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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, 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 articleWrench E, Kaur J, Rankin SM, et al., 2026,
The Ethical, Legal and Psychosocial Implications of Genetic Testing in Adoption: A Review of the Current Evidence
, Adoption Quarterly, Pages: 1-19, ISSN: 1092-6755 -
Journal articleBush A, Ramsey B, 2026,
Cystic fibrosis in 2026: Game over, or game on? Introduction to an AJRCCM special section on cystic fibrosis.
, Am J Respir Crit Care Med -
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 articleCanizales J, Schofield S, Shamji MH, et al., 2026,
Patterns of mouse allergen–specific IgE and IgG4 in contemporary animal research environments
, Clinical and Experimental Allergy, Vol: 56, Pages: 983-985, ISSN: 0954-7894 -
Journal articleLogan J, Martin K, Gillespie L, et al., 2026,
Asthma exacerbation profile of benralizumab for severe eosinophilic asthma (the BenRex study): a multicentre, prospective cohort study.
, Lancet Respir Med, Vol: 14, Pages: 683-693BACKGROUND: Benralizumab, an interleukin-5 receptor α antagonist, depletes blood eosinophils, reducing exacerbations of severe asthma by approximately 50% versus placebo. In this study, we aimed to characterise mechanisms underlying exacerbations occurring on benralizumab. METHODS: BenRex, a multicentre, prospective cohort study, recruited participants meeting national licensing criteria for benralizumab for asthma. The study was conducted in 15 UK severe asthma centres. After collecting baseline data, open-label benralizumab was administered for 12-18 months. At exacerbation, participants attended for medical review before initiating treatment, fractional exhaled nitric oxide (FeNO), spirometry, asthma control questionnaire, and blood and sputum sampling. FINDINGS: Between Sept 30, 2019, and April 23, 2024, 121 exacerbation events were assessed in 156 individuals. 90 participants (58%) were female and 66 (42%) were male; 147 (94%) of participants identified as White. Median blood eosinophil counts at exacerbation were 0 (IQR 0-0) cells per μL. Airway neutrophilia was present in 55% of exacerbations where sputum was available (27/49). Median C-reactive protein (CRP) increased from 3·00 mg/L (1·00-6·00) at baseline to 9·00 mg/L (3·00-17·00) at exacerbation (p=0·0067). Clinically relevant viral pathogens were seen in eight (20·5%) of 39 sputum samples; although viruses were detected in 22 (56·4%) of 39 samples. Influenza A, metapneumovirus, and rhinovirus were the most common viral pathogens (each found in 2 [5·1%] of 39 samples). New acquisition of Moraxella catarrhalis (3 [13·6%] of 22), Haemophilus influenzae (4 [18·2%] of 22), and Streptococcus pneumoniae (2 [9·1%] of 22) occurred. DNA-neutrophil elastase complexes (p=0·0080) and azurocidin-1 (p=0·012) concentrations rose from baseline to exacerbation. FeNO was ≥50 parts per billion in 56 (50·
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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 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.
, Allergy, Vol: 81, Pages: 2633-2655The 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 articlePeter J, Jindal A, Del Giacco S, et al., 2026,
Urticaria and Angioedema: When East Meets West-and the Middle.
, Allergy, Vol: 81, Pages: 2579-2581 -
Journal articleBognanni A, Sousa-Pinto B, Morais-Almeida M, et al., 2026,
World Allergy Organization (WAO) Consensus on the use and practice of precautionary allergen labelling: The international ACT-UP! e-Delphi.
, World Allergy Organ J, Vol: 19, ISSN: 1939-4551BACKGROUND: The Food and Agriculture Organization (FAO) of the United Nations and the World Health Organization (WHO) recently convened an expert consultation to address the increasing but inconsistent use of Precautionary Allergen ("may contain") Labelling (PAL). OBJECTIVES: We conducted a Delphi study to explore the perspectives of clinicians, patient representatives, and other interest-holders on PAL practice. METHODS: We followed previous guidance on Delphi study development and reporting. A narrative review exploring the FAO/WHO Expert Consultation informed the Delphi process. The working group generated 35 items based on the review of FAO/WHO consultation, categorized into 7 domains: (i) Importance of the issue, (ii) Informing use of PAL, (iii) Action level cut-offs, (iv) Communication, (v) Liability considerations, (vi) Free From statements, and (vii) Areas for further research. Items underwent 3 iterative Delphi rounds involving a panel of 35 experts who rated their agreement narratively and on a 5-point Likert scale. Consensus was defined as ≥70% consistency in agreement or disagreement (excluding neutral responses); stability was defined as <10% variation in average scores across rounds. A public consultation was held to collect different viewpoints arising from the consensus activity. RESULTS: The Delphi was concluded after 3 rounds with consensus achieved for 33/35 items. Response rate was 100% across all 3 rounds. The panel strongly agreed that PAL should only be applied when an unintended allergen may be present above a cut-off (action level) and that it should always be based on a formal risk assessment, preferably quantitative, and mandated through legislation. Furthermore, action levels should be based on "reference doses" (amount of total allergenic protein), rather than on a concentration (eg, 10 ppm), and more specifically on population-adjusted eliciting doses ED05 (amount of allergen expected to elicit an objective rea
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Journal articleLachover-Roth I, Chan ES, Erdle SC, et al., 2026,
The effect of transient early consumption of cow's milk formula on the risk of cow's milk allergy requires studies with sufficient power.
