Compromised Lung Function Research Articles

Prognostic significance of pretreatment PET parameters in inoperable, node-positive NSCLC patients with poor prognostic factors undergoing hypofractionated radiotherapy: a single-institution retrospective study

BackgroundNode-positive non-small cell lung cancers (NSCLCs) present a challenge for treatment decisions, particularly in patients ineligible for concurrent chemoradiotherapy (CRT) due to poor performance status and compromised lung function. We aimed to investigate the prognostic value of pretreatment positron emission tomography (PET) parameters in high-risk patients undergoing hypofractionated radiotherapy.MethodsA retrospective analysis was conducted on 42 consecutive patients with inoperable node-positive NSCLC, who underwent hypofractionated radiotherapy between 2014 and 2021 at a single institution. Clinical, treatment-related, and [18F]FDG PET-based parameters were correlated with progression-free survival (PFS) and overall survival (OS). Median dichotomisation was performed to establish risk groups. Statistical analyses included univariable and multivariable Cox regression and Kaplan-Meier survival analyses.ResultsAfter a median follow-up of 47.1 months (range: 0.5-101.7), the median PFS and OS were 11.5 months (95% CI: 7.4-22.0), and 24.3 months (95% CI: 14.1-31.8). In univariable Cox regression analysis, significant predictors of PFS included receipt of salvage systemic treatment (p=0.007), SUVmax (p=0.032), and tMTV (p=0.038). Similarly, ECOG-PS (p=0.014), Histology (p=0.046), and tMTV (p=0.028) were significant predictors of OS. Multivariable Cox regression analysis (MVA) identified SUVmax as a significant predictor for PFS [HR: 2.29 (95% CI: 1.02-5.15); p=0.044]. For OS, ECOG-PS remained a significant prognosticator [HR: 3.53 (95% CI: 1.49-8.39); p=0.004], and tMTV approached significance [HR: 2.24 (95% CI: 0.95-5.26); p=0.065]. Furthermore, the high tMTV group exhibited a median PFS of 5.3 months [95% CI: 2.8-10.4], while the low tMTV group had a PFS of 15.2 months [95% CI: 10.1-33.5] (p=0.038, log-rank test). Median OS was 33.5 months [95% CI: 18.3-56.8] for tMTV ≤ 36.6 ml vs. 14.1 months [95% CI: 8.1-27.2] for tMTV > 36.6 ml (p=0.028, log-rank test).ConclusionPretreatment PET parameters, especially tMTV, hold promise as prognostic indicators in NSCLC patients undergoing hypofractionated radiotherapy. The study highlights the potential of PET metrics as biomarkers for patient stratification.

A Randomized Case-Control Study on High-Frequency Chest Wall Oscillator Versus Conventional Chest Physical Therapy in Spinal Cord Injury Subjects

Study Design: This study is a randomized case-control trial. Setting: Indian Spinal Injuries Centre, Vasant Kunj, New Delhi, India. Background: Spinal cord injury (SCI) often results in severe respiratory dysfunction, leading to increased morbidity and mortality. Respiratory complications, including atelectasis and pneumonia, are prevalent and exacerbated by compromised lung function and ineffective cough. CCPT poses risks like hypoxemia and arrhythmias. HFCWO has emerged as a promising alternative, facilitating airway clearance and improving lung function without manual intervention. Despite its efficacy in other conditions, its specific benefits in SCI require further study. Objective: To study the effect of High-Frequency Chest Wall Oscillator versus Conventional Chest Physical Therapy in candidates with Spinal Cord Injury. Methodology: A sample of 78 SCI patients was selected, with 71 completing the study. Patients were divided into Group A (HFCWO) and Group B (CCPT). Baseline vital, clinical, and radiological parameters were recorded. Group A received HFCWO twice daily for 15 minutes over 5 days, while Group B received CCPT that included positioning, percussions on the affected lobe, and mechanical vibration for 5 days as indicated. Suctioning was performed post-intervention in both groups. Parameters were re-evaluated post-treatment and after 5 days by an intensivist. Results: The median (IQR) age of participants was 32 (18 to 60). Wilcoxon signed- rank test was used for intragroup analysis. The intervention group (HFCWO) had a median age of 49, and the control group (CCPT) had a median age of 22.In the HFCWO group, RR significantly decreased and SpO2 significantly increased (p<0.05) from Day 1 to Day 5. No significant changes were observed in HR and MAP. PEEP, FiO2, and ROASSCI significantly decreased (p<0.05). In the CCPT group, RR, HR, and MAP significantly increased (p<0.05), with no significant change in SpO2. PEEP and FiO2 significantly decreased, but ROASSCI did not change. Both groups showed significant improvement in Chest X-ray scores (p<0.05). Conclusion: This study compares High-Frequency Chest Wall Oscillator (HFCWO) with conventional chest physical therapy (CCPT) in spinal cord injury patients. HFCWO showed superior improvements in clinical and radiological parameters, facilitating earlier ventilator weaning. These findings suggest that HFCWO is a more effective alternative to CCPT for airway clearance in intubated SCI patients.

