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Background: Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by myofibroblast proliferation and extracellular matrix (ECM) deposition. However, current treatments are not satisfactory. Therefore, more effective therapies need to be explored. Cepharanthine (CEP) is a naturally occurring alkaloid that has recently been reported to have multiple pharmacological effects, particularly in chronic inflammation. Methods: For in vivo experiments, first, a pulmonary fibrosis murine model was generated via tracheal injection of bleomycin (BLM). Second, the clinical manifestations and histopathological changes of the mice were used to verify that treatment with CEP might significantly reduce BLM-induced fibrosis. Furthermore, flow cytometric analysis was used to analyze the changes in the number of M2 macrophages in the lung tissues before and after treatment with CEP to explore the relationship between macrophage M2 polarization and pulmonary fibrosis. In vitro, we constructed two co-culture systems (THP-1 and MRC5 cells, RAW264.7 and NIH 3T3 cells), and measured the expression of fibrosis-related proteins to explore whether CEP could reduce pulmonary fibrosis by regulating macrophage M2 polarization and fibroblast activation. Results: The results showed that the intranasal treatment of CEP significantly attenuated the symptoms of pulmonary fibrosis induced by BLM in a murine model. Our findings also indicated that CEP treatment markedly reduced the expression of fibrosis markers, including TGF-β1, collagen I, fibronectin and α-SMA, in the mouse lung. Furthermore, in vitro studies demonstrated that CEP attenuated pulmonary fibrosis by inhibiting fibroblast activation through modulating macrophage M2 polarization and reducing TGF-β1 expression. Conclusions: This study demonstrated the potential and efficacy of CEP in the treatment of pulmonary fibrosis. In particular, this study revealed a novel mechanism of CEP in inhibiting fibroblast activation by regulating macrophage M2 polarization and reducing the expression of fibrosis-associated factors. Our findings open a new direction for future research into the treatment of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background: The Global Initiative for Chronic Obstructive Lung Disease 2023 revision proposed that chronic obstructive pulmonary disease (COPD) has various etiologies including infections (COPD-I), such as tuberculosis and human immunodeficiency virus. While nontuberculous mycobacterial pulmonary disease (NTM-PD) and pulmonary tuberculosis share similar clinical manifestations, research on COPD development during longitudinal follow-up in patients with NTM-PD is limited. In this study, we aimed to evaluate the incidence and risk of COPD development in patients with NTM-PD. Methods: We retrospectively enrolled patients with NTM-PD with normal lung function and 1:4 age-, sex-, body mass index-, and smoking status-matched controls between November 1994 and January 2022. We compared the risks of spirometry-defined COPD between the NTM-PD and control groups (study 1). A nationwide cohort study using the health insurance claims database was conducted to validate the findings (study 2). Results: In study 1, during a mean follow-up of 3.3 years, COPD occurred in 14.0% (241/1,715) and 4.3% (293/6,860) of individuals in the NTM-PD and matched control cohorts, respectively. The NTM-PD cohort exhibited a higher risk of incident COPD (adjusted hazard ratio [aHR], 2.57; 95% CI, 2.15–3.09) compared to matched controls. In study 2, COPD occurred in 6.2% (24/386) and 2.5% (28/1,133) of individuals with and without NTM-PD, respectively. The NTM-PD cohort had a higher risk of incident COPD (aHR, 2.04; 95% CI, 1.21–3.42) compared to matched controls. Conclusion: These findings suggest that NTM-PD could be considered a new etiotype of COPD-I and emphasize the importance of monitoring lung function in individuals with NTM-PD. [ABSTRACT FROM AUTHOR]

Background: To explore the associations of computed tomography (CT) image features with the serum cryptococcal antigen (CrAg) titers measured by the lateral flow assay (LFA) in localized pulmonary cryptococcosis patients. Methods: A retrospective analysis of patients with pathologically confirmed pulmonary cryptococcosis admitted to the First Affiliated Hospital of Xiamen University from January 2016 to December 2022 was performed. Clinical data, CT results, serum CrAg-LFA test results, and follow-up data were collected and analyzed. Results: A total of 107 patients with localized pulmonary cryptococcosis were included, of which 31 had a single lesion in chest CT and the other 76 had multiple lesions. The positivity rate was (94.74% vs 64.52%) and titers of serum CrAg-LFA (1.77 ± 0.87 vs 0.91 ± 0.98) in the multiple lesion group were higher than those in the single lesion group, respectively. Multivariate linear regression analysis showed that the serum CrAg titers were positively associated with the number of lesions (β, 0.08; 95% CI, 0.05 to 0.12) and the lesion size (β, 0.40; 95% CI, 0.31 to 0.50) after adjusting other covariates. The serum CrAg-LFA titers of 60 pulmonary cryptococcosis patients showed a decreasing trend with the reduction in pulmonary lesion size after effective therapy. Conclusion: In pulmonary cryptococcosis patients, the number and size of lung lesions are positively correlated with the titers of the serum CrAg-LFA test. The CrAg-LFA test could be a useful tool for the diagnosis, severity assessment, and therapeutic monitoring of localized pulmonary cryptococcosis patients. [ABSTRACT FROM AUTHOR]

Background: A 3.0-mm ultrathin bronchoscope (UTB) with a 1.7-mm working channel provides better accessibility to peripheral bronchi. A 4.0-mm thin bronchoscope with a larger 2.0-mm working channel facilitates the use of a guide sheath (GS), ensuring repeated sampling from the same location. The 1.1-mm ultrathin cryoprobe has a smaller diameter, overcoming the limitation of the size of biopsy instruments used with UTB. In this study, we compared the endobronchial ultrasound localization rate and diagnostic yield of peripheral lung lesions by cryobiopsy using UTB and thin bronchoscopy combined with GS. Methods: We retrospectively evaluated 133 patients with peripheral pulmonary lesions with a diameter less than 30 mm who underwent bronchoscopy with either thin bronchoscope or UTB from May 2019 to May 2023. A 3.0-mm UTB combined with rEBUS was used in the UTB group, whereas a 4.0-mm thin bronchoscope combined with rEBUS and GS was used for the thin bronchoscope group. A 1.1-mm ultrathin cryoprobe was used for cryobiopsy in the two groups. Results: Among the 133 patients, peripheral pulmonary nodules in 85 subjects were visualized using r-EBUS. The ultrasound localization rate was significantly higher in the UTB group than in the thin bronchoscope group (96.0% vs. 44.6%, respectively; P < 0.001). The diagnostic yield of cryobiopsy specimens from the UTB group was significantly higher compared to the thin bronchoscope group (54.0% vs. 30.1%, respectively; p = 0.006). Univariate analysis demonstrated that the cryobiopsy diagnostic yields of the UTB group were significantly higher for lesions ≤ 20 mm, benign lesions, upper lobe lesions, lesions located lateral one-third from the hilum, and lesions without bronchus sign. Conclusions: Ultrathin bronchoscopy combined with cryobiopsy has a superior ultrasound localization rate and diagnostic yield compared to a combination of cryobiopsy and thin bronchoscopy. [ABSTRACT FROM AUTHOR]

Background: Traumatic pulmonary pseudocyst is a rare "cystlike" lung lesion that typically develops following blunt chest trauma. It differs from lung cancer associated with cystic airspaces in terms of pathogenic mechanisms, clinical manifestations, and radiological features. Furthermore, there are few reports of the diagnostic bias between traumatic pulmonary pseudocyst and lung cancer associated with cystic airspaces. Here, we present a rare case of lung cancer associated with cystic airspaces that mimicks traumatic pulmonary pseudocyst. Case presentation: A 61-year-old man with no chest medical or surgical history, no chest radiologic examination within the last five years, and no smoking history had an air-filled "cystlike" lesion surrounded by solid components and ground-glass opacities in the middle third of the right upper lobe of the lung during a computed tomography evaluation following blunt chest trauma. He was initially diagnosed with traumatic pulmonary pseudocyst and treated conservatively. On the third post-trauma day, he experienced hemoptysis, which was successfully treated with intravenous hemostatic medication. On the ninth post-trauma day, he exhibited a significant hemoptysis and a moderate dyspnea. A subsequent chest computed tomography scan demonstrated that the solid components had entered the lesion's cavity and significantly expanded, and the surrounding ground-glass opacities had slightly enlarged. A contrast-enhanced chest computed tomography scan and a three-dimensional reconstruction computed tomography image confirmed that the solid components were a hematoma caused by damage to the right upper pulmonary vein. A right upper lobectomy was performed based on the concern about severe intrapulmonary bleeding. An intraoperative frozen section analysis showed significant bleeding in the lung parenchyma. Adenosquamous carcinoma was unexpectedly identified during the postoperative pathological examination of the resected specimen. A diagnosis of primary lung adenosquamous carcinoma was made. He was discharged on the seventh postoperative day and followed up for two years without any recurrence. Conclusions: The potential of lung cancer associated with cystic airspaces should be considered for "cystlike" lung lesions discovered in elderly patients after blunt chest trauma. A comprehensive review of the medical history, meticulous analysis of the radiological findings, and close monitoring can help clinicians reduce the risk of diagnostic bias. [ABSTRACT FROM AUTHOR]

