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Journal articleWang M, He Y, Hu H, et al., 2026,
Protective role of fatty acid oxidation against epithelial barrier dysfunction in allergic asthma.
, Redox Rep, Vol: 31BACKGROUND: Fatty acid oxidation (FAO) is implicated in lung diseases, but its role in bronchial asthma is not fully understood. We investigated its effect on airway epithelial barrier integrity. METHODS: Using a house dust mite (HDM)-induced murine asthma model and HDM, IL-4, IL-13, or TNF-α stimulated human primary bronchial epithelial cells (BECs) and bronchial epithelial (Beas-2b) cells, we modulated FAO with L-carnitine (agonist) and Etomoxir (inhibitor). BECs and Beas-2b cells were infected with lentivirus-mediated CPT1A shRNA prior to stimulation. Barrier function, mitochondrial oxidative stress, inflammation, and metabolism were assessed. RESULTS: FAO level in lungs negatively correlated with increased inflammation and tissue injury in HDM-induced asthmatic mice (all p < 0.05), while positively regulating tight junction protein expression. In BECs and Beas-2b cells, Etomoxir treatment and CPT1A knockdown exacerbated the impairment of FAO caused by various stimulants (all p < 0.05). Furthermore, FAO negatively regulated HDM/cytokine-induced epithelial barrier damage, hyperactive inflammatory response, and mitochondrial dysfunction in Beas-2b cells (all p < 0.05). In contrast, treatment with L-carnitine significantly alleviated these pathophysiological features in both in vivo and in vitro models. CONCLUSION: FAO plays a protective role in the occurrence and development of asthma by maintaining airway epithelial cell homeostasis and barrier function.
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Journal articleAndersson LI, Kupczyk M, Dahlén B, et al., 2026,
Adipokines in Obese Asthma: A Complex Relationship Influenced More by Sex, Weight, and Oral Steroid Treatment Than Disease Severity.
, AllergyBACKGROUND: Obesity-related asthma (OBA) is a distinct asthma phenotype, with increased severity. Adipokine release from excessive adipose tissue is suggested to be a key feature of OBA pathophysiology. However, it is unclear how the clinical characteristics of severe asthma associate with adipokine mediators. We examined systemic adipokine levels and evaluated relationships with disease severity, weight, sex, and steroid treatment in asthma. METHODS: A multiplex immunoassay for nine adipokines with proposed involvement in obesity-related inflammation (adiponectin, adipsin, BAFF, chemerin, FGF-21, leptin, lipocalin-2/NGAL, osteonectin and resistin) was designed. Plasma adipokines were measured in 127 patients with mild-to-moderate asthma (MMA) or severe asthma (SA) from the European BIOAIR cohort at baseline and after a controlled 2-week oral corticosteroid (OCS) intervention. RESULTS: Leptin and chemerin were significantly increased in patients with SA vs. MMA. Leptin, adiponectin, adipsin, and NGAL were affected by sex, whereas leptin and adipsin were strongly affected by weight. OCS increased leptin and adiponectin, decreased adipsin and BAFF, and did not affect osteonectin, resistin, or chemerin. No adipokines showed positive associations with exhaled NO, blood or sputum eosinophils, although certain correlations with serum CRP, blood, and sputum neutrophils were observed. CONCLUSIONS: Overall, we observe variable relationships between the nine adipokines, obesity and asthma severity. There were no relationships between adipokine levels and type-2 airway inflammation, yet associations with systemic neutrophilic inflammation were seen. Although one adipokine, chemerin, was independently associated with asthma severity, deciphering the role of adipokines in OBA is complex due to the influence of sex, BMI, and OCS.
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Journal articleKarp T, Merid SK, Kermani NZ, et al., 2026,
Nasal gene expression shows a distinct signature in type 2-high asthma but not in type 2-low disease.