Senescent lung-resident mesenchymal stem cells drive pulmonary fibrogenesis through FGF-4/FOXM1 axis

BackgroundIdiopathic pulmonary fibrosis (IPF) is an age-related disease featured with abnormal fibrotic response and compromised lung function. Cellular senescence is now considered as an essential driving mechanism for IPF. Given the poor knowledge of the mechanisms underpinning IPF progression, understanding the cellular processes and molecular pathways is critical for developing effective therapies of IPF.MethodsLung fibrosis was induced using bleomycin in C57BL/6 mice. Cellular senescence was measured by immunofluorescence. The effects of FGF-4 on fibroblast activation markers and signaling molecules were assessed with western blot and qPCR.ResultsWe demonstrated elevated abundance of senescent mesenchymal stem cells (MSCs) in IPF lung tissues, which was tightly correlated with the severity of pulmonary fibrosis in vivo. In addition, senescent MSCs could effectively induce the phenotype of pulmonary fibrosis both in vitro and in vivo. To further confirm how senescent MSCs regulate IPF progression, we demonstrate that FGF-4 is significantly elevated in senescent MSCs, which can induce the activation of pulmonary fibroblasts. In vitro, FGF-4 can activate Wnt signaling in a FOXM1-dependent manner. Inhibition of FOXM1 via thiostrepton effectively impairs FGF-4-induced activation of pulmonary fibroblast and dramatically suppresses the development of pulmonary fibrosis.ConclusionThese findings reveal that FGF-4 plays a crucial role in senescent MSCs-mediated pulmonary fibrogenesis, and suggests that strategies aimed at deletion of senescent MSCs or blocking the FGF-4/FOXM1 axis could be effective in the therapy of IPF.

Acute exacerbation of interstitial lung diseases and mortality post-cryobiopsy: a multicenter cohort study.

Interstitial lung diseases (ILDs) are a group of pulmonary disorders affecting the lung's structure. Acute exacerbation of ILD (AE-ILD) following medical procedures is a significant clinical concern. Lung cryoprobe transbronchial biopsy (cryobiopsy) is a relatively new diagnostic technique for ILD, but data on AE-ILD post-cryobiopsy is limited. This study aims to fill this gap by examining the prevalence, risk factors, and outcomes of AE-ILD following cryobiopsy. This multicenter retrospective study analyzed data from patients who underwent cryobiopsy for ILD diagnosis at three U.S. institutions between January 2014 and August 2022. The study included patients over 18 years with confirmed or suspected ILD, categorized into those who experienced AE-ILD post-cryobiopsy and those who did not. Out of 111 patients, 3.6% experienced AE-ILD, with a 50% mortality rate in these cases. The study cohort was predominantly white, with a median age of 69.0 years. Common comorbidities included tobacco use and hypertension. Patients who developed AE-ILD had an increased median number of biopsies. The overall 30-day mortality was 1.8%. Overall complication rate was 32%, including pneumonia, pneumothorax, AE-ILD, and bleeding requiring intervention. The study findings suggest that bronchoscopic cryobiopsy may be associated with lower overall mortality, particularly in patients with compromised lung function. This study provides significant insights into AE-ILD following cryobiopsy, underscoring the need for careful patient selection and procedural assessment. While cryobiopsy may offer a safer alternative to surgical lung biopsy in specific patient cohorts, the elevated risk of AE-ILD necessitates further research to optimize patient outcomes and procedural safety.

