Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by pronounced epithelial remodeling and barrier dysfunction, contributing to a high rate of postoperative recurrence. However, molecular mechanisms associated with early recurrence remain poorly understood. Methods We performed paired proteomic profiling of nasal polyp tissues obtained from the same patients before initial surgery and at the time of recurrence (discovery cohort) to identify recurrence-associated proteins. Candidate proteins were validated in an independent cohort, and their association with recurrence risk was assessed by receiver operating characteristic (ROC) curve and Kaplan-Meier analyses. The expression and cellular localization of the identified candidate were further characterized by immunofluorescence. Mechanistic investigations were conducted in primary human nasal epithelial cells using ATP stimulation and specific pharmacological inhibitors. Results Paired proteomic analysis identified P2X7, PDE4D, and JADE2 as the top 3 upregulated proteins in recurrent tissues. Among these, only P2X7 was consistently elevated in the validation cohort and predominantly localized to the nasal epithelium (P < 0.01). ROC curve analysis indicated that tissue P2X7 level might serve as a potential predictive marker for postoperative recurrence of CRSwNP. (AUC = 0.678, P = 0.022). Kaplan-Meier analysis further showed that the risk of recurrence was significantly higher in the high P2X7 expression group (HR = 2.323, P = 0.015). Recurrent tissues exhibited elevated levels of NLRP3 and IL-1β, reduced expression of epithelial barrier markers occludin and E-cadherin, accompanied by increased extracellular ATP concentrations. In vitro, ATP stimulation upregulated P2X7 expression, induced NLRP3 and cleaved IL-1β, and downregulated occludin and E-cadherin. Notably, these effects were reversed by a P2X7-specific inhibitor (A-438079). Conclusion Paired proteomic profiling revealed distinct protein expression profiles between pre- and post-recurrence nasal polyps, with P2X7 serving as a promising predictive biomarker for early recurrence. Mechanistically, the ATP/P2X7 axis may drive disease recurrence by potentially promoting inflammasome activation and epithelial barrier disruption.
Purpose:Idiopathic angioedema (AE-UN) is a heterogeneous, exclusion-based clinical category rather than a single disease entity. The clinical characteristics and potential exploratory markers in patients currently classified as AE-UN remain poorly understood. This study aimed to evaluate clinical features and laboratory mediators in a selected cohort of patients fulfilling the current diagnostic definition of AE-UN. Methods:We compared 16 patients classified as AE-UN according to a stepwise diagnostic approach with 20 patients with hereditary angioedema (HAE), 20 patients with mast cell-mediated angioedema (AE-MC), and 24 healthy controls. AE-MC classification required recurrent angioedema with or without wheals, normal C4 and C1-inhibitor levels, and a convincing clinical response to mast cell-directed therapy, including H1-antihistamines up to four-fold standard dose when clinically indicated, corticosteroids, or standard-dose omalizumab (4-6 months). Patients without such a response and without confirmed HAE, drug-induced angioedema, or other recognized causes were classified as AE-UN. Baseline features, treatments, and laboratory factors were analyzed, including serum markers of inflammation, endothelial dysfunction, and serine proteases, as determined by ELISA. Results:AE-UN showed shorter disease duration compared to AE-MC and HAE (2.26 vs. 3.02 vs. 15.78, p < 0.0001), but experienced a relatively higher frequency of life-threatening attacks than AE-MC (25% vs. 10%). Meanwhile, facial edema was most common in AE-UN (68.75%). We did not find a significant difference regarding age and sex among all angioedema (AE) subtypes. IgG4 levels were increased in AE-UN rather than other AE groups, and demonstrated a statistical difference with HAE (p = 0.049). Besides, Ang-1, Ang-2, and Tie-2 were significantly elevated in all AE compared to controls. By contrast, the Ang-2/Ang-1 ratio was decreased in AE patients. Notably, in AE-UN compared to AE-MC and HAE, Fibroblast Activation Protein (FAP) concentration was significantly reduced, whereas for tPA and PLA2G7, the difference was not significant compared to controls and among AE subtypes. Conclusions:Lower FAP levels may represent an exploratory biomarker candidate in this selected AE-UN cohort, rather than a diagnostic marker for a homogeneous disease. Ang-1, Ang-2, and Tie-2 were increased across angioedema groups. Because of the small sample size, the exclusion-based nature of AE-UN, and the possibility of diagnostic reclassification, these findings should be interpreted as hypothesis-generating.
