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Journal articleWang M, He Y, Hu H, et al., 2026, , Redox Rep, Vol: 31
BACKGROUND: 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 articleVassileva SM, Khamas SS, Dyhre-Petersen N, et al., 2026, , Respir Med, Vol: 262
Volatile organic compounds (VOCs) in exhaled breath reflect biological processes in the lungs. Exploring VOC profiles in severe asthma patients starting biologics may reveal treatment-related biological changes over time. This study aimed to assess the performance and feasibility of applying a sparse partial least squares-discriminant analysis (sPLS-DA) analytical approach in detecting longitudinal changes in exhaled VOCs of patients with severe asthma initiating biologic treatment. Exhaled breath was collected in the 3 TR-ABC study, a multicenter observational prospective cohort study, at baseline and 4 months after starting biologics (benralizumab or dupilumab). VOCs were trapped on thermal desorption tubes and analyzed by gas chromatography-mass spectrometry. Paired sPLS-DA was used to distinguish baseline from post-treatment VOC profiles, and Kendall rank correlation assessed associations with clinical parameters at baseline. Data from two sites (Amsterdam and Copenhagen) were available of 25 severe asthma patients. The sPLS-DA resulted in a model containing five VOCs (methyl isobutyl ketone, 2-ethyl-1-hexanol, 5-methyl octadecane, 2-methylundecane and 1,1'-oxybis(decane)) with an area under the receiver operating characteristic curve of 0.89 (95% confidence interval: 0.79-0.99) for distinguishing baseline and 4 months post treatment. At baseline, a positive correlation was observed between 2-ethyl-1-hexanol and asthma control (Asthma Control Questionnaire); τ = 0.40, p < 0.01. A negative correlation was found between 1,1'- oxybis(decane) and blood eosinophil counts (τ = -0.30, p = 0.04). Based on our results, the proposed analytical approach appears feasible for analyzing longitudinal data in patients with severe asthma initiating biologics. Further validation in larger cohorts is warranted to confirm robustness and generalizability.
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Journal articleRowbotham NJ, Jeanpierre M, Bush A, et al., 2026, , Thorax, Vol: 81, Pages: 1017-1019
Protein tyrosine phosphatase non-receptor type 2 (PTPN2) is a tyrosine phosphatase involved in T cell receptor signal transduction and cytokine response. Loss of function variants have previously been linked with immune mediated diseases such as inflammatory bowel disorders, rheumatoid arthritis and type 1 diabetes. We present a case of childhood interstitial lung disease with a newly identified pathogenic (PTPN2) gene variant in a boy aged 4 years.
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Journal articleJiménez-Saiz R, Iborra S, Blanco C, et al., 2026, , Allergy
Type 2 (T2) immunity is classically associated with defense against helminths and environmental threats, from a physiological perspective, and with allergies and eosinophilic inflammatory diseases, in a pathological sense. However, growing evidence reveals that T2 pathways also support other essential homeostatic functions, including tissue protection and repair. There are major clues from the early evolution of T2 responses for protection against massive tissue damage and positive selection for survival against parasites starting over 500 million years ago. These responses likely co-evolved stepwise with immune-regulatory circuits, culminating in the emergence of the fully functional human-type IgG4 in the great apes (Hominidae) within the last ~10 million years. The involvement of body barriers along with the strong influence of local epithelial cells and their interaction with the microbiome and the immune system is a common characteristic of T2 inflammation. An expanding list of new T2 diseases is being reported, characterized by epithelial cell and immune system activation, epithelial barrier damage, and microbial dysbiosis, including opportunistic pathogen colonization and loss of commensals. This evolving understanding coincides with the clinical success of biologics targeting key T2 mediators such as IL-4, IL-5, IL-13, IL-31, TSLP, and IgE, which have transformed the management of severe allergic diseases and other T2-driven pathologies. However, the contribution of T2 immunity to homeostatic programs raises questions about the long-term consequences of sustained T2 suppression. In this review, we examine the dual role of T2 immunity in health and disease, revisit its evolutionary origins, highlight its protective functions beyond allergy, and discuss the potential implications of prolonged T2 pathway blockade.