Introduction. To date, radical surgery remains the best curative option in patients with early-stage lung cancer. In patients with small lung lesions, video-assisted thoracic surgery (VATS) should be increasingly chosen as a fundamental alternative to thoracotomy as it is associated with less postoperative pain and better quality of life. This scenario necessarily increases the need for thoracic surgeons to implement new localization techniques. The conventional near-infrared (NIR) indocyanine green (ICG) method demonstrated a significant limitation in deep cancer recognition, principally due to its intrinsic low-depth tissue penetration. Similarly, the lymph-node sentinel approach conducted by the ICG method was demonstrated to be inefficient, mainly due to the non-specificity of the tracker and the irregular pathway of pulmonary lymph node drainage. Our study aims to evaluate the effectiveness of Cetuximab- IRDye800CW in marking lung nodules and mediastinal lymph nodes. Methods and analysis. This study is defined as an open-label, single-arm, single-stage phase II trial evaluating the effectiveness of Cetuximab-IRDye800CW in detecting tumors and lymph-node metastases in patients with lung cancer who are undergoing video-assisted thoracic surgery (VATS). Cetuximab is a monoclonal antibody that binds, inhibits, and degrade the EGFR. The IRDye® 800CW, an indocyanine-type NIR fluorophore, demonstrated enhanced tissue penetration compared to other NIR dyes. The combination with the clinical approved monoclonal antibody anti-epidermal growth factor EGFR Cetuximab (Cetuximab-IRDye800) has shown promising results as a specific tracker in different cancer types (i.e., brain, pancreas, head, and neck). The study's primary outcome is focused on the proportion of patients with lung nodules detected during surgery using an NIR camera. The secondary outcomes include a broad spectrum of items, including the proportion of patients with detection of unexpected cancer localization during surgery by NIR camera and the proportion of patients with negative surgical margins, the evaluation of the time spawns between the insertion of the NIR camera and the visualization of the nodule and the possible morbidity of the drug assessed during and after the drug infusion. Ethics and dissemination. This trial has been approved by the Ethical Committee of Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino (Torino, Italy) and by the Italian Medicines Agency (AIFA). Findings will be written as methodology papers for conference presentations and published in peer-reviewed journals. The Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, the University of Torino, and the AIRC Public Engagement Divisions will help identify how best to publicize the findings. Trial registration EudraCT 202,100,645,430. ClinicalTrials.gov NCT06101394 (October 23, 2023). [ABSTRACT FROM AUTHOR]

Objective: To intelligently evaluate the invasiveness of pure ground-glass nodules with multiple classifications using deep learning. Methods: pGGNs in 1136 patients were pathologically confirmed as lung precursor lesions [atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS)], minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IAC). Four different models [EfficientNet-b0 2D, dual-head ResNet_3D, a 3D model combining three features (3D_3F), and a 3D model combining 19 features (3D_19F)] were constructed to evaluate the invasiveness of pGGNs using the EfficientNet and ResNet networks. The Obuchowski index was used to evaluate the differences in diagnostic efficiency among the four models. Results: The patients with pGGNs (360 men, 776 women; mean age, 54.63 ± 12.36 years) included 235 cases of AAH + AIS, 332 cases of MIA, and 569 cases of IAC. In the validation group, the areas under the curve in detecting the invasiveness of pGGNs as a three-category classification (AAH + AIS, MIA, IAC) were 0.8008, 0.8090, 0.8165, and 0.8158 for EfficientNet-b0 2D, dual-head ResNet_3D, 3D_3F, and 3D_19F, respectively, whereas the accuracies were 0.6422, 0.6158, 0.651, and 0.6364, respectively. The Obuchowski index revealed no significant differences in the diagnostic performance of the four models. Conclusions: The dual-head ResNet_3D_3F model had the highest diagnostic efficiency for evaluating the invasiveness of pGGNs in the four models. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the radiological changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) having bronchiolitis patterns on computed tomography (CT). Methods: We retrospectively reviewed the final diagnosis and radiologic changes of patients suspected of having NTM-PD without cavity or bronchiectasis on CT image, between January 1, 2005 and March 31, 2021. NTM-PD was diagnosed based on the American Thoracic Society and Infectious Diseases Society of America criteria. The initial and final CT findings (bronchiectasis, cellular bronchiolitis, cavity formation, nodules, and consolidation) were compared between patients diagnosed with and without NTM-PD. Results: This study included 96 patients and 515 CT images. The median CT follow-up duration was 1510.5 (interquartile range: 862.2–3005) days. NTM-PD was recognized in 43 patients. The clinical variables were not significantly different between patients with and without NTM-PD, except for underlying chronic airway disease (P < 0.001). Nodule and consolidation were more frequently observed on the initial CT scans of patients with NTM-PD compared with those without (P < 0.05). On the final follow-up CT scan, bronchiectasis (P < 0.001), cavity (P < 0.05), nodule (P < 0.05), and consolidation (P < 0.05) were more frequently observed in patients with NTM-PD. Among the 43 patients with NTM-PD, 30 showed a radiological progression on CT, with bronchiectasis (n = 22) being the most common finding. The incidence of bronchiectasis increased over time. Conclusion: The bronchiolitis pattern on CT images of patients with NTM-PD showed frequent radiological progression during the follow-up period. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a persistent, chronic inflammatory disease of the lungs. Tiotropium, used in the treatment of COPD, is a muscarinic receptor antagonist that provides long-acting bronchodilation. Our study aimed to investigate the effects of Tiotropium on anterior chamber parameters. Methods: The study was conducted as an observational cross-sectional and prospectively between October 2023 and April 2024. Patients were examined in three groups: Group 1 consisted of untreated COPD patients; Group 2 consisted of healthy volunteers similar age and gender, and Group 3 included COPD patients receiving Tiotropium 18 mcg via HandiHaler. Anterior chamber parameters, intraocular pressure values, and photopic-mesopic pupil diameters were measured at the initial visit for Group 1 and Group 2 patients, and at the third month of treatment for Group 3 patients. Results: Thirty-six patients were included in each group in the study. No significant differences were observed in ocular findings between the patient and control groups. In COPD patients receiving Tiotropium, narrowing of angle parameters, an increase in photopic-mesopic pupil diameters, and intraocular pressure were observed at the third month of treatment. Conclusion: This study is the first research that investigate the effects of Tiotropium on anterior chamber parameters, pupil diameters, and intraocular pressure in COPD treatment. In conclusion, patients with COPD receiving Tiotropium therapy for three months showed narrowing in angle parameters, an increase in intraocular pressure, and photopic-mesopic pupil diameter; however, no patients developed drug-induced acute angle closure glaucoma. Trial registration: An independent ethics committee approved the study (Giresun EAH KEAK 2023/180 and 9.10.2023/02) which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice. The study was conducted as prospectively, observational case–control. The Clinical Trial Number obtained for the study is NCT06525051 and was taken on 2024–07-29. [ABSTRACT FROM AUTHOR]

Background: Albeit smoking cessation has unequivocal health benefits, attempts to quit are not unanimous, even in patient populations at high risk for smoking-related diseases cessation. Allelic variations of enzymes involved in dopamine metabolism are being considered as candidates for nicotine addiction. We set out to assess whether rs4680 G/A and rs2235186 G/A polymorphisms of COMT and MAO-A, respectively are associated with the ability to quit smoking in chronic inflammatory pulmonary disease patients. Methods: Patients managed for chronic inflammatory pulmonary disease by the Department of Pulmonology (University of Debrecen, Hungary), with a current or past smoking habit were included in the current analysis. The study was designed in line with the STROBE statement for cross-sectional studies and was approved by the National Center for Public Health, Hungary. Genomic DNA was extracted from peripheral blood specimens. SNPs were genotyped using TaqMan SNP genotyping assays. Results: rs4680 COMT polymorphism showed significant effect for successful smoking cessation in patients with pulmonary disease. Accordingly, A/A subjects had lower odds for successful smoking cessation (odds ratio 0.37; 95% confidence interval 0.20–0.69, p = 0.002 (additive model). On the other hand, patients homozygous for the minor allele (A) at rs2235186 of MAO-A showed a non-significant trend toward increased odds for successful smoking cessation. Conclusions: The presence of the minor allele for rs4680 COMT was shown to decrease the odds for successful smoking cessation, a finding that may be interpreted in view of the altered balance between tonic and phasic dopamine release. [ABSTRACT FROM AUTHOR]

Background: Cerebellar abscesses are rare, life-threatening infections often originating from bacterial sources, while metastatic brain lesions from lung adenocarcinoma are relatively common. However, the coexistence of a cerebellar abscess secondary to metastatic lung adenocarcinoma is exceedingly rare and presents unique diagnostic and management challenges. Case Presentation: We report a case of a 35 year-old Pakistani female patient with persistent headaches, nausea, and vertigo, who was found to have a large cerebellar mass with features suggestive of metastatic lung adenocarcinoma. Further investigation revealed a concomitant cerebellar abscess. Surgical excision and broad-spectrum antibiotics were initiated, resulting in a favorable outcome. Conclusion: This case showcases the rarity and complexity of cerebellar abscesses due to metastatic lung adenocarcinoma. Timely intervention, including surgery and targeted therapy, is crucial for successful management. Further research is needed to enhance treatment strategies. [ABSTRACT FROM AUTHOR]

