Respiratory Research最新文献

{"title":"Effects of riociguat on right ventricular size and function in pulmonary arterial hypertension (RIVER II): a prospective, phase IV study.","authors":"Satenik Harutyunova, Jonathan Heinz, Nicola Benjamin, Lena Brückner, Faruk Sehic, Benjamin Egenlauf, Antonio Cittadini, Alberto M Marra, Ekkehard Grünig, Panagiota Xanthouli","doi":"10.1186/s12931-026-03843-8","DOIUrl":"10.1186/s12931-026-03843-8","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary arterial hypertension (PAH) is characterized by right ventricular (RV) pressure overload, dilatation and dysfunction, which are key prognostic determinants. While riociguat improves exercise capacity and hemodynamics, prospective data on reverse remodeling remain limited. This prospective, phase IV study evaluated the effects of riociguat on right-heart size, function, hemodynamics, exercise capacity and safety in PAH patients.</p><p><strong>Methods: </strong>Treatment-naïve or pretreated PAH patients were enrolled. Patients receiving phosphodiesterase-5 inhibitors (PDE5i) could be switched to riociguat upon clinical indication. The primary endpoint was the change in right atrial (RA) and RV area at 24 weeks. Secondary endpoints included additional echocardiographic, clinical, exercise, hemodynamic and laboratory parameters, as well as quality-of-life (QoL) and safety.</p><p><strong>Results: </strong>Thirty patients (61.2 ± 14.5 years; 76.7% male; 24 PDE5i-pretreated) were enrolled. Marked right-heart dilatation and impaired RV function were prominent at baseline. At week 24, riociguat significantly reduced RA (Δ -3.17 ± 5.91 cm²; p = 0.006) and RV area (Δ -6.00 ± 3.80 cm²; p < 0.0001). Furthermore, RV-fractional area change, 6-minute walking distance and functional class improved significantly. In patients with invasive follow-up, cardiac index increased significantly, with favorable trends in further parameters. N-terminal pro-brain natriuretic peptide and QoL remained unchanged. The study terminated early following the decision by the supplier Merck/MSD; the termination was not safety related. Riociguat was generally well tolerated with no new safety concerns.</p><p><strong>Conclusion: </strong>Riociguat therapy resulted in a statistically significant improvement in right ventricular and atrial size and function with further improvements in exercise capacity and functional class. This prospective trial confirms the findings of previous retrospective studies and supports riociguat as an effective treatment option to improve RV geometry and performance.</p><p><strong>Trial registration: </strong>This trial was registered on clinicaltrials.gov with the ClinicalTrials.gov ID NCT04954742.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649585","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":"Increased high sensitivity C-reactive protein in more severe wheeze/asthma phenotypes in child- and adulthood in ALLIANCE.","authors":"Lena Lagally, Lena Ullemeyer, Jimmy Omony, Kristina Gottschau, Francesco Foppiano, Mustafa Abdo, Vera Veith, Clemens Thölken, Alexander Hose, Nicole Maison, Ruth Grychtol, Anna-Maria Dittrich, Lennart Riemann, Markus Weckmann, Inke König, Lea Kronziel, Sabina Illi, Silke van Koningsbruggen-Rietschel, Klaus F Rabe, Harald Renz, Gesine Hansen, Folke Brinkmann, Matthias V Kopp, Erika von Mutius, Thomas Bahmer, Markus Ege, Chrysanthi Skevaki, Bianca Schaub","doi":"10.1186/s12931-026-03840-x","DOIUrl":"10.1186/s12931-026-03840-x","url":null,"abstract":"<p><strong>Background: </strong>The relevance of high-sensitivity C-reactive protein (hsCRP), a marker of low-grade systemic inflammation, remains unclear with regard to its association with severity and clinical outcomes in wheeze/asthma. We aimed to assess the role of hsCRP across different phenotypes and severity levels.</p><p><strong>Methods: </strong>We studied children with preschool wheeze (≥ 2 episodes), and patients with GINA-defined asthma (school-age/adult) compared with healthy controls (HCs) in the well-characterized ALLIANCE (All Age Asthma Cohort) study. HsCRP was measured (AU5800®-CRP-Latex test) in 944 study participants (pediatric: n = 728; adult: n = 216) at baseline. Age-stratified analyses (age groups 0-5, 6-18, ≥ 18 years) of standardized log₁₀-transformed hsCRP concentrations (age, sex, BMI, site) were performed using univariable tests and regression models. The validated ASSESS score and its dimensions (exacerbations, lung function, inhaled corticosteroids, symptom control) were primary outcomes.