Background： Sepsis-induced acute lung injury (ALI) is characterized by disruption of the epithelial barrier and activation of alveolar macrophages (AMs), which leads to uncontrolled pulmonary inflammation. However, effective treatments for ALI are unavailable. This study aimed to discover potential diagnostic molecular biomarkers based on bioinformatics, which will benefit the diagnosis and treatment of sepsis-induced ALI. Methods: GSE10474 was analyzed for differentially expressed genes (DEGs) in sepsis patients with ALI (sepsis + ALI) compared with sepsis patients without ALI. Functional enrichment analysis and protein-protein interaction (PPI) network were performed. on the DEGs via R package “clusterProfiler”, and visualized via Cytoscape. Prediction analysis of microarrays (PAM) was performed to identify diagnostic biomarkers and the diagnostic ability of diagnostic biomarkers was accessed via receiver operating characteristic (ROC) curves. Moreover, interactions among diagnostic biomarkers were analyzed via GeneMANIA. We also analyzed the function of diagnostic biomarkers and predicted their corresponding drugs via Cytoscape plugin BiNGO and web tool DGIdb. At last, we analyzed the transcriptional regulation of the diagnostic biomarkers via the web tool miRNet. Results: 71 genes were found to be differentially expressed in the sepsis + ALI group, mainly involved in immune-related biological processes and pathways. STRING database indicated 31 DEGs have protein-protein interactions. In addition, the PAM identified 6 diagnostic biomarkers, including HIST1H4H, CDKN1A, HMOX1, NQO2, RHOB, and TREM1, from these 31 DEGs. Conclusion: In conclusion, through bioinformatics analyses, we identified 6 potential diagnostic biomarkers and targets for sepsis-induced ALI.

Fasudil, a potent Rho kinase (ROCK) inhibitor, can ameliorate LPS-induced acute lung injury (ALI) in mice, but the mechanism remains obscure. In this study, a mice model of ALI was established by intra-tracheal instillation of LPS. Histological changes, cytokine levels, lung permeability, and endothelial apoptosis were determined to evaluate the effects of fasudil on lung injury. The cellular and molecular biological mechanisms were explored by culturing human pulmonary microvascular endothelial cells (PMECs). The results showed that fasudil reduced LPS-induced lung inflammation, pulmonary hyperpermeability, and endothelial apoptosis in mice. In cultured human PMECs, fasudil inhibited LPS-induced caspse-3 cleavage and cell apoptosis. It also decreased LPS-induced hyperpermeability of human PMECs monolayer by reversing the down-regulation of intercellular junctions. Moreover, fasudil inhibited LPS-induced overexpression of chemokines and intercellular adhesion molecule (ICAM)-1 in human PMECs, which in turn suppressed neutrophil chemotaxis and neutrophil-endothelial adhesion. Further molecular researches showed fasudil inhibited LPS-induced activation of ROCK, NF-κB, and p38 in human PMECs. Our findings demonstrated that fasudil alleviated LPS-induced ALI by protecting endothelial function via inhibiting endothelial apoptosis, maintaining endothelial barrier integrity, and reducing endothelial inflammation. These effects of fasudil could be attributed to the inhibition of ROCK and its downstream NF-κB and p38 signaling pathways.

HMGB1 is a key late inflammatory mediator upregulated during air pollution-induced oxidative stress. Extracellular HMGB1 accumulation in the airways and lungs plays significant roles in the pathogenesis of inflammatory lung injury. Decreasing extracellular HMBG1 level may restore innate immune cell functions to protect the lungs from harmful injuries. Current therapies for air-pollution induced respiratory problems are inadequate. Dietary antioxidants from natural sources could serve as a frontline defense for air pollution-induced oxidative stress lung damage. Here, a standardized bioflavonoid antioxidant composition from Scutellaria baicalensis and Acacia catechu was evaluated for its efficacy in attenuating acute inflammatory lung injury and sepsis induced by oxidative stress and endotoxemia. Murine hyperoxia-exposed, bacterial-challenged acute lung injury, LPS-induced sepsis, and LPS-induced acute inflammatory lung injury models were utilized in vivo. Effect of the bioflavonoid composition on phagocytic activity and HMGB1 release was assessed using hyperoxia-stressed macrophages in vitro. Hematoxylin-eosin (HE) staining for lung tissue damage evaluation, ELISA for inflammatory cytokines and chemokines, western blot analysis for protein and HMGB1 as well as bacterial counts in the lung and airways have been performed. Statistically significant decrease in mortality (50%), reduced proinflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines (CINC-3) in serum and bronchoalveolar lavage, increased bacterial clearance of airways and lungs; reduced airway total protein, and extracellular HMGB1 were observed in vivo. A statistically significant 75.9% reduction in the level of HMGB1 and increased phagocytosis activity were also observed in vitro. The compilation of data in this report strongly suggest that the bioflavonoid composition could be indicated for oxidative stress induced lung damage protection possibly through attenuation of extracellular HMGB1.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Radiation-induced lung injuries (RILI) are a notable complication of thoracic radiotherapy, significantly affecting the quality of life and prognosis for cancer patients. We present the case of a 68-year-old man with metastatic prostate cancer who underwent radiation therapy for a metastatic thoracic vertebral lesion identified with high uptake on a PET-PSMA scan. Four months later, a follow-up PET-PSMA scan indicated that the pathological uptake in the vertebra had resolved, but it also revealed a new lung consolidation with PSMA uptake. This case illustrates a potential pitfall in interpreting PSMA PET-CT findings, as the uptake in the lung lesion was due to RILI rather than malignancy, infection, or another form of pneumonia, highlighting the necessity for careful clinical correlation to avoid misdiagnosis and potentially inappropriate and unnecessary treatment.

One-third of approximately 10 million deaths due to sepsis in a year are due to acute lung injury, and there is no effective treatment yet. Due to its high phenol content, Punica granatum L. bark extract exhibits high antioxidant activity. Amifostine is a free radical scavenger that converts into active thiol in tissues. This study aimed to investigate the antioxidative and anti-inflammatory effects of 2 different doses of PG peel extract and amifostine in sepsis-related acute lung injury. Fifty rats were randomly allocated into 5 groups. Group 1 served as the control group with no sepsis. The remaining groups 2-5 served as the cecal-ligation-puncture (CLP) groups. Group 3 was administered 200 mg/kg amifostine intraperitoneally (ip) 15 minutes before sepsis induction. Groups 4 and 5 received, respectively, 250 mg/kg and 500 mg/kg PG peel extract by oral gavage 9 days before and 30 minutes after the CLP procedure, with a total of 10 doses. MMP-2 and MMP-9 were investigated by immunohistochemical methods. MMP-2 and MMP-9 concentrations significantly increased in the sepsis group compared to the other 4 groups. This study provides evidence that Amifostine and Punica granatum pericarp benefit lung tissue in a rat model of sepsis induced by cecal-ligation puncture.

Background: Ventilatory strategies in acute respiratory distress syndrome patients aim to mitigate the risk of acute lung injury (ALI). However, prolonged utilization of these strategies may precipitate alveolar carbon dioxide elevation and pH reduction. This scoping review endeavors to present extant knowledge concerning hypercapnia effects in experimental models, with or without ALI, specifically focusing on delineating the immunologically mediated pulmonary tissue damage; Methods: A systematic exploration encompassing PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and Scielo databases was undertaken. Articles published between January 1, 2008, and December 31, 2022, were screened for their elucidation of hypercapnia's immunological impact on lung tissue, utilizing experimental or biological models, irrespective of ALI presence; Results: Following duplicate removal and predefined criteria filtering, 30 pertinent articles scrutinizing hypercapnia's influence on pulmonary epithelium were identified. It was observed that hypercapnia induces perturbations in innate immune response gene transcription, mediated via Nuclear Factor-kappa B attenuation. Furthermore, a compromised innate immune response against injurious agents was noted. Concurrently, disruption and subsequent resealing of alveolar epithelial cells were evidenced, primarily through Na/K-ATPase endocytosis, impeding fluid reabsorption at the alveolar epithelium level; Conclusions: In experimental settings, with or without ALI, hypercapnia's immunomediated mechanisms exacerbate innate immune system impairment and disrupt the respiratory epithelium's repair and healing processes.

The electronic cigarette or e-cigarette is the new alternative method to deliver nicotine. In 2007, the United States introduced vaping devices on the market. Due to their attractive taste and lack of adverse effects, these vaping devices have gained popularity among youth and adults. However, there has been increasing evidence that vaping can cause severe lung injury, and these devices release toxic chemicals into the body. E-cigarettes are recognized as a global threat to public health. Nicotine, the most prevalent chemical in vaping devices, is associated with neurological problems and cognitive decline. Long-term use of e-cigarettes can cause adverse health problems, including respiratory illnesses, asthma, bronchitis, and lung inflammation. In 2019, the Centers for Disease Control and Prevention (CDC) officially declared vaping-associated illness EVALI (e-cigarette or Vaping Product Associated Lung Injury). The US Surgeon General published an alarm in December 2016 that e-cigarette consumption among adolescents and teens in the US is a "major public health concern" and that more young people are now vaping than smoking traditional cigarettes and cigars. Since its commercial introduction in 2003, modern electronic cigarettes (or E-cigarette s) have become increasingly popular with smokers, non-smokers, and those who used to smoke who have switched to them. With such a rise in consumption, people are becoming more aware of the irritating, harmful, and perhaps cancer-causing effects on the lungs. (Chadi et al., 2019; Dinardo & Rome, 2019; Lyzwinski et al., 2022; Marrocco et al., 2022; O’Callaghan et al., 2022)

The anti-inflammatory effect of ginsenoside Rh2 (GRh2) is one of the most important ginsenosides. The purpose of this study is to identify the anti-inflammatory and antioxidant effects of GRh2 after LPS challenge lung injury animal model. GRh2 reduced LPS-induced NO, TNF-α, IL-1, IL-4, IL-6 and IL-10 productions in lung tissues. GRh2 treatment decreased the histological alterations in the lung tissues and BALF protein content and total cells number also diminished in LPS-induced lung injury mice. Moreover, GRh2 blocked iNOS, COX-2, the phosphorylation of IκB-α, ERK, JNK, p38, Raf-1 and MEK protein expression which is corresponded to the growth of HO-1, Nrf-2, catalase, SOD and GPx expressions in LPS-induce lung injury. An experimental study has suggested that GRh2 has provided with anti-inflammatory effects in vivo, and its potential therapeutic efficacy in major anterior segment lung diseases.

COVID-19 is a highly infectious respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major cause of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6, TNF-α, and TGF-β1) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

Chest trauma is one of the most serious and difficult injuries, with various complications that can lead to ventilation - perfusion (V/Q) mismatch and systemic hypoxia. We are presenting a case of 53 – year - old male with no comorbidities or chronic therapy, who was admitted to the Intensive Care Unit due to severe respiratory failure after chest trauma. He developed right - sided pneumothorax and then thoracic drain was placed. On admission, the patient was hemodynamically unstable and tachypneic. The patient was intubated and mechanically ventilated, febrile (38.9°C) and unconscious. A lung CT showed massive non-ventilated areas predominantly in the right lung. He was ventilated with PEEP of 10 cmH2O with a FiO2 of 0.6 – 0.8. Empirical broad-spectrum antimicrobial therapy was immediately initiated. Both high FiO2 and moderate PEEP were maintained and adjusted according to the current blood gas values and oxygen saturation. After Stenotrophomonas maltophilia was identified and treated with sulfamethoxazole/trimethoprim his general condition gradually improved, and he was weaned from mechanical ventilation. In conclusion, both ventilatory and antibiotic therapy were needed to improve oxygenation and outcome of the patient with pneumonia due to the resistant S. maltophilia with V/Q mismatch.

