Understanding the modulations of glycero-lysophospholipids in an elastase-induced murine emphysema model.

BACKGROUND: Increasing evidence indicates that bioactive lipid mediators are involved in chronic obstructive pulmonary disease (COPD) pathogenesis. Recently, glycero-lysophospholipids, such as lysophosphatidic acid (LysoPA) and lysophosphatidylserine (LysoPS), have been recognized as significant inflammation-related lipid mediators. However, their association with COPD remains unclear. METHODS: We used an elastase-induced murine emphysema model to analyze the levels of lysophospholipids and diacyl-phospholipids in the lungs. Additionally, we assessed the expression of LysoPS-related genes and published data on smokers. RESULTS: In the early phase of an elastase-induced murine emphysema model, the levels of LysoPS and its precursor (phosphatidylserine [PS]) were significantly reduced, without significant modulations in other glycero-lysophospholipids. Additionally, there was an upregulation in the expression of lysoPS receptors, specifically GPR34, observed in the lungs of a cigarette smoke-exposed mouse model and the alveolar macrophages of human smokers. Elastase stimulation induces GPR34 expression in a human macrophage cell line in vitro. CONCLUSIONS: Elastase-induced lung emphysema affects the LysoPS/PS-GPR34 axis, and cigarette smoking or elastase upregulates GPR34 expression in alveolar macrophages. This novel association may serve as a potential pharmacological target for COPD treatment.

Anti-Inflammatory Effects of Japanese Herbal Medicine Hochuekkito in a Mouse Model of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

INTRODUCTION: The traditional Japanese herbal medicine hochuekkito (TJ-41) has been reported to ameliorate systemic inflammation and malnutrition in patients with chronic obstructive pulmonary disease (COPD). TJ-41 has also been known to have preventive effects against influenza virus infection. However, its role in the acute exacerbation of COPD (AECOPD) remains to be elucidated. Our previous study established a murine model of viral infection-associated AECOPD that was induced by intratracheal administration of porcine pancreatic elastase (PPE) and polyinosinic-polycytidylic acid [poly(I:C)]. Here, we used this model and investigated the effects of TJ-41 in AECOPD. METHODS: Specific pathogen-free C57BL/6J mice were used. A COPD model was induced by treating mice intratracheally with PPE on day 0. To generate the murine model of AECOPD, poly(I:C) was administered intratracheally following PPE treatment on days 22-24. Mice were sacrificed and analyzed on day 25. Mice were fed a diet containing 2% TJ-41 or a control diet. RESULTS: Daily oral intake of TJ-41 significantly decreased the numbers of neutrophils and lymphocytes in the bronchoalveolar lavage fluid (BALF), which was accompanied by decreased transcripts of CXC chemokines involved in neutrophil migration, viz., Cxcl1 and Cxcl2, in whole lung homogenates and reduced Cxcl2 concentration in BALF. CONCLUSION: This study demonstrates the anti-inflammatory effects of TJ-41 in a mouse model of AECOPD, suggesting the effectiveness of TJ-41 for the management of COPD. Clinical investigations evaluating the therapeutic efficacy of TJ-41 in AECOPD would be meaningful.

Association between Inhalation Instruction Method in Community Pharmacies and Inhaler Device Handling Error in Patients with Obstructive Lung Disease: An Evaluation of the Impact of Practical Demonstration by Pharmacists.

