Administration Of Budesonide Research Articles

Effect of electronic fibrobronchoscope alveolar lavage combined with local administration of budesonide on the efficacy of Mycoplasma pneumoniae pneumonia in children.

This study investigates the effect of electronic fibrobronchoscope alveolar lavage combined with local administration of budesonide on the efficacy of treating Mycoplasma pneumoniae pneumonia (MPP) in children. A retrospective analysis was conducted on the clinical data of 100 children with MPP treated at our hospital from April 2022 to April 2024. The patients were divided into an experimental group (50 cases) and a control group (50 cases) based to the treatment method. Both groups received routine treatment, however, the control group was treated with electronic fibrobronchoscope alveolar lavage alone, while the experimental group received electronic fibrobronchoscope alveolar lavage combined with local administration of budesonide. The efficacy of the two treatments was compared. The experimental group showed a significantly higher overall effective rate than the control group (p<0.05). After treatment, the time for cough relief, lung rales resolution, fever reduction, and hospital stay were significantly shorter in the experimental group compared to the control group (p<0.05). One week after treatment, the levels of tidal volume, vital capacity, and peak expiratory flow in the experimental group were higher than those in the control group (p<0.05). Post-treatment levels of WBC and CRP were lower in the experimental group than in the control group (p<0.05). Additionally, the incidence of complications in the experimental group was lower than in the control group (p<0.05). Electronic fibrobronchoscope alveolar lavage combined with local administration of budesonide improves the efficacy of treatment for children with MPP, enhances clinical indicators, reduces inflammation levels, and has high safety, making it worthy of clinical promotion.

Impact of twice-daily budesonide foam administration on early clinical response and endoscopic remission in patients with ulcerative colitis: a post hoc analysis.

Early treatment response of ulcerative colitis (UC) symptom resolution is desirable. This post hoc analysis evaluated efficacy outcomes, including endoscopic remission, by responder status and the influence of once-daily (QD) versus twice-daily (BID) budesonide foam dosing in patients with UC. Data were pooled from phase 2 and phase 3 clinical trials of budesonide rectal foam QD or BID or placebo for up to 12weeks. Outcomes were evaluated by treatment and budesonide administration regimen and by responder group: early (rectal bleeding subscore [RBS] 0 from Week 2 through Week 6), delayed (RBS 0 at Week 6), and nonresponder (RBS>0 at Week 6). The main analysis set included 55 (QD) and 120 (BID) budesonide-treated patients and 116 placebo-treated patients. At Week 6, the trend in early response rate was significant among treatment groups (BID, 45.3%; QD, 32.1%; placebo, 12.8%; P<0.0001). Among BID recipients, trends for complete endoscopic remission rate (Mayo endoscopic score [MES]=0) and endoscopic remission rate (MES=0 or 1) were significant among responder status groups (early responder, 67.4% and 95.4%, respectively; delayed responder, 48.1% and 85.2%; nonresponder, 24.0% and 64.0%; P<0.001 for both). Regardless of the administration regimen, most early responders achieved endoscopic remission at Week 6. Among responder status groups, early responders' cumulative non-relapse period was greatest (P=0.07). A BID budesonide administration regimen is preferred to increase the probability of early response and, following endoscopic remission, a better prognosis after stopping treatment.

The impact of combined administration of surfactant and intratracheal budesonide compared to surfactant alone on bronchopulmonary dysplasia (BPD) and mortality rate in preterm infants with respiratory distress syndrome: a single-blind randomized clinical trial