Psychological stress and psychiatric comorbidities are highly prevalent in patients with asthma, with evidence supporting bidirectional links. Excessive psychological stress is associated with immune dysregulation, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, and neuroimmune crosstalk that increases Type 2 inflammation associated with poorly controlled asthma. Anxiety and depression worsen asthma control and quality of life through complex and bidirectional mechanisms. Both cognitive-behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR) can help reduce distress and increase quality of life for people with asthma. However, their effects on lung function and exacerbation rates remain inconsistent.Integrating interventions that address stress and mental health factors into asthma care is essential for optimal care. Distinguishing formal psychiatric illness from stress-related emotional distress allows for specific interventions to be utilized. Embedding validated screening tools and behavioral health into routine clinical practice can address the value of managing psychosocial burden while complementing pharmacologic therapy.
Introduction:Atopic dermatitis (AD) is a prevalent inflammatory skin disease with origins increasingly traced to the intrauterine environment. While maternal diet and immunity influence infant health, the optimal time window and specific metabolic signatures conferring protection against AD remain unclear. This study aims to characterize longitudinal perinatal metabolic profiles to identify stage-specific predictive biomarkers and critical windows for fetal metabolic exposure. Methods:A longitudinal birth cohort study was conducted with 109 mother-infant pairs recruited between 2021 and 2023. Biological samples including maternal plasma (collected at early-mid gestation and pre-delivery), umbilical cord blood, and meconium were analyzed using untargeted LC-MS metabolomics. Infants were followed for 1 year to ascertain AD status (AD group n = 39; Healthy group n = 70). Logistic regression was performed to identify significant metabolites associated with health outcomes, and Random Forest classification was utilized to compare predictive performance across different developmental windows. Results:Distinct metabolic phenotypes were identified. In early-mid gestation maternal plasma, the Healthy group exhibited a significant enrichment of protective metabolites across 2 major classes: Polyunsaturated Fatty Acids (PUFAs), including 13S-HODE (OR = 0.11, P < 0.001) and Alpha-Linolenic Acid (OR = 0.51, P = 0.014); and Flavonoids, including Formononetin (OR = 0.33, P = 0.005), Equol (OR = 0.48, P = 0.012), and Quercetin (OR = 0.87, P = 0.027). Fewer metabolic alterations were observed in subsequent phases, such as ergocalciferol (OR = 0.56, P = 0.028) in late gestation and isovitexin (OR = 0.88, P = 0.037) in meconium. In cord blood, key predictive markers included phenyl acetate (OR = 0.28, P = 0.025), the antioxidant Ribose-1,5-bisphosphate (OR = 0.09, P = 0.017), and sterculic acid (OR = 1.23, P = 0.026). Notably, the latter 2 were consistently identified across both early-mid gestation maternal plasma and cord blood. Crucially, Random Forest modeling revealed that integrating early-mid gestation metabolites significantly improved AD prediction over the Baseline Clinical Model (AUC 0.831, 95% CI 0.73-0.93 vs. AUC 0.463, 95% CI 0.35-0.57), vastly outperforming late gestation metabolites (AUC 0.669, 95% CI 0.48-0.86). In neonates, the cord blood model (AUC 0.817, 95% CI 0.69-0.95) demonstrated superior predictive value compared to meconium (AUC 0.644, 95% CI 0.46-0.83). This predictive pattern remained highly robust in parsimonious models restricted to only 6 core metabolites. Conclusion:This study highlights potential protective and risk perinatal metabolic profiles, suggesting that the early maternal metabolic milieu plays a critical role in 'priming' the infant immune system against AD and identifying early-mid gestation as an optimal window for early risk prediction. These predictive associations require confirmation in future mechanistic and interventional trials before informing targeted nutritional strategies.
Objective We aimed to investigate the associations of the daily mean and short-term variation in ambient relative humidity (RH), temperature, and fine particulate matter (PM2.5) with asthma treatment steps. Methods We consecutively recruited 288 newly diagnosed adult patients with asthma and followed them for at least 6 months according to the Global Initiative for Asthma (GINA) strategy. Odds ratios (ORs) for higher GINA treatment steps required to achieve asthma control were estimated using logistic regression. We also conducted exposure-response analyses to explore potentially nonlinear relationships between environmental exposure and asthma treatment step across seasons. Results A 1% increase in the 1-day RH difference and a 1-μg/m3 increase in the 7-day PM2.5 difference were associated with 1.054-fold and 1.052-fold higher odds of step 4 treatment, respectively. A 1% increase in the 1-day RH difference and a 1-μg/m3 increase in the 7-day PM2.5 difference were associated with 1.047-fold and 1.056-fold higher odds of medium-dose inhaled corticosteroids plus long-acting beta-agonists (ICS + LABA), respectively. A 1% increase in the 7-day RH mean and a 1-μg/m3 increase in the 30-day PM2.5 difference were associated with 1.075-fold and 1.205-fold higher odds of triple inhaler therapy and biologics use, respectively. Exposure-response analyses suggested noticeable seasonal patterns for temperature and RH in relation to asthma treatment strategy. Conclusions Our exploratory and hypothesis-generating findings showed that greater short-term variation in RH and PM2.5 was associated with higher treatment intensity in adult asthma, particularly the use of medium-dose ICS + LABA and biologics. Higher RH mean was also associated with triple inhaler therapy. These associations were more evident during the cold season. Multicenter validation studies in larger population studies are warranted.
The recent ARIA-MeDALL hypothesis proposed in 2023 that allergic rhinitis (AR) alone and allergic rhinitis and asthma (A) multimorbidity (AR + A) represent 2 distinct diseases. To improve the knowledge on this topic, we have gathered data from real-world studies using MASK-air®. According to our analyses: (i) An “extreme allergy phenotype” [A + AR + C, Conjunctivitis] was confirmed and found to be more severe (symptoms and work productivity) than single diseases alone. (ii) Patients with AR + A required more rhinitis medications, and had more severe VAS levels for nasal and ocular symptoms than those with AR alone in all countries tested. (iii) In clusters with poorly controlled AR, the frequency of co-medicating with more than 1 rhinitis drug was higher in AR + A than in AR alone. (iv) In the CONSTANCES general population cohort, a co-medication pattern (intranasal corticosteroid and oral H1-antihistamines) was associated with the presence of AR + A (vs AR alone). This co-medication pattern was associated in MASK-air® with a poorer AR control than monotherapy. (v) Patients with AR + A had different EQ-5D patterns than those with AR alone. (vi) Large differences were found between AR alone and AR + A in work impairment, resulting in higher weekly indirect costs in all OECD countries in AR + A by comparison to AR alone. Although mHealth studies are hypothesis-generating, and usually not reliable for testing or confirming hypotheses, our results are strongly in support of the nosologic distinction between A + AR and AR alone.
Background Asthma is the most common chronic disease in childhood and although many children with asthma achieve disease control with low- to medium-dose inhaled corticosteroids, 2-10% have severe asthma (SA). Biologics have been available for treatment in adults and adolescents for almost twenty years, and currently 5 biologic therapies have been approved by regulatory agencies for SA in children and/or adolescents. Objective To describe the evolution and remission rate of pediatric SA patients on biologics, including after switch of biologic. Methods A retrospective observational study was conducted January 2023 to January 2024 in SA children (6-18 years) in a tertiary care hospital. American Thoracic Society/European Respiratory Society (ATS/ERS) criteria classified asthma as severe. Patients who started biologic therapy, or who switched from a previous biologic, were included. Index date is the timepoint at which biologic therapy was started or switched. We compare clinical and biomarker (fractional exhaled nitric oxide, blood eosinophil count [BEC], IgE) data from 12 months pre- with 12 months postindex- date. Results Sixty children were included (mean age 14.1 ± 3.2 years); 34/60 (56%) female. Our 46 biologic-naïve patients received omalizumab in 21/46 (46%), dupilumab in 23/46 (50%), and mepolizumab in 2 (4%). Fourteen switchers (23%), who presented incomplete improvement on their first biologic, were changed to a second/third biologic including benralizumab and tezepelumab. Our children experienced an average of 2.4 severe exacerbations 12 months pre-index date. Twelve months post-index-date, no child experienced severe exacerbations and 98% (59/60) reached complete, 4- parameter, clinical remission plus a significant reduction of all biomarkers. Conclusion The use of biologic therapies in pediatric patients with SA allowed for adequate disease control. With correct biologic selection or timely switch when incomplete response, clinical remission, normalization of lung function and a reduction in ICS daily dose was achieved in a very high percentage. Moreover, controlling asthma enables allergen-specific immunotherapy for children with allergic SA.
Background: 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 reaction in no more than 5% of the allergic population). To achieve a balance between protection and the risk of PAL overuse, ED05 was deemed preferable to ED01. There was 70% agreement that consumers should be informed of residual risk (ie, unintended allergen presence below the reference dose), but no consensus as to how this might be done. Finally, PAL should not be used for an allergen declared to be absent with a “free from” statement, nor should a PAL appear for an allergen listed as an ingredient. Conclusions: This Delphi explored a comprehensive set of statements across multiple aspects of PAL development, application, and communication. On the one hand, it provides systematically derived considerations, aligned with the FAO/WHO consultation recommendations, to support future harmonization of practices. On the other, it highlights several areas of uncertainty to prioritize for future research.
Background: Anaphylaxis is a potentially life-threatening allergic reaction requiring prompt recognition and treatment. Although increasing trends in pediatric anaphylaxis have been reported worldwide, nationwide epidemiological data from Southeast Asia remain limited. This study aimed to investigate the epidemiology, clinical characteristics, and healthcare burden of pediatric anaphylaxis in Thailand using a national administrative database. Methods: We conducted a nationwide retrospective study using the Thai National Health Security Office database from 2019 to 2023. Children aged 1 month to <18 years hospitalized with anaphylaxis were identified using ICD-10-TM codes. Demographic characteristics, triggers, comorbidities, complications, and outcomes were analyzed. Temporal trends, regional variation, and factors associated with in-hospital mortality were evaluated. Results: A total of 42,290 pediatric anaphylaxis hospitalizations were identified, increasing from 7877 cases in 2019 to 10,519 in 2023. School-aged children and adolescents accounted for the largest proportion, with male predominance (59.4%). Food-related reactions were more common in younger children, whereas insect-related reactions were more frequent in older age groups. Most patients had favorable outcomes, with a median hospital stay of 1 day and in-hospital mortality of 0.04%. Severe complications and certain comorbidities were associated with increased risk of adverse outcomes. Geographic variation was observed across regions. Conclusions: Pediatric anaphylaxis hospitalizations in Thailand increased during the study period, while mortality remained low. Age-related trigger patterns and regional differences highlight the need for improved surveillance, documentation, and targeted prevention strategies.
Background: Eosinophilic inflammation is a key feature of chronic rhinosinusitis with nasal polyps (CRSwNP); however, the extent to which peripheral blood eosinophil counts reflect local nasal eosinophilia remains controversial, particularly across different geographic regions and socioeconomic contexts. Methods: We conducted a multicenter retrospective study involving 1047 patients with CRSwNP who underwent endoscopic sinus surgery at 3 tertiary hospitals in Jiangsu Province, China. Peripheral blood eosinophil counts and nasal mucosa eosinophil counts from polyp tissue were measured at 3 time points (2008, 2012, and 2016). Correlation analyses, receiver operating characteristic (ROC) curve analysis, linear regression models, and linear mixed-effects models were used to evaluate the association between blood and tissue eosinophil counts, as well as their temporal and regional variability. City-level gross domestic product (GDP) and annual mean PM2.5 concentrations were incorporated to explore potential socioeconomic and environmental associations. Results: Peripheral blood eosinophil counts showed a weak correlation with nasal mucosa eosinophil counts (ρ = 0.28) and had limited predictive value for CRSwNP (AUC = 0.607). Eosinophil levels varied significantly across hospitals and time points, with no consistent temporal trends observed. Linear regression analysis revealed a modest overall association between peripheral blood and nasal mucosa eosinophil counts (adjusted R2 = 0.053). Linear mixed-effects models confirmed heterogeneous temporal trends in both blood and tissue eosinophil counts across hospitals (P < 0.01). Additionally, city-level analyses revealed positive correlations between mean peripheral blood eosinophil counts and total GDP (ρ = 0.80, P = 0.014) and between nasal mucosa eosinophil counts and GDP per capita (ρ = 0.72, P = 0.037). In contrast, annual mean PM2.5 concentration was not significantly associated with either peripheral blood or nasal mucosa eosinophil counts. Conclusion: Peripheral blood eosinophil count is a poor surrogate for local tissue inflammation in CRSwNP. Substantial regional, temporal, and socioeconomic heterogeneity underscores the need to consider geographic context when interpreting eosinophil-based biomarkers in clinical assessment and disease stratification.
Background:Clinical remission is increasingly recognized as a primary treatment goal in severe asthma, particularly severe eosinophilic asthma (SEA), where comorbidities such as chronic rhinosinusitis with nasal polyps (CRSwNP) contribute to persistent inflammation and treatment burden. Benralizumab, an anti-IL-5Rα monoclonal antibody, has shown efficacy in achieving sustained control in SEA, but long-term real-world data beyond 36 months remain limited. Objective:To evaluate the long-term (48-month) effectiveness of benralizumab in SEA patients, focusing on clinical remission, airway function, and reduction of background therapy, including oral corticosteroids (OCS) and inhaled corticosteroids (ICS). Methods:In this retrospective, multicenter study across 9 Italian centers, 128 adult SEA patients (mean age 57.1 years, 57% female; 59.4% with CRSwNP) were treated with subcutaneous benralizumab for up to 48 months. Clinical remission was assessed using SANI criteria: partial (pCR, meeting ≥2 of 3 criteria without OCS) and complete (cCR, all criteria fulfilled without OCS). Outcomes included annualized exacerbation rate (AER), pulmonary function (FEV1, FEV1/FVC, FEF25-75%), airway inflammation (FeNO, blood eosinophils), patient-reported outcomes (ACT, ACQ-6, AQLQ), and background therapy use. Mixed-effects regression models evaluated longitudinal changes. Results:Benralizumab induced rapid and sustained improvements. AER decreased from 3.62 to 0.33 at 48 months; blood eosinophils were nearly undetectable throughout. FEV1 increased from 2.04 L to 2.49 L, with proportional gains in FEV1/FVC and FEF25-75%. ACT and ACQ-6 scores improved significantly (p < 0.001), and sinonasal symptoms in CRSwNP patients declined (VAS 4.70 → 2.31). OCS discontinuation was achieved in 88.5% of patients at 48 months, with mean ICS dose reduced by 35%. Overall, clinical remission was observed in 87.9% of patients, with cCR in 63.8%. Improvements were consistent regardless of ICS dose reduction. Conclusions:Long-term benralizumab treatment in SEA patients leads to rapid, sustained clinical remission, improved large and small airway function, and significant reduction of background therapy, including OCS and ICS. These results support the role of benralizumab as a disease-modifying therapy and highlight the feasibility of remission-based management in real-world practice.
