Whole-course management of chronic obstructive pulmonary disease in primary healthcare: an internet of things-enabled prospective cohort study in China.

BACKGROUND: Despite substantial progress in reducing the global burden of chronic obstructive pulmonary disease (COPD), traditional methods to promote understanding and management of COPD are insufficient. We developed an innovative model based on the internet of things (IoT) for screening and management of COPD in primary healthcare (PHC). METHODS: Electronic questionnaire and IoT-based spirometer were used to screen residents. We defined individuals with a questionnaire score of 16 or higher as high-risk population, COPD was diagnosed according to 2021 Global Initiative for COPD (Global Initiative for Chronic Obstructive Lung Disease) criteria. High-risk individuals and COPD identified through the screening were included in the COPD PHC cohort study, which is a prospective, longitudinal observational study. We provide an overall description of the study's design framework and baseline data of participants. RESULTS: Between November 2021 and March 2023, 162 263 individuals aged over 18 from 18 cities in China were screened, of those 43 279 high-risk individuals and 6902 patients with COPD were enrolled in the cohort study. In the high-risk population, the proportion of smokers was higher than that in the screened population (57.6% vs 31.4%), the proportion of males was higher than females (71.1% vs 28.9%) and in people underweight than normal weight (57.1% vs 32.0%). The number of high-risk individuals increased with age, particularly after 50 years old (χ2=37 239.9, p<0.001). Female patients are more common exposed to household biofuels (χ2=72.684, p<0.05). The majority of patients have severe respiratory symptoms, indicated by a CAT score of ≥10 (85.8%) or an Modified Medical Research Council Dyspnoea Scale score of ≥2 (65.5%). CONCLUSION: Strategy based on IoT model help improve the detection rate of COPD in PHC. This cohort study has established a large clinical database that encompasses a wide range of demographic and relevant data of COPD and will provide invaluable resources for future research.

Advances in the Treatment of Pulmonary Nodules.

BACKGROUND: Early detection and accurate diagnosis of pulmonary nodules are crucial for improving patient outcomes. While surgical resection of malignant nodules is still the preferred treatment option, it may not be feasible for all patients. We aimed to discuss the advances in the treatment of pulmonary nodules, especially stereotactic body radiotherapy (SBRT) and interventional pulmonology technologies, and provide a range of recommendations based on our expertise and experience. SUMMARY: Interventional pulmonology is an increasingly important approach for the management of pulmonary nodules. While more studies are needed to fully evaluate its long-term outcomes and benefits, the available evidence suggests that this technique can provide a minimally invasive and effective alternative for treating small malignancies in selected patients. We conducted a systematic literature review in PubMed, designed a framework to include the advances in surgery, SBRT, and interventional pulmonology for the treatment of pulmonary nodules, and provided a range of recommendations based on our expertise and experience. KEY MESSAGES: As such, alternative therapeutic options such as SBRT and ablation are becoming increasingly important and viable. With recent advancements in bronchoscopy techniques, ablation via bronchoscopy has emerged as a promising option for treating pulmonary nodules. This study reviewed the advances of interventional pulmonology in the treatment of peripheral lung cancer patients that are not surgical candidates. We also discussed the challenges and limitations associated with ablation, such as the risk of complications and the potential for incomplete nodule eradication. These advancements hold great promise for improving the efficacy and safety of interventional pulmonology in treating pulmonary nodules.

Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis.

BACKGROUND: Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive. METHODS: Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed. RESULTS: Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized. CONCLUSIONS: Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN. Video Abstract.

Feasibility and Safety of Endosonography-Guided Transvascular Needle Aspiration in the Diagnosis of Thoracic and Abdominal Lesions: A Meta-Analysis.

