記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although corticosteroids are expected to be a candidate therapy for coronavirus disease 2019 (COVID-19) through the suppression of cytokine production, the efficacy in non-severe patients who do not require supplemental oxygen remains controversial. The aim of this study was to investigate the efficacy of corticosteroid therapy for non-severe patients. METHODS: We performed a retrospective observational study for 10 patients with non-severe COVID-19 who received corticosteroid therapy at our institute between July 1, 2020, and January 31, 2021. RESULTS: The median age of the 10 patients was 60 years, and nine patients were male. Nine of the 10 patients had multiple comorbid conditions (e.g., hypertension, diabetes and obesity). Although blood oxygen saturation was maintained above 95%, all patients showed persistent fever and deterioration of their chest imaging findings. Thus, we decided to initiate corticosteroid treatment. The median duration from the onset of symptoms to the initiation of corticosteroid therapy was eight days. All patients used dexamethasone (6 mg/day) as corticosteroid therapy, and the median period was 7.5 days. After the start of corticosteroid therapy, all patients showed a rapid clinical improvement, and no patients showed severe progression. CONCLUSION: The latest World Health Organization guidance recommends against corticosteroid treatment for non-severe patients. In this report, we showed that the early administration of corticosteroids during the non-critical phase, when oxygen supplementation is not required, was useful for the early improvement and prevention of severe disease in patients with risk factors for severe COVID-19 and worsening clinical symptoms.

DOI： 10.1272/jnms.JNMS.2022_89-409

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：英語  

A 59-year-old woman complaining of wet cough, hemoptysis, slight fever, anorexia, and malaise was admitted to hospital with suspected lobar pneumonia. She received treatment for myocardial infarction and deep venous thrombosis caused by familial protein C deficiency. Rapid deterioration due to respiratory failure occurred despite intensive care with broad-spectrum antibiotics. At a later date, sputum examination revealed the presence of Aspergillus niger. Based on clinical and autopsy findings, she was diagnosed with acute respiratory failure due to pulmonary aspergillosis with acute fibrinous and organizing pneumonia. This is the first reported case of pulmonary aspergillosis with acute fibrinous and organizing pneumonia complicated by calcium oxalate resulting from Aspergillus niger infection, leading to severe inflammation and tissue injury in the lungs.

DOI： 10.1016/j.rmcr.2022.101641

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記述言語：日本語   出版者・発行元：(株)ライフメディコム  

副鼻腔気管支症候群(sinobronchial syndrome:SBS)は上気道の炎症である慢性副鼻腔炎と、下気道の炎症である気管支拡張症、慢性気管支炎、びまん性汎細気管支炎(diffuse panbronchiolitis:DPB)などが同時に存在する病態である。SBSは慢性湿性咳嗽を呈する疾患のひとつとして重要で、日本呼吸器学会による『咳嗽に関するガイドライン』(2005年発刊)でその診断基準が示された。また、後鼻漏による咳嗽-後鼻漏症候群(postnasal drip syndrome:PNDS)も耳鼻科専門医との連携が必要な慢性咳嗽の原因として、呼吸器内科医が理解しておくべき疾患として重要である。本稿では、日本呼吸器学会より2019年に発表された『咳嗽・喀痰の診療ガイドライン2019』を中心に、SBS、PNDSの診断・治療について概説する。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)ライフメディコム  

副鼻腔気管支症候群(sinobronchial syndrome:SBS)は上気道の炎症である慢性副鼻腔炎と、下気道の炎症である気管支拡張症、慢性気管支炎、びまん性汎細気管支炎(diffuse panbronchiolitis:DPB)などが同時に存在する病態である。SBSは慢性湿性咳嗽を呈する疾患のひとつとして重要で、日本呼吸器学会による『咳嗽に関するガイドライン』(2005年発刊)でその診断基準が示された。また、後鼻漏による咳嗽-後鼻漏症候群(postnasal drip syndrome:PNDS)も耳鼻科専門医との連携が必要な慢性咳嗽の原因として、呼吸器内科医が理解しておくべき疾患として重要である。本稿では、日本呼吸器学会より2019年に発表された『咳嗽・喀痰の診療ガイドライン2019』を中心に、SBS、PNDSの診断・治療について概説する。(著者抄録)