Iatrogenic pneumothorax is a relevant complication of computed tomography (CT)-guided percutaneous lung biopsy. The aim of the present study was to analyze the prognostic significance of texture analysis, emphysema score and muscle mass derived from CT-imaging to predict postinterventional pneumothorax after CT-guided lung biopsy. Consecutive patients undergoing CT-guided percutaneous lung biopsy between 2012 and 2021 were analyzed. Multivariate logistic regression analysis included clinical risk factors and CT-imaging features to detect associations with pneumothorax development. Overall, 479 patients (178 females, mean age 65 ± 11.7 years) underwent CT-guided percutaneous lung biopsy of which 180 patients (37.5%) developed pneumothorax including 55 patients (11.5%) requiring chest tube placement. Risk factors associated with pneumothorax were chronic-obstructive pulmonary disease (COPD) (p = 0.03), age (p = 0.02), total lung capacity (p < 0.01) and residual volume (p = 0.01) as well as interventional parameters needle length inside the lung (p < 0.001), target lesion attached to pleura (p = 0.04), and intervention duration (p < 0.001). The combined model demonstrated a prediction accuracy of the occurrence of pneumothorax with an AUC of 0.78 [95%CI: 0.70–0.86] with a resulting sensitivity 0.80 and a specificity of 0.66. In conclusion, radiomics features of the target lesion and the lung lobe CT-emphysema score are predictive for the occurrence of pneumothorax and need for chest insertion after CT-guided lung biopsy. [ABSTRACT FROM AUTHOR]

Introduction: Celiac disease is a disease triggered by a protein called gluten. Celiac disease has intestinal and extraintestinal manifestations. Bronchiectasis is a permanent dilation of the bronchi that causes symptoms, such as cough producing a large amount of sputum, recurrent respiratory infections, and breathlessness. In addition, bronchiectasis can present in 60% of cases with chronic rhinosinusitis. Case presentation: A 40-year-old Arab woman presented with a worsening old cough with an increased amount of sputum; the patient was diagnosed with Celiac disease 7 months prior. Investigations started with laboratory tests followed by a computed tomography scan for the head and chest, bronchoscopy, bronchoalveolar lavage, and spirometry; the final diagnosis was bronchiectasis with chronic rhinosinusitis. She was advised to commit to the gluten-free diet, in addition to the medications prescribed for her bronchiectasis and chronic rhinosinusitis. Conclusion: Celiac disease and bronchiectasis might share an immunologic disturbance that caused both entities, so Celiac disease should be kept in mind as an etiology for pulmonary diseases. [ABSTRACT FROM AUTHOR]

Background: Progressive pulmonary fibrosis is the symptomatic, physiological, and radiological progression of interstitial lung diseases. The aim of this study was to examine the relationship between progressive pulmonary fibrosis and demographic characteristics and to evaluate the effect on clinical outcomes and mortality. Methods: This cross-sectional study included 221 patients diagnosed with non-idiopathic pulmonary fibrosis interstitial lung diseases who were followed in the last 5 years. Patient symptoms, clinical, radiological, and demographic data were examined. Risk factors for the development of progressive pulmonary fibrosis and the relationship with clinical outcomes and mortality were examined. Results: Of the patients, 33.0% (n = 73) had fibrotic idiopathic nonspecific interstitial pneumonia (iNSIP), 35.7% (n = 79) had fibrotic hypersensitivity pneumonia (HP), 18.1% (n = 40) had fibrotic connective tissue disease (CTD) interstitial lung diseases (ILD), and 13.1% (n = 29) had postinfectious fibrotic ILD. The progressive pulmonary fibrosis development rates of the subtypes were 46.5% iNSIP (n = 34), 86.0% fibrotic HP (n = 68), 42.5% fibrotic CTD-ILD (n = 17), and 20.7% postinfectious ILD (n = 6). The presence of progressive pulmonary fibrosis was associated with the development of respiratory failure and mortality (odds ratio [OR]: 2.70, 95% CI: 1.04–7.05 and OR: 2.13, 95% CI: 1.23–3.69). Progressive pulmonary fibrosis development was higher in hypersensitivity pneumonia patients with farmer's lung (OR: 5.06, 95% CI: 1.02–25.18). Conclusion: Progressive pulmonary fibrosis was more prevalent in older patients. Farming was an important risk factor in the development of hypersensitivity pneumonia-progressive pulmonary fibrosis. Respiratory failure and mortality were higher in those who developed progressive pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma (M.) hyopneumoniae is associated with respiratory disease in pigs and is the primary agent of enzootic pneumonia. Quantification of M. hyopneumoniae-related outcome parameters can be difficult, expensive, and time-consuming, in both research and field settings. In addition to well-established methods, technological tools are becoming available to monitor various aspects of relevant animal- and environment-related features, often in real-time. Therefore, this study aimed to assess whether certain parameters, such as animal movement and body temperature using microchips (IMT), correlate with established parameters and whether the currently used parameters can be rationalized. Results: The percentage of movement was significantly reduced by M. hyopneumoniae infection in pigs (p < 0.05), where the M. hyopneumoniae-infected group showed a lower percentage of movement (1.9%) when compared to the negative control group (6.9%). On the other hand, macroscopic (MLCL) and microscopic (MLL) lung lesions, respiratory disease score (RDS), M. hyopneumoniae-DNA load, and anti-M. hyopneumoniae antibody levels increased significantly in the M. hyopneumoniae-infected group 28 days post-inoculation (p < 0.05). Moderate (r > 0.30) to very strong correlations (> 0.80) were observed between the abovementioned parameters (p < 0.05), except for IMT. A significant and moderate correlation was reported between IMT and rectal temperature (r = 0.49; p < 0.05). Last, the average daily weight gain and the percentage of air in the lung were not affected by M. hyopneumoniae infection (p > 0.05). Conclusions: M. hyopneumoniae infection significantly reduced the movement of piglets and increased lung lesions, M. hyopneumoniae-DNA load, and anti-M. hyopneumoniae antibody levels; and, good correlations were observed between most parameters, indicating a direct relationship between them. Thus, we suggest that changes in movement might be a reliable indicator of M. hyopneumoniae infection in pigs, and that a selected group of parameters—specifically RDS, MLCL, MLL, M. hyopneumoniae-DNA load, anti-M. hyopneumoniae antibody levels, and movement—are optimal to assess M. hyopneumoniae infection under experimental conditions. [ABSTRACT FROM AUTHOR]

Background: Surgery is the main treatment option for destroyed-lung (DL) patients with life-threatening massive hemoptysis. However, short-term and long-term surgical safety and efficacy are unclear, prompting this study. Methods: Data from 124 DL patients undergoing surgery between November 2001 and January 2022 at Beijing Chest Hospital were retrospectively analyzed. Data of the DL group (82 cases) and DL + massive hemoptysis group (42 cases) were compared with regard to clinical characteristics, long-term postoperative residual lung reinfection. Results: As compared with DL group rates, The DL + massive hemoptysis group had greater incidence rates of postoperative complications, invasive postoperative respiratory support, long-term postoperative residual lung reinfection, and postoperative tuberculosis recurrence. Revealed risk factors for postoperative complications (Extent of lung lesion resection), postoperative invasive respiratory therapy (preoperative Hb < 9 g/L, severe intraoperative hemoptysis), and postoperative long-term residual lung reinfection (DL with massive hemoptysis). Conclusions: DL patients with massive hemoptysis had greater rate of invasive respiratory support therapy and postoperative complications. Extensive lesion removal, preoperative anaemia, severe intraoperative bleeding associated with recent postoperative complications for the patient. [ABSTRACT FROM AUTHOR]

Background: Pneumoconiosis has a significant impact on the quality of patient survival. This study aims to evaluate the performance and application value of improved Unet network technology in the recognition and segmentation of lesion areas of lung CT images in patients with pneumoconiosis. Methods: A total of 1212 lung CT images of patients with pneumoconiosis were retrospectively included. The improved Unet network was used to identify and segment the CT image regions of the patients' lungs, and the image data of the granular regions of the lungs were processed by the watershed and region growing algorithms. After random sorting, 848 data were selected into the training set and 364 data into the validation set. The experimental dataset underwent data augmentation and were used for model training and validation to evaluate segmentation performance. The segmentation results were compared with FCN-8s, Unet network (Base), Unet (Squeeze-and-Excitation, SE + Rectified Linear Unit, ReLU), and Unet + + networks. Results: In the segmentation of lung CT granular region with the improved Unet network, the four evaluation indexes of Dice similarity coefficient, positive prediction value (PPV), sensitivity coefficient (SC) and mean intersection over union (MIoU) reached 0.848, 0.884, 0.895 and 0.885, respectively, increasing by 7.6%, 13.3%, 3.9% and 6.4%, respectively, compared with those of Unet network (Base), and increasing by 187.5%, 249.4%, 131.9% and 51.0%, respectively, compared with those of FCN-8s, and increasing by 14.0%, 31.2%, 4.7% and 9.7%, respectively, compared with those of Unet network (SE + ReLU), while the segmentation performance was also not inferior to that of the Unet + + network. Conclusions: The improved Unet network proposed shows good performance in the recognition and segmentation of abnormal regions in lung CT images in patients with pneumoconiosis, showing potential application value for assisting clinical decision-making. [ABSTRACT FROM AUTHOR]