Inhaler devices play an important role in the management of obstructive lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap. Some of these patients show suboptimal inhaler techniques; however, time for inhaler instruction by pharmacists is limited in daily clinical practice. Therefore, sufficient education regarding inhaler device handling should be provided within a limited time frame. The current study aimed to investigate the instruction methods provided by community pharmacists and their influence on inhaler device handling techniques in outpatient clinical care settings. We retrospectively collected the data of outpatients with obstructive lung diseases who were referred to our hospital and who underwent inhalation technique assessments conducted by community pharmacists. The prevalence of handling errors, clinical characteristics of patients, and instruction methods were analyzed. In total, 138 patients (170 devices) were included in this study. Approximately 70.0% of patients received verbal explanations combined with leaflets about inhaler instructions. In a device-based analysis, 63 (37.1%) of 170 devices had at least one technical error and 18 (10.6%) of the devices had critical errors. Patients without critical errors received practical demonstration instructions from pharmacists combined with leaflets and verbal explanations more frequently than those with critical errors (22.8 vs. 0%, p < 0.01). This study revealed that patients with obstructive lung diseases commonly present with inhaler device handling errors and critical errors were observed with non-negligible frequency in daily practice in Japan. Combined instruction with leaflet, verbal explanation, and pharmacist demonstration may be effective in improving proper inhaler treatment.

Interpretations of SARS-CoV-2 IgM and IgG antibody titers in the seroepidemiological study of asymptomatic healthy volunteers.

INTRODUCTION: The usefulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests in asymptomatic individuals has not been well validated, although they have satisfied sensitivity and specificity in symptomatic patients. In this study, we investigated the significance of IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects. METHODS: From June 2020, we recruited 10,039 participants to the project named the University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS), and measured iFlash-SARS-CoV-2 IgM and IgG (YHLO IgM and IgG) titers in the collected serum. For the samples with increased IgM or IgG titers, we performed additional measurements using Elecsys Anti-SARS-CoV-2 Ig (Roche total Ig) and Architect SARS-CoV-2 IgG (Abbott IgG) and investigated the reactivity to N, S1, and receptor binding domain (RBD) proteins. RESULTS: After setting the cutoff value at 5 AU/mL, 61 (0.61%) were positive for YHLO IgM and 104 (1.04%) for YHLO IgG. Few samples with elevated YHLO IgM showed reactivity to S1 or RBD proteins, and IgG titers did not increase during the follow-up in any samples. The samples with elevated YHLO IgG consisted of two groups: one reacted to S1 or RBD proteins and the other did not, which was reflected in the results of Roche total Ig. CONCLUSIONS: In SARS-CoV-2 seroepidemiological studies of asymptomatic participants, sufficient attention should be given to the interpretation of the results of YHLO IgM and IgG, and the combined use of YHLO IgG and Roche total Ig might be more reliable.

The Japanese Herbal (Kampo) Medicine Hochuekkito Attenuates Lung Inflammation in Lung Emphysema.

Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder. It often causes weight loss, which is considered a poor prognostic factor. A Japanese herbal Kampo medicine, Hochuekkito (TJ-41), has been reported to prevent systemic inflammation and weight loss in COPD patients, but the underlying biological mechanisms remain unknown. In the present study, we investigated the role of TJ-41 in vivo using a mouse model of lung emphysema. We used lung epithelium-specific Taz conditional knockout mice (Taz CKO mice) as the lung emphysema model mimicking the chronic pulmonary inflammation in COPD. Acute inflammation was induced by intratracheal lipopolysaccharide administration, simulating COPD exacerbation. Mice were fed a diet containing 2% TJ-41 or a control diet. Taz CKO mice showed increased numbers of inflammatory cells in the bronchoalveolar lavage fluid compared to control mice. This effect was reduced by TJ-41 treatment. In the acute exacerbation model, TJ-41 mitigated the increased numbers of inflammatory cells in the bronchoalveolar lavage fluid and attenuated lung inflammation in histopathological studies. Additional in vitro experiments using the human macrophage cell line U-937 demonstrated that lipopolysaccharide-induced tumor necrosis factor-alpha expression was significantly downregulated by TJ-41. These results suggest that TJ-41 has anti-inflammatory effects in lung emphysema both in the chronic phase and during an acute exacerbation. In conclusion, our study sheds light on the anti-inflammatory effects of TJ-41 in lung emphysema. This establishes its potential as a new anti-inflammatory therapy and a preventive medicine for exacerbations during the long-time maintenance of COPD patients.

