Fusobacterium nucleatum putatively affects the alveoli by disrupting the alveolar epithelial cell tight junction, enlarging the alveolar space, and increasing paracellular permeability.

Fusobacterium nucleatum (Fn) is abundant in the human oral cavity and has been associated with periodontal disease, which in-turn has been linked to respiratory disease development. Tight junctions (TJs) line the airway and alveoli surfaces serving as a first line of defense against multiple pathogens. Fn has already been linked to respiratory diseases, however, how Fn affects the alveolar TJ was not fully elucidated. Here, we designed and analyzed a TJ network, grew Fn cells and inoculated it in vitro (16HBE and primary cells) and in vivo (mice lung), measured transepithelial electrical resistance, performed RT-PCR, checked for in vitro cell and mice lung permeability, and determined air space size through morphometric measurements. We found that Fn can potentially affect TJs proteins that are directly exposed to the alveolar surface. Additionally, Fn could possibly cause neutrophil accumulation and an increase in alveolar space. Moreover, Fn putatively may cause an increase in paracellular permeability in the alveoli.

A Changing Anti-Neutrophil Cytoplasmic Antibody Profile in a Patient With a Diagnosis of Eosinophilic Granulomatosis With Polyangiitis.

This report describes a hitherto unique case of eosinophilic granulomatosis with polyangiitis (EGPA), a subtype of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The patient was an 81-year-old man whose clinical course involved notable changes in the ANCA profile, specifically a transition from positive proteinase 3 (PR3)-ANCA to myeloperoxidase (MPO)-ANCA, followed by simultaneous positivity for both. The patient's medical history included bronchial asthma, allergic rhinitis, sinusitis, and multiple comorbidities. Despite being initially PR3-ANCA-positive, subsequent admissions demonstrated MPO-ANCA positivity along with eosinophilic manifestations, highlighting the complexity of diagnosis of EGPA. Diagnostic evaluation included imaging, serological markers, and clinical symptoms, which collectively supported the classification of EGPA. Notably, this case challenges the conventional diagnostic paradigms and emphasizes the evolving nature of ANCA profiles in vasculitis. The shift in ANCA profile prompted a reevaluation of the patient's diagnosis and treatment strategy. This case underscores the importance of considering fluctuations in ANCA in patients with a diagnosis of EGPA, management decisions, and potential implications for disease progression. Further research is warranted to elucidate the mechanisms underlying changes in ANCA and their clinical significance in vasculitis.

Anti-UBE2T antibody: A novel biomarker of progressive-fibrosing interstitial lung disease.

BACKGROUND: Anti-fibrotic therapy has demonstrated efficacy against progressive-fibrosing interstitial lung disease (PF-ILD); therefore, identifying disease behavior before progression has become a priority. As autoimmunity is implicated in the pathogenesis of various ILDs, this study explored circulating biomarkers that could predict the chronic progressive behavior of ILDs. METHODS: A single-center retrospective cohort study was conducted. Circulating autoantibodies in patients with ILD were screened using microarray analysis to identify candidate biomarkers. An enzyme-linked immunosorbent assay was performed with a larger sample set for the quantification of antibodies. After 2 years of follow-up, ILDs were reclassified as PF or non-PF. The relationship between the participants' autoantibody levels measured at enrolment and final diagnosis of PF-ILD was determined. RESULTS: In total, 61 healthy participants and 66 patients with ILDs were enrolled. Anti-ubiquitin-conjugating enzyme E2T (UBE2T) antibody was detected as a candidate biomarker. Anti-UBE2T antibody levels were elevated in patients with idiopathic pulmonary fibrosis (IPF). After following up on the study participants for 2 years, anti-UBE2T levels measured at enrolment significantly correlated with the new PF-ILD diagnosis. Immunohistochemical staining of normal lung tissues revealed sparsely located UBE2T in the bronchiole epithelium and macrophages, whereas IPF lung tissues showed robust expression in the epithelial lining of honeycomb structures. CONCLUSION: To our knowledge, this is the first report to describe an anti-UBE2T antibody, a new biomarker that is significantly elevated in patients with ILD who present future disease progression.

Periodontopathic Bacterium Fusobacterium nucleatum Affects Matrix Metalloproteinase-9 Expression in Human Alveolar Epithelial Cells and Mouse Lung.

