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Transbronchial Lung Cryobiopsy Performed with Cone Beam Computed Tomography Guidance Versus Fluoroscopy: A Retrospective Cohort Review. 在锥形束计算机断层扫描引导下进行经支气管肺冷冻活组织检查与透视检查的对比:回顾性队列研究。
IF 5 2区 医学
Lung Pub Date : 2024-02-01 Epub Date: 2023-12-21 DOI: 10.1007/s00408-023-00663-1
Syed O Ali, Carson Castellani, Bryan S Benn
{"title":"Transbronchial Lung Cryobiopsy Performed with Cone Beam Computed Tomography Guidance Versus Fluoroscopy: A Retrospective Cohort Review.","authors":"Syed O Ali, Carson Castellani, Bryan S Benn","doi":"10.1007/s00408-023-00663-1","DOIUrl":"10.1007/s00408-023-00663-1","url":null,"abstract":"<p><strong>Purpose: </strong>Determining the cause of interstitial lung disease (ILD) remains challenging. While surgical lung biopsy remains the gold standard approach, risks associated with it may be prohibitive. Transbronchial lung cryobiopsy (TBLC) is a minimally invasive alternative with an improved safety profile and acceptable diagnostic accuracy. We retrospectively assessed whether the use of Cone Beam computed tomography guidance for TBLC (TBLC-CBCT) improves safety and diagnostic yield compared to performing TBLC with fluoroscopic guidance (TBLC-F).</p><p><strong>Methods: </strong>A retrospective cohort review of 120 patients presenting for evaluation of newly diagnosed ILD was performed. Demographic data, pulmonary function test values, chest imaging pattern, procedural information, and final multidisciplinary discussion (MDD) diagnosis were recorded.</p><p><strong>Results: </strong>62 patients underwent TBLC-F and 58 underwent TBLC-CBCT. Patients undergoing TBLC-CBCT were older (67.86 ± 10.97 vs 61.45 ± 12.77 years, p = 0.004) and had a higher forced vital capacity percent predicted (73.80 ± 17.32% vs 66.00 ± 17.45%, p = 0.03) compared to the TBLC-F group. The average probe-to-pleura distance was 5.1 ± 2.3 mm in the TBLC-CBCT group with 4.0 ± 0.3 CBCT spins performed. Pneumothorax occurred more often in the TBLC-F group (n = 6, 9.7%) compared to the TBLC-CBCT group (n = 1, 1.7%, p = 0.06). Grade 2 bleeding only occurred in the TBLC-F group (n = 4, 6.5%). A final MDD diagnosis was obtained in 89% (n = 57) of TBLC-F patients and 95% (n = 57) of TBLC-CBCT patients.</p><p><strong>Conclusions: </strong>TBLC-CBCT appears to be safer compared to TBLC-F with both approaches facilitating an MDD diagnosis. Further studies from multiple institutions randomizing patients to each modality are needed to confirm these findings.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"73-81"},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and Safety of Re-administration of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) After EGFR-TKI-Induced Interstitial Lung Disease (CS-Lung-005). 表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)诱发间质性肺病后再用药的有效性和安全性(CS-Lung-005)。
IF 5 2区 医学
Lung Pub Date : 2024-02-01 Epub Date: 2024-01-24 DOI: 10.1007/s00408-023-00669-9
Nobuhiro Kanaji, Eiki Ichihara, Takaaki Tanaka, Takashi Ninomiya, Toshiyuki Kozuki, Nobuhisa Ishikawa, Kazuya Nishii, Hiroyasu Shoda, Kakuhiro Yamaguchi, Keita Kawakado, Yuko Toyoda, Masaaki Inoue, Nobuyuki Miyatake, Naoki Watanabe, Takuya Inoue, Hitoshi Mizoguchi, Yuta Komori, Kazuki Kojima, Norimitsu Kadowaki
{"title":"Efficacy and Safety of Re-administration of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) After EGFR-TKI-Induced Interstitial Lung Disease (CS-Lung-005).","authors":"Nobuhiro Kanaji, Eiki Ichihara, Takaaki Tanaka, Takashi Ninomiya, Toshiyuki Kozuki, Nobuhisa Ishikawa, Kazuya Nishii, Hiroyasu Shoda, Kakuhiro Yamaguchi, Keita Kawakado, Yuko Toyoda, Masaaki Inoue, Nobuyuki Miyatake, Naoki Watanabe, Takuya Inoue, Hitoshi Mizoguchi, Yuta Komori, Kazuki Kojima, Norimitsu Kadowaki","doi":"10.1007/s00408-023-00669-9","DOIUrl":"10.1007/s00408-023-00669-9","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigated the safety and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) re-administration after recovery from EGFR-TKI-induced interstitial lung disease (ILD).</p><p><strong>Methods: </strong>This multicenter retrospective study collected data from consecutive advanced NSCLC patients who underwent EGFR-TKI re-administration after recovery from EGFR-TKI-induced ILD.