Chinese medical journal pulmonary and critical care medicine最新文献

{"title":"Trends in lung cancer burden, risk factors, and disease projections in China and the United States, 1990–2023","authors":"Lanwei Guo, Yaxin Li, Lin Cai, Huamei Luan, Jiani Yuan, Chenxin Zhu, Hongda Chen","doi":"10.1016/j.pccm.2026.08.006","DOIUrl":"10.1016/j.pccm.2026.08.006","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer is among the most burdensome malignancies worldwide, with marked disparities between China and the United States in terms of its epidemiological characteristics, risk factors, and prevention outcomes. In this study, the long-term trends in lung cancer burden and risk factors in China and the United States from 1990 to 2023 were systematically analyzed using Global Burden of Disease (GBD) Study 2023 data, and disease burden was projected through 2050, aiming to provide evidence for optimizing lung cancer prevention and control strategies in both countries.</div></div><div><h3>Methods</h3><div>Data, including incident cases, deaths, prevalence cases, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), age-standardized prevalence rates (ASPRs), and age-standardized DALY rates (ASDRs) for lung cancer in China and the United States, along with data on smoking, air pollution, occupational exposure, and metabolic and dietary risk factors, were extracted from the GBD 2023 database. Joinpoint regression was used to calculate annual percentage changes (APCs) and average annual percentage changes (AAPCs). The three-factor Das–Gupta decomposition analysis was used to quantify independent contributions of population size, population aging, and epidemiological change to variations in the absolute case burden of lung cancer in China and the United States, and Bayesian age–period–cohort models were used to project disease burden trends from 2024 to 2050.</div></div><div><h3>Results</h3><div>From 1990 to 2023, the numbers of lung cancer incident cases, deaths, prevalent cases and DALYs in China increased substantially and were far greater than those in the United States by 2023; the ASIR remained relatively stable (36.91 <em>vs.</em> 37.28 per 100,000), while ASMR decreased from 36.95 to 32.86 per 100,000, the ASPR increased from 40.04 to 53.03 per 100,000, and ASDR decreased from 935.08 to 742.26 per 100,000. In the United States, the ASIR, ASMR, and ASDR declined continuously and substantially, with a significant reduction in disease burden. With respect to risk factors, China experienced a continuous increase in the burden attributable to smoking (DALYs increased by 109.97%), ambient particulate matter pollution (DALYs increased by 414.84%), secondhand smoke (DALYs increased by 79.99%), high fasting plasma glucose (DALYs increased by 102.05%), and occupational exposure (including asbestos, diesel engine exhaust, and silica, with attributable DALY increasing by 219.97%, 164.39% and 110.59%, respectively), with only household air pollution from solid fuels declining (DALYs decreased by 85.58%). In the United States, the DALY burden attributable to all major risk factors decreased significantly. Sex-specific analyses revealed that the DALY burden was consistently higher in males than in females in both countries; the sex disparity remained stable in Ch","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"4 3","pages":"Pages 267-277"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149071700","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}

{"title":"GDF-15 and immune resistance: A new frontier in non-small cell lung cancer immunotherapy","authors":"Jun Lu, Hua Zhong, Baohui Han","doi":"10.1016/j.pccm.2026.07.001","DOIUrl":"10.1016/j.pccm.2026.07.001","url":null,"abstract":"","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"4 3","pages":"Pages 286-288"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149071931","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}

