Pub Date : 2025-03-01DOI: 10.1016/j.pccm.2025.02.005
Zhenyu Mao , Xiaoyan Zhu , Pengdou Zheng , Lingling Wang , Fengqin Zhang , Lixiang Chen , Ling Zhou , Wei Liu , Huiguo Liu
<div><h3>Background</h3><div>Asthma is a prevalent non-communicable disease that affects individuals of all ages and has emerged as a significant global public health concern. This study aims to conduct a comprehensive assessment of the burden of asthma worldwide, as well as at regional and national levels, utilizing the Global Burden of Diseases (GBD) 2021 database for the years 1990 to 2021.</div></div><div><h3>Methods</h3><div>This study utilized the GBD 2021 database to report the prevalent cases and incident cases of asthma, alongside age-standardized prevalence rates (ASPR), age-standardized incidence rate (ASIR), the number of disability-adjusted life years (DALYs), age-standardized DALY rates (ASDR), the number of deaths, and age-standardized mortality rates (ASMR) at global, regional, and national levels for the year 2021. Additionally, it computed the estimated annual percentage change (EAPC) for these asthma burden indicators from 1990 to 2021. This study further analyzed the levels of the above indicators in different gender and age groups, and investigated the association between asthma ASDR/ASMR levels and socio-demographic index (SDI). It also provided an analysis of the contribution of four risk factors to the overall asthma burden.</div></div><div><h3>Results</h3><div>From 1990 to 2021, the global EAPC for asthma ASIR was −1.04 (95 % confidence interval [CI]:−1.18 to −0.89), the EAPC for ASPR was −1.59 (95 % CI:−1.74 to −1.43), the EAPC for ASDR was −1.91 (95 % CI:−1.98 to −1.84), and the EAPC for ASMR was −2.03 (95 % CI:−2.09 to −1.98). In 2021, the prevalent cases of asthma remained alarmingly high at 260.48 million (95 % UI: 227.21 million to 297.97 million). Developed countries, exemplified by the United States, exhibited elevated asthma ASPR. However, the burden of asthma-related mortality and DALYs predominantly afflicted low- and middle-income nations. In China, there has been a significant decline in ASIR, ASPR, ASDR and ASMR for asthma. In most age groups, the burden of asthma among women was markedly higher than that among men, particularly evident in prevalence and DALYs. Children and the elderly bore a heavier burden of asthma. In 2021, ASDR and ASMR levels varied across countries, generally exhibiting a negative correlation with SDI levels. A high body-mass index continued to be a primary risk factor for asthma on a global scale. Decomposition analysis reveals that population growth plays a significant role in exacerbating the burden of asthma-related deaths and DALYs.</div></div><div><h3>Conclusions</h3><div>From 1990 to 2021, the burden of asthma as measured by age-standardized rate (ASR) has shown a declining trend. However, the overall burden of asthma remains significantly high. Moreover, there is a notable inequality in the burden of asthma across different regions and populations worldwide. This highlights the urgent need for countries to prioritize asthma management and control strategies to address these dis
{"title":"Global, regional, and national burden of asthma from 1990 to 2021: A systematic analysis of the global burden of disease study 2021","authors":"Zhenyu Mao , Xiaoyan Zhu , Pengdou Zheng , Lingling Wang , Fengqin Zhang , Lixiang Chen , Ling Zhou , Wei Liu , Huiguo Liu","doi":"10.1016/j.pccm.2025.02.005","DOIUrl":"10.1016/j.pccm.2025.02.005","url":null,"abstract":"<div><h3>Background</h3><div>Asthma is a prevalent non-communicable disease that affects individuals of all ages and has emerged as a significant global public health concern. This study aims to conduct a comprehensive assessment of the burden of asthma worldwide, as well as at regional and national levels, utilizing the Global Burden of Diseases (GBD) 2021 database for the years 1990 to 2021.