Epidemiological study using IgM and IgG antibody titers against SARS-CoV-2 in The University of Tokyo, Japan (UT-CATS).

INTRODUCTION: The worldwide pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to date. Given that some of the patients with coronavirus disease 2019 (COVID-19) are asymptomatic, antibody tests are useful to determine whether there is a previous infection with SARS-CoV-2. In this study, we measured IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects in The University of Tokyo, Japan. METHODS: From June 2020, we recruited participants, who were students, staff, and faculty members of The University of Tokyo in the project named The University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS). Following blood sample collection, participants were required to answer an online questionnaire about their social and health information. We measured IgG and IgM titers against SARS-CoV-2 using iFlash-SARS-CoV-2 IgM and IgG detection kit which applies a chemiluminescent immunoassay (CLIA) for the qualitative detection. RESULTS: There were 6609 volunteers in this study. After setting the cutoff value at 10 AU/mL, 32 (0.48%) were positive for IgG and 16 (0.24%) for IgM. Of six participants with a history of COVID-19, five were positive for IgG, whereas all were negative for IgM. The median titer of IgG was 0.40 AU/mL and 0.39 AU/mL for IgM. Both IgG and IgM titers were affected by gender, age, smoking status, and comorbidities. CONCLUSIONS: Positive rates of IgG and IgM titers were relatively low in our university. Serum levels of these antibodies were affected by several factors, which might affect the clinical course of COVID-19.

Epithelial Expression of YAP and TAZ Is Sequentially Required in Lung Development.

TAZ (transcriptional coactivator with PDZ-binding motif) and YAP (Yes-associated protein) are key molecules of the Hippo pathway. Recent studies revealed that these molecules are essential in lung development; however, the precise signaling cascade involving these molecules and the differences in their roles during lung development remain unknown. We aimed to investigate YAP and TAZ functions using lung epithelium-specific Taz and Yap conditional knockout mice. We generated lung epithelium-specific Taz and Yap conditional knockout mice and investigated the functions of YAP and TAZ in lung development. Selective TAZ deficiency in mouse lung epithelial cells resulted in abnormal alveolarization, which mimics lung emphysema, in adults, whereas YAP deficiency caused disruption of bronchial morphogenesis during the embryonic stage. We report that TAZ and YAP are sequentially expressed in the lung and that this could explain their different phenotypes. Furthermore, we report that YAP stimulates Shh (Sonic hedgehog) expression and regulates the FGF (fibroblast growth factor)-SHH feedback loop, thereby contributing to normal bronchial morphogenesis. We also found that TGF-ß (transforming growth factor-ß) stimulation induced Shh expression in the lung epithelial cells, and both TAZ and YAP are essential in this novel pathway. Our results provide a novel insight into the molecular mechanisms underlying lung development and contribute to a better understanding of the characteristics of TAZ and YAP.

Active mTOR in Lung Epithelium Promotes Epithelial-Mesenchymal Transition and Enhances Lung Fibrosis.

The mTOR pathway is one of the key signal cascades in the pathogenesis of idiopathic pulmonary fibrosis. Previous studies have mainly focused on this pathway in the fibroblasts and/or myofibroblasts, but not in the epithelial cells. In this study, we sought to investigate the role of the mTOR pathway in lung epithelial cells in lung fibrosis. Using Sftpc-mTORSL1+IT transgenic mice, in which active mTOR is conditionally expressed in lung epithelial cells, we assessed the effects of chronically activated mTOR in lung epithelial cells on lung phenotypes as well as bleomycin-induced lung fibrosis. Furthermore, we isolated alveolar epithelial cell type 2 from mice and performed RNA sequencing. Sftpc-mTORSL1+IT transgenic mice had no obvious abnormal findings, but, after bleomycin administration, showed more severe fibrotic changes and lower lung compliance than control mice. RNA sequencing revealed Angptl4 (angiopoietin-like protein 4) as a candidate downstream gene of the mTOR pathway. In vitro studies revealed that ANGPTL4, as well as mTOR, promoted tight junction vulnerability and epithelial-mesenchymal transition. mTOR activation in lung epithelial cells promoted lung fibrosis and the expression of ANGPTL4, a novel downstream target of the mTOR pathway, which could be related to the etiology of fibrosis.