{"title":"Adoptive cell therapy in lung cancer: progress, challenges, and prospects","authors":"Jingyi Li,&nbsp;Chan Tong,&nbsp;Yongchang Chen,&nbsp;Bo Zhu","doi":"10.1016/j.pccm.2026.08.002","DOIUrl":"10.1016/j.pccm.2026.08.002","url":null,"abstract":"<div><div>Lung cancer is the leading cause of cancer-related deaths worldwide. Over the past decade, immunotherapy, represented by immune checkpoint inhibitors (ICIs) targeting programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) or cytotoxic T lymphocyte associated antigen-4 (CTLA-4), has revolutionized the treatment paradigm of lung cancer, reducing the risk of death by approximately 30%. However, approximately 70% of patients with advanced non-small cell lung cancer are either non-responsive to ICIs or initially respond to treatment but eventually experience disease progression due to acquired resistance. This subset of non-responsive or ultimately resistant patients is often characterized by complete exhaustion of endogenous anti-tumor T cells, which are unable to exert anti-tumor effects, thereby leading to ICI non-response or resistance. Correspondingly, the adoptive transfer of immune cells has shown promising efficacy in numerous clinical studies involving this patient population. Nevertheless, the Food and Drug Administration (FDA) has not yet approved any cell therapy strategy for lung cancer, primarily because of factors such as the hostile tumor microenvironment and T cell exhaustion. Herein, we summarize the current progress in cell therapy for lung cancer, analyze key challenges, and propose potential solutions.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"4 3","pages":"Pages 235-249"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067665","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}

{"title":"Treatable traits-based management of bronchiectasis: moving from theory to clinical practice","authors":"Guiyin Zhu,&nbsp;James D. Chalmers,&nbsp;Jin-Fu Xu","doi":"10.1016/j.pccm.2026.08.004","DOIUrl":"10.1016/j.pccm.2026.08.004","url":null,"abstract":"<div><div>Bronchiectasis is a chronic airway disease characterized by irreversible bronchial dilatation and substantial clinical heterogeneity. Accumulating evidence from large international observational cohorts has highlighted wide variation in the features of this disease and unmet clinical needs. The treatable traits-based approach has emerged as a means to prioritize identifiable and clinically actionable problems over traditional diagnostic labels. In this review, we summarize the reported prevalence of major treatable traits across large cohorts and describe notable regional differences, alongside the ongoing absence of data relating to behavioral and environmental traits. We further update the treatable traits framework based on recent guideline recommendations, clarifying the strength of evidence supporting the interventions available. We also review selected molecular mechanisms relevant to key treatable traits. Despite growing interest, the use of treatable traits in routine practice is restricted by ambiguous terminology, insufficient prospective data, and inadequate evidence for many therapies. However, the fundamental constraint for implementation is not insufficient characteristic identification, but rather the attempt to manage a complicated and non-linear disease system with a static checklist. Future research should emphasize standardized definitions and real-world longitudinal studies, and develop practical tools to help clinicians determine which traits should be addressed first. Such efforts may support transparent, individualized, and adaptive decision-making in bronchiectasis.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"4 3","pages":"Pages 219-234"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067717","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}

{"title":"Advances in metabolic reprogramming of pulmonary fibrosis","authors":"Huan Zhou,&nbsp;Tiantian Zhang","doi":"10.1016/j.pccm.2026.07.003","DOIUrl":"10.1016/j.pccm.2026.07.003","url":null,"abstract":"<div><div>Pulmonary fibrosis (PF) refers to a common pathological change that occurs in a series of lung diseases. It is manifested by fibroblast proliferation and excessive extracellular matrix (ECM) deposition, resulting in destruction of lung structure and deterioration of lung function. PF represents a widespread global health problem, particularly in developing countries, and poses a substantial threat to public health. Despite its clinical significance, effective and specific pharmacological therapies remain unavailable. Therefore, identifying novel therapeutic targets is urgently needed and holds considerable clinical importance. A clearer understanding of the underlying pathogenic mechanisms of PF is essential for improving both prevention and treatment strategies. In recent years, increasing evidence has indicated that metabolic reprogramming including alterations in glucose, lipid, and amino acid metabolism plays an important role in the initiation and progression of PF. In this review, we summarize current knowledge regarding metabolic reprogramming in PF and highlight the potential of metabolic pathways as targets for diagnosis and therapy, thereby offering new perspectives for future research.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"4 3","pages":"Pages 250-266"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067716","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}