</div></div><div><h3>Methods</h3><div>This study utilized the GBD 2021 database to report the prevalent cases and incident cases of asthma, alongside age-standardized prevalence rates (ASPR), age-standardized incidence rate (ASIR), the number of disability-adjusted life years (DALYs), age-standardized DALY rates (ASDR), the number of deaths, and age-standardized mortality rates (ASMR) at global, regional, and national levels for the year 2021. Additionally, it computed the estimated annual percentage change (EAPC) for these asthma burden indicators from 1990 to 2021. This study further analyzed the levels of the above indicators in different gender and age groups, and investigated the association between asthma ASDR/ASMR levels and socio-demographic index (SDI). It also provided an analysis of the contribution of four risk factors to the overall asthma burden.</div></div><div><h3>Results</h3><div>From 1990 to 2021, the global EAPC for asthma ASIR was −1.04 (95 % confidence interval [CI]:−1.18 to −0.89), the EAPC for ASPR was −1.59 (95 % CI:−1.74 to −1.43), the EAPC for ASDR was −1.91 (95 % CI:−1.98 to −1.84), and the EAPC for ASMR was −2.03 (95 % CI:−2.09 to −1.98). In 2021, the prevalent cases of asthma remained alarmingly high at 260.48 million (95 % UI: 227.21 million to 297.97 million). Developed countries, exemplified by the United States, exhibited elevated asthma ASPR. However, the burden of asthma-related mortality and DALYs predominantly afflicted low- and middle-income nations. In China, there has been a significant decline in ASIR, ASPR, ASDR and ASMR for asthma. In most age groups, the burden of asthma among women was markedly higher than that among men, particularly evident in prevalence and DALYs. Children and the elderly bore a heavier burden of asthma. In 2021, ASDR and ASMR levels varied across countries, generally exhibiting a negative correlation with SDI levels. A high body-mass index continued to be a primary risk factor for asthma on a global scale. Decomposition analysis reveals that population growth plays a significant role in exacerbating the burden of asthma-related deaths and DALYs.</div></div><div><h3>Conclusions</h3><div>From 1990 to 2021, the burden of asthma as measured by age-standardized rate (ASR) has shown a declining trend. However, the overall burden of asthma remains significantly high. Moreover, there is a notable inequality in the burden of asthma across different regions and populations worldwide. This highlights the urgent need for countries to prioritize asthma management and control strategies to address these dis","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 1","pages":"Pages 50-59"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.pccm.2024.12.001
Yan Xu, Ruxuan Chen, Ruili Pan, Xiaoxing Gao, Hui Huang, Mengzhao Wang
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for various malignancies by demonstrating exceptional antitumor effects and significant improvement in patient survival. Despite their overt therapeutic advantages, ICIs also induce immune-related adverse events (irAEs). Of these, checkpoint inhibitor pneumonitis (CIP) represents a prominent manifestation of pulmonary toxicity following ICI therapy, with incidence rates ranging from 2.7 % to 20.0 %. Notably, a substantial proportion of CIP cases show severe manifestations, often leading to life-threatening complications, which emphasizes its clinical significance. Understanding the risk factors and potential pathogenetic mechanisms of CIP, combined with vigilant monitoring during immunotherapy, is pivotal for early detection and management of this condition. Proactive strategies for the timely identification, accurate diagnosis, and effective management of CIP are essential to optimize patient outcomes. However, several challenges persist in CIP management, including management of severe and refractory cases, determining the timing of ICI rechallenge after CIP, management of long-term chronic CIP, and mitigating secondary infections. In order to manage this potentially life-threatening irAE effectively, it is urgent to establish multi-disciplinary treatment (MDT) management, precision CIP management, and practical surveillance systems for CIP monitoring, diagnosis, and management and to call for prospective multi-center clinical trials.