BackgroundRespiratory distress syndrome (RDS) is one of the most important and common disorders among premature infants.ObjectiveThis study aimed to compare the effect of the combination of surfactant and budesonide with surfactant alone on Bronchopulmonary dysplasia (BPD) and mortality rate among premature infants with RDS.MethodAn outcome assessor-blind randomized clinical trial was conducted on 134 premature infants with RDS who were born in Ayatollah Mousavi Hospital, Zanjan, Iran in 2021. The covariate adaptive randomization method was utilized to allocate participants into two groups (surfactant alone and a combination of surfactant and budesonide). The primary outcomes were BPD and Mortality rate from admission to hospital discharge. The data in this study were analyzed using SPSS software version 18.ResultsOverall the comparison of mortality rate and BPD between the two groups did not show a significant difference(p > 0.05). The subgroup results showed that administering surfactant with budesonide to infants under 30 weeks of age significantly reduced the number of deaths compared to using surfactant alone (5 vs. 17). Similar positive effects were observed for the occurrence of Pulmonary Hemorrhage, the need for a second dose of surfactant, oxygen index, mean blood pressure and mean arterial pressure (MAP) in infants under 34 weeks of age compared to more than 34 weeks (p < 0.05).ConclusionThese findings suggest that the combination therapy of surfactant and budesonide may be beneficial, particularly in preterm infants with less than 34 weeks gestational age and 1500 birth weight. However, further studies with larger sample sizes and longer follow-up periods are needed to confirm these results and assess long-term outcomes.Trial registrationThe study was registered at the Iranian Registry of Clinical Trials website under the code IRCT20201222049802N1. https://en.irct.ir/user/trial/48117/view.Registration date28/02/2021.Public repository: Data setThis research data set link is displayed on the Zanjan-Iran Medical Sciences website: https://repository.zums.ac.ir/cgi/users/login? target=https%3 A%2 F/repository.zums.ac.ir/id/eprint.

The Effect of Salbutamol and Budesonide Pediatric Doses on Dental Enamel and Packable and Flowable Composites: Microhardness, Surface Roughness and Color.

To assess and compare the effects of two pediatric anti-asthmatic medication doses on the microhardness of enamel and microhardness, surface roughness and color of restorative materials. Human enamel samples and packable and flowable composite restorations were used. The samples were exposed to Salbutamol (0.6 mL/6 mL saline) and Budesonide (2 mL/2 mL saline) via a custom-made chamber connected to a nebulizer. Medication administration was conducted for 10 days. The samples were brushed with an electronic brush in a continuous and circular mode for 10 s after 10 min of medication administration. Assessments of microhardness, surface roughness and color were carried out at three different time intervals: baseline (T0), 5 days (T1) and 10 days (T2). One-way analysis of variance (ANOVA), a two-sample t-test and a Bonferroni multiple comparison test were used to analyze the data and compare between the groups. Both medications significantly (p < 0.05) decreased the microhardness of the enamel and composite samples after 10 days. Both medications lowered the surface roughness of both types of composite with a greater effect observed after 10 days of Budesonide administration (p < 0.05). Both medications had comparable detectable color change on both types of composite with a greater effect observed after 10 days of Budesonide administration (p < 0.05). Salbutamol and Budesonide significantly decreased microhardness in the enamel samples. Both medications affected the properties of packable and flowable composites. The packable composite showed more resistance to microhardness changes. Both medications showed a clinically detectable change in the color of packable and flowable composites.

Intratracheal Administration of Budesonide with Surfactant in Very Low Birth Weight Infants to Prevent Bronchopulmonary Dysplasia

Intratracheal Administration of Budesonide with Surfactant in Very Low Birth Weight Infants to Prevent Bronchopulmonary Dysplasia

Systemic administration of budesonide in pegylated liposomes for improved efficacy in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a chronic inflammatory condition affecting the nasal and paranasal sinuses of approximately 11.5% of the United States adult population. Oral corticosteroids are effective in controlling sinonasal inflammation in CRS, but the associated adverse effects limit their clinical use. Topical budesonide has demonstrated clinical efficacy in patients with CRS. Herein, we investigated the systemic delivery of liposomes tethered with poly(ethylene glycol) (PEG) and loaded with budesonide in a murine model of CRS. PEGylated liposomes encapsulated with budesonide phosphate (L-BudP) were administered via tail vein injection, and the feasibility of L-BudP to reduce sinonasal inflammation was compared to that of free budesonide phosphate (F-BudP) and topical budesonide phosphate (T-BudP) treatment over a 14-day study period. Compared to a single injection of F-BudP and repeat T-BudP administration, a single injection of L-BudP demonstrated increased and prolonged efficacy, resulting in the significant improvement of sinonasal tissue histopathological scores (p<0.05) with decreased immune cell infiltration (p<0.05). Toxicities associated with L-BudP and T-BudP treatment, assessed via body and organ weight, as well as peripheral blood liver enzyme and differential white blood cell analyses, were transient and comparable. These data suggest that systemic liposomal budesonide treatment results in improved efficacy over topical treatment.

