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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 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 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 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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Journal articleWilliams TJ, Kermani NZ, Gonzales-Huerta LE, et al., 2026,
A Role for Non-Canonical Caspases in Fungal Allergic Airway Disease.
, Clin Exp Allergy -
Journal articleRoth-Walter F, Adcock IM, Benito-Villalvilla C, et al., 2026,
Update on Non-Biological and RNA-Based Therapeutics in Chronic Inflammatory Diseases: Precision Medicine Through Small Molecules: An EAACI Position Paper.
, AllergyIn the last decades, critical advancements in research technology and knowledge on disease mechanisms steered therapeutic approaches for chronic inflammatory diseases towards unprecedented target specificity. For allergic and chronic lung diseases, biologic drugs pioneered this goal, acquiring on the way-through the clinical use of monoclonal antibodies-a deeper understanding of how inflammatory and immune pathways are configured in disease-specific patterns. In this biomarker-driven approach, synthetic small molecule drugs (SMDs) were perceived as lagging behind in innovation for their relative lack of specificity. This was, however, mostly due to a shift in focus towards biologics rather than true obsolescence of SMDs. In the same timeframe, in fact, advances in structural biology and medicinal chemistry, bioinformatics and artificial intelligence held steadily SMDs' innovation and relevance. The use of kinase inhibitors, well established in the treatment of cancer and rheumatological diseases, is now approved for some allergic skin diseases and is approaching asthma and COPD with several clinical trials; moreover, new therapeutics targeting mast cell receptors and molecules involved in innate immunity are entering preclinical and clinical testing. Alongside, the portfolio of biologics is harboring the expansion of RNA therapeutics, which gained global recognition during the COVID-19 pandemic due to RNA vaccines. Different types of RNA therapeutics, including those based on different non-coding RNAs, are advancing to agency approval and market, thanks to improvements in molecule stability and delivery systems. In summary, the evidence presented in this position paper illustrates that precision medicine is becoming a goal shared between synthetic SMDs and biologics, both protein/antibody-based and RNA therapeutics. We review the current state, unmet needs and opportunities within this evolving landscape, highlighting how small molecular species, both synthetic as S
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Journal articleTomas Catala A, 2026,
In vivo functional profiling and structural characterisation of the human GLP1R A316T variant
, Science Advances, ISSN: 2375-2548Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective therapies for type 2 diabetes (T2D)and obesity, yet patient responses are variable, with GLP1R gene variation potentially linked to therapeutic outcomes. A GLP1R natural missense variant, A316T, protects against T2D and cardiovascular disease. Here, we generated and characterised a human GLP1R A316T mouse model. Human GLP1RA316T/A316T mice displayed lower fasting blood glucose versus wildtype littermates even under metabolic stress, as well as slower weight gain and alterations in islet cytoarchitecture, glucagon secretion and liver metabolism under a high-fat, high sucrose diet. This was however associated with blunted responses to pharmacological GLP-1RAs in vivo. Further investigations in b-cell models demonstrated that human GLP1R A316T exhibits characteristics of constitutive activation but dampened GLP-1RA responses. Results are further supported by cryo-EM analyses and molecular dynamics simulations of GLP-1R A316T structure, collectively demonstrating that the A316T variant governs basal GLP-1R activity and pharmacological responses to GLP-1R-targeting therapies.
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Journal articleKlimek L, Mullol J, Hummel T, et al., 2026,
The Unmet Need of Olfactory Testing in Inflammatory Disorders of the Upper Airways-An EAACI Position Paper.
, AllergyThe sense of smell, with its extensive evolutionary history, is highly prone to disorders that can have a profound impact on daily life. Anosmia affects approximately 5% of the population, with an additional 15% exhibiting reduced olfactory function. The prevalence of olfactory dysfunction (OD) varies by population and age group, and standardized testing reveals a broad range of impacts. OD includes various causes, most commonly aging, inflammation of the olfactory epithelium, upper respiratory tract infections (URTI), traumatic brain injury, and neurological conditions. The recent COVID-19 pandemic has highlighted the association between viral infections and olfactory dysfunction, with severe hyposmia/anosmia being an early marker of infection. Despite its importance, the assessment of olfactory function remains inconsistent across clinical practices. Psychophysical smell tests, while vital for diagnosis and patient management, are underutilized, especially outside of specialized centers. Standardized testing methods are crucial for objective diagnosis, but significant challenges, including test variability, lack of comparability, and healthcare reimbursement issues, persist. The European Academy of Allergy and Immunology (EAACI) advocates for improvements in the quality and standardization of chemosensory assessments. Future efforts must prioritize education, incentives for better testing, and the integration of digital tools to expand access to olfactory testing and diagnosis in remote or quarantine situations. However, office-based testing remains irreplaceable, even with advancements in telemedicine.