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Idiopathic pulmonary fibrosis (IPF), a progressive disorder of unknown etiology, is characterized by pathological lung fibroblast activation and proliferation resulting in abnormal deposition of extracellular matrix proteins within the lung parenchyma. The pathophysiological roles of exosomal microRNAs in pulmonary fibrosis remain unclear; therefore, we aimed to identify and characterize fibrosis-responsive exosomal microRNAs. We used microRNA array analysis and profiled the expression of exosome-derived miRNA in sera of C57BL/6 mice exhibiting bleomycin-induced pulmonary fibrosis. The effect of microRNAs potentially involved in fibrosis was then evaluated in vivo and in vitro. The expression of exosomal microRNA-16 was increased by up to 8.0-fold on day 14 in bleomycin-treated mice, compared to vehicle-treated mice. MicroRNA-16 mimic administration on day 14 after bleomycin challenge ameliorated pulmonary fibrosis and suppressed lung and serum expression of secreted protein acidic and rich in cysteine (SPARC). Pretreatment of human lung fibroblasts with the microRNA-16 mimic decreased the expression of rapamycin-insensitive companion of mTOR (Rictor) and TGF-β1-induced expression of SPARC. This is the first study reporting the anti-fibrotic properties of microRNA-16 and demonstrating that these effects occur via the mTORC2 pathway. These findings support that microRNA-16 may be a promising therapeutic target for IPF.

DOI： 10.1016/j.yexcr.2020.112416

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(公社)日本化学療法学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：日本結核・非結核性抗酸菌症学会関東支部学会・日本呼吸器学会関東地方会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We report a case of pneumonitis with alveolar hemorrhage induced by herbal medicines in a 73-year-old woman who was admitted to our hospital because of dyspnea and an abnormal shadow on a chest radiograph. She had received treatment with numerous drugs, including the herbal medicines Seisin-renshi-in, Chotosan, Rikkunshi-to, and Shakuyakukannzo-to. Chest radiography revealed diffuse ground-glass shadows in both lungs, and bronchoalveolar lavage fluid was progressively hemorrhagic. A culture of the fluid showed no evidence of microorganisms. Moreover, there were no findings suggestive of rheumatic disease or vasculitides. On the basis of this evidence, we suspected drug-induced diffuse alveolar hemorrhage. She discontinued all medicines and started treatment with corticosteroids. Her respiratory condition and chest radiographic findings improved. The timing of administration and rechallenge with other drugs suggested that the herbal medicines were the causative drugs. The primary concern was Seisin-renshi-in, because it contains Ougon (skullcap; a known cause of pneumonitis) and because a drug lymphocyte stimulation test was positive for Seisin-renshi-in. This is the first report indicating that Seisin-renshi-in may cause diffuse alveolar hemorrhage. Diffuse alveolar hemorrhage due to herbal medicines is a rare but emergent disorder. Therefore, treating physicians should be aware that it may be caused by herbal medicines, including Seisin-renshi-in.

DOI： 10.1272/jnms.JNMS.2019_86-504

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：英語  

We report a case of pneumonitis with alveolar hemorrhage induced by herbal medicines. A 73-year-old female was admitted to our hospital due to dyspnea and the presence of an abnormal shadow on the chest roentgenogram. She had received treatment with numerous drugs, including the following herbal medicines: Seisin-renshi-in, Chotosan, Rikkunshi-to, and Shakuyakukannzo-to. Chest radiography revealed diffuse ground-glass shadows in both lungs. The bronchoalveolar lavage fluid was progressively bloody. In addition, culture did not show the presence of microorganisms in the fluid. Moreover, there were no findings suggestive of rheumatic disease or vasculitides. Based on this evidence, we suspected drug-induced diffuse alveolar hemorrhage. She discontinued the use of all previous agents, and received treatment with corticosteroids. Her respiratory condition and the chest roentgenogram improved. According to the timing of administration and rechallenge with other drugs, the herbal medicines were suspected to be the causative drugs. Among those, Seisin-renshi-in was the most suspicious. Firstly, Seisin-renshi-in contains Ougon (skullcap), which is known to cause pneumonitis. Secondly, a dr