{"title":"Respiratory immunology: an ancient yet emerging interdisciplinary field","authors":"Yuqing Lv,&nbsp;Weining Xiong,&nbsp;Bin Cao","doi":"10.1016/j.pccm.2026.07.002","DOIUrl":"10.1016/j.pccm.2026.07.002","url":null,"abstract":"","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"4 3","pages":"Pages 193-196"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067664","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}

{"title":"Therapeutic vaccines for NSCLC: From mechanisms to clinical translation","authors":"Weijing Liu,&nbsp;Jiefei Han,&nbsp;Kailun Fei,&nbsp;Yiting Dong,&nbsp;Man Li,&nbsp;Jie Zhao,&nbsp;Mingzhao Wang,&nbsp;Zhuoran Li,&nbsp;Siyuan Chen,&nbsp;Jiachen Xu,&nbsp;Amit Jain","doi":"10.1016/j.pccm.2026.08.001","DOIUrl":"10.1016/j.pccm.2026.08.001","url":null,"abstract":"<div><div>Despite advances in targeted therapy and immune checkpoint inhibitors (ICIs), durable disease control remains elusive for most patients with non-small cell lung cancer (NSCLC), particularly those with advanced-stage disease. Therapeutic cancer vaccines offer the potential for sustained immune surveillance by inducing tumor-specific effector and memory T-cell responses. However, their clinical benefits have been inconsistent to date. In advanced disease, rapid tumor progression, an immunosuppressive tumor microenvironment (TME), defective antigen presentation, and immune escape collectively impair the infiltration, persistence, and cytotoxic function of vaccine-induced T cells. These biological factors suggest that vaccine activity may depend on a therapeutic window characterized by lower tumor burden, preserved antigen presentation, and limited immunosuppression. Combination strategies with ICIs, chemotherapy, or radiotherapy are being investigated to increase antigen release and reduce TME-mediated immunosuppression. Vaccine development has also expanded beyond shared tumor-associated antigens to include personalized and shared tumor-specific antigens, as well as multi-epitope designs intended to improve immunogenicity and patient selection. Nonetheless, antigen heterogeneity, immune editing, manufacturing timelines, and the safety of combination regimens remain key translational challenges. Therapeutic vaccines may therefore be viewed as immunomodulatory agents whose long-term value in NSCLC will depend on antigen selection, treatment timing, and integration with multimodal therapy.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"4 3","pages":"Pages 197-218"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067666","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}