Purpose: To identify the key risk factors for venous thromboembolism (VTE) in urological inpatients based on the Caprini scale using an interpretable machine learning method. Methods: VTE risk data of urological inpatients were obtained based on the Caprini scale in the case hospital. Based on the data, the Boruta method was used to further select the key variables from the 37 variables in the Caprini scale. Furthermore, decision rules corresponding to each risk level were generated using the rough set (RS) method. Finally, random forest (RF), support vector machine (SVM), and backpropagation artificial neural network (BPANN) were used to verify the data accuracy and were compared with the RS method. Results: Following the screening, the key risk factors for VTE in urology were "(C1) Age," "(C2) Minor Surgery planned," "(C3) Obesity (BMI > 25)," "(C8) Varicose veins," "(C9) Sepsis (< 1 month)," (C10) "Serious lung disease incl. pneumonia (< 1month) " (C11) COPD," "(C16) Other risk," "(C18) Major surgery (> 45 min)," "(C19) Laparoscopic surgery (> 45 min)," "(C20) Patient confined to bed (> 72 h)," "(C18) Malignancy (present or previous)," "(C23) Central venous access," "(C31) History of DVT/PE," "(C32) Other congenital or acquired thrombophilia," and "(C34) Stroke (< 1 month." According to the decision rules of different risk levels obtained using the RS method, "(C1) Age," "(C18) Major surgery (> 45 minutes)," and "(C21) Malignancy (present or previous)" were the main factors influencing mid- and high-risk levels, and some suggestions on VTE prevention were indicated based on these three factors. The average accuracies of the RS, RF, SVM, and BPANN models were 79.5%, 87.9%, 92.6%, and 97.2%, respectively. In addition, BPANN had the highest accuracy, recall, F1-score, and precision. Conclusions: The RS model achieved poorer accuracy than the other three common machine learning models. However, the RS model provides strong interpretability and allows for the identification of high-risk factors and decision rules influencing high-risk assessments of VTE in urology. This transparency is very important for clinicians in the risk assessment process. [ABSTRACT FROM AUTHOR]

Background: Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). Methods: This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. Results: Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1β, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (−), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (−) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. Conclusion: Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression. Methods and results: The therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4's protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions. Conclusion: P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved. [ABSTRACT FROM AUTHOR]

Background: This study compares the effect of positive end-expiratory pressure (PEEP) on postoperative pulmonary complications (PPCs) in patients with obesity undergoing laparoscopic bariatric surgery (LBS) under general anesthesia with mechanical ventilation. Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Internet, Wanfang database, and Google Scholar for studies published up to July 29, 2023, without time or language restrictions. The search terms included "PEEP," "laparoscopic," and "bariatric surgery." Randomized controlled trials comparing different levels of PEEP or PEEP with zero-PEEP (ZEEP) in patients with obesity undergoing LBS were included. The primary outcome was a composite of PPCs, and the secondary outcomes were intraoperative oxygenation, respiratory compliance, and mean arterial pressure (MAP). A fixed-effect or random-effect model was selected for meta-analysis based on the heterogeneity of the included studies. Results: Thirteen randomized controlled trials with a total of 708 participants were included for analysis. No statistically significant difference in PPCs was found between the PEEP and ZEEP groups (risk ratio = 0.27, 95% CI: 0.05–1.60; p = 0.15). However, high PEEP ≥ 10 cm H2O significantly decreased PPCs compared with low PEEP < 10 cm H2O (risk ratio = 0.20, 95% CI: 0.05–0.89; p = 0.03). The included studies showed no significant heterogeneity (I2 = 20% & 0%). Compared with ZEEP, PEEP significantly increased intraoperative oxygenation and respiratory compliance (WMD = 74.97 mm Hg, 95% CI: 41.74-108.21; p < 0.001 & WMD = 9.40 ml cm H2O− 1, 95% CI: 0.65–18.16; p = 0.04). High PEEP significantly improved intraoperative oxygenation and respiratory compliance during pneumoperitoneum compared with low PEEP (WMD = 66.81 mm Hg, 95% CI: 25.85-107.78; p = 0.001 & WMD = 8.03 ml cm H2O− 1, 95% CI: 4.70-11.36; p < 0.001). Importantly, PEEP did not impair hemodynamic status in LBS. Conclusions: In patients with obesity undergoing LBS, high PEEP ≥ 10 cm H2O could decrease PPCs compared with low PEEP < 10 cm H2O, while there was a similar incidence of PPCs between PEEP (8–10 cm H2O) and the ZEEP group. The application of PEEP in ventilation strategies increased intraoperative oxygenation and respiratory compliance without affecting intraoperative MAP. A PEEP of at least 10 cm H2O is recommended to reduce PPCs in patients with obesity undergoing LBS. Registration number: CRD42023391178 in PROSPERO. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease(COPD) is a gradually worsening and fatal heterogeneous lung disease characterized by airflow limitation and increasingly decline in lung function. Currently, it is one of the leading causes of death worldwide. The consistent feature of COPD is airway inflammation. Several inflammatory factors are known to be involved in COPD pathogenesis; however, anti-inflammatory therapy is not the first-line treatment for COPD. Although bronchodilators, corticosteroids and roflumilast could improve airflow and control symptoms, they could not reverse the disease. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway plays an important novel role in the immune system and has been confirmed to be a key mediator of inflammation during infection, cellular stress, and tissue damage. Recent studies have emphasized that abnormal activation of cGAS-STING contributes to COPD, providing a direction for new treatments that we urgently need to develop. Here, we focused on the cGAS-STING pathway, providing insight into its molecular mechanism and summarizing the current knowledge on the role of the cGAS-STING pathway in COPD. Moreover, we explored antagonists of cGAS and STING to identify potential therapeutic strategies for COPD that target the cGAS-STING pathway. [ABSTRACT FROM AUTHOR]

Background: Double-lumen tubes (DLTs) and bronchial blockers (BBs) can be used to establish one-lung ventilation (OLV) for thoracic surgery. BBs are a good alternative when DLTs are not suitable or patients have difficult airways. However, BBs are more prone to malposition, leading to adverse events. Case presentation: We present a 68-year-old male patient who was scheduled for thoracoscopic left lower lobectomy. The patient was not expected to have airway malformation preoperatively. When the DLT could not be inserted into the bronchus after general anesthesia induction, we used a BB to perform OLV. During surgery, malposition of the BB resulted in the development of an "incomplete balloon valve", leading to a cardiopulmonary crisis. Conclusions: Previewing chest computed tomography scans to assess the airway anatomy before thoracic surgery is essential. Three-dimensional reconstruction of the airway can provide a more intuitive assessment of airway anatomy. During OLV with BBs, we should pay attention to balloon malposition to prevent cardiopulmonary crises. [ABSTRACT FROM AUTHOR]

Background: Fiberglass has a larger aerodynamic diameter and is less likely to be inhaled into the lungs. Further, it will be cleared even if it is mechanically broken into smaller pieces and inhaled into the lungs. Fiberglass lung disease has been well documented if long term exposure but was thought reversible and would not cause severe diseases. The diagnosis of fiberglass lung disease depends on exposure history and histopathological findings. However, the exact occupational exposure history is often difficult to identify because mixed substance exposure often occurs and fiberglass disease is not as well-known as asbestosis. Case presentation: A 66-year-old man had unexplained transudative pericardial effusion requiring pleural pericardial window operation twice at another medical center where asbestosis was told because of his self-reported long-term asbestosis exposure and the histopathological finding of a ferruginous body in his lung. Constrictive pericarditis developed two years later and resulted in congestive heart failure. Radical pericardiectomy combined with lung biopsy was performed following chest computed tomography imaging and the transudative nature of pericardial effusion not compatible with asbestosis. However, the histopathologic findings of his lung and pericardium at our hospital only showed chronic fibrosis without any asbestosis body. The patient's lung was found to be extremely fragile during a lung biopsy; histopathologic specimens were reviewed, and various fragments of fiberglass were found in the lung and pericardium. The patient's occupational exposure was carefully reevaluated, and he restated that he was only exposed to asbestosis for 1–2 years but was heavily exposed to fiberglass for more than 40 years. This misleading exposure history was mainly because he was only familiar with the dangers of asbestos. Since most fiberglass lung diseases are reversible and the symptoms of heart failure resolve soon after surgery, only observation was needed. Ten months after radical pericardiectomy, his symptoms, pleural effusion, and impaired pulmonary function eventually resolved. Conclusion: Fiberglass could cause inflammation of the pericardium, resulting in pericardial effusion and constrictive pericarditis, which could be severe and require radical pericardiectomy. Exact exposure history and histopathological examinations are the key to diagnosis. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of peripheral pulmonary lesions (PPL) is still challenging. We describe a novel method for sampling PPL without bronchial signs by creating invisible tunnel under electromagnetic navigation without the transbronchial access tool (TABT). Methods: During electromagnetic navigation, we adjust the angle of the edge extended working channel catheter based on the real-time position of the lesion in relation to the locating guide rather than preset route. A biopsy brush or biopsy forceps is used to punch a hole in the bronchial wall. A locating guide is then re-inserted to real-time navigate through the lung parenchyma to the lesion. Safety and feasibility of this method was analyzed. Results: A total of 32 patients who underwent electromagnetic navigation bronchoscopy were retrieved. The mean size of the lesion is 23.1 mm. The mean operative time of all patients was 12.4 min. Ten of the patients did not have a direct airway to the lesion, thus creating an invisible tunnel. For them, the length of the tunnel from the bronchial wall POE to the lesion was 11–30 mm, with a mean length of 16.9 mm and a mean operation time of 14.1 min. Adequate samples were obtained from 32 patients (100%), and the diagnostic yield was 87.5% (28/32). Diagnostic yield of with create the invisible tunnel TBAT was 90% (9/10), and one patient undergone pneumothorax after operation. Conclusions: This method is feasible and safe as a novel approach sampling pulmonary lesions without bronchial signs, and it further improves current tunnel technique. [ABSTRACT FROM AUTHOR]