, J Allergy Clin Immunol, Vol: 157, Pages: 879-889BACKGROUND: Type 2 (T2)-low asthma is defined by low levels of T2 inflammation and is associated with resistance to inhaled corticosteroids. Its molecular mechanisms are mostly unknown, and treatment options are limited. We previously showed that nasal brush transcriptomes differ between asthma and controls, reflecting disease-relevant biology. OBJECTIVE: We explored nasal gene expression related to T2-low asthma in the ATLANTIS cohort. METHODS: We compared nasal brush RNA sequencing data between 82 T2-low and 63 T2-high asthma patients and 57 controls. T2-low asthma was defined as blood eosinophil counts < 0.15 × 109/L and Feno < 25 ppb and T2-high as blood eosinophil counts > 0.3 × 109/L and Feno > 25 ppb. Weighted gene coexpression network analysis (WGCNA) was applied to identify gene modules associated with T2-low asthma. The BAMSE and U-BIOPRED cohorts were used for replication analyses. RESULTS: Although differentially expressed genes were found in patients with T2-high asthma across all 3 cohorts, no differentially expressed genes were observed in individuals with T2-low disease compared to controls in ATLANTIS, nor consistently across other cohorts. Our assessment of molecular heterogeneity could not attribute this result to greater intersample variability within the T2-low group. WGCNA in ATLANTIS identified "black" and "purple" gene modules linked to T2-low asthma, with genes enriched in T-cell immunity and ribosomal RNA biology pathways, respectively. The "black" module was replicated in U-BIOPRED and showed the same direction in BAMSE. CONCLUSION: T2-high asthma shows a distinct nasal gene expression signature compared to healthy controls, while patients with T2-low asthma exhibit no consistent changes. Future studies should explore T-cell immunity in T2-low asthma and integrate lower airway multiomics data.
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Journal articleFreeman A, Rink S, Bansal AT, et al., 2026,
Multimorbidity phenotypes and associated characteristics in severe asthma: an observational study of European severe asthma registries.
, Lancet Reg Health Eur, Vol: 63BACKGROUND: The phenotypic nature of multimorbidity in severe asthma is poorly understood. Our aims in this study were to define multimorbidity phenotypes and their characteristics in severe asthma across Europe by identifying and characterising co-aggregation of comorbidities. METHODS: Cross-sectional patient data were analysed from the pan-European Severe Heterogenous Asthma Research Collaboration: Patient Centred (SHARP) Central database of national severe asthma registries. Patients were grouped by four European regions (North, South, East, and West). Hierarchical clustering of comorbidities was applied to characterise the correlation structure of the ten commonest comorbidities within these geographical regions. Subsequent multimorbidity phenotypes (MMP) and their clinical features were then defined. FINDINGS: Data were available for 2690 severe asthma patients and 23 comorbidities from 11 countries. Three comorbidity clusters were consistently seen across the four European regions: 1) osteoporosis plus steroid-induced weight gain, 2) eczema plus rhinitis, and 3) chronic sinusitis plus nasal polyps. Four further comorbidities (obesity, bronchiectasis, gastro-oesophageal reflux disease, psychological factors) showed variable clustering. Multimorbidity was ubiquitous. Patients were assigned multimorbidity phenotypes (MMP) according to comorbidity cluster alignment. MMP sn (sinonasal-associated) and MMP u (no specific cluster alignment) were commonest. MMP ster (steroid-associated multimorbidity) had highest maintenance oral steroid (m-OCS) use, and Body Mass Index, plus worst lung function, asthma control, and asthma exacerbation frequency. MMP max (maximal multimorbidity) showed high prevalence of variably assigned comorbidities, higher m-OCS and biologic treatment needs. INTERPRETATION: Multimorbidity is common in severe asthma and can be classified into replicable novel phenotypes with characteristic clinical traits and outcomes. Recognising these phenotypes c
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Journal articleXie M, Chang Q, Li C, et al., 2026,
TRPA1 mediates ozone-induced murine model of COPD through the Wnt5a/GSK-3β/β-catenin pathway.