Efficacies of omadacycline + amikacin + imipenem and an all-oral regimen omadacycline + clofazimine + linezolid in a mouse model of M. abscessus lung disease.

Treatment outcomes for Mycobacteroides abscessus (Mab, also known as Mycobacterium abscessus) disease are still unsatisfactory, mainly due to issues with drug toxicity, tolerability, and efficacy. Treating Mab disease is challenging due to its high baseline antibiotic resistance, initial requirement for intravenous therapy, and poor medication tolerance. Omadacycline, a new tetracycline, is active against Mab. Since any new antibiotic effective against Mab is expected to be used in combination with other antibiotics, we evaluated the efficacy of two triple-drug combinations comprising omadacycline, omadacycline + amikacin + imipenem, and omadacycline + clofazimine + linezolid against two contemporary Mab clinical isolates in a mouse model of Mab lung disease. Antibiotic administration was initiated 1-week post-infection and was given daily, with Mab burden in the lungs at treatment completion serving as the endpoint. Omadacycline alone moderately reduced Mab levels and maintained better health in mice compared to untreated ones, which typically suffered from the infection. The omadacycline + clofazimine + linezolid combination showed immediate bactericidal activity and enhanced efficacy over 6 weeks, particularly against the more resistant strain (M9507). However, the clofazimine + linezolid combination lacked early bactericidal activity. When combined with amikacin and imipenem, omadacycline did not improve the regimen's effectiveness over 4 weeks of treatment. Our study showed that omadacycline + clofazimine + linezolid exhibited significant bactericidal activity over an extended treatment duration. However, adding omadacycline to amikacin and imipenem did not improve regimen effectiveness against the evaluated clinical isolates within 4 weeks. Further research in Mab disease patients is needed to determine the most effective omadacycline-containing regimen.IMPORTANCEMycobacteroides abscessus is a common environmental bacterium that causes infections in people with compromised lung function, including those with bronchiectasis, cystic fibrosis, chronic obstructive pulmonary disease, and weakened immune systems, especially among older individuals. Treating M. abscessus disease is challenging due to the limited effectiveness and toxicity of current antibiotics, which often require prolonged use. Omadacycline, a new antibiotic, shows promise against M. abscessus. Using a mouse model that mimics M. abscessus disease in humans, we studied the effectiveness of including omadacycline with recommended antibiotics. Adding omadacycline to clofazimine and linezolid significantly improved treatment outcomes, rapidly clearing the bacteria from the lungs and maintaining effectiveness throughout. This oral combination is convenient for patients. However, adding omadacycline to amikacin and imipenem did not improve treatment effectiveness within 4 weeks. Further study with M. abscessus patients is necessary to optimize omadacycline-based treatment strategies for this disease.