DOI： 10.1272/jnms.JNMS.2019_86-504

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives Acute exacerbation of idiopathic pulmonary fibrosis (IPF-AE) has been recognized as a fatal pulmonary disorder, but the exact prognostic factors are unknown. The aim of the present study was to analyze the clinical characteristics of patients with IPF-AE and identify the prognostic factors. Methods The medical records of 59 cases of IPF-AE were retrospectively reviewed. Clinical data, laboratory data, radiographic findings, treatment, and time from the onset of symptoms to the initiation of corticosteroid pulse therapy, i.e. symptom duration, and outcome were analyzed. Results The IPF Stage, Gender-Age-Physiology (GAP) Index, symptom duration, and the high-resolution computed tomography (HRCT) score were significantly related to the prognosis in the univariate analysis. In the multivariate analysis, the symptom duration remained a significant prognostic factor (hazard ratio of 1-day increase, 1.11; 95% confidence interval, 1.01-1.15; p=0.0427). The area under the receiver operating characteristics curve of symptom duration was statistically significant for survivors versus non-survivors (area under the curve, 0.73; p=0.012). The survival period was significantly shorter in the late-treatment groups (≥5 days; n=30) than in the early-treatment groups (<5 days; n=29; log-rank test; p<0.0001). Conclusion The time interval between the onset of symptoms and the initiation of corticosteroid pulse therapy may be an independent prognostic factor in patients with IPF-AE.

DOI： 10.2169/internalmedicine.9331-17

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記述言語：英語   出版者・発行元：Blackwell Publishing  

DOI： 10.1111/ajd.12643

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

Pathogenesis of idiopathic pulmonary fibrosis (IPF) remains unclear. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that participates in the assembly and turnover of the extra cellular matrix, whose expression is regulated by transforming growth factor (TGF)-beta 1 through activation of mammalian target of rapamycin complex 2 (mTORC2). Exchange factor found in platelets, leukemic, and neuronal tissues (XPLN) is an endogenous inhibitor of mTORC2. However, whether XPLN modulates SPARC expression remains unknown. Herein, we investigated the regulatory mechanisms of XPLN in human lung fibroblasts. Effect of XPLN on mTORC2 activity was evaluated by silencing XPLN in human foetal lung fibroblasts (HFL-1 cells), using small interfering RNA. SPARC expression was quantified by quantitative real-time RT-PCR and western blotting. Fibroblasts were treated with TGF-beta 1, histone deacetylase (HDAC) inhibitors, entinostat, or vorinostat, to assess their effects on XPLN expression. Moreover, the effect of mTORC1 inhibition on SPARC and XPLN was examined. XPLN depletion stimulated SPARC expression and Akt phosphorylation on Ser473. TGF-beta 1 treatment down-regulated XPLN via Smad 2/3. XPLN mRNA expression was up-regulated upon treatment with HDAC inhibitors in a concentration dependent manner, and TGF-beta 1-induced SPARC expression was reversed by entinostat treatment. mTORC1 inhibition by rapamycin and Raptor depletion stimulated SPARC expression. In conclusion, this is the first study describing the involvement of XPLN in the regulation of SPARC. These findings may help uncover the regulatory mechanisms of the mTORC2-SPARC axis. The up-regulation of XPLN by HDAC inhibitors may be a novel therapeutic approach in patients with IPF. (C) 2017 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.pupt.2017.03.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MATTIOLI 1885  

Background: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) was recently proposed as an entity to be included among rare idiopathic interstitial pneumonias (IIPs). However, the cause, clinical features and prognosis of this rare entity have not been elucidated. Objectives: We aimed to examine the clinical features, outcomes and prognostic factors for IPPFE in comparison to those of idiopathic pulmonary fibrosis (IPF). Methods: We retrospectively analyzed 20 patients with IPPFE and 71 with IPF. We compared clinical features, blood examination data, and respiratory functions at the time of diagnosis. Results: The IPPFE group had a significantly lower body mass index (BMI), percent forced vital capacity (% FVC), total lung capacity (% TLC) and expiratory reserve volume (% ERV), as well as a higher residual volume to TLC (RV/TLC) ratio than the IPF group. The annual FVC changes in the IPPFE group (-326ml/year) were significantly larger than those in the IPF group (-142ml/year). Survival was significantly poorer in the IPPFE than in the IPF group (P = 0.021). BMI and the partial pressure of oxygen in arterial blood (PaO2) were significantly related to the outcome of IPPFE. Conclusions: Our present results indicate the prognosis of IPPFE patients to be poorer than that of IPF patients. We advocate that BMI and arterial blood PaO2 be determined at the first visit as these parameters are closely related to patients' outcomes. Prospective evaluation of IPPFE starting in the subclinical phase is necessary to assure that appropriate measures are taken before progression.