, Environ Pollut, Vol: 393Ambient ozone (O3), a ubiquitous oxidant gas and key component of photochemical smog, damages the airway epithelium, provokes oxidative stress, and sustains chronic inflammation, which favors the onset and advancement of chronic obstructive pulmonary disease (COPD). Yet the molecular sensors linking long-term ozone exposure to COPD remain incompletely defined. We examined whether the oxidant-sensitive channel Transient receptor potential ankyrin 1 (TRPA1) mediates ozone-driven murine model of COPD through the Wnt5a/GSK3β/β-catenin pathway. C57BL/6J or TRPA1-deficient mice underwent ozone exposure (2.5 ppm, 3 h/session) every 3 days for 2 months, following administration of either the TRPA1 antagonist A967079 or the Wnt5a/GSK3β/β-catenin inhibitor XAV-939. Similarly, BEAS-2B cells treated with A967079 or XAV-939 or TRPA1-silenced cells were subjected to ozone (1 ppm, 3 h/day) for 4 consecutive days. Oxidative stress, inflammatory responses, emphysematous changes, mitochondrial dysfunction, and airway remodeling were assessed. In addition, gene set variation analysis (GSVA) was used to quantify Reactome Wnt5a/GSK3β/β-catenin pathway activity through public COPD transcriptomic cohorts. Pharmacological inhibition or genetic deficiency of TRPA1 significantly attenuated ozone-induced lung function impairment, and ozone-triggered oxidative stress, emphysematous changes, mitochondrial dysfunction, and airway remodeling. Notably, pharmacological suppression of the Wnt5a/GSK3β/β-catenin pathway using XAV-939 produced comparable protective effects to TRPA1 blockade in both ozone-exposed murine models and BEAS-2B cells. GSVA demonstrated tissue-specific associations between TRPA1 and Wnt5a/GSK3β/β-catenin pathway in COPD patients. TRPA1 mediates crucially ozone-induced COPD through modulation of the Wnt5a/GSK-3β/β-catenin signaling. Therapeutic targeting of both TRPA1 and Wnt5a/GSK3β/β-cat
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Journal articleDinh C-T, Lee Y-L, Chang L-T, et al., 2026,
Assessing the impact of air pollution on anemia: a comprehensive review and meta-analysis.
, Expert Rev Hematol, Pages: 1-10INTRODUCTION: Air pollution and household fuel use may impair hematologic health through inflammation and oxidative stress. We synthesized evidence on associations of ambient/household air pollution with anemia risk and erythrocyte indices. METHODS: We searched PubMed, Embase, and Web of Science (inception-27 September 2025). Two reviewers independently screened and extracted data, and assessed risk of bias using Joanna Briggs Institute checklists. Random-effects meta-analyses pooled risk ratios (RRs) per 10 µg/m3 for particulate matter with aerodynamic diameter ≤10 µm (PM10), ≤2.5 µm (PM2.5), and nitrogen dioxide (NO2), and by household fuel type. RESULTS: Thirty-six studies were included. Each 10 µg/m3 increase in PM2.5 and NO2 was associated with higher anemia risk (RR 1.200, 95% CI 1.041-1.384, I2 98.2%; RR 1.127, 95% CI 1.025-1.241, I2 98.0%). Solid and biomass fuel increased anemia risk (RR 1.143, 95% CI 1.027-1.274, I2 82.9%; RR 1.271, 95% CI 1.050-1.539, I2 91.7%). PM10 was associated with lower hemoglobin (0.074 g/dL, 95% CI -0.124 to -0.023, I2 90.7%). Effects were generally stronger in males and in low- and middle-income countries. CONCLUSIONS: Ambient and household air pollution are associated with increased anemia risk and reductions in hemoglobin; high heterogeneity and observational designs limit causal inference.
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Journal articleWen H, Kole T, Carpaij OA, et al., 2026,
Nasal Airway Transcriptome Reflects Selected Asthma-Associated Gene Signatures in the Lower Airways.
, AllergyBACKGROUND: Transcriptomic analysis of bronchial brushes reveals asthma-associated gene signatures but is limited by the invasiveness of bronchoscopy. Based on the "united airways" hypothesis, we evaluated whether and to what extent nasal brushes reflect asthma-associated transcriptomic changes in the lower airways. METHODS: In the ARMS study, we included 26 asthma patients and 28 healthy controls, all fully clinically characterized. Nasal and bronchial brushes were collected for RNA sequencing. We used edgeR and WGCNA to identify asthma-associated genes and modules in bronchial brushes. We assessed their expression patterns in ARMS nasal brushes and validated the findings in the independent ATLANTIS study (n = 427). RESULTS: We identified 51 asthma-associated genes in the lower airways, of which 40 were up-regulated and 11 were down-regulated in asthma compared to healthy controls. Seven of the 40 up-regulated genes were also up-regulated in ARMS nasal brushes and validated in ATLANTIS: CLCA1, FETUB, CST1, NTRK2, CDH26, TPSAB1, and DHX35. WGCNA revealed two modules that were consistently elevated in asthma across bronchial and nasal brushes in ARMS and confirmed in ATLANTIS. One module represents IL-13 related inflammation, whereas the other represents mast cell activity. CONCLUSION: The asthma-associated gene signatures of the lower and upper airways show a limited but biologically coherent overlap, with seven genes and two gene modules consistently elevated in asthma. The shared gene signatures reflect two separate components of type 2 inflammation: IL-13 related inflammation and mast cell activity. Selected nasal gene signatures offer a non-invasive tool to identify asthma endotypes with distinct molecular mechanisms driving underlying disease biology.