Background and Objectives: Acute lung injury (ALI) is an inflammatory response in the lung caused by bacteria, viruses, trauma and other factors that results in lack of alveolar surfactant and subsequently respiratory distress. Endothelial-to-mesenchymal transition (EndoMT) is closely related to ALI-induced pulmonary fibrosis development and progression. This study examined the effect of milk fat globulin factor 8 (MFGE8) knockdown and overexpression on lipopolysaccharide (LPS)-induced EndoMT. Methods: Total MFGE8 activity in patients with acute respiratory distress syndrome (ARDS) and healthy volunteers was assessed using a colorimetric kit. In vitro, cell morphology was observed by microscopy, and invasion and migration were tested by Transwell and scratch assays. Specific siRNAs were transfected into HLMECs to downregulate MFGE8, and CD31 and α-SMA protein expression was detected by fluorescence microscopy and FCM. MFGE8, BMP, Smad 1, Smad4, Smad5, Snail, CD31 and α-SMA protein and gene expression was assessed by western blotting (WB) and qRT‒PCR. In vivo, the changes in cell morphology and alveolar septum in the lung of mice (C57BL/6, aged 7-8 weeks, male) were observed by H&E staining. In addition, ECM deposition in lung tissue was detected by Masson staining. CD31 and α-SMA protein expression in lung tissue was measured by WB. Results: The serum level of MFGE8 was lower in the ARDS group than in the control group. MFGE8 was identified as a protective factor associated with hospital survival. In vitro, the treatment of human lung microvascular endothelial cells (HLMECs) with LPS for 96 h clearly changed the cells from the typical cobblestone shape of ECs to spindle-like fibroblasts. The scratch and Transwell assay results indicated that endothelial cell migration and invasion were enhanced in the LPS group compared with the control group. Fluorescence microscopy, FCM, WB and PCR showed that LPS greatly inhibited CD31 (endothelial marker) expression and increased α-SMA (mesenchymal marker) expression. These data showed that LPS could induce EndoMT in HLMECs. Notably, siRNA-treated HLMECs yielded the same results. The administration of rhMFGE8 to HLMECs in the LPS or LPS+siRNA group ameliorated the changes in cell morphology and decreased cell migration and invasion. rhMFGE8 attenuated the effect of LPS or LPS+siRNA on EndoMT induction by increasing CD31 and decreasing α-SMA protein and gene expression. Moreover, activation of BMP/Smad1/5-Smad4 signalling in response to LPS and Snail (related to EndoMT transcription factors) expression were increased by MFGE8 knockdown but inhibited by rhMFGE8. In vivo, H&E staining revealed a thickened alveolar septum in the LPS group, and the thickness increased over time; in contrast, rhMFGE8 reversed this effect. ECM deposition occurred early in ALI induced by LPS and increased over time, and the administration of rhMFGE8 reversed this effect. WB showed that LPS inhibited CD31 protein expression and increased α-SMA protein expression in lung tissue. Conclusions: rhMFGE8 exerts a protective effect early in LPS-induced EndoMT through BMP/Smad1/5/Smad4 signalling and could be a therapeutic target in ALI.

To date, the percentage composition of the lung microbiome in bronchopulmonary cancer has not been summarized. Existing studies on identifying the lung microbiome in bronchopulmonary cancer through 16S rRNA sequencing have shown variable results regarding the abundance of bacterial taxa. Objectives: To identify the predominant bacteria in the lung microbiome of bronchopulmonary cancer from samples collected through bronchoalveolar lavage and to assess their potential role in the diagnosis of bronchopulmonary cancers. Data Sources: A systematic review of English articles using MEDLINE, Embase, and Web of Science. Search terms included lung microbiome, lung cancer, bronchoalveolar lavage. Study Selection: Randomized clinical trials that investigated the lung microbiome in bronchopulmonary cancer with samples collected via bronchoalveolar lavage. Data Extraction: Independent extraction of articles using predefined data fields, including study quality indicators. Data Synthesis: Nine studies met the inclusion criteria, focusing on those that utilized a percentage expression of the microbiome at the phylum or genus level. There was noted heterogeneity between studies, both in terms of phylum and genus, with a relatively constant percentage of the Firmicutes phylum and the genera Streptococcus and Veillonella being mentioned. Significant differences were also observed regarding the inclusion criteria for study participants, the method of sample collection, and data processing. Conclusions: To date, there is no consistent percentage pattern at the phylum or genus level in bronchopulmonary cancer, with the predominance of a phylum or genus varying across different patient cohorts, resulting in non-overlapping outcomes.

Background/Objectives: Lung carcinoma is the leading cause of cancer-related deaths globally, with lung adenocarcinoma being the most prevalent subtype. This study aims to review the clinical data and survival outcomes of patients diagnosed with lung adenocarcinoma who underwent surgical treatment. Methods: We conducted a retrospective analysis of 471 patients who had surgery for lung adenocarcinoma at our institution. Their medical histories, including previous neoplasms, comorbidities, tumor characteristics, and symptoms, were thoroughly reviewed. We calculated the overall survival rate and evaluated the impact of tumor grading and spread through air spaces (STAS) on patient outcomes. Results: The survival rate for the entire cohort was 76.23%. There was no significant difference in survival rates between patients classified as G1 and G2, suggesting that a simplified two-tier grading system may be more effective. Patients with STAS had a lower survival rate than those without STAS. Conclusions: Our findings indicate that a simplified grading system may improve prognostic evaluations for lung adenocarcinoma patients. Furthermore, STAS is a crucial factor affecting survival rates and should be considered in future treatment strategies. Expanding research in this area is essential to enhance treatment approaches for lung adenocarcinoma patients.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide. There is evidence of a complex interplay between lung cancer and interstitial lung disease (ILD), affecting disease progression, management strategies, and patient outcomes. Both conditions develop as the result of common risk factors such as smoking, environmental exposures, and genetic predispositions. The presence of ILD poses diagnostic and therapeutic challenges in lung cancer management, including difficulties in interpreting radiological findings, increased susceptibility to treatment-related toxicities, such as acute exacerbation of ILD after surgery and pneumonitis after radiation therapy and immunotherapy. Moreover, due to the lack of large, phase III randomized controlled trials in patients with lung cancer and ILDs, the evidence-based therapeutic options remain limited. The role of antifibrotic treatment in the prevention of lung-cancer-related treatment toxicities remains to be elucidated. Emerging diagnostic modalities and biomarkers, and optimizing personalized treatment strategies are essential to improve outcomes in this patient population.

Summarizing radiological characteristics between primary lung adenocarcinoma subtypes and correlate them with FDG uptake on PET-CT are important for further treatment. A PET-CT examination was performed on some of the patients and the values of SUV-max were also correlated with the histological and morphological characteristics of masses in the lungs. Results of this analysis showed that the mean size of AIS-MIA cancer was significantly lower than for all other cancer types, while mean size of the acinar cancer was smaller than in solid type of cancer. Metastases were significantly more frequent in solid adenocarcinoma than in acinar, lepidic and AIS-MIA cancer subtypes. The maximum standardized FDG uptake was significantly lower in AIS-MIA than in all other cancer types, and in acinar compared to solid cancer. Papillary adenocarcinoma had higher odds to develop contralateral lymph node involvement compared to other types. Solid adenocarcinoma was associated with higher odds of having metastases and with higher SUVmax. AIS-MIA was associated with lower odds of one unit increase in tumour size, ipsilateral lymph node involvement. Radiology has a significant role in the diagnosis and monitoring of the disease, and in determining its prognosis, and influence on the decision on the method of treatment.

There is disagreement on the associations between chorioamnionitis and pneumonia/sepsis, respiratory distress syndrome (RDS), and bronchopulmonary (BPD)dysplasia, three pulmonary outcomes of concern for preterm newborns. Determining clear correlations is challenging due to the intricacy of the prenatal, postnatal, and therapeutic practices that affect the diagnosis of RDS, pneumonia/sepsis, and BPD, two long-term outcomes, as well as their short- and long-term consequences. Owing to the interconnected nature of the variables, the vaguely defined fetal exposures, and the imprecise identification of disorders like RDS and BPD, multivariant studies of huge data sets are unreliable methods for defining associations. On the other hand, research using animal models offers reliable data regarding the effects of exploratory chorioamnionitis on the fetal lung. Understanding the clinical intricacy and the experimental consequences of chorioamnionitis together will help us understand on the impact on the fetal lung .

Respiratory diseases are common in rabbits, but subclinical conditions can be challenging to diagnose and may cause respiratory problems during anesthesia. CT is the preferred method for diagnosing lung diseases, but anesthesia can alter lung volume and cause lung lobe collapse. In this study, seventeen healthy 5-month-old male New Zealand white rabbits underwent thoracic CT scans under different conditions. Rabbits were sedated with midazolam and butorphanol and scanned in a sphinx position they were then anesthetized with dexmedetomidine and ketamine and scanned again in sternal recumbency during spontaneous breathing. Lastly, apnea was induced using intermittent positive pressure ventilation (IPPV) for a final scan. Lung volume and density were measured using the 3D Slicer software, with thresholds set between -1050 and -100 Hounsfield Units (HU). Sedated animals had significantly higher total lung volume (69.39±10.04 cm³) than anesthetized (47.10±9.28 cm³) and anesthetized in apnea rabbits (48.60±7.40cm³). Mean lung attenuation during sedation was -611.26 HU (right) and -636.00 HU (left). After anesthesia induction, values increased to -552.75 HU (right) and -561.90 HU (left). Following apnea induction, attenuation slightly decreased to -569.40 HU (right) and -579.94 HU (left). The results indicate that sedation may be preferable for rabbit lung CT to minimize anesthesia-related changes.

Lung nodules detected by chest computed tomography (CT) often require invasive biopsies for definitive diagnosis, leading to unnecessary procedures for benign lesions. A blood-based biomarker test that predicts lung cancer risk in CT-detected nodules could help stratify patients and direct invasive diagnostics toward high-risk individuals. In this multicenter, single-blinded clinical trial, we evaluated a test measuring plasma levels of p53, anti-p53 autoantibody, CYFRA 21-1, and anti-CYFRA 21-1 autoantibody in patients with CT-detected lung nodules. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated, and subgroup analyses by gender, age, and smoking status were performed. A total of 1,132 patients who had CT-detected lung nodules, including 885 lung cancer cases and 247 benign lesions, were enrolled from two academic hospitals in South Korea. The test demonstrated a sensitivity of 78.4% (95% CI: 75.7-81.1) and specificity of 93.1% (95% CI: 90.0-96.3) in predicting lung cancer in CT-detected nodules. The PPV was 97.6%, and the NPV was 54.6%. Performance was consistent across gender (sensitivity 79.3% in men and 76.8% in women) and age groups, with a specificity of 93.4% in men and 92.7% in women. Stage I lung cancer was detected with a sensitivity of 80.6%. The lung cancer test based on 9G technology presented here offers a non-invasive method for stratifying lung cancer risk in patients with CT-detected nodules. Its integration into clinical practice could reduce unnecessary interventions and foster earlier detection.

Systemic sclerosis (also known as scleroderma) is a chronic fibrosing autoimmune disease with both skin and multisystem organ involvement. Scleroderma has the highest mortality among all rheumatic diseases. The pathophysiology mechanism of systemic sclerosis is a progressive self-amplifying process, which implicates the widespread microvascular damage, followed by a dysregulation of innate and adaptive immunity and inflammation, and diffuse fibrosis of the skin and visceral organs. Fibrosis of internal organs is a hint for systemic sclerosis, moreover associated with interstitial lung disease (SSc-ILD) is a complex process. We report a case of a 56 years old female, diagnosed with Systemic Sclerosis 16 years ago. The systemic and clinical manifestations, respiratory functional tests, radiological aspects and specific therapy were discussed.