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記述言語：日本語   出版者・発行元：(公財)日本感染症医薬品協会  

菌の増殖速度、培養上清による気道上皮細胞への傷害性、トータルプロテアーゼ(TP)、ピオシアニン(PC)産生量、バイオフィルム(BF)形成能、遊走アッセイ(MA)、病原因子の遺伝子発現への影響について検討した。クラリスロマイシン(CAM)長期服用中の慢性気道感染症患者より分離された緑膿菌(Pa)11株、CAM未投与患者から分離されたPa2株(ムコイド型)、標準株としてPa P.aeruginosa PAO1の合計14株を対象とした。増殖速度はCAM投与菌群ではCAM未投与菌群と比べ増殖速度は緩徐な傾向であった。CAM投与菌の培養上清による肺胞上皮細胞への傷害性はCAM投与菌群においてCAM未投与菌群と比べ低かった。TPアッセイはCAM投与菌11株中7株でTPが非産生、CAM未投与菌では2株中2株ともTPを産生し、CAM投与菌ではTP産生株が少ない傾向にあった。PC産生量はCAM投与菌群ではCAM未投与菌群と比べ低い傾向であった。CAM投与菌群とCAM未投与菌群間でBF形成に有意差はなかったがCAM投与菌では菌株間でBF形成にばらつきが認められた。MAについて遊走は両群間に差は認められなかった。病原因子の遺伝子発現への影響は、CAM投与菌11株中4株でQS関連遺伝子であるLasI、rhlI遺伝子の発現を認めなかったのに対し、CAM未投与菌では2株中2株ともに発現を認めた。aprA、exoS、exoT、exoYでは両群間に差を認めなかった。

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a high mortality rate. Signalling pathways activated by several tyrosine kinase receptors are known to be involved in lung fibrosis, and this knowledge has led to the development of the triple tyrosine kinase inhibitor nintedanib, an inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR), for the treatment of IPF. Pulmonary surfactant protein D (SP-D), an important biomarker of IPF, reportedly attenuates bleomycin-induced pulmonary fibrosis in mice. In this study, we investigated whether nintedanib modulates SP-D expression in human lung epithelial (A549) cells using quantitative real-time reverse transcriptase polymerase chain reaction and western blotting. To investigate the mechanisms underlying the effects of nintedanib, we evaluated the phosphorylation of c-Jun N-terminal kinase (JNK) and its downstream target c-Jun. The effect of the JNK inhibitor SP600125 on c-Jun phosphorylation was also tested. Activation of activator protein-1 (AP-1) was examined using an enzyme-linked immunosorbent assay-based test, and cell proliferation assays were performed to estimate the effect of nintedanib on cell proliferation. Furthermore, we treated mice with nintedanib to examine its in vivo effect on SP-D levels in lungs. These experiments showed that nintedanib up-regulated SP-D messenger RNA expression id a dose-dependent manner at concentrations up to 5 mu M, with significant SP-D induction observed at concentrations of 3 mu M and 5 mu M, in comparison with that observed in vehicle controls. Nintedanib stimulated a rapid increase in phosphorylated JNK in A549 cells within 30 min of treatment and stimulated c-Jun phosphorylation, which was inhibited by the JNK inhibitor SP600125. Additionally, nintedanib was found to activate AP-1. A549 cell proliferation was not affected by nintedanib at any of the tested concentrations. Moreover, blocking FGFR, PDGFR, and VEGFR function did not affect nintedanib-induced SP-D expression, suggesting that nintedanib mediates its effects through a mechanism that is distinct from its known role as a tyrosine kinase inhibitor. Nintedanib is also reported to inhibit Src kinase although pre-treatment of cells with a Src kinase inhibitor had no effect on nintedanib-induced SP-D expression. Increased expression of SFTPD mRNA and SP-D protein in the lungs of nintedanib-treated mice was also observed. In this work, we demonstrated that nintedanib up-regulated SP-D expression in A549 cells via the JNK-AP-1 pathway and did not affect cell proliferation. This is the first report describing SP-D induction by nintedanib. (C) 2015 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.pupt.2015.03.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Bone marrow-derived fibrocytes reportedly play important roles in the pathogenesis of idiopathic pulmonary fibrosis. Pirfenidone is an anti-fibrotic agent; however, its effects on fibrocytes have not been investigated. The aim of this study was to investigate whether pirfenidone inhibits fibrocyte pool size in the lungs of bleomycin-treated mice.
Methods: Bleomycin (100 mg/kg) was infused with osmotic pumps into C57BL/6 mice, and pirfenidone (300 mg/kg/day) was orally administered daily for 2 wk. The lungs were removed, and single-cell suspensions were subjected to fluorescence-activated cell sorter (FACS) analysis to detect fibrocytes, which were defined as CD45 and collagen-I double-positive cells. Immunohistochemistry was performed on the lung specimens to quantify fibrocytes. Chemokines in the lung digests were measured with enzyme-linked immunosorbent assay. The effect of pirfenidone on alveolar macrophages was evaluated with bronchoalveolar lavage (BAL). In a therapeutic setting, pirfenidone administration was initiated 10 days after bleomycin treatment. For chemotaxis assay, lung fibrocytes were isolated with immunomagnetic selection (CD45-positive mesenchymal cells) after culture and allowed to migrate toward chemokines in the presence or absence of pirfenidone. Moreover, the effect of pirfenidone on the expression of chemokine receptors on fibrocytes was evaluated.
Results: Pirfenidone significantly ameliorated bleomycin-induced pulmonary fibrosis as assessed with quantitative histology and collagen measurement. Fibrocyte pool size in bleomycin-treated mice lungs was attenuated from 26.5% to 13.7% by pirfenidone on FACS analysis. This outcome was also observed in a therapeutic setting. Immunohistochemistry revealed that fibrocytes were significantly decreased by pirfenidone administration compared with those in bleomycin-treated mice (P = 0.0097). Increased chemokine (CC motif) ligand-2 (CCL2) and CCL12 production in bleomycin-treated mouse lungs was significantly attenuated by pirfenidone (P=0.0003 and P &lt; 0.0001, respectively). Pirfenidone also attenuated macrophage counts stimulated by bleomycin in BAL fluid. Fibrocyte migration toward CCL2 and chemokine (CC motif) receptor-2 expression on fibrocytes was significantly inhibited by pirfenidone in vitro.
Conclusions: Pirfenidone attenuated the fibrocyte pool size in bleomycin-treated mouse lungs via attenuation of CCL2 and CCL12 production in vivo, and fibrocyte migration was inhibited by pirfenidone in vitro. Fibrocyte inhibition is considered a mechanism of anti-fibrotic action of pirfenidone.