Background: Severe COVID-19 infection has been associated with the development of pulmonary fibrosis, a condition that significantly affects patient prognosis. Understanding the underlying cellular communication mechanisms contributing to this fibrotic process is crucial. Objective: In this study, we aimed to investigate the role of the TNFSF12-TNFRSF12A pathway in mediating communication between alveolar macrophages and fibroblasts, and its implications for the development of pulmonary fibrosis in severe COVID-19 patients. Methods: We conducted single-cell RNA sequencing (scRNA-seq) analysis using lung tissue samples from severe COVID-19 patients and healthy controls. The data was processed, analyzed, and cell types were annotated. We focused on the communication between alveolar macrophages and fibroblasts and identified key signaling pathways. In vitro experiments were performed to validate our findings, including the impact of TNFRSF12A silencing on fibrosis reversal. Results: Our analysis revealed that in severe COVID-19 patients, alveolar macrophages communicate with fibroblasts primarily through the TNFSF12-TNFRSF12A pathway. This communication pathway promotes fibroblast proliferation and expression of fibrotic factors. Importantly, silencing TNFRSF12A effectively reversed the pro-proliferative and pro-fibrotic effects of alveolar macrophages. Conclusion: The TNFSF12-TNFRSF12A pathway plays a central role in alveolar macrophage-fibroblast communication and contributes to pulmonary fibrosis in severe COVID-19 patients. Silencing TNFRSF12A represents a potential therapeutic strategy for mitigating fibrosis in severe COVID-19 lung disease. [ABSTRACT FROM AUTHOR]

Background: While spontaneous pneumothorax has been documented in COVID-19 patients, reports on recurrent spontaneous pneumothorax due to cystic lesions in convalescent COVID-19 patients are scarce. The progression of these lung cystic lesions remains inadequately explored. Case presentation and literature review: An 81-year-old male, a non-smoker with a history of rheumatoid arthritis, presented with fever, cough, and expectoration for 14 days. Initially diagnosed with moderate COVID-19, he deteriorated to severe COVID-19 despite adherence to local treatment guidelines. Successive identification of three cystic lesions termed "bulla" or "pneumatocele", and one cystic lesion with air-fluid level, referred to as "pneumo-hamatocele" (PHC), occurred in his lungs. Gradual improvement followed anti-inflammatory therapy and optimal supportive care. However, on day 42, sudden worsening dyspnea prompted a computed tomography (CT) scan, confirming a right spontaneous pneumothorax and subcutaneous emphysema, likely due to PHC rupture. Discharge followed chest tube implementation for pneumothorax resolution. On day 116, he returned to the hospital with mild exertional dyspnea. Chest CT revealed recurrent right pneumothorax from a remaining cyst in the right lung. Apart from our patient, literature retrieval identified 22 COVID-19 patients with spontaneous pneumothorax due to cystic lesions, with a male predominance (95.6%; 22/23). Diagnosis of pneumothorax and lung cystic lesions occurred around day 29.5 (range: 18–35) and day 26.4 (± 9.8) since symptom onset, respectively. Except for one patient whose pneumothorax occurred on day seven of illness, all patients eventually recovered. Conclusions: Recurrent spontaneous pneumothorax secondary to lung cystic lesions may manifest in convalescent COVID-19 patients, particularly males with COVID-19 pneumonia. Chest CT around 2 to 3 weeks post-symptom onset may be prudent to detect cystic lesion development and anticipate spontaneous pneumothorax. [ABSTRACT FROM AUTHOR]

Background: As a subtype of pulmonary hypertension (PH), pulmonary veno-occlusive disease (PVOD) is devastating and life-threatening disease without effective therapy. Hydrogen has been reported to exhibits antioxidant and anti-inflammatory effects in a rat model induced by monocrotaline of PH. In this study, we investigated the effects of inhaled hydrogen gas on the prevention and treatment of PVOD induced by mitomycin C (MMC) in rats. Methods: PVOD was induced in female Sprague-Dawley rats through intraperitoneal injection of MMC at a concentration of 3 mg·kg− 1·wk− 1 for 2 weeks. Inhalation of hydrogen gas (H2) was administered through a designed rat cage concurrently or two weeks after MMC administration. The severity of PVOD was assessed by using hemodynamic measurements and histological analysis. The expression levels of general control nonderepressible 2 (GCN2), nuclear factor erythroid 2-related factor-2 (Nrf2), heme oxygenase-1 (HO-1) and endothelial-to-mesenchymal transition (EndoMT) related proteins in lung tissue were measured. Levels of lipid peroxidation pro-inflammatory cytokines in serum were determined. Results: Inhaled H2 improved hemodynamics and right heart function, reversed right ventricular hypertrophy, and prevented pulmonary vessel reconstitution in both prevention and treatment approaches. It decreased malondialdehyde (MDA) levels in the serum and the expression of NADPH oxidase 1 (NOX-1) in lung tissue. It regulated Nrf2/HO-1 signaling pathway and anti-inflammatory factor GCN2 in lung tissue, accompanied by a decrease in macrophages and pro-inflammatory cytokines. Our data suggested that H2 inhalation effectively countered EndoMT induced by MMC, as evidenced by the detection of endothelial markers (e.g., VE-cadherin and CD31) and mesenchymal markers (e.g., vimentin and fibronectin). Further research revealed that H2 preserved p-Smad3 and induced p-Smad1/5/9. Conclusion: Inhalation of H2 effectively inhibits the pathogenesis of PVOD induced by MMC in rats. This inhibitory effect may be attributed to the antioxidant and anti-inflammatory properties of H2. [ABSTRACT FROM AUTHOR]

Background: Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function. Methods: The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point. Results: Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8–8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV1 z-score was − 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load. Conclusion: There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function. Trial registration: ClinicalTrials.gov NCT02426112. First registered on 24/04/2015. [ABSTRACT FROM AUTHOR]

Background: Recent advances in Vision Transformer (ViT)-based deep learning have significantly improved the accuracy of lung disease prediction from chest X-ray images. However, limited research exists on comparing the effectiveness of different optimizers for lung disease prediction within ViT models. This study aims to systematically evaluate and compare the performance of various optimization methods for ViT-based models in predicting lung diseases from chest X-ray images. Methods: This study utilized a chest X-ray image dataset comprising 19,003 images containing both normal cases and six lung diseases: COVID-19, Viral Pneumonia, Bacterial Pneumonia, Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and Tuberculosis. Each ViT model (ViT, FastViT, and CrossViT) was individually trained with each optimization method (Adam, AdamW, NAdam, RAdam, SGDW, and Momentum) to assess their performance in lung disease prediction. Results: When tested with ViT on the dataset with balanced-sample sized classes, RAdam demonstrated superior accuracy compared to other optimizers, achieving 95.87%. In the dataset with imbalanced sample size, FastViT with NAdam achieved the best performance with an accuracy of 97.63%. Conclusions: We provide comprehensive optimization strategies for developing ViT-based model architectures, which can enhance the performance of these models for lung disease prediction from chest X-ray images. [ABSTRACT FROM AUTHOR]

Background: Early screening and detection of lung cancer is essential for the diagnosis and prognosis of the disease. In this paper, we investigated the feasibility of serum Raman spectroscopy for rapid lung cancer screening. Methods: Raman spectra were collected from 45 patients with lung cancer, 45 with benign lung lesions, and 45 healthy volunteers. And then the support vector machine (SVM) algorithm was applied to build a diagnostic model for lung cancer. Furthermore, 15 independent individuals were sampled for external validation, including 5 lung cancer patients, 5 benign lung lesion patients, and 5 healthy controls. Results: The diagnostic sensitivity, specificity, and accuracy were 91.67%, 92.22%, 90.56% (lung cancer vs. healthy control), 92.22%,95.56%,93.33% (benign lung lesion vs. healthy) and 80.00%, 83.33%, 80.83% (lung cancer vs. benign lung lesion), repectively. In the independent validation cohort, our model showed that all the samples were classified correctly. Conclusion: Therefore, this study demonstrates that the serum Raman spectroscopy analysis technique combined with the SVM algorithm has great potential for the noninvasive detection of lung cancer. [ABSTRACT FROM AUTHOR]