</p><p><strong>Results: </strong>Adult patients with asthma showed higher hsCRP than HCs (OR 2.22, 95% CI 1.56-3.24). Across all ages, hsCRP increased with clinical severity of wheeze/asthma. The ASSESS score correlated positively with hsCRP in patients aged ≥ 6 years (R = 0.19, p = 0.007). hsCRP was increased in school-age asthmatics with prior exacerbations (OR 1.37, 95% CI 1.01-1.87), and in adult asthmatics with impaired lung function (R = 0.2, p = 0.013). Inhaled corticosteroid use was associated with lower hsCRP in preschool wheezers (OR 0.66, 95% CI 0.50-0.85) but higher levels in adults (OR 1.99, 95% CI 1.02-4.09).</p><p><strong>Conclusions: </strong>HsCRP was increased in adult asthmatics compared to HCs and was associated with several severity-related clinical characteristics. ICS use was associated with higher hsCRP levels in adults, potentially reflecting greater disease severity, whereas ICS use in preschool wheezers was associated with lower hsCRP levels. These age-dependent effects may mirror varying disease courses across the lifespan and progression of asthma. The association of hsCRP with asthma severity in child- and adulthood may indicate its potential relevance for the course of disease and monitoring clinical outcomes. Future longitudinal studies are needed to assess, whether hsCRP may support therapy monitoring.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov; Pediatric arm: NCT02496468, Registration date: 03 July 2015; Adult arm: NCT02419274, Registration date: 14 April 2015.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148609510","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":"Sarcoidosis data-driven patient trajectories and predictors of chronic disease.","authors":"Marios Rossides, Susanna Kullberg, Pernilla Darlington, Anders Eklund, Elizabeth V Arkema","doi":"10.1186/s12931-026-03830-z","DOIUrl":"10.1186/s12931-026-03830-z","url":null,"abstract":"<p><strong>Background: </strong>Sarcoidosis is a heterogeneous granulomatous disease with an unpredictable course. Population-level evidence describing its long-term trajectories and their prognostic implications remains limited.</p><p><strong>Methods: </strong>We identified individuals newly diagnosed with sarcoidosis in the Swedish National Patient Register (≥ 2 ICD-coded visits; 2006-2018). Sarcoidosis-related visits over five years were modeled using zero-inflated Poisson finite mixture models to identify trajectories. Baseline demographic and clinical predictors of trajectory membership were assessed with Poisson regression. Associations between trajectories and long-term outcomes were estimated using multivariable Cox regression. Supplementary analyses incorporated clinical, genetic, and physiological data from the Karolinska cohort.</p><p><strong>Results: </strong>Among 9665 patients, two distinct trajectories were identified: a resolving trajectory (71.5%) with near-complete remission of sarcoidosis-related visits within two years, and a chronic trajectory (28.5%) with persistently elevated visit rates over five years. Older age modestly increased the risk of chronic disease. The strongest predictor of chronic disease was immunosuppressive treatment around diagnosis (risk ratio 2.18 [95% CI 2.04, 2.33]). Diagnosis in neurology, ophthalmology, or cardiology, uveitis, and hospitalization at diagnosis were also associated with chronicity, whereas diagnosis in rheumatology and dispensation of non-steroidal anti-inflammatory drugs were protective. In the Karolinska cohort, Löfgren's syndrome and HLA-DRB1*03 were strongly associated to a resolving course. Chronic sarcoidosis was associated with higher risks of infection, heart failure, diabetes, depression, anxiety, and early death.</p><p><strong>Conclusions: </strong>Sarcoidosis follows two long-term trajectories. Clinical phenotype and need of early treatment predict chronicity, which is associated with substantial long-term morbidity and mortality. Early prognostication may support personalized sarcoidosis management.