</p><p><strong>Results: </strong>Fifty-eight patients were registered. The grades of initial TKI-induced ILD were grade 1 to 4. TKIs used for re-administration were erlotinib for 15 patients, osimertinib for 15, gefitinib for 14, afatinib for 13 patients, and dacomitinib for 1 patient. ILD recurred in 13 patients (22.4%), comprising 3 patients with grade 1, 6 patients with grade 2, and 4 patients with grade 3. No significant associations were found between ILD recurrence and age, smoking history, performance status, time from initial ILD to TKI re-administration, or concomitant corticosteroid use. However, the incidence of ILD recurrence was high in cases of repeated use of gefitinib or erlotinib or first time use of osimertinib at TKI re-administration. The ILD recurrence rate was lowest in patients treated with first time use of gefitinib (8%) or erlotinib (8%), followed by patients treated with repeated use of osimertinib (9%). The response rate, median progression-free survival by TKI re-administration, and median overall survival were 55%, 9.6 and 84.8 months, respectively.</p><p><strong>Conclusion: </strong>This study showed that EGFR-TKI re-administration is a feasible and effective treatment for patients who recovered from EGFR-TKI-induced ILD. Our results indicate that re-administration of EGFR-TKI is an important option for long-term prognosis after recovery from EGFR-TKI-induced ILD.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"63-72"},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Therapeutic Landscape in Chronic Cough. 慢性咳嗽的治疗前景
IF 5 2区 医学
Lung Pub Date : 2024-02-01 Epub Date: 2023-12-21 DOI: 10.1007/s00408-023-00666-y
Jaclyn A Smith
{"title":"The Therapeutic Landscape in Chronic Cough.","authors":"Jaclyn A Smith","doi":"10.1007/s00408-023-00666-y","DOIUrl":"10.1007/s00408-023-00666-y","url":null,"abstract":"<p><p>In recent years, there has been a substantial increase in the development of antitussive therapies and the first new therapy, gefapixant has been licenced in Europe. This review describes current unlicenced treatments for chronic cough and details treatments currently in development for refractory chronic cough and cough in idiopathic pulmonary fibrosis, as well as compounds previously explored.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"5-16"},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diaphragm Ultrasonography: Reference Values and Influencing Factors for Thickness, Thickening Fraction, and Excursion in the Seated Position. 横膈膜超声:厚度、增厚分数和坐位偏移的参考值和影响因素。
IF 5 2区 医学
Lung Pub Date : 2024-02-01 Epub Date: 2023-11-29 DOI: 10.1007/s00408-023-00662-2
Toru Yamada, Taro Minami, Syumpei Yoshino, Ken Emoto, Suguru Mabuchi, Ryoichi Hanazawa, Akihiro Hirakawa, Masayoshi Hashimoto
{"title":"Diaphragm Ultrasonography: Reference Values and Influencing Factors for Thickness, Thickening Fraction, and Excursion in the Seated Position.","authors":"Toru Yamada, Taro Minami, Syumpei Yoshino, Ken Emoto, Suguru Mabuchi, Ryoichi Hanazawa, Akihiro Hirakawa, Masayoshi Hashimoto","doi":"10.1007/s00408-023-00662-2","DOIUrl":"10.1007/s00408-023-00662-2","url":null,"abstract":"<p><strong>Introduction: </strong>Measurements of diaphragm function by ultrasonography are affected by body position, but reference values in the seated position have not been established for an Asian population. This study aimed to determine reference values for diaphragm thickness, thickening fraction, and dome excursion by ultrasonography and to investigate the effects of sex, height, and body mass index.</p><p><strong>Methods: </strong>Diaphragm ultrasonography was performed on 109 seated Japanese volunteers with normal respiratory function who were enrolled between March 2022 and January 2023. Thickness, thickening fraction, and excursion were measured. Reference values and the measurement success rate were calculated. Multivariate analysis adjusted for sex, height, and body mass index was performed.</p><p><strong>Results: </strong>The measurement success rate was better for thickness than for excursion. The mean (lower limit of normal) values on the right/left sides were as follows. During quiet breathing, thickness at end expiration(mm) was 1.7 (0.9)/1.6 (0.80), thickening fraction(%) was 50 (0.0)/52 (0.0), and excursion(cm) was 1.7 (0.5)/1.9 (0.5). During deep breathing, the thickening fraction was 111 (24)/107 (22), and the excursion was 4.4 (1.7)/4.1 (2.0). In multivariate analysis, body mass index was positively associated with thickness but not with the thickening fraction.</p><p><strong>Conclusion: </strong>The reference values in this study were smaller than those in previous reports from Europe. Considering that thickness is influenced by body mass index, using Western reference values in Asia, where the average body mass index is lower, might not be appropriate. The thickening fraction in deep breathing is unaffected by other items and can be used more universally.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"83-90"},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138451864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study. PRISM 研究中使用 2 型生物制剂的严重嗜酸性粒细胞性哮喘患者早期和晚期肺功能改善的预测因素