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Journal articlePiccirilli E, Troia SG, Fontanella S, et al., 2026, , AJNR Am J Neuroradiol, Vol: 47, Pages: 2416-2423
BACKGROUND AND PURPOSE: The adult hippocampal head (HH) is characterized by sulci and digitations visible both histologically and on MRI. The aim of the study was to describe the emergence and progression of HH digitations in the fetal brain across different gestational ages (GAs) using MRI. MATERIALS AND METHODS: A retrospective assessment was performed on 383 fetal brain MRIs (19-39 weeks' GA) acquired on 1.5T (n = 351) and 3T (n = 32) scanners. Imaging included single-shot fast spin-echo T2, T1-weighted sequences, and axial DWI. The fetal HH was identified on coronal T2 images, and HH morphologic variants were classified using an established adult classification system: class 0 (no sulci, 1 digitation), class 1 (1 sulcus, 2 digitations), and class 2 (2 sulci, 3 digitations). MRIs with brain anomalies identified prenatally or postnatally, abnormal sulcation, or severe artifacts were excluded. Variant frequencies in both hemispheres were grouped by GA. Correspondence analysis and cumulative link mixed models were used to assess the association between GA and class distribution. RESULTS: Two hundred seventy-one fetuses were included, grouped into 8 GA categories. Overall frequencies were 33.6% for class 0, 48.9% for class 1, and 17.5% for class 2. With increasing GA, class 0 frequency decreased, while classes 1 and 2 increased. Between 23 and 25 weeks' GA, detection of more digitated HH variants rose sharply from 1% to 64%. Follow-up in 30 fetuses showed an increase in HH digitations, with no observed reductions. Regression analysis revealed greater digitation complexity in the right hemisphere. CONCLUSIONS: Digitations in the fetal HH begin to appear around 24 weeks' GA, reaching frequencies similar to those observed in adults by the later stages of gestation. The right hemisphere shows higher complexity, possibly reflecting faster growth. These findings contribute to the understanding of hippocampal development and may ser
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Journal articleBush A, Chotirmall SH, Han MK, et al., 2026, , Am J Respir Crit Care Med, Vol: 212, Pages: 1879-1881
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Journal articleBilska AG, Chaszczewska-Markowska M, Gajdanowicz P, et al., 2026, , Ecotoxicol Environ Saf, Vol: 322
Plastics continuously fragment into micro- and nanoplastics (MPs/NPs), which are increasingly recognized as emerging environmental contaminants of global concern. Human exposure to nanoplastics through air, food, and water is becoming unavoidable; however, their direct effects on human immune cells remain poorly understood. Due to their small size, NPs can enter the circulation and directly interact with immune cells, yet their cellular effects in humans remain poorly understood. In this study, we investigated the impact of polystyrene NPs on human peripheral blood mononuclear cells (PBMCs) using an integrated approach that combined imaging, mitochondrial stress testing, basophil activation assays, and single-cell RNA sequencing. Confocal microscopy confirmed efficient cytoplasmic internalization of 25-nm NPs. Optical diffraction tomography revealed that even short-term (1 h) exposure induced pronounced biophysical remodeling, including reduced cell volume and dry mass alongside increased intracellular density and refractive index. Seahorse metabolic profiling demonstrated substantial suppression of mitochondrial respiration across major immune subsets, reflected in reduced basal and maximal respiration, ATP-linked oxygen consumption, and spare respiratory capacity. Basophil activation remained unaffected by NP exposure. Single-cell transcriptomics identified a distinct NP-induced "stress-cell" population, characterized by upregulation of heat-shock and proteostasis pathways and concomitant downregulation of mitochondrial-encoded transcripts. Together, these data show that NPs rapidly disrupt mitochondrial function and activate proteotoxic stress programs in human immune cells. By situating these mechanisms within the One Health framework (human, animal and the planet health), our findings highlight how environmental nanoplastic pollution may translate into immune dysregulation and inform integrated environmental-public health risk assessments.