BACKGROUND: Endoscopic techniques, including endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS), are used as the initial approach for the diagnosis and staging of lung cancer and the diagnosis of thoracic and abdominal lesions. Historically, the transvascular approach has been avoided because of concerns about bleeding. OBJECTIVES: This article is a systematic review of studies evaluating the feasibility and safety of transvascular needle aspiration (TVNA) under the guidance of EBUS or EUS in the diagnosis of thoracic and abdominal lesions. METHODS: We performed a systematic search of the MEDLINE, Embase, and Cochrane databases to identify studies evaluating the application of EBUS/EUS-guided TVNA (EBUS/EUS-TVNA) for lesions located at the contralateral side of the vessel for which the transvascular approach was the best puncture path. We performed a meta-analysis of diagnostic yield estimations. We also reviewed the complications related to the procedure. RESULTS: Eleven observational studies were included in the final analysis. Meta-analysis yielded a pooled overall diagnostic yield of 82.10% (95% confidence interval, 0.74-0.89) for TVNA, with an I2 value of 52%. No publication bias was detected by Egger's test (p = 0.8528). The overall complications included minor bleeding, minor hematoma, pseudo-aneurysm of the aorta, hemoptysis, acute hypoxic respiratory failure, and moderate bleeding. The major complication rate was 2.71%. CONCLUSIONS: EBUS/EUS-TVNA is feasible and probably safe when performed by experienced endoscopists in carefully selected patients. In view of the potential risks associated with the transvascular approach, especially the development of hematoma and pseudoaneurysm, the fanning technique was avoided, and the area of aspiration should be assessed by EUS for 3 min after each aspiration. Most importantly, EBUS/EUS-TVNA should only be performed if the results will impact the clinical management.

Epithelial-mesenchymal transition-related lncRNAs associated with prognosis and immune cell infiltration in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) remains the most common type of lung cancer and is associated with distant metastasis and poor prognosis. Epithelial-mesenchymal transition (EMT) plays crucial roles in carcinogenesis, embryogenesis, and wound healing. EMT-related molecules may be adopted for early diagnosis and prognosis of cancer and targeting them may constitute an attractive strategy for treatment. This study aims to identify the EMT-related long non-coding RNAs (lncRNAs) and develop a risk signature to accurately predict the prognosis of LUAD patients. METHODS: The RNA-seq data and corresponding clinical profiles were obtained from LUAD cohort of The Cancer Genome Atlas (TCGA) database. EMT-related lncRNAs significantly associated with prognosis were identified by Pearson correlation analysis and univariate regression analysis. Subsequently, an EMT-related prognostic risk signature was developed through LASSO and multivariate regression analyses. Kaplan Meier and receiver operating characteristic curve analysis were implemented to assess the predictive performance of the signature. The nomogram was constructed to predict the 1-year, 3-year, and 5-year overall survival of LUAD patients. Additionally, enrichment analyses were carried out to identify probable biologic processes and cellular pathways involved in the signature. The correlation of immune cell infiltration and risk score was also evaluated by CIBERSORT algorithm. Finally, we constructed a ceRNA network to further study possible downstream targets and molecular mechanisms of EMT-related lncRNAs in LUAD. RESULTS: Eight EMT-related lncRNAs were identified to develop a prognostic risk signature in LUAD. Patients with high-risk scores had worse survival outcomes than those with low-risk scores. The signature showed robust predictive potential, and was verified to be an independent prognostic factor. Moreover, the risk score based on the signature was significantly correlated with immune cell infiltration in LUAD. CONCLUSIONS: We established and validated a prognostic signature that reflects the tumor microenvironment characteristics and predicts the outcomes for LUAD.

Diagnostic yield of virtual bronchoscope navigation combined with radial endobronchial ultrasound guided transbronchial cryo-biopsy for peripheral pulmonary nodules: a prospective, randomized, controlled trial.