Herbal Remedies Effective on Treating Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis (IPF) poses a significant challenge in the realm of respiratory diseases, characterized by progressive lung scarring and compromised breathing function. While conventional medical interventions provide some relief, the exploration of complementary therapies has gained traction, and herbal remedies stand out as a promising avenue. This abstract delves into the efficacy of numerous herbal remedies in the treatment of IPF, shedding light on their potential impact on disease progression and symptom management. Turmeric, derived from Curcuma longa, emerges as a golden healer due to its anti-inflammatory and antioxidant properties, with curcumin exhibiting promise in mitigating lung inflammation and fibrosis. Boswellia serrata, or Indian frankincense, demonstrates anti-inflammatory effects through boswellic acids, suggesting its potential role in suppressing pathways leading to fibrosis. Gingko biloba, renowned for enhancing blood circulation, may contribute to improved oxygenation in individuals with IPF, offering support for compromised lung function. Licorice root, with its anti-inflammatory and expectorant qualities, presents a potential ally in soothing inflammation associated with IPF. Green tea, rich in antioxidants like catechins, shows promise in protecting lung tissues from oxidative stress and inflammation. This abstract emphasizes the importance of caution in integrating herbal remedies, particularly licorice root, and encourages consultation with healthcare professionals to ensure safety, especially in individuals with pre-existing conditions like high blood pressure. In conclusion, the integration of herbal remedies into the treatment paradigm for IPF presents a holistic approach to addressing the complexities of this debilitating condition. As ongoing research explores the mechanisms and efficacy of these herbal interventions, the potential for natural remedies to play a crucial role in managing idiopathic pulmonary fibrosis continues to offer hope for improved patient outcomes.

Obesity and Asthma: Implementing a Treatable Trait Care Model.

Recognition of obesity as a treatable trait of asthma, impacting its development, clinical presentation and management, is gaining widespread acceptance. Obesity is a significant risk factor and disease modifier for asthma, complicating treatment. Epidemiological evidence highlights that obese asthma correlates with poorer disease control, increased severity and persistence, compromised lung function and reduced quality of life. Various mechanisms contribute to the physiological and clinical complexities observed in individuals with obesity and asthma. These encompass different immune responses, including Type IVb, where T helper 2 cells are pivotal and driven by cytokines like interleukins 4, 5, 9 and 13, and Type IVc, characterised by T helper 17 cells and Type 3 innate lymphoid cells producing interleukin 17, which recruits neutrophils. Additionally, Type V involves immune response dysregulation with significant activation of T helper 1, 2 and 17 responses. Finally, Type VI is recognised as metabolic-induced immune dysregulation associated with obesity. Body mass index (BMI) stands out as a biomarker of a treatable trait in asthma, readily identifiable and targetable, with significant implications for disease management. There exists a notable gap in treatment options for individuals with obese asthma, where asthma management guidelines lack specificity. For example, there is currently no evidence supporting the use of incretin mimetics to improve asthma outcomes in asthmatic individuals without Type 2 diabetes mellitus (T2DM). In this review, we advocate for integrating BMI into asthma care models by establishing clear target BMI goals, promoting sustainable weight loss via healthy dietary choices and physical activity and implementing regular reassessment and referral as necessary.

Case Commentary: Dual β-lactam as part of regimen to treat Mycobacterium abscessus lung disease.

Individuals with compromised lung function and immunity are susceptible to developing chronic Mycobacterium abscessus infection. Current treatment recommendations typically involve using one β-lactam antibiotic in combination with non-β-lactam antibiotics. However, a recent case study (B. Becken, K. M. Dousa, J. L. Johnson, S. M. Holland, and R. A. Bonomo, Antimicrob Agents Chemother 68:e00319-24, 2024, https://doi.org/10.1128/aac.00319-24) demonstrated successful treatment of chronic M. abscessus lung disease in a child using two β-lactam antibiotics simultaneously. This commentary reviews the emerging evidence and outstanding questions regarding dual β-lactam therapy for M. abscessus infections.

Novel locally nebulized indocyanine green for simultaneous identification of tumor margin and intersegmental plane.