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Journal articleXie M, Weng J, Li C, et al., 2026,
Mechanisms of Anti-Oxidants, N-Acetylcysteine and Elamipretide (SS-31), on Ozone-Induced Airway Hyperresponsiveness and Mucus Hypersecretion.
, Lung, Vol: 204BACKGROUND: Ozone (O₃) exposure induces acute airway injury characterized by airway hyperresponsiveness (AHR) and airway mucus hypersecretion (AMH). Oxidative stress and mitochondria-derived reactive oxygen species (mtROS) are key contributors. We investigated and compared the protective mechanisms of N-acetylcysteine (NAC) and the mitochondria-targeted antioxidant Elamipretide (SS-31) in O₃-induced airway inflammation, AHR and AMH. METHODS: Wild-type C57BL/6J mice received intraperitoneal NAC or SS-31 1 h before a single O₃ exposure. AHR, bronchoalveolar lavage (BAL) inflammatory cells, mucus production and mucin expression, inflammatory mediators, oxidative stress indices, and PI3K/AKT and NLRP3/caspase-1/GSDMD pathway activation were assessed in vivo. BEAS-2B cells were pretreated with NAC, SS-31, or the PI3K/AKT inhibitor LY294002 before O₃ exposure, and pathway activation was evaluate d in vitro. RESULTS: NAC and SS-31 comparably attenuated O₃-induced AHR, reduced BAL inflammatory cell influx, and decreased AMH and MUC5B expression. Both treatments improved redox balance by reducing ROS/mtROS, lowering malondialdehyde (MDA), increasing superoxide dismutase (SOD) activity, and improving GSH/GSSG. NAC and SS-31 also suppressed O₃-induced inflammatory gene expression and inhibited activation of PI3K/AKT and NLRP3/caspase-1/GSDMD signaling in mouse lungs and BEAS-2B cells. PI3K inhibition recapitulated these protective effects in vitro, supporting a mechanistic role for PI3K/AKT signaling during acute O₃ exposure. CONCLUSIONS: NAC and SS-31 protect against acute O₃-induced AHR and AMH by alleviating oxidative stress and suppressing PI3K/AKT-driven inflammatory and pyroptotic pathways. Targeting oxidative stress, including mitochondrial ROS, may represent a viable strategy to mitigate airway damage caused by acute O₃ exposure.