Naftopidil reduced the proliferation of lung fibroblasts and bleomycin-induced lung fibrosis in mice.

Naftopidil, an α-1 adrenoceptor antagonist with few adverse effects, is prescribed for prostate hyperplasia. Naftopidil inhibits prostate fibroblast proliferation; however, its effects on lung fibroblasts and fibrosis remain largely unknown. Two normal and one idiopathic pulmonary fibrosis human lung fibroblast lines were cultured with various naftopidil concentrations with or without phenoxybenzamine, an irreversible α-1 adrenoceptor inhibitor. We examined the incorporation of 5-bromo-2'-deoxyuridine into DNA and lactic acid dehydrogenase release by enzyme-linked immunosorbent assay, cell cycle analysis by flow cytometry, scratch wound-healing assay, and mRNA expressions of type IV collagen and α-smooth muscle actin by polymerase chain reaction. Effects of naftopidil on bleomycin-induced lung fibrosis in mice were evaluated using histology, micro-computed tomography, and surfactant protein-D levels in serum. Naftopidil, dose-dependently but independently of phenoxybenzamine, inhibited 5-bromo-2'-deoxyuridine incorporation in lung fibroblasts. Naftopidil induced G1 cell cycle arrest, but lactic acid dehydrogenase release and migration ability of lung fibroblasts were unaffected. Naftopidil decreased mRNA expressions of type IV collagen and α-smooth muscle actin in one normal lung fibroblast line. Histological and micro-computed tomography examination revealed that naftopidil attenuated lung fibrosis and decreased serum surfactant protein-D levels in bleomycin-induced lung fibrosis in mice. In conclusion, naftopidil may have therapeutic effects on lung fibrosis.

Pleural thickening on screening chest X-rays: a single institutional study.

Although pleural thickening is a common finding on routine chest X-rays, its radiological and clinical features remain poorly characterized. Our investigation of 28,727 chest X-rays obtained from annual health examinations confirmed that pleural thickening was the most common abnormal radiological finding. In most cases (92.2%), pleural thickening involved the apex of the lung, particularly on the right side; thus, it was defined as a pulmonary apical cap. Pleural thickening was more common in males than in females and in current smokers or ex-smokers than in never smokers. The prevalence increased with age, ranging from 1.8% in teenagers to 9.8% in adults aged 60 years and older. Moreover, pleural thickening was clearly associated with greater height and lower body weight and body mass index, suggesting that a tall, thin body shape may predispose to pleural thickening. These observations allowed us to speculate about the causative mechanisms of pleural thickening that are attributable to disproportionate perfusion, ventilation, or mechanical forces in the lungs.

CISH is a negative regulator of IL-13-induced CCL26 production in lung fibroblasts.

BACKGROUND: Bronchial asthma is a chronic airway disease characterized by eosinophilic airway inflammation. Lung fibroblasts activated by IL-13 serve as important sources of chemokines, such as eotaxins, contributing to persistent eosinophilic inflammation. Src-homology 2-containing protein (CISH), belonging to the suppressor of cytokine signaling (SOCS) family, acts as a negative regulator of cytokine induction. The aim of this study was to elucidate the role of CISH in the production of eosinophil chemotactic chemokines in human lung fibroblasts. METHODS: Normal human lung fibroblasts were stimulated by IL-13, and global gene expression profile was assessed by cDNA microarray. Expression changes and downstream of IL-13 signaling were evaluated by quantitative RT-PCR, ELISA or western blotting. Loss- and gain-of-function analyses of CISH were performed by small interfering RNA and vector overexpression, respectively. RESULTS: Ingenuity pathway analysis revealed that IL-13 induced chemokine signaling, including the eotaxin family, while significantly suppressing IFN-α/ß signaling. Among eight SOCS family members, CISH was most strongly induced by IL-13 via phosphorylation of signal transducer and activator of transcription 6 (STAT6). Loss- and gain-of-function studies demonstrated that CISH negatively regulated the expression of CCL26. CONCLUSIONS: These findings suggest that CISH plays a key role in the eosinophilic inflammation associated with bronchial asthma by regulating IL-13-induced CCL26 production. Augmentation of CISH function could be a novel approach for treating eosinophilic inflammation in severe asthma.