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":"27 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148585939","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":"Evaluating Alpha-1 Antitrypsin Deficiency testing across Europe to ensure diagnostic accuracy: an EARCO multicentre project.","authors":"Joanna Chorostowska-Wynimko, Stefania Ottaviani, Magdalena Pelc, Malika Balduyck, Tomás P Carroll, Timm Greulich, N Gerard McElvaney, Marc Miravitlles, Francisco Rodríguez-Frías, Marie-Françoise Odou, Adriana Rozy, Susana Seixas, Gerard Orriols, Martina Veith, Farid Zerimech, Angelo Guido Corsico, Maria Cristina Monti, Marion Wencker, Ilaria Ferrarotti","doi":"10.1186/s12931-026-03796-y","DOIUrl":"https://doi.org/10.1186/s12931-026-03796-y","url":null,"abstract":"<p><strong>Background: </strong>Alpha-1 Antitrypsin Deficiency (AATD) is a rare, underdiagnosed genetic disorder caused by pathogenic variants of the SERPINA1 gene, which can lead to reduced levels and/or dysfunctional forms of the Alpha-1 Antitrypsin (AAT) protein. Accurate AATD diagnosis is critical due to its implications for pulmonary and hepatic health. However, diagnostic practices vary across laboratories, particularly in the detection and reporting of rare variants. This study aimed to evaluate the consistency and reliability of AATD diagnostic testing across European laboratories through a non-commercial external quality assessment (EQA)-like initiative.</p><p><strong>Methods: </strong>Seven European laboratories participated in six assessment rounds between 2019 and 2021. Each round involved blinded analysis of serum and dried blood spot (DBS) samples using local standard operating procedures. Tests included AAT and C-reactive protein quantification, isoelectric focusing for AAT phenotyping, and genotyping/sequencing for common and rare SERPINA1 variants. Interrater agreement was assessed using Fleiss' kappa statistic. Allele error rates were calculated for each variant and Kruskal-Wallis tests were used to compare AAT concentrations across laboratories.</p><p><strong>Results: </strong>For common variants (M [normal], S [p.E288V], and Z [p.E366K]), interlaboratory concordance was high, with Fleiss' kappa values indicating almost perfect agreement (0.85-1.00). Genotyping and sequencing error rates for these variants were zero. However, detection of rare variants (e.g., M_Procida [p.L65P], M_Heerlen [p.P393L], and M_Wurzburg [p.P393S]) was inconsistent, with error rates ranging from 0.14 to 0.29. Sequencing was more effective than phenotyping or simple genotyping for rare variant identification. AAT concentration measurements were generally consistent across laboratories, though DBS samples showed more variability. Reporting nomenclature also varied widely, highlighting the need for standardisation.</p><p><strong>Conclusions: </strong>This initiative demonstrated strong interlaboratory agreement in detecting common AATD variants but revealed challenges in identifying and reporting rare variants. The findings support the need for SERPINA1 sequencing in AATD diagnostics and the adoption of standardised nomenclature. Centralised testing in validated reference laboratories is also recommended to ensure diagnostic accuracy and consistency across Europe.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551101","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":"Associations of household air pollution from solid cooking fuel use with risk of chronic respiratory diseases: evidence from the CHARLS study.","authors":"Luhua Yu, Canlei Liu, Jun Jiang, Peng Guan, Yonghao Wu, Xin Zhang, Shujuan Lin, Jianbing Wang","doi":"10.1186/s12931-026-03837-6","DOIUrl":"https://doi.org/10.1186/s12931-026-03837-6","url":null,"abstract":"<p><strong>Background: </strong>Traditional solid fuels remain the primary energy sources for household across China, with particularly widespread use in rural areas. However, evidence linking household use of solid fuels to risk of chronic respiratory diseases (CRDs) remains insufficient.</p><p><strong>Objective: </strong>This study aimed to investigate the association between solid cooking fuel use and risk of CRDs in middle aged and elderly adults.</p><p><strong>Methods: </strong>Participants were recruited from the China Health and Retirement Longitudinal Study (CHARLS). Cooking fuel was categorized into solid fuel (e.g., wood and coal) and clean fuel (e.g., petroleum gas and electric). The diagnosis and timing of the first diagnosis of CRDs, mainly including incident chronic lung diseases (CLDs) or asthma, were ascertained by face-to-face computer-assisted personal interviews using standardized, validated questionnaires. Cox proportion hazards models were used to examine the association between solid cooking fuel use and risk of CRDs.