BACKGROUND:Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and paranasal sinuses. Comorbid asthma, environmental allergies, and eosinophilia are associated with CRS. Exhalation delivery system with fluticasone (EDS-FLU) is approved for CRS; however, the influence of these features on treatment response remains unclear. OBJECTIVE:To evaluate whether baseline blood eosinophil (EOS) count, asthma, or allergies affect response to EDS-FLU in patients with CRS. METHODS:ReOpen1 and ReOpen2 were randomized, EDS-placebo-controlled studies. Patients with CRS were assigned (1:1:1) to EDS-FLU 186 μg, EDS-FLU 372 μg, or EDS-placebo, administered twice daily for 24 weeks. Endpoints included composite symptom score (CSS) at weeks 4, 8, and 12, 22-item Sino-Nasal Outcome Test (SNOT-22) and Patient Global Impression of Change (PGIC) at week 24. Outcomes were analysed for subgroups defined by asthma (yes/no), environmental allergy (yes/no), and EOS count (0-299 vs ≥300 cells/µL). RESULTS:Baseline characteristics were similar across groups (N=547). CSS improvement with EDS-FLU vs EDS-placebo was observed across subgroups (LS mean change at week 12 for EDS-FLU vs EDS-placebo in patients with asthma, -2.12 vs -1.36; without asthma, -2.40 vs -1.52; with allergy -2.12 vs -1.24; without allergy -2.37 vs -1.60; with EOS 0-299 cells/µL -2.11 vs -1.56; and with EOS ≥300 cells/µL -2.48 vs -1.36, respectively; all P<0.01). Similar results were observed for SNOT-22 and PGIC. Treatment-by-subgroup interaction showed consistent benefits irrespective of asthma, allergies, or EOS count. CONCLUSION:These results support EDS-FLU as an effective treatment for CRS, independent of underlying inflammatory endotype or common comorbid conditions. Due to the limitations of this analysis, further investigation is warranted. TRIAL REGISTRATION:Clinicaltrials.gov Identifiers: NCT03781804 and NCT03960580.
BACKGROUND:Complement activation has long been implicated in chronic spontaneous urticaria (CSU), but the underlying mechanisms and its clinical relevance remain unclear. OBJECTIVE:To investigate the role of complement C3, C4, C5 and C5a in CSU and their associations with immunological profiles and response to omalizumab. METHODS:We conducted a multicenter cross-sectional study involving 159 CSU patients from five Immunology and Clinical Allergology centers in Portugal. Clinical data, patient-reported outcomes, complement fractions, total IgE and IgG/IgE autoantibodies were assessed. Patients were stratified according to serum C5 levels. RESULTS:Serum C5 showed a bimodal distribution identifying two distinct subgroups, that broadly aligned with the immunological features previously described for autoallergic and autoimmune CSU. The low/normal C5 group (n=61) had lower C3 and C5a, higher total IgE, lower frequencies of autoantibodies (IgG and IgE anti-TPO, and IgG anti-IgE), and an 89% response rate to standard-dose omalizumab. The high C5 group (n=98) exhibited elevated C3 and C5a, higher rates of autoimmune thyroid disease, higher prevalence of IgG and IgE autoantibodies, and a 36% response rate to standard-dose omalizumab. C5a showed a similar bimodal distribution and association with omalizumab response. CONCLUSION:Serum C5 identifies two biologically distinct CSU subgroups: a low/normal C5 group characterized by higher total IgE, limited complement activation, and a high response rate to omalizumab; and a high C5 group characterized by lower IgE, enhanced complement activation, increased autoimmune burden, and a low response rate to omalizumab. These findings suggest that C5 may represent a clinically useful biomarker for therapeutic stratification.
BACKGROUND:Chronic rhinosinusitis (CRS) is associated with substantial psychological burden, yet tools for identifying patients with psychological distress are lacking in otolaryngologic practice. OBJECTIVE:To develop and validate an interpretable machine learning model for screening psychological distress in patients with CRS. METHODS:This multicenter study used preoperative data from 408 adults with CRS undergoing endoscopic sinus surgery and an independent external validation cohort of 61 patients. Psychological distress was assessed using the Hospital Anxiety and Depression Scale. After feature selection, nine machine learning models were compared in training and internal test sets. The final model was applied to the external cohort without refitting. Performance was evaluated using discrimination, calibration, and decision curve analysis (DCA), with interpretability assessed using SHapley Additive exPlanations. RESULTS:Psychological distress was present in 42.9% of the development cohort and 37.7% of the external cohort. Key predictors were SNOT-22 score, nasal congestion, nasal polyps, antihypertensive drug use, and ear fullness. CatBoost showed the best performance, achieving an AUC of 0.864 (95% CI, 0.793-0.927) in the internal test set, with a Brier score of 0.146. DCA showed the model outperformed the treat-all and treat-none strategies across a broad range of threshold probabilities. In external validation, the model achieved an AUC of 0.792 (95% CI, 0.653-0.913). The final model was translated into a web-based tool for individualized risk estimation. CONCLUSION:Psychological distress is common in CRS. An interpretable CatBoost model using routine clinical variables showed good discrimination and external validity, supporting its potential use for screening and risk stratification.