{"title":"Clinical management of checkpoint inhibitor pneumonitis: Focus, challenges, and future directions","authors":"Yan Xu, Ruxuan Chen, Ruili Pan, Xiaoxing Gao, Hui Huang, Mengzhao Wang","doi":"10.1016/j.pccm.2024.12.001","DOIUrl":"10.1016/j.pccm.2024.12.001","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionized the treatment landscape for various malignancies by demonstrating exceptional antitumor effects and significant improvement in patient survival. Despite their overt therapeutic advantages, ICIs also induce immune-related adverse events (irAEs). Of these, checkpoint inhibitor pneumonitis (CIP) represents a prominent manifestation of pulmonary toxicity following ICI therapy, with incidence rates ranging from 2.7 % to 20.0 %. Notably, a substantial proportion of CIP cases show severe manifestations, often leading to life-threatening complications, which emphasizes its clinical significance. Understanding the risk factors and potential pathogenetic mechanisms of CIP, combined with vigilant monitoring during immunotherapy, is pivotal for early detection and management of this condition. Proactive strategies for the timely identification, accurate diagnosis, and effective management of CIP are essential to optimize patient outcomes. However, several challenges persist in CIP management, including management of severe and refractory cases, determining the timing of ICI rechallenge after CIP, management of long-term chronic CIP, and mitigating secondary infections. In order to manage this potentially life-threatening irAE effectively, it is urgent to establish multi-disciplinary treatment (MDT) management, precision CIP management, and practical surveillance systems for CIP monitoring, diagnosis, and management and to call for prospective multi-center clinical trials.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 1","pages":"Pages 29-40"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.pccm.2024.09.001
{"title":"Erratum regarding previously published articles","authors":"","doi":"10.1016/j.pccm.2024.09.001","DOIUrl":"10.1016/j.pccm.2024.09.001","url":null,"abstract":"","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 1","pages":"Pages 64-65"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.pccm.2025.02.001
Hongli Liu , Jiaxi Shen , Chao He
Significant advances have been made in diagnosing and treating idiopathic pulmonary fibrosis (IPF) in the last decade. The incidence and prevalence of IPF are increasing, and morbidity and mortality remain high despite the two Food and Drug Administration (FDA)-approved medications, pirfenidone and nintedanib. Hence, there is an urgent need to develop new diagnostic tools and effective therapeutics to improve early, accurate diagnosis of IPF and halt or reverse the progression of fibrosis with a better safety profile. New diagnostic tools such as transbronchial cryobiopsy and genomic classifier require less tissue and generally have good safety profiles, and they have been increasingly utilized in clinical practice. Advances in artificial intelligence-aided diagnostic software are promising, but challenges remain. Both pirfenidone and nintedanib focus on growth factor-activated pathways to inhibit fibroblast activation. Novel therapies targeting different pathways and cell types (immune and epithelial cells) are being investigated. Biomarker-based personalized medicine approaches are also in clinical trials. This review aims to summarize recent diagnostic and therapeutic development in IPF.
{"title":"Advances in idiopathic pulmonary fibrosis diagnosis and treatment","authors":"Hongli Liu , Jiaxi Shen , Chao He","doi":"10.1016/j.pccm.2025.02.001","DOIUrl":"10.1016/j.pccm.2025.02.001","url":null,"abstract":"<div><div>Significant advances have been made in diagnosing and treating idiopathic pulmonary fibrosis (IPF) in the last decade. The incidence and prevalence of IPF are increasing, and morbidity and mortality remain high despite the two Food and Drug Administration (FDA)-approved medications, pirfenidone and nintedanib. Hence, there is an urgent need to develop new diagnostic tools and effective therapeutics to improve early, accurate diagnosis of IPF and halt or reverse the progression of fibrosis with a better safety profile. New diagnostic tools such as transbronchial cryobiopsy and genomic classifier require less tissue and generally have good safety profiles, and they have been increasingly utilized in clinical practice. Advances in artificial intelligence-aided diagnostic software are promising, but challenges remain. Both pirfenidone and nintedanib focus on growth factor-activated pathways to inhibit fibroblast activation. Novel therapies targeting different pathways and cell types (immune and epithelial cells) are being investigated. Biomarker-based personalized medicine approaches are also in clinical trials. This review aims to summarize recent diagnostic and therapeutic development in IPF.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"3 1","pages":"Pages 12-21"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143715474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.pccm.2024.11.004
Meiyu Quan , Qiang Guo , Xihua Yan , Chenhua Yu , Linglong Yang , Yuting Zhang , Jiaqi Li , Qiongxia Weng , Bin Liu , Quan Li , Li Dong , Junjie Chen , Zhenkun Lou , Xuru Jin , Chengshui Chen , Jin-San Zhang
Background
Necroptosis is a form of programmed cell death resulting in tissue inflammation due to the release of intracellular contents. Its role and regulatory mechanism in the context of acute lung injury (ALI) are unclear. Parkin (Prkn), an E3 ubiquitin ligase, has recently been implicated in the regulation of necroptosis. In this study, we aimed to investigate the role and mechanism of Parkin in the process of ALI.