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Journal articleMassenet T, Stefanuto P-H, Peltrini R, et al., 2026, , Am J Respir Crit Care Med, Vol: 212, Pages: 2075-2078
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Journal articleSiddiqui SH, Ding B, Dolin P, et al., 2026, , World Allergy Organization Journal, Vol: 19
Background Real-world data on the healthcare resource utilisation (HCRU) and cost burden of eosinophilic granulomatosis with polyangiitis (EGPA) are limited. We assessed all-cause HCRU and costs in patients with EGPA versus a matched general population cohort without EGPA and a severe uncontrolled asthma (SUA) cohort. Methods Primary care data in England from the Clinical Practice Research Datalink Aurum database, with linkage to Hospital Episode Statistics inpatient, outpatient and emergency department records, were analysed. Patients with a new EGPA diagnosis in 2006–2020 and ≥ 1 year of data before diagnosis (index date [ID]) were included and matched using a matching ratio of up to 1:4 with a general population cohort without EGPA and patients with SUA. Follow-up was from ID until deregistration, last data collection, death or study end. HCRU and associated costs were assessed across the 12 months prior to ID, and annually from ID to end of the study period, and by disease states and Five-Factor Score [FFS]. Results A total of 486 patients with EGPA were identified, with a corresponding matched general population cohort of 1938 and SUA cohort of 1005 patients. Annual all-cause HCRU rates during follow-up were higher in the EGPA cohort versus the general population and SUA cohorts for all types of care, particularly in the first year after ID. Patients with an FFS of 0 generally had lower HCRU than those with an FFS ≥1. Annualised total HCRU-associated costs (95% confidence interval [CI]) were higher in the EGPA cohort (£13,978 [12,068, 15,888]) versus the general population (£2303 [2145, 2461]) and matched SUA cohorts (£3571 [3326, 3816]), with cost ratios (95% CI) of 8.3 (7.1, 9.6) and 4.1 (3.6, 4.6) respectively, both p < 0.0001. The greatest cost driver was hospital admissions with cost ratios (95% CI) of 12.3 (9.8, 15.5) and 5.8 (4.7, 7.2) compared with the general population and SUA cohorts, respectively. Median all-cause an
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Journal articleSiddiqui S, Brooks L, Menzies-Gow A, et al., 2026, , Am J Respir Crit Care Med, Vol: 212, Pages: 2111-2112
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Journal articleMoffatt MF, Nishimura T, Cox MJ, et al., 2026, , American Journal of Respiratory and Critical Care Medicine, Vol: 212, Pages: 1962-1974, ISSN: 1073-449X
RationaleAsthma is characterized by disruption of the thoracic airway mucosae and loss of microbial diversity. Spatial profiling of the mucosal transcriptome may systematically discover mechanisms for microbial influences on immunity.ObjectivesWe investigated relationships between clinical measures, microbial communities, and the host mucosal transcriptome within different strata of bronchial biopsies in subjects with and without asthma.MethodsWe bronchoscoped 65 adult asthmatics and 44 healthy controls, quantifying bacterial operational taxonomic units (OTUs) in bronchial brushings by 16S rRNA gene amplicon sequences. Biopsy histologic features were scored blind to diagnosis. Following 16S rRNA in situ hybridization of 44 biopsies, bacterial foci were scored in epithelium, basement membrane and stroma. Global human gene expression was quantified in epithelial and stromal compartments using Digital Spatial Profiling.Measurements and main resultsClinical asthma was independently predicted by basement membrane abnormalities (BaseMA), endobronchial bacterial diversity and circulating eosinophil counts, but not by specific OTU abundances. 16S rRNA staining revealed bacteria within epithelium and mucosa of all biopsies. Intra-mucosal bacteria (IMCBs) counts correlated negatively with spatially organized co-expression networks encoding antigen-specific immunity, neutrophil functions, and matrix activation, whereas BaseMA correlated positively with the adaptive immunity module. Eosinophil counts correlated with epithelial bacterial counts and senescence pathways. Clinical asthma was accompanied by upregulation of a Treg cell network.ConclusionsAsthma and its related phenotypes are accompanied by complex mucosal events that extend beyond eosinophilic pathways. Components of diverse airway microbiota may modify immunity by beneficial interactions within the mucosa.
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Journal articleBaraldi F, Mah JSY, Almuhanna A, et al., 2026, , Am J Respir Crit Care Med, Vol: 212, Pages: 2071-2074
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Journal articleShih Y-S, Han C-L, Lee YL, et al., 2026, , Expert Rev Respir Med, Vol: 20, Pages: 1055-1066
INTRODUCTION: Climate change has significantly increased the frequency and intensity of extreme temperature events, posing growing threats to respiratory health. Among the underlying mechanisms, airway dehydration is a critical yet underrecognized pathway that disrupts the airway surface liquid (ASL), which is essential for mucociliary clearance, epithelial integrity, and immune defense. AREAS COVERED: This article examines evidence linking airway dehydration to respiratory disease during temperature extremes. We discuss how hot, dry air and cold, low-humidity conditions disrupt airway hydration balance, leading to impaired mucociliary clearance and increased susceptibility to infection and inflammation. The review summarizes the impacts of airway dehydration on vulnerable populations, including individuals with pre-existing respiratory conditions (asthma, allergic rhinitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis), children, older adults, outdoor workers, and socioeconomically disadvantaged groups. EXPERT OPINION: Airway dehydration represents a unifying mechanism linking climate extremes to respiratory vulnerability but remains underrepresented in clinical practice and public health strategies. We advocate for greater recognition of airway hydration in disease prevention, development of practical measurement tools, and targeted interventions for at-risk populations. Emphasizing airway dehydration as a key mediator offers opportunities to improve clinical management and develop effective climate adaptation strategies for respiratory health protection.