Background: Transbronchial lung biopsy (TBLB) was a useful method for the diagnosis of peripheral pulmonary nodules (PPNs), but the smaller tissue samples obtained often could not meet the subsequent molecular pathological diagnosis. The purposes of this study were to assess the diagnostic yield of virtual bronchoscope navigation (VBN) combined with radial endobronchial ultrasound (rEBUS) guided transbronchial cryo-biopsy (TBCB) and to compare it with TBLB. Methods: Patients with PPNs, who planned to undergo bronchoscopy and were admitted to Henan Provincial People's Hospital and Zhoukou Central Hospital from January 1, 2020 to December 31, 2020, were divided into the TBCB group (experimental group) and TBLB group (control group) using the block randomization method. TBCB and TBLB were performed with the guidance of VBN-rEBUS. The diagnostic yields, complications, specimen surface areas, and operation times were observed. The differences between the two groups were measured by the independent sample t-test or Chi-square test. Results: A total of 152 patients were enrolled, of whom 138 completed the study, and 102 received a definite diagnosis by bronchoscopy. The diagnostic yield showed no statistically significant difference between TBCB group and TBLB group (79.1% vs. 69.0%, P=0.124). For PPNs with the diameter <2 cm, TBCB group had a significantly higher diagnostic yield than TBLB group (76.5% vs. 50.0%, P=0.022); For PPNs with eccentric and adjacent radial ultrasonic images, TBCB group also had a significantly higher diagnostic yield than TBLB group (78.1% vs. 55.9%, P=0.023). The specimen surface area of TBCB group was larger than that of TBLB group (P=0.030). The incidence of moderate bleeding in TBCB group was higher than that in TBLB group (P=0.006), but no serious complications were observed in either group. Conclusions: Although the incidence rate of moderate bleeding was higher than that of TBLB, VBN-rEBUS guided TBCB is still a safe and effective diagnostic method for PPNs, and is superior to TBLB for PPNs with a diameter <2 cm or with an eccentric and adjacent radial ultrasonic image. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100054949.

A Classifier for Improving Early Lung Cancer Diagnosis Incorporating Artificial Intelligence and Liquid Biopsy.

Lung cancer is the leading cause of cancer-related deaths worldwide and in China. Screening for lung cancer by low dose computed tomography (LDCT) can reduce mortality but has resulted in a dramatic rise in the incidence of indeterminate pulmonary nodules, which presents a major diagnostic challenge for clinicians regarding their underlying pathology and can lead to overdiagnosis. To address the significant gap in evaluating pulmonary nodules, we conducted a prospective study to develop a prediction model for individuals at intermediate to high risk of developing lung cancer. Univariate and multivariate logistic analyses were applied to the training cohort (n = 560) to develop an early lung cancer prediction model. The results indicated that a model integrating clinical characteristics (age and smoking history), radiological characteristics of pulmonary nodules (nodule diameter, nodule count, upper lobe location, malignant sign at the nodule edge, subsolid status), artificial intelligence analysis of LDCT data, and liquid biopsy achieved the best diagnostic performance in the training cohort (sensitivity 89.53%, specificity 81.31%, area under the curve [AUC] = 0.880). In the independent validation cohort (n = 168), this model had an AUC of 0.895, which was greater than that of the Mayo Clinic Model (AUC = 0.772) and Veterans' Affairs Model (AUC = 0.740). These results were significantly better for predicting the presence of cancer than radiological features and artificial intelligence risk scores alone. Applying this classifier prospectively may lead to improved early lung cancer diagnosis and early treatment for patients with malignant nodules while sparing patients with benign entities from unnecessary and potentially harmful surgery. Clinical Trial Registration Number: ChiCTR1900026233, URL: http://www.chictr.org.cn/showproj.aspx?proj=43370.

Malfunction of airway basal stem cells plays a crucial role in pathophysiology of tracheobronchopathia osteoplastica.

Understanding disease-associated stem cell abnormality has major clinical implications for prevention and treatment of human disorders, as well as for regenerative medicine. Here we report a multifaceted study on airway epithelial stem cells in Tracheobronchopathia Osteochondroplastica (TO), an under-detected tracheobronchial disorder of unknown etiology and lack of specific treatment. Epithelial squamous metaplasia and heterotopic bone formation with abnormal cartilage proliferation and calcium deposits are key pathological hallmarks of this disorder, but it is unknown whether they are coincident or share certain pathogenic mechanisms in common. By functional evaluation and genome-wide profiling at both transcriptional and epigenetic levels, we reveal a role of airway basal cells in TO progression by acting as a repository of inflammatory and TGFß-BMP signals, which contributes to both epithelial metaplasia and mesenchymal osteo-chondrogenesis via extracellular signaling and matrix remodeling. Restoration of microenvironment by cell correction or local pathway intervention may provide therapeutic benefits.

Diagnostic value of LungPoint navigation combined with EBUS-GS & ROSE in peripheral pulmonary nodules.

