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Journal articleVassileva SM, Khamas SS, Dyhre-Petersen N, et al., 2026,
The impact of benralizumab and dupilumab on exhaled volatile organic compound profiles of severe asthma patients - a preliminary analysis.
, Respir Med, Vol: 262Volatile 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 articleMorelli T, Purcell M, Panaguiton J, et al., 2026,
Understanding risk of poor outcomes in adults hospitalised with respiratory syncytial virus infection: evidence from a multicentre UK cohort.
, Thorax, Vol: 81, Pages: 988-998BACKGROUND: Respiratory syncytial virus (RSV) causes substantial winter pressure on adult services. In the UK, RSV vaccination currently targets adults aged ≥75 years and care home residents; it remains uncertain whether this age criterion alone meaningfully discriminates risk of poor outcome among adults hospitalised with RSV. METHODS: We pooled three UK hospital cohorts (one prospective, two retrospective) of adults admitted with acute respiratory infection (ARI) and PCR-confirmed RSV. The primary outcome was intensive care unit/high dependency unit (ICU/HDU) admission or all-cause mortality within 60 days. Prespecified predictors (age, sex and comorbidities) entered a least absolute shrinkage and selection operator (LASSO) penalised logistic regression; selected variables were refitted using standard logistic regression. Discrimination, calibration and decision-analytic performance were assessed using 1000-bootstrap internal validation and decision-curve analysis. RESULTS: Among 334 adults, 37 (11.1%) experienced the primary outcome. An age-only rule mirroring current UK vaccine age-eligibility (≥75 years) demonstrated only modest discrimination (optimism-adjusted area under the receiver operating characteristic curve (AUC) 0.58, 95% CI 0.48 to 0.65) and a compressed distribution of predicted risks. A four-predictor model-including age, COPD, active/previous cancer and dementia-achieved higher discrimination AUC (0.77 (0.69 to 0.85)), a wider spread of predicted risks and the greatest net benefit across clinically plausible escalation thresholds (5-20%). CONCLUSIONS: In adults hospitalised with RSV-associated ARI, simple age-based heuristics-including the UK ≥75-year threshold-showed only modest ability to discriminate risk of ICU/HDU admission/60-day mortality once hospitalised. Comorbidity-inclusive approaches may provide more informative hospital-level risk stratification and warrant evaluation in future RSV vaccine-effectiveness and outcome st
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Journal articleRowbotham NJ, Jeanpierre M, Bush A, et al., 2026,
New pathogenic PTPN2 variant leading to childhood interstitial lung disease.
, Thorax, Vol: 81, Pages: 1017-1019Protein 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 articleMassenet T, Abuhelal S, Rastegar L, et al., 2026,
Rapid screening of aldehydes by SICRIT-HRMS: understanding ionization behavior in breath analysis
, ACS Measurement Science Au, ISSN: 2694-250XExhaled breath aldehydes represent clinically relevant biomarkers of oxidative stress and lipid peroxidation, yet their reliable online detection remains analytically challenging due to their trace concentrations, chemical reactivity, and structural similarity. This study highlights Soft Ionization by Chemical Reaction in Transfer coupled to high-resolution cyclic ion mobility mass spectrometry (SICRIT-cIMS-HRMS) for the direct detection and characterization of 16 clinically relevant volatile aldehydes in exhaled breath.A controlled offline spiking methodology using Tedlar® sampling bags was developed, enabling systematic investigation of ionization behavior under realistic breath matrix conditions. Comparative analysis in ultra-pure nitrogen and exhaled breath matrices revealed that SICRIT preferentially generates protonated [M+H]⁺, dehydrated [M+H−H₂O]⁺, and oxidation-derived species, with exhaled breath shifting ionization patterns toward oxygen-containing adducts. Ionization competition from N,N-dimethylacetamide, a Tedlar® bag contaminant, was identified and mitigated through standardized bag usage protocols.Quantitative assessment demonstrated good linearity (R² ≥ 0.99 for 13 aldehydes), with LOD values ranging from 1.33 to 25.13 ppbv. Intra-day variability was low across all adducts (CV < 11%), while inter-day variability was significantly lower for [M+H]⁺ species (CV < 13%) compared to oxidation-derived adducts, establishing protonated ions as the preferred targets for long-term biomarker monitoring.Cyclic ion mobility separation was evaluated for isomer differentiation. Although tentative separation of 2-ethylhexanal and octanal was observed, sensitivity losses approaching three orders of magnitude were encountered, likely attributed to instrument geometry and travelling wave-based ion transmission. Nevertheless, the demonstrated ability of ion mobility to discriminate VOCs from chemical noise and isobaric interferences is encour
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Journal articleJiménez-Saiz R, Iborra S, Blanco C, et al., 2026,
Understanding the Type 2 Immunity: An Evolving View Beyond Allergic Diseases.