IF 5 2区 医学
Lung Pub Date : 2024-02-01 Epub Date: 2024-01-22 DOI: 10.1007/s00408-024-00670-w
Duong Duc Pham, Ji-Hyang Lee, Hyouk-Soo Kwon, Woo-Jung Song, You Sook Cho, Hyunkyoung Kim, Jae-Woo Kwon, So-Young Park, Sujeong Kim, Gyu Young Hur, Byung Keun Kim, Young-Hee Nam, Min-Suk Yang, Mi-Yeong Kim, Sae-Hoon Kim, Byung-Jae Lee, Taehoon Lee, So-Young Park, Min-Hye Kim, Young-Joo Cho, ChanSun Park, Jae-Woo Jung, Han Ki Park, Joo-Hee Kim, Ji-Yong Moon, Pankaj Bhavsar, Ian Adcock, Kian Fan Chung, Tae-Bum Kim
{"title":"Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.","authors":"Duong Duc Pham, Ji-Hyang Lee, Hyouk-Soo Kwon, Woo-Jung Song, You Sook Cho, Hyunkyoung Kim, Jae-Woo Kwon, So-Young Park, Sujeong Kim, Gyu Young Hur, Byung Keun Kim, Young-Hee Nam, Min-Suk Yang, Mi-Yeong Kim, Sae-Hoon Kim, Byung-Jae Lee, Taehoon Lee, So-Young Park, Min-Hye Kim, Young-Joo Cho, ChanSun Park, Jae-Woo Jung, Han Ki Park, Joo-Hee Kim, Ji-Yong Moon, Pankaj Bhavsar, Ian Adcock, Kian Fan Chung, Tae-Bum Kim","doi":"10.1007/s00408-024-00670-w","DOIUrl":"10.1007/s00408-024-00670-w","url":null,"abstract":"<p><strong>Background: </strong>The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive.</p><p><strong>Objective: </strong>We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT.</p><p><strong>Methods: </strong>140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV<sub>1</sub>). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment.</p><p><strong>Results: </strong>More than a third of patients with SEA using BioT showed early and sustained improvements in FEV<sub>1</sub> after 1 month. A significant association was found between low baseline FEV<sub>1</sub> and high blood eosinophil count and sustained FEV<sub>1</sub> improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV<sub>1</sub> improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98]).</p><p><strong>Conclusion: </strong>Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"41-51"},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mucus Transpiration as the Basis for Chronic Cough and Cough Hypersensitivity. 粘液排出是慢性咳嗽和咳嗽过敏的基础
IF 5 2区 医学
Lung Pub Date : 2024-02-01 Epub Date: 2023-12-22 DOI: 10.1007/s00408-023-00664-0
David A Edwards, Kian Fan Chung
{"title":"Mucus Transpiration as the Basis for Chronic Cough and Cough Hypersensitivity.","authors":"David A Edwards, Kian Fan Chung","doi":"10.1007/s00408-023-00664-0","DOIUrl":"10.1007/s00408-023-00664-0","url":null,"abstract":"<p><p>Chronic cough is characterized by a state of cough hypersensitivity. We analyze the process of transpiration, by which water appears to evaporate from laryngeal and tracheal mucus as from the surface of a leaf, as a potential cause of cough hypersensitivity. In this process, osmotic pressure differences form across mucus, pulling water toward the air, and preventing mucus dehydration. Recent research suggests that these osmotic differences grow on encounter with dry and dirty air, amplifying pressure on upper airway epithelia and initiating a cascade of biophysical events that potentially elevate levels of ATP, promote inflammation and acidity, threaten water condensation, and diminish mucus water permeability. Among consequences of this inflammatory cascade is tendency to cough. Studies of isotonic, hypotonic, and hypertonic aerosols targeted to the upper airways give insights to the nature of mucus transpiration and its relationship to a water layer that forms by condensation in the upper airways on exhalation. They also suggest that, while hypertonic NaCl and mannitol may provoke cough and bronchoconstriction, hypertonic salts with permeating anions and non-permeating cations may relieve these same upper respiratory dysfunctions. Understanding of mucus transpiration and its role in cough hypersensitivity can lead to new treatment modalities for chronic cough and other airway dysfunctions promoted by the breathing of dry and dirty air.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"17-24"},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138885241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Osteopontin: A Novel Therapeutic Target for Respiratory Diseases. 骨桥蛋白:一种新的呼吸系统疾病治疗靶点。
