patency, hemodynamics, and symptoms.

Small airway dysfunction (SAD) is common but little is known about the longitudinal prognosis of spirometry-defined SAD. Therefore, we aimed to evaluate the risk of lung function decline and incident chronic obstructive pulmonary disease (COPD) of spirometry-defined SAD. It was a population-based prospective cohort study conducted in Guangdong, China. Participants were enrolled in the years 2002, 2008, 2012, 2017, and 2019, and those who completed baseline demographic data, a standardized epidemiological questionnaire for COPD, and spirometry were included. Follow-up visits were conducted every three years after enrolment, with a maximum follow-up time of 15 years and a minimum follow-up time of 3 years. Spirometry-defined SAD was defined as having at least two out of three parameters (maximal mid-expiratory flow, forced expiratory flow 50

Abstract 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.

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 <prebronchodilator FVC or postbronchodilator FVC ≥prebronchodilator FVC).Results The final analysis included 1140 participants with preserved spirometry (169 in the variable obstruction group) at baseline. Participants with variable obstruction were older, had lower lung function and had greater severe emphysema and computed tomography-defined air trapping than participants without variable obstruction. Participants with variable obstruction had a significantly increased risk of incident spirometry-defined COPD (relative risk: 3.22, 95% confidence interval 2.23 to 4.64, p <0.001) than those without variable obstruction after adjustment for covariates. These findings remained consistent among both former and current smokers, never smokers, and different variable obstruction types. Additionally, participants with variable obstruction had a faster decline in postbronchodilator FEV1/FVC (2.3±0.5%/year vs 0.9±0.4%/year, mean difference: 1.4 (95% confidence interval 0.5 to 2.3), p=0.002) than participants without variable obstruction after adjustment for covariates.Conclusions The results of our study revealed that variable obstruction can identify individuals who are at risk for the development of COPD and accelerated postbronchodilator FEV1/FVC decline in preserved spirometry.

Recently, fibroblast activation protein (FAP), an overexpressed transmembrane protein of activated fibroblast in pulmonary fibrosis, has been considered as the new target for diagnosing and treating pulmonary fibrosis. In this work, mesoporous polydopamine (MPDA), which is facile prepared and easily modified, is developed as a carrier to load antifibrosis drug pirfenidone (PFD) and linking FAP inhibitor (FAPI) to realize lesion-targeted drug delivery for pulmonary fibrosis therapy. We have found that PFD@MPDA-FAPI is well biocompatible and with good properties of antifibrosis, when ICG labels MPDA-FAPI, the accumulation of the nanodrug at the fibrosis lung in vivo can be observed by NIR imaging, and the antifibrosis properties of PFD@MPDA-FAPI in vivo were also better than those of pure PFD and PFD@MPDA; therefore, the easily produced and biocompatible nanodrug PFD@MPDA-FAPI developed in this study is promising for further clinical translations in pulmonary fibrosis antifibrosis therapy.

Idiopathic pulmonary fibrosis (IPF) is an age-related disease with no cure. Mesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy for IPF treatment. Nevertheless, MSCs derived from patients with IPF (IPF-MSCs) become senescent, thereby reducing their beneficial effects in IPF. MicroRNAs (miRNAs) mediate the senescence of MSCs, but the underlying mechanisms are not fully understood. We investigated the mechanisms by which miR-199a-5p regulates IPF-MSC senescence and whether its inhibition could rejuvenate IPF-MSCs and enhance their therapeutic efficacy. Control-MSCs and IPF-MSCs were isolated from the adipose tissue of age-matched healthy and IPF donors, respectively. Cell senescence was examined by senescence-associated β-galactosidase (SA-β-gal) staining. The level of miR-199a-5p was measured by RT-PCR. Autophagy was determined using a transmission electron microscope (TEM). The therapeutic efficacy of anti-miR-199a-5p-IPF-MSCs was assessed using a mouse model of bleomycin-induced lung fibrosis. Despite similar surface makers, IPF-MSCs exhibited increased cellular senescence and decreased proliferative capacity compared with control-MSCs. The expression of miR-199a-5p was significantly enhanced in the serum of IPF patients and IPF-MSCs compared with that of healthy donors and control-MSCs. The upregulation of miR-199a-5p induced senescence of control-MSCs, whereas the downregulation rescued IPF-MSC senescence. Mechanistically, miR-155-5p suppressed autophagy of MSCs via the AMPK signaling pathway by downregulating the expression of Sirtuin 1(Sirt1), resulting in cellular senescence. Accordingly, miR-155-5p inhibition promoted autophagy and ameliorated IPF-MSC senescence by activating the Sirt1/AMPK signaling pathway. Compared with IPF-MSCs, the transplantation of anti-miR-199a-5p-IPF-MSCs increased the ability to prevent progression of pulmonary fibrosis in bleomycin-treated mice. Our study shows that miR-199a-5p regulates MSC senescence in patients with IPF by regulating the Sirt1/AMPK signaling pathway and miR-199a-5p is a novel target to rejuvenate IPF-MSCs and enhance their beneficial effects.