BACKGROUND:Peanut oral immunotherapy (POIT) in infants and toddlers is highly efficacious and can facilitate ad lib peanut consumption. However, traditional protocols require all updosing to occur in the office setting, creating logistical barriers for both families and allergy/immunology practices. OBJECTIVE:To evaluate caregiver satisfaction and safety of POIT with home updosing, facilitated through telephone and video encounters. METHODS:Children aged 6-47 months with peanut allergy underwent POIT with updosing through telephone, video, and in-office encounters. Reaction rates were prospectively recorded, and caregivers completed a satisfaction survey at protocol completion. RESULTS:Fifty-three children completed the POIT protocol (median age, 13 months [IQR, 11-18]). Fourteen children (26.4%) experienced 24 treatment-related reactions; 54.2% resolved spontaneously, 41.7% improved with antihistamines, and one reaction (4.2%) required epinephrine during an in-office updosing encounter. Three reactions occurred during updosing, for a rate of 0.4% risk of reaction per dose, with 0.1% risk of requiring epinephrine. Although the odds of reaction were higher during updosing (OR = 2.34, 95% CI = 0.69-7.96), the difference in reaction rate did not reach statistical significance when comparing updosing to home maintenance dosing (p=0.16). Most caregivers (71.7%) preferred a combination of all three encounter types for updosing, citing convenience and reduced travel time as advantages. CONCLUSION:Updosing encounters for infant and toddler POIT are safe to complete via video and telephone encounters. Families prefer a combination of encounter types for updosing, including in-office, video and telephone encounters, commonly citing added convenience and lack of travel time as advantages of this hybrid approach.
BACKGROUND:Intranasal corticosteroids (INCS) are the most effective monotherapy for allergic rhinitis (AR), but daily adherence remains challenging. Evidence comparing regular versus as-needed INCS use in pediatric perennial allergic rhinitis (PAR) is limited. OBJECTIVE:To evaluate the efficacy, safety, and anti-inflammatory effects of regular versus as-needed INCS in pediatric PAR. METHODS:In this 8-week, randomized, double-blind, double-dummy trial, 70 children aged 6-18 years with PAR were assigned (1:1) to regular or as-needed intranasal fluticasone furoate. Key outcomes included total, nasal, and ocular symptom scores (TSS, TNSS, TOSS), visual analog scale (VAS), parent-assessed scores, Rhinoconjunctivitis Quality of Life-36 (RCQ-36), peak nasal inspiratory flow (PNIF), nasal cytology, INCS exposure, and adverse events. RESULTS:Sixty-eight patients completed the trial (as-needed, n=33; regular, n=35). Regular treatment demonstrated greater improvements in TSS, TNSS, TOSS, VAS, PVAS, and PNIF than as-needed treatment at selected early time points (all P<0.05). However, these differences were not sustained through week 8. No significant between-group differences were observed in PTSS, PTNSS, PTOSS, or RCQ-36 scores. At week 8, regular treatment yielded greater reductions in mucosal eosinophils and basophilic metachromatic cells (P<0.05). Cumulative INCS exposure was lower with as-needed treatment (P<0.05). Adverse events were comparable, although epistaxis occurred only in the as-needed group (P=0.02). CONCLUSION:Regular INCS use was associated with greater early clinical and antiinflammatory benefits than as-needed use in pediatric PAR, without increased adverse events. However, between-group clinical differences were not sustained through week 8. As-needed treatment also improved outcomes from baseline and may be an alternative for symptom control in selected patients.
BACKGROUND:Food allergy (FA) is increasing in prevalence among children worldwide, and this diagnosis creates substantial health, psychosocial, and financial burdens. Although some children may eventually achieve resolution of certain food allergies, the factors associated with resolution are poorly understood. OBJECTIVE:The objective of this study was to identify factors associated with FA resolution at baseline enrollment, focusing on children with at least one active FA and the determinants of resolution of their other allergies. METHODS:Children younger than 12 years old with physician-diagnosed IgE-mediated FA were enrolled in FORWARD, a multicenter observational study. Data from caregiver surveys completed at enrollment regarding resolution of other FA and electronic health records were analyzed. Unadjusted analyses compared demographic and clinical characteristics between children with and without reported resolution of at least one FA at enrollment. Multivariable logistic regression models then evaluated associations between resolution of FA and covariates, including race/ethnicity, household income, health literacy scores (HLS), and area deprivation index (ADI). RESULTS:The study included 1,359 participants. Children most often experienced resolution of allergies to milk (35%), soy (32%), and wheat (27%), whereas resolution of peanut (3.8%) and shellfish (3.5%) allergies were less common. White children more frequently reported resolution of FA to all common food allergens when compared to Black and Hispanic children. Furthermore, lower family income, lower parental HLS and higher ADI were observed among children who did not report FA resolution for all 9 common food/food groups. CONCLUSION:Socioeconomic disadvantage, parental health literacy, and racial/ethnic disparities were associated with a lower likelihood of FA resolution in this cohort.