Background: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. Method: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. Results: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. Conclusions: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. Trial registration: www.clinicaltrials.gov (ID: NCT04180319). [ABSTRACT FROM AUTHOR]

Introduction: Chronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case–control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naive children with (HCLD +) and without HCLD (HCLD-) established on antiretroviral treatment (ART). Methods: Nasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6–19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher's exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively. Results: A total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8–18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 104 genomic equivalents [GE/ml] vs. 3 × 102 GE/ml, p = 0.006) and MC (1 × 104 GE/ml vs. 1 × 103 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 – 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 – 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 – 0.9], p = 0.039). Conclusion: Children with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further. Trial registration: The BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112, registered date: 24 April 2015). [ABSTRACT FROM AUTHOR]

Background: Pulmonary fibrosis (PF) represents the pathologic end stage of several interstitial lung diseases (ILDs) associated with high morbidity and mortality rates. However, current treatments can only delay disease progression rather than provide a cure. The role of inflammation in PF progression is well-established, but new insights into immune regulation are fundamental for developing more efficient therapies. c-MET signaling has been implicated in the migratory capacity and effector functions of immune cells. Nevertheless, the role of this signaling pathway in the context of PF-associated lung diseases remains unexplored. Methods: To determine the influence of c-MET in immune cells in the progression of pulmonary fibrosis, we used a conditional deletion of c-Met in immune cells. To induce pulmonary fibrosis mice were administered with bleomycin (BLM) intratracheally. Over the course of 21 days, mice were assessed for weight change, and after euthanasia at different timepoints, bronchoalveolar lavage fluid cells and lung tissue were assessed for inflammation and fibrosis. Furthermore, c-MET expression was assessed in cryobiopsy sections, bronchoalveolar lavage fluid cells samples and single cell RNA-sequencing dataset from human patients with distinct interstitial lung diseases. Results: c-MET expression was induced in lung immune cells, specifically in T cells, interstitial macrophages, and neutrophils, during the inflammatory phase of BLM-induced PF mouse model. Deletion of c-Met in immune cells correlated with earlier weight recovery and improved survival of BLM-treated mice. Moreover, the deletion of c-Met in immune cells was associated with early recruitment of the immune cell populations, normally found to express c-MET, leading to a subsequent attenuation of the cytotoxic and proinflammatory environment. Consequently, the less extensive inflammatory response, possibly coupled with tissue repair, culminated in less exacerbated fibrotic lesions. Furthermore, c-MET expression was up-regulated in lung T cells from patients with fibrosing ILD, suggesting a potential involvement of c-MET in the development of fibrosing disease. Conclusions: These results highlight the critical contribution of c-MET signaling in immune cells to their enhanced uncontrolled recruitment and activation toward a proinflammatory and profibrotic phenotype, leading to the exacerbation of lung injury and consequent development of fibrosis. [ABSTRACT FROM AUTHOR]

Objective and results description: The study objective was to investigate the potential of quantitative measures of pulmonary inflammation by [18 F]Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) as a surrogate marker of inflammation in COPD. Patients treated with anti-inflammatory Liraglutide were compared to placebo and correlated with inflammatory markers. 27 COPD-patients (14 receiving Liraglutide treatment and 13 receiving placebo) underwent 4D-respiratory-gated FDG-PET/CT before and after treatment. Two raters independently segmented the lungs from CT images and measured activity in whole lung, mean standard uptake values (SUVmean) corrected for lean-body-mass in the phase-matched PET images of the whole segmented lung volume, and total lesion glycolysis (TLG; SUVmean multiplied by volume). Inter-rater reliability was analyzed with Bland-Altman analysis and correlation plots. We found no differences in metabolic activity in the lungs between the two groups as a surrogate of pulmonary inflammation, and no changes in inflammation markers. The purpose of the research and brief summary of main findings. The degree of and changes in pulmonary inflammation in chronic obstructive pulmonary disease (COPD) may be difficult to ascertain. Measuring metabolic activity as a surrogate marker of inflammation by FDG-PET/CT may be useful, but data on its use in COPD including reproducibility is still limited, especially with respiration-gated technique, which should improve quantification in the lungs. We assessed several quantitative measures of metabolic activity and correlated them with inflammation markers, and we assessed reproducibility of the methods. We found no differences in metabolic activity between the two groups (before and after 40 weeks treatment with Liraglutide vs. placebo). Bland-Altman analysis showed good agreement between the two raters. Trial registration: The study was conducted between February 2018 and March 2020 at the Department of Pulmonary Diseases at Hospital South West Jutland and Lillebaelt Hospital, Denmark, and registered from March 2018 at clinicaltrials.gov with trial registration number NCT03466021. [ABSTRACT FROM AUTHOR]

Background: Although the Mini Nutritional Assessment (MNA) is recognized as a useful tool for evaluating nutritional status in patients with various diseases, its applicability in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) remains undetermined. Methods: We designed a prospective cross-sectional study to investigate whether the MNA Short-Form (MNA-SF) score can serve as a screening tool to assess the nutritional status of patients with NTM-PD. The MNA-SF was conducted upon patient enrollment, and correlation analyses were performed to compare MNA-SF scores with other nutritional measurements and disease severity. Multivariable logistic regression analyses were conducted to evaluate the association between MNA-SF scores and NTM-PD severity. Results: The 194 patients with NTM-PD included in the analysis had a median age of 65.0 (59.0–69.0) years; 59.3% (n = 115) had low MNA-SF scores (< 12). The low MNA-SF group exhibited a lower body mass index (19.7 vs. 22.4 kg/m2, p < 0.001) and fat-free mass index (14.7 vs. 15.6 kg/m2, p < 0.001) than the normal MNA-SF group, as well as higher incidences of sarcopenia (20.0% vs. 6.3%, p = 0.008) and adipopenia (35.7% vs. 5.1%, p < 0.001). However, no significant differences in calorie and protein intakes were observed between the two groups. Low MNA-SF scores were associated with radiographic severity (adjusted odds ratio 2.72, 95% confidence interval 1.38–5.36) but not with forced vital capacity. Conclusions: The MNA-SF can effectively assess the nutritional status of patients with NTM-PD and can serve as an important clinical indicator in NTM-PD where treatment timing is determined by clinical judgment. [ABSTRACT FROM AUTHOR]

The use of nanomaterials in gene editing and synthetic biology has emerged as a pivotal strategy in the pursuit of refined treatment methodologies for pulmonary disorders. This review discusses the utilization of nanomaterial-assisted gene editing tools and synthetic biology techniques to promote the development of more precise and efficient treatments for pulmonary diseases. First, we briefly outline the characterization of the respiratory system and succinctly describe the principal applications of diverse nanomaterials in lung ailment treatment. Second, we elaborate on gene-editing tools, their configurations, and assorted delivery methods, while delving into the present state of nanomaterial-facilitated gene-editing interventions for a spectrum of pulmonary diseases. Subsequently, we briefly expound on synthetic biology and its deployment in biomedicine, focusing on research advances in the diagnosis and treatment of pulmonary conditions against the backdrop of the coronavirus disease 2019 pandemic. Finally, we summarize the extant lacunae in current research and delineate prospects for advancement in this domain. This holistic approach augments the development of pioneering solutions in lung disease treatment, thereby endowing patients with more efficacious and personalized therapeutic alternatives. [ABSTRACT FROM AUTHOR]

Background: Postoperative pulmonary complications (PPCs) are among the most severe complications following total hip arthroplasty revision (THAR), imposing significant burdens on individuals and society. This study examined the prevalence and risk factors of PPCs following THAR using the NIS database, identifying specific pulmonary complications (SPCs) and their associated risks, including pneumonia, acute respiratory failure (ARF), and pulmonary embolism (PE). Methods: The National Inpatient Sample (NIS) database was used for this cross-sectional study. The analysis included patients undergoing THAR based on NIS from 2010 to 2019. Available data include demographic data, diagnostic and procedure codes, total charges, length of stay (LOS), hospital information, insurance information, and discharges. Results: From the NIS database, a total of 112,735 THAR patients in total were extracted. After THAR surgery, there was a 2.62% overall incidence of PPCs. Patients with PPCs after THAR demonstrated increased LOS, total charges, usage of Medicare, and in-hospital mortality. The following variables have been determined as potential risk factors for PPCs: advanced age, pulmonary circulation disorders, fluid and electrolyte disorders, weight loss, congestive heart failure, metastatic cancer, other neurological disorders (encephalopathy, cerebral edema, multiple sclerosis etc.), coagulopathy, paralysis, chronic pulmonary disease, renal failure, acute heart failure, deep vein thrombosis, acute myocardial infarction, peripheral vascular disease, stroke, continuous trauma ventilation, cardiac arrest, blood transfusion, dislocation of joint, and hemorrhage. Conclusions: Our study revealed a 2.62% incidence of PPCs, with pneumonia, ARF, and PE accounting for 1.24%, 1.31%, and 0.41%, respectively. A multitude of risk factors for PPCs were identified, underscoring the importance of preoperative optimization to mitigate PPCs and enhance postoperative outcomes. [ABSTRACT FROM AUTHOR]

Background: The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes. Methods: Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365. Results: The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27–0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6–1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3–4.5) in the control group, p = 0.037. Conclusions: Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial. Trial Registration: ClinicalTrials.gov, NCT03262142, registration date 2017–08-25. [ABSTRACT FROM AUTHOR]

Precision Cut Lung Slices (PCLS) have emerged as a sophisticated and physiologically relevant ex vivo model for studying the intricacies of lung diseases, including fibrosis, injury, repair, and host defense mechanisms. This innovative methodology presents a unique opportunity to bridge the gap between traditional in vitro cell cultures and in vivo animal models, offering researchers a more accurate representation of the intricate microenvironment of the lung. PCLS require the precise sectioning of lung tissue to maintain its structural and functional integrity. These thin slices serve as invaluable tools for various research endeavors, particularly in the realm of airway diseases. By providing a controlled microenvironment, precision-cut lung slices empower researchers to dissect and comprehend the multifaceted interactions and responses within lung tissue, thereby advancing our understanding of pulmonary pathophysiology. [ABSTRACT FROM AUTHOR]

Background: This study assessed the diagnosis, staging and treatment guidance of lung cancer (LC) based on seven tumor-associated autoantibodies (TAAbs) —p53, PGP9.5, SOX2, GBU4-5, MAGE A1, CAGE, and GAGE7. Methods: ELISA was used to determine the TAAb serum levels in 433 patients diagnosed with LC (161 surgical patients) and 76 patients with benign lung disease (16 surgical patients). The statistical characteristic of the TAAbs was compared among patients with different clinicopathological features. Pre- to postoperative changes in TAAb levels were analyzed to determine their value of LC. Results: Among all patients, the positive rate of the seven TAAbs was 23.4%, sensitivity was 26.3%, accuracy was 36.3%, specificity was 93.4%, positive predictive value was 95.8%, and negative predictive value was 18.2%; the positive rate for the LC group (26.3%) was significantly higher than that for the benign group (6.6%; P < 0.001). Significant differences in the positive rate of the seven autoantibodies according to age (P < 0.001), smoking history (P = 0.009) and clinical LC stage (P < 0.001) were found. Smoking was positively associated with the positive of TAAbs (Τ = 0.118, P = 0.008). The positive rates of the seven TAAbs for squamous carcinoma (54.5%), other pathological types (44.4%) and poorly differentiated LC (57.1%) were significantly higher than those for the other types. The positive rate of GBU4-5 was highest among all TAAbs, and the SOX2 level in stage III-IV patients was much higher than that in other stages. For patients undergoing surgery, compared with the preoperative levels, the postoperative levels of the 7 markers, particularly p53 (P = 0.027), PGP9.5 (P = 0.007), GAGE7 (P = 0.014), and GBU4-5 (P = 0.002), were significantly different in the malignant group, especially in stage I-II patients, while no clear pre- to postoperative difference was observed in the benign group. Conclusions: When the seven TAAbs was positive, it was very helpful for the diagnosis of LC. The 7 TAAbs was valuable for staging and guiding treatment of LC in surgical patients. [ABSTRACT FROM AUTHOR]

Background: The role of mechanical power on pulmonary outcomes after thoracic surgery with one-lung ventilation was unclear. We investigated the association between mechanical power and postoperative pulmonary complications in patients undergoing thoracoscopic lung resection surgery. Methods: In this single-center, prospective observational study, 622 patients scheduled for thoracoscopic lung resection surgery were included. Volume control mode with lung protective ventilation strategies were implemented in all participants. The primary endpoint was a composite of postoperative pulmonary complications during hospital stay. Multivariable logistic regression models were used to evaluate the association between mechanical power and outcomes. Results: The incidence of pulmonary complications after surgery during hospital stay was 24.6% (150 of 609 patients). The multivariable analysis showed that there was no link between mechanical power and postoperative pulmonary complications. Conclusions: In patients undergoing thoracoscopic lung resection with standardized lung-protective ventilation, no association was found between mechanical power and postoperative pulmonary complications. Trial registration: Trial registration number: ChiCTR2200058528, date of registration: April 10, 2022. [ABSTRACT FROM AUTHOR]

Background: Measurement of exhaled nitric oxide (FeNO) is a potentially useful diagnostic test for asthma. However, no study has explored the relationship between FeNO and respiratory symptoms of nontuberculous mycobacterial pulmonary disease (NTM-PD) complicated with asthma. The objective of this study was to assess the utility of measuring FeNO levels in patients with NTM-PD complicated by asthma. Methods: In this single-center retrospective cohort study, 140 NTM-PD patients with FeNO measured were enrolled. We selected NTM-PD patients who complicated with asthma as the NTM+BA group, defined using the following criteria: NTM patients with symptoms consistent with asthma, and NTM patients with symptomatic improvement after diagnostic therapy with ICS ± a long-acting beta 2-agonist (LABA). We then calculated a diagnostic cutoff point to distinguish between the NTM+BA groups and the NTM groups (all others). High-resolution computed tomography (HRCT) images were evaluated using the CT scoring system and their association with FeNO was examined. Results: A total of 89 patients were included in the study. (31 in the NTM+BA group and 58 in the NTM group). Compared with the NTM group, the NTM+BA group had higher rates of allergic disease (51.6% vs. 22.4%; p=0.0085) and higher FeNO values (median, 23 [interquartile range {IQR}, 15.0-43.0] ppb vs. median, 17 [IQR, 11.8-23.0] ppb; p=0.015). With diagnostic asthma care using mainly ICS/LABA with reference to the FeNO, most patients (91.0%, 20/22) in the NTM-preceding subgroup in the NTM+BA group demonstrated a prompt improvement of their symptoms and AFB culture findings did not worsen (Culture positive rate (%): Pre-treatment: 59.1% vs. Post-treatment: 40.9%, p=0.3660) at 6 months after starting diagnostic therapy. The optimal diagnostic cutoff point of FeNO to distinguish between the two groups was calculated as 21.5 ppb by the ROC curve (sensitivity 75%, specificity 71.93%, p<0.0001; area under the curve: 0.7989). No significant correlation was observed between FeNO and the severity of CT images in the patients. Conclusions: A certain number of patients with NTM-PD showed exacerbated respiratory symptoms due to asthmatic complications. Elevated FeNO levels suggest asthma complications, even in patients with NTM. [ABSTRACT FROM AUTHOR]

Background: Fractional exhaled nitric oxide (FeNO) has been extensively studied in various causes of pulmonary hypertension (PH), but its utility as a noninvasive marker remains highly debated. The objective of our study was to assess FeNO levels in patients with idiopathic pulmonary arterial hypertension (IPAH) and mixed connective tissue disease complicating pulmonary hypertension (MCTD-PH), and to correlate them with respiratory functional data, disease severity, and cardiopulmonary function. Methods: We collected data from 54 patients diagnosed with IPAH and 78 patients diagnosed with MCTD-PH at the Shanghai Pulmonary Hospital Affiliated to Tongji University. Our data collection included measurements of brain natriuretic peptide (pro-BNP), cardiopulmonary exercise test (CPET), pulmonary function test (PFT), impulse oscillometry (IOS), and FeNO levels. Additionally, we assessed World Health Organization functional class (WHO-FC) of each patient. Results: (1) The fractional exhaled concentration of nitric oxide was notably higher in patients with IPAH compared to those with MCTD-PH. Furthermore, within the IPAH group, FeNO levels were found to be lower in cases of severe IPAH compared to mild IPAH (P = 0.024); (2) In severe pulmonary hypertension as per the WHO-FC classification, FeNO levels in IPAH exhibited negative correlations with FEV1/FVC (Forced Expiratory Velocity at one second /Forced Vital Capacity), MEF50% (Maximum Expiratory Flow at 50%), MEF25%, and MMEF75/25% (Maximum Mid-expiratory Flow between 75% and 25%), while in severe MCTD-PH, FeNO levels were negatively correlated with R20% (Resistance at 20 Hz); (3) ROC (Receiving operator characteristic curve) analysis indicated that the optimal cutoff value of FeNO for diagnosing severe IPAH was 23ppb; (4) While FeNO levels tend to be negatively correlated with peakPETO2(peak end-tidal partial pressure for oxygen) in severe IPAH, in mild IPAH they had a positive correlation to peakO2/Heart rate (HR). An interesting find was observed in cases of severe MCTD-PH, where FeNO levels were negatively correlated with HR and respiratory exchange ratio (RER), while positively correlated with O2/HR throughout the cardiopulmonary exercise test. Conclusion: FeNO levels serve as a non-invasive measure of IPAH severity. Although FeNO levels may not assess the severity of MCTD-PH, their significant makes them a valuable tool when assessing severe MCTD-PH. [ABSTRACT FROM AUTHOR]