Segmentectomy, recommended for early-stage lung cancer or compromised lung function, demands precise tumor detection and intersegmental plane identification. While indocyanine green (ICG) commonly aids in these aspects using near-infrared imaging, its separate administrations through different routes and times can lead to complications and patient anxiety. This study aims to develop a lung-specific delivery method by nebulizing low-dose ICG to targeted lung segments, allowing simultaneous detection of lung tumors and intersegmental planes across diverse animal models. To optimizing the dose of ICG for lung tumor and interlobar fissure detection, different doses of ICG (0.25, 0.1, and 0.05mg/kg) were nebulized to rabbit lung tumor models. The distribution of locally nebulized ICG in targeted segments was studied to evaluate the feasibility of detecting lung tumor and intersegmental planes in canine lung pseudotumor models. Near-infrared fluorescence imaging demonstrated clear visualization of lung tumor margin and interlobar fissure using local nebulization of 0.1mg/kg ICG for only 4min during surgery in the rabbit models. In the canine model, the local nebulization of 0.05mg/kg of ICG into the target segment enabled clear visualization of pseudotumor and intersegmental planes for 30min. This innovative approach achieves a reduction in ICG dose and prolonged the visualization time of the intersegmental plane and effectively eliminates the need for the hurried marking of tumors and intersegmental planes. The authors anticipate that lung-specific delivery of ICG will prove valuable for image-guided limited resection of lung tumors in clinical practice.

ZBP1 regulates cytokine production and cell death in lung fibroblasts following influenza virus infection

Abstract Regulated cell death following influenza viral infection is an important determinant of disease severity and is required for effective viral clearance. However, extensive cell death can lead to severe tissue damage and compromised lung function. Z-DNA binding protein-1 (ZBP1) is a critical sensor of influenza A virus (IAV) that can activate both apoptotic (non-inflammatory) or necrotic (inflammatory) cell death pathways. The cell type-specific effects of ZBP1 activation during influenza virus infection have not been clearly defined. Here, our single-cell gene expression studies identified lung fibroblasts as a cell type expressing high levels of Zbp1 following IAV infection in vivo. Following infection in vitro, we observed that ~20% of primary lung fibroblasts were readily infected by IAV but did not support high levels of spreading infection. Lung fibroblasts from wildtype mice underwent cell death with ~50% reduction in cell survival at 24 hours while lung fibroblasts from Zbp1 knockout mice were almost completely resistant to cell death. Analysis of cytokine production prior to cell death demonstrated that IAV infection in lung fibroblasts triggered an early ZBP1-dependent production of inflammatory proteins. Knockout of ZBP1 reduced inflammatory cytokine/chemokine production, but left interferon pathways intact. These studies identify lung fibroblasts as a key cell type activating Zbp1-mediated cytokine production and cell death during influenza virus infection.

DeepChestGNN: A Comprehensive Framework for Enhanced Lung Disease Identification through Advanced Graphical Deep Features.

Lung diseases are the third-leading cause of mortality in the world. Due to compromised lung function, respiratory difficulties, and physiological complications, lung disease brought on by toxic substances, pollution, infections, or smoking results in millions of deaths every year. Chest X-ray images pose a challenge for classification due to their visual similarity, leading to confusion among radiologists. To imitate those issues, we created an automated system with a large data hub that contains 17 datasets of chest X-ray images for a total of 71,096, and we aim to classify ten different disease classes. For combining various resources, our large datasets contain noise and annotations, class imbalances, data redundancy, etc. We conducted several image pre-processing techniques to eliminate noise and artifacts from images, such as resizing, de-annotation, CLAHE, and filtering. The elastic deformation augmentation technique also generates a balanced dataset. Then, we developed DeepChestGNN, a novel medical image classification model utilizing a deep convolutional neural network (DCNN) to extract 100 significant deep features indicative of various lung diseases. This model, incorporating Batch Normalization, MaxPooling, and Dropout layers, achieved a remarkable 99.74% accuracy in extensive trials. By combining graph neural networks (GNNs) with feedforward layers, the architecture is very flexible when it comes to working with graph data for accurate lung disease classification. This study highlights the significant impact of combining advanced research with clinical application potential in diagnosing lung diseases, providing an optimal framework for precise and efficient disease identification and classification.

Effect of diaphragmatic stretch technique on thoracic excursion and pulmonary function in COPD patients: Study protocol for randomized controlled trial.