</p><p><strong>Results: </strong>A total of 13,686, 14,986, and 13,414 participants were included in the analysis for the outcome of CLDs, asthma and CRDs, respectively. Compared with clean cooking fuel users, solid cooking fuel users had an adjusted hazard ratios (HRs) of 1.26 (95% confidence intervals [CI]: 1.10-1.45) for CLDs and 1.20 (95%CI: 0.95-1.52) for asthma, respectively. Among all participants, 12.60% (95% CI: 5.39%-19.90%) of CLDs cases could be attributable to participants using solid cooking fuels. Meanwhile, the HRs were higher among users of biomass fuels (e.g., crop residue and wood) than coal users. Of note, participants who switched from solid to clean cooking fuel or persistent clean cooking fuel had a lower risk of CRDs, with the HRs of 0.81 (95%CI: 0.58-1.15) and 0.71 (95%CI: 0.52-0.97) for CLDs, and the corresponding HRs were 0.85 (95%CI: 0.43-1.65) and 1.06 (95%CI: 0.60-1.88) for asthma.</p><p><strong>Conclusions: </strong>Use of solid cooking fuel is associated with a higher risk of CRDs, particularly for CLDs. Our findings suggest that decreasing dependence on solid fuels and transitioning to clean energy sources could contribute to alleviating the burden of CRDs.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551154","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":"UHRF1 inhibits cuproptosis in lung adenocarcinoma via promoting FDX1 promoter methylation.","authors":"Bin Shen, Yichen Luo, Zhangrui Huang, Ruyi Zhou, Shimin Pei, Siyuan Sun, Jianwei Huang, Chen Zhang, Jingwei Yan, Yifan Zhou","doi":"10.1186/s12931-026-03824-x","DOIUrl":"https://doi.org/10.1186/s12931-026-03824-x","url":null,"abstract":"<p><strong>Background: </strong>UHRF1 is a key epigenetic regulator implicated in the tumorigenesis of various cancers through DNA methylation; however, its specific mechanisms in the progression of lung adenocarcinoma (LUAD) remain poorly understood. This study aims to elucidate the regulatory role of UHRF1 in LUAD, focusing on its impact on cuproptosis.</p><p><strong>Methods: </strong>UHRF1 expression and its correlation with patient prognosis were analyzed using the TCGA-LUAD dataset. Expression levels of UHRF1 and FDX1 in LUAD cell lines were verified via qPCR and Western blot. Gene Set Enrichment Analysis (GSEA) was employed to explore UHRF1-associated pathways. The impact of UHRF1 on cuproptosis was assessed using CCK-8 assays, metabolite detection, and apoptosis analysis. Mechanistically, Chromatin Immunoprecipitation (ChIP) and Methylation-Specific PCR (MSP) were performed to investigate the binding and methylation status of the FDX1 promoter. Finally, the oncogenic role of UHRF1 was validated in vivo using a xenograft mouse model.</p><p><strong>Results: </strong>Clinical analysis revealed that elevated UHRF1 expression in LUAD tissues is significantly associated with poor prognosis. At the cellular level, UHRF1 overexpression downregulated FDX1 expression and inhibited DLAT oligomerization. Functional enrichment analysis indicated that UHRF1 is involved in metabolic reprogramming; specifically, its overexpression enhanced glycolysis while suppressing cuproptosis. Mechanistic studies demonstrated that UHRF1 binds directly to the FDX1 promoter, inducing hypermethylation and subsequent transcriptional silencing. Rescue experiments confirmed that restoring FDX1 expression reverses the cuproptosis-suppressive effects of UHRF1. In vivo, UHRF1 knockdown retarded tumor growth and promoted cell death, whereas concurrent FDX1 knockdown attenuated these tumor-suppressive effects.</p><p><strong>Conclusion: </strong>UHRF1 negatively regulates FDX1 expression through DNA methylation, thereby inhibiting cuproptosis and driving LUAD progression. These findings clarify a novel epigenetic mechanism underlying LUAD and highlight the UHRF1/FDX1 axis as a potential therapeutic target.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537533","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":"Transcriptomic profiling of pediatric asthma by diseases state and severity.","authors":"Jihoon Kim, Jelte Kelchtermans, Frank Mentch, Fengxiang Wang, James Snyder, Yichuan Liu, Joseph Glessner, Hakon Hakonarson","doi":"10.1186/s12931-026-03805-0","DOIUrl":"https://doi.org/10.1186/s12931-026-03805-0","url":null,"abstract":"<p><strong>Background: </strong>Despite the high prevalence of pediatric asthma, the molecular basis of its pathogenesis remains incompletely understood, in part due to the complex and heterogeneous nature of the disease.</p><p><strong>Methods: </strong>In this study, we performed bulk RNA sequencing of peripheral blood mononuclear cells (PBMCs) from 183 children (114 asthma cases, 69 controls) across two independent cohorts as a minimally invasive approach to capture the gene expression changes underlying asthma status and severity.