, AllergyType 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,
Growing Folds: Fetal MR Imaging Anatomy of the Hippocampal Head Digitations.
, AJNR Am J Neuroradiol, Vol: 47, Pages: 2416-2423BACKGROUND 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 articleBilska AG, Chaszczewska-Markowska M, Gajdanowicz P, et al., 2026,
Polystyrene nanoplastics induce mitochondrial dysfunction and stress responses in human PBMCs.
, Ecotoxicol Environ Saf, Vol: 322Plastics 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 articleSiddiqui S, Brooks L, Menzies-Gow A, et al., 2026,
Prioritizing efficacy over convenience.
, Am J Respir Crit Care Med, Vol: 212, Pages: 2111-2112 -
Journal articleBush A, Chotirmall SH, Han MK, et al., 2026,
To the airway and beyond: introduction to an AJRCCM special section on airway disease.
, Am J Respir Crit Care Med, Vol: 212, Pages: 1879-1881 -
Journal articleMassenet T, Stefanuto P-H, Peltrini R, et al., 2026,
Eosinophil-derived breath biomarkers and response to anti-IL-5/5R biologics in severe asthma.
, Am J Respir Crit Care Med, Vol: 212, Pages: 2075-2078 -
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.
, Allergy, Vol: 81, Pages: 3185-3196BACKGROUND: 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 articleDeBerg HA, Baloh CH, DeGottardi Q, et al., 2026,
Differential effects of subcutaneous and sublingual immunotherapy on timothy grass-specific TH2 CD4+ T-cell subsets.
, J Allergy Clin Immunol, Vol: 158, Pages: 845-856BACKGROUND: 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 articleScheire S, Lourijsen E, Blauwblomme M, et al., 2026,
Meta-Analysis on the Harm of Systemic Glucocorticosteroids in Inflammatory Upper Airway Disease and Asthma: An EAACI Task Force.
, Allergy, Vol: 81, Pages: 3071-3106Systemic 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 articleSiddiqui SH, Ding B, Dolin P, et al., 2026,
Healthcare resource utilisation and associated costs in patients with eosinophilic granulomatosis with polyangiitis in England: A retrospective observational cohort study.
, World Allergy Organ J, Vol: 19, ISSN: 1939-4551BACKGROUND: 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 annua
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Journal articleSiddiqui S, Ding B, Dolin P, et al., 2026,
Epidemiology, clinical management, and outcomes in patients with eosinophilic granulomatosis with polyangiitis in England: A retrospective observational cohort study.
, J Allergy Clin Immunol Glob, Vol: 5BACKGROUND: 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 articleSaunders LC, Collier GJ, Smith LJ, et al., 2026,
Longitudinal 1H and 129Xe Lung MRI in Patients With Post-COVID Residual Lung Abnormalities.
, J Magn Reson Imaging, Vol: 64, Pages: 669-682BACKGROUND: It is unclear how lung function may recover in patients with residual lung abnormalities (RLAs) following COVID-19 pneumonia. PURPOSE: To evaluate lung function trends over time in patients with RLAs following hospitalization due to COVID-19. STUDY TYPE: Prospective, multicenter longitudinal cohort study. POPULATION: Twenty-four participants hospitalized due to COVID-19 with RLAs identified on CT ≥ 3 months postdischarge (median [IQR] age 69 (15) years; 3 female) underwent at least one MRI at 6 months (n = 16), 1 year (n = 19), or 2 years (n = 14). FIELD STRENGTH/SEQUENCE: 1.5 T. Dynamic contrast enhanced (DCE) 3D spoiled gradient echo, 129Xe steady state free precession (ventilation), 129Xe 3D spoiled gradient echo multiple b-value (diffusion-weighted), 129Xe 4-echo flyback 3D radial (dissolved phase). ASSESSMENT: Pulmonary blood flow, volume, and mean transit time (MTT) were calculated from DCE MRI. The fraction of 129Xe signal in the red blood cells to membrane (RBC:M) was calculated from the dissolved phase 129Xe acquisition. Ventilation defect percentage (VDP) was calculated from the 129Xe ventilation acquisition. Mean diffusive length scale (LmD) was calculated from the 129Xe diffusion-weighted acquisition. STATISTICAL TESTS: Changes in metrics with time and associations between metrics were assessed using mixed-effect linear regression. Correlations were tested using Spearman's correlation coefficient. Regional differences were assessed using a Friedman's test with a Bonferroni adjustment. p < 0.05 was considered significant. RESULTS: Pulmonary blood flow and MTT improved significantly over time (MTT: 6 months, 15.3 (IQR, 2.0); 1 year, 15.6 (1.4); 2 years, 15.0 (5.3); pulmonary blood flow: 6 months, 75.4 (IQR, 22.0); 1 year, 83.2 (47.4); 2 years, 107.3 (51.1)). RBC:M z-score was low at all three visits (
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Journal articleSong W-J, Kermani NZ, Versi A, et al., 2026,
Clinical Features of Cellular Senescence Pathways in Severe Asthma.
