ENT and Allergy

Fibrosis involves sustained changes in fibroblast gene expression, leading to excessive extracellular matrix (ECM) deposition and progressive tissue stiffening. Although matrix stiffness is a potent regulator of cell fate and transcription, it is not clear how nuclear mechanosensing contributes to fibrosis. Here, we define a central role for SUN2, a component of linker of nucleoskeleton and cytoskeleton (LINC) complexes, as a mediator of stiffness-dependent nuclear and chromatin responses during skin fibrosis. SUN2 transcripts are upregulated in dermal fibroblasts of patients with systemic sclerosis and Sun2 protein is elevated in fibrotic mouse skin. Nuclear size, A-type lamins and Sun2 are elevated in dermal fibroblasts plated on stiff substrates. Loss of Sun2 protects against bleomycin-induced skin fibrosis in vivo and abolishes stiffness-induced changes in nuclear size and fibrotic gene expression in vitro. Mechanistically, we identify three Sun2-dependent mechanosensitive chromatin states and show that mechanical induction of the histone methyltransferase Ezh2 requires Sun2. These findings define SUN2 as a nuclear mechanosensor that couples matrix stiffness to chromatin regulation and transcriptional programs that drive fibrosis, identifying it as a potential therapeutic target pathway in fibrotic disease.

This systematic review consolidates current evidence on the efficacy, safety, and tolerability of awake, office-based procedures for chronic rhinosinusitis (CRS). It aims to evaluate whether these minimally invasive interventions performed under local anesthesia are viable alternatives to conventional sinus surgery under general anesthesia. A systematic search of PubMed/MEDLINE, Google Scholar, and Scopus databases was performed through November 2025, following PRISMA guidelines. Studies were selected using the PICOS framework, including adult patients undergoing in-office procedures (e.g., balloon sinus dilation, endoscopic sinus surgery, polypectomy, steroid-eluting implant placement) for CRS. Data were extracted and narratively synthesized due to heterogeneity. Eleven studies involving 1,283 patients were included. The procedures demonstrated significant and sustained improvements in patient-reported (SNOT-22, SNOT-20, NOSE, VAS) and objective (Lund-Mackay, Nasal Polyp Score) outcomes. Complication rates were low, with minor adverse events. Intraoperative pain was generally mild, tolerability was high (82-95%), and patients reported rapid recovery (often within 48h) and high satisfaction (72-95% willing to repeat the procedure). Awake sinus procedures are an effective, safe, and well-tolerated treatment option for selected CRS patients. They offer significant symptom relief, high patient satisfaction, and rapid recovery while avoiding general anesthesia. These techniques represent a transformative, patient-centered, and resource-efficient component of modern rhinology.

Introduction and Objectives: Lebrikizumab received U.S. Food and Drug Administration approval on September 13, 2024, for adults and adolescents (≥12 years, ≥40 kg) with moderate-to-severe atopic dermatitis (AD). The recommended dosing regimen consists of a 500-mg loading dose (two 250-mg injections) at Week 0 and Week 2, followed by 250 mg every 2 weeks (Q2W) until Week 16 or adequate clinical response. The approved maintenance dose is lebrikizumab 250 mg every 4 weeks (Q4W). Due to prescribing information (PI) flexibility and clinician discretion, real-world evidence describing the proportion of patients who transition to lebrikizumab Q4W dosing is warranted. Methods: We assessed the proportion of patients treated with lebrikizumab who transitioned from Q2W to Q4W dosing using the IQVIA Longitudinal Access and Adjudication Data (LAAD) database. Patients who initiated lebrikizumab between September 13, 2024, and August 31, 2025 were identified; only final paid claims were included. The index date was defined as the date of the first paid lebrikizumab prescription. Patients were required to be ≥12 years old and to have pharmacy activity for ≥6 months following the index date. Data from weeks 16, 20, and 24 were assessed. If a patient receives five lebrikizumab prescriptions (28-day supply), the first, consistent opportunity to move to Q4W dosing per the label is at Week 16. However, the first opportunity to identify an Q4W dosing interval in the data would be between fills five and six, Week 16 and 20. Results: Overall, 2,948 patients were included had pharmacy activity for ≥6 months and were ≥12 years old. The mean age of the study population was 44.1 years (SD 18.9). The majority (78.6%) of patients utilizing lebrikizumab were 18–64 years. Among patients who initiated lebrikizumab, Q2W dosing, and had ≥5 lebrikizumab claims (n = 1,717) over 6 months, 72.7% had transitioned from Q2W to Q4W dosing by Week 16, 83.3% by Week 20, and 88.1% by Week 24. Of the 83.3% of patients that transitioned from Q2W to Q4W dosing by Week 20, the average time (mean) to dosing transition (Q2W to Q4W) was 13.3 weeks. Conclusion: By Week 20, 83.3% of patients receiving lebrikizumab transitioned to Q4W maintenance dosing, a proxy for adequate clinical response. This analysis was restricted to patients with consistent lebrikizumab fills and is subject to the inherent limitations of claims administrative data. Additional research will further elucidate broader lebrikizumab treatment patterns. Funding sources: this study was funded by Eli Lilly and Company.

Background: Hereditary angioedema (HAE) is a rare, potentially fatal genetic disorder characterized by unpredictable attacks of bodily swelling that substantially impair patients' quality of life (QoL). Lanadelumab is approved for long-term prophylaxis (LTP) in patients with HAE; however, there are limited real-world data that compare lanadelumab with other treatments to guide patient care. Objective: The objective was to describe real-world QoL and related outcomes of patients with HAE who received lanadelumab versus other LTP. Methods: Data were drawn from a real-world, cross-sectional survey of physicians and their consulting patients with HAE in the United States from January 2023 to January 2024. Physician-reported attack and disease severity, pain, fatigue, QoL, and patient-reported outcomes were compared among patients receiving lanadelumab or other LTP. Results: Physicians reported data on 86 patients treated with lanadelumab and 84 treated with other LTP. A statistically significantly higher proportion of patients receiving lanadelumab had no chronic pain (58.1%) and no chronic fatigue (51.2%) at the time of the survey than those receiving other LTP (38.1% [p = 0.0023] and 34.9% [p = 0.0037], respectively). More patients receiving lanadelumab had "very good" physician-reported QoL and less patient-reported QoL impairment at the time of the survey compared with those receiving other LTP (p = 0.0102). A higher proportion of patients receiving lanadelumab compared with other LTP reported complete satisfaction overall with their treatment (30.2% versus 17.9%, respectively; p = 0.0144) and complete satisfaction with the efficacy of their treatment (44.2% versus 11.9%, respectively; p < 0.0001). Conclusion: In this real-world study, physicians reported a higher proportion of patients receiving lanadelumab had no chronic pain or fatigue compared with those receiving other LTP. Both physicians and patients reported higher QoL in those receiving lanadelumab. Continued real-world research in patients with HAE to further assess the effect of lanadelumab on QoL will help guide patient care.

Food allergies in children represent a growing clinical and public health concern worldwide, yet their causes remain poorly understood. To investigate the role of circulating IgG antibodies to food allergens and viral antigens at birth and during early childhood in the development of food allergies, using data from a prospective birth cohort. This study included 458 children composed of 80 with food allergies, 151 with food sensitization, and 227 who were non-allergic and non-sensitized to these food allergens and had no other allergic diseases (asthma, atopic dermatitis, and allergic rhinitis). Phage ImmunoPrecipitation Sequencing (PhIP-Seq) was used to profile the IgG antibody reactome against thousands of environmental antigens (including allergens and viruses) in matched cord blood and childhood plasma samples from these children. We then investigated whether IgG profiles were associated with allergies to egg, milk, and peanut. Children with food allergies had a significantly elevated diversity of IgG reactivity to thousands of allergen peptides in early childhood compared to non-allergic controls. No such associations were found in cord blood at birth. We identified that peanut-allergic children have higher IgG reactivity to 24 peanut peptides, and egg-allergic children had higher IgG reactivity to 17 egg peptides compared to non-allergic controls. Additionally, patterns of shared IgG reactivity to wheat peptides were observed across different food allergy groups in early childhood. Notably, milk-allergic children exhibited lower magnitudes of IgG reactivities to eight milk peptides in cord blood and reduced IgG reactivities to enteroviral peptides during childhood (all FDR < 0.05), relative to non-allergic controls. These results suggest that unbiased IgG reactome profiling in a prospective birth cohort provides new insights into early life immune regulation and its influence on childhood allergic phenotypes.

Exposomic determinants substantially influence the variability of molecular IgE-mediated sensitization in allergic rhinitis and conjunctivitis across bioclimatic regions, underscoring their relevance in precision allergology. This study aimed to characterize molecular sensitization profiles in Spanish patients with respiratory allergy from distinct geographic and climatic areas. A cross-sectional, multicenter study was performed in 12 Spanish cities. The study population comprised 291 patients diagnosed with allergic rhinitis and/or conjunctivitis according to the modified ARIA/DECA criteria. Participants underwent skin prick testing with standardized allergen extracts and multiplex molecular IgE analysis. Clinical, demographic, and regional bioclimatic variables were integrated to define exposomic sensitization patterns. Patients previously treated with allergen immunotherapy or biologics were excluded. Regional pooled sera were analyzed by ELISA and IgE immunoblotting to validate molecular data and identify IgE binding to nonrecombinant or poorly characterized allergenic components. Distinct regional sensitization profiles were identified. Grass pollen allergens predominated in oceanic and continental climates, while olive and cypress pollens were more frequent in Mediterranean areas. Sensitization to house dust mite, particularly Dermatophagoides pteronyssinus and Blomia tropicalis, was highly prevalent in subtropical and humid zones. Molecular assays confirmed skin test findings and identified major allergenic molecules, including Phl p 1, Ole e 1, Der p 1, and Der p 2, along with region-specific components such as Der p 23, Cup a 1, Alt a 1, and Pla a 2. This multicenter exposomic study demonstrated that climatic diversity modulates allergen sensitization in Spain, supporting region-tailored precision diagnostic and therapeutic strategies in respiratory allergy.

Sequencing-based spatial transcriptomics (sST) enables transcriptome-wide gene expression mapping but falls short of reaching the optical resolution (200-300 nm) of imaging-based methods. Here, we present Seq-Scope-X (Seq-Scope-eXpanded), which empowers submicrometer-resolution Seq-Scope with tissue expansion to surpass this limitation. By physically enlarging tissues, Seq-Scope-X minimizes transcript diffusion effects and increases spatial feature density by an additional order of magnitude. In liver tissue, this approach resolves nuclear and cytoplasmic compartments in nearly every single cell, uncovering widespread differences between nuclear and cytoplasmic transcriptome patterns. Independently confirmed by imaging-based methods, these results suggest that individual hepatocytes can dynamically switch their metabolic roles. Seq-Scope-X also works in brain and colon, and can be adapted for spatial proteomics, profiling hundreds of barcode-tagged antibody stains at microscopic resolutions in mouse spleens and human tonsils. Together, these findings establish Seq-Scope-X as a powerful platform for ultra-high-resolution whole-transcriptome and proteome profiling, expanding the spatial precision achievable for studying cellular architecture, function, and disease mechanisms.

About 15% of hospitalized adults report a penicillin allergy. Of these patients, approximately 90% tolerate penicillin when re-challenged, potentially due to misattribution of nonallergic rash as hypersensitivity or outgrowing the index reaction. Patients with penicillin allergy labels are more likely to receive less effective therapy, develop antibiotic resistance, incur higher healthcare costs, and have poorer outcomes. Although cephalosporins are recommended for most patients with a reported or confirmed penicillin allergy, de-labeling and removing penicillin allergies represent an impactful antimicrobial stewardship activity. A recently developed scoring tool (PEN-FAST) identifies those at low risk for a recurrent reaction and is less cumbersome than traditional testing methods.