Lung cancer is one of the deadliest cancers, leading to about 125,070 deaths in the U.S. each year. Survival rates depend on the type and spread of cancer, with localized non-small cell lung cancer (NSCLC) having a 5-year survival rate of 64%. High mortality is primarily due to late detection and the older age of patients, making surgery too risky. As a result, preventative measures like vaccines are crucial. This paper reviews the literature on CIMAvax-EGF, an EGF-based vaccine for lung cancer, evaluating its preventive potential, impact on survival in advanced NSCLC, and effect on lung cancer mortality in combination with other therapies. CIMAvax-EGF is a promising vaccine targeting the Epidermal Growth Factor (EGF), which promotes cancer cell growth. The vaccine prevents EGF from binding to its receptor by inducing anti-EGF antibodies, potentially halting cancer progression. It shows significant potential for treating advanced NSCLC, with vaccinated patients having a median overall survival of 12.43 months compared to 9.43 months in unvaccinated individuals. A Phase III trial showed that 78.8% of patients had a good antibody response (GAR), leading to longer survival. CIMAvax-EGF is well-tolerated, with mild to moderate side effects, and its efficacy is enhanced when combined with other therapies, such as immune checkpoint inhibitors. Given its ability to target cancer's underlying mechanisms and boost other treatments, CIMAvax-EGF represents a significant advancement in the fight against lung cancer. Administering this vaccine preventively and during treatment could be a major step in reducing lung cancer mortality.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Recurrent respiratory papillomatosis (RRP) is a non- malignant disease, characterized by the production of wart-like growths in respiratory tract, affecting both young and adults (Juvenile-Onset Recurrent Respiratory Papillomatosis, JORRP and Adult-Onset Recurrent Respiratory Papillomatosis, AORRP, respectively). Infection caused by Human Papillomavirus (HPV) is known as the main factors involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review was aimed to evaluate the prevalence of severe complications, as lung involvement and lung tumor in JORRP and AORRP patients, following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). Among the 378 studies were found on PubMed and Scopus using the following MESH terms “recurrent respiratory papillomatosis and lung tumor” and “pulmonary tumor and recurrent respiratory papillomatosis”. Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI:4%-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7%-18%; I2 :85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1%- 7%; I2: 67.1%), and a pooled prevalence mortality for this group of 4% (95% CI:2%-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV 11 was 21% (95% CI: 5%-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11 positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

Background/Objectives: Different approaches are required in treating patients with multiple pulmonary lesions. A multistage procedure may increase the risk of complications and patient discomfort. This study provides an initial experience with single-stage management of multiple lung lesions using percutaneous ablation with thoracoscopic resection in a hybrid operating room (HOR). Methods: We retrospectively evaluated patients who underwent combined ablation and resection in a HOR between May 2022 and July 2024. All patients received a single anesthesia via endotracheal tube intubation. Clinical data, operative findings, and pathological characteristics of the lung nodules were recorded. Results: A total of 23 patients were enrolled in this study. Twenty patients underwent unilateral procedures, and the other three patients underwent bilateral procedures. Ablations were performed before lung resection in 22 patients; only one patient underwent surgery first. The median global operating room time was 227.0 min. The median total radiation dose (dose area product) was 14076 μGym2. The median hospital postoperative length of stay was 2 days. Conclusion: The single-stage procedure of percutaneous ablation with thoracoscopic resection under general anesthesia in a HOR is feasible and safe. This procedure is an alternative method for managing multiple pulmonary lesions.

Lung cancer remains the leading cancer killer worldwide. Early diagnosis can effectively increase the patient cure rate but existing diagnostic methods limit early lung cancer diagnosis. Therefore, development of a simple but efficient lung cancer screening method is important to improvement of both the diagnosis rate and the survival rate of lung cancer patients. In this study, ten photosensitive materials with high sensitivity and high specificity were screened accurately to construct a microarray sensor that can rapidly identify six types of lung cancer biomarkers in exhaled breath. Results from hierarchical cluster analysis (HCA), principal component analysis (PCA) and difference maps showed that the classification of the analytes agreed with structure similarity laws. The detection results from parallel experiments and structurally similar analytes, in turn, cluster into a group; the fingerprints of the different analytes have specific response regions. The well-screened sensor chip fabrication workload and cost were both reduced by approximately two thirds, while the microfluidic device sensitivity and stability increased by approximately 1.3 times their corresponding values before optimization. The dual-channel device also offers real-time contrast detection and synchronous parallel detection functions and has potential application prospects for use in extensive screening of high-risk populations for lung cancer.

Distinguishing the level of pathology in the lungs through the sound of a cough is a complicated process that includes many factors. This paper explores the challenges of diagnosing lung pathology based solely on cough sounds. It emphasizes that while cough type can offer initial clues, it is just one piece of a complex diagnostic puzzle. For example, the differentiation of dry, productive, barking, hacking, and wheezing coughs provides initial insights into potential pathologies, which can range from respiratory infections to chronic diseases. The examination of cough characteristics, such as frequency, strength, and persistence, aids in identifying the severity of underlying conditions. Moreover, associated respiratory and systemic symptoms further contribute to the diagnostic landscape, with manifestations such as dyspnea, wheezing, chest pain, and hemoptysis offering valuable clinical information. Diagnostic tests, such as imaging studies and laboratory analyses, play a pivotal role in confirming diagnoses. However, challenges in diagnosis based solely on cough sounds require a more holistic approach, taking into consideration the complexity of lung pathologies. The paper concludes that accurately diagnosing lung pathologies based on cough sounds alone is difficult and requires careful consideration of multiple factors and stresses on contextualizing cough characteristics with other clinical features and diagnostic tests for an accurate assessment and comprehensive treatment planning.

Objectives- We prospectively analyzed children with acute chest pain and clinical suspicion of pneumothorax (PNX) evaluated at the pediatric Emergency Department. Methods- After clinical examination and before Chest X-Ray, children underwent LUS to evaluate the presence of PNX. We enrolled 70 children, 13 (18,57%) received a final diagnosis of PNX. Results- In all 13 (100%) patients LUS showed the “bar-code sign”, the absence of lung sliding and the absence of B lines while in 12 (92,3%) there was the lung point, giving a diagnosis of PNX. All cases had PNX features on CXR. The “bar-code sign”, the absence of lung sliding and the absence of B lines had a sensitivity of 100% and a specificity of 100%. The “bar-code sign” had a positive predictive value of 100% and a negative predictive value of 100% for the detection of PNX. Conclusions- LUS is highly accurate in detecting or excluding pneumothorax in children with acute chest pain evaluated in the pediatric emergency department.

Background: Peroxiredoxins (Prxs) comprise antioxidant factors that are widely found in prokaryotes and eukaryotes. Abnormal expression of Prxs is closely related to tumorigenesis. Methods: This study examined the prognostic value and expression of Prxs in lung cancer by Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier Plotter, cBioPortal and Functional Enrichment Analysis Tool (FunRich) databases. Results: We found that Prx1/2/3/4/5 were overexpressed in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) relative to normal lung cells. However, the expression level of Prx6 was lower in LUAD and higher in LUSC than normal lung cells. The level of Prx3 and Prx6 were associated with pathological stage. Prognostic analysis showed that elevated Prx1 and Prx2 expression were correlated with low Overall Survival (OS), whereas high Prx5 and Prx6 expression level predicted high OS. Conclusions: Our results effectively revealed the level of Prxs in lung cancer and its influence on the prognosis of lung carcinoma, contributing to the study of the role of Prxs in tumorigenesis.

Lung cancer (LC) stands as the foremost cause of cancer-related fatality rates worldwide. Early diagnosis significantly enhances patient survival rate. Nowadays, low dose computed tomography (LDCT) is widely employed on chest as a tool for large-scale lung cancer screening. Nonetheless, a large amount of chest radiographs causes an onerous burden on radiologists. Some computer-aided diagnostic (CAD) tools can provide insights to medical images for diagnosis and augmenting diagnostic speed. However, due to variation in parameter settings across different patients, substantial discrepancies in image voxels persist. We find different voxel-size causing a compromise between model generalization and diagnostic efficacy. This study investigates the performance disparities of diagnostic models trained on original images and LDCT images reconstructed to different voxel-sizes but isotropic. The application is to differentiate a nodule to be benign or malignant. Using 11 features, a support vector machine (SVM) is trained on LDCT images with an isotropic voxel having side-length of 1.5 mm for 225 patients in house. The result yields a favorable model performance with an accuracy of 0.9596 and an area under the receiver operating characteristic curve (ROC/AUC) of 0.9855. In addition to furnish CAD tools for clinical applications, future research is encouraged to include LDCT images from multi-centers.

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents may be beneficial in patients with CPFE, but further studies are needed.

Epidermal Growth Factor Receptor (EGFR) expression is an important aspect in the non-small cell lung cancer (NSCLC) diagnosis and treatment. Therefore, it becomes important to identify factors that may influence EGFR level. There are reports suggesting that one of the positive EGFR gene transcription regulators may be Special AT-rich Binding Protein 1 (SATB1), but so far these ob-servations have not been confirmed in NSCLC. The main aim of the present study was to investigate the possible links between the EGFR and SATB1 expression on both protein and mRNA levels in NSCLC clinical samples, and to correlate the obtained results with the clinical-pathological data of the patients. Additionally, we analysed the relationships between the expression levels of EGFR and the known tumour promoters, in-cluding Ki67 proliferative antigen and EMT-promoting transcription factors - SLUG, SNAIL, and Twist1. We demonstrated that EGFR expression in NSCLC was positively correlated both with the SATB1 level and with the expression of EMT-promoting proteins. Moreover, we were the first to analyse EGFR expression exclusively in NSCLC cancer cells without the interference caused by respiratory epithelium and tumour stroma. Our analysis revealed that the prognostic significance of EGFR expression was dependent on tumour histology and differed significantly between the AC and LSCC samples.

Small-cell lung cancer (SCLC) is a cancer with poor prognosis. For relapsed extensive-stage (ES) SCLC, second-line treatment options are scarce. Topotecan was the only approved treatment in this setting until 2020. Since topotecan induces significant toxicities, alternative off-label regimens are being used. This study evaluated real-world efficacy and safety of Paclitaxel Gemcitabine chemotherapy in patients with relapsed ES-SCLC. We retrospectively reviewed data from all consecutive patients with relapsed ES-SCLC who received Paclitaxel Gemcitabine chemotherapy from september 2008 to january 2022 in two centers. Patient characteristics (n=188) were: PS≥2: 24.5%; brain metastasis: 42%; platinum-sensitive disease: 41%. Patients received Paclitaxel Gemcitabine as second- (77%) third (18%) or fourth (6%) line of therapy. Median progression-free and overall survival were 2.1 (95CI 1.8–2.4) and 3.8 (95CI 3.3–4.8) months in the overall population, respectively, with 17% response rate (RR) and 28% disease-control rate. PS, history of brain radiation, platinum-sensitive disease, liver, and adrenal gland metastasis were associated with longer survival in univariate analysis. PS was the only prognostic factor in multivariate analysis, with 21% RR and 4.1 months median DOR in PS 0-1 patients. Paclitaxel Gemcitabine chemotherapy may represent a treatment option in PS0-1 relapsed SCLC.

Background: The clinical spectrum of fibrotic interstitial lung diseases (ILD) is highly heterogeneous. We aimed to evaluate the prognostic value of widely available baseline biomarkers for improvement of lung function in patients with fibrotic ILD. Methods: This registry-based study included 142 patients with fibrotic ILD as defined by presence of reticulation, traction bronchiectasis or honeycombing on initial high-resolution computed tomography (HRCT). Functional improvement at 1 year was defined as relative increase of 5% in forced vital capacity (FVC) or of 10% in diffusion capacity for carbon monoxide (DLCO). The prognostic value of baseline biomarkers was evaluated for all patients and the subgroup with anti-inflammatory treatment. Results: At one year, 44 patients showed improvement while 73 progressed. Multivariate analyses found prognostic significance for age <60 years (OR 5.4; 95%CI 1.9-15.4; p=0.002), lactate dehydrogenase (LDH) >250U/L (OR 2.5; 95%CI 1.1-5.8; p=0.043) and blood monocyte count <0.8G/L (OR 3.5; 95%CI 1.1-11.3; p=0.034). In 84 patients undergoing anti-inflammatory treatment, multivariate analysis revealed age <60 years (OR 8.5 (95%CI 2.1-33.4; p=0.002) as the only significant variable. Conclusion: Younger age, higher LDH and lower blood monocyte count predicted functional improvement in fibrotic ILD patients, while in those treated with anti-inflammatory drugs, only age had significant implications.

