An Allosteric Anti-tryptase Antibody for the Treatment of Mast Cell-Mediated Severe Asthma.

Severe asthma patients with low type 2 inflammation derive less clinical benefit from therapies targeting type 2 cytokines and represent an unmet need. We show that mast cell tryptase is elevated in severe asthma patients independent of type 2 biomarker status. Active ß-tryptase allele count correlates with blood tryptase levels, and asthma patients carrying more active alleles benefit less from anti-IgE treatment. We generated a noncompetitive inhibitory antibody against human ß-tryptase, which dissociates active tetramers into inactive monomers. A 2.15 Å crystal structure of a ß-tryptase/antibody complex coupled with biochemical studies reveal the molecular basis for allosteric destabilization of small and large interfaces required for tetramerization. This anti-tryptase antibody potently blocks tryptase enzymatic activity in a humanized mouse model, reducing IgE-mediated systemic anaphylaxis, and inhibits airway tryptase in Ascaris-sensitized cynomolgus monkeys with favorable pharmacokinetics. These data provide a foundation for developing anti-tryptase as a clinical therapy for severe asthma.

Transcriptional regulation and chromatin architecture maintenance are decoupled functions at the Sox2 locus.

How distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing and chromatin interaction analyses of the Sox2 locus in mouse embryonic stem cells, we found a striking disconnection between transcriptional control and chromatin architecture. We traced nearly all Sox2 transcriptional activation to a small number of key transcription factor binding sites, whose deletions have no effect on promoter-enhancer interaction frequencies or topological domain organization. Local chromatin architecture maintenance, including at the topologically associating domain (TAD) boundary downstream from the Sox2 enhancer, is widely distributed over multiple transcription factor-bound regions and maintained in a CTCF-independent manner. Furthermore, partial disruption of promoter-enhancer interactions by ectopic chromatin loop formation has no effect on Sox2 transcription. These findings indicate that many transcription factors are involved in modulating chromatin architecture independently of CTCF.

Factors Associated With Head and Neck Polytrauma Presentation and Admissions at Emergency Departments of Varying Sizes.

Timely diagnosis of acute head and neck polytrauma presenting to emergency departments (EDs) optimizes outcomes. Since ED capacity influences triage and admission, the authors utilized the National Electronic Injury Surveillance System database to understand how ED size and trauma characteristics affect head and neck polytrauma presentation and admissions. Demographics and injury characteristics from the National Electronic Injury Surveillance System database from 2018 to 2021 were analyzed to delineate factors contributing to polytrauma presence and admission through multivariable logistic regressions. The authors' 207,951-patient cohort was primarily females (48.6%), non-Hispanic (62.4%), and white (51.4%) people who averaged 57.2 years old. Nonspecific head injuries were predominant (59.7%), followed by facial trauma (22.6%) with rare substance involvement (alcohol, 6.3%; drugs, 4.1%) presenting to high-volume EDs (48.5%). Of the patients, 20% were admitted, whereas 31.1% sustained polytrauma. Substance use [alcohol, odds ratio (OR) = 4.44; drugs, OR = 2.90] increased polytrauma likelihood; neck (OR = 1.35), face (OR = 1.14), and eye (OR = 1.26) associated with polytrauma more than head injuries. Burns (OR = 1.38) increased polytrauma likelihood more than internal organ injuries. Black patients sustained higher polytrauma when presented to non-small EDs (OR = 1.41-1.90) than white patients showed to small EDs. Admissions were higher for males (OR = 1.51). Relative to small EDs, large EDs demonstrated a higher increase in admissions (OR = 2.42). Neck traumas were more likely admitted than head traumas (OR = 1.71). Fractures (OR = 2.21) and burns (OR = 2.71) demonstrated an increased admission likelihood than internal organ injuries. Polytrauma presence and admissions likelihood are site, injury, and substance dependent. Understanding the impact of factors influencing polytrauma presence or admission will enhance triage to optimize outcomes.

IL-13-associated epithelial remodeling correlates with clinical severity in nasal polyposis.