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Journal articleFu H, Sun P, Yuan X, et al., 2026,
Epithelial-Associated CD207+ DCs Link Allergen Sensing and IL-25-Driven Th2 Inflammation in Asthma.
, AllergyBACKGROUND: IL-25 is a key epithelial-derived alarmin associated with T2-high asthma, yet its downstream mechanisms remain poorly defined. CD207 (Langerin)+ dendritic cells (DCs) are localized at the airway epithelial interface. However, whether these cells respond to epithelial-derived cytokines and contribute to the Th2 immune response in asthma remains unclear. METHODS: Single-cell RNA-seq from healthy human lungs was analyzed to define the transcriptomic features of CD207+ DCs. Their function was validated in a house dust mite (HDM)-induced asthma model using Cd207-/- mice. Flow cytometry was performed on lung and mediastinal lymph nodes. DC-T cell co-cultures were used to assess Th2 polarization. Epithelial-DC interactions were evaluated using transwell co-culture with ALI-differentiated tracheal epithelial cells. Clinical relevance was examined in airway samples from asthma patients in the U-BIOPRED cohort. RESULTS: CD207+ DCs were enriched in intraepithelial compartments and exhibited increased MHC-II and Claudin-1 expression. In asthma, their abundance correlated with T2 signatures and Th2 markers (CRTH2, ST2). CD207 deletion reduced HDM uptake, Th2 cytokines, airway inflammation, and Th2 differentiation. IL-25 induced CD207+ DCs and enhanced their Th2-polarizing capacity in vitro. An IL-25-CD207 co-expression score correlated with IL-4/IL-5/IL-13 levels and was higher in steroid-naïve patients with severe asthma. CONCLUSION: Our study identifies CD207+ DCs as epithelial-associated antigen-presenting cells that bridge IL-25 signaling and Th2 polarization in allergic asthma. Targeting the IL-25-CD207 axis may offer therapeutic opportunities for T2-high asthma.
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Journal articleUwagboe I, Mumby S, Dunlop IE, et al., 2026,
Does mechanobiology drive respiratory disease? Biomechanical induction of mucus hypersecretion in human bronchial organoids using a photocontrolled biomaterial gel
, Biomaterials Science, Vol: 14, Pages: 452-461, ISSN: 2047-4830Respiratory diseases such as COPD, IPF and severe asthma are major causes of death globally, characterized by chronic inflammation and by fibrotic biomechanical remodelling of the lung ECM. However, present treatments focus on relieving inflammation and symptoms and do not address the mechanobiological aspect. This is in great part because the role of mechanobiology in disease progression and aetiology is not well-understood, indicating a need for new investigatory models. Here we introduce a combined biomaterial and 3D-organoid model, based on a hybrid biomaterial-matrix double-network gel, whose mechanical properties are dynamically photocontrolled by the application of light. This combines basement membrane extract (Matrigel) with biocompatible polymer (poly(ethylene glycol) diacrylate), and a low-toxicity photoinitation system. We achieve rapid (<5 mins) photoinduced stiffening over the range of remodelled lung tissue (up to ~140 kPa). Bronchosphere organoids from primary human bronchial epithelial cells, embedded within the hybrid gel, replicate airway physiology and exhibit a dynamic biological response to matrix stiffening. We show that the expression of mucus proteins Muc5AC and Muc5B is biomechanically enhanced over a period of 24 – 72 h, with in particular Muc5B showing a substantial response at 48 h after matrix stiffening. Mucus hypersecretion is a symptom of respiratory disease, and these results support the hypothesis that biomechanics is a driver of disease aetiology. We combine the photostiffened hybrid matrix gel with organoids from COPD donors, generating an advanced disease model including both cellular and biomechanical aspects. We propose this technology platform for evaluating mechanomodulatory therapeutics in respiratory disease.
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Journal articleBertels X, Scadding G, Backer V, et al., 2026,
Shaping the Future of Respiratory Care: A look into the next decade and strategic recommendations by EUFOREA.