IF 5 2区 医学
Lung Pub Date : 2024-02-01 Epub Date: 2023-12-07 DOI: 10.1007/s00408-023-00665-z
Qi Jia, Yeling Ouyang, Yiyi Yang, Shanglong Yao, Xiangdong Chen, Zhiqiang Hu
{"title":"Osteopontin: A Novel Therapeutic Target for Respiratory Diseases.","authors":"Qi Jia, Yeling Ouyang, Yiyi Yang, Shanglong Yao, Xiangdong Chen, Zhiqiang Hu","doi":"10.1007/s00408-023-00665-z","DOIUrl":"10.1007/s00408-023-00665-z","url":null,"abstract":"<p><p>Osteopontin (OPN) is a multifunctional phosphorylated protein that is involved in physiological and pathological events. Emerging evidence suggests that OPN also plays a critical role in the pathogenesis of respiratory diseases. OPN can be produced and secreted by various cell types in lungs and overexpression of OPN has been found in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), pulmonary fibrosis diseases, lung cancer, lung infection, chronic obstructive pulmonary disease (COPD), and asthma. OPN exerts diverse effects on the inflammatory response, immune cell activation, fibrosis and tissue remodeling, and tumorigenesis of these respiratory diseases, and genetic and pharmacological moudulation of OPN exerts therapeutic effects in the treatment of respiratory diseases. In this review, we summarize the recent evidence of multifaceted roles and underlying mechanisms of OPN in these respiratory diseases, and targeting OPN appears to be a potential therapeutic intervention for these diseases.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"25-39"},"PeriodicalIF":5.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment and Management of Cough in Idiopathic Pulmonary Fibrosis: A Narrative Review. 特发性肺纤维化咳嗽的评估和治疗:叙述性综述。
IF 5 2区 医学
Lung Pub Date : 2023-12-01 Epub Date: 2023-11-07 DOI: 10.1007/s00408-023-00653-3
Shangxiang Liu, Xu Ye
{"title":"Assessment and Management of Cough in Idiopathic Pulmonary Fibrosis: A Narrative Review.","authors":"Shangxiang Liu, Xu Ye","doi":"10.1007/s00408-023-00653-3","DOIUrl":"10.1007/s00408-023-00653-3","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal disease with an unknown cause. It is characterized by symptoms such as cough and breathlessness, which significantly impact patients' quality of life. Cough, in particular, has emerged as a burdensome symptom for individuals with IPF. The etiology of cough in IPF patients is believed to be complex, involving factors related to the disease itself, such as increased sensitivity of cough nerves, lung structural changes, inflammation, and genetic factors, as well as comorbidities and medication effects. Unfortunately, effective treatment options for cough in IPF remain limited, often relying on empirical approaches based on studies involving chronic cough patients in general and the personal experience of physicians. Medications such as opioids and neuromodulators are commonly prescribed but have shown suboptimal efficacy, imposing significant physical, psychological, and economic burdens on patients. However, there is hope on the horizon, as specific purinergic P2 receptor ligand-gated ion channel (P2X3) inhibitors have demonstrated promising antitussive effects in ongoing clinical trials. This review aims to provide a comprehensive overview of the evaluation and management of cough in IPF patients, as well as highlight emerging pharmacological and non-pharmacological approaches that target the cough reflex and are currently being investigated in clinical settings.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"531-544"},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of Prostaglandin-Degrading Enzyme 15-PGDH Mitigates Acute Murine Lung Allograft Rejection. 前列腺素降解酶15-PGDH的抑制减轻小鼠急性肺移植排斥反应。
IF 5 2区 医学
Lung Pub Date : 2023-12-01 Epub Date: 2023-11-07 DOI: 10.1007/s00408-023-00651-5
Ye Cui, Zhe Lv, Zeran Yang, Jianfeng Lei
