Budesonide

BackgroundThe mechanism underlying severe asthma with fungal sensitization (SAFS) is unknown. IL-33 is important in fungus-induced asthma exacerbations, but its role in fungal sensitization is unexplored.ObjectiveWe sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33.MethodsEighty-two children (median age, 11.7 years; 63% male) with severe therapy-resistant asthma were included. SAFS (n = 38) was defined as specific IgE or skin prick test response positivity to Aspergillus fumigatus, Alternaria alternata, or Cladosporium herbarum. Clinical features and airway immunopathology were assessed. Chronic exposure to house dust mite and A alternata were compared in a neonatal mouse model.ResultsChildren with SAFS had earlier symptom onset (0.5 vs 1.5 years, P = .006), higher total IgE levels (637 vs 177 IU/mL, P = .002), and nonfungal inhalant allergen-specific IgE. Significantly more children with SAFS were prescribed maintenance oral steroids (42% vs 14%, P = .02). SAFS was associated with higher airway IL-33 levels. In neonatal mice A alternata exposure induced higher serum IgE levels, pulmonary IL-33 levels, and IL-13(+) innate lymphoid cell (ILC) and TH2 cell numbers but similar airway hyperresponsiveness (AHR) compared with those after house dust mite exposure. Lung IL-33 levels, IL-13(+) ILC numbers, TH2 cell numbers, IL-13 levels, and AHR remained increased with inhaled budesonide during A alternata exposure, but all features were significantly reduced in ST2(-/-) mice lacking a functional receptor for IL-33.ConclusionPediatric SAFS was associated with more oral steroid therapy and higher IL-33 levels. A alternata exposure resulted in increased IL-33-mediated ILC2 numbers, TH2 cell numbers, and steroid-resistant AHR. IL-33 might be a novel therapeutic target for SAFS.

BackgroundImmune checkpoint inhibitors (CPIs) are effective against a variety of malignancies but can be limited by inflammatory toxicities such as enterocolitis. Enterocolitis is typically treated with systemically active glucocorticoids. Endoscopy can stratify patients by the severity of mucosal inflammation, including identifying patients with colitis in the absence of visible mucosal changes: microscopic colitis. Whether patients with CPI microscopic colitis could be managed differently from colitis with more severe mucosal involvement is unclear. The objective of this study was to describe outcomes in CPI microscopic colitis focusing on the response to first line treatment with budesonide.MethodsWe evaluated data from a retrospective cohort from a single-center large academic hospital. The participants were all adult patients evaluated by endoscopy for suspected CPI enterocolitis between 3/2017 and 3/2019. The exposures were: Mayo Endoscopic Score (range 0-3). The subset was: oral budesonide, maximum dose 12 mg daily, administered minimum of 5 weeks. The main outcomes and measures were: Primary: time from first CPI exposure to first glucocorticoid use; use of systemic glucocorticoids; time from symptom onset to resolution; continuation of CPI therapy; number of additional CPI infusions received. Secondary: admissions for symptom control; novel irAE development; need for second-line immunosuppression; oncologic outcomes.ResultsWe identified 38 patients with biopsy confirmed CPI enterocolitis, 13 in the microscopic colitis cohort, and 25 in the non-microscopic colitis cohort. Budesonide use was higher in the microscopic colitis cohort (12/13 vs 3/25, p ConclusionsGastrointestinal mucosal inflammation without visible mucosal injury is a distinct, prevalent CPI enterocolitis subset that can be diagnosed by endoscopy. First-line budesonide appears effective in controlling "microscopic colitis" symptoms and prolonging immunotherapy duration. These findings present a compelling rationale for routine endoscopic evaluation of suspected CPI enterocolitis and suggest an alternative glucocorticoid-sparing treatment strategy for a subset of such patients.

An optimum carrier rugosity is essential to achieve a satisfying drug deposition efficiency for the carrier based dry powder inhalation (DPI). Therefore, a non-organic spray drying technique was firstly used to prepare nanoporous mannitol with small asperities to enhance the DPI aerosolization performance. Ammonium carbonate was used as a pore-forming agent since it decomposed with volatile during preparation. It was found that only the porous structure, and hence the specific surface area and carrier density were changed at different ammonium carbonate concentration. Furthermore, the carrier density was used as an indication of porosity to correlate with drug aerosolization. A good correlation between the carrier density and fine particle fraction (FPF) (r2 = 0.9579) was established, suggesting that the deposition efficiency increased with the decreased carrier density. Nanoporous mannitol with a mean pore size of about 6 nm exhibited 0.24-fold carrier density while 2.16-fold FPF value of the non-porous mannitol. The enhanced deposition efficiency was further confirmed from the pharmacokinetic studies since the nanoporous mannitol exhibited a significantly higher AUC0-8h value than the non-porous mannitol and commercial product Pulmicort. Therefore, surface modification by preparing nanoporous carrier through non-organic spray drying showed to be a facile approach to enhance the DPI aerosolization performance.

IntroductionThe targeted-release budesonide formulation (Nefecon) addresses IgA nephropathy (IgAN) by inhibiting mucosal immune dysregulation in gut-associated lymphoid tissue (GALT), leading to reduced production of galactose-deficient IgA1 (Gd-IgA1). Randomized controlled trials (NEFIGAN, NefIgArd) have shown that Nefecon effectively decreases proteinuria and decelerates the progression of chronic kidney disease (CKD) in patients with IgA nephropathy (IgAN). However, evidence in real-world clinical settings and high-risk subgroups remains limited.MethodsWe performed a retrospective cohort study involving 60 IgAN patients treated with Nefecon (16 mg/day) for no less than 6 months at the First Affiliated Hospital of Zhengzhou University between October 2024 and November 2025. The study focused on evaluating alterations in proteinuria and estimated glomerular filtration rate (eGFR). Subgroup analyses were further carried out according to the use of concomitant immunosuppressive therapy, baseline proteinuria levels, and baseline renal function.ResultsProteinuria decreased significantly after 4 and 6 months of Nefecon treatment (median reduction 31.9% and 43.5%, respectively; both p vs. 35.8% at 6 months, p=0.04). Notably, patients with a baseline eGFR ConclusionIn routine clinical practice, Nefecon effectively reduces proteinuria and preserves renal function in IgAN, even in patients excluded from randomized trials. The combination with immunosuppressive therapy may provide additive benefit that requires further validation. These findings extend trial results to real-world settings and highlight Nefecon as a practical treatment option for high-risk IgAN patients.