Limited airflow is a defining feature of COPD, a respiratory disease that frequently results in reduced thoracic movement and compromised lung function. The diaphragm, which is the main breathing muscle, is essential for healthy lung expansion and ventilation. The diaphragm muscle’s flexibility and mobility are intended to be enhanced via diaphragmatic stretching. This method can enhance respiratory health and assist in returning the diaphragm to its original state. Patients with COPD may benefit from improved lung expansion and ventilation because of this. The usefulness of integrating the diaphragmatic stretch approach with traditional chest physical therapy is not well-established. Thus, research is needed to ascertain how the diaphragmatic stretch technique affects lung function and thoracic excursion in COPD patients. This study aims to ascertain how the diaphragmatic stretch technique affects thoracic excursion and pulmonary function (FEV1, FVC, FEV1/FVC, FEF25%-75%, PEFR) in individuals with COPD. There will be 58 COPD patients enrolled in total for this trial; 29 will receive traditional chest physiotherapy along with the diaphragmatic stretch technique, and 29 will receive traditional chest physiotherapy exclusively. Two weeks will pass throughout the intervention. Prior to the intervention, pre-outcome measures will be evaluated, and two weeks later, post-outcome measures will be evaluated once more. The anticipated outcome of this study is that the diaphragmatic stretch technique can enhance thoracic excursion and improve pulmonary function just as well as traditional chest physiotherapy when used in conjunction with it.

Deep Learning Model for Prediction of Bronchopulmonary Dysplasia in Preterm Infants Using Chest Radiographs

Bronchopulmonary dysplasia (BPD) is common in preterm infants and may result in pulmonary vascular disease, compromising lung function. This study aimed to employ artificial intelligence (AI) techniques to help physicians accurately diagnose BPD in preterm infants in a timely and efficient manner. This retrospective study involves two datasets: a lung region segmentation dataset comprising 1491 chest radiographs of infants, and a BPD prediction dataset comprising 1021 chest radiographs of preterm infants. Transfer learning of a pre-trained machine learning model was employed for lung region segmentation and image fusion for BPD prediction to enhance the performance of the AI model. The lung segmentation model uses transfer learning to achieve a dice score of 0.960 for preterm infants with ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le$$\\end{document} 168 h postnatal age. The BPD prediction model exhibited superior diagnostic performance compared to that of experts and demonstrated consistent performance for chest radiographs obtained at ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le$$\\end{document} 24 h postnatal age, and those obtained at 25 to 168 h postnatal age. This study is the first to use deep learning on preterm chest radiographs for lung segmentation to develop a BPD prediction model with an early detection time of less than 24 h. Additionally, this study compared the model’s performance according to both NICHD and Jensen criteria for BPD. Results demonstrate that the AI model surpasses the diagnostic accuracy of experts in predicting lung development in preterm infants.

Excess of body weight is associated with accelerated T-cell senescence in hospitalized COVID-19 patients

BackgroundSeveral risk factors have been involved in the poor clinical progression of coronavirus disease-19 (COVID-19), including ageing, and obesity. SARS-CoV-2 may compromise lung function through cell damage and paracrine inflammation; and obesity has been associated with premature immunosenescence, microbial translocation, and dysfunctional innate immune responses leading to poor immune response against a range of viruses and bacterial infections. Here, we have comprehensively characterized the immunosenescence, microbial translocation, and immune dysregulation established in hospitalized COVID-19 patients with different degrees of body weight.ResultsHospitalised COVID-19 patients with overweight and obesity had similarly higher plasma LPS and sCD14 levels than controls (all p < 0.01). Patients with obesity had higher leptin levels than controls. Obesity and overweight patients had similarly higher expansions of classical monocytes and immature natural killer (NK) cells (CD56+CD16−) than controls. In contrast, reduced proportions of intermediate monocytes, mature NK cells (CD56+CD16+), and NKT were found in both groups of patients than controls. As expected, COVID-19 patients had a robust expansion of plasmablasts, contrasting to lower proportions of major T-cell subsets (CD4 + and CD8+) than controls. Concerning T-cell activation, overweight and obese patients had lower proportions of CD4+CD38+ cells than controls. Contrasting changes were reported in CD25+CD127low/neg regulatory T cells, with increased and decreased proportions found in CD4+ and CD8+ T cells, respectively. There were similar proportions of T cells expressing checkpoint inhibitors across all groups. We also investigated distinct stages of T-cell differentiation (early, intermediate, and late-differentiated – TEMRA). The intermediate-differentiated CD4 + T cells and TEMRA cells (CD4+ and CD8+) were expanded in patients compared to controls. Senescent T cells can also express NK receptors (NKG2A/D), and patients had a robust expansion of CD8+CD57+NKG2A+ cells than controls. Unbiased immune profiling further confirmed the expansions of senescent T cells in COVID-19.ConclusionsThese findings suggest that dysregulated immune cells, microbial translocation, and T-cell senescence may partially explain the increased vulnerability to COVID-19 in subjects with excess of body weight.