, J Allergy Clin Immunol Pract, Vol: 14, Pages: 1934-1937 -
Journal articleMolyneaux PL, Hirani NA, Chia CCK, et al., 2026,
Inhaled LTI-03 for idiopathic pulmonary fibrosis: a randomized dose escalation study.
, Nat Commun, Vol: 17Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited treatment options. LTI-03 promotes alveolar epithelial cell survival and reduces profibrotic protein expression in experimental models of IPF. In this Phase 1b, randomized, double-blind, placebo-controlled dose-escalation study, 24 participants with IPF were randomized 3:1 to inhaled LTI-03 5 mg/day (N = 9), LTI-03 10 mg/day (N = 9) or placebo (N = 6) for 14 days and included in all analyses (ClinicalTrials.gov: NCT05954988). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs). Exploratory analyses included pharmacokinetics and disease-related biomarkers. LTI-03 was well-tolerated, with no treatment-related discontinuations, no severe TEAEs, and no evidence of airway obstruction by spirometry and associated symptoms. In deep bronchial brushings, both LTI-03 doses significantly reduced interleukin-11 (p = 0.0406 at 5 mg/day; p = 0.044 at 10 mg/day) and thymic stromal lymphopoietin (p = 0.0256 at 5 mg/day; p = 0.0128 at 10 mg/day) versus placebo. The 10 mg/day dose suppressed collagen type 1 alpha chain 1 (p = 0.0248), CXC chemokine ligand 7 (p = 0.0248) and galectin-7 (p = 0.0332). Other measured biomarkers were not significantly changed. The favorable safety profile and reductions in disease-related biomarkers support further evaluation of inhaled LTI-03 for IPF. This study was fully funded by Rein Therapeutics, Inc.
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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.
, Am J Respir Crit Care Med -
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 articleDribin TE, Sobolewski B, Campbell RL, et al., 2026,
Anaphylaxis Clinical Care Pathway: Incorporating Intranasal Epinephrine (Adrenaline).
, J Allergy Clin Immunol PractHealth care providers across settings must be trained to manage anaphylaxis by (1) removing the offending allergen if still present; (2) positioning the patient with legs elevated, and if respiratory distress is present, allow the patient to sit upright with legs extended and elevated; (3) immediately administering epinephrine (adrenaline) intramuscularly (IM) or intranasally (IN) every 5 to 15 minutes for persistent anaphylaxis; and (4) optimizing airway, breathing, and cardiovascular (ABC) resuscitation. This may include supplemental oxygen, noninvasive or invasive positive-pressure ventilation, and intravenous fluid resuscitation. For life-threatening or refractory presentations, (5) IM/IN epinephrine should be administered every 5 minutes while addressing ABC derangements; this includes aggressive intravenous fluid resuscitation for patients in anaphylactic shock. Providers may continue IM or IN epinephrine or switch to the other, as both routes are considered equally efficacious based on pharmacokinetic data. An intravenous epinephrine infusion should be prepared for patients with persistent anaphylaxis after 2 doses of IM/IN epinephrine and initiated after the third dose, or earlier at the provider's discretion. In settings without epinephrine infusions, repeat IM/IN epinephrine should be administered every 5 minutes, along with other ABC interventions, and the patient should be transferred quickly to a setting equipped to provide advanced resuscitative care.
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Journal articleLau R, Giblin S, Sugar A, et al., 2026,
SpyCEP dismantles neutrophil immunity via disorder-driven chemokine remodeling and GAG targeting
, Proceedings of the National Academy of Sciences of the United States of America, Vol: 123, ISSN: 0027-8424Streptococcus pyogenes evades neutrophil-mediated immunity by secreting the protease SpyCEP, which inactivates chemokines such as CXCL8; however, the mechanism by which SpyCEP targets CXCL8 for cleavage has remained unclear. This work uncovers an intrinsically disordered autocatalytic maturation loop that binds CXCL8 and induces a conformationally heterogeneous state in the chemokine. A model is proposed in which this disorder-mediated recognition facilitates access to the substrate cleavage site and is compatible with SpyCEP acting at glycosaminoglycan (GAG)-bound CXCL8 reservoirs. This disorder-mediated mode of substrate recognition departs from classical protease–substrate interfaces and identifies the SpyCEP cleaved autocatalytic matu-ration loop (CAML) as a potential target for anti-virulence strategies against S. pyogenes.
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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
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