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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 articleBush A, Chotirmall SH, Han MK, et al., 2026,
To the Airway and Beyond: Introduction to an AJRCCM Special Section on Airway Disease
, American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X -
Journal articleGiblin SP, Moiseanu VR, Carrington CJ, et al., 2026,
The small ubiquitin-like modifier SUMO-3 acts as a neutrophil chemoattractant via the chemokine receptors CXCR1 and CXCR2.
, J Innate Immun, Pages: 1-29INTRODUCTION: Small ubiquitin-like modifiers (SUMOs) are small peptides conjugated to proteins during post-translational modification which have been reported to modulate several aspects of the immune system, notably in auto-immune disorders. METHODS: We used a SUMO-based bacterial expression system to create a recombinant protein putatively expressed by Toxocara canis, which we hypothesised might antagonise responses via the chemokine receptor CXCR1. RESULTS: Although our recombinant Toxocara canis protein was devoid of antagonist activity, we serendipitously observed that recombinant SUMO-3 protein had chemotactic activity for CXCR1 transfectants. Further study found that SUMO-3 acted as a full agonist of CXCR1 and the closely related receptor CXCR2, the latter responses ablated by a CXCR2 antagonist. SUMO-3 showed similar efficacy at both receptors but reduced potency when compared to CXCL8, with chemotaxis observed at high nanomolar to micromolar concentrations. In receptor endocytosis assays, SUMO-3 induced internalisation of CXCR1 and CXCR2, with inferior potency and efficacy to CXCL8. Translating our findings to primary cells, a broad range of SUMO-3 concentration gradients were shown to induce the chemotaxis of human neutrophils. Finally, SUMO-3 was found to be released by necrotic cells into the extracellular milieu. CONCLUSIONS: Collectively, our findings suggest that SUMO-3 can induce the chemotaxis of neutrophils via CXCR1 and CXCR2. We postulate that in vivo, release of SUMO-3 from necrotic cells may serve to recruit neutrophils, contributing to tissue homeostasis and the resolution of inflammation.
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Journal articleSilva AE, Ferrante G, Silveyra P, et al., 2026,
Peripubertal Changes in Asthma.
, Am J Respir Crit Care MedAsthma is a heterogeneous disease affecting nearly 300 million people around the world. It is the most common chronic respiratory disease of childhood. There are significant sex differences in asthma incidence, severity, and morbidity around the time of puberty. The reasons for these peri-pubertal changes around the time of puberty are still not fully understood but they are likely multifactorial. In this review, we will discuss several proposed contributing mechanisms, including sex differences in anatomy and development, the effects of sex hormones on airway inflammation and reactivity, the immunomodulatory effects of sex hormones, differences in mucociliary function, and sex differences in genetic and epigenetic factors.
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Journal articleKhor YH, Luppi F, Adegunsoye A, et al., 2026,
Acute exacerbation in fibrotic interstitial lung disease: An International Working Group Report.
, Am J Respir Crit Care MedAcute exacerbations (AEs) occur both in patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic interstitial lung disease (fILD). These events confer high morbidity and mortality, with a lack of proven effective therapeutic interventions. The objective of this state-of-the-art document is to summarize latest evidence since the 2016 international working group report on AE-IPF, expanding it across the spectrum of all fILDs. A comprehensive literature review on the epidemiology, associated and risk factors, prognosis, and management of AE-fILD is summarized. In addition to revising the AE definition and diagnostic criteria for broad application across different fILDs, a conceptual framework for acute respiratory worsening (ARW) has been proposed to encompass a variety of acute respiratory deteriorations, both related and unrelated to AE. This allows structured evaluation in both clinical and research settings. The proposed revised definition for AE-fILD is an acute respiratory event characterized by increased respiratory symptoms or signs and associated with radiologic or histologic features consistent with diffuse alveolar damage (with or without superimposed organizing pneumonia) in a patient with known or newly diagnosed fILD. On the other hand, ARW refers to a heterogeneous group of clinical events with acute symptom worsening not attributable to DAD in patients with fILD, such as pulmonary edema, bronchitis, and pneumonia, although severe pneumonia can trigger AE-fILD. Additionally, we discuss considerations for inclusion of AE as a clinical trial endpoint, as well as research priorities for advancing knowledge on the pathogenic mechanisms, event prediction, risk stratification, and development of drugs and supportive treatments.