{"title":"Inhibition of Prostaglandin-Degrading Enzyme 15-PGDH Mitigates Acute Murine Lung Allograft Rejection.","authors":"Ye Cui, Zhe Lv, Zeran Yang, Jianfeng Lei","doi":"10.1007/s00408-023-00651-5","DOIUrl":"10.1007/s00408-023-00651-5","url":null,"abstract":"<p><strong>Purpose: </strong>Acute rejection is a frequent complication among lung transplant recipients and poses substantial therapeutic challenges. 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme responsible for the inactivation of prostaglandin E2 (PGE2), has recently been implicated in inflammatory lung diseases. However, the role of 15-PGDH in lung transplantation rejection remains elusive. The present study was undertaken to examine the expression of 15-PGDH in rejected lung allografts and whether inhibition of 15-PGDH ameliorates acute lung allograft rejection.</p><p><strong>Methods: </strong>Orthotopic mouse lung transplantations were performed between donor and recipient mice of the same strain or allogeneic mismatched pairs. The expression of 15-PGDH in mouse lung grafts was measured. The efficacy of a selective 15-PGDH inhibitor (SW033291) in ameliorating acute rejection was assessed through histopathological examination, micro-CT imaging, and pulmonary function tests. Additionally, the mechanism underlying the effects of SW033291 treatment was explored using CD8<sup>+</sup> T cells isolated from mouse lung allografts.</p><p><strong>Results: </strong>Increased 15-PGDH expression was observed in rejected allografts and allogeneic CD8<sup>+</sup> T cells. Treatment with SW033291 led to an accumulation of PGE2, modulation of CD8<sup>+</sup> T-cell responses and mitochondrial activity, and improved allograft function and survival.</p><p><strong>Conclusion: </strong>Our study provides new insights into the role of 15-PGDH in acute lung rejection and highlights the therapeutic potential of inhibiting 15-PGDH for enhancing graft survival. The accumulation of PGE2 and modulation of CD8<sup>+</sup> T-cell responses represent potential mechanisms underlying the benefits of 15-PGDH inhibition in this model. Our findings provide impetus for further exploring 15-PGDH as a target for improving lung transplantation outcomes.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"591-601"},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71483239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chronic Cough as a Genetic Neurological Disorder? Insights from Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS). 慢性咳嗽是遗传性神经系统疾病吗?小脑共济失调伴神经病变和前庭反射综合征(CANVAS)的观察。
IF 5 2区 医学
Lung Pub Date : 2023-12-01 Epub Date: 2023-11-18 DOI: 10.1007/s00408-023-00660-4
Richard D Turner, Barnaby Hirons, Andrea Cortese, Surinder S Birring
{"title":"Chronic Cough as a Genetic Neurological Disorder? Insights from Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS).","authors":"Richard D Turner, Barnaby Hirons, Andrea Cortese, Surinder S Birring","doi":"10.1007/s00408-023-00660-4","DOIUrl":"10.1007/s00408-023-00660-4","url":null,"abstract":"<p><p>Chronic cough is common, and in many cases unexplained or refractory to otherwise effective treatment of associated medical conditions. Cough hypersensitivity has developed as a paradigm that helps to explain clinical and research observations that frequently point towards chronic cough as a neuropathic disorder. Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described neurological condition whose clinical features include gait ataxia, unsteadiness, peripheral neuropathy, and autonomic dysfunction. Chronic cough is also a common feature of the syndrome, with features of hypersensitivity, often preceding core neurological symptoms by up to 30 years or more. The genetic basis in a majority of cases of CANVAS appears to be biallelic variable repeat intron expansion sequences within RFC1, a gene normally involved in the regulation of DNA replication and repair. The same polymorphism has now been identified at an increased frequency in patients with unexplained or refractory chronic cough in the absence of defining clinical features of CANVAS. This review expands on these points, aiming to increase the awareness of CANVAS amongst clinicians and researchers working with chronic cough. We discuss the implications of a link between RFC1 disease and cough. Improved understanding of CANVAS may lead to an enhanced grasp of the pathophysiology of chronic cough, and new approaches to antitussive treatments.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":" ","pages":"511-519"},"PeriodicalIF":5.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136398088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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