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Journal articleCarlsten C, Salvi S, Wong GWK, et al., 2026,
Supplements and medications for respiratory resilience against air pollution
, ERJ Open Research, Pages: 01127-2025<jats:p>Air pollution is a major threat to respiratory health. We review the current literature on accessible interventions that could help patients build resilience against this threat. We explore the potential benefits of antioxidant-rich diets, including supplements such as fish oil, vitamins C, D, E and prebiotics, which have shown promise in reducing inflammation and oxidative stress, thereby mitigating air pollution-related respiratory decline. Nasal washes are commonly used to clear nasal passages, which could support may aid to clearing pollutants from the nasal passages and improve mucociliary clearance. Furthermore, medications such as nonsteroidal anti-inflammatory drugs and intranasal corticosteroids may have been reported to reduce pollutant- related airway inflammation and lung function deterioration triggered by pollutant exposure. Given the generally favourable safety profile of these interventions, they are reasonable to consider in consultation with a care provider. Further research is needed to establish optimal dosing, safety and long-term efficacy, particularly for those exposed to chronic air pollution. Healthcare professionals should work together to further identify and implement effective interventions to mitigate the impact of air pollution on respiratory health.</jats:p>
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Journal articleLee B, Anpalagan H, Wong E, et al., 2026,
Hormone replacement therapy and the risk of asthma attacks: population-based cohort study
, ERJ Open Research, ISSN: 2312-0541Background Women experience higher rates and greater severity of asthma after puberty, suggesting that sex hormones play a key role in airway disease. Hormone replacement therapy (HRT), which acutely alters circulating sex hormone levels, provides a useful model to examine their effects on asthma attacks. We sought to examine the association between HRT use and asthma attacks. Methods We obtained a cohort of women with asthma, aged 45 to 60 years, using nationwide U.K. primary care health records linked to hospital and mortality data, 2004-2020, to compare HRT-users to non-users. We applied inverse-probability of treatment weighting and Cox proportional hazards, accounting for demographics, asthma severity and comorbidities; stratifying by potential modifiers: body mass index (BMI), blood eosinophil count, smoking and HRT-type (oestrogen-only, progesterone-only and combined). Results 182,010 women were eligible for the study, of whom 9,663 were incident HRT users and 172,347 were non-users. Median age was 52 years (IQR: 50-55 years). HRT-users and non-users were broadly similar in terms of BMI, smoking history but non-users had slightly higher proportions residing in more deprived areas, with more comorbidities, higher reliever use and asthma attacks in the year before study entry, but lower use of preventer inhalers. After applying weighting, there was no association found between HRT use and asthma attacks (weighted-HR 0.97, 95% CI 0.90-1.04). There was no modification of that association by blood eosinophil level, BMI, smoking history or HRT-type. Conclusion Hormone replacement therapy use is not associated with asthma attacks in women with established asthma aged 45 to 60 years old.
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Journal articleAlimohammadi M, Tahmasebi S, Amani D, et al., 2026,
MiR-146a-armed exosomes reverse immunosuppressive networks in NSCLC by dual-targeting of MYD88/STAT3 and PD-L1 axes.
, Int Immunopharmacol, Vol: 172BACKGROUND: MiR-146a has been found to be a tumor suppressor and is downregulated in NSCLC cells. This study investigated the effects of delivering miR-146a via tumor-derived exosomes (TEX-MiR-146a) on the behavior of malignant cells and immunological modulation in NSCLC models. METHODS: miR-146a expression was evaluated in A-549 and normal MRC-5 lung epithelial cells. Exosomes were isolated from A-549 cells, loaded with a miR-146a mimic, and characterized for size, morphology, surface markers, and loading efficiency. In vitro, the functional effects of TEXmiR-146a were compared to controls using tests for cell survival, apoptosis, migration, invasion, wound healing, colony formation, and gene expression. Co-culture immunological assays, including T cell subset and cytokine profiling, were also performed using patient-derived peripheral blood mononuclear cells (PBMCs). RESULTS: TEXmiR-146a efficiently loaded miR-146a into cells (60.1 % ± 4.0 efficiency, P < 0.0001). Treatment with TEXmiR-146a (25 μg/ml) significantly reduced the viability of A-549 cells by ∼51 % after 48 h (P < 0.0001). Cell migration and invasion were inhibited by >50 %, with migrating cells reduced to 116.7 ± 7.09 (P < 0.001) and invading cells to 171.7 ± 6.028 (P < 0.001), respectively, compared to controls. Pro-apoptotic genes Bax/Bcl-2 (P = 0.0002) and Caspase-3 were upregulated (P = 0.0003), while metastatic and immunoregulatory genes VEGF-A, MMP-9, STAT3, MYD88, and PD-L1 were downregulated (all P < 0.05). In patient PBMCs, TEXmiR-146a increased the frequency of cytotoxic CD8+ T cells (24.75 ± 1.23 % versus 20.15 ± 1.26 %, P < 0.0001) and decreased Treg cells (2.01 ± 1.22 % versus 4.04 ± 1.72 %, P = 0.015) compared to th
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Journal articleAnanth S, Wedzicha JA, 2026,
COPD exacerbations: Major events in the course of the disease
, PRESSE MEDICALE, Vol: 55, ISSN: 0755-4982 -
Journal articleLin Z, Huang J, He L, et al., 2026,
Integrative genomics reveal genetic links of chronic cough with risk factors and brain regional volumes.