DOI： 10.1186/1465-9921-15-16

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC MICROBIOLOGY  

The capsular antigen detection (CAD) kit is widely used in clinics to detect Streptococcus pneumoniae infection from urine, because it is rapid, convenient, and effective. However, there are several disadvantages, including false-positive results in children colonized with S. pneumoniae and prolonged positive readings even after the bacteria have been cleared. RP-L7/L12 is a component of the 50S ribosome that is abundant in all bacteria and is specific for each bacterial species. We investigated whether RP-L7/L12 could be used to accurately diagnose pneumococcal pneumonia infection in mouse models of pneumonia and colonization generated by infecting CBA/JN or CBA/N mice, respectively, with S. pneumoniae strain 741. RP-L7/L12 detection by enzyme-linked immunosorbent assay accurately assessed active lung infection, as RP-L7/L12 levels decreased simultaneously with the bacterial lung burden after imipenem administration in the pneumonia mouse model. Based on the data, antibodies detecting RP-L7/L12 were applied to rapid immunochromatographic strips (ICS) for urine sample testing. When we compared the ICS test with the CAD kit in the pneumonia model, the results correlated well. Interestingly, however, when the lung bacterial burden became undetectable after antibiotic treatment, the ICS test was correspondingly negative, even though the same samples tested by the CAD kit remained positive. Similarly, while the ICS test exhibited negative results in the nasal colonization model, the CAD kit demonstrated positive results. Bacterial RP-L7/L12 may be a promising target for the development of new methods to diagnose infectious disease. Further studies are warranted to determine whether such a test could be useful in children.

DOI： 10.1128/JCM.01871-12

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Histiocytic sarcoma (HS) is a rare malignancy of soft tissues with an unknown etiology. The CHOP (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride and prednisolone) regimen is often adopted as first-line chemotherapy; however, its therapeutic efficacy against HS is usually low. We herein first present the case of a patient with HS who was infected with human immunodeficiency virus-1 (HIV) in whom treatment with a combination of CHOP and antiretroviral therapy (ART) was successful. The patient has been in complete remission for 12 months following the discontinuation of chemotherapy under continuous ART. This case report may help to promote further investigation of both HS and HIV-related malignancy.

