Lung最新文献

{"title":"Sputum Transcriptomic Analysis and Clustering Reveals Insight Into Asthma Heterogeneity.","authors":"Janne Goossens, Anne-Charlotte Jonckheere, Sien De Boodt, Ellen Dilissen, Nora Marain, Tatjana Decaesteker, Alvaro Cortes, Jeroen A Vanoirbeek, Sven F Seys, Lieven Dupont, Dominique M A Bullens","doi":"10.1007/s00408-025-00843-1","DOIUrl":"10.1007/s00408-025-00843-1","url":null,"abstract":"<p><strong>Introduction: </strong>Asthma is a heterogenous disease shaped by different inflammatory pathways. The aim is to investigate transcriptomic profiles in asthmatic patients and associate these with inflammation, airway damage and lung function.</p><p><strong>Methods: </strong>Adult asthma patients attending the outpatient pneumology clinic in our tertiary center, underwent diagnostic sputum induction and upon consent remaining sputum RNA was used for bulk RNA-sequencing (n = 56) coupled with unsupervised clustering. A retrospective analysis of comorbidities was performed. Sputum cytokine mRNA levels were determined via qPCR. Airway damage markers were determined in sputum supernatant RESULTS: Unsupervised clustering subdivided all asthmatic patients in one of three clusters. Cluster 1 contained most of the pauci-granulocytic asthma patients in whom oxidative stress was upregulated and TLR-signalling and several cytokine pathways down-regulated. Cluster 2 had upregulated S100 family signalling pathway genes, was mostly associated to type 2 inflammation with elevated sputum eosinophils, epithelial damage, IL-4 mRNA levels and allergy. Asthma patients in cluster 3 had worse lung function, upregulated inflammatory genes, increased sputum neutrophils and calprotectin levels.</p><p><strong>Conclusion: </strong>Three different asthma clusters could be identified bridging over the classical type 2/non-type 2 classification.</p><p><strong>Clinical trial: </strong>ClinicalTrials.gov Identifier: NCT01224938 registered on 19 October 2010.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"89"},"PeriodicalIF":3.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883144","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}

{"title":"Modified Tracheobronchoplasty for Chronic Cough Due to Excessive Dynamic Airway Collapse: A Case Series.","authors":"Alessandro Gonfiotti, Alessandra Sorano, Massimo O Jaus, Giulia Fabietti, Luca Voltolini, Giovanni A Fontana, Federico Lavorini","doi":"10.1007/s00408-025-00842-2","DOIUrl":"10.1007/s00408-025-00842-2","url":null,"abstract":"","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"88"},"PeriodicalIF":3.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855723","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}

{"title":"Serum Cytokeratin 18 and Fragment as Biomarkers for Severity and Prognosis in Acute Exacerbation of Chronic Obstructive Pulmonary Disease.","authors":"Ming-Yan Liu, Kai-Xin Qu, Kai-Shu Ma, Zhen-Yu Cheng, Xiang Cai, Hai-Long Miu, Meng-Xue Liu, Yi-Qun Wang, Hui Zhao, Ling Zheng, Lin Fu, Jin Yang","doi":"10.1007/s00408-025-00841-3","DOIUrl":"10.1007/s00408-025-00841-3","url":null,"abstract":"<p><strong>Background: </strong>Cytokeratin (CK)18 is present in the bronchi and alveolar epithelium of the lung, and its cleavage product, CK-18M30, serves as a biological marker of apoptosis. However, the specific roles of CK-18 and CK-18M30 in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) remain unclear.</p><p><strong>Methods: </strong>This study enrolled 289 patients with AECOPD who met the inclusion criteria. Demographic information and clinical characteristics of the patients were documented. A 3-year follow-up period was implemented to evaluate acute exacerbations and mortality. Serum CK-18 and CK-18M30 concentrations were measured using enzyme-linked immunosorbent assays.</p><p><strong>Results: </strong>Serum concentrations of CK-18/CK-18M30 at admission in patients with AECOPD were higher than those in the control group. As severity increased, serum CK-18/CK-18M30 levels increased progressively in AECOPD patients. Pearson's correlation analysis revealed that serum CK-18/CK-18M30 concentrations were positively correlated with several clinical parameters. Linear and logistic regression models demonstrated positive correlations between serum CK-18 and CK-18M30 levels at admission and severity scores. Furthermore, higher serum CK-18/CK-18M30 levels at admission were associated with increased frequency of death and acute exacerbation in patients with AECOPD within 3 years.</p><p><strong>Conclusion: </strong>Serum CK-18/CK-18M30 levels at admission were positively correlated with severity and poor prognosis in patients with AECOPD within 3 years. Therefore, serum CK-18 and CK-18M30 concentrations may serve as novel diagnostic and prognostic biomarkers for patients with AECOPD.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"87"},"PeriodicalIF":3.9,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144821941","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}