Impact of ambient air pollution on lung function in preterm-born school-aged children

RationaleIncreased outdoor air pollution worsens lung function in children. However, these associations are less well studied in preterm-born individuals.ObjectivesWe assessed associations between ambient air pollutants and spirometry measures in preterm-born...

Impact of surgical approach on 90-day mortality after lung resection for nonsmall cell lung cancer in high-risk operable patients.

Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients. We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients. Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV1 and DLCO above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV1 and/or preoperative DLCO below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%) versus 1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10% versus 3.18% respectively). By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV1 or DLCO below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.

Pulmonary Injury as a Complication of Urinary Tract Infection in Pregnancy.

Pulmonary injuries resulting from urinary tract infections (UTIs) during pregnancy are rare. Prompt detection of pulmonary complications in pregnant patients with UTIs is crucial to prevent adverse outcomes in both the mother and the fetus. These complications may include respiratory issues, pulmonary edema, and exacerbation of preexisting conditions, such as asthma. We aimed to detect reported cases of pulmonary injury after UTIs among pregnancies. We retrospectively reviewed the reported cases and articles in the PubMed database up to September 2023 on pulmonary injury after UTIs among pregnancies through a detailed search strategy. The titles and abstracts of the selected 15 articles were assessed, and ultimately, 7 articles were chosen based on adherence to our inclusion and exclusion criteria. Approximately 1-2% of women may develop acute pyelonephritis due to persistent UTIs, which has been associated with an increased risk of pulmonary edema in certain cases. UTIs can affect pulmonary health. Uremia, a consequence of UTIs, can lead to alterations in the respiratory drive, mechanics, muscle function, and gas exchange. Furthermore, urinary infection-induced inflammation activates neutrophils and promotes their recruitment to the lungs, compromising lung function and damaging the surrounding tissue. Although systematic research on this topic is limited, there may be a link between UTIs and pulmonary damage. However, it remains unclear whether pregnancy exacerbates this association. For maternal health, child health, and the whole public health, it is important to raise awareness of physicians and gynecologists, as well as the different specialties like emergency and intensive care units, with more information about pulmonary injury after UTI in pregnancy; it is important to note that UTIs may not directly cause pulmonary complications, but physiological changes associated with pregnancy can increase this risk, so more care, observation, early detection, and treatment are critical for treating these complications and achieving best outcome in pregnant women with UTIs. More research is needed in this area, as the mechanism underlying the existence of pulmonary damage post-UTI in pregnancy is unclear.

Metabolic reprograming and increased inflammation by cadmium exposure following early-life respiratory syncytial virus infection-the involvement of protein S-palmitoylation.

