Tezepelumab improved chronic eosinophilic pneumonia in severe asthma patients with liver cirrhosis

Systemic administration of corticosteroids is used in the treatment of chronic eosinophilic pneumonia (CEP). However, in patients with CEP as well as other comorbidities, the adverse effects of corticosteroids should be minimized as much as possible. A 71-year-old woman was presented with aggravating asthma with CEP and sinusitis, and she had uncompensated liver cirrhosis (LC) with a Child-Pugh score of 7. Initial treatment with a low dose of oral corticosteroids (OCSs) in combination with tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) antibody, resulted in rapid improvement of asthma and CEP without deteriorating LC. Sinusitis also improved after ceasing OCS. This case suggested that tezepelumab may be useful as a treatment option for patients with CEP, especially those with liver dysfunction

Dipeptidyl peptidase-4 is highly expressed in bronchial epithelial cells of untreated asthma and it increases cell proliferation along with fibronectin production in airway constitutive cells

DPP4 mRNA showed significant correlation with iNOS mRNA in the freshly isolated BECs from snBA. (PPTX 1447 kb

ケッカクセイ キョウマクエン ノ シンダン ニオケル キョクショ マスイカ キョウコウキョウ ノ ユウヨウセイ ニ カンスル ケントウ

局所麻酔下胸腔鏡が施行され,胸膜生検検体にて乾酪性肉芽腫を認め,結核性胸膜炎と診断された症例の臨床的検討を行った.対象は,1999 年12 月から2011 年1 月までに局所麻酔下胸腔鏡により病理学的に診断された結核性胸膜炎32例.男性25例,女性7例.平均年齢62.8歳( 24〜89歳).右側胸水が14例,左側胸水が16 例,両側胸水が2 例.胸水リンパ球比率の平均は90.9%,胸水ADA の平均は69.1 IU/l であった.胸水のTb-PCR( tuberculosis-polymerase chain reaction) は全例で陰性,胸水抗酸菌培養は1例のみ陽性で,陽性率は極めて低値であった.胸腔鏡所見では,壁側胸膜のびまん性の白色小結節病変が最も多く19例( 59.4%)で認められ,胸膜肥厚や癒着,血管増生などの非特異的な所見も高率に認めた.胸膜生検検体の結核菌培養陽性率は約40%であった.結節病変を認めた例では,結節病変を認めなかった例と比較してより年齢が若く,発症から検査までの日数が有意に短かった.結核性胸膜炎の診断は,胸水穿刺だけでは診断効率が低く,局所麻酔下胸腔鏡を行うことにより診断効率は大きく向上し,内科医が施行できる安全性の高い極めて有用性の高い検査法といえる.We reviewed our patients with tuberculous pleurisy underwentmedical thoracoscopy. From December 1999 toJanuary 2011, 32 patients were diagnosed as having tuberculouspleurisy by pleural biopsy pathologically. The typicalthoracoscopic findings of tuberculous pleurisy such as diffusesmall white nodules on the parietal pleura were seen in23 cases (71.9 %). Non-specific pleural findings such asthickness on the pleura or adhesion were seen in 9 cases(22.2 %). In all these patients, pathological diagnoses of tuberculouspleurisy were made by pleural biopsies. Sincemedical thoracoscopy is useful for the diagnosis of tuberculouspleurisy, it is recommended as a diagnostic procedurefor cases with pleural effusion

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Measurement of PM2.5 and Water-Soluble Ions at Central Tokyo, Japan and Source Apportionment

Air pollution by fine particulate matter, PM2.5 has been inviting considerable concerns in East Asia. This study then aimed to characterize PM2.5 and its water-soluble ions collected at Shibuya, central Tokyo, Japan from July 2013 to May 2015, in order to better understand the air pollution mechanism and potential sources of PM2.5 of the city. Analytical results showed the PM2.5 was a mixture of aggregates of formless particles and its concentration ranged from 5.4 to 39μg/m3, with a mean of 14 ± 6.7μg/m3 (n=46). SO42- and NH4+ were abundant in PM2.5 and their presence mostly determined the variation of PM2.5 level. High concentration episodes were found in the season when air masses came from Asian continent, and a long-range transport of urban aerosols and soil-derived particles was suggested by changes in the chemical compositions

Lipid Accumulation in Peripheral Blood Dendritic Cells and Anticancer Immunity in Patients with Lung Cancer

We studied the subsets of peripheral blood dendritic cells (DCs) and lipid accumulation in DCs to investigate the involvement of DCs in the decreased anticancer immunity of advanced lung cancer patients. We analyzed the population of DC subsets in peripheral blood using flow cytometry. We then determined lipid accumulation in the DCs using BODIPY 650/665, a fluorophore with an affinity for lipids. Compared with healthy controls, the number of DCs in the peripheral blood of treatment-naive cancer patients was significantly reduced. In patients with stage III + IV disease, the numbers of myeloid DCs (mDCs) and plasmacytoid DCs were also significantly reduced. Lipid accumulation in DCs evaluated based on the fluorescence intensity of BODIPY 650/665 was significantly higher in stage III + IV lung cancer patients than in the controls. In the subset analysis, the fluorescence was highest for mDCs. The intracellularly accumulated lipids were identified as triglycerides. A decreased mixed leukocyte reaction was observed in the mDCs from lung cancer patients compared with those from controls. Taken together, the results show that lung cancer patients have a notably decreased number of peripheral blood DCs and their function as antigen-presenting cells is decreased due to their high intracellular lipid accumulation. Thereby, anticancer immunity is suppressed

Measurement of PM2.5 and Water-Soluble Ions at Central Tokyo, Japan and Source Apportionment

Air pollution by fine particulate matter, PM2.5 has been inviting considerable concerns in East Asia. This study then aimed to characterize PM2.5 and its water-soluble ions collected at Shibuya, central Tokyo, Japan from July 2013 to May 2015, in order to better understand the air pollution mechanism and potential sources of PM2.5 of the city. Analytical results showed the PM2.5 was a mixture of aggregates of formless particles and its concentration ranged from 5.4 to 39μg/m3, with a mean of 14 ± 6.7μg/m3 (n=46). SO42- and NH4+ were abundant in PM2.5 and their presence mostly determined the variation of PM2.5 level. High concentration episodes were found in the season when air masses came from Asian continent, and a long-range transport of urban aerosols and soil-derived particles was suggested by changes in the chemical compositions