The objective of standard guideline for utilization of human lung organoids is to provide the basic guidelines required for the manufacture, culture, and quality control of the lung organoids for use in non-clinical efficacy and inhalation toxicity assessments of the respiratory system. As a first step towards the utilization of human lung organoids, the current guideline provides basic, minimal standards that can promote development of alternative testing methods, and can be referenced not only for research, clinical, or commercial uses, but also by experts and researchers at regulatory institutions when assessing safety and efficacy.

Tumor immune evasion is a complex process that involves various mechanisms, such as antigen recognition restriction, immune system suppression, and T cell exhaustion. The tumor microenvironment contains various immune cells involved in immune evasion. Recent studies have demonstrated that granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce immune evasion in lung cancer by modulating neutrophils and myeloid-derived suppressor cells. Here we describe the origin and function of G-CSF and GM-CSF, particularly their role in immune evasion in lung cancer. In addition, their effects on programmed death-ligand 1 expression and clinical implications are discussed.

Stage 3 non-small cell lung cancer (NSCLC) exhibits significant diversity, making it challenging to define an optimal treatment. A collaborative multidisciplinary approach is essential in crafting individualized treatments. Previously, targeted therapies and immunotherapies were commonly used to treat patients with advanced and metastatic lung cancer. Such treatments are now being extended to individuals considered surgery, as well as patients once considered unsuitable for surgery. These changes have increased surgical success and substantially reduced postoperative recurrence. However, the possibility of severe adverse effects from immunotherapy can deter some patients from performing surgery. It is essential to carefully explore the clinical traits and biomarkers of patients who may benefit the most from immunotherapy, and patients for whom immunotherapy should not be prescribed. In summary, it’s crucial to effectively integrate the latest immunotherapy in treating stage 3 NSCLC patients, thereby increasing their opportunities for surgical intervention, and ensuring they receive the best possible care.

The stethoscope has long been used for the examination of patients, but the importance of auscultation has declined due to its several limitations and the development of other diagnostic tools. However, auscultation is still recognized as a primary diagnostic device because it is non-invasive and provides valuable information in real-time. To supplement the limitations of existing stethoscopes, digital stethoscopes with machine learning (ML) algorithms have been developed. Thus, now we can record and share respiratory sounds and artificial intelligence (AI)-assisted auscultation using ML algorithms distinguishes the type of sounds. Recently, the demands for remote care and non-face-to-face treatment diseases requiring isolation such as coronavirus disease 2019 (COVID-19) infection increased. To address these problems, wireless and wearable stethoscopes are being developed with the advances in battery technology and integrated sensors. This review provides the history of the stethoscope and classification of respiratory sounds, describes ML algorithms, and introduces new auscultation methods based on AI-assisted analysis and wireless or wearable stethoscopes.

Background: Complementary and alternative medicine (CAM) has been used frequently, and its use continues to increase in lung cancer patients, despite insufficient scientific of its efficacy. To investigate this situation, we analyzed the current awareness and use of CAM in Korean lung-cancer patients. Methods: This prospective survey–based study was performed at seven medical centers in South Korea between August and October 2019. The survey assessed general patient characteristics and the awareness and use of CAM. We analyzed differences in the clinical parameters of patients aware and not aware of CAM and of CAM non-users and users. Results: Of the 434 patients included in this study, 68.8% responded that they were aware of CAM and 30.9% said they had experienced it. In univariate analysis, the patients aware of CAM were younger with poor performance status, had advanced-stage lung cancer, received more systemic therapy, and received concurrent chemoradiation therapy (CCRT). By multiple logistic regression, younger age, poor performance status, advanced stage, and prior CCRT were identified as independent risk factors for CAM awareness. There were no significant differences in the general characteristics and cancer-associated clinical parameters of CAM non-users and users. Conclusion Specific clinical parameters were associated with patients’ awareness of CAM, although there were no significantly different characteristics between CAM users and non-users.

Although transthoracic needle biopsy (TTNB) was introduced for lung biopsy about 40 years ago, it is still mainstay of pathologic diagnosis in lung cancer, because it is relatively inexpensive and can obtain tissue regardless of the tumor-bronchus relationship. With several technological advances, proceduralists can perform TTNB more safely and accurately. Utilizing ultrasound-guided biopsy for peripheral lesions in contact with the pleura and rapid onsite evaluation during the procedure are expected to make up the weakness of TTNB. However, due to the inherent limitations of the percutaneous approach, the incidence of complications such as pneumothorax or bleeding is inevitably higher than that of other lung biopsy techniques. Thorough understating of each biopsy modality and additional technique are fundamental for maximizing diagnostic accuracy and minimizing the complications.