Methods
Lipopolysaccharides (LPS)-induced mouse ALI model was utilized, and the pathological changes in lung tissues were characterized. To elucidate the roles of Parkin and necroptosis in this context, mixed lineage kinase domain-like (Mlkl) knockout mice, Prkn conditional knockout mice, and the necroptosis inhibitor were employed. Additionally, alveolar type 2 (AT2) cell-specific Parkin deletion and lineage-tracing mice were introduced to explore the specific roles and mechanisms of Parkin in AT2 cells.
Results
A dose-dependent increase in Parkin expression in mouse lung tissues following LPS administration was observed, correlating with a shift from epithelial apoptosis to necroptosis. Notably, depletion of MLKL significantly mitigated the pathological changes associated with ALI, particularly the inflammatory response. Conversely, the deletion of Parkin exacerbated the injury pathology, significantly enhancing necroptosis, particularly in AT2 cells. This led to increased inflammation and post-LPS fibrosis. However, treatment with GSK872, a necroptosis inhibitor, substantially mitigated the phenotype induced by Parkin deletion. Importantly, Parkin deletion impaired the proliferation and differentiation of AT2 cells into AT1 cells.
Conclusions
These findings underscore the multifaceted role of Parkin in the progression of lung injury, inflammation, and fibrosis through the regulation of AT2 cell necroptosis. Therefore, Parkin may hold potential as a therapeutic target for managing lung injury and fibrosis.
{"title":"Parkin deficiency aggravates inflammation-induced acute lung injury by promoting necroptosis in alveolar type II cells","authors":"Meiyu Quan , Qiang Guo , Xihua Yan , Chenhua Yu , Linglong Yang , Yuting Zhang , Jiaqi Li , Qiongxia Weng , Bin Liu , Quan Li , Li Dong , Junjie Chen , Zhenkun Lou , Xuru Jin , Chengshui Chen , Jin-San Zhang","doi":"10.1016/j.pccm.2024.11.004","DOIUrl":"10.1016/j.pccm.2024.11.004","url":null,"abstract":"<div><h3>Background</h3><div>Necroptosis is a form of programmed cell death resulting in tissue inflammation due to the release of intracellular contents. Its role and regulatory mechanism in the context of acute lung injury (ALI) are unclear. Parkin (Prkn), an E3 ubiquitin ligase, has recently been implicated in the regulation of necroptosis. In this study, we aimed to investigate the role and mechanism of Parkin in the process of ALI.</div></div><div><h3>Methods</h3><div>Lipopolysaccharides (LPS)-induced mouse ALI model was utilized, and the pathological changes in lung tissues were characterized. To elucidate the roles of Parkin and necroptosis in this context, mixed lineage kinase domain-like (<em>Mlkl</em>) knockout mice, <em>Prkn</em> conditional knockout mice, and the necroptosis inhibitor were employed. Additionally, alveolar type 2 (AT2) cell-specific Parkin deletion and lineage-tracing mice were introduced to explore the specific roles and mechanisms of Parkin in AT2 cells.</div></div><div><h3>Results</h3><div>A dose-dependent increase in Parkin expression in mouse lung tissues following LPS administration was observed, correlating with a shift from epithelial apoptosis to necroptosis. Notably, depletion of MLKL significantly mitigated the pathological changes associated with ALI, particularly the inflammatory response. Conversely, the deletion of Parkin exacerbated the injury pathology, significantly enhancing necroptosis, particularly in AT2 cells. This led to increased inflammation and post-LPS fibrosis. However, treatment with GSK872, a necroptosis inhibitor, substantially mitigated the phenotype induced by Parkin deletion. Importantly, Parkin deletion impaired the proliferation and differentiation of AT2 cells into AT1 cells.</div></div><div><h3>Conclusions</h3><div>These findings underscore the multifaceted role of Parkin in the progression of lung injury, inflammation, and fibrosis through the regulation of AT2 cell necroptosis. Therefore, Parkin may hold potential as a therapeutic target for managing lung injury and fibrosis.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"2 4","pages":"Pages 265-278"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.pccm.2024.11.007
Yingyu Zhang , Yuanyuan Jiang , Daimo Zhang , Xinyue Hu , Shuanglinzi Deng , Xiaozhao Li , Juntao Feng
Background
Glucocorticoid-induced transcript 1 (GLCCI1) has been reported to be associated with the efficiency of inhaled glucocorticoids in patients with asthma. This study aimed to investigate the role of GLCCI1 in the regulation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) by the phosphatidylinositol 3-kinase (PI3K) pathway in the pathogenesis of allergic asthma.