BACKGROUND: Epithelial remodeling is a histopathologic feature of chronic inflammatory airway diseases including chronic rhinosinusitis (CRS). Cell-type shifts and their relationship to CRS endotypes and severity are incompletely described. OBJECTIVE: We sought to understand the relationship of epithelial cell remodeling to inflammatory endotypes and disease outcomes in CRS. METHODS: Using cell-type transcriptional signatures derived from epithelial single-cell sequencing, we analyzed bulk RNA-sequencing data from sinus epithelial brushings obtained from patients with CRS with and without nasal polyps in comparison to healthy controls. RESULTS: The airway epithelium in nasal polyposis displayed increased tuft cell transcripts and decreased ciliated cell transcripts along with an IL-13 activation signature. In contrast, CRS without polyps showed an IL-17 activation signature. IL-13 activation scores were associated with increased tuft cell, goblet cell, and mast cell scores and decreased ciliated cell scores. Furthermore, the IL-13 score was strongly associated with a previously reported activated ("polyp") tuft cell score and a prostaglandin E2 activation signature. The Lund-Mackay score, a computed tomographic metric of sinus opacification, correlated positively with activated tuft cell, mast cell, prostaglandin E2, and IL-13 signatures and negatively with ciliated cell transcriptional signatures. CONCLUSIONS: These results demonstrate that cell-type alterations and prostaglandin E2 stimulation are key components of IL-13-induced epithelial remodeling in nasal polyposis, whereas IL-17 signaling is more prominent in CRS without polyps, and that clinical severity correlates with the degree of IL-13-driven epithelial remodeling.

Outcomes are Compromised When Revising Patellofemoral Arthroplasties for Patellar Component Failures.

BACKGROUND: Outcomes of patellofemoral arthroplasty (PFA) to total knee arthroplasty (TKA) conversion are reported to be similar to primary cases. The purpose of this study was to determine whether the cause for conversion from PFA to TKA correlated to outcomes when compared to a matched cohort. METHODS: A retrospective chart review was performed to identify aseptic PFA to TKA conversions between 2000 and 2021. A cohort of primary TKAs was matched by patient sex, body mass index, and American Society of Anesthesiology score. Clinical outcomes, including range of motion, complication rates, and patient reported outcomes measurement information systems scores, were compared. Chi-squared, Fisher's Exact, and t-tests were performed. There were 20 PFA to TKA conversions that met inclusion criteria and were matched to 60 primary cases. RESULTS: There were 7 cases revised for arthritis progression, 5 for femoral component failure, 5 for patellar component failure, and 3 for patellar maltracking. PFA to TKA conversions for patellar failure (fracture, component loosening) had worse postoperative flexion (115 versus 127°, P = .023) and more complications of stiffness (40 versus 0%, P = .046) than primary TKAs. Conversions for failed patellar components had worse patient reported outcomes measurement information systems physical function (32 versus 45, P = .0046), physical health (42 versus 49, P = .0258), and pain scores (45 versus 24, P = .0465). No differences were found in rates of infection, manipulations under anesthesia, or reoperations. CONCLUSION: PFA to TKA conversion outcomes were similar to primary TKA, except in patients who had failed patellar components and demonstrated worse postoperative range of motion and patient-reported outcomes. Surgeons should avoid thin patellar resections and extensive lateral releases to minimize patellar failures.

A Pilot Randomized Trial of Heart Rate Monitoring Using Conventional Versus a New Electrocardiogram Algorithm during Neonatal Resuscitation at Birth.

Current guidelines support the use of a cardiac monitor during neonatal resuscitation. Infants born preterm randomized to a novel electrocardiogram algorithm displayed a heart rate sooner than the conventional electrocardiogram algorithm. Although resuscitation outcomes were not different, the availability of an earlier heart rate may benefit neonatal providers during high-risk resuscitations. TRIAL REGISTRATION: ClinicalTrials.govNCT04587934.

A Sox2 distal enhancer cluster regulates embryonic stem cell differentiation potential.

The Sox2 transcription factor must be robustly transcribed in embryonic stem (ES) cells to maintain pluripotency. Two gene-proximal enhancers, Sox2 regulatory region 1 (SRR1) and SRR2, display activity in reporter assays, but deleting SRR1 has no effect on pluripotency. We identified and functionally validated the sequences required for Sox2 transcription based on a computational model that predicted transcriptional enhancer elements within 130 kb of Sox2. Our reporter assays revealed three novel enhancers--SRR18, SRR107, and SRR111--that, through the formation of chromatin loops, form a chromatin complex with the Sox2 promoter in ES cells. Using the CRISPR/Cas9 system and F1 ES cells (Mus musculus(129) × Mus castaneus), we generated heterozygous deletions of each enhancer region, revealing that only the distal cluster containing SRR107 and SRR111, located >100 kb downstream from Sox2, is required for cis-regulation of Sox2 in ES cells. Furthermore, homozygous deletion of this distal Sox2 control region (SCR) caused significant reduction in Sox2 mRNA and protein levels, loss of ES cell colony morphology, genome-wide changes in gene expression, and impaired neuroectodermal formation upon spontaneous differentiation to embryoid bodies. Together, these data identify a distal control region essential for Sox2 transcription in ES cells.

The Role of Complementary and Alternative Medicine in Facial Plastic Surgery.

Complementary and alternative medicine (CAM) has become increasingly popular among facial plastic surgery patients. Over the last few decades, there has been a surge in the use of CAM. Despite the increasing prevalence of CAM, patients may feel uncomfortable discussing these therapies with their physicians, and physicians feel under-equipped to engage in meaningful discussions regarding these nontraditional therapies. This article reviews recent literature on the use of CAM for skin treatment in an attempt to provide additional resource. To date, the evidence to support statistically significant symptom improvement with use of non-traditional therapies remains limited. While preliminary data supports essential oil therapy in some cases, the results of the studies investigating other CAM therapies (traditional Chinese medicine, Ayurveda, and homeopathy) have been mixed and inconclusive.

Down syndrome caregivers' support needs: a mixed-method participatory approach.

BACKGROUND: The purpose of the study was to explore the support needs of caregivers of children with Down syndrome from their perspective using a mixed-method participatory research approach. METHODS: Concept mapping methodology was used to obtain caregiver perspectives. Twenty-one caregivers answered the question 'Are parents of individuals with Down syndrome supported, why or why not?' Caregivers were involved in the analysis of the data through concept mapping procedures. RESULTS: Sorted data were analysed with multidimensional scaling and cluster analysis. Participants generated eight thematic clusters representing the support needs of caregivers of children with Down syndrome. The themes included online and social support, support system gaps, areas where support is lacking, Down syndrome community support, financial support, advocacy needs, educational support and concerns for community programming. CONCLUSIONS: Themes align with previous research on support needs of parents of children with developmental disabilities. The study highlights the need for more local organisations to offer support that is affordable and accessible for families. Results will support future programme planning for services for individuals caring for those with Down syndrome.

Woody hardness classification impact on salvage laryngectomy functional outcomes.

PURPOSE: Post-radiation therapy salvage surgeries are challenging for surgeons due to tissue fibrosis. The woody hardness classification is valuable in differentiating the degree of neck stiffness, but its clinical utility has not been evaluated. We applied it to patients undergoing salvage laryngectomy to study the impact of woody hardness on postoperative outcomes. MATERIALS AND METHODS: A retrospective observational study was performed on patients undergoing salvage laryngectomy between 2014 and 2019. Patients were assigned into the A (extremely woody hard), B (moderately woody hard), or C (mildly woody hard) woody hardness class. The primary outcome was pharyngoesophageal stricture development. Secondary outcomes included time to pharyngoesophageal stricture, pharyngocutaneous fistula development, time to pharyngocutaneous fistula, development of post-operative complications, and tracheoesophageal puncture complications. RESULTS: Fifty-one patients were included in the study: Class A 1 patient, Class B 30 patients, and Class C 20 patients. The single Class A patient was grouped with the Class B patients. The development of a pharyngoesophageal stricture shows consistent negative association with woody hardness despite most analyses not reaching statistical significance. These associations are robust to a number of confounding variables in multivariate logistic and time to event analyses. Furthermore, the time to event analysis controlling for squamous cell carcinoma diagnosis led to a statistically significant association between woody hardness (i.e., A/B higher risk) and time to stricture (HR=5, p=0.02). CONCLUSIONS: This study suggests that this classification may be useful in predicting pharyngoesophageal stricture formation in salvage laryngectomy patients and could be used to implement stricture preventive measures.

Pre-intervention SNOT-22 scores predict outcomes in aspirin exacerbated respiratory disease.

PURPOSE: This study evaluated whether stratified preoperative, pre- aspirin desensitization (AD) sinonasal symptom scores predict postoperative, post-AD outcomes in Aspirin exacerbated respiratory disease (AERD). MATERIALS AND METHODS: Retrospective chart review of patients with aspirin challenge-proven AERD who underwent endoscopic sinus surgery followed by AD was performed. Preoperative, postoperative/pre-AD, and postoperative/post-AD sinonasal symptom scores were collected (22-item Sino-Nasal Outcomes Test, SNOT-22). A longitudinal linear mixed-effects model was used for data analysis. RESULTS: Forty-seven patients (59.6% female) aged 48.0 ± 13.2 were included. Average time from surgery to AD was 70.0 ± 52.8 days. Preoperative SNOT-22 scores (n = 47) were divided into tertiles (cutoffs of 36 and 54 indicating mild [22.5 ± 13.7], moderate [44.3 ± 12.2], and severe [72.9 ± 19.7] disease). This corresponded to 12 (25.5%), 18 (38.3%), and 17 (36.2%) subjects being categorized into mild, moderate, and severe tertiles, respectively. Postoperative, pre-AD SNOT-22 in all disease groups decreased and were not significantly different (12.3 ± 13.7, 11.1 ± 12.2, 22.7 ± 19.7; p = 0.074). At short-term post-AD, only the severe group worsened (35.0 ± 20.3, p < 0.001), whereas other groups demonstrated negligible change (9.3 ± 14.3 and 14.4 ± 12.2). At long-term post-AD, all groups redemonstrated convergence in symptom scores (23.7 ± 20.9, 19.4 ± 15.4, and 31.0 ± 27.6, p = 0.304). CONCLUSION: Preoperative SNOT-22 scores may be used as a predictor of postoperative, post-AD patient-reported outcomes in AERD. Patients with mild and moderate disease may derive benefit from surgery and AD alone, while those with severe disease may require additional interventions (e.g., biologics).

Facelift Surgery: History, Anatomy, and Recent Innovations.

Facelift surgery has become a beautifully predictable, safe, and extremely effective operation. Our patients can expect natural and long-lasting results as a direct outcome of our improved understanding and applications of surgical facial anatomy. Rhytidectomy, once an operation of simple well-placed elliptical skin excisions, evolved to include longer skin flaps, skin and platysma flaps with various superficial muscular aponeurotic system (SMAS) manipulations, and various deep plane techniques involving the skin and SMAS as a single unit composite flap. Extended deep plane rhytidectomy and vertical vector neck and SMAS lifting have emerged in recent years as techniques that extend the traditional deep plane dissection into the neck in a subplatysmal plane to allow for release of the platysma from the cervical retaining ligaments. This, ultimately, allows for the creation of a dramatically more youthful appearing face, neck, and jawline.

Enhancers and super-enhancers have an equivalent regulatory role in embryonic stem cells through regulation of single or multiple genes.

Transcriptional enhancers are critical for maintaining cell-type-specific gene expression and driving cell fate changes during development. Highly transcribed genes are often associated with a cluster of individual enhancers such as those found in locus control regions. Recently, these have been termed stretch enhancers or super-enhancers, which have been predicted to regulate critical cell identity genes. We employed a CRISPR/Cas9-mediated deletion approach to study the function of several enhancer clusters (ECs) and isolated enhancers in mouse embryonic stem (ES) cells. Our results reveal that the effect of deleting ECs, also classified as ES cell super-enhancers, is highly variable, resulting in target gene expression reductions ranging from 12% to as much as 92%. Partial deletions of these ECs which removed only one enhancer or a subcluster of enhancers revealed partially redundant control of the regulated gene by multiple enhancers within the larger cluster. Many highly transcribed genes in ES cells are not associated with a super-enhancer; furthermore, super-enhancer predictions ignore 81% of the potentially active regulatory elements predicted by cobinding of five or more pluripotency-associated transcription factors. Deletion of these additional enhancer regions revealed their robust regulatory role in gene transcription. In addition, select super-enhancers and enhancers were identified that regulated clusters of paralogous genes. We conclude that, whereas robust transcriptional output can be achieved by an isolated enhancer, clusters of enhancers acting on a common target gene act in a partially redundant manner to fine tune transcriptional output of their target genes.

Trigeminal Nerve Blockade in the Pterygopalatine Fossa for the Management of Postoperative Pain in Three Adults Undergoing Tonsillectomy: A Proof-of-Concept Report.

SETTING: Post-tonsillectomy pain in adults can be severe and is often poorly controlled. Pain can lead to decreased oral intake, bleeding, longer hospital stays, emergency department visits, dehydration, and weight loss. Due to persistent pain despite scheduled medications, other methods for pain control are needed. Local/regional anesthetic options have been previously studied in this population. Unfortunately, neither the injection of local anesthetics into the tonsillar fossa nor the postoperative topical application of local anesthetics to the tonsillar bed has demonstrated efficacy in large systematic reviews. PATIENTS: Here we report on the post-tonsillectomy pain experience of three patients who were treated with perioperative nerve blocks placed in the pterygopalatine fossa. This represents an as-yet unexplored option for post-tonsillectomy pain control. INTERVENTION: After induction of general anesthesia, before surgical incision, a 25-gauge spinal needle was advanced into the pterygopalatine fossa using a suprazygomatic, ultrasound-guided approach. Ropivacaine and dexamethasone were deposited into the pterygopalatine fossa. RESULTS: All three patients experienced excellent pain control for the duration of their recovery and required ≤10 mg of oxycodone over the two weeks after surgery. CONCLUSIONS: Our case series of three patients provides proof of concept that use of nerve blocks in the pterygopalatine fossa can be useful for the control of post-tonsillectomy pain. Further study is needed to confirm these initial results.

Septal Deviation after Septorhinoplasty: Causes and Surgical Management.

Revision rhinoplasty exists because the perfect primary rhinoplasty technique does not. The benefit of revision surgery is that it offers us the opportunity to study and identify what did not work well during previous surgery. Thoughtful approaches to technique and outcomes allow us to recognize which maneuvers are dependable and worth repeating, and which are not reliable and therefore worth avoiding. As surgeons seek safer, more predictable results to improve patient outcomes, new techniques emerge which we then apply, study, and modify again, based on what works and what does not over the short term and the long term. There is no substitute for experience or for learning from trusted surgeons' experiences. Revision rhinoplasty presents many challenges including surgically induced anatomical changes, weakened structural support, a lack of available tissue for reconstruction, tissue remodeling responses, and other iatrogenic and wound healing complications. The septum, as the primary source of structural nasal integrity, forms the foundation for functional and aesthetic rhinoplasty. Herein, we describe strategies in septorhinoplasty for patients who have undergone prior nasal septal surgery.

Development of solitary chemosensory cells in the distal lung after severe influenza injury.

H1N1 influenza virus infection induces dramatic and permanent alveolar remodeling mediated by p63+ progenitor cell expansion in both mice and some patients with acute respiratory distress syndrome. This persistent lung epithelial dysplasia is accompanied by chronic inflammation, but the driver(s) of this pathology are unknown. This work identified de novo appearance of solitary chemosensory cells (SCCs), as defined by the tuft cell marker doublecortin-like kinase 1, in post-influenza lungs, arising in close proximity with the dysplastic epithelium, whereas uninjured lungs are devoid of SCCs. Interestingly, fate mapping demonstrated that these cells are derived from p63-expressing lineage-negative progenitors, the same cell of origin as the dysplastic epithelium. Direct activation of SCCs with denatonium + succinate increased plasma extravasation specifically in post-influenza virus-injured lungs. Thus we demonstrate the previously unrecognized development and activity of SCCs in the lung following influenza virus infection, implicating SCCs as a central feature of dysplastic remodeling.

Gene signatures common to allograft rejection are associated with lymphocytic bronchitis.

Lymphocytic bronchitis (LB) precedes chronic lung allograft dysfunction. The relationships of LB (classified here as Endobronchial or E-grade rejection) to small airway (A- and B-grade) pathologies are unclear. We hypothesized that gene signatures common to allograft rejection would be present in LB. We studied LB in two partially overlapping lung transplant recipient cohorts: Cohort 1 included large airway brushes (6 LB cases and 18 post-transplant referents). Differential expression using DESeq2 was used for pathway analysis and to define an LB-associated metagene. In Cohort 2, eight biopsies for each pathology subtype were matched with pathology-free biopsies from the same subject (totaling 48 samples from 24 subjects). These biopsies were analyzed by multiplexed digital counting of immune transcripts. Metagene score differences were compared by paired t tests. Compared to referents in Cohort 1, LB demonstrated upregulation of allograft rejection pathways, and upregulated genes in these cases characterized an LB-associated metagene. We observed statistically increased expression in Cohort 2 for this LB-associated metagene and four other established allograft rejection metagenes in rejection vs paired non-rejection biopsies for both E-grade and A-grade subtypes, but not B-grade pathology. Gene expression-based categorization of allograft rejection may prove useful in monitoring lung allograft health.

Prospective observational study of early respiratory management in preterm neonates less than 35 weeks of gestation.

BACKGROUND: Current guidelines for management of respiratory distress syndrome (RDS) recommend continuous positive airway pressure (CPAP) as the primary mode of respiratory support even in the most premature neonates, reserving endotracheal intubation (ETI) for rescue surfactant or respiratory failure. The incidence and timing of ETI in practice is poorly documented. METHODS: In 27 Level III NICUs in the US (n = 19), Canada (n = 3) and Poland (n = 5), demographics and baseline characteristics, respiratory support modalities including timing of ETI, administration of surfactant and caffeine/other methylxanthines, and neonatal morbidities were prospectively recorded in consecutive preterm neonates following written parental consent. Infants were divided into three groups according to gestational age (GA) at birth, namely 26-28, 29-32 and 33-34 weeks. Statistical comparisons between groups were done using Chi-Square tests. RESULTS: Of 2093 neonates (US = 1507, 254 Canada, 332 Poland), 378 (18%) were 26-28 weeks gestational age (GA), 835 (40%) were 29-32 weeks, and 880 (42%) were 33-34 weeks. Antenatal steroid use was 81% overall, and approximately 89% in neonates ≤32 weeks. RDS incidence and use of ventilatory or supplemental oxygen support were similar across all sites. CPAP was initiated in 43% of all infants, being highest in the 29-32-week group, with a lower proportion in other GA categories (p < 0.001). The overall rate of ETI was 74% for neonates 26-28 weeks (42% within 15 min of birth, 49% within 60 min, and 57% within 3 h), 33% for 29-32 weeks (13 16 and 21%, respectively), and 16% for 33-34 weeks (5, 6 and 8%, respectively). Overall intubation rates and timing were similar between countries in all GAs. Rates within each country varied widely, however. Across US sites, overall ETI rates in 26-28-week neonates were 30-60%, and ETI within 15 min varied from 0 to 83%. Similar within 15-min variability was seen at Polish sites (22-67%) in this GA, and within all countries for 29-32 and 33-34-week neonates. CONCLUSION: Despite published guidelines for management of RDS, rate and timing of ETI varies widely, apparently unrelated to severity of illness. The impact of this variability on outcome is unknown but provides opportunities for further approaches which can avoid the need for ETI.

Solitary chemosensory cells are a primary epithelial source of IL-25 in patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: IL-25 can function as an early signal for the respiratory type 2 response characteristic of allergic asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). In the mouse gut, tuft cells are the epithelial source of IL-25. However, the source of human airway epithelial IL-25 has remained elusive. OBJECTIVE: In this study we sought to determine whether the solitary chemosensory cell (SCC) is the predominant source of IL-25 in the sinonasal epithelium. METHOD: Flow cytometry and immunofluorescence for SCCs and IL-25 were used to interrogate polyp and turbinate tissue from patients with CRSwNP. Mucus was collected during acute inflammatory exacerbations from patients with CRSwNP or chronic rhinosinusitis without nasal polyps and IL-25 levels determined by using ELISA. Lastly, sinonasal epithelial cultures derived from polyp and turbinate tissue were stimulated with IL-13 and analyzed for SCC proliferation and IL-25 production. RESULTS: This study demonstrates that a discrete cell type, likely an SCC, characterized by expression of the taste-associated G protein gustducin and the intestinal tuft cell marker doublecortin-like kinase 1, is the predominant source of IL-25 in the human upper airway. Additionally, we show that patients with CRSwNP have increased numbers of SCCs in nasal polyp tissue and that in vitro IL-13 exposure both increased proliferation and induced apical secretion of IL-25 into the mucosal layer. CONCLUSIONS: Inflammatory sinus polyps but not adjacent turbinate tissue show expansion of the SCC population, which is the source of epithelial IL-25.