Venous thromboembolic events in patients with lung cancer treated with cisplatin-based versus carboplatin/nedaplatin-based chemotherapy.

An association between chemotherapy and venous thromboembolic events (VTEs) in patients with cancer is well established, with cisplatin (CDDP) being one of the most well-studied risk factors. However, whether CDDP is more strongly associated with occurrence of VTEs than carboplatin (CBDCA) or nedaplatin (CDGP) is controversial. Our purposes were to characterize patients with lung cancer and in-hospital VTEs, identify risk factors associated with VTEs, and compare the risks associated with CDDP-based versus CBDCA/CDGP-based chemotherapy. We retrospectively identified patients with lung cancer who underwent platinum-based chemotherapy from April 2012 to March 2015 from a national inpatient database in Japan. We used multivariable logistic regression analysis to analyze associations between various factors, including chemotherapy regimens and VTE. Of 235 104 eligible patients, 675 (0.29%) had VTEs after receiving platinum-based chemotherapy while hospitalized. Multivariable analysis showed that age, activity of daily living index, and invasive medical procedures were significant risk factors for the occurrence of VTE. Furthermore, CDDP-based chemotherapy was associated with a higher rate of VTE than CBDCA/CDGP-based chemotherapy (adjusted odds ratio: 1.35; 95% confidence interval: 1.08-1.68; P<0.01). In conclusion, CDDP-based chemotherapy is a stronger risk factor for VTEs than CBDCA/CDGP-based chemotherapy in patients with lung cancer.

Adjuvant chemotherapy versus chemoradiotherapy for small cell lung cancer with lymph node metastasis: a retrospective observational study with use of a national database in Japan.

BACKGROUND: The optimal postoperative treatment strategy for small cell lung cancer (SCLC) remains unclear, especially in patients with lymph node metastasis. We aimed to compare the outcomes of patients with SCLC and lymph node metastasis treated with postoperative adjuvant chemotherapy or chemoradiotherapy. METHODS: We retrospectively collected data on patients with postoperative SCLC diagnosed with N1 and N2 lymph node metastasis from the Diagnosis Procedure Combination database in Japan, between July 2010 and March 2015. We extracted data on patient age, sex, comorbidities, and TNM classification at lung surgery; operative procedures, chemotherapy drugs, and radiotherapy during hospitalization; and discharge status. Recurrence-free survival was compared between the chemotherapy and chemoradiotherapy groups using multivariable Cox regression analysis. RESULTS: Median recurrence-free survival was 1146 days (95% confidence interval [CI], 885-1407) in the chemotherapy group (n = 489) and 873 days (95% CI, 464-1282) in the chemoradiotherapy group (n = 75). There was no significant difference between these after adjusting for patient backgrounds (hazard ratio, 1.29; 95% CI, 0.91-1.84). CONCLUSIONS: There was no significant difference in recurrence-free survival between patients with SCLC and N1-2 lymph node metastasis treated with postoperative adjuvant chemotherapy and chemoradiotherapy. Further randomized clinical trials are needed to address this issue.

Quercetin restores corticosteroid sensitivity in cells from patients with chronic obstructive pulmonary disease.

Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD). Oxidative stress from cigarette smoke and chronic inflammation is likely to induce this corticosteroid insensitivity. Quercetin is a polyphenol that has been reported to be an active oxygen scavenger as well as a functional adenosine monophosphate-activated protein kinase (AMPK) activator. The aim of this study was to investigate the effect of quercetin on corticosteroid responsiveness in COPD cells. Corticosteroid sensitivity was examined in human monocytic U937 cells exposed to cigarette smoke extract (CSE) and peripheral blood mononuclear cells (PBMC) collected from patients with COPD. Corticosteroid sensitivity was determined as the dexamethasone concentration causing 40% inhibition of tumor necrosis factor alpha-induced CXCL8 production (Dex-IC40) in the presence or absence of quercetin. In U937 cells, treatment with quercetin activated AMPK and induced expression of nuclear factor erythroid 2-related factor 2, and consequently reversed CSE-induced corticosteroid insensitivity. PBMC from patients with COPD showed corticosteroid insensitivity compared with those from healthy volunteers, and treatment with quercetin restored corticosteroid sensitivity. In conclusion, quercetin restores corticosteroid sensitivity, and has the potential to be a novel treatment in combination with corticosteroids in COPD.

Restoration of Corticosteroid Sensitivity in Chronic Obstructive Pulmonary Disease by Inhibition of Mammalian Target of Rapamycin.

RATIONALE: Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD). Several molecular mechanisms have been proposed, such as activations of the phosphoinositide-3-kinase/Akt pathway and p38 mitogen-activated protein kinase. However, the mechanism for corticosteroid resistance is still not fully elucidated. OBJECTIVES: To investigate the role of mammalian target of rapamycin (mTOR) in corticosteroid sensitivity in COPD. METHODS: The corticosteroid sensitivity of peripheral blood mononuclear cells collected from patients with COPD, smokers, and nonsmoking control subjects, or of human monocytic U937 cells exposed to cigarette smoke extract (CSE), was quantified as the dexamethasone concentration required to achieve 30% inhibition of tumor necrosis factor-α-induced CXCL8 production in the presence or absence of the mTOR inhibitor rapamycin. mTOR activity was determined as the phosphorylation of p70 S6 kinase, using Western blotting. MEASUREMENTS AND MAIN RESULTS: mTOR activity was increased in peripheral blood mononuclear cells from patients with COPD, and treatment with rapamycin inhibited this as well as restoring corticosteroid sensitivity. In U937 cells, CSE stimulated mTOR activity and c-Jun expression, but pretreatment with rapamycin inhibited both and also reversed CSE-induced corticosteroid insensitivity. CONCLUSIONS: mTOR inhibition by rapamycin restores corticosteroid sensitivity via inhibition of c-Jun expression, and thus mTOR is a potential novel therapeutic target for COPD.

The incidence and risk factors of asymptomatic primary spontaneous pneumothorax detected during health check-ups.

BACKGROUND: Patients with primary spontaneous pneumothorax (PSP) usually complain of sudden-onset dyspnea and pleuritic chest pain. However, asymptomatic PSP has been incidentally detected on chest X-rays. In this study, we analyzed the incidence, characteristics, risk factors, and prognosis of asymptomatic PSP detected during regular medical check-ups in university students. METHODS: In this study, 101,709 chest X-rays were performed during medical check-ups for students at the University of Tokyo between April 2011 and March 2016. Among them, 43 cases of asymptomatic PSP (0.042%) were detected. We calculated the lung collapse rate of pneumothorax using Kircher's method. We also analyzed risk factors associated with asymptomatic PSP using characteristics inspected in medical check-ups. RESULTS: The incidence of asymptomatic PSP was significantly higher in men than in women (0.050% vs 0.018%). Multivariate analysis revealed an association of younger age, greater height, lower body mass index, and greater height growth per year with an increased risk of asymptomatic PSP in male students. Mild lung collapse (<10%) was present in 22 of 43 students with asymptomatic PSP; among these, eight students eventually underwent an invasive therapy. CONCLUSIONS: The prevalence of asymptomatic PSP among university students was as high as 0.042%. In addition to known risk factors for conventional PSP, greater height growth was a risk factor for asymptomatic PSP. Careful follow-up is very important because a considerable number of patients with mild lung collapse eventually require an invasive medical procedure.