Methods
The expression levels of genes encoding GLCCI1, NLRP3 inflammasome components, and PI3K pathway-related indicators were detected in cells isolated from induced sputum from patients with asthma and healthy controls. Next, we induced asthma in wild-type C57BL/6 mice and Glcci1 knockout (Glcci1-/-) mice by injecting them with ovalbumin (OVA) and treated the asthmatic mice with a PI3K pathway inhibitor (LY294002) or left them untreated. We also performed adoptive transfer of macrophages into the mice and assessed lung inflammation, as well as GLCCI1, PI3K pathway component, and NLRP3 inflammasome component expression levels. Finally, primary bone marrow-derived macrophages (BMDMs) from wild-type and Glcci1-/- mice were treated with OVA, either in the presence or absence of LY294002 and the NLRP3 inhibitor (MCC950), to validate our findings.
Results
The mRNA level of Glcci1 in induced sputum cells from asthmatic patients was lower compared to that of healthy controls. Additionally, Glcci1 mRNA expression correlated negatively with NLRP3 inflammasome indicators and the PI3K pathway components, as well as with IL-1β expression in induced sputum macrophages. In vivo, Glcci1-/- asthmatic mice showed elevated levels of airway inflammation and NLRP3 inflammasome activation compared to wild-type asthmatic mice. Surprisingly, the efficacy of LY294002 in reducing lung tissue inflammation and NLRP3 inflammasome activity in wild-type asthmatic mice was attenuated by Glcci1 knockout. LY294002 enhanced GLCCI1 levels in macrophages within the lung tissue of wild-type asthmatic mice. Moreover, LY294002 did not inhibit lung inflammation in wild-type asthmatic mice depleted of macrophages that had received adoptive transfer of Glcci1-/- BMDMs. In vitro experiments further illustrated that LY294002 suppressed NLRP3 activation by upregulating GLCCI1 expression in BMDMs. The introduction of MCC950 led to a marked decrease in NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) protein levels, but did not affect the expression levels of GLCCI1 or the phospho-protein kinase B (p-AKT)/AKT ratio.
Conclusions
GLCCI1 deficiency promotes asthma inflammation through PI3K-induced NLRP3 inflammasome activation.
{"title":"Role of GLCCI1 in inhibiting PI3K-induced NLRP3 inflammasome activation in asthma","authors":"Yingyu Zhang , Yuanyuan Jiang , Daimo Zhang , Xinyue Hu , Shuanglinzi Deng , Xiaozhao Li , Juntao Feng","doi":"10.1016/j.pccm.2024.11.007","DOIUrl":"10.1016/j.pccm.2024.11.007","url":null,"abstract":"<div><h3>Background</h3><div>Glucocorticoid-induced transcript 1 (GLCCI1) has been reported to be associated with the efficiency of inhaled glucocorticoids in patients with asthma. This study aimed to investigate the role of GLCCI1 in the regulation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) by the phosphatidylinositol 3-kinase (PI3K) pathway in the pathogenesis of allergic asthma.</div></div><div><h3>Methods</h3><div>The expression levels of genes encoding GLCCI1, NLRP3 inflammasome components, and PI3K pathway-related indicators were detected in cells isolated from induced sputum from patients with asthma and healthy controls. Next, we induced asthma in wild-type C57BL/6 mice and <em>Glcci1</em> knockout (<em>Glcci1</em><sup>-/-</sup>) mice by injecting them with ovalbumin (OVA) and treated the asthmatic mice with a PI3K pathway inhibitor (LY294002) or left them untreated. We also performed adoptive transfer of macrophages into the mice and assessed lung inflammation, as well as GLCCI1, PI3K pathway component, and NLRP3 inflammasome component expression levels. Finally, primary bone marrow-derived macrophages (BMDMs) from wild-type and <em>Glcci1</em><sup>-/-</sup> mice were treated with OVA, either in the presence or absence of LY294002 and the NLRP3 inhibitor (MCC950), to validate our findings.