{"title":"Unnerving Cough in CANVAS: Cough Hypersensitivity Despite Airway Nerve Depletion.","authors":"Barnaby Hirons, Katherine Rhatigan, William McNulty, Richard D Turner, James H Hull, Caroline J Jolley, Robert D Hadden, Ana Ribeiro, Andrea Cortese, Peter S P Cho, Safa Al-Sarraj, Jordi Serra, Peter Bannister, Chadwick B Smith, Matthew G Drake, Surinder S Birring","doi":"10.1007/s00408-025-00838-y","DOIUrl":"10.1007/s00408-025-00838-y","url":null,"abstract":"<p><strong>Introduction: </strong>Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a genetic neurodegenerative condition associated with chronic cough and cough hypersensitivity. The neuropathic mechanisms underlying cough in CANVAS are unknown. In a father and son with CANVAS-associated cough, we investigated clinical and neuropathophysiological features including bronchial and skin biopsies.</p><p><strong>Methods: </strong>Patients completed assessments for cough severity (visual analogue scale, VAS), impact (Leicester Cough Questionnaire, LCQ), triggers (Cough Hypersensitivity Questionnaire), objective frequency with Leicester Cough Monitor, and reflex sensitivity with capsaicin cough challenge. Bronchoscopic airway biopsies were analysed for nerve morphology and compared to a healthy control. Neurological assessments included skin biopsies, nerve conduction studies, and microneurography.</p><p><strong>Results: </strong>The father (age 62) and son (age 37) had advanced and early CANVAS, with a refractory chronic cough of 37 and 9 years duration, respectively. The cough in the father and son was of moderate severity (VAS 58 and 54 mm) and impact (LCQ score 15.9 and 13.1), with raised objective cough frequencies of 6 and 16 coughs hr^-1, and heightened cough reflex sensitivity to capsaicin with concentrations to evoke five coughs (C5) of 14.9 and 3.3 μmol L^-1, respectively. Bronchoscopic airway biopsies demonstrated severely depleted sensory small nerve fibres in the father and son compared to a healthy control: median (IQR) total nerve length 0 (0-0) and 0 (0-125) μm vs 944 (461-1323) μm, respectively. Skin biopsies showed absent intraepidermal nerve fibres, with densities of 0.0 fibres.mm^-1 in both patients. Functional microneurography revealed nociceptor fibre paucity and dysfunction.</p><p><strong>Conclusion: </strong>In CANVAS, despite the loss of bronchial and cutaneous nerve fibres, there was heightened cough reflex sensitivity. Further studies are needed to elucidate underlying neural mechanisms.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"86"},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799545","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}

{"title":"Stratifying GAP Stages by MUC5B rs35705950 T-Allele Carriage Refines Survival Prediction in IPF.","authors":"Joanne J van der Vis, Antje Prasse, Elisabetta A Renzoni, Carmel J W Stock, Toby M Maher, Francesco Bonella, Raphael Borie, Bruno Crestani, Wim A Wuyts, Philip L Molyneaux, Johannes C Kelder, Jan C Grutters, Coline H M van Moorsel","doi":"10.1007/s00408-025-00837-z","DOIUrl":"https://doi.org/10.1007/s00408-025-00837-z","url":null,"abstract":"<p><p>The genetic contribution to idiopathic pulmonary fibrosis (IPF) has become increasingly evident, enabling its translation into clinical practice. MUC5B rs35705950 has emerged as a promising prognostic biomarker. The gender-age-physiology (GAP)-model is regularly used for IPF survival prediction. In this retrospective real-world study, GAP-stages were stratified by MUC5B T-allele carriage. European patients with IPF were included in a discovery (n = 663), and replication (n = 738) cohort. The GAP+MUC5B-model was significantly more accurate compared to the GAP-model (all cohorts p < 0.001), with a modest improvement in discrimination (ΔC = 0.023; C = 0.685, 95%CI 0.665-0.704). Within each GAP-stage, T-allele carriers had significantly better median transplant-free survival outcomes than non-carriers (p < 0.001): In the combined cohort (n = 1401) survival for GAP-stage I T carriers was 70 months (m) vs 48m for T non-carriers; stage II T vs non-T: 41 vs 31m; stage III T vs non-T: 23 vs 12m. Addition of MUC5B rs35705950 T-carriership enhances GAP-based prognostication and aids clinical decision-making.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"85"},"PeriodicalIF":3.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742440","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}