, ERJ Open Res, Vol: 12, ISSN: 2312-0541OBJECTIVES: Chronic cough is a common condition, particularly among women in their sixties, and is associated with a high disease burden and reduced quality of life. Limited understanding of its risk factors and genetic associations represents a barrier to its effective management. METHODS: We used genome-wide association study datasets for respiratory and other diseases, as well as behavioural phenotypes from the UK Biobank, FinnGen, Global Biobank Meta-analysis Initiative and Psychiatric Genomics Consortium. We identified pleiotropic genetic associations with chronic cough using linkage disequilibrium score regression, pleiotropy analysis and Bayesian colocalisation analysis. We conducted Mendelian randomisation analysis to determine the association between brain regional volumes and chronic cough risk. RESULTS: We identified 19 significant genetic correlations between chronic cough and various risk factors and associations. Among 74 pleiotropic genomic loci identified, the 4p14 locus had the strongest effect on cough-associated asthma, with RFC1 linked to cerebellar ataxia, neuropathy and vestibular areflexia syndrome. Gene enrichment analyses highlighted that the central nervous system and ion channel activity play roles in the pathogenesis of cough. A reduction in the volume of isthmus cingulate, thalamus proper and pallidum was associated with an increased risk of chronic cough. In ageing-associated cough, the direct effect of ageing on chronic cough showed an increased odds ratio of 1.044, while a reduction in left pallidum volume was associated with a decreased risk, with an odds ratio of 0.902. CONCLUSIONS: This genetic basis of chronic cough risk and its associations highlights both structural and functional genetic overlap, confirming the impact of reductions in brain regional volumes on chronic cough as a result of ageing.
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Journal articleToumpanakis D, Kim Y, Usmani OS, 2026,
Small Airways Disease in Patients With COPD: A Question-and-Answer Approach for Everyday Clinical Practice.
, Chest, Vol: 169, Pages: 641-651TOPIC IMPORTANCE: Small airways are recognized as the main site of disease progression and airflow limitation in patients with COPD. Whereas conventional lung function testing, for example spirometry, is nonspecific to small airways disease (SAD), the advent and wider availability of techniques sensitive to SAD, such as oscillometry, has improved our understanding of the clinical importance of small airways dysfunction. Despite this progress, a gap between the recent advances in knowledge of SAD and its implementation in daily clinical practice remains. We aimed to answer key questions that would allow practitioners (eg, family doctors, internists, pulmonologists) to introduce oscillometry into their clinical practice. REVIEW FINDINGS: COPD pathogenesis is characterized by SAD, with an increasing prevalence with more advanced disease. Evaluation of small airways dysfunction with sensitive techniques (eg, oscillometry, nitrogen washout) contributes to early disease detection and plays a significant role in almost every aspect of disease assessment, including confirmation of diagnosis, functional severity grading, and monitoring of lung function decline. Moreover, small airways dysfunction shows equivalent or even better correlation with patient-reported outcomes, including symptoms, quality of life, and exacerbations, compared with conventional lung function testing. This suggests a role for small airways assessment as a treatable trait in COPD to target and monitor therapeutic interventions. SUMMARY: Accumulating evidence and recent advances have delineated the role of small airways assessment in COPD and warrant its implementation in the management plan of patients with COPD in daily clinical practice.
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Journal articleXuan S, Wu Y, Liu F, et al., 2026,
CD207-Positive Dendritic Cells Promote Emphysema Through CD8+ T Cell Pathway in Chronic Obstructive Pulmonary Disease.
, Adv Sci (Weinh), Vol: 13Emphysema remains a major challenge in the management of chronic obstructive pulmonary disease (COPD). This study identifies CD207-positive dendritic cells (CD207+ DCs) as pivotal mediators of emphysema progression. In patients with COPD, the abundance of CD207+ DCs in small airways correlates with both emphysema severity and lung function decline (FEV1%pred). In a murine emphysema model, adoptive transfer of CD207+ DCs reversed the attenuation of emphysema, inflammation and CD8+ T-cell expansion in CD207-knockout mice. Mechanistically, cigarette smoke-induced epithelial GM-CSF drives the expansion of CD207+ DCs. Upon activation by damage-associated molecular patterns (DAMPs), these DCs promote CD8+ T cell proliferation and activation via Birbeck granule-mediated MHC-I antigen cross-presentation. Collectively, these findings demonstrate that CD207+ DCs orchestrate a pathogenic CD8+ T-cell response in emphysema and represent a promising therapeutic target.