Lung adenocarcinoma (LUAD) is the most common lung cancers, which accounts for about 35%-40% of all lung cancer patients. Despite therapeutic advancements in recent years, the overall survival time of the LUAD patients still remain poor, especially KRAS mutant LUAD. Therefore, it is necessary to further explore novel targets and drugs to improve the prognosis of LUAD. Ferroptosis, an iron-dependent regulated cell death (RCD）caused by lipid peroxidation, has attracted much attention recently as an alternative target for apoptosis in LUAD therapy. Ferroptosis has been found closely related with LUAD, at its every stage, including initiation, proliferation and progression. In this review, we will provide a comprehensive overview on ferroptosis mechanisms, it’s regulation in LUAD, and application of targeting ferroptosis for LUAD therapy.

Asbestos-related risks have been estimated on the basis of data from the past, when professional exposures were higher. Fibers are present in the environment due to erosion of surface deposits and human activities unrelated to asbestos industry. If searched for, asbestos fibers are frequently found at autopsies. Bias can be encountered in asbestos research e.g. attributing of mesothelioma and lung cancer to asbestos when fibers are present, although cause-effect relationships remain unproven. Some studies rely on work or residence histories of questionable reliability. Asbestos is banned in some countries while others are increasing production and exports. Asbestos is a low-cost material and an excellent reinforcing fiber. Different asbestos types have their technical advantages and preferred application areas. The traffic is safer with asbestos-containing brake linings. Asbestos cement constructions are sturdy and inexpensive. The fireproofing properties of asbestos are well known. It can be reasonably assumed that the non-use of asbestos-containing brakes, fireproofing and insulation lagging has increased the damage and numbers of victims of traffic accidents, fires and armed conflicts. Nowadays, when a probability of conflicts seems to be enhanced, the attitude to asbestos should be changed. Most importantly, asbestos-related science must be separated from economical and political interests. Reliable information can be obtained in lifelong bioassays.

:Pulmonary fibrosis is a chronic and fatal lung disease that significantly impacts the aging population globally. To date, anti-fibrotic, immunosuppressive, and other adjunct therapy demonstrate a limited efficacy. Advancing our understanding of pathogenic mechanisms of lung fibrosis provides a future path for the cure. Cellular senescence has gained substantial interest in the past decades due to the increased incidence of fibroproliferative lung diseases in the older age group. Furthermore, the pathologic state of cellular senescence that includes maladaptive tissue repair, decreased regeneration, and chronic inflammation resembles key features of progressive lung fibrosis. This review describes regulatory pathways of cellular senescence and discusses the current knowledge on the senescence of critical cellular players of lung fibrosis, including epithelial cells (alveolar type 2 cells, basal cells, etc.), fibroblasts, and immune cells, their phenotypic changes, and the cellular and molecular mechanisms by which these cells contribute to the pathogenesis of pulmonary fibrosis. A few challenges in the field include establishing appropriate in vivo experimental models and identifying senescence targeted signaling molecules and specific therapy to target senescent cells, known collectively as "senolytic" or “senotherapeutic” agents.

Autoantibodies against specific lung cancer-associated antigens have been suggested for lung cancer diagnosis. This study aimed to evaluate the diagnostic performance of anti-gen-autoantibody immune complex (AIC) against its free antigens for CYFRA21-1, ProGRP, NGAL, and NSE in non-small cell lung cancer (NSCLC). In total, 85 patients with NSCLC and 120 healthy controls (HCs) were examined using a 9G DNA chip method. The ratios of AICs to their antigens and combinations of ratios consisting of two to four markers were calculated. The levels of AICs for CYFRA21-1, ProGRP, NGAL, and NSE were higher than their free antigens in all participants. The levels of each free antigen distinguished patients with NSCLC from HCs. The ratios of AIC to its antigen and seven combinations consisting of two to four ratios were significantly higher in patients with NSCLC than those in HCs. Excellent diagnostic performance was observed for all combination ratios (C4-1), with 85.9% sensitivity and 86.7% specificity at cutoff 3.51. Higher sensitivity was observed in the very early stages (0–I) and adenocarcinoma than in stages II–IV and other pathological types. The combination of all ratios of AICs and their antigens for all four markers is useful in the diagnosis of NSCLC.

Background: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer(ES-SCLC). Intergrated the clinical benefits of pembrolizumab and its high cost into account, this study aim to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the the US payer perspective. Methods: A Markov model was developed to compared the costs and quality-adjusted life-years (QALYs) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy, treatment utilization and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examined the robustness of our model. Results: Adding pembrolizumab to standard first-line EP, resulted in better effectiveness than the use of EP alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio(ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerts no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide rang of willingness to pay were modest. Conclusion: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compare with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary measure to improve its cost-effectiveness.

Epidemiologic studies have shown an association between tuberculosis and lung cancer. The al-tered tumor microenvironment after tuberculosis infection appears to contribute to cancer pro-gression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of select exosomal microRNAs. TPE-derived exosome treatment en-hanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell inva-sion. Exosome-mediated transfer of select microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phos-phorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p sup-pressed the promotion of lung cancer by TPE derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TBE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer.

Breast cancer (BC) is a prevalent malignancy with various subtypes, each presenting unique diagnostic and therapeutic challenges. Triple-negative breast cancer (TNBC), which comprises 12-17% of breast cancers, is particularly aggressive due to its lack of estrogen receptor (ER), progesterone receptor (PR), and HER2 expression. This case report details the management of a 64-year-old woman with TNBC. Initially presenting with a left breast nodule, she underwent a biopsy that confirmed triple-negative infiltrating ductal carcinoma. Despite negative BRCA genetic testing, her significant family history of cancer and a newly detected right breast lesion led to a bilateral mastectomy. Post-surgery imaging revealed multiple hypodense nodules and a spiculated pulmonary nodule, prompting further investigation. An endoscopic lung biopsy identified a primary pulmonary carcinoma with histological features similar to the breast cancer, indicating the lung as the primary source. This case underscores the complexity of TNBC, the importance of comprehensive diagnostic evaluations, and the need for considering extramammary origins in metastatic cases. The findings emphasize the role of multidisciplinary teams in managing such rare and challenging cases and highlight the necessity for thorough and repeated evaluations in atypical BC presentations.

First-line treatment for advanced large-cell neuroendocrine carcinoma of the lung (LCNEC) has limited efficacy. This study aimed to explore the efficacy and safety of everolimus combined with EP regimen chemotherapy (etoposide + cisplatin, EP) in the first-line treatment for LCNEC. The patients were randomly assigned to the experimental or control group, with 20 patients in each group. The experimental group received the mTOR inhibitor everolimus 5 mg once a day combined with EP ivgtt, d1-3, every 3 weeks for 4–6 cycles. The control group received EP only and the infusion method was the same as that of the experimental group. The safety in the experimental group was controllable and not inferior to that in the control group. Serious adverse effects were observed in approximately 10% of patients. Objective response rate (ORR) for the experimental and control groups were 15% vs. 0 (P=0.231), disease control rate (DCR) was 100% vs. 32% (P

Background: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. Patients and methods: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. Results: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1>49% in combination with a negative KRAS result had a median survival of 40 months compared to patients with a positive KRAS result (9 months, p<0.05). In addition, patients diagnosed with adenocarcinoma, PDL1<49% and negative KRAS result had a median survival of 39 months compared to patients with a positive result (28 months, p<0.05). Conclusions: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

The aim of this scoping review was to investigate and synthesize existing evidence on the airway microbiome of preterm infants, to outline the prognostic and therapeutic significance of these microbiomes within the preterm population, and identify gaps in current knowledge, proposing avenues for future research. We performed a scoping review of the literature following the Arskey and O'Malley framework. In accordance with our inclusion criteria and the intended purpose of this scoping review, we identified a total of 21 articles. The investigation of the airway microbiome in preterm infants has revealed new insights into its unique characteristics, highlighting distinct dynamics when compared to term infants. Perinatal factors, such as mode of delivery, chorioamnionitis, the respiratory support, and antibiotic treatment, could impact the composition of the airway microbiome. The 'gut-lung axis’, examining the link between the lung and gut microbiome, as well as modifications in respiratory microbiome across different sites and over time, has also been explored. Furthermore, correlations between the airway microbiome and adverse outcomes, such as bronchopulmonary dysplasia (BPD), have been established. Additional research in neonatal care is essential to understand early colonization of infants’ airways and explore methods for its optimization. The critical opportunity to shape long-term health through microbiome-mediated effects likely lies within the neonatal period.

(1) Background: Bronchial artery embolization has been shown to be effective in the management of neoplastic hemoptysis. However, knowledge of pulmonary artery embolization is lacking. To evaluate safety and efficacy of pulmonary artery embolization in patients presenting with hemoptysis related to lung tumors. (2) Methods: This retrospective study reviewed all consecutive patients with cancer and at least one episode of hemoptysis that required pulmonary artery embolization from December 2008 to December 2020. The endpoints of the study were technical success, clinical success, recurrence of hemoptysis and complications. (3) Results: A total of 92 patients were treated with pulmonary artery embolization (63.1 years ± 9.9; 70 men). Most patients had stage III or IV advanced disease. Pulmonary artery embolization was technically successful in 82 (89%) patients and clinically successful in 77 (84%) patients. Recurrence occurred in 49% of patients. Infectious complications occurred in 15 patients (16%). The 30-days mortality rate was 31%. At 3 years, survival rate was 3.6%. Tumor size, tumor cavitation and necrosis and pulmonary artery pseudo-aneurysm were significantly associated with recurrence and higher mortality. (4) Conclusions: Pulmonary artery embolization is an effective treatment to initially control hemoptysis in patient with lung carcinoma but recurrence rate remains high and overall survival remains poor.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheu-matoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and eth-nicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the his-topathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

Primary carcinomas of the lung are vastly represented by the conventional types of adenocarcinomas or squamous cell carcinomas. However, there are other types of non-small cell carcinomas that although uncommon represent a meaningful group that often pose a problem not only in diagnosis but also in classification. Spindle and giant cell carcinomas although uncommon primary lung carcinomas are well known to occur. Important to highlight is that current criteria are rather ambiguous and likely not up to date, which renders the classification of these tumors somewhat more obscure. In addition, with the daily use of immunohistochemical stains, the classification of these tumors may also pose a different problem in the proper allocation of these tumors. Proper classification is highly important in the selection process that takes place using such material for molecular analysis. Current molecular characteristics of these tumors is limited and lacks more in-depth studies and analysis that can provide specific targets for the treatment of patients with these tumors. The current review attempts to highlight the shortcomings in the current classification and definitions of these neoplasms as well as the more current view regarding these tumors when the use of immunohistochemical stains is employed.

Diseases of the lung account for more than 5 million deaths worldwide and are a burden to healthcare. Improving clinical outcomes including mortality and quality of life involves a holistic understanding the etiopathogenesis, which can be provided by multi-omics integration of lung data. An enhanced understanding of large comprehensive datasets provides opportunities to mine those datasets for features that contribute to prevention and amelioration of disease. In this review, we evaluate lung disease models including animal models, organoids and single cell lines as mechanisms to study multiomics in lung health and disease. We provide examples of lung diseases where multi-omics investigations have provided a deeper insight into pathogenesis that has resulted in improved preventive and therapeutic interventions.