Background: Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a complex condition characterized by shared clinical and pathophysiological features of asthma and COPD in older individuals. However, the pathophysiology of ACO remains unexplored. We aimed to identify the major inflammatory cells in ACO, examine senescence within these cells, and elucidate the genes responsible for regulating senescence. Methods: Bioinformatic analyses were performed to investigate major cell types and cellular senescence signatures in a public single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO. Similar analyses were carried out in an independent cohort study Immune Mechanisms Severe Asthma (IMSA), which included bulk RNA-Seq and CyTOF data from bronchoalveolar lavage fluid (BALF) samples. Results: The analysis of the scRNA-Seq data revealed that monocytes/ macrophages were the predominant cell type in the lung tissues of ACO patients, constituting more than 50% of the cells analyzed. Lung monocytes/macrophages from patients with ACO exhibited a lower prevalence of senescence as defined by lower enrichment scores of SenMayo and expression levels of cellular senescence markers. Intriguingly, analysis of the IMSA dataset showed similar results in patients with severe asthma. They also exhibited a lower prevalence of senescence, particularly in airway CD206 + macrophages, along with increased cytokine expression (e.g., IL-4, IL-13, and IL-22). Further exploration identified alveolar macrophages as a major subtype of monocytes/macrophages driving cellular senescence in ACO. Differentially expressed genes related to oxidation-reduction, cytokines, and growth factors were implicated in regulating senescence in alveolar macrophages. PPARγ (Peroxisome Proliferator-Activated Receptor Gamma) emerged as one of the predominant regulators modulating the senescent signature of alveolar macrophages in ACO. Conclusion: The findings suggest that senescence in macrophages, particularly alveolar macrophages, plays a crucial role in the pathophysiology of ACO. Furthermore, PPARγ may represent a potential therapeutic target for interventions aimed at modulating senescence-associated processes in ACO.Key words ACO, Asthma, COPD, Macrophages, Senescence, PPARγ. [ABSTRACT FROM AUTHOR]

Background: Chronic lung disease affects nearly 37 million Americans and often results in significant quality of life impairment and healthcare burden. Despite guidelines calling for palliative care (PC) integration into pulmonary care as a vital part of chronic lung disease management, existing PC models have limited access and lack scalability. Use of telehealth to provide PC offers a potential solution to these barriers. This study explored perceptions of patients with chronic lung disease regarding a telehealth integrated palliative care (TIPC) model, with plans to use findings to inform development of an intervention protocol for future testing. Methods: For this qualitative study, we conducted semi-structured interviews between June 2021- December 2021 with patients with advanced chronic lung disease. Interviews explored experiences with chronic lung disease, understanding of PC, and perceived acceptability of the proposed model along with anticipated facilitators and barriers of the TIPC model. We analyzed findings with a content analysis approach. Results: We completed 20 interviews, with two that included both a patient and caregiver together due to patient preference. Perceptions were primarily related to three categories: burden of chronic lung disease, pre-conceived understanding of PC, and perspective on the proposed TIPC model. Analysis revealed a high level of disease burden related to chronic lung disease and its impact on day-to-day functioning. Although PC was not well understood, the TIPC model using a shared care planning approach via telehealth was seen by most as an acceptable addition to their chronic lung disease care. Conclusions: These findings emphasize the need for a patient-centered, shared care planning approach in chronic lung disease. The TIPC model may be one option that may be acceptable to individuals with chronic lung disease. Future work includes using findings to refine our TIPC model and conducting pilot testing to assess acceptability and utility of the model. [ABSTRACT FROM AUTHOR]

Background: Longitudinal studies have identified childhood asthma as a risk factor for obstructive pulmonary disease (COPD) and asthma-COPD overlap (ACO) where persistent airflow limitation can develop more aggressively. However, a causal link between childhood asthma and COPD/ACO remains to be established. Our study aimed to model the natural history of childhood asthma and COPD and to investigate the cellular/molecular mechanisms that drive disease progression. Methods: Allergic airways disease was established in three-week-old young C57BL/6 mice using house dust mite (HDM) extract. Mice were subsequently exposed to cigarette smoke (CS) and HDM for 8 weeks. Airspace enlargement (emphysema) was measured by the mean linear intercept method. Flow cytometry was utilised to phenotype lung immune cells. Bulk RNA-sequencing was performed on lung tissue. Volatile organic compounds (VOCs) in bronchoalveolar lavage-fluid were analysed to screen for disease-specific biomarkers. Results: Chronic CS exposure induced emphysema that was significantly augmented by HDM challenge. Increased emphysematous changes were associated with more abundant immune cell lung infiltration consisting of neutrophils, interstitial macrophages, eosinophils and lymphocytes. Transcriptomic analyses identified a gene signature where disease-specific changes induced by HDM or CS alone were conserved in the HDM-CS group, and further revealed an enrichment of Mmp12, Il33 and Il13, and gene expression consistent with greater expansion of alternatively activated macrophages. VOC analysis also identified four compounds increased by CS exposure that were paradoxically reduced in the HDM-CS group. Conclusions: Early-life allergic airways disease worsened emphysematous lung pathology in CS-exposed mice and markedly alters the lung transcriptome. [ABSTRACT FROM AUTHOR]

Background: Environmental/occupational exposures cause significant lung diseases. Agricultural organic dust extracts (ODE) and bacterial component lipopolysaccharide (LPS) induce recruited, transitioning murine lung monocytes/macrophages, yet their cellular role remains unclear. Methods: CCR2 RFP+ mice were intratracheally instilled with high concentration ODE (25%), LPS (10 μg), or gram-positive peptidoglycan (PGN, 100 μg) for monocyte/macrophage cell-trafficking studies. CCR2 knockout (KO) mice and administration of intravenous clodronate liposomes strategies were employed to reduce circulating monocytes available for lung recruitment following LPS exposure. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected. Pro-inflammatory and/or pro-fibrotic cytokines, chemokines, and lung extracellular matrix mediators were quantitated by ELISA. Infiltrating lung cells including monocyte/macrophage subpopulations, neutrophils, and lymphocytes were characterized by flow cytometry. Lung histopathology, collagen content, vimentin, and post-translational protein citrullination and malondialdehyde acetaldehyde (MAA) modification were quantitated. Parametric statistical tests (one-way ANOVA, Tukey'smultiple comparison) and nonparametric statistical (Kruskal–Wallis, Dunn's multiple comparison) tests were used following Shapiro–Wilk testing for normality. Results: Intratracheal instillation of ODE, LPS, or PGN robustly induced the recruitment of inflammatory CCR2+ CD11cintCD11bhi monocytes/macrophages and both CCR2+ and CCR2− CD11c−CD11bhi monocytes at 48 h. There were also increases in CCR2+ CD4+ and CD8+ T cells and NK cells. Despite reductions in LPS-induced lung infiltrating CD11cintCD11bhi cells (54% reduction), CCR2 knockout (KO) mice were not protected against LPS-induced inflammatory and pro-fibrotic consequences. Instead, compensatory increases in lung neutrophils and CCL2 and CCL7 release occurred. In contrast, the depletion of circulating monocytes through the administration of intravenous clodronate (vs. vehicle) liposomes 24 h prior to LPS exposure reduced LPS-induced infiltrating CD11cintCD11bhi monocyte-macrophage subpopulation by 59% without compensatory changes in other cell populations. Clodronate liposome pre-treatment significantly reduced LPS-induced IL-6 (66% reduction), matrix metalloproteinases (MMP)-3 (36%), MMP-8 (57%), tissue inhibitor of metalloproteinases (61%), fibronectin (38%), collagen content (22%), and vimentin (40%). LPS-induced lung protein citrullination and MAA modification, post-translational modifications implicated in lung disease, were reduced (39% and 48%) with clodronate vs. vehicle liposome. Conclusion: Highly concentrated environmental/occupational exposures induced the recruitment of CCR2+ and CCR2− transitioning monocyte-macrophage and monocyte subpopulations and targeting peripheral monocytes may reduce the adverse lung consequences resulting from exposures to LPS-enriched inhalants. [ABSTRACT FROM AUTHOR]

Background: Bronchiectasis is a pulmonary disease characterized by irreversible dilation of the bronchi and recurring respiratory infections. Few studies have described the microbiology and prevalence of infections in large patient populations outside of specialized tertiary care centers. Methods: We used the Cerner HealthFacts Electronic Health Record database to characterize the nature, burden, and frequency of pulmonary infections among persons with bronchiectasis. Chronic infections were defined based on organism-specific guidelines. Results: We identified 7,749 patients who met our incident bronchiectasis case definition. In this study population, the organisms with the highest rates of isolate prevalence were Pseudomonas aeruginosa with 937 (12%) individuals, Staphylococcus aureus with 502 (6%), Mycobacterium avium complex (MAC) with 336 (4%), and Aspergillus sp. with 288 (4%). Among persons with at least one isolate of each respective pathogen, 219 (23%) met criteria for chronic P. aeruginosa colonization, 74 (15%) met criteria for S. aureus chronic colonization, 101 (30%) met criteria for MAC chronic infection, and 50 (17%) met criteria for Aspergillus sp. chronic infection. Of 5,795 persons with at least two years of observation, 1,860 (32%) had a bronchiectasis exacerbation and 3,462 (60%) were hospitalized within two years of bronchiectasis diagnoses. Among patients with chronic respiratory infections, the two-year occurrence of exacerbations was 53% and for hospitalizations was 82%. Conclusions: Patients with bronchiectasis experiencing chronic respiratory infections have high rates of hospitalization. [ABSTRACT FROM AUTHOR]

Background: Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny. Case presentation: A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid–Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte–macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal. Conclusions: This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind. [ABSTRACT FROM AUTHOR]