{"title":"Lung Tissue Compliance Interacts with Smooth Muscle and Drives Hyperresponsiveness in Mice with Experimental Asthma.","authors":"Sébastien Hecht, Andrés Rojas-Ruiz, Magali Boucher, Cyndi Henry, Jorge Soliz, Ynuk Bossé","doi":"10.1007/s00408-025-00840-4","DOIUrl":"10.1007/s00408-025-00840-4","url":null,"abstract":"<p><strong>Introduction: </strong>A recent study on BALB/c and C57BL/6 mice demonstrated a clear lack of association between the in vivo response to nebulized methacholine and the degree of airway narrowing ex vivo in a model of asthma induced by a daily exposure to house dust mite over 10 consecutive days. This finding raises the question of which factors determine the methacholine response in vivo.</p><p><strong>Methods: </strong>Herein, multiple linear regression analyses were used to determine which baseline physiological characteristics are associated with the methacholine response.</p><p><strong>Results: </strong>Among the 10 baseline characteristics studied, and depending on how the methacholine response was monitored during a concentration-response, lung tissue compliance was the most commonly and robustly associated with the methacholine response. Inspiratory capacity was the second most frequently associated.</p><p><strong>Conclusion: </strong>These results suggest that lung tissue compliance and inspiratory capacity may be two important determinants of the methacholine response in BALB/c and C57BL/6 mice with and without experimental asthma.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"84"},"PeriodicalIF":3.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742439","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}

{"title":"Evidence that Mast Cells Regulate the Cough Hypersensitivity Associated with Eosinophilic Bronchitis.","authors":"Li Yu, Qi Liu, Brendan J Canning","doi":"10.1007/s00408-025-00835-1","DOIUrl":"10.1007/s00408-025-00835-1","url":null,"abstract":"<p><strong>Purpose: </strong>Eosinophils have been implicated as key effectors in the emergence of chronic cough. But causality has not been firmly established, and many patients with cough secondary to eosinophilic bronchitis (EB) are likely misdiagnosed as asthmatics based on successful empiric trials using inhaled corticosteroids. Better diagnostics and more precise therapeutic strategies for EB and other diseases that lead to chronic cough remain important but unmet clinical needs.</p><p><strong>Methods: </strong>With the goal of better defining the mechanisms of cough in disease, we established a model of EB in guinea pigs using allergen challenges that induce a cough hypersensitivity responsive to steroid therapy.</p><p><strong>Results: </strong>The heightened cough responsiveness associated with the eosinophilic inflammation was mimicked by LTD₄ inhalation and prevented by cysLT₁ receptor blockade with pranlukast or montelukast. But cysLT₁ receptor antagonism failed to prevent the eosinophilic infiltration of the airways evoked by allergen challenge. Additionally, inhalation of the mast cell selective stimulant Compound 48/80 mimicked the effects of allergen challenge on cough but failed to significantly increase eosinophilic infiltration of the airways. We also observed that thromboxane A2, through TP receptor engagement, acts downstream from and simultaneously with the leukotrienes to promote cough hypersensitivity in EB.</p><p><strong>Conclusions: </strong>These results suggest that mast cells and not eosinophils may be essential to the emergence of cough hypersensitivity in EB. We speculate that therapeutic strategies targeting mast cells, cysLT₁ receptors, and TP receptors may represent endotype-specific treatments for chronic cough.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"82"},"PeriodicalIF":3.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698960","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}