Therapeutic efficacy of retroviral replicating vector (RRV)-mediated prodrug activator gene therapy has been demonstrated in a variety of tumor models, but clinical investigation of this approach has so far been restricted to glioma and gastrointestinal malignancies. In the present study, we evaluated replication kinetics, transduction efficiency, and therapeutic efficacy of RRV in experimental models of lung cancer. RRV delivering GFP as a reporter gene showed rapid viral replication in a panel of lung cancer cells in vitro, as well as robust intratumoral replication and high levels of tumor transduction in subcutaneous and orthotopic pleural dissemination models of lung cancer in vivo. Toca 511 (vocimagene amiretrorepvec), a clinical-stage RRV encoding optimized yeast cytosine deaminase (yCD) which converts the prodrug 5-fluorocytosine (5-FC) to the active drug 5-fluorouracil (5-FU), showed potent cytotoxicity in lung cancer cells upon exposure to 5-FC prodrug. In vivo, Toca 511 achieved significant tumor growth inhibition following 5-FC treatment in subcutaneous and orthotopic pleural dissemination models of lung cancer in both immunodeficient and immunocompetent hosts, resulting in significantly increased overall survival. This study demonstrates that RRV can serve as highly efficient vehicles for gene delivery to lung cancer, and indicates the translational potential of RRV-mediated prodrug activator gene therapy with Toca 511/5-FC as a novel therapeutic strategy for pulmonary malignancies.

The risk of lung cancer continues to elevate for both smokers and never-smokers. With the increasing morbidities and mortalities related to lung cancer, there is much interest on establishing other confounding factors that lead to lung cancer, other than smoking which is the most common cause. Some of the environmental factors have been identified as potential lung cancer causes. Therefore, the aim of this systematic review is to assess the relationship of environmental factors and lung cancer incidences by investigating various carcinogenic risks exposures that predispose an individual to lung cancer. The objective of this systematic review is thus to assess the evidence of relationship between environmental carcinogens and lung cancer incidence by systematically reviewing relevant studies. A standard criterion for the review methodology was formulated to guide the review process and data extraction. Online databases like PubMed, MEDLINE, Scopus (EMBASE), Google Scholar, Web of Science, and CINAHL were systematically searched for articles published between 2000 and 2021 that explored potential environmental carcinogens that were believed to expose occupational workers and individuals within the environment with lung cancer risks. 25 studies were eligible based on the selection criteria, and were finally included in the systematic review among which four were case-control studies, seven were cohorts, five was prospective, four were previous systematic reviews and four were systematic analysis. Chemical exposures like pesticides were analyzed for their carcinogenesis. Air pollution was also discussed with particulate and coal being the core of evidence of association with lung cancer. Second hand smoke, Asbestos, metal compounds like copper, PVC dust particles and ionizing radiations also provided evidence of environmental carcinogenesis associating to lung cancer cases.

Background: Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic, progressive lung ailments which are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Exosomes are small extracellular vesicles attributed to carry proteins, mRNA, miRNA and sncRNA to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF in independent cohorts. Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were approximately 89.85 nm in size and ~2.95 X 1010 particles/mL. Lung-derived exosomes were ~146.04 nm in size and ~2.38 X 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls. Conclusions: Overall, we identified specific miRNAs to develop as biomarkers or targets for pathogenesis of these chronic lung diseases.

The quarantine imposed as the response to the COVID 19 pandemic has been related to an increase in cases of thromboembolism in Non-COVID19 patients .We report the case of a patient with pulmonary thromboembolism without usual triggering causes during the quarantine period, related to a previously undiagnosed hypercoagulable condition.

As lung cancer shows the highest mortality in cancer related death, serum biomarkers are demanded for the lung cancer diagnosis and its treatment. To discover lung cancer protein biomarkers, secreted proteins from primary cultured lung cancer and adjacent normal tissues from patients were subjected to LC/MS-MS proteomic analysis. Quescin sulfhydryl oxidase(QSOX1) was selected as a biomarker candidate from the proteins enriched in the secretion of lung cancer cells. QSOX1levels were higher in 82% (51 of 62 tissues) of lung cancer tissues compared to adjacent normal tissues. Importantly, QSOX1 serum levels were significantly higher in cancer patients (p<0.05, AUC=0.89), when measured by multiple reaction monitoring(MRM). Higher levels of QSOX1 are also uniquely detected in lung cancer tissues among several other solid cancers by immunohistochemistry. QSOX1 knock-downed Lewis lung cancer (LLC) cells was less viable from oxidative stress and had reduced migration and invasion. In addition, LLC mouse models with QSOX1 knock-down also proved that QSOX1 functions in promoting cancer metastasis. In conclusion, QSOX1 might be a lung cancer tissue-derived biomarker and involved in the promotion of lung cancers, and thus can be a therapeutic target for lung cancers.

Chronic eosinophilic pneumonia (CEP) is an idiopathic disorder characterized by an abnormal and marked accumulation of eosinophils in the interstitial and alveolar spaces of the lung. Idiopathic chronic eosinophilic pneumonia is reported to comprise anywhere from 0-2.5% of cases within the registries of interstitial lung disease. Diagnosis is based on the clinical constellation of symptoms, characteristic radiographic findings and peripheral blood or BAL eosinophilia, in the absence of infection or drug-induced eosinophilia. There is no consensus on the dose and duration of treatment, but most authors recommend initial doses of prednisone at 0.5–1 mg/kg/day with gradual tapering of the dose for total treatment duration of 6–12 months.

The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as Lung Cancer associated with Cystic Airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs biennial pace of LDCT, choice between opportunistic or population-based recruitment and between uni or multi-center screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention and prospective validation of the biomarkers.

(1) Background: LUS has emerged as a simple, rapid and non-invasive method for the dynamic assessment of pulmonary congestion, a major prognostic factor and a therapeutic target in AHF. (2) Methods: In the single-center prospective observational study, 42 patients hospitalized for AHF in the post-emergency polyvalent medicine department of CHU Grenoble were successively included between May 2021 and July 2022. Clinical examination, LUS and electrolyte panel results were collected daily. Vital status was assessed 30 days after the last LUS. The primary endpoint was the evolution of the number of B-lines according to the dose of diuretic administered ; (3) Results: We performed 188 LUS. Our patients were elderly (85.8 [SD 8.1]) and comorbid. The median number of B-lines decreased from 17 at admission to 7 in the middle of the hospital stay, then stagnated until discharge. Simultaneously, the median dose of diuretics, initially stable at a maximum of 40 mg/d IV, decreased to 20mg/d IV by the end of hospital stay. Patients with CKD had a higher mean number of B-lines at entry (24.2 [SD 11.6]) compared to those without CKD (8.2 [SD 8.8]). However, the evolution of B-lines number was independent of creatinine levels. 30-day all-causes mortality was significantly related to the number of B-lines at discharge (15.2 [SD 10.1] in deceased patients versus 3.9 [SD 5.4] in living patients, p

Interferon-gamma (IFN-γ) is an important cytokine in host defense against tuberculosis infection. In some cases, administration of IFN-γ during tuberculosis infection can promote faster cure. In the present work, we have shown that in a mouse model, human interferon-gamma, exhibits some anti-tuberculosis activity, especially in combination with isoniazid.

Current epidemiological data about interstitial lung disease (ILD) are still poor. The principal cause of the discordant data is associated with a heterogeneous group of respiratory diseases that includes a large number, about 200 families, with low frequency, distinct and sometimes unknown etiology, and different progression. Furthermore, epidemiological data are limited. Scope of the narrative review is to report ILD incidence and prevalence in Registries from different Countries in the second millennium. We identified 16 ILD Registries (14 prospective and 2 retrospective) from major Countries in Europe (n = 10), Asia (n = 7), North America (n =2) and Oceania (n = 1). Significant discrepancies in ILD and ILD subtypes prevalence and incidence among countries are reported in Registries. These discrepancies could be determined by different ethnicities and socio-economic conditions as well as by updates in disease diagnosis and classification. ILD epidemiological Registries are progressively ameliorating through a better adherence to updated Guidelines and Classification codes. An accurate and definite compilation of ILD epidemiological Registries will be useful for a more precise monitoring of disease progression and treatment.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

To identify factors associated with interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) and build an algorithm to better define this association, for a personalized application in clinical practice. Methods. 78 SSc patients underwent HRCT to assess ILD. Demographic, clinical and laboratory variables were collected, focusing on those associated either directly or indirectly with lung involvement. The discriminant value of each variable was determined using the operating characteristic curves (ROC) and included in a model to estimate the strength of ILD association in SSc. Results. Thirty-three (42.31%) patients showed ILD on HRCT. DLco, M-Borg, GERD-Q, and capillary density were significantly associated with the presence of ILD-SSc. A model including these variables had a coefficient of determination (R2) of 0.697. DLco had an AUC of 0.861 (p&lt;0.001) with a cut-off ≤72.3% (sensitivity 78.8%, specificity 91.1%, +LR 8.86). The m-Borg scale showed an AUC of 0.883 (p&lt;0.001) with a cut-off &gt;2 (sensitivity 84.8%, specificity 82.2%, +LR 4.77), GERD-Q had an AUC of 0.815 (p&lt;0.001) with a cut-off &gt;7 (sensitivity 72.7%, specificity 86.7%, +LR 5.45). The capillary density showed an AUC of 0.815 (p&lt;0.001) with a cut-off ≤4.78 (sensitivity 87.9%, specificity 68.9%, +LR 2.82). Based on the pre-test probability values, these four variables were applied to Fagan's nomogram to calculate the post-test probability of this association. Conclusions. Our study identified four associated clinical factors of ILD in SSc patients. Moreover, their inclusion in an algorithm for the post-test probability, tailored to the specific patients’ characteristics, significantly increases the ability to find out the presence of SSc-ILD.

Several Lung diseases can result in lung damage structural changes, with lung transplantation as a only therapeutic option when the disease reaches an advanced progression, unfortunately, the success of lung transplantation is limited. In this context, lung bioengineering is considered a potential therapeutic alternative and the current approach is based on the use of the natural extracellular matrix (ECM) of the decellularized lung. The use of undifferentiated cells to seed an ECM can be a more practical strategy for lung bioengineering but the sterilization of the organ for this recellularization process is still a challenge. In this sense, Low-Level Laser Therapy (LLLT) can emerge as a potential treatment alternative. Therefore, the objective of this study was to verify if LLLT, can optimize lung recelularization with mesenchymal stem cells by cytokine modulation. For this, we decellularized lungs from C57BL/6 mice perfusing SDS 1% via pulmonary artery, sterilized with LLL (660nm, 100mW, 30s). Whole lung scaffolds were recellularized: (1) Recellularized Lung (2) Recellularized Lung + LLLT. Mesenchymal stem cells derived from human tooth pulp (DPSc) were seeded into lungs and incubated for 24 hours at 37ºC, 5% CO₂, in a bioreactor-like conditions, maintaining CPAP at 20cmH2O, 90% O2, and LLL at wavelength of 808nm, 100mW, 30s. Culture medium were analyzed at 24 hours. H&amp;E, immunostaining, SEM and ELISA assay were performed. We produced viable biological scaffolds absent of DNA content, preserving glycosaminoglycans and collagen I, III and IV, fibronectin, laminin and elastin and lung structure (SEM). The levels of IL-6 and IL-8 were stable during the 24 hours of culture. IFN-γ levels showed significant difference in the DPSc and DPSc+LLLT group in the 24-hour evaluation. The levels of IL-10 decreased after LLLT. These findings highlight LLLT's role in cytokine regulation and contamination prevention during lung recellularization with mesenchymal stem cells. Overall, these results demonstrated that LLLT's modulated cytokine levels and could prevent contamination during the lung recellularization process with mesenchymal stem cells, offering promise for enhanced therapeutic strategies in lung bioengineering.