, Allergy, Vol: 81, Pages: 3273-3285BACKGROUND: 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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Journal articleTorres MJ, Atanaskovic Marković M, Gelincik A, et al., 2026,
EAACI Spring Meeting 2026: Prevention as Treatment-A New Paradigm.
, Allergy -
Journal articleMassen G, Jenkins G, Stewart I, et al., 2026,
Temporal trends in single and multiple organ fibrosis prevalence and primary care consultations: a population based cohort study of 5·8 million individuals in England
, BMJ Open, ISSN: 2044-6055ObjectiveTo understand how prevalence estimates of single and multiple organ fibrosis have changed from 2012 to 2022.DesignRetrospective population-based cohort studySettingData from primary (Clinical Practice Resource Datalink Aurum) and secondary care (Hospital Episode Statistics Admitted Patient Care) electronic health records were used to conduct this study.ParticipantsAdults age 18 years and over whose primary and secondary care records were available for research.Main outcome measureFibrotic conditions previously determined from a Delphi survey of clinicians; diagnoses were found in either primary or secondary care records. The primary analysis estimated the prevalence of both single and multiple organ fibrosis prevalence. A secondary analysis used Cox proportional hazards models to investigate the association between the time-updated number of fibrotic conditions and risk of death adjusting for age and sex.ResultsThe cohort consisted of 5,839,459 people with at least one fibrotic condition and a denominator of 18,784,962 people. Over the study period prevalence of fibrotic conditions increased by 6.72%, as of 2022, 19·95% (95%CI:19·92 to 19·98) of adults had at least one fibrotic condition. Prevalence of multiple organ fibrosis increased from 4·78% (95%CI:4·76 to 4·79) in 2012 to 8·51% (95%CI:8·50 to 8·53) in 2022. In the year preceding diagnosis of single organ fibrosis, the median number of primary care consultations was 14 compared with 21 consultations for people with multiple organ fibrosis. Compared with people with single organ fibrosis, people with two fibrotic conditions had a mortality hazard ratio of 2.90 (95%CI: 2.87-2.93), whilst people with three fibrotic conditions had a mortality hazard ratio of 5.22 (95% CI:5.14-5.30).ConclusionsPrevalence of single and multiple organ fibrosis has substantially increased over a decade. People with multiple organ fibrosis access healthcare more tha
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Journal articleHillson K, Hay S, Gore M, et al., 2026,
High oral corticosteroid use during acute attacks of preschool wheeze irrespective of clinical phenotype
, Archives of Disease in Childhood, ISSN: 0003-9888Objective: This study aims to evaluate the burden of oral corticosteroid (OCS) use and any relationship to clinical phenotype in preschool children presenting with acute wheeze attacks.Methods: Single centre prospective study in which children with recurrent, severe preschool wheeze (PSW) who were referred to a tertiary respiratory centre, had symptom questionnaire, point-of-care blood eosinophil count (BEC) and aeroallergen sensitisation tests, undertaken on the same day as their outpatient clinic appointment. Results: 100 children with PSW (median age 3.5 years; interquartile range (IQR) 2.8-4.9 years; 51% male) were recruited. Clinical atopy, based on parental reporting, was present in 42%, while objective sensitisation, confirmed by testing, was observed in 35%. Median lifetime OCS courses per child was 10 (IQR 6-18), and 5 (IQR 3-7) during the preceding 12 months. Regardless of which definition of atopy was used, atopic children had higher BEC when well, compared to non-atopic children: using clinical atopy classification, median BEC was 0.65 vs 0.3×10⁹/L, (p=0.003) and using objective atopy, median BEC was 0.7 vs 0.3 ×10⁹/L, (p<0.0001). There was no difference in the use of OCS in the acute setting between higher and lower BEC, between clinical or objective atopy, or a combination of these, either over the child’s lifetime or during the previous 12 months. Conclusion: Children with severe, recurrent PSW are being treated with large numbers of OCS courses despite the lack of evidence of significant efficacy. There is an urgent need for trials which include phenotyping of acute attacks to guide OCS treatment.
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