BACKGROUND/AIM: Despite evidence of an association between pulmonary diseases and periodontopathic bacteria, the molecular mechanisms remain unknown. Matrix metalloproteinase-9 (MMP9) plays important roles in pneumonia, chronic obstructive pulmonary disease, and asthma; therefore, we assessed the effects of Fusobacterium nucleatum on MMP9 expression in mouse lung and A549 human alveolar epithelial cells. MATERIALS AND METHODS: Heat-killed F. nucleatum was administered to the trachea of mice or added to A549 cell cultures. MMP9 expression was determined using real-time PCR and western blotting. The involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) in MMP9 expression was examined. RESULTS: F. nucleatum induced expression of MMP9 in mouse lung and bronchoalveolar lavage fluid. In A549 cells, F. nucleatum induced production of MMP9 protein and mRNA in a density-dependent manner; this was inhibited by inhibitors of extracellular-regulated kinase 1/2 and NF-κB, but not of p38 and Jun N-terminal protein kinase. CONCLUSION: F. nucleatum may contribute to the onset of pulmonary diseases via MMP9 expression through extracellular-regulated kinase 1/2 and NF-κB activation.

Iron-Dependent Mitochondrial Dysfunction Contributes to the Pathogenesis of Pulmonary Fibrosis.

Although the pathogenesis of pulmonary fibrosis remains unclear, it is known to involve epithelial injury and epithelial-mesenchymal transformation (EMT) as a consequence of cigarette smoke (CS) exposure. Moreover, smoking deposits iron in the mitochondria of alveolar epithelial cells. Iron overload in mitochondria causes the Fenton reaction, leading to reactive oxygen species (ROS) production, and ROS leakage from the mitochondria induces cell injury and inflammation in the lungs. Nevertheless, the mechanisms underlying iron metabolism and pulmonary fibrosis are yet to be elucidated. In this study, we aimed to determine whether iron metabolism and mitochondrial dysfunction are involved in the pathogenesis of pulmonary fibrosis. We demonstrated that administration of the iron chelator deferoxamine (DFO) reduced CS-induced pulmonary epithelial cell death, mitochondrial ROS production, and mitochondrial DNA release. Notably, CS-induced cell death was reduced by the administration of an inhibitor targeting ferroptosis, a unique iron-dependent form of non-apoptotic cell death. Transforming growth factor-ß-induced EMT of pulmonary epithelial cells was also reduced by DFO. The preservation of mitochondrial function reduced Transforming growth factor-ß-induced EMT. Furthermore, transbronchial iron chelation ameliorated bleomycin-induced pulmonary fibrosis and leukocyte migration in a murine model. Our findings indicate that iron metabolism and mitochondrial dysfunction are involved in the pathogenesis of pulmonary fibrosis. Thus, they may be leveraged as new therapeutic targets for pulmonary fibrosis.

Porphyromonas gingivalis gingipains potentially affect MUC5AC gene expression and protein levels in respiratory epithelial cells.

Porphyromonas gingivalis (Pg) is a periodontopathic pathogen that may affect MUC5AC-related mucus hypersecretion along airway epithelial cells. Here, we attempted to establish whether Pg virulence factors (lipopolysaccharide, FimA fimbriae, gingipains) affect MUC5AC in immortalized and primary bronchial cells. We report that MUC5AC gene expression and protein levels are affected by Pg culture supernatant, but not by lipopolysaccharide or FimA fimbriae. Cells treated with either Pg single (Kgp or Rgp) or double (Kgp/Rgp) mutants had altered levels of MUC5AC gene expression and protein levels, and MUC5AC staining of double mutant-treated mouse lung cells showed that MUC5AC protein levels were unaffected. Taken together, we propose that Pg gingipains may be the primary virulence factor that influences both MUC5AC gene expression and protein levels.

Effective ferroptotic small-cell lung cancer cell death from SLC7A11 inhibition by sulforaphane.