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

Although a growing number of evidence emphasizes superior of VATS over conventional thoracotomy, still is little known about early postoperative diaphragm muscle function after lobectomy via these two approahces. To fill the gap in existing literature, we conducted comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, magnitude of effort and potential risk of dysfunction such as: atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled into this study. The control group was consisted of 28 health subjects without medical condition could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function - compared to baseline data. Postoperative reduction of diaphragm contraction was demonstrated in all of 59 patients. In case of control group, the differences between measurements were no observed. We noted that lobectomy via thoracotomy was linked with greater percentage of patients with diaphragm paralysis or/and atrophy that VATS. Similar findings were observed in refer to diaphragm magnitude effort, as well as, diaphragm contraction strength, where minimal invasive surgery was associated with better diaphragm function parameters - in comparison to thoracotomy. Disturbance of diaphragm work was reported both at operated and non-operated side. Upper right and left lobectomy was connected with greater diaphragm function impairment than other segments. In conclusion, VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of a main respiratory muscle.

Pulmonary Hypertension (PH) is a terminal disease characterized by severe pulmonary vascular remodeling. Unfortunately, targeted therapy to prevent disease progression is limited. Here, the vascular cell populations that contribute to the molecular and morphological changes of PH in conjunction with current animal models for studying vascular remodeling in PH will be examined. The status quo of epigenetic targeting for treating vascular remodeling in different PH subtypes will be dissected, while parallel epigenetic threads between pulmonary hypertension and pathogenic cancer provide insight into future therapeutic PH opportunities.

Lung cancer is a prevalent and aggressive neoplasm worldwide, contributing to significant mortality rates. Dehydroepiandrosterone (DHEA) constitutes the bulk of the steroid hormone in human plasma, has a robust antiproliferative effect, and induces cell death in various tumor cells. However, its role in lung cancer cells remains unexplored. This study aimed to investigate the influence of DHEA on the proliferation, viability, autophagy, and migration of several lung cancer cell lines, including A549, HCC827, and NCI-H2347. Cell proliferation was assessed through crystal violet staining; cell number and viability were evaluated using trypan blue staining; viability was confirmed by MTT reduction, a method that is also an indicator of metabolic activity; migration was assessed via a wound healing assay. Autophagy was evaluated using a specific kit, while cell death was determined by annexin-V-FITC/propidium iodide staining and caspase-3/7 activity assay. The results indicate that DHEA significantly reduced proliferation, cell number, metabolic activity, and migration in all examined lung tumor cells. These effects correlate with an increased autophagy induced by DHEA. No signs of apoptosis or necrosis were observed across the range of DHEA concentrations used. Although these findings are preliminary, they suggest that DHEA could hold promise as an alternative treatment option for various subtypes of lung cancer.

Prostate cancer (PCa) Lung metastases are rarely resected, therefore PCa lung metastases are insufficiently molecularly characterized. We recently identified carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as a potential driver of pulmonary metastatic spread. Here, we show the biological significance of CEACAM6 in PCa cell proliferation, apoptosis and migration. CEACAM6 was silenced by siRNA in PC3 cells. Functional assessment of apoptosis, cell viability, proliferation and migration were performed in siRNA-CEACAM6 PC3 cells. Non-treated and scrambled (scr) RNA PC3 cells were used as control. Following a specific knockdown of CEACAM6 in PC3 cells, the expression of CEACAM6 protein was significantly decreased in comparison to controls. Cell viability and cell counts decreased in CEACAM6 silent PC3 cells. In contrast, caspase-3 activity was highly elevated in siRNA-CEACAM6 PC3. Furthermore, by performing a cell scratch assay, the migration ratio in siRNA-CEACAM6 PC3 cells were significantly diminished compared with the control group after 48 hours of post transfection incubation. CEACAM6 as a cell adhesion molecule has been implicated in promoting metastatic disease in several solid tumours such as colorectal or gastric cancer. We could show that silencing of CEACAM6 has a significant functional effect on PCa cells. CEACAM6 might play an important role in fostering metastatic spread to the lung of PCa patients via enhancing proliferation and suppressing apoptosis. CEACAM6 might therefore pose an attractive therapeutic target to prevent metastatic disease.

Background:Malignant pleural effusion (MPE),a frequent complication of advanced malignancies. This pilot study characterized and compared the immune landscapes of breast carcinoma (BC) and lung adenocarcinoma (LADC) primary tumors(PTs) and their corresponding MPEs and tested the incorporation of multiplexed image technology for the study of malignant fluids. Methods: We studied the immune contexture of 6 BC and 5 LADC PT samples and their MPEs using 3 multiplex immunofluorescence panels. We explored associations between sample characteristics and pleural effusion–free survival. Results: Although we found 3 out of 11 PTs PD-L1 positive more than 1% by malignant cells, no MPE samples reached positive expression by malignant cells. In addition, CD3+ T cells and CD3+CD8+ cytotoxic T cells predominated (median percentages for MPEs vs. PTs: 45.5% vs. 40.7% and 4.7% vs. 6.6%, respectively). In the BC samples, CD68+ macrophages predominated (median percentages for MPEs vs. PTs:61% vs. 57.1%). Generally, CD3+CD8+FOXP3+ T cells in PTs and the distances from the malignant cells to CD3+CD8+Ki67+ and CD3+PD-1+ T cells were correlated in the first event of MPE after diagnosis. Conclusions: The immune cell phenotypes in the MPEs and PTs were similar within each cancer type but were different for LADC vs. BC.MPE analysis could be used as a substitute for PT analysis, but an expanded study on this topic is essential.

Streptococcus intermedius is frequently associated with brain and liver abscesses, while pleuropulmonary infections are considered rarer. Even less frequent is the association of lung and brain abscess due to this agent with left heart endocarditis. We describe the case of a 40-year-old man with a brain abscess due to S. intermedius and concomitant lung abscess and aortic native valve endocarditis. He was treated with surgical drainage of the brain abscess and a 4-week course of intravenous ceftriaxone, followed by oral amoxicillin/clavulanate, obtaining healing of the lesions without relapse of the infection.

In comparison to the general population, lung cancer patients are more likely to suffer from severe Coronavirus disease (COVID-19) and mortality associated with it. Considering this increased risk, and in order to prevent symptoms and severe disease, patients with lung cancer have been prioritized for COVID-19 vaccinations, primary and booster doses. Despite this, the pivotal clinical trials did not include these patients, which leaves open questions regarding vaccine efficacy and humoral immune response. This review outlines the findings of recent investigations into the humoral responses of lung cancer patients to COVID-19 vaccination, particularly the primary doses and first boost.

In recent years, lung ultrasound (LUS) has been increasingly used for the diagnosis of respiratory diseases in both adult and pediatric patients. However, asthma is a field in which the use of LUS is not yet well defined or is in development. In the following case series, we describe clinical, laboratory, radiological results as well as detailed lung ultrasound findings of 6 children with asthma: some of them with acute asthma attack and with inadequately controlled allergic asthma or childhood asthma; others with acute asthma and allergic or infantile asthma adequately controlled by preventive therapy. Finally we describe the clinical, laboratory and imaging parameters of a child with severe allergic asthma in the absence of exacerbation. In these cases, albeit at different times, LUS played an important role in both the initial diagnostic process and follow-up. It also showed different ultrasound features depending on the severity of the individual asthma based on the type of asthmatic phenotype and control of it.

Obesity is a significant public health concern with higher morbidity. Obesity patients are at risk of severe COVID-19 infection and obesity is a higher risk factor for intensive Care Unit admission in COVID-19 infection. Obesity status affects lung volumes, cardiac structure and hemodynamics. Obesity is associated with a low inflammation state, endothelial dysfunction, hyperinsulinaemia and metabolic disorders. The authors review cardio-respiratory pathophysiological aspects involved in obesity and propose clinical management in obese patients infected by COVD-19.

Pulmonary arterial hypertension is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors, and likely gene x environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 36% of pediatric-onset idiopathic PAH (IPAH) compared to ~11% of adult-onset IPAH. De novo variants are frequently associated with PAH in children, and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, the increased etiologic heterogeneity, poorer prognosis and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

Background: Lung cancer is one of the common causes of death worldwide. Although the incidence rate of lung cancer in Western countries is decreasing, it presents a growing trend in developed countries. Since there is no accurate enough information about the epidemiological and Histopathologic features of lung cancer in central Iran, Isfahan, we were motivated to conduct this research. Materials and Methods: This was a descriptive, cross-sectional study carried out in central Iran, Isfahan. All demographic, histopathological and clinical data of the lung cancer patients registered in MACSA, a referral charity-based cancer center in central Iran, was analyzed within 2012-2018 using SPSS v.22 software. Results: Altogether 260 patients with lung cancer were included in this study from 6127 cancer patients registered within 2012-2018 (4.2%). Out of them, 66.2% were men, and 18.8 % of the patients were alive at the time of the study. The mean age of the patients at diagnosis was 61.56 (SD=14.11, range: 9-93). Altogether, 63.1% of patients had metastasis of whom 57.6% were in stage IV at diagnosis. The Frequency of different types of lung cancer was 36.9% adenocarcinomas, 14.2% squamous cell carcinoma, 9.6% bronchogenic carcinoma and 8.1% small cell lung cancer, respectively. Altogether, 128 cases were smokers with an average 35.45 ± 14 pack- years. Only in 36.2% of the patients, the diagnostic and therapeutic biomarkers had been checked, and CK7 was positive in 88.9% of the cases in which the biomarker had been checked. Conclusion: Despite to similar Iranian studies, the most common histopathologic type of lung cancer among the patients was adenocarcinoma that it may be attributed to the lower consumption of smoking in our population and their different genetic context. Molecular biomarkers had been checked in a small portion of the patients. More education of the clinicians along with the development of cancer molecular testing may lead to promote the personalized-based approach.

The metastasis of lung cancer can spread to the lymph nodes around the lungs. Metastasis, rather than the primary cancer, judges patients survival. Wherefore, a more detailed study on transcriptome of metastatic lung adenocarcinoma including primary carcinoma was carried out. LUAD RNA-seq data and the corresponding clinical information were available from The Cancer Genome Atlas (TCGA), which included 522 cases but only 515 cases have transcriptome data. Differential expression analyses between cases and controls, between primary cancer and metastasis subgroup, or between TNM stages, were respectively carried out using edgeR package. Then, the Kruskal-Wallis tests were used to verify the gradient changes of cancer metastasis or staging with the differential expression genes. The survival analyses were calculated using the Kaplan-Meier algorithm and log-rank test. The functional predictions for the differentially expressed genes were porformed with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (GO/KEGG). Single gene set enrichment analysis (single GSEA) was run to explore the biological pathways associated with the expressions of RN7SL494P gene based on the Molecular Signatures Database (MSigDB). 406 and 439 differentially expressed genes were identified respectively in lymph node metastasis or TNM stages. 112/296 intersection genes were associated with nodal metastasis and/or staging, among them only 25 genes were associated with the nodal metastasis, 13 genes were associated with the staging with gradient changes. Only one gene (RN7SL494P) was found to be associated with prognosis. But RN7SL494P was not found joining any biological functions or processes or cellular components with GO/KEGG analyses. Finally, single GSEA enrichment and pathway analyses showed that RN7SL494P might be involving in cancer development process and poor outcome in lung adenocarcinoma. These findings highlight the potential applications of RN7SL494P as a promising molecular predictor not only in nodal metastasis but prognosis evalution in lung adenocarcinoma patients.