{"title":"Airway Mucus Plugs in Patients with Chronic Cough: A Single-Center Observational Study.","authors":"Kyongmin Sarah Beck, Dae Hee Han, Hyun-Seob Jeon, Juyoung Shin, Sook Young Lee, Woo-Jung Song, Hwa Young Lee","doi":"10.1007/s00408-025-00839-x","DOIUrl":"10.1007/s00408-025-00839-x","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the prevalence of mucus plugs and their clinical associations in patients with chronic cough.</p><p><strong>Methods: </strong>Chest computed tomography (CT) scans were evaluated in patients with chronic cough and healthy controls.</p><p><strong>Results: </strong>Among 82 patients with chronic cough and 71 controls, mucus plugs were identified in 31.7% and 5.6%, respectively. Higher mucus plug scores were associated with older age, elevated fractional exhaled nitric oxide (FeNO), and lower total Cough Hypersensitivity Questionnaire (CHQ) scores (all P < 0.05). Regression analysis revealed associations with higher FeNO and lower total CHQ scores (Model 1: R² = 0.396, P < 0.001), and with higher immunoglobulin (Ig) E levels (Model 2: R² = 0.388, P < 0.001). Mucus plug scores did not differ by 1-month treatment response.</p><p><strong>Conclusions: </strong>Mucus plugs were prevalent in chronic cough and associated with type 2 airway inflammation. Their clinical significance warrants further investigation.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"83"},"PeriodicalIF":4.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144698959","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}

{"title":"ICD-10 Diagnostic Coding Patterns and Clinical Correlates in Refractory Chronic Cough: Analysis from the Korean Chronic Cough Registry.","authors":"Min-Hye Shin, Young-Jae Lee, Kyung Eun Park, Yeonhee Kim, Ha-Kyeong Won, Kyung-Min Ahn, Ji-Su Shim, Min-Hye Kim, Jin An, Jiung Jeong, Young-Chan Kim, Hwa Young Lee, Sung-Yoon Kang, Han-Ki Park, Eun-Jung Jo, Seung-Eun Lee, So Ri Kim, Yoon-Seok Chang, Byung-Jae Lee, Alyn H Morice, Woo-Jung Song","doi":"10.1007/s00408-025-00836-0","DOIUrl":"https://doi.org/10.1007/s00408-025-00836-0","url":null,"abstract":"<p><p>The International Classification of Diseases (ICD) system plays a key role in health data classification but currently lacks a specific code for refractory chronic cough (RCC). This study analyzed ICD-10 coding patterns among 331 RCC patients enrolled in the Korean Chronic Cough Registry. Each patient had a median of 3 [IQR: 2-4] ICD-10 codes at their most recent outpatient visit. The most frequently assigned primary code was R05 (Cough), recorded in 80.4% of cases. Patients with R05 as their primary code tended to have fewer identifiable etiologies but reported more cough hypersensitivity symptoms. Additionally, the number of ICD-10 codes correlated with both cough severity and cough-specific quality-of-life impairment. In a pooled analysis including RCC and non-RCC cases, the R05 code showed high specificity (80.5%) but low sensitivity (25.8%) for RCC. These findings support the need for a dedicated ICD code to accurately capture RCC in clinical and epidemiological contexts.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"81"},"PeriodicalIF":4.6,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667927","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}

{"title":"From Glucotoxicity to Lung Injury: Emerging Perspectives on Diabetes-Associated Respiratory Complications.","authors":"Hongmei Yu, Jie Liu, Xiaojuan He","doi":"10.1007/s00408-025-00834-2","DOIUrl":"https://doi.org/10.1007/s00408-025-00834-2","url":null,"abstract":"<p><p>Emerging evidence highlights glucose toxicity as a pivotal driver of diabetic respiratory complications, characterized by hyperglycemia-induced metabolic dysregulation and multi-organ damage. The lung, a metabolically active organ, exhibits unique susceptibility to glucose toxicity due to its exposure to oxidative stress, inflammatory cascades, and disrupted metabolic reprogramming, particularly in glycolysis and mitochondrial dysfunction. Diabetes-associated respiratory complications encompass increased susceptibility to respiratory infections, acute respiratory distress syndrome (ARDS) with macrophage-driven glycolytic shifts, and gestational diabetes mellitus (GDM)-associated fetal lung dysplasia via impaired epithelial differentiation. Future research should prioritize metabolic dysregulation-targeted therapies, gut-lung axis modulation, and personalized approaches to address the interplay between hyperglycemia, oxidative stress, and immune dysregulation. Elucidating genetic and epigenetic modifiers of glucotoxicity will further advance therapeutic strategies for diabetes-associated pneumopathy. This review provides an overview of epidemiological burden, lung structural and functional changes, pathophysiological mechanisms, clinical outcomes and complications, therapeutic and preventive strategies, unanswered questions, and future directions of diabetes-associated respiratory complications.</p>","PeriodicalId":18163,"journal":{"name":"Lung","volume":"203 1","pages":"80"},"PeriodicalIF":4.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642915","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}