Small-cell lung cancer (SCLC) is a highly aggressive cancer with poor prognosis, due to a lack of therapeutic targets. Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables and has shown anticancer effects against numerous types of cancer. However, its anticancer effect against SCLC remains unclear. The present study aimed to demonstrate the anticancer effects of SFN in SCLC cells by investigating cell death (ferroptosis, necroptosis and caspase inhibition). The human SCLC cell lines NCI-H69, NCI-H69AR (H69AR) and NCI-H82 and the normal bronchial epithelial cell line, 16HBE14o- were used to determine cell growth and cytotoxicity, evaluate the levels of iron and glutathione, and quantify lipid peroxidation following treatment with SFN. mRNA expression levels of cystine/glutamate antiporter xCT (SLC7A11), a key component of the cysteine/glutamate antiporter, were measured using reverse transcription-quantitative PCR, while the levels of SLC7A11 protein were measured using western blot analysis. Following the addition of SFN to the cell culture, cell growth was significantly inhibited, and cell death was shown in SCLC and multidrug-resistant H69AR cells. The ferroptotic effects of SFN were confirmed following culture with the ferroptosis inhibitor, ferrostatin-1, and deferoxamine; iron levels were elevated, which resulted in the accumulation of lipid reactive oxygen species. The mRNA and protein expression levels of SLC7A11 were significantly lower in SFN-treated cells compared with that in the control cells (P<0.0001 and P=0.0006, respectively). These results indicated that the anticancer effects of SFN may be caused by ferroptosis in the SCLC cells, which was hypothesized to be triggered from the inhibition of mRNA and protein expression levels of SLC7A11. In conclusion, the present study demonstrated that SFN-induced cell death was mediated via ferroptosis and inhibition of the mRNA and protein expression levels of SLC7A11 in SCLC cells. The anticancer effects of SFN may provide novel options for SCLC treatment.

Role of Nrf2 in the pathogenesis of respiratory diseases.

Nuclear factor erythroid 2-related factor (Nrf)2 is a transcription factor that integrates cellular stress signals by directing various transcriptional programs. As an evolutionarily conserved intracellular defense mechanism, Nrf2 and its endogenous inhibitor Kelch-like ECH-associated protein (Keap)1 inhibit oxidative stress in the lung, which is the internal organ that is continuously exposed to the environment. Oxidative stress is implicated in the pathogenesis of various lung diseases including asthma, acute lung injury, chronic obstructive pulmonary disease (COPD), and interstitial lung disease (ILD). Thus, Nrf2 is considered as a potential therapeutic target in lung diseases owing to its antioxidant effect. Nrf2 also plays a complex role in lung cancer, acting as a tumor suppressor and promoter; recent studies have revealed the tumor-promoting effects of Nrf2 in tumors that have undergone malignant transformation. Lung cancer-associated mutations in Keap1 disrupt Keap1-Nrf2 complex formation, resulting in the ubiquitination and degradation of Keap1, and the constitutive activation of Nrf2. In lung cancer cells, persistently high nuclear Nrf2 levels induce the expression of genes that contribute to metabolic reprogramming, and stimulate cell proliferation. In this review, we outlined the major functions of Nrf2, and discussed its importance in pulmonary diseases such as asthma, acute respiratory distress syndrome, and lung cancer. Elucidating the mechanisms through which Nrf2 modulates the initiation and progression of pulmonary diseases can lead to the development of therapeutics specifically targeting this pathway.

Molecular techniques for respiratory diseases: MicroRNA and extracellular vesicles.

miRNA are a class of evolutionarily conserved non-coding 19- to 22-nt regulatory RNA. They affect various cellular functions through modulating the transcriptional and post-transcriptional levels of their target mRNA by changing the stability of protein-coding transcripts or attenuating protein translation. miRNA were discovered in the early 1990s, and they have been the focus of new research in both basic and clinical medical sciences. Today, it has become clear that specific miRNA are linked to the pathogenesis of respiratory diseases, as well as cancer and cardiovascular disease. In addition, EV, including exosomes, which are small membrane-bound vesicles secreted by cells, were found to contain various functional miRNA that can be used for diagnostic and therapeutic purposes. As body fluids, such as blood and respiratory secretions, are major miRNA sources in the body, EV carrying extracellular miRNA are considered potentially useful for the diagnosis and assessment of pathological conditions, as well as the treatment of respiratory or other diseases. Although research in the field of lung cancer is actively progressing, studies in other respiratory fields have emerged recently as well. In this review, we provide an update in the topics of miRNA and EV focused on airway inflammatory diseases, such as asthma and COPD, and explore their potential for clinical applications on respiratory diseases.

The Diagnosis of Exogenous Lipoid Pneumonia Caused by the Silent Aspiration of Vegetable Oil Using a Lipidomic Analysis.

We herein report a case of refractory exogenous lipoid pneumonia that was successfully attributed to vegetable oil through a lipidomic analysis of bronchoalveolar lavage fluid (BALF). As a 25-year-old woman diagnosed with lipoid pneumonia experienced repeated exacerbations and improvement, we performed a BALF lipidomic analysis. The major lipid components were oleic acid, linoleic acid, and α-linolenic acid, which are constituents of vegetable oil. She stopped consuming any vegetable oil and has since experienced no instances of lipoid pneumonia relapse. A lipidomic analysis appears to be useful for identifying causative lipids, since patients with lipoid pneumonia are sometimes unaware of aspiration episodes.