</p><p><strong>Results: </strong>Our analysis identified robust signatures of pediatric asthma, including differential expression of a canonical asthma gene (RAB7B) and two novel genes (RPP38-DT, NCAL1), which encode long non-coding RNAs. Additionally, severity-stratified analyses revealed upregulation of several immune-related genes (CCL8, ACOD1, CXCL9, SLAMF1, EPN2) and downregulation of an uncharacterized transcript (ENSG00000288973) as asthma severity increased. Enrichment and co-expression analysis further implicate impaired type I interferon signaling in asthma disease severity.</p><p><strong>Conclusions: </strong>Our results demonstrate contributions to the pathobiology of asthma among several novel molecular candidate genes, which may support future efforts towards molecular stratification of pediatric asthma.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537528","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":"Aspartame and asthma: immunomodulatory effects on airway inflammation.","authors":"Fasty Arum Utami, Shih-Yi Huang, Yu-Hsiang Liu, Jhih-Wei Hsu, Jose Roberto Rodriguez Mazariegos, Nam Nhat Nguyen, Shiu-Wen Huang, Chih-Ming Weng, Hsiao-Chi Chuang, Chung-Hsiung Huang, Wan-Ling Tsai, Yang-Ching Chen","doi":"10.1186/s12931-026-03820-1","DOIUrl":"https://doi.org/10.1186/s12931-026-03820-1","url":null,"abstract":"<p><strong>Background and objective: </strong>Asthma is a heterogeneous inflammatory airway disease influenced by genetic and environmental factors, including diet. Aspartame, a widely used artificial sweetener, has been implicated in immunometabolic changes that may affect asthma risk, but the potential role evidence remains limited. We aimed to examine the association between aspartame intake and asthma outcomes using integrated human analyses and complementary animal experiments.</p><p><strong>Methods: </strong>Human data were obtained from 1021 adolescents in the Taiwan Puberty Longitudinal Study. Aspartame consumption, assessed using a validated food frequency questionnaire, was categorized as none, low, or high based on median intake. Asthma status was determined based on physician diagnosis and symptom history. In parallel, BALB/c mice were sensitized with house dust mite (HDM) extract and administered oral aspartame at 15, 30, or 60 mg/kg/day for 10 weeks. Immunological, microbiome, metabolic, and histopathological parameters were evaluated.</p><p><strong>Results: </strong>Low aspartame consumption was significantly associated with higher odds of asthma (odds ratio = 2.852; 95% confidence interval: 1.038-8.014; p = 0.0369). In mice, aspartame exposure increased serum IgE levels, airway inflammation, and MMP-12 and MCP-1 expression. Although lung function changes were not statistically significant, histological analyses revealed more pronounced goblet cell hyperplasia, peribronchial collagen deposition, and eosinophilic infiltration, especially in the 60 mg/kg group. Aspartame also reduced microbial α-diversity and altered microbial composition. Short-chain fatty acids profiling revealed significantly decreased isobutyric, hexanoic, and heptanoic acid levels in aspartame-treated mice.</p><p><strong>Conclusions: </strong>Aspartame intake exacerbates asthma-related immunological, microbial, and histological disturbances.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473825","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":"Chronic obstructive pulmonary disease and risk of digestive diseases: observational and mendelian randomization analyses in the China Kadoorie Biobank.","authors":"Yuxuan Zhao, Yalei Ke, Dianjianyi Sun, Pei Pei, Ling Yang, Iona Y Millwood, Robin G Walters, Yiping Chen, Huaidong Du, Junshi Chen, Zhengming Chen, Jun Lv, Liming Li, Canqing Yu","doi":"10.1186/s12931-026-03825-w","DOIUrl":"https://doi.org/10.1186/s12931-026-03825-w","url":null,"abstract":"<p><strong>Background: </strong>Several digestive diseases have been reported as comorbidities of COPD. However, consistent evidence supporting their associations is limited. Our study aims to investigate the associations between prevalent COPD and incident digestive diseases in the Chinese population.