</div></div><div><h3>Results</h3><div>The mRNA level of <em>Glcci1</em> in induced sputum cells from asthmatic patients was lower compared to that of healthy controls. Additionally, <em>Glcci1</em> mRNA expression correlated negatively with NLRP3 inflammasome indicators and the PI3K pathway components, as well as with IL-1β expression in induced sputum macrophages. <em>In vivo, Glcci1</em><sup>-/-</sup> asthmatic mice showed elevated levels of airway inflammation and NLRP3 inflammasome activation compared to wild-type asthmatic mice. Surprisingly, the efficacy of LY294002 in reducing lung tissue inflammation and NLRP3 inflammasome activity in wild-type asthmatic mice was attenuated by <em>Glcci1</em> knockout. LY294002 enhanced GLCCI1 levels in macrophages within the lung tissue of wild-type asthmatic mice. Moreover, LY294002 did not inhibit lung inflammation in wild-type asthmatic mice depleted of macrophages that had received adoptive transfer of <em>Glcci1</em><sup>-/-</sup> BMDMs. <em>In vitro</em> experiments further illustrated that LY294002 suppressed NLRP3 activation by upregulating GLCCI1 expression in BMDMs. The introduction of MCC950 led to a marked decrease in NLRP3 and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) protein levels, but did not affect the expression levels of GLCCI1 or the phospho-protein kinase B (p-AKT)/AKT ratio.</div></div><div><h3>Conclusions</h3><div>GLCCI1 deficiency promotes asthma inflammation through PI3K-induced NLRP3 inflammasome activation.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"2 4","pages":"Pages 279-288"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.pccm.2024.08.005
Dan Xiao , Chen Wang
{"title":"Integrating tobacco control into China's health management: Strategies for healthier China","authors":"Dan Xiao , Chen Wang","doi":"10.1016/j.pccm.2024.08.005","DOIUrl":"10.1016/j.pccm.2024.08.005","url":null,"abstract":"","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"2 4","pages":"Pages 211-213"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.pccm.2024.11.003
Junjie Hu , Jing Zhang , Shiyue Wan , Peng Zhang
Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for resectable non-small cell lung cancer. Numerous trials have explored the use of ICIs, either as monotherapy or in combination with other therapies, in the neoadjuvant setting for stage I–III non-small cell lung cancer. Most trials have demonstrated neoadjuvant immunotherapy to be safe and to have remarkable efficacy, with a high pathological response rate and significantly improved event-free survival. This review summarizes the findings of Phase I–III clinical trials investigating various neoadjuvant regimens, including ICI monotherapy, ICI therapy combined with chemotherapy, ICI plus anti-angiogenic therapy, dual ICI therapy, and ICI therapy in combination with radiotherapy or chemoradiotherapy. We discuss the benefits and outcomes associated with each approach. Despite the results being promising, several unresolved issues remain, including identification of reliable biomarkers, the appropriate duration of therapy, the optimal treatment regimen for tumors with high programmed cell death ligand 1 (PD-L1) expression, the false-negative pathological complete response rate, and the role of digital pathology in assessing the response to treatment. Resistance to immunotherapy, in particular, remains a significant barrier to effective use of ICIs. Given the critical influence of the tumor microenvironment (TME) on the response to treatment, we examine the characteristics of the TME in both responsive and resistant tumors as well as the dynamic changes that occur in the TME in response to neoadjuvant immunotherapy. We also summarize the mechanisms underlying T cell responses following neoadjuvant immunotherapy and provide a perspective on strategies to enhance the understanding of tumor heterogeneity, therapy-driven TME remodeling, and overcoming resistance to therapy. Finally, we propose future directions for advancements in personalized neoadjuvant immunotherapy.