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Journal articleTorres MJ, Shamji M, Arasi S, et al., 2026,
Decalogue of the Declaration of Salamanca: Advancing Undergraduate Education in Allergy and Clinical Immunology Across Europe.
, Allergy -
Journal articleKuks PJM, Aabed AMA, Premereur LCA, et al., 2026,
Clinical phenotyping of asthma patients with elevated sputum eosinophils and low blood eosinophils: a post-hoc analysis of the multicentre ATLANTIS cohort.
, EBioMedicine, Vol: 130BACKGROUND: Patients with eosinophilic asthma are responsive to treatment with corticosteroids and biologics. Eosinophilia is usually identified based on blood eosinophil counts, but there is discordance between blood and sputum in some cases. A subset of patients may have sputum eosinophilia despite low blood eosinophil levels. The clinical implications of this so-called isolated sputum eosinophilia are unknown. The aim of this study is to investigate the clinical expression of asthma in patients with isolated sputum eosinophilia. METHODS: In this post-hoc ATLANTIS analysis we included patients with available blood and/or sputum data from ATLANTIS. Patients were classified according to blood eosinophils (< or ≥300 cells/μL). Patients with isolated sputum eosinophilia were compared with those with low eosinophils in both compartments. FINDINGS: Of the 487 patients with low blood eosinophils counts, sputum samples were available in 146. Among these, 25 (17%) had isolated sputum eosinophilia. Compared with patients with low eosinophils in both compartments (n = 121), patients with isolated sputum eosinophilia had more airflow obstruction (FEV1/FVC ratios (68.8% vs. 75.4%, p <0.01)) and small airways dysfunction (Scond0.05 vs. 0.03 1/L, p = 0.02) and more frequently reported exacerbations in the year prior to inclusion (28% vs. 9%, p = 0.01). Clinical characteristics were broadly comparable to those observed in patients with blood eosinophilia. INTERPRETATION: Isolated sputum eosinophilia occurs in a subgroup of patients with asthma, in association with worse clinical outcomes. These findings suggest that airway eosinophilia may not always be captured by conventional blood biomarkers and warrant further investigation into the clinical implications of this phenotype to determine whether these patients may benefit from treatment strategies targeting type 2 inflammation, such as intensified steroids or biologics. FUNDING: Chiesi Farmaceutici sponsored the ATLA
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Journal articleYang F, Seo S, Hasegawa T, et al., 2026,
Longer Asthma Duration Is Associated With Elevated Non-T2 Sputum Biomarkers and Reduced T2 Inflammation in Severe Asthma.
, AllergyBACKGROUND: 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 articleLau R, Giblin S, Sugar A, et al., 2026,
SpyCEP dismantles neutrophil immunity via disorder-drivenchemokine remodeling and GAG targeting
, Proceedings of the National Academy of Sciences of the United States of America, ISSN: 0027-8424Streptococcus pyogenes (Group A Streptococcus; GAS) employs sophisticated virulence strategies to evade human immunity, including secretion of the cell envelope protease SpyCEP, which cleaves and inactivates key neutrophil‑attracting chemokines such as CXCL8. Here, we integrate cryo‑electron microscopy (cryo‑EM), nuclear magnetic resonance (NMR) spectroscopy, and native mass spectrometry (MS) to investigate how SpyCEP disrupts CXCL8 function. We demonstrate that a disordered aromatic and acidic region within the cleaved autocatalytic maturation loop (CAML) of SpyCEP mimics receptor N-domains and binds an allosteric site on CXCL8. The resulting interaction forms a dynamic fuzzy complex and is coupled to dimer dissociation, consistent with enhanced access to the cleavage site. This disorder‑mediated substrate engagement differs from classical protease mechanisms that rely on rigid recognition interfaces. Additionally, glycan microarray and NMR analyses show that the CAML region mediates glycosaminoglycan (GAG) binding, suggesting a means to recruit SpyCEP and maximize encounters with GAG‑enriched CXCL8 reservoirs. Together, these findings provide a structural and biophysical framework for understanding how SpyCEP combines substrate engagement with GAG targeting to dismantle chemokine gradients and inhibit neutrophil recruitment. More broadly, this work highlights the role of intrinsic disorder in protease recognition and suggests new avenues for anti‑virulence therapies and vaccine strategies targeting SpyCEP.