Although transthoracic needle biopsy (TTNB) was introduced for lung biopsy about 40 years ago, it is still mainstay of pathologic diagnosis in lung cancer, because it is relatively inexpensive and can obtain tissue regardless of the tumor-bronchus relationship. With several technological advances, proceduralists can perform TTNB more safely and accurately. Utilizing ultrasound-guided biopsy for peripheral lesions in contact with the pleura and rapid onsite evaluation during the procedure are expected to make up the weakness of TTNB. However, due to the inherent limitations of the percutaneous approach, the incidence of complications such as pneumothorax or bleeding is inevitably higher than that of other lung biopsy techniques. Thorough understating of each biopsy modality and additional technique are fundamental for maximizing diagnostic accuracy and minimizing the complications.

Vitamin D signaling plays an essential role in innate defense against intracellular microorganisms via the generation of the antimicrobial protein cathelicidin. In addition to directly binding to and killing a range of pathogens, cathelicidin acts as a secondary messenger driving vitamin D-mediated inflammation during infection. Recent studies have elucidated the biological and clinical functions of cathelicidin in the context of vitamin D signaling. The vitamin D-cathelicidin axis is involved in the activation of autophagy, which enhances antimicrobial effects against diverse pathogens. Vitamin D studies have also revealed positive and negative regulatory effects of cathelicidin on inflammatory responses to pathogenic stimuli. Diverse innate and adaptive immune signals crosstalk with functional vitamin D receptor signals to enhance the role of cathelicidin action in cell-autonomous effector systems. In this review, we discuss recent findings that demonstrate how the vitamin D-cathelicidin pathway regulates autophagy machinery, protective immune defenses, and inflammation, and contributes to immune cooperation between innate and adaptive immunity. Understanding how the vitamin D-cathelicidin axis operates in the host response to infection will create opportunities for the development of new therapeutic approaches against a variety of infectious diseases.

Although various studies on predictive markers in the use of PD-1/PD-L1 inhibitors are in progress, only PD-L1 expression levels in tumor tissues are currently used. In the present study, we investigated whether baseline serum levels of IL-6 can predict the treatment response of patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors. In our cohort of 125 NSCLC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in those with low IL-6 (<13.1 pg/ml) than those with high IL-6 (ORR 33.9% vs. 11.1%, p=0.003; DCR 80.6% vs. 34.9%, p<0.001). The median progression-free survival was 6.3 months (95% confidence interval [CI], 3.9–8.7) in the low IL-6 group, significantly longer than in the high IL-6 group (1.9 months, 95% CI, 1.6–2.2, p<0.001). The median overall survival in the low IL-6 group was significantly longer than in the high IL-6 group (not reached vs. 7.4 months, 95% CI, 4.8–10.0). Thus, baseline serum IL-6 levels could be a potential biomarker for predicting the efficacy and survival benefit of PD-1/PD-L1 inhibitors in NSCLC.

Background: Observational studies of the ongoing coronavirus disease 2019 (COVID-19) outbreak suggest that a ‘cytokine storm’ is involved in the pathogenesis of severe illness.However, the molecular mechanisms underlying the altered pathological inflammation in COVID-19 are largely unknown. We report here that toll-like receptor (TLR) 4-mediated inflammatory signaling molecules are upregulated in peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, compared with healthy controls (HC). Methods: A total of 48 subjects including 28 COVID-19 patients (8 severe/critical vs. 20 mild/ moderate cases) admitted to Chungnam National University Hospital, and age/sex-matched 20 HC were enrolled in this study. PBMCs from the subjects were processed for nCounter Human Immunology gene expression assay to analyze the immune related transcriptome profiles. Recombinant proteins of severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) were used to stimulate the PBMCs and monocyte-derived macrophages, and real-time polymerase chain reaction was performed to quantify the mRNA expressions of the proinflammatory cytokines/chemokines. Results: Among the most highly increased inflammatory mediators in severe/critically ill patients, S100A9, an alarmin and TLR4 ligand, was found as a noteworthy biomarker, because it inversely correlated with the serum albumin levels. We also observed that recombinant S2 and nucleocapsid proteins of SARS-CoV2 significantly increased proinflammatory cytokines/chemokines and S100A9 in human primary PBMCs. Conclusion These data support a link between TLR4 signaling and pathological inflammation during COVID-19 and contribute to develop therapeutic approaches through targeting TLR4-mediated inflammation.