目的 探索并优化医院教师参与临床药学理论教学的模式.方法 对比分别采用LBL和CBL教学的学生在课堂效果、医院入科及临床实践三个方面的评估结果 ,对医院教师开展理论教学的模式及课程设计进行讨论.结果 通过教学目标及内容的差异化制定,医院教师采用CBL教学法能够有效提高学生在理论教学阶段的学习兴趣和自学热情,提高学生实践的临床思维和服务意识,以及解决部分专业问题的能力,但在理论知识的掌握上并不存在显著差异.结论 医院教师可通过CBL方式将临床需求及工作经验渗透到临床药学的理论教学中,更好地培养学生的临床实践能力.

Objective To observe the effects of the combinative educational methods on the intem doctors' clinical practice outcomes,which were consisted of the problem-based learning (PBL) and the guidelines for disease diagnosis and treatment learning.Methods The study recruited 39 clinical students who took up their clerkship in the department of the respiratory medicine,First Affiliated Hospital of Guangzhou Medical University.The students were randomly divided into two groups:the experimental group (PBL and guidelines,n =20) and the control one (n =19) ; the former was given the combinative teaching methods consisted of PBL and learning of guidelines for disease diagnosis and treatment,and the latter was given the traditionally teaching methods.The outcome of the clinical practice was evaluated for each student at the end of their clerkship,which covered each student' s usual-time mark and overall mark,and the overall mark was made up of the theory examination and practice skills assessment.Results The experimental group presented a better performance in the clerkship,with the overall mark significantly higher in the experimental group than that in control one (P＜0.05); the usual-time mark,final theory exam and practice mark were all significantly higher in the experimental group relative to the control one,with each P＜ 0.05.Conclusions The study results conclude that the combinative teaching methods consisted of PBL and learning of guidelines can improve the effects of the clerkship outcomes substantially.

Objective To analyze the clinical features,characteristics of imaging and laboratory examination of pulmonary nocardiosis.Methods The clinical data of 7 patients with pulmonary nocardiosis admitted to the First Affiliated Hospital of Guangzhou Medical University from January 2012 to April 2014 were retrospectively analyzed,including medical history,symptoms and signs,imaging and laboratory data,etiologic features and management.Results Of 7 patients,2 were otherwise healthy,and 5 were with underlying diseases.Two patients had been treated with immunosuppressants or glucocorticoids.The clinical manifestations included cough (n=7),expectoration (n=7),fever (n=4),dyspnea (n=3),chest pain (n=1),hemoptysis (n=1) and emaciation (n=1).Pulmonary high-resolution CT scan revealed single or multiple nodular shadows (n=3),infiltrates (n=3),lung masses (n=l),complicated with cavity formation (n=3),mediastinal lymphadenectasis (n=2),and pleural effusion (n=3).Among 7 patients with pulmonary nocardiosis,there were 3 strains of Nocardia brasiliensis,1 of Nocardia asteroids,and other 3 of nonclassified Nocardia.Sulfonamides were effective for most patients.Conclusions Most patients with pulmonary nocardiosis may have underlying diseases with nonspecific clinical manifestations.Single or multiple pulmonary nodules and infiltrates are the most common presentation in imaging studies.Sulfonamides are effective for most of the patients.

Objective To assess the severity distribution proportion and quality of life (QOL) of chronic obstructive pulmonary disease(COPD)among population in Southern China.Methods Data were from the cross-sectional survey of COPD which was conducted in an urban and a rural of Guangdong for residents aged over 40 years old.The recruited populations were interviewed with questionnaire and were tested with spirometry.Those with less than 70％ of post-bronchodialator FEV1/FVC were identified as the COPD.The quality of life was assessed with 12-item Short-Form health survey questionnaire (SF-12).Groups (A,B,C and D) were classified according to GOLD using combination of mMRC,FEV1 ％pred and acute exacerbation of COPD in last year.Results Three hundred and three patients with COPD indentified by spirometry testing among population,there were 109 (36.0 ％),77 (25.4 ％),38 (12.5 ％)and 79 (26.1 ％) patients in Group A,B,C and D,respectively.There was statistically difference between each two groups in physical component scores of SF-12 (F =39.593,P ＜0.001) except for difference between Group B and C,with 49.28±4.25,43.21±7.94,44.67±7.90 and 37.45±9.68 for Group A,B,C and D,respectively.A statistically difference was found between four groups in mental component scores of SF-12 (F =2.978,P =0.032),with 57.62±3.31,57.89±4.25,57.22±4.83,55.63±7.95 for Group A,B,C and D,respectively.Group D had a lower mental component scores of SF-12 compare to Group A and C (both P ＜0.05).Conclusions Group A is the highest proportion in population with a minimum of impaired quality of life,and Group D has the most serious damage of quality of life.