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Journal articleGuerrero-Fonseca IM, Hernández-Almaraz KB, León-Vega II, et al., 2026,
Neutrophil serine proteases degrade endothelial cortactin and promote extravasation.
, J Cell Biol, Vol: 225The adhesive interactions of neutrophils with postcapillary venules during inflammation have been well studied. However, how neutrophils trigger molecular changes in endothelial cells (EC) during their extravasation requires further exploration. The endothelial actin-binding protein cortactin regulates endothelial contacts and neutrophil-endothelial interactions, but the associated mechanisms remain elusive. Hypothesizing that endothelial cortactin dynamics change during inflammation, using super-resolution confocal microscopy of inflamed mouse cremasteric venules and HUVEC, we report that neutrophil interaction with EC induces reduction in EC cortactin levels. This response was specifically mediated by neutrophil serine proteases, including cathepsin G, that were detected inside EC. The observed cortactin degradation was abolished after inhibition of serine proteases or blockade of neutrophil exocytosis. Finally, the endogenous serine protease inhibitor α1-antitrypsin suppressed cortactin degradation in vivo and reduced neutrophil adhesion and extravasation. Collectively, our data unveil a new mechanism by which neutrophils manipulate proteins inside EC to facilitate their extravasation.
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Journal articleWells C, Rosewarne C, Taylor K, et al., 2026,
Swimming against the tide in implementing change in paediatric physiotherapy for asthma and dysfunctional breathing: stakeholder reflections through digital storytelling
, Design for Health, Pages: 1-13, ISSN: 2473-5132 -
Journal articleLeung AS-Y, Tham EH, Yamamoto-Hanada K, et al., 2026,
Global Variation in Timing of Allergenic Food Introduction for Food Allergy Prevention: An International Survey of Healthcare Professionals.
, AllergyBACKGROUND: IgE-mediated food allergy prevention guidelines are now established in many countries, but their implementation in routine clinical practice globally remains unclear. METHODS: An anonymous online survey was distributed to healthcare professionals (HCPs) through the World Allergy Organization network between December 2024 and April 2025, collecting data on food allergy prevention recommendations in daily clinical practice. RESULTS: The analysis included 731 healthcare professionals from 80 countries worldwide: Asia (36.7%), Europe (27.1%), North America (15.9%), and Rest of the World (20.0%; Russia, South America, Africa, Oceania). Unsupervised clustering revealed two distinct practice patterns-one favoring early allergen introduction and one favoring later introduction-with timing varying by allergen type. For peanuts, clusters diverged between early (median 6 months of age) and late (median 18 months of age) introduction recommendations for high-risk infants. Allergen introduction timing was independently driven by region and specialty: North American HCPs recommend peanut introduction 6.7 months earlier than those in Asia (5.48 ± $$ \pm $$ 3.32 vs. 12.18 ± $$ \pm $$ 7.27 months; p < 0.001), and pediatric allergists globally advocate for introduction 2.37 months earlier than non-allergists (8.72 ± $$ \pm $$ 5.85 vs. 11.09 ± $$ \pm $$ 7.14 months, p = 0.024). This disparity is more pronounced in high-risk infants than in normal-risk infants. CONCLUSIONS: The variability in allergen introduction practices, driven by geography and medical specialty, highlights a persistent gap in prevention guidelines adoption. This divergence likely reflects both suboptimal implementation of existing recommendations and regional differences in food allergy epidemiology. These findings underscore the need for population-tailored allergen introduction strategies acro
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Journal articleTanskanen E, Sun H, Cheng K-C, et al., 2026,
Co-formulation of IL-12 mRNA and doxorubicin in polymeric nanoparticles for simultaneous delivery in murine melanoma