, ChestChronic respiratory diseases (CRDs) remain one of the leading causes of preventable morbidity and disability worldwide, and affect up to one-third of the total Western population in 2025. Recognising the substantial burden of inflammatory airway diseases such as asthma, chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis (CRS) and respiratory allergy, the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organised the symposium "Shaping the Future of Respiratory Care" in April 2025 in Brussels, Belgium at the occasion of the 10 year jubilee. Featuring keynote speakers from the World Health Organization (WHO) and EUFOREA, this initiative had the following aims: (i) promoting dialogue on translating innovations into daily clinical practice, (ii) encouraging collaboration between the different stakeholders in the respiratory field, and (iii) defining strategic priorities to transform respiratory care and arrest the CRD epidemic over the next decade. The symposium highlighted the importance of moving towards predictive, preventive, and patient-centred medicine, while supporting value-based healthcare systems to improve long-term patient outcomes. This report summarises the main insights and strategic directions discussed at the meeting.
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Journal articleKobiela A, Klimczuk M, Serafin PK, et al., 2026,
Remodeling of the cell membrane-associated protein pool affects adhesive membrane properties in filaggrin insufficient keratinocytes and impacts distinct cellular and organellar functions
, BMC Biology, Vol: 24, ISSN: 1741-7007BackgroundAtopic dermatitis (AD) is a highly prevalent inflammatory skin disease, affecting up to 30% of children at some point in their life and frequently persisting into adulthood. Insufficiency in the late epidermal protein filaggrin is frequently observed in the lesional skin of patients, with direct and indirect impact on the skin barrier quality and function. We hypothesized that filaggrin reduction influences intracellular, surface, and derived extracellular membranes of keratinocytes with multiple impacts on the cell function.ResultsUsing filaggrin knockdown keratinocytes generated by shRNA interference (shFLG), we determined that the physical characteristics of the cellular membranes (reported by refractive index) are changed on a filaggrin insufficiency background. Using proteomics, protein binding modeling, and functional assays, we established that filaggrin insufficiency in keratinocytes results in changes in both organelles comprised of internal cellular membranes (i.e., small extracellular vesicles, sEVs) and the plasma membrane. We detected increased association of anti-adhesive proteins (tenascin-C and matrilin-2) with sEVs, resulting in a reduction of the fibronectin-1-mediated sEV uptake by dendritic cell subsets. At the same time, dysregulation of the tight junction and cell adhesion molecules at the level of the cell increased keratinocyte adhesiveness to reconstituted basement membrane substratum as well as faster gap closure in the wound healing assay. We also independently confirmed the findings on sEV uptake and wound healing in filaggrin knockout N/TERT-2G keratinocytes, which more closely resemble primary cells.ConclusionsWe conclude that the alterations in different membrane compartments in filaggrin insufficiency are reflected in changes in keratinocyte functions of relevance to AD pathology, and strategies to target those could open up new therapeutic approaches.
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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)Emphysema 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 articleEvison M, Naylor R, Malcolm R, et al., 2026,
Health economic model to evaluate the cost-effectiveness of smoking cessation services integrated within lung cancer screening in the United Kingdom.
, ThoraxINTRODUCTION: Integrating smoking cessation supports into lung cancer screening can improve abstinence rates. However, healthcare decision-makers need evidence of cost-effectiveness to understand the cost/benefit of adopting this approach. METHODS: To evaluate the cost-effectiveness of smoking cessation interventions, and service delivery, we used a cohort-based Markov model, adapted from previous National Institute for Health and Care Excellence (NICE) guidelines on smoking cessation. This uses long-term epidemiological data to capture the prevalence of the smoking-related illnesses, updated through targeted literature searches as required from the core NICE model, with costs extracted from publicly recognised UK sources. RESULTS: All smoking cessation interventions appeared cost-effective at a threshold of £20 000 per quality-adjusted life year, compared with no intervention or behavioural support alone. Offering immediate smoking cessation as part of lung cancer screening appointments, compared with usual care (onward referral to stop smoking services), was also estimated to be cost-effective with a net monetary benefit of £2198 per person, and a saving of between £34 and £79 per person in reduced workplace absenteeism among working age attendees. Estimated healthcare cost savings were more than four times greater in the most deprived quintile compared with the least deprived, alongside a fivefold increase in quality adjusted life years accrued. CONCLUSIONS: Smoking cessation interventions within lung cancer screening are cost-effective and should be integrated, so that treatment is initiated during screening visits. This is likely to reduce overall costs to the health service, and wider integrated care systems, improve quality and length of life, and may lessen health inequalities.