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Journal articleMao R, Zhang H, Chang Q, et al., 2026,
Progression of interstitial lung abnormalities and its impact on mortality in patients with lung cancer resection.
, Chin Med J Pulm Crit Care Med, Vol: 4, Pages: 81-91BACKGROUND: Interstitial lung abnormalities (ILAs) are incidental abnormal lung findings on computed tomography that can co-exist with lung cancer, but risk factors for their progression and impact on survival after lung cancer resection remain unclear. This study aimed to identify risk factors for ILA progression, develop a radiomics-based model to predict it, and evaluate the association between ILA progression and mortality. METHODS: Patients with ILAs who underwent lung cancer resection in Shanghai Chest Hospital between January 2016 and May 2019 were retrospectively selected and divided into three subcategories at baseline: non-subpleural ILAs, subpleural non-fibrotic ILAs, and subpleural fibrotic ILAs; and three subcategories during follow-up: improved ILAs, unchanged ILAs, and progressive ILAs. Multivariate logistic regression was used to identify clinical and laboratory risk factors associated with ILA progression, and radiomics-based machine learning models were independently constructed to predict ILA progression using baseline CT imaging features. Survival data were analyzed using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: There were 1363 ILA cases among 10,295 patients who underwent primary lung cancer resection, with a proportion of 13.24%. After 2- and 4-year follow-up, the progression rates of ILAs were 9.86% (65/659) and 10.19% (43/422), respectively. Subpleural fibrotic ILAs (2-year follow-up: OR = 6.078, 95% confidence interval [CI]: 2.633-14.028, P < 0.001; 4-year follow-up: OR = 3.339, 95% CI: 1.085-10.272, P = 0.035), and radiotherapy (OR = 13.595, 95% CI: 4.540-40.710, P < 0.001; OR = 11.496, 95% CI: 2.864-46.141, P = 0.001) were risk factors for ILA progression. Using radiomics features extracted from baseline CT, the AutoGluon machine learning model demonstrated high performance in predicting ILA progression among patients with confirmed ILAs (for all ILAs, mean area under curve value: 0.790, accuracy: 0.801 &
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Journal articleKinoshita R, Sathyapala A, Polkey MI, 2026,
Has the time come for workplace screening for obstructive sleep apnoea (OSA)?
, Thorax -
Journal articleManullang A, Tran XN, Lee Y-L, et al., 2026,
Impact of ambient particulate matter and meteorological factors on COPD risk and its association with blood eosinophilia.
, BMC Pulm Med, Vol: 26BACKGROUND: While the association between air pollution and chronic obstructive pulmonary disease (COPD) is well-documented, limited studies investigate the effects of meteorological factors in COPD. The objective of this study is to examine the impact of particulate matter less than < 2.5 μm (PM2.5), temperature and relative humidity (RH) on COPD detection, with a specific focus on the importance of blood eosinophil levels. METHODS: This case-control study was conducted in Taiwan from December 2010 to April 2022, including 937 COPD patients and 833 controls. The average daily exposure and differences in PM2.5, temperature, and RH over 1-day, 7-day and 1-month periods were calculated using the radial basic function interpolation model. The associations between PM2.5, temperature, and RH with COPD were assessed using logistic regression, and non-linear exposure-response associations were further examined using generalized additive mixed models. RESULTS: We observed that each 1 µg/m³ increase in PM2.5 daily average over the 7-day and 1-month periods were associated with a 1.051-fold and 1.059-fold increase in the odds ratio (OR) of COPD, respectively. The exposure-response curves indicate that individuals with blood eosinophilia (≥ 2%) exhibit consistent increases in the odds of COPD in response to rising PM2.5 levels. The exposure-response relationship between temperature and COPD was also observed in subjects with blood eosinophilia. We observed that a 1-month average PM2.5 was associated with a 1.044-fold increase in the OR of GOLD stages 3–4 among COPD with eosinophil levels ≥ 2%. CONCLUSION: PM2.5 levels were associated with increased odds of COPD detection, with individuals exhibiting blood eosinophilia being especially vulnerable to PM2.5 exposure and more likely to detect severe COPD. Improving air quality for human health protection is important in response to climate change challenges.