Background: Multiple severity scoring systems exist for classifying reactions during OFCs; however, the lack of uniformity among them results in inconsistent identification and management of anaphylaxis. Objective: This study aimed to evaluate the clinical characteristics and severity of anaphylactic and non-anaphylactic reactions during oral food challenges (OFCs) in children and to compare the concordance and discrepancies among 7 different severity scoring systems. Methods: In this single-center, retrospective, and observational study, positive OFCs were retrospectively graded using 7 different severity classification systems. The concordance and discrepancies among the classification systems, including the World Allergy Organization (WAO) 2024 criteria, the International Classification of Diseases 11th Revision (ICD-11), and the European Academy of Allergy and Clinical Immunology (EAACI) classifications, were evaluated. Results: Of the 1901 OFCs performed on 855 patients, 344 (18.1%) were positive, and among these, 61 (17.7%) were classified as anaphylactic reactions. Patients with anaphylactic reactions were significantly older than those with non-anaphylactic reactions (median age: 27 months vs. 15 months; p < 0.001). Using the WAO2024 criteria as the reference standard, both ICD-11 and EAACI classifications showed 100% sensitivity, while specificity for all systems ranged from 86.2% to 99.3%. Discrepancies among severity scoring systems were primarily due to differences in the interpretation of gastrointestinal manifestations. EAACI showed the most favorable balance between sensitivity and specificity, whereas CoFAR and Dribin demonstrated the highest specificity. Conclusion: The findings emphasize the need for a harmonized severity classification system that is applicable in both clinical practice and research. Such standardization would enhance diagnostic accuracy and improve the management of food allergies in children.
Background Sublingual immunotherapy (SLIT) has been shown to be effective in controlling the symptoms of allergic rhinitis and asthma, but few studies have assessed its long-term preventive effects on lower-airway inflammation and asthma onset. Objective We sought to evaluate prospectively the long-term effects of SLIT on lower-airway function in patients with allergic rhinitis caused by house dust mites (HDM). Methods We performed a post hoc analysis of a previously published prospective, open-label study involving patients with allergic rhinitis who were monosensitized to mites and followed for 15 years. All participants had bronchial hyperreactivity and were originally assigned to 4 groups receiving either pharmacological therapy alone or SLIT for 3, 4, or 5 years (SLIT 3, SLIT 4, and SLIT 5). Skin sensitization, methacholine reactivity, and respiratory function were evaluated annually during the winter months. Results Seventy-eight patients were enrolled, and 59 completed the study. Over 15 years of observation, new sensitizations occurred in all participants in the control group but in fewer than one-quarter of patients who received SLIT for 3, 4, or 5 years (21%, 12%, and 11%, respectively). Among patients with rhinitis treated only with intranasal corticosteroids and systemic antihistamines, the development of asthma, defined as a decline in FEV to below 80% of the predicted value, was observed in 58% (7 of 12). In contrast, progression to asthma was significantly less frequent among patients with rhinitis treated with SLIT, regardless of treatment duration: 1 of 14 patients in the SLIT 3 group (7%), 1 of 16 in the SLIT 4 group (6%), and 1 of 17 in the SLIT 5 group (6%). Conclusion In the long term, SLIT provided a significant clinical benefit in HDM-induced allergic rhinitis by reducing both the allergic march and asthma onset and by limiting the decline in lung function, as measured by FEV1.
Background:Pediatric chronic rhinosinusitis with nasal polyps (CRSwNP) exhibits a high rate of postoperative recurrence, yet effective molecular predictors remain lacking. This study aims to explore recurrence-associated proteins and evaluate their predictive value. Methods:Proteomic analysis was performed on nasal mucosa from a discovery cohort, with >1 year of follow-up to identify differentially expressed proteins (DEPs) associated with postoperative recurrence. Candidate proteins were validated in an independent cohort using western blotting, immunofluorescence, qRT-PCR, and serum ELISA. Results:In the discovery cohort, 6 pediatric patients suffering postoperative recurrence were classified as rCRSwNP, and 10 as non-rCRSwNP. Proteomic analysis revealed distinct expression patterns among control, non-rCRSwNP, and rCRSwNP groups. Four candidate proteins (CERS4, PLEKHA6, RAB29, SPRR3) were identified by intersecting the top 50 DEPs. SPRR3 and RAB29 were significantly upregulated in rCRSwNP, primarily localized to the nasal epithelium, as confirmed by western blotting and immunofluorescence. qRT-PCR further validated their increase in the recurrence group. Notably, paired tissue samples showed increased SPRR3 expression at revision surgery compared to baseline, and ELISA revealed higher serum SPRR3 levels in recurrent cases, correlating with recurrence risk. ROC and Kaplan-Meier analyses demonstrated potential predictive value for serum SPRR3. Conclusion:Our study identified a recurrence-associated proteomic signature in pediatric CRSwNP, marked by selective epithelial upregulation of SPRR3. Elevated serum SPRR3 was strongly linked to postoperative recurrence risk, supporting its utility as a predictive biomarker for identifying children at higher risk of relapse.