Recent changes in lung cancer care, including new approvals in first line and the introduction of high throughput molecular technologies in routine testing led us to question ourselves on how deeper molecular testing may be helpful for the optimal use of targeted drugs. In this article we review recent results in the scope of personalized medicine in lung cancer. We discuss biomarkers that have a therapeutic predictive value in lung cancer with a focus on recent changes and on the clinical value of large scale sequencing strategies. We review the use of second and third generation EGFR and ALK inhibitors with a focus on secondary resistance alterations. We discuss anti-BRAF and anti-MEK combo, emerging biomarkers as NRG1 and NTRKs fusions and immunotherapy. Finally we discuss the different technical issues of comprehensive molecular profiling and show how large screenings might refine the prediction value of individual markers. Based on a review of recent publications (2012–2018), we address promising approaches for the treatment of patients with lung cancers and the technical challenges associated to the identification of new predictive markers.

Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously [1]. In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis.

The signal transduction pathways of estrogen receptors (ER) mainly includes gene pathway and non-gene pathway. Studies have shown that the gene pathway of ER is related with the expression of nuclear proteins, and this is the key issue for our current research. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in adenocarcinoma of lung (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells. Meanwhile, CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). Knockdown of CENPF gene significantly inhibited the biological effects of LUAD cells, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). Further, group experiments showed that knockdown CENPF inhibits biological effects of LUAD cells mediated by ERβ pathway. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown of CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 subtype and CENPF remained more effective in improving the therapeutic effect of LUAD.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and as such provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may results in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in the epigenetic regulation primarily via modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extra nuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases and we will discuss the potential of their inhibitors for lung injury prevention.

Diffuse interstitial lung diseases (DILD) are a heterogeneous group of over 200 entities, some with dramatical evolution and poor prognostic. Because of their overlapping clinical, physiopathological and imagistic nature, successful management requires early detection and proper progression evaluation. This paper tests a complex networks (CN) algorithm for imagistic aided diagnosis fitness for the possibility of achieving relevant and novel DILD management data. 65 DILD and 31 normal high resolution computer tomography (HRCT) scans were selected and analyzed with the CN model. The algorithm is showcased in two case reports and then statistical analysis on the entire lot shows that a CN algorithm quantifies progression evaluation with a very fine accuracy, surpassing functional parameters’ variations. The CN algorithm can also be successfully used for early detection, mainly on the ground glass opacity Hounsfield Units band of the scan.

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

This review article explores the significance and prospects of using diverse T-cell variants in the context of combined therapy for lung cancer treatment. Recently, there has been an increase in research focused on understanding the critical role of tumor-specific T-lymphocytes and the potential benefits of autologous T-cell-based treatments for individuals with lung cancer. One promising approach involves intravenous administration of ex vivo-activated autologous lymphocytes to improve the immune status of patients with cancer. Investigations are also exploring the factors that influence the success of T-cell therapy and the methods used to stimulate them. Achieving a comprehensive understanding of the characteristics of activated lymphocytes and deciphering the mechanisms underlying their activation of innate anti-tumor immunity will pave the way for numerous clinical trials and the development of innovative strategies for cancer therapy.

The immune system attempts to eliminate foreign substances, such as pathogens and viruses, that invade the body. As normal cells transform into cancerous cells, the immune system can eliminate these cells and suppress cancer onset. The immune system is regulated so that it does not become overactive or attack normal cells. When cancer cells transform from normal cells, they acquire various characteristics, and some cancer cells influence the regulatory function of the immune system to suppress it and escape immune attack. Therefore, treatments have been developed to eliminate the suppression of the immune system by cancer cells and to restore the immune system's ability to eliminate cancer cells. Immunotherapies include immune checkpoint inhibitors, cytokines, cancer vaccines, and effector cell therapies. Cytokine therapy activates the immune system by injecting substances produced by immune cells (such as interleukin 2 and interferon alpha) into the body, thereby increasing the ability of the immune system to attack cancer cells. Cancer vaccine therapy enhances the attack on cancer cells by injecting substances (antigens) that serve as markers for cancer cells into the body to make it easier for immune cells to detect the cancer. Depending on the type of antigen, cancer peptides, tumor cells, and dendritic cell vaccines are available. Effector cell therapy is a treatment method in which immune cells that directly attack cancer cells (CD8+ T cells, NK cells, etc.) are taken from the patient's body, expanded outside the body, activated, and returned to the body to attack cancer cells. To develop these treatments, it is essential to understand the cells and molecules related to immunity as well as the local tumor environment. In this article, we consider the factors related to antitumor immunity.

Background: Lung cancer remains the leading cause of cancer-related mortality globally, predo-minantly affecting older individuals. Despite the increasing use of immune checkpoint inhibitors (ICIs) like nivolumab in non-small cell lung cancer (NSCLC), the efficacy and safety in elderly pa-tients, particularly those aged 65 and above, remain underexplored due to their underrepresenta-tion in clinical trials. Methods: This retrospective study analyzed data from 60 elderly patients (≥65 years) with metastatic NSCLC who received nivolumab as second-line or later therapy between January 2020 and May 2023. Results: The median age was 67 years, with a predominance of males (78%). Nivolumab was administered for a median of 8 cycles, with 33.3% of patients recei-ving 15 or more cycles. The median OS was 23 months, and the 1-, 3-, and 5-year survival rates were 93.3%, 54.1%, and 18.6%, respectively. Multivariate analysis identified adenocarcinoma histology, fewer than 15 cycles of nivolumab, and non-response to prior therapies as independent predictors of poor OS. Nivolumab treatment was generally well-tolerated, with 45% of patients experiencing at least grade 1 toxicity. Conclusion: Nivolumab is effective and well-tolerated in elderly patients with metastatic NSCLC, providing survival benefits comparable to those observed in younger populations. The number of treatment cycles and initial response to therapy are key determinants of survival, underscoring the importance of continued treatment in this age group.

Lung cancer, including both non-small cell lung cancer and small cell lung cancer, remains the leading cause of cancer-related mortality worldwide representing 18% of the total cancer deaths in 2020. Many patients are identified already at an advanced stage with metastatic disease and have a worsening prognosis. Recent advances in the genetic understanding of lung cancer have opened new avenues for personalized treatments and targeted therapies. This review examines the latest discoveries in the genetics of lung cancer, discusses key biomarkers, and analyzes current clinical therapies based on this genetic information. It will conclude with a discussion of future prospects and potential research directions.

Driven by the importance of early detection for improving patient outcomes, this study investigates the effectiveness of various machine learning algorithms in predicting lung cancer based on clinical data. Lung cancer remains a significant global health concern, and this research seeks to contribute to advancements in early diagnosis through the application of machine learning techniques. The dataset consists of 385 training and 97 test samples, with a k-fold cross-validation approach (k=5) utilized to mitigate overfitting. Additionally, the ADASYN oversampling technique is employed to address class imbalance. Our analysis includes traditional algorithms such as Logistic Regression and Decision Trees, as well as ensemble methods like XGBoost, LGBM, and AdaBoost. Furthermore, we explore the effectiveness of deep learning models, particularly Deep Neural Networks (DNN). Results demonstrate promising accuracy rates across all models, with some outperforming others in terms of precision, recall, and F1-score. Our findings reveal that LGBM achieves the highest accuracy among all models, with an accuracy rate of 96.91%. It also exhibits superior performance in terms of precision, recall, and F1-score, particularly in classifying both positive and negative instances of lung cancer.

Cigarette smoke (CS) is a major driver of many respiratory diseases including chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). Tobacco causes oxidative stress, impaired phagocytosis of alveolar macrophages (AMs), and alterations in gene expression in the lungs of smokers. MicroRNAs (miRNAs) are small non-coding RNAs that influence several bi-ological processes and interfere with several regulatory pathways. The purpose of this study was to assess the effect of active CS on miRNAs expression in AMs obtained from bronchoalveolar lavage (BAL) of ever- or never-smoker subjects and patients with COPD or NSCLC. BAL specimens were collected from 43 sex-matched subjects to determine the expression of has-miR-34a-5p, 17-5p, 16-5p, 106a-5p, 223-5p, and 20a-5p before and after in vitro CS exposure by RT-PCR. In addition, bioin-formatic analysis of miRNAs target genes linked to inflammation was performed. Distinct and common miRNA expression profiles were identified in response to CS, suggesting their possible role in smoking-related diseases. It is noteworthy that, following exposure to CS, the expression levels of hsa-miR-34a-5p and 17-5p in both ever- or never-smokers, 106a-5p in never-smokers and 20a-5p in ever-smokers, shifted towards those found in individuals with COPD, suggesting them like a risk factor in developing this lung condition. Moreover, we identified miRNA targets involved in the immune system or AMs property regulation using in silico analysis. In conclusion, our study iden-tified miRNA signatures in AMs exposed to CS, indicating that CS is an important driver of epige-netic changes that contribute to the onset of various lung diseases.

Introduction: Lung cancer remains a global health concern, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Early detection of lung cancer has led to an increased number of cases identified in the earlier stages of NSCLC. This required the revaluation of the NSCLC treatment approaches for early-stage NSCLC. Methods: We conducted a comprehensive search using multiple databases to identify relevant studies on treatment modalities for early-stage NSCLC. Inclusion criteria prioritized but were not limited to, clinical trials and meta-analyses on surgical approaches to early-stage NSCLC conducted from 2021 onwards. Discussion: Minimally invasive approaches, such as VATS and RATS, along with lung resection techniques, including sublobar resection have emerged as treatments for early-stage NSCLC. Ground-glass opacities (GGOs) hve shown prognostic significance, especially when analyzing the consolidation-tumor ratio (CTR). There have also been updates on managing GGOs, including the non-surgical approaches, the extent of lung resection indicated, and the level of lymphadenectomy required. Conclusion: The management of early-stage NSCLC requires further assessment of treatment strategies. This includes understanding the required extent of surgical resection, interpreting the significance of GGOs (specifically GGOs with a high CTR), and evaluating the efficacy of alternative therapies. Customized treatment involving surgical and non-surgical interventions is essential for advancing patient care.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Purpose: This study analysed the impact of the COVID-19 pandemic on the diagnosis of malignant neoplasia of the bronchus and lung. Cases diagnosed in the Burgos region in the year prior to the official declaration of the pandemic were compared with those in the year after the pandemic. The research sought to identify whether there was a decrease in the number of cases during the pandemic, and whether this may have led to a delay in diagnosis, reflected in more advanced stages of the disease. Mortality and survival time in each of the periods were also analysed.

Background: Interstitial lung disease (ILD) is a frequent complication in systemic sclerosis (SSc). So, an increased awareness of this complication is a real need in the clinical setting, because it may affect the prognosis of patients. In particular, an accurate strategy is desirable in order to detect ILD in its stages. So, we investigate the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to determine its potential in disease progression. Methods: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), pulmonary auscultation, chest radiographs and respiratory function tests (RFT) were performed. An expert rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. After the baseline assessment, the patients were followed every 3 months for 12 months. Results: A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p=0.0001). The clinical and laboratory variables associated with ILD were anti-centromere antibodies (p=0.005) and RSS (p=0.004). A positive correlation was demonstrated between the US and HRCT findings (p=0.001). Sensitivity and specificity of US in detecting ILD was 91.2% and 88.6% respectively. A good inter-observer reliability was observed (k = 0.72). In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. Conclusions: US showed a high prevalence of subclinical ILD in SSc patients. It demonstrated to be a valid, reliable and feasible tool to detect ILD in SSc and to monitoring the disease progression.

The lung epithelium regulates gas exchange and is the first line of defense against airborne toxicants and microbial infections. Disruption of the integrity of lung epithelium results in altered permeability and severely impacts normal lung functions. To develop biomarkers of potential harm (BoPH) for assessing adverse health effects of cigarette smoking, we have evaluated lung barrier function. In a single-center, ambulatory, clinical study we measured lung permeability, as the half-life (T1/2) of inhaled 99mTC-DTPA, in 17 subjects consisting of 6 Smokers (SMK), 5 Moist Snuff Consumers (MSC), and 6 Non-Tobacco Consumers (NTC) at three weekly test visits. Smokers, relative to MSC and NTC, exhibited significantly faster clearance of the inhaled probe (shorter T1/2), indicating increased lung permeability. NTC and MSC had comparable clearance times of the inhaled probe (longer T1/2). Least squares regression modeling showed that the variability of the test was minimal and was not significant. Prediction profiling showed that the repeatability of the lung permeability test was robust and was able to differentiate the tobacco product use groups in this study. Thus, altered lung barrier function may serve as a BoPH for assessing the effects of tobacco use.