Long-term Effects of Intratracheal Budesonide and Surfactant for the Prevention of Bronchopulmonary Dysplasia: A Narrative Review.

This study aimed to compare the safety and efficacy of intratracheal administration of budesonide and surfactant with surfactant alone for bronchopulmonary dysplasia (BPD) prevention in premature infants with respiratory distress syndrome. A literature search was performed in MEDLINE, Embase, Cochrane, ClinicalTrials.gov, and gray literature. Assessment of quality was conducted using CASP tool, ROBIS tool, and GRADE framework. A systematic review and meta-analysis and three observational studies were identified. Budesonide was associated with reduced incidence and severity of BPD, reduced mortality, patent ductus arteriosus, need for additional surfactant doses, hypotension, duration of invasive ventilation, hospital stays, salbutamol prescriptions, and hospitalizations in the first 2 years of life. The safety of budesonide on neurodevelopmental outcomes at 2 to 3 years of corrected age was reported. Budesonide might be associated with a reduction in BPD incidence and severity, without evidence of impaired neurodevelopment at 2 to 3 years of age. According to the GRADE framework, the level of evidence is low due to significant heterogeneity of studies and other bias. · BPD prevention is urgently needed.. · Intratracheal budesonide and surfactant for neonatal RDS could reduce BPD.. · The grade of evidence for this intervention is low due to study heterogeneity and other bias..

The effect of therapeutic bronchoalveolar lavage in combination with glucocorticoids on children with acute exogenous lipoid pneumonia.

Exogenous lipoid pneumonia (ELP) is a rare disease caused by the inhalation of oily materials in the alveoli with the pathological characterization by the presence of laden-lipid macrophages in the respiratory specimens. At present, the treatment norm for ELP has not well defined, and so the aim of this study is to evaluate the effect of bronchoalveolar lavage in combination with glucocorticoids on children with ELP. We retrospectively reviewed 17 children with a confirmed history of exogenous oily materials aspiration, admitted to the First Affiliated Hospital of Guangzhou Medical University from June 2012 to December 2021. Clinical features, blood investigations, tomographic evaluations, therapeutic bronchoalveolar lavage and glucocorticoids use were carried out at the beginning of therapy and throughout a follow-up period. The included children are the median age of 2 years. Fever, dypnea and tachypnea were the most common symptoms. The most common radiological features were airspace consolidations (15, 93.75%). Chest CT scans showed areas of consolidation with air bronchogram (15, 93.75%), poorly defined centrilobular nodules (13, 81.25%), areas of ground-glass attenuation (11, 68.75%) and 'crazy-paving' pattern (6, 37.5%) in the both lower, right middle lung lobes. Neutrophil percentage of peripheral blood and bronchoalveolar lavage fluid exhibited a significantly higher than the normal range. After treatment with multiple bronchoalveolar lavages and local administration of budesonide during the hospital stay, taken by oral prednisolone (1 ~ 2 mg/kg) after discharge, all of children became asymptomatic and presented normal radiological imagings in the follow-up period. The most frequently findings in the CT scan of ELP were consolidations and ground-glass attenuation in the both lower and right middle lung lobes. Multiple bronchoalveolar lavages in combination with oral prednisolone for children who had a confirmed history of exogenous oily substances ingestion were an efficient and safe for the clearance of oily materials from the lung and the prevention of fibrosis. This strategy contributed to reducing the damage of ELP in children patients.