Screening for Systemic Diseases Associated with Dental Self-Care in Japanese Adolescents.

Background: Toothbrushing is important for maintaining oral health and preventing periodontal disease. However, the association between toothbrushing and systemic diseases remains unclear in adolescence. In this study, the association between dental self-care (frequency and duration of toothbrushing) and systemic diseases/disorders in adolescents was examined. Methods: We conducted a retrospective review of mandatory medical questionnaires administered during legally mandated freshman medical checkups between 2017 and 2019 at the University of Tokyo, Japan. Out of 9376 total responses, 9098 cases involving individuals under the age of 20 were included in the analysis. Respondents were classified into three groups based on their daily toothbrushing frequency: "1 time or less", "twice", and "3 times or more". For the duration of each toothbrushing session, they were classified into three groups: "1 min or less", "2-3 min", and "4 min or more". A statistical analysis was performed by Pearson's χ2 test and multinomial logistic regression analysis. Results: Regarding frequency of daily toothbrushing: The χ2 test showed no significant relationship between frequency of toothbrushing and 17 systemic diseases/disorders. A multivariate analysis found that gingival bleeding and sex were independent factors. The risk of gingival bleeding decreased dramatically with increased frequency of toothbrushing (odds ratio (OR): 0.428; 95% confidence interval (CI), 0.366-0.501; p < 0.001). Regarding the amount of time spent on toothbrushing: The χ2 test showed atopic dermatitis and arrhythmia were significantly associated with the duration of toothbrushing (p = 0.032 and p = 0.016, respectively). In the multivariate analysis, atopic dermatitis, gingival bleeding, and sex were independent factors regarding the duration of toothbrushing; longer brushing time was associated with a lower risk of atopic dermatitis (OR: 0.731, 95% CI: 0.578-0.924, p = 0.009) and a lower risk of gingival bleeding (OR: 0.643, 95% CI: 0.567-0.729, p < 0.001). Conclusions: Dental self-care was most strongly associated with gingival bleeding, while the risk of atopic dermatitis was found to increase with shorter toothbrushing times. The results suggest that dental self-care during adolescence is important not only for oral health but also for general health.

Reduction in the need for surgery and mortality after early administration of fibrinolytics following empyema drainage.

OBJECTIVES: Although intrapleural administration of fibrinolytics is an important treatment option for the management of empyema, the addition of fibrinolytics failed to reduce the need for surgery and mortality in previous randomized controlled trials. This study aimed to investigate the effects of administrating fibrinolytics in the early phase (within 3 days of chest tube insertion) of empyema compared with late administration or no administration. METHODS: We used the Japanese Diagnosis Procedure Combination Inpatient Database to identify patients aged ≥16 years who were hospitalized and underwent chest tube drainage for empyema. A 1:2 propensity score matching and stabilized inverse probability of treatment weighting were conducted. RESULTS: Among the 16 265 eligible patients, 3082 and 13 183 patients were categorized into the early and control group, respectively. The proportion of patients who underwent surgery was significantly lower in the early fibrinolytics group than in the control group; the odds ratio (95% confidence interval) was 0.69 (0.54-0.88) in the propensity score matching (P = 0.003) and 0.64 (0.50-0.80) in the stabilized inverse probability of treatment weighting analysis (P < 0.001). All-cause 30-day in-hospital mortality, length of hospital stay, duration of chest tube drainage, and total hospitalization costs were also more favourable in the early fibrinolytics group. CONCLUSIONS: The early administration of fibrinolytics may reduce the need for surgery and death in adult patients with empyema.

A Japanese herbal medicine (kampo), hochuekkito (TJ-41), has anti-inflammatory effects on the chronic obstructive pulmonary disease mouse model.

Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway.