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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 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 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 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 articleLevy ML, Bush A, 2026,
Draft charter for asthma in children and young people, inspired by Martha’s rule
, Archives of Disease in Childhood, ISSN: 0003-9888 -
Journal articleSong W-J, Kermani NZ, Versi A, et al., 2026,
Clinical Features of Cellular Senescence Pathways in Severe Asthma.
, AllergyBACKGROUND: 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 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 articleSakamachi Y, Wiley E, Trempus CS, et al., 2026,
Toll-like receptor 5 protects against murine lung fibrosis through reduced dysbiosis, and TLR5 deficiency is associated with human IPF.
, Sci Transl Med, Vol: 18Idiopathic pulmonary fibrosis (IPF) is a devastating pulmonary disease with no curative treatment other than lung transplantation that results from maladaptive responses to lung epithelial injury; however, the underlying mechanisms remain unclear, and treatment options are limited. Here, we showed that deficiency in the innate immune receptor toll-like receptor 5 (TLR5) is associated with IPF in humans and with increased susceptibility to bleomycin-induced pulmonary fibrosis in mice and that activation of lung epithelial TLR5 through a synthetic flagellin analog protected mice from experimental fibrosis. Mechanistically, epithelial TLR5 activation induced antimicrobial gene expression and ameliorated lung dysbiosis after injury. In contrast, TLR5 deficiency in mice and patients with IPF was associated with lung dysbiosis. Elimination of the microbiome in mice through administration of antibiotics abolished the protective effect of TLR5, and reconstitution of the microbiome by fecal microbiota transplantation rescued the observed phenotype. In conclusion, these studies revealed that TLR5 protects against pulmonary fibrosis through effects on the lung microbiota, providing insight into therapeutic approaches that may ultimately benefit patients with IPF.
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Journal articleNguyen TH, Akdis C, Baccarelli A, et al., 2026,
Leveraging Artificial Intelligence in Allergy, Asthma, and Immunology With Environmental Exposures.
, AllergyArtificial intelligence (AI) in environmental health science is revolutionizing data analysis and problem-solving approaches. These technologies facilitate the prediction of environmental exposures and disease outcomes and enable the identification of causal relationships for subsequent hypothesis testing. AI techniques improve pollution research through the analysis of satellite imagery and the modeling of pollutant dispersion, while AI advances chemical safety evaluations in toxicology by examining extensive datasets. AI is instrumental in addressing pressing environmental challenges, including remediation of polluted sites and ensuring equitable healthcare applications to mitigate biases. The expanding availability of large-scale environmental, geospatial, and health outcome databases offers unprecedented opportunities for innovative applications. Their predictive capabilities are essential in disaster management, enabling real-time analysis and optimizing resource deployment amid climate-related crises. AI-driven approaches play a critical role in carbon capture and waste management efforts aimed at reducing environmental impact. Furthermore, AI can elucidate complex relationships between the exposome-defined as the totality of exposures throughout an individual's life-and health outcomes, facilitating preventative strategies. This review examines the capabilities and limitations of AI in environmental health and safety, providing insights into its judicious and effective use for environmental management and healthcare.
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Journal articleBaraldi E, Bonadies L, Grutta SL, et al., 2026,
Long term lung health in children: new emerging threats and preventive strategies.
, Paediatr Respir RevThe long-term consequences of early adverse exposures are well known but is becoming clear that early means not just in pregnancy but also in at least the two preceding generations. Furthermore, there are new existential threats to long term respiratory health, some of which have been presented at the INSPiRED meeting in Bologna and are reviewed in this manuscript. One such is premature delivery, with ever smaller babies surviving with new respiratory and systemic complications, but there is also an appreciation that even those who do not develop bronchopulmonary dysplasia may have long term complications. New environmental hazards include vapes and other devices designed to produce a new generation of nicotine addicts; gas flaring which ruthlessly maximises profit at the expense of the environment and those living close by; and climate change, perhaps the greatest threat of all. Compounding these challenges is the effects of displacement by war or natural disasters on increasing numbers of children. On the other hand, encouragingly, two new highly effective strategies for the prevention of respiratory syncytial virus infection are becoming widely available, namely maternal immunisation with a pre-fusion vaccine in the third trimester of pregnancy and a long-acting monoclonal antibody. We await data as to whether these strategies will prevent impairment of lung function and later asthma. However, strong political action is essential if the expanding range of threats to the health of children and young people are to be averted. Awareness of new threats and advocacy are important roles for all paediatricians.
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Journal articleKonstantinidi R, Yates L, Lloyd C, et al., 2026,
Investigating the impact of PBAE-mediated FOXJ1 mRNA delivery on differentiation of primary human bronchial epithelial cells
, Biology Open, Vol: 15, ISSN: 2046-6390Primary human basal bronchial epithelial cells (HBECs) are an important population of progenitor cells capable of self-renewal and differentiation to maintain airway homeostasis. At air-liquid interface (ALI) culture, HBECs undergo mucociliary differentiation, providing a robust physiologic model to evaluate novel therapeutics such as in vitro transcribed messenger RNA (IVT-mRNA). However, the impact of IVT-mRNA delivery on the differentiation potential of basal HBECs remains poorly characterised. Poly (beta amino) ester (PBAE) nanoparticles have demonstrated effective airway delivery of IVT-mRNA in various pre-clinical studies. Here, we aimed to understand the impact of PBAE-mediated mRNA transfection on basal HBEC differentiation at ALI. We investigated IVT-mRNA encoding the ciliogenesis transcription factor Forkhead box J1 (FOXJ1) as a model tool for transient overexpression in primary basal HBECs and characterised its subsequent impact on epithelial integrity and differentiation at ALI. PBAE-mediated delivery of FOXJ1 mRNA to submerged primary HBECs resulted in approximately 50% FOXJ1-positive cells and transient upregulation of key ciliogenesis-related genes, including DNALI1 and RSPH9. Following 28 days of differentiation at ALI, FOXJ1 or reporter mRNA transfected cultures displayed normal epithelial morphology, with tight junction and differentiation markers, proportions of secretory and ciliated cells, and cilia ultrastructure comparable to non-transfected controls. These data indicate that PBAE-mediated IVT-mRNA delivery can transiently increase encoded protein expression in basal primary HBECs, without impeding mucociliary differentiation.
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Journal articleCastagnoli R, Votto M, Taietti I, et al., 2026,
Bridging Rare to Common Diseases: Precision Medicine and the Transforming Landscape of Pediatric Allergy and Immunology.
, Pediatr Allergy Immunol, Vol: 37Pediatric immunological and allergic conditions represent a broad spectrum, ranging from highly prevalent polygenic disorders (e.g., food allergy, atopic dermatitis, asthma, and allergic rhinitis) to rarer monogenic primary atopic disorders. The management of these conditions has undergone a paradigm shift in recent years. Moving away from a "one-size-fits-all" approach, precision medicine aims to deliver the right treatment to the right patient at the right time. By integrating clinical phenotypes with molecular endotypes and using specific biomarkers and "Omics" techniques, scientists and clinicians can now employ targeted biological therapies that significantly improve patient outcomes. By identifying early therapeutic windows and specific biomarkers, pediatric specialists can implement personalized interventions that halt the atopic march and mitigate the global burden of chronic allergic diseases. By shifting the focus from symptom management to the neutralization of specific molecular pathways, it is now possible to achieve better disease control, reduce side effects associated with broad-spectrum treatments such as systemic corticosteroids, and improve the quality of life for patients with refractory allergic diseases. This review, generated during a seminar funded by the Clemens von Pirquet Foundation, aims to delineate the "rare to common" pipeline, illustrating how precision medicine tools, including multi-omics, biomarkers, and artificial intelligence methods, can connect mechanistic pathways across the immunological spectrum.
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Journal articleOgbogu PU, Roufosse F, Akuthota P, et al., 2026,
Author Correction: Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial.
, Nat Med, Vol: 32 -
Journal articleArasi S, Bärhold F, Alvaro-Lozano M, et al., 2026,
Correspondence: First Peanut (Arachis hypogaea) Allergen Oral Immunotherapy Product Out of Sale-A Major Drawback for Food Allergy Immunotherapy?
, Allergy, Vol: 81, Pages: 2233-2235 -
Journal articleVieira RJ, Sousa-Pinto B, Bousquet J, et al., 2026,
Allergic Rhinitis and Its Impact on Asthma (ARIA)-EAACI Guidelines-2024-2025 Revision: Part II-Guidelines on Oral and Ocular Treatments.
, Allergy, Vol: 81, Pages: 1947-1970BACKGROUND: Oral and ocular medications are frequently used in the treatment of allergic rhinitis (AR). As part of the update of the Allergic Rhinitis and its Impact on Asthma (ARIA)-EAACI guidelines, this manuscript presents the ARIA-EAACI 2024-2025 recommendations for oral and ocular treatments. METHODS: The ARIA-EAACI 2024-2025 guideline panel issued recommendations following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence-to-decision framework. Several sources of evidence were used to inform panel judgements and recommendations, including systematic reviews, mHealth and pharmacovigilance data as well as a survey on costs. RESULTS: Eight guideline questions concerning oral treatments for AR and three questions concerning ocular treatments were addressed. These questions led to the recommendations. Overall, these questions concern the choice between different classes of medication. They also discuss the role of oral antihistamines (OAH), leukotriene receptor antagonists (LTRA), ocular antihistamines (OcAH) and ocular mast cell stabilisers. Four questions had not been previously evaluated in ARIA guidelines, while, for the other four, there was a change in the strength or directionality of the recommendations. Overall, these guidelines recommend using intranasal corticosteroids over OAH and using OAH over LTRA. Moreover, they suggest using OAH over OcAH and suggest being against adding LTRA to OAH. Finally, considerations for choosing between different individual OAHs are presented. CONCLUSION: This ARIA-EAACI 2024-2025 article supports patients, their caregivers and healthcare professionals in choosing oral and ocular treatments for AR. Decisions on treatment should consider the clinical variability of the disease, patients' values and the affordability of medications.
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Journal articleCustovic D, Custovic A, Gern J, et al., 2026,
Reply.
, J Allergy Clin Immunol, Vol: 157, Pages: 1479-1480 -
Journal articleOgbogu PU, Roufosse F, Akuthota P, et al., 2026,
Benralizumab versus placebo for hypereosinophilic syndrome: a randomized, placebo-controlled phase 3 trial.
, Nat Med, Vol: 32, Pages: 2017-2025Benralizumab, an eosinophil-depleting anti-IL-5 receptor α antibody, has demonstrated efficacy in severe eosinophilic asthma and eosinophilic granulomatosis with polyangiitis and shown promising results in hypereosinophilic syndrome (HES). NATRON was a randomized, double-blind placebo-controlled phase 3 study evaluating the efficacy and safety of benralizumab in FIP1L1::PDGFRA-negative HES. The primary endpoint was time to first HES flare. In total, 133 patients (median (range) age 51 (14-87) years, 62% female) were randomized (1:1) to receive benralizumab 30 mg every 4 weeks or placebo for 24 weeks, in addition to background therapy. Benralizumab significantly reduced the risk of first flare versus placebo (hazard ratio 0.35, 95% CI 0.18 to 0.69, P = 0.0024). Adverse events occurred in 64.2% and 66.7% of benralizumab- and placebo-treated patients, respectively. Benralizumab's safety was consistent with its known profile. These results demonstrate the efficacy and safety of add-on benralizumab in the treatment of HES. ClinicalTrials.gov identifier: NCT04191304 .
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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 MedBACKGROUND: 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 articleUllah A, Fontanella S, Granell R, et al., 2026,
Joint modelling of wheeze and lung function from childhood to early adulthood: four population-based birth cohorts
, EClinicalMedicine, ISSN: 2589-5370Background: Wheeze and lung function (LF) during childhood are key indicators of respiratory health, yet their trajectories are usually examined separately. We aimed to identify joint developmental patterns of wheeze and LF.Methods: We used data from four unselected birth cohorts established between 1989 and 1996 with repeated assessments of wheeze from infancy and spirometry from early school-age to early adulthood. We used group-based multi-trajectory modelling to derive trajectories based on joint modelling of current wheeze and forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC).Findings: In the discovery analysis (n=4,645), we identified 6 trajectories: (1) Never/infrequent wheeze with normal LF (NIFW-NLF, 2925/4645 [62.97%]); (2) Never/infrequent wheeze with reduced LF (NIFW-RLF, 475/4645 [10.22%]); (3) Early-transient wheeze with normal LF (ETW-NLF, 559/4645 [12.03%]); (4) Late-onset wheeze with NLF (LOW-NLF, 335/4645 [7.21%]); (5) Persistent wheeze with NLF (PEW-NLF, 202/4645 [4.34%]); and (6) PEW with RLF (PEW-RLF, 149/4645 [3.21%]). Risk profiles of two trajectories characterised by persistent wheeze but differentiated by normal or reduced LF differed significantly. Elevated fractional exhaled nitric oxide (FeNO) and allergic sensitisation were highly prevalent in both, but only PEW-RLF was significantly associated with perinatal and early-life factors/exposures (prematurity; lower gestational age: RRRs [95% CI] 2.21 [1.49–3.28], low birth weight: 2.60 [1.47–4.60]: and exposure to smoking during gestation: 2.00 [1.49–2.63]). Two low lung function trajectories (with and without symptoms; PEW-RLF and NIFW-RLF) had similar LF impairment, but divergent clinical and risk factor profiles. PEW-RLF was associated with high rates of asthma diagnosis, high FeNO, bronchodilator reversibility, and family history of atopy. In contrast, those in NIFW-RLF trajectory had no elevation in inflammatory biomarkers and low prevalence o
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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 ImagingBACKGROUND: 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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