Design, Development and In vivo Evaluation of Core in Cup Tablets of Budesonide

Budesonide is widely used drug for treatment of active inflammatory bowel disease (IBD). Core in-cup tablets were prepared to achieve a prolonged release of Budesonide and for alleviating the symptoms of inflammatory bowel disease. The objective of this study was to investigate differences in the pharmacokinetic patterns between an optimized core in cup tablet formulation and pure Budesonide suspension. In-vivo evaluation studies were performed based on the uniform and reliable results of in-vitro drug release studies. Various pharmacokinetic parameters were compared to obtain mean plasma drug concentration curve versus time. The pure drug suspension and Core-in-cup tablets formulation of Budesonide were administered to two groups of white New Zealand rabbits (n=6) through the oral route following cross over design pattern. The drug concentration in plasma samples were measured using LC-MS/MS method. Pharmacokinetic parameters were determined for each formulation. The comparison of the plasma time curves of the dosage forms showed that each dosage form caused significant differences in the drug plasma levels. The optimized core in cup tablet formulation shown some lag phase initially before releasing the drug. The mean residence time of core in cup tablet formulation was found to be more than the pure drug suspension formulation. The oral administration of Budesonide resulted in a low and quite variable AUC of 154.1±1.44 ng/ml/hr., whereas the optimized core-in-cup tablets resulted in AUC of 918.2±3.11 ng/ml/hr. The bioavailability of optimized formulation was enhanced six times compared with pure drug suspension. From the above results, it can be concluded that the prepared core in cup tablet can be considered as one of the promising formulation techniques for chronotherapeutic management of inflammatory bowel disease.

A “hydroxyl radicals standard” for evaluating the efficacy of anti-asthma drugs by using a two-photon NIR optical sensor

Asthma is a common chronic inflammatory disease of the airways and a condition closely associated with oxidative stress. However, the lack of effective biomarkers and non-invasive real-time monitoring tools remains a great challenge for the early diagnosis and therapy of asthma. Hydroxyl radicals represent a key reactive oxygen species in biological systems, and therefore the change of hydroxyl radical level may be observed to be elevated in asthmatic mice. To verify this conjecture, in this paper, we designed the first two-photon (TP) near-infrared (NIR) fluorescent probe to be used with high selectivity for monitoring the fluctuating changes of hydroxyl radicals. More importantly, using this new probe, we have successfully observed the changes of hydroxyl radicals during asthma by visualization means for the first time. Immediately following the imaging experiments on mice, we also found that the therapeutic effect of using the combination of budesonide and terbutaline administration in asthmatic mice was effective than what was achieved by the administration of budesonide or terbutaline alone. These findings suggest that this probe has the potential to be a powerful tool for future asthma diagnosis and assessment of the therapeutic effect of asthma co-administration. Notably, it is expected to establish a “hydroxyl radicals standard” for evaluating the efficacy of anti-asthma drug therapy by using fluorescence imaging techniques.

Effect of Local Corticosteroid Administration on CD8+CD25+Foxp3+ Tregs in Neutrophilic CRSwNP

Introduction: CD8⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) play an important role in human’s immune tolerance. The study was aimed to assess the influence of budesonide nasal spray on CD8⁺CD25⁺Foxp3⁺ Tregs and to evaluate their cellular functions in neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNPs). Methods: Fifteen patients with neutrophilic CRSwNPs were enrolled and received physiological saline or budesonide nasal spray treatment (Saline or Budesonide group) for 3 months. Nasal tissue samples were obtained from normal subjects or those patients and cultured in vitro. CD8⁺CD25⁺Foxp3⁺ Tregs were separated from normal or NP tissues and also cultured in vitro. Then interleukin (IL)-10 and its mRNA were evaluated in the above cell cultures. The cells were applied into NP cultures. Finally, myeloperoxidase (MPO), interferon (IFN)-γ, IL-1β, and tumor necrosis factor (TNF)-α were assessed in the tissue cultures. Results: CD8⁺CD25⁺Foxp3⁺ Tregs decreased in NP tissues. Budesonide administration did not enhance the percentage of these cells in polypoid tissues. IL-10 and its mRNA were increased in the above cell cultures from NPs. However, there were no statistical differences between the two treatments in the IL-10 expression. Additionally, levels of MPO, IFN-γ, IL-1β, and TNF-α were totally elevated in NP tissue cultures and reduced after the administration of CD8⁺CD25⁺Foxp3⁺ Tregs. However, there were no significant differences in concentrations of these mediators between these two groups of the CD8⁺CD25⁺Foxp3⁺ Tregs treatment in vitro. Conclusion: The findings indicate that CD8⁺CD25⁺Foxp3⁺ Tregs might regulate the neutrophilic inflammation, and budesonide nasal spray therapy could not ameliorate the inflammation in neutrophilic CRSwNPs.

Efficacy and safety of intratracheal administration of budesonide combined with pulmonary surfactant in preventing bronchopulmonary dysplasia: a prospective randomized controlled trial.

To study the efficacy and safety of early intratracheal administration of budesonide combined with pulmonary surfactant (PS) in preventing bronchopulmonary dysplasia (BPD). A prospective randomized controlled trial was designed. A total of 122 infants with a high risk of BPD who were admitted to the neonatal intensive care unit of the Third Affiliated Hospital of Zhengzhou University from January to July 2021 were enrolled. The infants were randomly divided into a conventional treatment group with 62 infants (treated with PS alone at an initial dose of 200 mg/kg, followed by a dose of 100 mg/kg according to the condition of the infant) and an observation group with 60 infants (treated with PS at the same dose as the conventional treatment group, with the addition of budesonide 0.25 mg/kg for intratracheal instillation at each time of PS application). The two groups were compared in terms of the times of PS use, ventilator parameters at different time points, oxygen inhalation, incidence rate and severity of BPD, incidence rate of complications, and tidal breathing pulmonary function at the corrected gestational age of 40 weeks. Compared with the conventional treatment group, the observation group had a significantly lower proportion of infants using PS for two or three times (P<0.05). Compared with the conventional treatment group, the observation group had a significantly lower fraction of inspired oxygen at 24 and 48 hours and 3, 7, and 21 days after administration, significantly shorter durations of invasive ventilation, noninvasive ventilation, ventilator application, and oxygen therapy, a significantly lower incidence rate of BPD, and a significantly lower severity of BPD (P<0.05). There was no significant difference in the incidence rate of glucocorticoid-related complications between the two groups (P>0.05). Compared with PS use alone in preterm infants with a high risk of BPD, budesonide combined with PS can reduce repeated use of PS, lower ventilator parameters, shorten the duration of respiratory support, and reduce the incidence rate and severity of BPD, without increasing the incidence rate of glucocorticoid-related complications.

New Strategies for Improving Budesonide Skin Retention.

The aim of this work was to evaluate the ex vivo effect of the combination of two strategies, complexation with cyclodextrin, and poloxamer hydrogels, for improving water solubility in the dermal absorption of budesonide. Two hydrogels containing 20% poloxamer 407, alone or in combination with poloxamer 403, were prepared. Each formulation was loaded with 0.05% budesonide, using either pure budesonide or its inclusion complex with hydroxypropyl-β-cyclodextrin, and applied in finite dose conditions on porcine skin. The obtained results showed that for all formulations, budesonide accumulated preferentially in the epidermis compared to the dermis. The quantity of budesonide recovered in the receptor compartment was, in all cases, lower than the LOQ of the analytical method, suggesting the absence of possible systemic absorption. The use of a binary poloxamer mixture reduced skin retention, in line with the lower release from the vehicle. When the hydrogels were formulated with the inclusion complex, an increase in budesonide skin retention was observed with both hydrogels. Poloxamer hydrogel proved to be a suitable vehicle for cutaneous administration of budesonide.

Inhaled Budesonide in Neonatal Respiratory Distress Syndrome of Near-Term Neonates: A Randomized, Placebo-Controlled Trial.