</p><p><strong>Methods: </strong>We used data from the China Kadoorie Biobank (CKB), enrolling 512,724 participants aged 30-79 years at baseline from 10 areas in China. COPD was defined by spirometry (without bronchodilator) and self-reported emphysema/chronic bronchitis at baseline. We employed stratified Cox proportional regression models to assess the prospective associations of prevalent COPD and airflow obstruction severity with the risks of incident digestive diseases. A total of 31 digestive diseases were included, including the overall digestive diseases, 15 major disease categories, and 15 specific subtypes nested within the major categories. We further conducted one-sample Mendelian randomization analyses to assess the associations of genetically predicted COPD with digestive diseases.</p><p><strong>Results: </strong>During a median follow-up of 15.3 years, a total of 131,993 participants experienced at least one hospitalization or death due to the included digestive diseases. For the composite outcome and major categories, prevalent COPD at baseline was significantly associated with a higher risk of overall digestive diseases (hazard ratio and 95% confidence interval: 1.05 [1.03-1.08]), gastrointestinal inflammation (1.11 [1.07-1.15]) and abdominal pain (1.20 [1.12-1.28]). Dose-response associations of airflow obstruction severity with the overall digestive diseases (P value for trend: < 0.001) and six other disease types were identified. In MR analyses, a genetically predicted higher probability of COPD was significantly associated with overall digestive diseases (OR per doubling of genetically-predicted COPD prevalence: 3.21 [1.71-6.03]) and three other disease types.</p><p><strong>Conclusions: </strong>Prevalent COPD is associated with various digestive diseases in the Chinese population, with MR analyses further supporting a potential causal link. These findings underscore the importance of considering disease severity when managing COPD-related digestive diseases. While COPD was defined based on baseline spirometry in this study, future research incorporating post-bronchodilator assessment could further refine these associations and help distinguish COPD from other reversible airflow limitations.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473753","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":"Cancer risk in patients with nontuberculous mycobacterial pulmonary disease: a nationwide population-based cohort study.","authors":"Chanho Lee, Hyeon Kyu Choi, Hyeok-Hee Lee, Young Ae Kang, Eun Young Kim, Hyung Woo Kim, Naeun Shin, Youngmok Park","doi":"10.1186/s12931-026-03811-2","DOIUrl":"https://doi.org/10.1186/s12931-026-03811-2","url":null,"abstract":"<p><strong>Background: </strong>Although nontuberculous mycobacterial pulmonary disease (NTM-PD) is becoming increasingly prevalent worldwide, its associated cancer risk remains largely unknown. In this study, we aimed to determine whether patients with NTM-PD are at a higher risk of developing cancer than the general population.</p><p><strong>Methods: </strong>In this retrospective nationwide cohort study using the National Health Insurance Service-National Health Information Database of South Korea, we identified 21,879 patients newly diagnosed with NTM-PD between 2010 and 2020, and included 218,790 age- and sex-matched control participants. Cumulative incidences of various cancer types were analyzed using competing risk analysis with all-cause mortality as a competing event, and cause-specific hazard ratios (HRs) were estimated using Cox proportional hazards models adjusted for demographic factors and baseline health checkup results.</p><p><strong>Results: </strong>After adjustment, patients with NTM-PD showed a significantly higher risk of overall cancer than did matched controls (adjusted HR, 1.22; 95% confidence interval, 1.17-1.27; P < .001). In the analysis according to cancer type, the following cancers showed significant changes in risk (adjusted HR [95% confidence interval]): lung cancer (2.25 [2.06-2.45]), multiple myeloma (1.74 [1.26-2.42]), ovarian cancer (1.33 [1.06-1.68]), pancreatic cancer (1.26 [1.09-1.45]), and liver cancer (1.22 [1.07-1.39]). By contrast, stomach (0.83 [0.72-0.96]) and colorectal (0.83 [0.73-0.95]) cancers showed a reduced risk. These associations remained robust across multiple sensitivity analyses.</p><p><strong>Conclusions: </strong>Compared with the general population, patients with NTM-PD are at an increased risk of various cancers, particularly lung cancer. These findings underscore the need for increased cancer surveillance and long-term monitoring of patients with NTM-PD.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148473739","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}