, RSC Pharmaceutics, ISSN: 2976-8713Liposomal or polymeric nanoparticles have been instrumental in improving delivery of poorly soluble chemotherapeutics and those with dose limiting toxicity such as doxorubicin (DOX). More recently, nanoformulations have shown to enable simultaneous delivery of emerging biomolecules such as siRNA. However, for larger nucleic acids such as mRNA this remains challenging. In this study, we developed a poly(β-amino ester) (PBAE) based platform, capable of co-formulation of mRNA and doxorubicin into nanoparticles. To demonstrate proof of concept using therapeutically relevant cargo, immunomodulatory interleukin-12 (IL-12) was selected as a model mRNA. IL-12 is a pro-inflammatory cytokine that promotes anti-tumour immunity partly through amplifying effector cytokines such as interferon-γ (IFNγ). We found that PBAE complexed DOX and mRNA into positively charged nanoparticles of 120 nm and size-exclusion chromatography indicated a DOX loading efficiency of over 97%. Co-association of both DOX and mRNA was characterised at a single nanoparticle level by nano-flow cytometry. Following delivery to B16F10 murine melanoma cells, more than 95% of cells were double positive for DOX and cy5-labelled mRNA, and confocal microscopy confirmed co-localised regions of DOX with mRNA. Interestingly, nanoformulated DOX had increased nuclear accumulation by 1.7-fold relative to free DOX which correlated with a significantly reduced cell viability of 12.9% with PBAE-DOX/mRNA, compared to 26.6% for free DOX at the same dose. Moreover, despite this strong cytotoxic effect, reporter mRNA translation remained robust, with luciferase expression approximately two orders of magnitude above non-transfected controls at the highest DOX doses. Co-formulation of IL-12 mRNA and DOX with PBAE demonstrated effective IL-12 protein secretion in transfected B16F10 cells with simultaneous DOX dose dependent reduction in viability. Secreted IL-12 was bioactive, inducing dose dependent STAT4 pho
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Journal articleYang W, Giblin SP, Pease JE, 2026,
Evidence for a Two-Step Model for Activation of GPR25 by the Chemoattractant CXCL17.
, Basic Clin Pharmacol Toxicol, Vol: 139CXCL17 was recently reported to activate GPR25, a receptor expressed by T-regulatory cells. Although classified as a chemokine, the activity of CXCL17 is ablated by minor C-terminal truncation, suggesting a novel mode of receptor activation. We set out to test this hypothesis by mutagenesis. GPR25 was expressed in the murine pre-B cell line L1.2 and mediated robust migration of transfectants to nanomolar concentrations of recombinant CXCL17 (24-119). The N-terminally truncated form of CXCL17 (64-119) was also chemotactic for GPR25 transfectants, albeit with severely reduced potency. Modelling of CXCL17:GPR25 implied multiple interactions between the N- and C-termini of CXCL17 with GPR25, which was validated by mutagenesis. Cells expressing a chimeric FPR1:GPR25 construct responded chemotactically to CXCL17 but with significantly reduced potency compared with wild-type GPR25 transfectants, implicating the GPR25 N-terminus in CXCL17 recognition. Mutagensis of the GPR25 residues W95, R178 and R264 resulted in a complete loss of chemotactic responsiveness to CXCL17, consistent with the residues interacting with the C-terminal CXCL17 motif. In conclusion, we verify GPR25 as a bona fide CXCL17 receptor and suggest a two-step model of GPR25 activation, in which the receptor N-terminus orients CXCL17 for activation of GPR25 via its C-terminus. We also advocate the reclassification of CXCL17 as a chemoattractant distinct from the chemokine family.
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Journal articleChin D, Hernandez-Beeftink T, Donoghue L, et al., 2026,
Genome-wide association study of idiopathic pulmonary fibrosis susceptibility using clinically curated European ancestry datasets.
, Eur Respir J, Vol: 68New association signals suggest a potentially causal role for the gene encoding KL-6, a known biomarker of fibrosis, and implicate genes involved in angiogenesis in IPF development https://bit.ly/3Ocr01s
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Journal articlede Benedictis FM, Beasley R, Pavord I, et al., 2026,
50 years on: how inhaled corticosteroids have changed the treatment of asthma.