Background The recently published PROMUSE study performed by the GA2LEN UCARE (Urticaria Centers of Reference and Excellence) and ADCARE (Angioedema Centers of Reference and Excellence) networks found that patient-reported outcome measures (PROMs) are underused in clinical practice for atopic dermatitis (AD) and chronic urticaria (CU). The reasons for this remain unknown. We studied why physicians have reservations about using PROMs, how PROM use is affected by the barriers they perceive, and what the physician demographics/characteristics associated with these barriers are. Methods This is an observational, cross-sectional study where the PROMUSE questionnaire was used and applied to physicians from 45 specialized centers worldwide. Of the 2534 physicians surveyed in the PROMUSE study, 474 who treated patients with AD and CU were included in the analysis. Results For the 474 physicians who treat AD and CU patients, the most common issues perceived as primary barriers to PROM use were “time constraints” (n = 455/474), “not mandated to complete” (n = 428/474), and “patients dislike PROMs” (n = 425/474). Higher rates of barrier perception were observed for males, younger physicians, and non-specialist physicians. The more barriers physicians perceive, the less frequently PROMs are used, with a strong and significant negative correlation between the number of barriers perceived and the frequency of PROM use. Two of the 15 perceived barriers significantly prevented using PROMs: the belief that PROMs constrain the doctor-patient relationship and the belief that patients dislike them. Conclusions The underutilization of PROMs in AD and CU is strongly driven by physicians' perceptions that patients dislike them and that they constrain the doctor-patient relationship. This suggests physicians may have deeper insights into the practical shortcomings of current instruments. Therefore, rather than solely focusing on physician education, existing AD and CU PROMs urgently require re-evaluation and co-development with direct patient involvement (eg, Core Outcome Sets) to ensure they are genuinely patient-centered and clinically relevant.
Background: Data about hereditary angioedema (HAE) from Latin American countries are lacking. Our main objective was to characterize the epidemiology, clinical presentation, and treatment patterns of HAE patients from Argentina at a nationwide level. Methods: A non-interventional, observational, web-based survey was conducted, aimed at physicians treating patients with a confirmed diagnosis of HAE. Data about demographic characteristics, HAE type and family history, clinical pattern, attack frequency and triggers, treatment patterns, and use of validated HAE scores were collected to develop a patient registry. Results: Data from 538 patients submitted by 75 physicians were obtained. Median age was 33 years (IQR:20-46). Most patients were female (58.73%). Median age at presentation of first symptoms was 12 years (IQR:5-18). Median time from presentation to a confirmed diagnosis of HAE was 10 years (IQR:5-18). Most patients had deficiency of C1-INH (HAE-1, 76%). Variants in the F12 gene (HAE-FXII) were found in 7% of subjects; variants in DAB2IP (p.D239 N) (HAE-DAB2IP) were identified in 7 subjects. Severity of HAE was predominantly moderate (37%). Most reported triggers were emotional stress (75.55%) and physical trauma (69.59%). Specific treatment for attacks was prescribed for 88% of patients. Icatibant was the most prescribed drug (76.91%). Long-term prophylaxis (LTP) was used in 28.34% of subjects, with lanadelumab being the most prescribed agent (58.45%). Conclusion: Argentine HAE patients share several characteristics with patients from real-world studies, but some findings (time to diagnosis, low LTP rates, relatively high rates of HAE-FXII and a novel, recently characterized form of HAE-DAB2IP) require further research.