{"title":"Prevalence of anxiety and depression and diagnostic utility of the CAT scale in spirometry-confirmed COPD patients: Findings from the Chinese Population Health and Multimorbidities Study","authors":"Sinan Wu,&nbsp;Jian Kang,&nbsp;Xiangyan Zhang,&nbsp;Lan Yang,&nbsp;Fuqiang Wen,&nbsp;Yuanlin Song,&nbsp;Jianping Zhao,&nbsp;Jianying Xu,&nbsp;Wen Li,&nbsp;Pixin Ran,&nbsp;Kewu Huang,&nbsp;Yahong Chen,&nbsp;Yanfei Guo,&nbsp;Guangliang Shan,&nbsp;Ting Yang,&nbsp;Chen Wang,&nbsp;Jieping Lei,&nbsp;Chinese Population Health and Multimorbidities Study (CPHMS) Investigators","doi":"10.1016/j.pccm.2026.08.003","DOIUrl":"10.1016/j.pccm.2026.08.003","url":null,"abstract":"<div><h3>Background</h3><div>Patients with chronic obstructive pulmonary disease (COPD) frequently present with psychological comorbidities, including anxiety and depression, which may contribute to poorer clinical outcomes. However, the prevalence and impact of these mental health conditions in COPD patients have long been underrecognized. Leveraging data from the Chinese Population Health and Multimorbidities Study (CPHMS), a large epidemiological survey on chronic respiratory diseases in China, this study aimed to estimate the prevalence of anxiety and depression comorbidities among community-dwelling COPD patients and to evaluate the diagnostic utility of the COPD Assessment Test (CAT) scale for detecting these conditions in spirometry-confirmed COPD patients.</div></div><div><h3>Methods</h3><div>Analytical data were derived from the CPHMS. Comprehensive information on sociodemographic characteristics, lifestyle factors, and health status was collected. COPD-related pulmonary and extra-pulmonary symptoms were assessed using the CAT scale, and anxiety and depression were evaluated via the Hospital Anxiety and Depression Scale. Multivariable logistic regression was employed to identify factors associated with anxiety or depression comorbidities, and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of the CAT scale.</div></div><div><h3>Results</h3><div>Among 3641 spirometry-confirmed community COPD patients, the prevalence of anxiety and depression was 11.07% (95% confidence interval [CI]: 10.05–12.09%) and 14.23% (95% CI: 13.09–15.36%), respectively. Female gender, rural residence, unemployment, lower annual family income, and higher total CAT score, as well as higher scores on both the pulmonary and extra-pulmonary symptom subscales of the CAT, were independently associated with an increased likelihood of anxiety and/or depression in COPD patients. The diagnostic yield of the CAT scale for identifying anxiety and depression in COPD patients was evaluated. In the overall COPD patients, the optimal total CAT cut-off value for detecting anxiety was 9 (area under the ROC curve [AUC]: 0.637; 95% CI: 0.607–0.666), and for depression was 7 (AUC: 0.633; 95% CI: 0.607–0.659). Notably, among rural-dwelling COPD patients, the optimal cut-off was 7 for both anxiety (AUC: 0.624; 95% CI: 0.582–0.665) and depression (AUC: 0.616; 95% CI: 0.579–0.653), whereas in urban patients, the corresponding cut-offs were 11 for anxiety (AUC: 0.652; 95% CI: 0.610–0.694) and 10 for depression (AUC: 0.654; 95% CI: 0.618–0.691).</div></div><div><h3>Conclusions</h3><div>This study delineated the prevalence of anxiety and depression among community COPD patients and validated the clinical utility of the CAT scale in detecting these psychological comorbidities. Our findings underscore the pressing need for tailored psychological support, particularly for COPD patients residing in rural area of China.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"4 3","pages":"Pages 278-285"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149071930","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}