This study evaluates the value of inhaled budesonide (BUD) administration in neonatal respiratory distress syndrome (RDS) cases especially for near-term neonates. A randomized controlled trial involving 120 neonates with respiratory distress, which was diagnosed as RDS, was conducted from July 2016 to March 2018. The neonates studied were divided into 2 groups: group 1 (the inhaled BUD group), consisting of 60 neonates who received BUD (2 mL, 0.25-mg/mL suspension) inhalation, twice daily for 5 days; and group 2 (the placebo group), consisting of 60 neonates with RDS who received humidified distilled sterile water inhalation (2 mL). Downes score, RDS grades, and interleukin 8 (IL-8) levels were monitored and measured on the first and fifth days of incubation. Statistically significant differences (SSDs) in RDS grades, Downes score, and IL-8 levels on the fifth day of admission were observed between groups 1 and 2 (p = 0.001) and between the first and fifth days of incubation in group 1 (p = 0.001). The SSDs in the duration of hospitalization (p = 0.001) and the number of neonates receiving mechanical ventilation (p = 0.032) were found between both groups. Budesonide inhalation is associated with improvements in clinical and laboratory parameters in neonates with RDS.

A Randomized Clinical Trial of Intratracheal Administration of Surfactant and Budesonide Combination in Comparison to Surfactant for Prevention of Bronchopulmonary Dysplasia.

ObjectivesBronchopulmonary dysplasia (BPD) remains a major problem in preterm infants occurring in up to 50% of infants born at < 28 weeks gestational age. Inflammation plays an important role in the pathogenesis of BPD. This study was conducted to evaluate the efficacy of intratracheal budesonide administration in combination with a surfactant in preventing BPD in preterm infants.MethodsIn a randomized clinical trial, 128 preterm infants at < 30 weeks gestational age and weighing < 1500 g at birth were studied. All had respiratory distress syndrome (RDS) and needed surfactant replacement therapy. They were randomly allocated into two groups; surfactant group (n = 64) and surfactant + budesonide group (n = 64). Neonates in the surfactant group received intratracheal Curosurf 200 mg/kg/dose. Patients in the surfactant + budesonide group were treated with intratracheal instillation of a mixed suspension of budesonide 0.25 mg/kg and Curosurf 200 mg/kg/dose. Neonates were followed untill discharge for the primary outcome which was BPD and secondary outcomes including sepsis, patent ductus arteriosus (PDA), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC).ResultsThe mean gestational age and birth weight of the studied neonates were 28.3±1.6 weeks and 1072.0±180.0 g, respectively. The demographic characteristics and RDS score were similar in the two groups. BPD occurred in 24 (37.5%) neonates in the surfactant + budesonide group and 38 (59.4%) neonates in surfactant group, p = 0.040. Hospital stay was 29.7±19.2 days (median = 30 days) in the surfactant group and 23.3±18.1 days (median = 20 days) in the surfactant + budesonide group, p = 0.050. The rates of sepsis, PDA, ROP, and NEC were not significantly different in the two groups.ConclusionsThe use of budesonide in addition to surfactant for rescue therapy of RDS in preterm infants decreases the incidence of BPD and duration of respiratory support significantly. Large adequately powered clinical trials with long-term safety assessments are needed to confirm our findings before its routine use can be recommended.

Surfactant-Assisted Distal Pulmonary Distribution of Budesonide Revealed by Mass Spectrometry Imaging.

Direct lung administration of budesonide in combination with surfactant reduces the incidence of bronchopulmonary dysplasia. Although the therapy is currently undergoing clinical development, the lung distribution of budesonide throughout the premature neonatal lung has not yet been investigated. Here, we applied mass spectrometry imaging (MSI) to investigate the surfactant-assisted distal lung distribution of budesonide. Unlabeled budesonide was either delivered using saline as a vehicle (n = 5) or in combination with a standard dose of the porcine surfactant Poractant alfa (n = 5). These lambs were ventilated for one minute, and then the lungs were extracted for MSI analysis. Another group of lambs (n = 5) received the combination of budesonide and Poractant alfa, followed by two hours of mechanical ventilation. MSI enabled the label-free detection and visualization of both budesonide and the essential constituent of Poractant alfa, the porcine surfactant protein C (SP-C). 2D ion intensity images revealed a non-uniform distribution of budesonide with saline, which appeared clustered in clumps. In contrast, the combination therapy showed a more homogeneous distribution of budesonide throughout the sample, with more budesonide distributed towards the lung periphery. We found similar distribution patterns for the SP-C and budesonide in consecutive lung tissue sections, indicating that budesonide was transported across the lungs associated with the exogenous surfactant. After two hours of mechanical ventilation, the budesonide intensity signal in the 2D ion intensity maps dropped dramatically, suggesting a rapid lung clearance and highlighting the relevance of achieving a uniform surfactant-assisted lung distribution of budesonide early after delivery to maximize the anti-inflammatory and maturational effects throughout the lung.

Is zebrafish (Danio rerio) water tank model applicable for the assessment of glucocorticoids metabolism? The budesonide assessment

Knowledge of the metabolic profile is essential for doping control analysis in sport since most drugs are excreted after an elaborate biotransformation process. Currently, Zebrafish Water Tank (ZWT) model has been applied to investigate the metabolism of different doping agents. Nevertheless, the class of glucocorticoids has not been subjected to this model for metabolism studies. In the present work, budesonide (BUD) was applied as a pilot to investigate the metabolic pathways of glucocorticoids in the ZWT model. The BUD biotransformation in ZWT model was compared to the described metabolism in humans. Samples from ZWT experiments were collected after BUD administration and analyzed by Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-HRMS). Following the identification and characterization of all significant metabolites described for humans, it was observed that the ZWT was able to produce in a relevant amount the main target for doping control purposes: the 6β-hydroxy BUD. In addition, prior knowledge about the lack of butyrylcholinesterase activity in the zebrafish organism was considered for the evaluation for the formation of the 16α-hydroxy prednisolone, the most intense BUD metabolite in human urine. Biotransformation of BUD by ZWT focused on metabolites with the acetal fraction preserved, including the intermediate metabolite for the 16α-hydroxy prednisolone pathway. However,analternative metabolic pathway for the complete biotransformation of the 16α-hydroxy prednisolone intermediate was not observed, leading to the absence of the major human metabolite in the ZWT model. The findings reported in this study elucidate for the first time the application and limitations of the ZWT model to evaluate the metabolism of other glucocorticoids.

ProLung™-budesonide Inhibits SARS-CoV-2 Replication and Reduces Lung Inflammation.

Background:Inhaled budesonide benefits patients with COVID-19. ProLung™-budesonide enables the sustained, low dose administration of budesonide within a delivery vehicle similar to lung surfactant. ProLung™-budesonide may offer anti-inflammatory and protective effects to the lung in COVID-19, yet it’s effect on SARS-CoV-2 replication is unknown.Objective:To determine the efficacy of ProLung™-budesonide against SARS-CoV-2-infection in vitro, evaluate its ability to decrease inflammation, and airway hyperresponsiveness in an animal model of lung inflammation.Methods:SARS-CoV-2-infected Vero 76 cells were treated with ProLung™-budesonide ([0.03–100 µg/ml]) for 3 days, and virus yield in the supernatant was measured. Ovalbumin-sensitized C57BL/6 mice received aerosolized (a) ProLung™-budesonide weekly, (b) only budesonide, either daily or weekly, or (c) weekly empty ProLung™ carrier (without budesonide). All treatment groups were compared to sensitized untreated, or normal mice using histopathologic examination, electron microscopy (EM), airway hyperresponsiveness (AHR) to Methacholine (Mch) challenge, and eosinophil peroxidase activity (EPO) measurements in bronchioalveolar lavage (BAL).Results:ProLung™-budesonide showed significant inhibition of viral replication of SARS-CoV-2-infected cells with the selectivity index (SI) value >24. Weekly ProLung™-budesonide and daily budesonide therapy significantly decreased lung inflammation and EPO in BAL. ProLung™-budesonide localized in type II pneumocytes, and was the only group to significantly decrease AHR, and EPO in BAL with Mch challengeConclusions:ProLung™-budesonide significantly inhibited viral replication in SARS-CoV-2-infected cells. It localized into type II pneumocytes, decreased lung inflammation, AHR and EPO activity with Mch challenge. This novel drug formulation may offer a potential inhalational treatment for COVID-19.

The efficacy of intratracheal administration of surfactant and budesonide combination in the prevention of bronchopulmonary dysplasia.

Background:Bronchopulmonary dysplasia (BPD) remains a major problem in preterm infants that occurs in up to 50% of preterm infants. The inflammation plays an important role in its pathogenesis. This study was conducted to evaluate the efficacy intratracheal budesonide administration in combination with surfactant in the prevention of BPD in preterm infants.Materials and Methods:In a randomized controlled clinical trial, 128 preterm infants with gestation age <30 weeks and birth weight <1250 g who had respiratory distress syndrome (RDS) and need surfactant replacement therapy were studied. They randomly allocated into two groups, surfactant group (n = 64) and surfactant + budesonide group (n = 64). Patients were followed till discharge for the primary outcome which was BPD.Results:The mean gestation age and birth weight of studied neonates were 28.3 ± 1.6 weeks and 1072 ± 180 g, respectively. BPD was occurred in 20 (31.3%) neonates in surfactant + budesonide group and 38 (59.4%) patients in surfactant group, P = 0.02. Respiratory support was needed in two groups similarly, but the mean duration of respiratory support was significantly longer in surfactant group in comparison with surfactant + budesonide group (mechanical ventilation 2.8 ± 0.6 vs. 0.8 ± 0.1 days, P = 0.006, nasal continuous positive airway pressure 5.2 ± 3.0 vs. 4.0 ± 3.5 days, P = 0.04 and high flow nasal cannula 7.7 ± 0.9 vs. 4.1 ± 0.5 days, P = 0.001).Conclusion:Based on our findings, the use of budesonide in addition to surfactant for rescue therapy of RDS significantly decreases the incidence of BPD and duration of respiratory support. Future studies are recommended with a large number of patients before routine administration of surfactant and budesonide combination.

Efficacy of Budesonide Nasal Spray on Neutrophilic Chronic Rhinosinusitis with Nasal Polyps: A Combined Clinical and Experimental Study

Background: Neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNP) occur predominantly in Asian subjects. Appropriate treatments for this endotype have not been elucidated. This study aimed to evaluate the efficacy of budesonide nasal spray on neutrophilic CRSwNP. Materials and Methods: Fifteen neutrophilic CRSwNP patients were included, and then they received budesonide nasal spray treatment for 3 months. Biopsies of nasal polyps (NPs) were obtained from these subjects. Their clinical indexes were scored using Visual Analog Scale (VAS), Sino-Nasal Outcome Test (SNOT)-22, and Endoscopic Appearances (EAs). Histological analyses were used to assess numbers of neutrophils, goblet cells, and submucosal gland cells in NPs. Percentages of CD8⁺ T cells and CD4⁺CD25⁺Foxp3⁺ regulatory T cells (Tregs) were evaluated using flow cytometry. Mucin 5AC (MUC5AC), MUC5B, myeloperoxidase (MPO), interferon (IFN)-γ, and interleukin (IL)-1β and their mRNAs were also examined. After that, we cultured NP tissues in vitro and evaluated the abovementioned inflammatory parameters before and after the administration of budesonide. Results: Budesonide nasal spray did not improve clinical evaluations including VAS, SNOT-22, and EA scores. Numbers of neutrophils and goblet cells, the score of submucosal gland cells, percentages of CD8⁺ T cells and Tregs, MUC5AC, MUC5B, MPO, IFN-γ, and IL-1β and their mRNAs were not decreased in NPs after the budesonide treatment. Furthermore, the administration of budesonide into NP cultures also did not reduce their levels in comparison with those before the treatment. Conclusion: These findings demonstrate that budesonide treatment may not alleviate the inflammatory condition in neutrophilic CRSwNP.