Pathogenesis of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that is characterized by functional and structural alterations primarily caused by long-term inhalation of harmful particles. Cigarette smoke (CS) induces airway inflammation in COPD, which is known to persist even after smoking cessation. This review discusses the basic pathogenesis of COPD, with particular focus on an endogenous protective mechanism against oxidative stress via Nrf2, altered immune response of the airway inflammatory cells, exaggerated cellular senescence of the lung structural cells, and cell death with expanded inflammation. Recently, CS-induced mitochondria autophagy is reported to initiate programmed necrosis (necroptosis). Necroptosis is a new concept of cell death which is driven by a defined molecular pathway along with exaggerated inflammation. This new cell death mechanism is of importance due to its ability to produce more inflammatory substances during the process of epithelial death, contributing to persistent airway inflammation that cannot be explained by apoptosis-derived cell death. Autophagy is an auto-cell component degradation system executed by lysosomes that controls protein and organelle degradation for successful homeostasis. As well as in the process of necroptosis, autophagy is also observed during cellular senescence. Aging of the lungs results in the acquisition of senescence-associated secretory phenotypes (SASP) that are known to secrete inflammatory cytokines, chemokines, growth factors, and matrix metalloproteinases resulting in chronic low-grade inflammation. In future research, we intend to highlight the genetic and epigenetic approaches that can facilitate the understanding of disease susceptibility. The goal of precision medicine is to establish more accurate diagnosis and treatment methods based on the patient-specific pathogenic characteristics. This review provides insights into CS-induced COPD pathogenesis, which contributes to a very complex disease. Investigating the mechanism of developing COPD, along with the availability of the particular inhibitors, will lead to new therapeutic approaches in COPD treatment.

Factors Relating to Caregivers' Preference for Advance Care Planning of Patients in Japan: A Cross-Sectional Study.

OBJECTIVES: The aim of this study was to examine the preferences of home caregivers on patient advance care planning (ACP), including life-sustaining treatment (LST) and the factors relating to these preferences. BACKGROUND: Personalized ACP aims to respect the autonomy and choices of terminally ill patients regarding end-of-life care. However, there have been cases wherein doctors must instead discuss ACP with surrogates (including caregivers) for various reasons such as dementia, intractable neurologic diseases, and cerebrovascular accident. METHODS: In this cross-sectional study, self-written questionnaires (filled by individuals themselves) were distributed to 506 in-home caregivers in 6 Japanese prefectures; the questionnaires contained items on caregiver and patient demographics, number of people living together in a caregiver's home (aside from patients), care duration, comprehension level of doctors' explanations regarding their patient's condition, patient diseases, whether caregivers have or have not told patients about their disease, level of nursing care, and caregiver LST preference (preferred or not preferred). The questionnaire package also contained the Burden Index of Caregiver-11, Patient Health Questionnaire-9, and Short Form-8 Health Survey. RESULTS: Valid responses were obtained from 309 caregivers. More than half of them were not sure of their patient's LST preference. Sex, number of people living together in a care home, comprehension level of doctors' explanations, and care duration were found to be the significant factors relating to caregivers' LST preference (P < .05). CONCLUSION: Health providers should be cognizant of the background factors relating to caregiver ACP preference when deciding on LST for terminal patients.

Increased extracellular vesicle miRNA-466 family in the bronchoalveolar lavage fluid as a precipitating factor of ARDS.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening disease; however, its treatment has not yet been fully established. The progression of ARDS is considered to be mediated by altered intercellular communication between immune and structural cells in the lung. One of several factors involved in intercellular communication is the extracellular vesicle (EV). They act as carriers of functional content such as RNA molecules, proteins, and lipids and deliver cargo from donor to recipient cells. EVs have been reported to regulate the nucleotide-binding oligomerization like receptor 3 (NLRP3) inflammasome. This has been identified as the cellular machinery responsible for activating inflammatory processes, a key component responsible for the pathogenesis of ARDS. METHODS: Here, we provide comprehensive genetic analysis of microRNAs (miRNAs) in EVs, demonstrating increased expression of the miRNA-466 family in the bronchoalveolar lavage fluid of a mouse ARDS model. RESULTS: Transfection of bone marrow-derived macrophages (BMDMs) with miRNA-466 g and 466 m-5p resulted in increased interleukin-1 beta (IL-1ß) release after LPS and ATP treatment, which is an established in vitro model of NLRP3 inflammasome activation. Moreover, LPS-induced pro-IL-1ß expression was accelerated by miRNA-466 g and 466 m-5p in BMDMs. CONCLUSIONS: These findings imply that miRNA-466 family molecules are secreted via EVs into the airways in an ARDS model, and this exacerbates inflammation through the NLRP3 inflammasome. Our results suggest that the NLRP3 inflammasome pathway, regulated by extracellular vesicle miRNA, could act as a therapeutic target for ARDS.

A humanized mouse model to study asthmatic airway inflammation via the human IL-33/IL-13 axis.

Asthma is one of the most common immunological diseases and is characterized by airway hyperresponsiveness (AHR), mucus overproduction, and airway eosinophilia. Although mouse models have provided insight into the mechanisms by which type-2 cytokines induce asthmatic airway inflammation, differences between the rodent and human immune systems hamper efforts to improve understanding of human allergic diseases. In this study, we aim to establish a preclinical animal model of asthmatic airway inflammation using humanized IL-3/GM-CSF or IL-3/GM-CSF/IL-5 Tg NOD/Shi-scid-IL2rγnull (NOG) mice and investigate the roles of human type-2 immune responses in the asthmatic mice. Several important characteristics of asthma - such as AHR, goblet cell hyperplasia, T cell infiltration, IL-13 production, and periostin secretion - were induced in IL-3/GM-CSF Tg mice by intratracheally administered human IL-33. In addition to these characteristics, human eosinophilic inflammation was observed in IL-3/GM-CSF/IL-5 Tg mice. The asthmatic mechanisms of the humanized mice were driven by activation of human Th2 and mast cells by IL-33 stimulation. Furthermore, treatment of the humanized mice with an anti-human IL-13 antibody significantly suppressed these characteristics. Therefore, the humanized mice may enhance our understanding of the pathophysiology of allergic disorders and facilitate the preclinical development of new therapeutics for IL-33-mediated type-2 inflammation in asthma.

Autophagy, selective autophagy, and necroptosis in COPD.

COPD is characterized by persistent respiratory symptoms and airflow limitation, caused by a mixture of small airway disease and pulmonary emphysema. Programmed cell death has drawn the attention of COPD researchers because emphysema is thought to result from epithelial cell death caused by smoking. Although apoptosis has long been thought to be the sole form of programmed cell death, recent studies have reported the existence of a genetically programmed and regulated form of necrosis called necroptosis. Autophagy was also previously considered a form of programmed cell death, but this has been reconsidered. However, recent studies have revealed that autophagy can regulate programmed cell death, including apoptosis and necroptosis. It is also becoming clear that autophagy can selectively degrade specific proteins, organelles, and invading bacteria by a process termed "selective autophagy" and that this process is related to the pathogenesis of human diseases. In this review, we outline the most recent studies implicating autophagy, selective autophagy, and necroptosis in COPD. Strategies targeting these pathways may yield novel therapies for COPD.

Clinicopathological characteristics of thyroid transcription factor 1-negative small cell lung cancers.

Limitations in obtaining surgically resected or biopsy samples of small cell lung cancer (SCLC) tumors make comprehensive biological analyses difficult. The loss of thyroid transcription factor 1 (TTF-1) has been associated with the aggressive behavior of non-small cell lung cancer; however, clinicopathological features of TTF-1-negative SCLC remain unclear. This study aimed to elucidate the characteristics of TTF-1-negative SCLC. We studied the associations between the expression of TTF-1 and the clinicopathological factors associated with SCLC, including survival and expression of neuroendocrine markers (synaptophysin, chromogranin A, and CD56), neuroendocrine cell-specific transcription factors (ASCL1, BRN2), a proliferation marker (Ki-67 labeling index), and an oncogene (NF1B). Formalin-fixed and paraffin-embedded sections of SCLC tumors were subjected to immunohistochemistry and quantitative reverse-transcription polymerase chain reaction analyses. In a case-control cohort matched for basic clinical factors, expression of ProGRP, synaptophysin, chromogranin A, and ASCL1 was significantly decreased in TTF-1-negative SCLC samples. In contrast, there was no significant correlation between Ki-67 labeling index and TTF-1. In a larger serial case cohort, TTF-1-negative SCLC cases were older at diagnosis, but there was no significant difference in the overall survival of patients with TTF-1-negative and TTF-1-positive SCLC. In conclusion, TTF-1-negative SCLC showed decreased neuroendocrine differentiation, and significantly worse clinical outcomes were not observed.

NDRG1 is important to maintain the integrity of airway epithelial barrier through claudin-9 expression.

Impairment of epithelial barrier integrity caused by environmental triggers is associated with the pathogenesis of airway inflammation. Using human airway epithelial cells, we attempted to identify molecule(s) that promote airway epithelial barrier integrity. Microarray analyses were conducted using the Affimetrix human whole genome gene chip, and we identified the N-myc downstream-regulated gene 1 (NDRG1) gene, which was induced during the development of the epithelial cell barrier. Immunohistochemical analysis revealed strong NDRG1 expression in ciliated epithelial cells in nasal tissues sampled from patients with chronic rhinosinusitis (CRS), and the low expression of NDRG1 was observed in goblet cells or damaged epithelial cells. NDRG1 gene knockdown with its specific siRNA decreased the transepithelial electrical resistance and increased the dextran permeability. Immunocytochemistry revealed that NDRG1 knockdown disrupted tight junctions of airway epithelial cells. Next, we analyzed the effects of NDRG1 knockdown on the expression of tight and adhesion junction molecules. NDRG1 knockdown significantly decreased only claudin-9 expression, but did not decrease other claudin family molecules, such as E-cadherin, and ZO-1, -2, or -3. Knockdown of claudin-9 markedly impaired the barrier function in airway epithelial cells. These results suggest that NDRG1 is important for the barrier integrity in airway epithelial cells.

The role of necroptosis in pulmonary diseases.

By regulating the cell number and eliminating harmful cells, programmed cell death plays a critical role in development, homeostasis, and disease. While apoptosis is a recognized form of programmed cell death, necrosis was considered a type of uncontrolled cell death induced by extreme physical or chemical stress. However, recent studies have revealed the existence of a genetically programmed and regulated form of necrosis, termed necroptosis. Necroptosis is defined as necrotic cell death that is dependent on receptor-interacting protein kinase 3 (RIPK3). RIPK3, receptor-interacting protein kinase 1 (RIPK1), and a mixed-lineage kinase domain-like protein (MLKL) form a multiprotein complex called a necrosome. Although necroptosis generally provides a cell-autonomous host defense, on the other hand, cell rupture caused by necroptosis induces inflammation through the release of damage-associated molecular patterns, such as mitochondrial DNA, HMGB1, and IL-1. Previously, necroptosis was considered an alternative to apoptosis, but it is becoming increasingly clear that necroptosis itself is relevant to clinical disease, independent of apoptosis. According to some recent studies, autophagy, a cellular process for organelle and protein turnover, regulates necroptosis. This review outlines the principal components of necroptosis and provides an overview of the emerging importance of necroptosis in the pathogenesis of pulmonary disease, including chronic obstructive pulmonary disease, lung cancer, infection, and sepsis. We also discuss the molecular relationship between necroptosis and autophagy. Strategies targeting necroptosis may yield novel therapies for pulmonary diseases.

Evaluation of airway resistance in primary small cell carcinoma of the trachea by MostGraph: a case study.

The case subject was a 58-year-old woman who presented to our hospital with a chief complaint of respiratory discomfort. Wheezing could be heard in both lungs; treatment was initiated with inhaled steroids for suspected bronchial asthma. However, 1 week later, the respiratory discomfort had not improved and the wheezing sound had progressed to the neck area. Upper airway obstruction was suspected; therefore, chest computed tomography (CT) was performed, revealing tracheal stenosis caused by a tumor in the upper airway. Because of the high risk of airway obstruction, tracheotomy and tracheal tumor resection were performed. Histopathological examination of the resected tumor revealed small cell lung cancer (SCLC); the stage was determined to be clinical stage IIIB (cT4N2M0), for which chemotherapy with two cycles of cisplatin plus etoposide followed by radiation therapy were administered. Pulmonary function testing revealed no change in the forced expiratory volume in 1 sec and flow volume (FV) curve before and after tumor resection, whereas airway resistance measured by MostGraph-01 showed a marked decrease following treatment. We believe that MostGraph-01 may be useful for measuring airway resistance and evaluating a tracheal tumor, and report a case using MostGraph-01.