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Journal articleScheire S, Lourijsen E, Blauwblomme M, et al., 2026, , Allergy, Vol: 81, Pages: 3071-3106
Systemic glucocorticosteroids (sGCS) are widely used in the treatment of chronic inflammatory airway diseases such as rhinitis, rhinosinusitis and asthma. It is well-known that systemic use is linked to multiple adverse effects (AEs) both in the short- and the long-term. However, less is known about the safety of multiple short courses of sGCS. Currently there is no established agreement on the acceptable cumulative exposure to sGCS, considering the potential for various AEs. This systematic review and meta-analysis evaluated sGCS-related AEs in both upper and lower inflammatory airway disease, with a particular focus on short- and long-term risks. We further evaluated whether a dose-response relationship existed between the daily and cumulative dosages of sGCS and the occurrence of those AEs. Our meta-analysis confirmed that cumulative dosages between 500 mg and 1 g prednisolone-equivalent significantly increase the risk of most AEs, with risks increasing with incremental dose. These findings underscore the importance of: (a) judicious sGCS prescription and need for steroid stewardship, due to their potential for short- and long-term complications, occurring even with repeated short courses, and (b) prioritization of steroid-sparing approaches (e.g., biologicals) to avoid reaching a cumulative dose of 500 mg.
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Journal articleDeBerg HA, Baloh CH, DeGottardi Q, et al., 2026, , J Allergy Clin Immunol, Vol: 158, Pages: 845-856
BACKGROUND: Allergen-specific CD4+ T cells are a highly heterogenous population. Depletion of these cells has been proposed as essential to achieve allergen desensitization in allergen immunotherapy. OBJECTIVE: The overall aim of this study was to characterize the heterogeneity of timothy grass (Phleum pratense) allergen-specific CD4+ T cells and determine how the frequency and phenotype of these cells change in response to sublingual (SLIT) and subcutaneous (SCIT) immunotherapy. Correlations between frequencies of these cells with Total Nasal Symptom Score and grass-specific serum immunoglobulin were also investigated. METHODS: Mass cytometry with lanthanides-tagged peptide major histocompatibility complex class II multimers and CD154 upregulation assays were used to examine changes in the frequency and phenotype of Phl p-specific CD4+ T cells in longitudinal peripheral blood mononuclear cell samples from a randomized, double-blind, placebo-controlled trial of SLIT and SCIT. Supervised and unsupervised clustering was used for data analysis. RESULTS: Phenotypes of Phl p-specific T cells were highly heterogenous but could be categorized into two major metaclusters, CRTH2hiCD27lo and CRTH2loCD27hi, each with distinct phenotypic profiles. Weak positive correlations between Total Nasal Symptom Score and frequencies of T cells within both subsets were observed. SCIT preferentially depleted CRTH2hiCD27lo cells, whereas SLIT depleted CRTH2loCD27hi cells. CRTH2hiCD27lo cell frequency correlated with Phl p-specific IgE and IgG4, but not IgA, levels. CONCLUSION: Unsupervised clustering revealed distinct subpopulations of allergen-specific T cells that were differentially targeted and depleted by SCIT and SLIT, suggesting that SCIT and SLIT act through overlapping but distinct immunologic pathways.
