記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Respiratory diseases, such as chronic obstructive pulmonary disease(COPD)and asthma, are becoming increasingly prevalent in super-aging societies. In Japan, the estimated prevalence of COPD among individuals aged 40 years and above is 8.6%, while asthma affects about 10% of adults. These statistics highlight the similarities between COPD and asthma in clinical settings. Both diseases involve chronic airway inflammation and present with symptoms such as chronic cough, sputum production, wheezing, and dyspnea. Exacerbations of these symptoms and complications are critical concerns during the perioperative period. COPD, often caused by long-term smoking, leads to irreversible airway and lung damage, while asthma is characterized by episodic and reversible airway constriction due to chronic inflammation. COPD diagnosis involves spirometry and the exclusion of other diseases, with treatment goals focusing on symptom improvement and risk reduction through smoking cessation, pharmacotherapy(mainly bronchodilators), and non-pharmacological methods(such as pulmonary rehabilitation). Asthma management aims to control inflammation and prevent exacerbations using inhaled corticosteroids and bronchodilators as standard treatments. Perioperative management of both diseases involves improving respiratory function with pharmacotherapy, careful anesthesia selection, and early postoperative mobilization. Consultation with respiratory specialists is recommended for effective management, especially in complex cases.

DOI： 10.11477/mf.1436205039

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Uncontrolled type 2 immunity by type 2 helper T (Th2) cells causes intractable allergic diseases; however, whether the interaction of CD4+ T cells shapes the pathophysiology of allergic diseases remains unclear. We identified a subset of Th2 cells that produced the serine proteases granzyme A and B early in differentiation. Granzymes cleave protease-activated receptor (Par)-1 and induce phosphorylation of p38 mitogen-activated protein kinase (MAPK), resulting in the enhanced production of IL-5 and IL-13 in both mouse and human Th2 cells. Ubiquitin-specific protease 7 (USP7) regulates IL-4-induced phosphorylation of STAT3, resulting in granzyme production during Th2 cell differentiation. Genetic deletion of Usp7 or Gzma and pharmacological blockade of granzyme B ameliorated allergic airway inflammation. Furthermore, PAR-1+ and granzyme+ Th2 cells were colocalized in nasal polyps from patients with eosinophilic chronic rhinosinusitis. Thus, the USP7-STAT3-granzymes-Par-1 pathway is a potential therapeutic target for intractable allergic diseases.

DOI： 10.1073/pnas.2302903120

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Allergic rhinitis is a growing problem worldwide. Currently the only treatment that can modify the disease is antigen-specific immunotherapy, but its mechanism of action is not fully understood. OBJECTIVE: We comprehensively investigated the role and changes of antigen-specific T cells before and after sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. METHODS: We cultured peripheral blood mononuclear cells obtained both before and 1 year after initiating SLIT and used a combination of single-cell RNA sequencing and repertoire sequencing. To investigate biomarkers, we used cells from patients participating a phase 2/3 trial of SLIT tablets for Japanese cedar pollinosis and cells from outpatients with good and poor response. RESULTS: Antigen-stimulated culturing after SLIT led to clonal expansion of TH2 and regulatory T cells, and most of these CD4+ T cells retained their CDR3 regions before and after treatment, indicating antigen-specific clonal responses and differentiation resulting from SLIT. However, SLIT reduced the number of clonal functional TH2 cells but increased the trans-type TH2 cell population that expresses musculin (MSC), TGF-β, and IL-2. Trajectory analysis suggested that SLIT induced clonal differentiation of the trans-type TH2 cells differentiated into regulatory T cells. Using real-time PCR, we found that the MSC levels increased in the active SLIT group and those with good response after 1 year of treatment. CONCLUSION: The combination of single-cell RNA sequencing and repertoire analysis helped reveal part of the underlying mechanism: SLIT promotes the expression of MSC on pathogenic TH2 cells and suppresses their function. MSC may be a potential biomarker of SLIT for allergic rhinitis.

DOI： 10.1016/j.jaci.2022.06.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Prognostic factors have yet to be established for patients with interstitial lung disease (ILD). We aimed to clarify whether the Charlson Comorbidity Index score (CCIS) could help predict disease prognosis in patients with ILD. METHODS: Among ILD patients treated between April 2013 and April 2017, we retrospectively assessed the relationship between baseline clinical parameters including age, sex, CCIS, ILD diagnosis, pulmonary function test results, and 3-year ILD-related events including cause-specific death and first acute exacerbation (AE). RESULTS: We assessed 180 patients (mean age, 74 years), all of whom underwent pulmonary function testing including percentage predicted diffusion capacity for carbon monoxide (%DLco). Underlying pathologies included idiopathic pulmonary fibrosis (IPF) in 57 cases, idiopathic nonspecific interstitial pneumonia (iNSIP) and collagen vascular disease-related interstitial pneumonia in 117 cases, and chronic hypersensitivity pneumonia (CHP) in 6 cases. A composite scoring system comprising IPF diagnosis, CCIS, and %DLco provided a favorable C-index (0.825) for predicting 3-year ILD-related events. The nomogram for 3-year prognosis revealed the largest contributions from CCIS, %DLco and IPF diagnosis. CONCLUSIONS: This composite scoring system accounting for IPF diagnosis, CCIS, and %DLco could provide a useful tool for predicting prognosis in relatively mild ILD patients tolerated to pulmonary diffusion capacity testing.

DOI： 10.21037/jtd-20-1302

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The mechanisms underlying interstitial lung disease (ILD) are characterized by variable inflammation or fibrosis of the pulmonary interstitium. A negative heart sign (NHS) on 67Ga scintigrams of patients with ILD is due to considerably increased inflammatory activity in the lungs. We retrospectively analyzed relationships between NHS and established biomarkers of disease severity in patients with ILD. Among 81 consecutive non-smoking patients with ILD (mean age, 63 years) who had been hospitalized between April 2009 and October 2011, we selected 52 who had been assessed by 67Ga scintigraphy. We then evaluated relationships between NHS and blood biomarkers, pulmonary function and high-resolution computed tomography (HRCT). Among these 52 patients, 10 showed idiopathic pulmonary fibrosis and 42 had other ILD. Multivariate analysis with stepwise variable selection, serum surfactant protein (SP)-A (OR (odds ratio), 1.026; 95%CI (confidence interval), 1.003-1.050; P = 0.024) and inflammation index calculated from HRCT findings (OR, 1.358; 95%CI, 1.079-1.709; P = 0.009) were significant predictors of an NHS. Serum SP-A offered 85% sensitivity and 75% specificity for predicting NHS at an optimal cut-off of 45.8 ng/mL. Serum SP-A concentrations correlated positively with inflammation index (r = 0.344, P = 0.015). In conclusion, serum SP-A might serve as a surrogate biomarker for predicting an NHS in patients with ILD.

DOI： 10.18999/nagjms.82.3.499

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00060&link_issn=&doc_id=20220705010004&doc_link_id=issn%3D0039-2359%26volume%3D282%26issue%3D1%26spage%3D19&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0039-2359%26volume%3D282%26issue%3D1%26spage%3D19&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

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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