Background: Epidemiological research and meta-analyses of published data have shown that biomass smoke (BS) is a risk factor for chronic obstructive pulmonary disease (COPD). However, the link between BS and COPD lacks experimental confirmation. Objectives: To verify whether BS can induce pathologic changes and systemic oxidative stress, which may be relevant to the development of emphysema and chronic bronchitis in rats. Methods: Rats were exposed to BS, cigarette smoke (CS), or clean air (sham) for 14 weeks. During the exposure, the O-2, SO2, and CO levels were monitored. Pathological changes in the lungs, systemic oxidative stress, and inflammation biomarkers, together with GSTM(1) and GSTP(1) mRNA expression in the lung were measured. The glutamate cysteine ligase catalytic subunit (GCLC) protein expression in the lung was measured using immunohistochemistry and western blotting. Results: The O-2, CO, and SO2 levels were 20.31 +/- 0.03%, 981.72 +/- 64.76, and 2.59 +/- 0.26 mg/m(3) for the BS group, respectively, while their levels in the CS group were 20.28 +/- 0.15%, 745.56 +/- 30.83, and 12.64 +/- 0.591 mg/m(3) respectively. As with the rats exposed to CS, the BS rats showed an increased number of inflammatory cells in the bronchoalveolar lavage fluid, an increased pulmonary mean linear intercept and a decreased pulmonary mean alveolar number. Characteristics of chronic bronchitis and peribronchial fibrosis were also found in the BS-exposed rat lungs. Reduced body weight, systemic oxidative stress, and increased GCLC protein expression in the lungs were observed in the rats exposed to BS and CS. Conclusions: BS can cause emphysema and chronic bronchitis similar to that caused by CS, which is accompanied by systemic oxidative stress and inflammation.

Objective: COPD is often underdiagnosed in a primary care setting where the spirometry is unavailable. This study was aimed to develop a simple, economical and applicable model for COPD screening in those settings.Methods: First we established a discriminant function model based on Bayes' Rule by stepwise discriminant analysis, using the data from 243 COPD patients and 112 non-COPD subjects from our COPD survey in urban and rural communities and local primary care settings in Guangdong Province, China. We then used this model to discriminate COPD in additional 150 subjects (50 non-COPD and 100 COPD ones) who had been recruited by the same methods as used to have established the model. All participants completed pre- and post-bronchodilator spirometry and questionnaires. COPD was diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria. The sensitivity and specificity of the discriminant function model was assessed.Results: The established discriminant function model included nine variables: age, gender, smoking index, body mass index, occupational exposure, living environment, wheezing, cough and dyspnoea. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, accuracy and error rate of the function model to discriminate COPD were 89.00%, 82.00%, 4.94, 0.13, 86.66% and 13.34%, respectively. The accuracy and Kappa value of the function model to predict COPD stages were 70% and 0.61 (95% CI, 0.50 to 0.71).Conclusions: This discriminant function model may be used for COPD screening in primary care settings in China as an alternative option instead of spirometry.

Objective To investigate the current status of knowledge and activity to COPD, providing evidence of targeted intervention on COPD in China.Methods A cross-sectional survey of COPD was conducted in two communities which were sampled from Guangzhou City, using multiple-stage sampling strategy.In the selected community, all residents at least 40 years old were randomly recruited, and interviewed with self-made questionnaire that was tested having a good reliability and validity.Results In the 700 participants, 630 had completed questionnaire with a response rate of 90.0%;only 46.3%(292/630) had a idea of COPD, and 42.2%(266/630) did not known any risk factors of COPD.The percentage of smoking was 40%(252/630), with 75.5%(209/277) in male and 12.2%(43/353) in female, and the prevalence of current smoking was 26.3%(166/630).Among current smokers, 35.0%(59/166)planed to quit smoking.46.0%(290/630)of subjects were exposed to environmental cigarettes smoke.22.4%(141/630) of participants had nothing about smoking harmfulness, and 14.8%(93/630) of them thought it was permitted to smoke in public place.73.3%(462/630)of subjects wanted to received health education, and 93.7%(548/585)liked to get the knowledge of the prevention of COPD.Conclusion Subjects had considerably poor knowledge of prevention and management for COPD in community.Therefore, an enforced prevention and health education for COPD are urgent.