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Journal articleShamji MM, Rider NL, Adcock I, et al., 2026, , J Allergy Clin Immunol, Vol: 158, Pages: 694-714
Artificial intelligence (AI), first defined in 1955 by John McCarthy, has transformed daily life across industries through applications such as chatbots, autonomous vehicles, and navigation systems. The 2022 release of ChatGPT marked a pivotal moment, highlighting AI's rapidly expanding potential. The health care industry is increasingly embracing AI-enabled tools across oncology, pathology, and radiology to augment disease screening and clinical workflows. Ambient listening technologies support clinical documentation, reduce administrative burden, and improve patient-physician interactions. Large language models combined with natural language processing are being evaluated for generating clinical summaries managing patient portal messaging and converting freehand notes to electronic health records, while also uncovering patterns in patient data to support more personalized treatments. Forward-thinking health systems are establishing informatics departments to optimize these models. Notably, with 1 in 6 adults sourcing health information from AI, rising to nearly one-quarter among individuals younger than 30 years, there is a growing need to ensure that these technologies provide accurate and reliable information to safeguard patient safety and support appropriate clinical use. PRACTALL, a collaboration between the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy & Clinical Immunology, aims to equip allergist-immunologists with essential AI insights highlighting tools for clinical practice, education, and research. By addressing potential pitfalls and biases, PRACTALL illustrates how AI can enhance efficiency, improve patient care, and alleviate administrative burdens in health care.
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Journal articleShen J, Chaudhuri R, Bicknell S, et al., 2026, , Allergy, Vol: 81, Pages: 3300-3317
Severe asthma is a heterogeneous disease. The mechanisms driving airway pathology when type 2 (T2) cytokine activity is suppressed remain poorly understood. This study aimed to provide insight by identifying the airway molecular pathways of T2 biomarker-high and -low severe asthma. We analysed clinical and transcriptomic data from bronchial biopsies and brushes in the UK Refractory Asthma Stratification Programme multi-centre severe asthma cohort (18 corticosteroid-resistant T2 biomarker-high [T2-high], 23 T2 biomarker-intermediate [T2-intermediate], 11 T2 biomarker-low [T2-low]) plus 20 healthy controls pre- and post-treatment with high-dose inhaled corticosteroids (ICS). Many genes dysregulated in asthma vs. health were concordantly dysregulated in healthy subjects receiving ICS. Severe asthma as a whole, independent of confounding by ICS, was characterised by upregulation of mucins, CEACAM5, typical T2-genes (POSTN, CLCA1, CCL26), epithelial mast cell genes, and CPA4. T2-high severe asthma demonstrated upregulated T2-dependent genes, epithelial barrier and keratin genes, adaptive immune responses, and impaired ciliary function. T2-low asthma showed upregulated Th1- and IL-17-associated genes (IDO1, CXCL10, GBP1, LAG3), interferon-γ signalling, neuroimmune pathways, airway smooth muscle-related genes, and neutrophil enrichment. T2-intermediate asthma exhibited a mixed molecular profile sharing features of T2-high and T2-low endotypes, with selective expression of the pathogen defence and antiviral response genes. The results were validated using bronchoscopy data from the U-BIOPRED Consortium. This study defines airway molecular endotypes of severe asthma associated with T2 biomarker high and low phenotypes, independent of corticosteroid effects. These findings offer insights for severe asthma management and the development of targeted biologic therapies.
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Journal articleYang F, Seo S, Hasegawa T, et al., 2026, , Allergy, Vol: 81, Pages: 3286-3299
BACKGROUND: Longer asthma duration predicts non-remission in Type-2 (T2) biologic-treated severe asthma, but underlying mechanisms remain unclear. We investigated associations between asthma duration and inflammatory biomarkers that may explain differential biologic response. METHODS: We analysed cross-sectional data from adults with severe asthma in U-BIOPRED. Asthma duration was defined as years from diagnosis to study entry. T2 and non-T2 biomarkers were measured in blood and sputum. Identical assays were performed in PRISM, a validation cohort of biologic-initiators. Multivariable regression models adjusted for age, sex, ethnicity, BMI, smoking and oral corticosteroid dose. Associations between duration-related biomarkers and 12-month biologic remission were explored in PRISM. RESULTS: In U-BIOPRED (n = 411), median asthma duration was 23 years (IQR 12-38). Longer duration was associated with higher non-T2 biomarkers including sputum CXCL9 (β = 0.024, 95% CI 0.011-0.038), sputum IL-6 (β = 0.024, 95% CI 0.011-0.037) and sputum neutrophils (β = 0.009, 95% CI 0.001-0.017), but lower T2 biomarkers including plasma periostin (β = -0.006, 95% CI -0.009 to -0.003), eosinophils (blood: β = -0.002, 95% CI -0.003 to -0.001; sputum: β = -0.023, 95% CI -0.035 to -0.011), sputum EDN (β = -0.032, 95% CI -0.049 to -0.014) and FeNO (β = -0.006, 95% CI -0.010 to -0.001). PRISM (n = 474) confirmed these associations. Higher sputum CXCL9 was associated with reduced remission in anti-IL-4Rα-treated patients with asthma duration ≥ 20 years (β = -1.73, 95% CI -3.180 to -0.276). CONCLUSION: Longer asthma duration was associated with elevated airway non-T2 inflammation and reduced systemic and airway T2 inflammation. This highlights the importance of airway bio
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Journal articleSiddiqui S, Ding B, Dolin P, et al., 2026, , J Allergy Clin Immunol Glob, Vol: 5
BACKGROUND: Data on the clinical burden of eosinophilic granulomatosis with polyangiitis (EGPA) are limited. OBJECTIVE: We sought to evaluate the epidemiology and clinical burden of EGPA in England using real-world evidence. METHODS: Patients diagnosed with EGPA between January 1, 2006, and February 28, 2019, who had ≥1 year of data before diagnosis (index date) were identified using the Clinical Practice Research Datalink Aurum database. Epidemiology, diagnosis, mortality, treatment, and clinical outcomes were assessed. RESULTS: The incident and prevalent EGPA cohorts comprised 486 and 729 patients, respectively. The overall incidence and prevalence of EGPA were 3.04 (95% CI: 2.77-3.32) cases per million person-years and 2.7 (95% CI: 2.5-2.9) cases per 100,000 persons, respectively. Overall, 76.3% and 26.1% of patients had a Five Factor Score of 0 on the 1996 and 2009 versions. In the incident cohort (mean age 57.9 ± 15.2 years), most patients (97.1%) had ≥1 comorbidity; 79.8% had asthma coded. The median time from first major manifestation to EGPA diagnosis was 44.0 (Q1-Q3: 20.0-56.0) months. The death rate was 37.1 per 1000 person-years (95% CI: 30.1-45.2); the standardized mortality ratio for all-cause deaths was 2.3 (95% CI: 1.9-2.8). The 5-year survival rate was 82.3% (95% CI: 78.1%-85.7%). Most patients (86.2%) received oral glucocorticoids, of whom 27.0% successfully tapered. Six months post index date, 26.1% of patients had a new EGPA manifestation. CONCLUSION: This study emphasizes the substantial clinical burden and reliance on glucocorticoids in EGPA, highlighting the need for improved diagnosis of this disorder.
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Journal articleSong W-J, Kermani NZ, Versi A, et al., 2026, , Allergy, Vol: 81, Pages: 3273-3285
BACKGROUND: Asthma severity increases with age, suggesting a role for accelerated biological ageing. We hypothesised that cellular senescence pathways such as the senescence-associated secretory pathway (SASP) and the p53-cellular senescence pathway are enriched in the airways of patients with severe asthma. METHODS: We utilised transcriptomic data from the U-BIOPRED cohort to analyse enrichment scores (ES) of p53 and SASP pathways in different airway compartments using gene set variation analysis. Findings in bronchial biopsies were validated in the independent NOVA cohort. We examined associations between senescence ES, clinical parameters and other asthma-related gene signatures. Functional clusters of the SASP gene set were also explored. RESULTS: In the U-BIOPRED cohort, p53 and SASP ES were significantly elevated in bronchial biopsies of severe asthmatics compared to mild-to-moderate asthmatics and healthy volunteers, with SASP enrichment validated in the NOVA cohort. In bronchial biopsies, higher senescence ES correlated with frequent exacerbations, oral corticosteroid use, comorbid nasal polyps and lower FEV1%. No significant enrichment was found in other airway samples according to asthma severity. In nasal brushings, SASP ES was significantly higher in participants with comorbid nasal polyps. A distinct SASP functional cluster related to lung injury and repair (Cluster 2) was strongly associated with clinical severity and nasal polyps. Senescence signatures correlated positively with oxidative phosphorylation and macrophage activation signatures, but not with eosinophil signatures. CONCLUSIONS: Cellular senescence pathways are enriched in severe asthmatic bronchial tissues and correlate with disease severity, remodelling and nasal polyps. These findings warrant further investigation into their therapeutic implications. TRIAL REGISTRATION: NCT01982162.
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