Early-life respiratory syncytial virus (RSV) infection (eRSV) is one of the leading causes of serious pulmonary disease in children. eRSV is associated with higher risk of developing asthma and compromised lung function later in life. Cadmium (Cd) is a toxic metal, widely present in the environment and in food. We recently showed that eRSV re-programs metabolism and potentiates Cd toxicity in the lung, and our transcriptome-metabolome-wide study showed strong associations between S-palmitoyl transferase expression and Cd-stimulated lung inflammation and fibrosis signaling. Limited information is available on the mechanism by which eRSV re-programs metabolism and potentiates Cd toxicity in the lung. In the current study, we used a mouse model to examine the role of protein S-palmitoylation (Pr-S-Pal) in low dose Cd-elevated lung metabolic disruption and inflammation following eRSV. Mice exposed to eRSV were later treated with Cd (3.3 mg CdCl2/L) in drinking water for 6 weeks (RSV+Cd). The role of Pr-S-Pal was studied using a palmitoyl transferase inhibitor, 2-bromopalmitate (BP, 10 µM). Inflammatory marker analysis showed that cytokines, chemokines and inflammatory cells were highest in the RSV+Cd group, and BP decreased inflammatory markers. Lung metabolomics analysis showed that pathways including phenylalanine, tyrosine and tryptophan, phosphatidylinositol and sphingolipid were altered across treatments. BP antagonized metabolic disruption of sphingolipid and glycosaminoglycan metabolism by RSV+Cd, consistent with BP effect on inflammatory markers. This study shows that Cd exposure following eRSV has a significant impact on subsequent inflammatory response and lung metabolism, which is mediated by Pr-S-Pal, and warrants future research for a therapeutic target.

Assessment of inflammatory status and oxidative stress in readymade garment manufacturing workers of Garden Reach-Metiabruz area of Kolkata

Objectives: The textile industry including readymade garment manufacturing contributes substantially to the foreign exchange earned by India. More than 45 million people are employed in this industry. Our previous study revealed a compromised lung function (obstructive and mixed) in readymade garment manufacturing workers in the Garden Reach-Metiabruz region of Kolkata. The present study was undertaken to evaluate the impact of the work environment on the immune health at the local and systemic levels of the workers of this region. Oxidative stress encountered by the workers was also assessed. Materials and Methods: Male workers of age group 18–35 years (n = 80) from readymade garment manufacturing units of Garden Reach-Metiabruz region of Kolkata, India were selected for the study. The control group was selected from the same region unexposed to the factory environment. Blood samples were collected from both groups for estimation of cytokines, C-reactive protein (CRP), cortisol and anti-oxidants of the subjects. Sputum samples from dust-exposed workers were studied for alveolar macrophages. Results: Accumulation of alveolar macrophages in the sputum was noted in the workers which indicated a local inflammation. A systemic inflammatory state was revealed by elevated proinflammatory cytokines and CRP. Reduction in antioxidants noted is an indicator of oxidative stress in the workers. Conclusion: A chronic proinflammatory condition exists in these workers and may be the underlying cause of the compromised respiratory status noted in the workers of this region. The inflammatory condition may lead to the pathogenesis of cardiovascular disorders, autoimmune disorders, etc., later in life. This might also influence the outcome of various respiratory infections like the current COVID-19.

Advancing Treatment Strategies: A Comprehensive Review of Drug Delivery Innovations for Chronic Inflammatory Respiratory Diseases.

Chronic inflammatory respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, present ongoing challenges in terms of effective treatment and management. These diseases are characterized by persistent inflammation in the airways, leading to structural changes and compromised lung function. There are several treatments available for them, such as bronchodilators, immunomodulators, and oxygen therapy. However, there are still some shortcomings in the effectiveness and side effects of drugs. To achieve optimal therapeutic outcomes while minimizing systemic side effects, targeted therapies and precise drug delivery systems are crucial to the management of these diseases. This comprehensive review focuses on the role of drug delivery systems in chronic inflammatory respiratory diseases, particularly nanoparticle-based drug delivery systems, inhaled corticosteroids (ICSs), novel biologicals, gene therapy, and personalized medicine. By examining the latest advancements and strategies in these areas, we aim to provide a thorough understanding of the current landscape and future prospects for improving treatment outcomes in these challenging conditions.