{"title":"Respiratory microbiota transplantation: optimized framework and its impact on metabolic and immune characteristics","authors":"Shifen Xu,&nbsp;Xing Zhang,&nbsp;Yunfeng Shi,&nbsp;Xiang Tan,&nbsp;Hanqin Cai,&nbsp;Wei Cheng,&nbsp;Lei Yang,&nbsp;Xinzhu Yi,&nbsp;Zhiming Xiang,&nbsp;Chao Cao,&nbsp;Hong Wei,&nbsp;Zhang Wang","doi":"10.1016/j.pccm.2026.05.002","DOIUrl":"10.1016/j.pccm.2026.05.002","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The respiratory microbiota is critical to maintaining local immune homeostasis and respiratory health. Microbiota transplantation has proven transformative in gut microbiome studies. However, a standardized approach for the respiratory tract remains lacking, hindered by technical difficulty of establishing a recipient airway niche conducive to stable donor microbial engraftment, and limited systematic evaluation of key parameters that influence transplantation efficacy. This study aims to establish an optimized respiratory microbiota transplantation (RMT) framework and determine whether RMT reshapes metabolic and immunological characteristics.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We developed and optimized a method for RMT in murine models. Key parameters, including sample storage, delivery route, and treatment regimen, were systematically evaluated for their effects on the microbiome using 16S ribosomal RNA gene sequencing-based profiling. The influence of microbiota transplantation on host metabolism and immunity was also assessed through metabolomic and transcriptomic characterization. Wilcoxon rank-sum test was used to compare Bray-Curtis dissimilarity between groups. Additionally, a one-sample Wilcoxon signed-rank test was used to determine whether the relative abundance changes within each recipient–donor pair significantly deviated from zero. Differential metabolomic and transcriptomic features were identified using trend analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;We established mouse-to-mouse RMT by transferring bronchoalveolar lavage fluid (BALF)-derived microbial communities from specific pathogen-free (SPF) donors to germ-free (GF) recipients. To model lung dysbiosis, we induced sepsis via cecal ligation and puncture in SPF mice and transplanted their BALF microbiota into normal SPF recipients. The highest compatibility of donor–recipient microbiota was observed using glycerol-preserved samples, delivered either intratracheally or intranasally every other day, for a duration of 14 days (Wilcoxon rank-sum test, SPF–GF mice: intratracheal delivery 7 days &lt;em&gt;vs.&lt;/em&gt; 14 days, &lt;em&gt;W&lt;/em&gt; = 12.0, &lt;em&gt;P&lt;/em&gt; = 0.057, intranasal delivery 7 days &lt;em&gt;vs.&lt;/em&gt; 14 days, &lt;em&gt;W&lt;/em&gt; = 12.0, &lt;em&gt;P&lt;/em&gt; = 0.057; CLP–SPF mice: intratracheal delivery 7 days &lt;em&gt;vs.&lt;/em&gt; 14 days, &lt;em&gt;W&lt;/em&gt; = 35.0, &lt;em&gt;P&lt;/em&gt; = 0.003, intranasal delivery 7 days &lt;em&gt;vs.&lt;/em&gt; 14 days: &lt;em&gt;W&lt;/em&gt; = 36.0, &lt;em&gt;P&lt;/em&gt; = 0.035). This microbiota transplantation partially shifted the metabolomic and immunological characteristics of GF recipients toward those of SPF donors, reversing 188 metabolites and 2721 host genes that were altered in GF mice compared with SPF mice. We then adapted this protocol for human-to-mouse RMT, transplanting microbiota from human BALF and sputum into SPF mice. Intratracheal and intranasal delivery of human BALF yielded comparable donor–recipient microbiota similarity. However, intratracheal administration significant","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"4 2","pages":"Pages 184-192"},"PeriodicalIF":7.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378263","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}

{"title":"Structural and cellular mechanisms of mucus plugging in the larger airways","authors":"Zheqing Hu,&nbsp;Liyuan Yang,&nbsp;Yabo Ma,&nbsp;Juan Chen,&nbsp;Xiaoming Liu","doi":"10.1016/j.pccm.2026.05.001","DOIUrl":"10.1016/j.pccm.2026.05.001","url":null,"abstract":"<div><div>Intractable mucus plugging drives mortality in cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD). While surface metaplasia narrows small airways, the massive volumetric reservoir capacity of hypertrophied submucosal glands (SMGs) dictates catastrophic mucus plugging in the larger airways. This review proposes a flush-load model to explain this structural failure: a biophysical imbalance in which SMG serous fluid secretion (the flush) is insufficient to hydrate and clear the burden of high-molecular-weight mucins (the load), leading to osmotic compression, ciliary collapse, and intractable luminal occlusion. The review delineates the disease-specific etiologies of this imbalance. In CF, dysfunction of ion channels, such as the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channels (ENaC), causes mechanical uncoupling and mucin 5B (MUC5B) tethering to glandular ducts. In asthma, Type 2 inflammation disrupts the glandular stem cells, driving an explosive release of mucin. In COPD, epidermal growth factor receptor (EGFR)-driven remodeling and senescent inflammaging perpetuate chronic hypersecretion. Ultimately, anchored MUC5B strands from hypertrophic SMGs structurally integrate with surface-derived mucin 5AC (MUC5AC), forming an intractable adhesive mesh. Synthesizing these insights, we advocate shifting the therapeutic paradigm from symptomatic downstream clearance to upstream, disease-modifying interventions that target the glandular stem cell niche, restore ion channel homeostasis, and correct coordinated airway surface dysfunction.</div></div>","PeriodicalId":72583,"journal":{"name":"Chinese medical journal pulmonary and critical care medicine","volume":"4 2","pages":"Pages 155-170"},"PeriodicalIF":7.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13323556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378308","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}