, Lancet Respir Med, Vol: 14, Pages: 633-646Inhaled corticosteroids are the foundation of asthma therapy and now, 50 years on from their introduction, is an appropriate time to summarise some of the key studies that have progressed the field. We can now make better decisions in selecting the optimal inhaled corticosteroid-based regimens and identifying likely responders, based on biomarkers and patient characteristics. Inhaled corticosteroids reduce the risk of asthma attacks, but do not alter the course of the disease. Asthma remission, which is as yet an undefined therapeutic goal, is the aim, but the role of inhaled corticosteroids is unclear. High-dose inhaled corticosteroid therapy can cause systemic adverse events, suggesting that steps be taken to avoid this through the addition of long-acting β2-adrenergic agonists and the judicious use of biologics. Researchers will continue to learn more about the advantages and limitations of inhaled corticosteroids as they explore methods of disease prevention and remission in the future with new tools and treatments.
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Journal articleKlimek L, Mullol J, Reitsma S, et al., 2026,
Correspondence: The First Biosimilar for Biologics in Allergy: CT-P39 (Omlyclo-Omalizumab-Igec) Is Available for Asthma, Chronic Spontaneous Urticaria, and Chronic Rhinosinusitis With Nasal Polyps.
, Allergy, Vol: 81, Pages: 2568-2570 -
Journal articleGardiner LE, Lozano-Rojas D, Smith N, et al., 2026,
Investigating prognostic classifications of preexisting multiple long-term conditions for health outcomes 1 year after COVID-19 hospitalization: A UK prospective observational study.
, Int J Infect Dis, Vol: 168BACKGROUND: Preexisting multiple (two or more) long-term conditions (MLTCs) may negatively affect recovery after COVID-19. We investigated how preexisting MLTCs, including different categorization and patterns of MLTCs, affect 1-year health outcomes after severe COVID-19. METHODS: Adults post-hospitalization after COVID-19 were recruited during 2020-2021. We compared recovery at 1 year after discharge using adjusted multivariable logistic regression in 1:1 propensity-matched adults (for age, sex, ethnicity, social deprivation, obesity, and smoking history) with and without preexisting MLTCs. In adults with MLTCs, different categorization such as number of conditions, number and types of body systems involved (e.g. respiratory, cardiovascular), and latent class analysis-derived patterns of condition co-occurrence were assessed for their association with recovery at 1 year. RESULTS: A total of 647 adults with MLTCs were matched with 647 adults without MLTCs (n = 1294; 61.9% male, 79.6% of White ethnicity, median age 59 [interquartile range 52-67] years). The presence of MLTCs was associated with lower odds of feeling fully recovered (odds ratio 0.66 [95% confidence interval 0.51-0.85], P = 0.001). In those with MLTCs, recovery was negatively affected by number and type of body systems involved (e.g. respiratory [odds ratio 0.49 (95% confidence interval 0.34-0.69), P <0.001]) but not by the number of conditions (P >0.1). Four latent classes of MLTC co-occurrence were estimated with different risks of recovery (P <0.01). CONCLUSION: Adults with preexisting MLTCs were 34% less likely to feel fully recovered at 1 year after COVID-19 hospitalization than adults without MLTCs. We describe prognostic classifications of MLTCs, with future work needed to understand whether they have prognostication in broader post-acute infection sequalae.
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Journal articleBunyavanich S, Akdis M, Berin MC, et al., 2026,
Novel Biomarkers and Diagnostic Tools in Food Allergy.
, Allergy, Vol: 81, Pages: 2276-2289The double-blind placebo-controlled oral food challenge (DBPCFC) has been the "gold standard" for diagnosing IgE-mediated food allergy for the past 50 years. Despite tremendous strides in our understanding of basic mechanisms and clinical features of food allergy, we remain dependent on refinements of old technologies, i.e., skin tests and serum IgE measurements, to complement clinical history in making an accurate diagnosis of food allergies. However, recent technical advances in two effector cell assays, i.e., the basophil and mast cell activation tests, may soon bring these diagnostic biomarkers to the clinic. In addition, new advances in antibody assays, T-cell assays, transcriptomics, and metabolomics in conjunction with machine learning and artificial intelligence may soon enable us to diagnose food allergy and accurately monitor immunotherapeutic outcomes without the need for an oral food challenge.
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Journal articleLevy ML, Bush A, 2026,
Draft charter for asthma in children and young people, inspired by Martha's rule.
, Arch Dis Child
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