Background & objectives: Recently, there has been a surge to develop new devices and techniques for the diagnosis of peripheral pulmonary lesions such as the combination of LungPoint navigation and endobronchial ultrasound with a guide sheath (EBUS-GS). The present study aimed to explore the diagnostic value of LungPoint navigation in combination with EBUS-GS and rapid on-site evaluation (ROSE) particularly for peripheral pulmonary nodules. Methods: Patients (n=108) with pulmonary nodules (10 mm ≤ nodal diameter ≤30 mm) presenting to Henan Provincial People's Hospital were detected using chest computed tomographic (CT) scanning and bronchoscopy. All patients were evaluated using LungPoint navigation, EBUS-GS and ROSE techniques to evaluate the positive rate of combined diagnosis using the three methods. Results: A total of 108 patients participated in this study and successfully underwent all the three procedures. Of these, 82 patients were accurately diagnosed, making the overall diagnostic rate of 75.9 per cent for combined LungPoint navigation, EBUS-GS, and ROSE analyses. Further subgroup analysis of the diagnostic rate of the three combined techniques were conducted based on the size of the nodules which showed a diagnostic rate of 65.3 per cent for 10 mm ≤ nodule diameter ≤20 mm and 85.7 per cent for 20 mm ≤ nodal diameter ≤30 mm. Of the 108 patients, 85 had solid nodules and 23 had ground-glass nodules; the positive rate of diagnosis of solid nodules was the highest. The patients ultimately were diagnosed with lung cancer with a positive rate of 83.5 per cent. The sensitivity, specificity and positive and negative predicted values for ROSE were 90.3, 78.3, 84.8 and 83.6 per cent, respectively. Interpretation & conclusions: The combined use of the three techniques can effectively shorten the duration of the total diagnosis period and improve the safety of diagnosis without affecting the detection rate.

Combination of the Archimedes Navigation System and cryobiopsy in diagnosis of diffuse lung disease.

OBJECTIVE: To evaluate the efficacy of the Archimedes Navigation System (Broncus Medical, San Jose, CA, USA) for guidance during transbronchial cryobiopsy and the incidence of complications in patients with diffuse lung disease. METHODS: High-resolution computed tomography and transbronchial cryobiopsy were used to evaluate eight patients with diffuse lung disease. The Archimedes Navigation System was used before cryobiopsy to obtain the best path with which to avoid large vessels. Three to five cryobiopsy specimens were taken from each sampled segment. RESULTS: Preoperative planning using the Archimedes Navigation System was successfully performed on all eight patients. The probe-to-pleura distance was approximately 10 mm. No cases of pneumothorax occurred, one patient developed moderate bleeding, two developed minor bleeding, and five developed minimal bleeding that stopped spontaneously. A final diagnosis was obtained for seven patients, and ongoing follow-up was being conducted for the last patient at the time of this writing. CONCLUSIONS: This is the first report of combining navigation technology with cryobiopsy to diagnose diffuse lung disease. The Archimedes Navigation System, which provides real-time guidance, is helpful in pre-cryobiopsy planning and diagnosis of diffuse lung disease. Moreover, this system can reduce the pneumothorax rate and bleeding risk by avoiding large vessels.

Value of virtual bronchoscopic navigation and transbronchial ultrasound-guided sheath-guided exploration in diagnosis of peripheral lung cancer.

BACKGROUND: Peripheral lung cancer poses a substantial harm to human health, and it is easy to become exacerbated, potentially threatening the life and safety of patients. AIM: To assess the value of virtual bronchoscopic navigation (VBN) combined with transbronchial ultrasound-guided sheath-guided (EBUS-GS) exploration in the diagnosis of peripheral lung cancer. METHODS: A total of 236 patients with peripheral lung cancer (nodule diameter range, 8-30 mm; diagnosed using high-resolution computed tomography) were selected from three centers between October 2018 and December 2019. Patients who underwent EBUS-GS exploration alone were included in a control group, and those who received VBN in combination with EBUS-GS exploration were included in an observation group. The diagnostic rate and total operating time of different subgroups of the two groups were compared, and the time needed to determine the lesion was recorded. RESULTS: There were no significant differences in diagnosis rate or total operation time between the two groups (P > 0.05), and the time needed to determine the lesion in the observation group was less than that of the control group (P < 0.05). CONCLUSION: The combined use of VBN and EBUS-GS exploration technology has little effect on the diagnosis rate and total operation time of peripheral lung cancer, but it significantly shortens the time needed to determine the lesion and is a valuable diagnostic method.