DOI： 10.2169/internalmedicine.52.0523

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記述言語：日本語   出版者・発行元：特定非営利活動法人 日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.35.Special_S208_2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

This report presents the cases of three patients with fatal pneumonia that was highly suspected to be Pneumocystis pneumonia (PCP) based on serological diagnosis. Their chest radiographs showed bilateral pneumonia and each had presented with severe respiratory failure requiring mechanical ventilation when they arrived at the hospital. Although bronchoscopical sampling could not be performed, their chest computed tomography imaging and a marked elevation of serum KL-6 and -d-glucan levels were characteristic of Pneumocystis pneumonia. All three were found to have been treated with temozolomide after surgery for malignant glioma. Temozolomide can cause Pneumocystis pneumonia. The three patients did not receive prophylactic medication against Pneumocystis pneumonia during treatment with temozolomide, and their histories suggested that all had delayed seeking treatment. It may be difficult to diagnose Pneumocystis pneumonia because the symptoms are not specific for Pneumocystis pneumonia and they tend to be similar to those of common respiratory infectious diseases. Therefore, patients who receive temozolomide therapy have the potential to develop fatal pneumonia and should be carefully observed. The patients should also be adequately informed about Pneumocystis pneumonia, and prophylaxis against Pneumocystis pneumonia should be considered proactively before treatment with temozolomide is initiated.

DOI： 10.1093/jjco/hys058

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Background Pneumocystis jiroveci pneumonia (PCP) is a potentially fatal complication in interstitial pneumonia patients receiving glucocorticoid therapy. Prophylaxis of PCP during glucocorticoid therapy is an important issue in the treatment of interstitial pneumonia.
Objective We evaluated the prophylactic effect of sulfamethoxasole-trimethoprim (TMP-SMX) in interstitial pneumonia patients receiving glucocorticoids.
Methods We retrospectively analyzed 74 interstitial pneumonia patients who received glucocorticoid therapy.
Results Seven of the 74 patients developed PCP. At the time of diagnosis of PCP, the mean duration of glucocorticoid therapy was 71 days and the mean daily dose of prednisolone was 37 mg. Among the 7 patients, the circulating CD4+ lymphocyte count was 370/mu l on average and it was over 200/mu l in 3 cases. The PCP patients showed a significant reduction of the lymphocyte count at 4 weeks after initiation of steroid therapy. None of the patients who received prophylactic TMP-SMX therapy developed PCP even if the CD4+ lymphocyte count was less than 200/mu l.
Conclusion Interstitial pneumonia patients receiving glucocorticoid therapy can benefit from TMP-SMX prophylaxis against PCP. Development of PCP cannot be ruled out in patients with a CD4+ lymphocyte count of greater than 200/mu l.

DOI： 10.2169/internalmedicine.47.0402

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective Low-dose, long-term macrolide therapy has been shown to be effective for the treatment of diffuse paribronchiolitis (DPB) and similar disorders in terms of the presence of airway mucus hypersecretion such as bronchiectasis, chronic bronchitis and sinobronchial syndrome. However, there are some patients, especially advanced cases, whose volume of sputum does not decrease sufficiently with macrolide therapy. These patients suffer from copious expectoration. There is currently no effective treatment, and an effective therapy is therefore urgently required. The aim of this study was to clarify whether or not the inhalation of tiotropium improves the symptoms in these cases. Methods Tiotropium (18 mu g/day) was administered to patients with DPB and similar disorders with airway mucus hypersecretion who did not respond to macrolide. The symptoms were evaluated by a visual analog scale (VAS) prior to and at 1 and 3 months after tiotropium administration. Radiological and pulmonary function tests were also performed to evaluate the effects of tiotropium. Results Thirteen patients (DPB 5, sinobronchial syndrome 5, bronchiectasis 3) were enrolled. The VAS scores were dramatically improved after the introduction of tiotropium. FEV1 was significantly improved after 3 months of treatment with tiotropium. In contrast, the radiological findings remained unchanged. Conclusion Tiotropium improved the symptoms of cough, sputum and breathlessness in the macrolide-resistant cases of DPB or similar disorders. These beneficial effects might be due to the suppression of airway secretion through the anticholinergic effect of tiotropium on the submucosal gland, however, the long-term efficiency of this treatment still needs to be further assessed.