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Journal articleLewis A, Jung P, Williams P, et al., 2026,
Singing for lung health following completion of pulmonary rehabilitation: feasibility of a randomised controlled trial
, BMJ Open Respiratory Research, Vol: 13, ISSN: 2052-4439Background Pulmonary rehabilitation (PR) is a highly effective intervention for people with chronic respiratory disease; however, it is not known how best to sustain its benefits. Clinical trials are needed to establish if participation in singing for lung health (SLH) groups following PR will improve health-related quality of life, healthcare utilisation and exercise capacity compared with usual care. A feasibility study would help to guide development of these trials.Methods In a multicentre, mixed-methods randomised controlled feasibility trial, PR participants at four sites were prescreened at baseline assessment. An SLH taster session was included routinely as part of the PR programmes. Eligible PR completers were invited to take part in the trial and randomised to usual care or a 12-week SLH course. Feasibility outcomes included recruitment rate, intervention compliance (at least 8/12 sessions) and health economic analysis. Interviews with participants and study personnel were undertaken and thematic analysis of the results was completed.Results Between October 2022 and November 2023, 1311 patients were assessed to start PR, 838 completed. Of those completing, 243 were ineligible to take part (predominantly due to vaccination status and excluded diagnoses for PR referral), and 531 declined. 64 people (33 female, mean (SD) age 69 (12), 41 ethnically white, 33 with chronic obstructive pulmonary disease, 16 with asthma, 9 with interstitial lung disease, 6 with bronchiectasis) were recruited, with 30 (93.8%) SLH and 29 (90.6%) controls completing the study. 20 (62.5%) of the SLH group completed at least 8/12 SLH sessions. There was enthusiasm for a definitive trial from participants, clinicians and singing group leaders’ perspectives, based on positive experiences of trial involvement. Improvements to recruitment strategy, intervention structure, outcome measures and staffing were suggested.Conclusions A definitive randomised controlled trial of SLH post-PR
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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 ImmunolBACKGROUND: 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 articlede Santana MBR, Cruz AA, De Araujo JLF, et al., 2026,
Variants in the Glucocorticoid Receptor gene (NR3C1), asthma control and serum cytokine levels
, Respiratory Medicine, Vol: 251, ISSN: 0954-6111IntroductionAsthma is a heterogeneous disease usually treated with inhaled corticosteroids (ICS) and long-acting beta2 agonists. However, not all individuals achieve adequate control with ICS.AimTo identify genetic variants in the glucocorticoid receptor gene (NR3C1) associated with asthma endophenotypes, bronchodilator reversibility, and asthma control under medium-to-high ICS doses.MethodsAssociation analyses were performed in 365 patients with moderate-to-severe asthma, 383 with mild asthma, and 330 non-asthmatic individuals. Asthma severity was defined by the need for regular treatment with medium-to-high ICS doses. Bronchodilator reversibility was defined as an increase of ≥200 ml and ≥12 % in FEV1 from baseline. Asthma control was assessed using the ACQ6 score. Serum cytokine concentrations were measured with Luminex.ResultsThe A allele of rs2918417 was associated with reduced risk of moderate-to-severe asthma (OR: 0.50; 95 % CI: 0.26–0.98) and fewer exacerbations (OR: 0.54; 95 % CI: 0.30–0.96); GA/AA genotypes showed lower IL-8 and IL-13 levels compared to GG. The G allele of rs6877893 decreased the risk of uncontrolled asthma in the recessive model (OR: 0.53; 95 % CI: 0.29–0.98), with GG carriers showing reduced IL-17A. Conversely, the A allele of rs4585488 increased risk of uncontrolled asthma (OR: 4.42; 95 % CI: 1.06–18.48), and the C allele of rs4912650 was linked to poor control (OR: 1.64; 95 % CI: 1.01–2.69). The G allele of rs4607376 was associated with lack of bronchodilator reversibility (OR: 1.51; 95 % CI: 1.05–2.17) and asthma exacerbations (OR: 1.37; 95 % CI: 1.01–1.87).ConclusionsNR3C1 variants are associated with moderate-to-severe asthma, poor control, lack of bronchodilator reversibility, and differential cytokine profiles.
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