Protein expression shift and potential diagnostic markers through proteomics profiling of tuberculous pleurisy biopsy tissues.

OBJECTIVES: Tuberculous pleurisy is a common type of tuberculosis (TB), but its diagnosis is challenging. This study aimed to profile the protein expression of this disease and identify new diagnostic makers. METHODS: Biopsy tissues from patients with tuberculous pleurisy and controls were taken through thoracoscopy, and proteins were extracted for Tandem Mass Tag Mass Spectrometry. Differential protein expression was performed between patients and controls, and the identified proteins were analyzed for pathway enrichment. Selected proteins were further validated in another set of samples using a more quantitative method. RESULTS: A total of 5101 proteins were detected and quantified in a discovery set of patients and controls. Overall protein expression was quite different between patients and controls. Most proteins were down-expressed, while a minority were overly expressed in the patient samples. At p value < 0.05 and absolute fold change >2, 295 proteins were found to be up-expressed and 608 down-expressed. The top enriched pathways included ECM-receptor interaction, complement and coagulation cascades and focal adhesion. All 19 selected candidates were validated in an independent set of patient and control samples. CONCLUSION: This unbiased proteomics approach not only provided unique insights into protein expression and pathways, but also discovered potential diagnostic markers for tuberculous pleurisy.

Apatinib Reverses Paclitaxel-resistant Lung Cancer Cells (A549) Through Blocking the Function of ABCB1 Transporter.

BACKGROUND/AIM: Multidrug resistance (MDR) is often associated with overexpression of P-glycoprotein (ABCB1) in cancer cells. Apatinib is a novel Vascular endothelial growth factor receptor-TKI (VEGFR-TKI) which inhibits the function of ABCB1 in certain cancers. This study aimed to investigate the effect of apatinib on the reversal of paclitaxel (PTX) resistance in A549 lung cancer cells (A549/PTX) and related mechanisms. MATERIALS AND METHODS: A549/PTX cells were treated with apatinib alone, PTX alone, or PTX and apatinib. Cell viability was measured by the CCK8 assay. Apoptosis rate, cell-cycle arrest, Rhodamine efflux and reactive oxygen species (ROS) generation were determined by flow cytometry. The intracellular paclitaxel concentration was measured by ultra performance liquid chromatography (UPLC). Protein levels were analyzed by western blotting. RESULTS: A549/PTX cells had significant resistance to PTX and higher expression of ABCB1 compared to A549 cells. Apatinib increased the cytotoxicity of PTX, enhanced PTX-induced apoptosis and cycle arrest, and triggered intracellular ROS generation in A549/PTX cells. In addition, apatinib treatment increased the concentration of intracellular PTX in A549/PTX cells. Apatinib-PTX combination inhibited AKT and ERK pathways. CONCLUSION: Apatinib reverses the drug resistance to PTX in A549 PTX-resistant cells through inhibiting the function of ABCB1 and resumes anti-cancer effects.

STAT3-induced long noncoding RNA LINC00668 promotes migration and invasion of non-small cell lung cancer via the miR-193a/KLF7 axis.

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in non-small cell lung cancer (NSCLC) progression. Recently, a newly identified lncRNA, LncRNA LINC00668 (LINC00668), was reported to be involved in the regulation of progression of several tumors. However, the expression pattern and biological function of LINC00668 in NSCLC remains largely unclear. In this study, we found that LINC00668 expression was significantly up-regulated in both NSCLC tissues and cell lines. we also showed that LINC00668 upregulation was induced by transcription factor STAT3. Clinical investigation demonstrated that high expression level of LINC00668 was associated with advanced TNM stage, histological grade and lymph node metastasis. Moreover, multivariate analysis confirmed LINC00668 expression level to be an independent prognostic indicator for overall survival of NSCLC patients. Functional assays indicated that knockdown of LINC00668 suppressed NSCLC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistic studies indicated that LINC00668 is a direct target of miR-193a, leading to down-regulation in the expression of its target gene KLF7. Our findings suggested that STAT3-induced LINC00668 contributed to NSCLC progression through upregulating KLF7 expression by sponging miR-193a, and may serve as a prognostic biomarker and a potential target for NSCLC.