{"title":"Neoadjuvant immunotherapy for non-small cell lung cancer: Opportunities and challenges","authors":"Junjie Hu , Jing Zhang , Shiyue Wan , Peng Zhang","doi":"10.1016/j.pccm.2024.11.003","DOIUrl":"10.1016/j.pccm.2024.11.003","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for resectable non-small cell lung cancer. Numerous trials have explored the use of ICIs, either as monotherapy or in combination with other therapies, in the neoadjuvant setting for stage I–III non-small cell lung cancer. Most trials have demonstrated neoadjuvant immunotherapy to be safe and to have remarkable efficacy, with a high pathological response rate and significantly improved event-free survival. This review summarizes the findings of Phase I–III clinical trials investigating various neoadjuvant regimens, including ICI monotherapy, ICI therapy combined with chemotherapy, ICI plus anti-angiogenic therapy, dual ICI therapy, and ICI therapy in combination with radiotherapy or chemoradiotherapy. We discuss the benefits and outcomes associated with each approach. Despite the results being promising, several unresolved issues remain, including identification of reliable biomarkers, the appropriate duration of therapy, the optimal treatment regimen for tumors with high programmed cell death ligand 1 (PD-L1) expression, the false-negative pathological complete response rate, and the role of digital pathology in assessing the response to treatment. Resistance to immunotherapy, in particular, remains a significant barrier to effective use of ICIs. Given the critical influence of the tumor microenvironment (TME) on the response to treatment, we examine the characteristics of the TME in both responsive and resistant tumors as well as the dynamic changes that occur in the TME in response to neoadjuvant immunotherapy. We also summarize the mechanisms underlying T cell responses following neoadjuvant immunotherapy and provide a perspective on strategies to enhance the understanding of tumor heterogeneity, therapy-driven TME remodeling, and overcoming resistance to therapy. Finally, we propose future directions for advancements in personalized neoadjuvant immunotherapy.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"2 4","pages":"Pages 224-239"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.pccm.2024.11.006
Arka Sen Chaudhuri , Jie Sun
Recent scientific breakthroughs have blurred traditional boundaries between innate and adaptive immunity, revealing a sophisticated network of tissue-resident cells that deliver immediate, localized immune responses. These lymphocytes not only provide rapid frontline defense but also present a paradoxical role in the pathogenesis of respiratory diseases such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and the long-term tissue consequences of viral infections including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This review traverses the intricate landscape of lung-resident lymphocytes, delving into their origins, diverse functions, and their dualistic impact on pulmonary health. We dissect their interactions with the microenvironment and the regulatory mechanisms guiding their activity, with an emphasis on their contribution to both immune protection and immunopathology. This review aims to elucidate the complex narrative of these cells, enhancing our understanding of the development of precise therapeutic strategies to combat acute and chronic pulmonary diseases. Through this exploration, the review aspires to shed light on the potential of harnessing lung-resident lymphocytes for the treatment of respiratory conditions.
{"title":"Lung-resident lymphocytes and their roles in respiratory infections and chronic respiratory diseases","authors":"Arka Sen Chaudhuri , Jie Sun","doi":"10.1016/j.pccm.2024.11.006","DOIUrl":"10.1016/j.pccm.2024.11.006","url":null,"abstract":"<div><div>Recent scientific breakthroughs have blurred traditional boundaries between innate and adaptive immunity, revealing a sophisticated network of tissue-resident cells that deliver immediate, localized immune responses. These lymphocytes not only provide rapid frontline defense but also present a paradoxical role in the pathogenesis of respiratory diseases such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and the long-term tissue consequences of viral infections including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This review traverses the intricate landscape of lung-resident lymphocytes, delving into their origins, diverse functions, and their dualistic impact on pulmonary health. We dissect their interactions with the microenvironment and the regulatory mechanisms guiding their activity, with an emphasis on their contribution to both immune protection and immunopathology. This review aims to elucidate the complex narrative of these cells, enhancing our understanding of the development of precise therapeutic strategies to combat acute and chronic pulmonary diseases. Through this exploration, the review aspires to shed light on the potential of harnessing lung-resident lymphocytes for the treatment of respiratory conditions.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"2 4","pages":"Pages 214-223"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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