DOI： 10.2169/internalmedicine.47.0568

Web of Science

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：日本結核病学会関東支部学会・日本呼吸器学会関東地方会  

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記述言語：日本語   出版者・発行元：日本サルコイドーシス  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本結核病学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.6_695_4

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(公社)日本化学療法学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.Special_S253_4

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.Special_S316_1

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記述言語：日本語   出版者・発行元：(公社)日本化学療法学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.37.Special_S310_2

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

背景. 肺癌の縦隔リンパ節転移診断には、従来よりCT、FDG-PET、縦隔鏡検査などが用いられるが、近年超音波気管支鏡ガイド下針生検(endobronchial ultrasound-guided transbronchial needle aspiration:EBUS-TBNA)の臨床応用が検討されつつある。症例. 79歳女性。両側鼠径部リンパ節腫脹を主訴に近医を受診。胸部CT上右S5結節影、両側網状粒状影、両側肺門・縦隔リンパ節腫脹を認めた。右S5結節影に対する経気管支肺生検(TBLB)にて肺腺癌と診断した。またツベルクリン反応陰性、血清ACE高値よりサルコイドーシスが疑われ、TBLBにて非乾酪性類上皮細胞肉芽腫を認め、サルコイドーシスと診断した。EBUS-TBNAによる気管分岐下リンパ節生検はclass IIであり、臨床病期cT1bN0M0、stage IAと診断し、右中葉切除術を施行した。結論. サルコイドーシス合併肺癌においては、縦隔リンパ節転移の評価に難渋するが、EBUS-TBNAによる術前評価の上手術を施行し得た1例を経験したので報告する。(著者抄録)

DOI： 10.18907/jjsre.36.3_239

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：日本内科学会-関東地方会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-BLACKWELL  

Web of Science

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記述言語：日本語   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

背景。血管型Ehlers-Danlos症候群(vEDS)は、血管や組織の脆弱性のため、侵襲的処置に関して慎重な対応が必要である。症例。36歳男性。腹痛を主訴に近医を受診した際、多発性動脈瘤・動脈解離を指摘された。血管疾患による突然死の家族歴もあり、vEDSが疑われ紹介となった。遺伝子解析中に難治性の右気胸を2ヵ月間で計3回発症した。3回目の胸腔ドレナージは効果なく、Endobronchial Watanabe Spigot(EWS)による気管支充填術を施行したところ、エアリークは消失し、右肺拡張も得られたためドレーン抜去に成功した。皮膚線維芽細胞からのcDNAクローニングの結果、COL3A1遺伝子変異が同定され、vEDSの診断に至った。結論。組織脆弱性を理由に外科的治療を選択しにくい難治性気胸に対し、気管支充填術は有用な治療法の1つと考える。(著者抄録)

DOI： 10.18907/jjsre.35.5_506

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.35.1_116_3

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記述言語：日本語   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：(有)科学評論社  

CiNii Books

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(NPO)日本肺癌学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(一社)日本結核病学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(NPO)日本呼吸器内視鏡学会  

DOI： 10.18907/jjsre.34.Special_S189_3

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(一社)日本感染症学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：(株)医薬ジャーナル社  

副鼻腔気管支症候群(sinobronchial syndrome;SBS)は、上気道の炎症と下気道の炎症が同時に存在する病態で、本邦ではびまん性汎細気管支炎(diffuse panbronchiolitis;DPB)が代表的な疾患と1つとされる。本稿では、慢性咳嗽の主な原因の1つであるSBSを、その代表的疾患であるDPBを中心に解説する。(著者抄録)

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(公社)日本化学療法学会  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：(株)メディカルレビュー社  

近年のトピックスである高病原性鳥インフルエンザウイルス(H5N1)や2009年パンデミックインフルエンザAウイルス(H1N1)、SARSコロナウイルス(SARS-CoV)による肺炎は、重症例で急性肺損傷(acute lung injury;ALI)/急性呼吸(窮)促迫症候群(acute respiratory distress syndrome;ARDS)を発症し、致死的になることが知られている。その病理像の多くはびまん性肺胞障害(DAD)を示し、抗ウイルス薬投与とともにARDSに対する治療を必要とする。本稿では、DADの誘因となるこれら3つのウイルスによる肺炎の病態と治療について、現在までに得られている知見を中心に概説する。(著者抄録)

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（その他）   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   掲載種別：会議報告等   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）   出版者・発行元：(株)医薬ジャーナル社  

マクロライド系とは、12員環以上の大きなラクトン環を有する天然化合物の総称で、疎水性が高く、組織・細胞内への移行がよいことが特徴とされる抗菌薬である。マクロライド系抗菌薬は、主にグラム陽性菌や非定型病原体に抗菌力を示し、呼吸器感染症を中心とした感染症の治療薬として有用である。また、びまん性細気管支炎(DPB)に対するEM(エリスロマイシン)少量長期療法の有効性やウイルス感染に対する効果などにみられる、抗菌以外の作用も注目されており、新たな研究が試みられている。本稿では、古くて新しい抗菌薬であるマクロライド系抗菌薬について、最新の知見を交え概説する。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)呼吸研究  