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Journal articleKumar A, Chan R, Zounemat-Kermani N, et al., 2026,
Small Airways Dysfunction and Remission in Adults With Asthma: A Longitudinal Exploratory Analysis of the AssessmenT of smalL Airways involvemeNT In aSthma (ATLANTIS) Study.
, AllergyBACKGROUND: Asthma remission is a feasible treatment goal. However, remission definitions vary, and predictive biomarkers remain underexplored. METHODS: We conducted a post hoc analysis of ATLANTIS (NCT02123667), a multinational prospective study including 684 adult asthmatics. Remission was defined by 3-component (3C) and 4-component (4C) criteria. 3C remission included: (1) ACQ-6 < 1.5, (2) no maintenance oral corticosteroids, (3) no exacerbations. An absolute decline < 10% in pre-bronchodilator FEV1% predicted, was added for the 4C definition. Multivariate logistic regression identified remission predictors. A novel Low Disease Activity (LDA) score was developed using factor analysis of five clinical variables (ACQ-6, FeNO, BEC, and FEV1) including an innovative small airways dysfunction questionnaire tool (SADT). Nasal transcriptomics were analysed for differential gene expression and pathway enrichment and were replicated in U-BIOPRED (NCT01976767) using sputum transcriptomics. U-BIOPRED was included only to study omics replication of remission pathways identified in ATLANTIS. FINDINGS: Remission occurred in 48% (3C) and 45% (4C) of patients. Predictors included male sex, better lung function, fewer previous exacerbations, and higher SADT (fewer small airways symptoms). LDA identified milder disease and was associated with remission [OR 3C 4.43 (2.80, 7.10) and 4C 3.46 (2.23, 5.43)], improved QoL [OR 2.07 (1.65, 2.60)], and fewer future exacerbations [OR 0.43 (0.22, 0.85)]. Transcriptomic analyses revealed remission-associated upregulation of interleukin 4/13 signalling and downregulation of coagulation pathways, in both ATLANTIS and U-BIOPRED. INTERPRETATION: SAD was associated with reduced asthma remission. A novel LDA tool demonstrated clinical utility in stratifying prospective asthma risk. Key immunologic and haemostatic pathways may underpin remission, offering potential targets for future intervention.
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Journal articleHo V, Baker J, Fenwick P, et al., 2026,
Single cell microfluidic quantification of miRNA-21 and miRNA-34a reveals miRNA interactions in small airway epithelial cells and fibroblasts from COPD patients
, American Journal of Physiology - Lung Cellular and Molecular Physiology, ISSN: 1040-0605Rationale: MicroRNA-21 and microRNA-34a are implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, but their cell-specific expression patterns and interactions within individual airway cells remain unexplored.Objective: To develop a single cell microfluidic platform for dual, amplification-free detection of miR-21-5p and miR-34a-5p in primary small airway cells from COPD patients.Methods: Small airway epithelial cells (SAEC) and fibroblasts (SAF) were isolated from COPD patients and non-smokers (n = 6–8 per group). A microfluidic chip with dual miRNA sandwich hybridisation assays was used to quantify miR-21-5p and miR-34a-5p in single cells. Expression of miRNAs and their target genes was evaluated under oxidative stress using qPCR and Western blotting.Main Results: Single cell analysis revealed significantly higher miR-21-5p and miR-34a-5p expression in COPD-derived cells compared to controls. MiR-21 exhibited greater variability than miR-34a, and their positive correlation in control cells was disrupted in COPD. Oxidative stress elevated miR-21 and miR-34a while reducing expression of miR-21 targets and increasing senescence markers (p21Cip1/Waf1, p16INK4a). MiR-21 antagomir restored expression of suppressed targets in both cell types.Conclusions: Our novel single cell microfluidic platform enables precise, simultaneous detection of miR-21 and miR-34a in single small airway cells. This allows the interrelationship between the miRNAs to be assessed within the same cell. MiR-21 and miR-34a represent promising therapeutic targets for restoring gene regulatory balance in COPD.
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