Background: Olipudase alfa is the first disease-specific enzyme replacement therapy (ERT) approved for the treatment of noncentral nervous system manifestations of acid sphingomyelinase deficiency (ASMD); however, experience with the management of olipudase alfa–induced anaphylaxis remains limited. Case Presentation: We report a 13-year-old girl with chronic neurovisceral ASMD who developed anaphylaxis during an olipudase alfa infusion, presenting with periorbital edema, generalized urticaria, and hypotension. Following successful treatment with intramuscular adrenaline, olipudase alfa was reintroduced using a 12-step desensitization protocol. After two successful infusions at 2 mg/kg, the dose was re-escalated to the full therapeutic dose of 3 mg/kg, which has since been maintained every 2 weeks without recurrence of hypersensitivity reactions. Conclusion: In contrast to the previously reported real-world pediatric case, in which recurrent anaphylactic reactions ultimately necessitated omalizumab therapy, our patient successfully achieved and maintained the full therapeutic dose with desensitization alone. This case suggests that individualized desensitization may enable the safe continuation of olipudase alfa following anaphylaxis, thereby avoiding permanent discontinuation of ERT.
Background: Allergen sensitization is common in pediatric asthma, but its relationship with inflammatory phenotypes and acute clinical events remains incompletely characterized in real-world practice. Objective: To describe allergen sensitization patterns in children with asthma and evaluate their association with fractional exhaled nitric oxide (FeNO)-defined type 2 inflammatory phenotype, with acute exacerbation and abnormal lung function records as exploratory outcomes. Methods: This single-center retrospective real-world study included children recorded in an asthma monitoring database from January 2025 to May 2026. The primary analysis used the earliest visit after patient-level deduplication. Sensitization patterns were classified as any allergen, inhalant allergen, food allergen, multiple sensitization, and high-grade sensitization. Elevated FeNO was defined as FeNO >35 ppb. Complete-case analysis was performed for multivariable models. Group comparisons, false discovery rate correction, trend tests, Spearman correlation, and multivariable logistic regression were used. Results: Among 812 unique children, 396 (48.8%) had FeNO records. Inhalant allergen sensitization predominated, and dust mite was the most common sensitization category. Pollen sensitization and multiple sensitization increased across FeNO strata. The multivariable model included 393 complete cases and 51 events. Pollen sensitization (adjusted odds ratio [aOR], 2.56; 95% confidence interval [CI], 1.22–5.35) and multiple sensitization (aOR, 2.14; 95% CI, 1.11–4.12) were independently associated with FeNO > 35 ppb. The FeNO model showed acceptable discrimination (area under the curve, 0.761), good calibration by the Hosmer–Lemeshow test ( P = 0.773), and Nagelkerke R 2 of 0.162. Adding pollen and multiple sensitization to a clinical baseline model modestly improved prediction (Delta AUC, 0.027; continuous net reclassification improvement, 0.334), whereas integrated discrimination improvement (IDI) was not statistically significant. No stable independent association was observed between specific allergen categories and acute exacerbation or abnormal lung function records. Conclusion: In children with asthma, allergen sensitization patterns were more closely associated with FeNO-defined type 2 inflammatory phenotype than with acute clinical events. Combined FeNO and allergen assessment may support phenotype-oriented assessment.
Introduction: As neonatal intensive care unit (NICU) survival improves, the number of children with tracheostomy, along with those who require home care nursing (HCN), is rising. Discharge delays (DD) are an issue, with an emotional or financial toll on children, families, and the health care system. We aimed to investigate whether social drivers of health like socioeconomic status (SES), race, sex, and medical factors such as gestational age influenced DD for children with tracheostomy. Materials and Methods: We conducted a retrospective chart review of children who underwent tracheostomy in the NICU during a 5-year period. Four authors reviewed electronic medical records for demographics, clinical information, and DD. SES was determined based on the HOUsing-based SocioEconomic Status (HOUSES) index. The Kruskal-Wallis test and Spearman's correlation were used to assess the association between DD in days and independent variables. In addition, the cohort was divided into 2 groups based on DD >= 30 days to explore factors associated with it descriptively. Results: Sixteen children were included in the study (10 female, 6 male). Ten children were identified as White, and 3 as Black. Three children were not White or Black. Only one child did not experience DD. Median DD was 15 days (interquartile range [IQR]: 13-24; range 0-49). Three children had clinically significant DD (>30 days). The most common cause of DD was waiting for HCN (10/16, 63%, P = 0.065). Race (White versus Black versus other) was associated with DD (P = 0.045). Female sex (P = 0.039) was associated with significant DD, while birthweight (P = 0.19) and HOUSES index (P = 0.49) were not. Conclusion: DD is a common phenomenon in children with tracheostomy in the NICU, and lack of HCN is the major factor. Race and sex may play a role in DD. HCN shortages and other causes of DD should be further studied and addressed.
Shared decision-making (SDM) interventions have been shown to improve asthma control in adults but are less studied in pediatric-caregiver dyads. Because asthma imposes a disproportionate burden on Black and Hispanic adolescents, we adapted an adult asthma SDM intervention to minoritized dyads.Focus groups informed adaptation of the intervention. Feasibility, for example, intervention fidelity, and clinical outcomes, for example, effect of the active intervention on shared decision-making (SDM-9) scores and Asthma Control Questionnaire (ACQ) scores were assessed. Post-trial interviews assessed acceptability of study components based on implementation metrics.Nine focus groups were conducted with 25 adolescents (36% female; 84% Hispanic; mean age = 12.7 years) and 20 caregivers (95% female; 90% Hispanic; mean age = 39.8 years) to adapt the intervention to dyads. Sixty adolescents (aged 10-14 years; 53% female; 77% Hispanic; mean age = 11.3 years, caregivers (90% female; 77% Hispanic; mean age = 39.4 years), and dyads were enrolled in the trial. Clinician interventionists (n = 7) were randomized to the active SDM or dose-matched attention control condition. Feasibility was demonstrated by high fidelity to intervention delivery, high retention of subjects, and high rates of data collection. No outcomes were significant for example, ACQ: beta = 0.15, 95% confidence interval -0.22, 0.51, P = 0.43, although adolescents in the active arm reported higher SDM scores relative to controls (beta = 3.35 P = 0.14). Adolescents, caregivers, and clinicians completing posttrial interviews found the study acceptable.The intervention was feasible and acceptable. Although no significant health improvements were detected, targets for future refinements, for example, in-person-only intervention delivery and enrollment of younger children, warrant testing to determine if a dyadic SDM may be a useful patient-centered strategy for underserved pediatric populations.While an SDM intervention was feasible and acceptable, refinements are needed to translate SDM improvements to behavior change that impact asthma outcomes.
Introduction:Hereditary angioedema (HAE) is a rare, potentially life-threatening genetic condition characterized by recurrent episodes of localized tissue swelling, often affecting the skin, upper respiratory tract, and gastrointestinal system. HAE-FXII, also known as HAE with normal C1 inhibitor (C1INH), has been associated with mutations in only one of several genes, including FXII encoding coagulation factor XII (FXII). The aim of the study was to investigate the pathogenicity and functional consequences of the c.1681-7G>A intronic variant in the FXII gene according to ACMG guidelines in familial cases of HAE-FXII.Materials and Methods:Genetic analysis was performed using Sanger sequencing on affected individuals. To assess whether the variant affects splicing, in silico analysis and Messenger RNA (mRNA) studies were conducted on patient-derived samples.Results:The c.1681-7G>A variant was identified in multiple individuals from affected families. However, splicing analysis revealed that this intronic variant did not cause any alteration in mRNA processing. No aberrant transcripts were detected, and expression levels were comparable to controls, indicating that the variant does not have an effect on splicing or gene function.Discussion:The c.1681-7G>A variant in the FXII gene is unlikely to be a pathogenic alteration in HAE type III.Contribution to the Literature:These findings support its classification as a benign variant, emphasizing the importance of functional validation when interpreting intronic changes in genetic diagnostics.