特発性肺線維症(IPF)は原因不明かつ慢性の経過をとる予後不良な疾患である。従来から行われていたステロイドや免疫抑制薬による治療は反応性が乏しく、予後の改善をもたらしていない。近年、IPFは肺障害が先行し、正常な再生修復ができないために線維化が進行する病態であると理解され、インターフェロンγ(IFN-γ)やピルフェニドン(pirfenidone)などによる抗線維化治療や、オキシダント制御を目的としたN-アセチルシステインの有効性が注目されている。なかでもピルフェニドンは本邦で行われた無作為化二重盲検比較試験において、呼吸機能を改善させ、急性増悪の発症率を低下させるなど、現在抗線維化薬として最も期待されている薬剤で、国内では2007年3月に申請がなされ、承認完了が待たれている状態である。本稿では、臨床試験の結果を中心に、ピルフェニドンの有用性について概説する。(著者抄録)

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

37歳女。9年前に不明熱、頸部リンパ節腫脹で慢性Epstein-Barr(EB)ウイルス感染症および慢性気管支炎と診断され、その後徐々に湿性咳嗽が出現し、胸部CTで小葉中心性の粒状影を指摘された。ロキシスロマイシンで2年間は症状改善傾向を認めたが、その後徐々に増悪し、両側足趾扁平上皮癌手術目的で入院の際に精査を行った。検査所見で慢性活動性EBウイルス感染症を認め、入院後VCA-IgG、EA-IgGは徐々に上昇し、EBNA-IgGは陰性であった。生検した肺組織でEBウイルスDNA PCRが陽性であった。肺胞領域ではII型肺胞上皮の過形成、間質にリンパ球主体の炎症細胞浸潤が目立ち、肺胞腔内には壁在型の線維化を軽度認めた。比較的中枢の気管支壁にはリンパ球、好中球の浸潤を認め、慢性活動性気道炎症の所見であった。入院5ヵ月目に急性骨髄性白血病を発症し、化学療法を開始したところ、EBウイルスは検出感度以下となり、画像所見、呼吸機能、喀痰量などの自覚症状も改善した。

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

副鼻腔気管支症候群(Sinobronchial Syndrome:SBS)は上気道の炎症である慢性副鼻腔炎と、下気道の炎症である気管支拡張症、慢性気管支炎、びまん性汎細気管支炎(diffuse panbronchiolitis:DPB)などの慢性非特異性気管支炎が同時に存在する病態で、特にわが国においては、DPBはSBSの代表として重要な疾患と認識されている。SBSの症状は、8週間以上続く慢性の湿性咳嗽、後鼻漏、鼻汁、咳払いなど副鼻腔炎に伴う自覚症状と上・中咽頭における粘液性ないし粘液膿性の分泌物、cobblestone appearanceといった副鼻腔炎に伴う他覚症状、検査所見では、副鼻腔炎を示唆する画像所見を認めることを特徴とする。治療は、14員環マクロライド系抗菌薬や去痰薬が症状改善に有効で、特にDPBでは、工藤によるマクロライド少量療法の導入により、予後の著明な改善が得られ、早期に診断・治療がなされた場合、完治しうる疾患となった。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

特発性肺線維症(IPF)は慢性の経過をとる予後不良な疾患である.従来のステロイドに代表される治療は予後の改善に結びついていないが,ピルフェニドンはわが国で行われた無作為化重盲検比較試験において呼吸機能を改善,急性増悪の発症率を低下させたことから,現在抗線維化薬としてもっとも期待されている.本稿ではピルフェニドン臨床試験の結果を中心に,ピルフェニドンの有用性について概説する(著者抄録)

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

57歳男.約10年前,び漫性汎細気管支炎(DPB)と診断され,入退院を繰り返していた.マクロライド療法が無効であったため,10回目の入院時にtiotropium投与を開始したところ,喀痰量は減少し,退院1年経過後も急性増悪を起こさず病状は安定している.そこで,tiotropiumによる気道分泌抑制が,マイクロライド無効症例の病状を改善する可能性について検討した.対象は,マイクロライド療法が無効なDPB 3例,副鼻腔気管支症候群2例,気管支拡張症1例,primary ciliary dyskinesia 1例であった.その結果,tiotropiumは難治性気道感染症の咳嗽や喀痰症状を改善することが示唆された

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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