Definitive surgical resection is the preferred treatment for early-stage non-small-cell lung cancer (NSCLC). Research into genetic alterations, including epidermal growth factor receptor (EGFR) mutation, in early stage NSCLC remains insufficient. Here, we investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutation and recurrence after complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resection at a single regional cancer center were recruited. We compared the clinical and pathological data between the recurrence and non-recurrence groups. Multivariate logistic regression was used to predict the risk factors for recurrence. Among the 659 enrolled cases, the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutation was 43% (194/451). Among them, L858R point mutation and exon 19 deletion was 52.3% and 42%, respectively. ALK rearrangement was found at 5.7% (26/453), and ROS1 fusion was found at 1.6% (7/441). The recurrence rate of the entire population was 19.7%. In multivariate analysis, the presence of EGFR mutation, stage II or III (vs. stage I), and pathologic subtype (presence of solid type) were associated with recurrence. Among the recurred group, 86.5% of the patients with EGFR mutation experienced distant recurrence compared to only 66.7% of wild-type (p = 0.016), with no significant difference in median disease-free survival (p = 0.983). In conclusion, the prevalence of EGFR mutation, ALK rearrangement, and ROS1 fusion was 43.0%, 5.7%, and 1.6%, respectively in patients with early-stage NSCLC who underwent curative resection. Along with stage II/III and solid pathologic subtype, EGFR mutation was an independent risk factor for recurrence. In the recurrence group, the rate of distant metastasis was higher in patients with EGFR mutation than in those with wild-type.

In this study, we aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). We conducted a secondary analysis of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29 – 0.97). In multivariate analysis, patient age (p = 0.014) and gross tumor volume (GTV, p = 0.031) were significant factors associated with overall survival, while TLC reduction (p = 0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p = 0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, constraining the volume of the radiation dose to the whole heart must be prioritized to reduce TLC.

Indoleamine 2,3-dioxygenase 2 (IDO2) is a paralogue of IDO1, a tryptophan-degrading enzyme producing immunomodulatory molecules. However, the two proteins are unlikely to carry out the same functions. IDO2 shows little or no tryptophan catabolic activity and exerts contrasting immunomodulatory roles in a context-dependent manner, in both cancer and autoimmune diseases. The recently described potential non-enzymatic activity of IDO2 has suggested its possible involvement in alternative pathways resulting in either pro- or anti-inflammatory effects in different models. In a previous study on non-small cell lung cancer (NSCLC) tissues, we found that IDO2 expression, revealed at the plasma membrane level of tumor cells, was significantly associated with poor prognosis. In this study, the A549 human cell line, basally expressing IDO2, was used as an in vitro model of human lung adenocarcinoma to gain more insights on a possible alternative function of IDO2, different from the catalytic one. In these cells, immunocytochemistry and isopycnic sucrose gradient analyses confirmed the IDO2 protein localization in the cell membrane compartment, and immunoprecipitation of tyrosine-phosphorylated proteins revealed that IDO2 can be targeted by kinase activities. The different localization than the cytosolic one and the phosphorylation state are the first indications for the signaling function of IDO2, suggesting that the IDO2 non-enzymatic role in cancer cells is worthy of deeper understanding.

EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. However, remission is transient, and no further effective treatment options are available for EGFR-TKI-advanced EGFR-mutant NSCLCs. Immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs. However, ICI therapy exhibits limited activity in most EGFR-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in EGFR-mutant NSCLCs contributes to the non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8+ T cell infiltration, a high number of regulatory CD4+ T cells and a high number of inactivated infiltrated T cells. Besides, EGFR-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. However, current understanding only partially explains why a small population of EGFR-mutant NSCLCs durably respond to ICI therapy, resulting in many researchers actively working in this field. This review reviews the hope seen from pre-clinical studies and clinical trials which may be adopted to improve the outcome of ICI therapy in EGFR-mutant NSCLCs. Besides, the underlying mechanisms leading to the inferior clinical outcome of ICI therapy in EGFR-mutant NSCLCs are discussed.

Lung cancer accounts for the majority of cancer cases. In recent years, checkpoint inhibitor immunotherapy (ICI) has emerged as a new treatment. A better understanding of the tumor microenvironment, or TMJ, or the immune system surrounding the tumor is needed. Cytokines are small proteins that carry messages between cells and are known to play an important role in the body's response to inflammation and infection. Cytokines are important for immunity in lung cancer. It promotes tumor growth (oncogenic cytokines) or inhibits tumor growth (anti-tumor cytokines) by controlling signaling pathways for growth, proliferation, metastasis, and apoptosis. The immune system relies heavily on cytokines. They can also be produced in the laboratory for therapeutic use. Cytokine therapy helps the immune system stop the growth or kill cancer cells. Interleukins and interferons are two types of cytokines used to treat cancer. This article begins by addressing the role of the tumor microenvironment (TMJ) and its components in lung cancer. This review also highlights the functions of various cytokines such as IL, TGF and TNF.

Outdoor air pollution is a leading cause of death and premature death globally. Motorcycle-taxi drivers were most at risk associated with occupational exposure to ambient air pollution in urban areas. Therefore, a cross-sectional study was conducted to determine the influencing factors and prediction of lung function impairment in 308 motorcycle-taxi drivers living in Bangkok and adjacent provinces between February and June 2022. The study design included: data collection using questionnaires applied from the Thai version of ATS-DLD-78A: American Thoracic Society Division of Lung Diseases and Department of Disease Control, Ministry of Public Health, Thailand; a collection of respirable dust, and ambient air pollution parameters measured by per-sonal air sampling pump and real-time air quality index (AQI) station, and lung function determined by the spirometer. The results showed that 14 factors were significantly associated with lung function impairment (p<0.05). Apparently, seven influencing factors showing the most association were included: gender, the height of the subjects, history of allergies, exposure to respirable dust, mask types, helmet types, and family history of lung disease. The lung function impairment of motorcycle-taxi drivers was significantly predicted in 28.1% by regression analysis of these seven variables (R2=0.281). Therefore, this is the first report on influencing factors and prediction of lung function impairment among motorcycle-taxi drivers. These findings would be very useful for preventing and controlling measure ambient air pollution, setting policies and strategies to mitigate the risks for motorcycle-taxi drivers and the other ex-posed population.

Novel genetic and epigenetic factors involved in the development and prognosis of idiopathic pulmonary fibrosis (IPF) have been identified. We previously observed that EPB41L3 increased in the lung fibroblasts of IPF patients. Thus, we investigated the role of EPB41L3 in IPF by comparing EPB41L3 mRNA and protein expression of lung fibroblast between patients with IPF and controls. We also investigated the regulation of the epithelial-mesenchymal transition (EMT) in an epithelial cell line (A549), and the fibroblast-to-myofibroblast transition (FMT) in a fibroblast cell line (MRC5), by overexpressing and silencing EPB41L3. EPB41L3 mRNA and protein levels, as measured by RT-PCR, real-time PCR, and western blot, were significantly higher in fibroblasts derived from 14 IPF patients than in those from 10 controls. The mRNA and protein expression of EPB41L3 was upregulated during transforming growth factor-β-induced EMT and FMT. Overexpression of EPB41L3 in A549 cells using lenti-EPB41L3 transfection suppressed the mRNA and protein expression of N-cadherin and COL1A1. Treatment with EPB41L3 siRNA upregulated mRNA and protein expression of N-cadherin. Overexpression of EPB41L3 in MRC5 cells using lenti-EPB41L3 transfection suppressed mRNA and protein expression of fibronectin and α-SMA. Finally, treatment with EPB41L3 siRNA upregulated mRNA and protein expression of FN1, COL1A1, and VIM. Overall, these data strongly support an inhibitory effect of EPB41L3 on the process of fibrosis and suggest therapeutic potential of EPB41L3 as an anti-fibrotic mediator.

Background: Currently, many detection methods have high sensitivity to the diagnosis of lung cancer. However, some postoperative patients with pulmonary nodule were eventually diagnosed as benign nodules. The ideal evaluation of an individual with a pulmonary nodule would expedite therapy for a malignant nodule and minimize testing for those with a benign nodule.Methods: This case-control study is designed to explore the relationship between ACE1 rs4646994 polymorphism and the risk of lung cancer in patients with pulmonary nodules, 400 individuals with lung cancer and benign pulmonary nodules were included. A DNA extraction kit was used to extract plasm DNA from peripheral blood. The relationship between ACE1 rs4646994 and the risk of lung cancer in patients with pulmonary nodules was determined by chi-square test, logistic regression analysis and cross analysis. Results: The results showed that the DD genotype of ACE1 rs4646994 may increase the risk of lung cancer in patients with pulmonary nodules, and this correlation was more significant in the female subgroup. In the age stratification analysis, it was found that the risk of lung cancer was significantly increased in the DD genotype of ACE1 rs4646994 in the older subgroup (&gt; 45 years). In addition, the possibility of EGFR mutation in lung adenocarcinoma patients with ACE1 rs4646994 DD genotype was lower than that of II or ID genotype carriers. Conclusions: Our study indicated that ACE1 rs4646994 polymorphism increases the risk of lung cancer in patients with pulmonary nodules from China.

Transmembrane protein 100 (TMEM100) plays an important role in angiogenesis, vascular morphogenesis, integrity and cardiovascular development. TMEM100 is a downstream target of the BMP9/10 and BMPR2/ALK1 signaling pathways. Our recent study demonstrates TMEM100 is a lung endothelium enriched gene. Endothelial-specific deletion of Tmem100 impairs lung endothelial cells regeneration. Activation of Tmem100 signaling represents a novel strategy for lung vascular repair and regeneration. It is interesting and important to understand the roles of TMEM100 in the physiological and pathological conditions. In this review, we summarized the current knowledge of TMEM100.

Renal Cell Carcinoma (RCC) is generally represented by low-FDG avidity, and [18F]FDG-PET/CT is not recommended to stage the primary tumor. However, its role to assess metastases is still unclear. The aim of this study was to evaluate the diagnostic accuracy of [18F]FDG-PET/CT to correctly identify RCC lung metastases using histology as standard of truth. Records of 350 patients affected by RCC and with CT evidence of at least one lung nodule, were retrospectively analyzed. Inclusion criteria were: a) histologically proven RCC; b) [18F]FDG-PET/CT performed prior to lung surgery; c) lung surgery with histological analysis of surgical specimens; d) complete follow-up available. A per-lesion analysis was performed, and diagnostic accuracy was reported as sensitivity and specificity, using histology as standard of truth. [18F]FDG-PET/CT semiquantitative parameters (Standardized Uptake Value [SUVmax], Metabolic Tumor Volume [MTV] and Total Lesion Glycolysis [TLG]) were collected for each lesion. Sixty-seven (n=67) patients with a total of 107 lesions were included: lung metastases from RCC were detected in 57/107 of cases, while 50/107 lesions were related to others lung malignancies. Applying a cut-off of SUVmax ≥2, the sensitivity and the specificity of [18F]FDG-PET/CT for detect RCC lung metastases were 33.3% (95% CI: 21.4% - 47.1%) and 26% (95%CI: 14.6% - 40.3%), respectively. The analysis demonstrated sub-optimal diagnostic accuracy of [18F]FDG-PET/CT to discriminate between RCC lung metastases versus other malignancies. However, semiquantitative analysis including also volumetric parameters (MTV and TLG) can support [18F]FDG-PET/CT image interpretation.