RESUMEN
PURPOSE: To evaluate the therapeutic efficacy of intravenous amoxicillin clavulanate potassium combined with nebulized budesonide and ambroxol hydrochloride in pediatric community-acquired pneumonia (CAP) and its impact across various microbial strains and clinical symptoms. The primary objective of this study is to evaluate the efficacy of intravenous amoxicillin-clavulanate combined with nebulized budesonide and ambroxol hydrochloride in the treatment of pediatric community-acquired pneumonia (CAP), and to analyze their impact on different microbial strains and clinical symptoms. Secondary objectives include assessing the treatment's effect on the improvement of clinical symptoms, hospital stay duration, and the levels of inflammatory markers. DESIGN: Prospective, single-center study. METHODS: Fifty-six children with CAP, aged under 6 years, from Affiliated Maternity and Child Health Care Hospital of Nantong University were included. Patients were treated with conventional therapy and the study medication. Clinical characteristics, microbiological data, symptom improvement, and hospitalization times were analyzed. FINDINGS: Young children, particularly under 1 year, exhibited a higher incidence of multiple microbial infections and severe clinical manifestations. Treatment with budesonide and ambroxol hydrochloride led to significant clinical improvement across all age groups, with notable efficacy against various pathogens. CONCLUSIONS: Nebulized budesonide and ambroxol hydrochloride are effective in treating pediatric CAP, offering a promising therapeutic option, particularly for young children with severe presentations.
Asunto(s)
Ambroxol , Budesonida , Infecciones Comunitarias Adquiridas , Nebulizadores y Vaporizadores , Humanos , Ambroxol/administración & dosificación , Ambroxol/uso terapéutico , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Femenino , Masculino , Preescolar , Lactante , Estudios Prospectivos , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Resultado del Tratamiento , Administración por Inhalación , Combinación Amoxicilina-Clavulanato de Potasio/administración & dosificación , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Niño , Neumonía/tratamiento farmacológico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Expectorantes/administración & dosificación , Expectorantes/uso terapéutico , Biomarcadores/sangre , Quimioterapia Combinada , Tiempo de InternaciónRESUMEN
BACKGROUND: Fractional exhaled nitric oxide (FeNO) is used for the diagnosis and monitoring of asthma, although its utility to guide treatment and its correlation with other tools is still under discussion. We study the possibility to withdraw inhaled corticosteroid treatment in atopic patients with mild asthma based on the FeNO level, as well as to study its correlation with other clinical control tools. METHODS: Prospective and randomized study including atopic patients aged 18 to 65 with mild asthma, stable, on low-dose inhaled corticosteroid (ICS) treatment, who had their treatment withdrawn based on a FeNO level of 40 ppb. Patients were randomized into two groups: control group (treatment with ICS was withdrawn regardless of FeNO level) and experimental group (according to the FeNO levels, patients were assigned to one of two groups: FeNO > 40 ppb on treatment with budesonide 200 mcg every 12 h and SABA on demand; FeNO ≤ 40 ppb only with SABA on demand). Follow-up was conducted for one year, during which medical assessment was performed with FeNO measurements, asthma control test (ACT), lung function tests (FEV1, FEV1/FVC, PEF, and RV/TLC), and recording of the number of exacerbations. RESULTS: Ninety-two patients were included, with a mean age of 39.92 years (SD 13.99); 46 patients were assigned to the control group, and 46 patients to the experimental group. The number of exacerbations was similar between the groups (p = 0.301), while the time to the first exacerbation was significantly shorter in the control group (30.86 vs. 99.00 days), p < 0.001, 95% CI (43.332-92.954). Lung function tests (FEV1, FEV1/FVC, PEF, and RV/TLC) showed no differences between the groups (p > 0.05). Both FeNO and ACT showed significant changes in the groups in which ICS was withdrawn (p < 0.05 for both parameters). A significant negative correlation was observed between FeNO and ACT (r = -0.139, p = 0.008). CONCLUSIONS: In atopic patients with mild asthma, withdrawal of ICS based on an FeNO of 40 ppb led to worsened symptoms but without changes in lung function tests or an increase in exacerbations. There was a negative correlation between FeNO values and symptomatic control measured by the ACT. TRIAL REGISTRATION: Clinical Trial Number: 2012-000372-42. Start Date: 2012-07-23. Trial registered prospectively ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-000372-42 ). This study adheres to CONSORT guidelines of randomised control trials.
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Asma , Budesonida , Óxido Nítrico , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Administración por Inhalación , Corticoesteroides/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Pruebas Respiratorias , Budesonida/uso terapéutico , Prueba de Óxido Nítrico Exhalado Fraccionado , Óxido Nítrico/análisis , Estudios Prospectivos , Pruebas de Función RespiratoriaRESUMEN
OBJECTIVE: To assess the clinical effect of Qingre Bawei capsules combined with budesonide in the treatment of acute exacerbation of chronic obstructive pulmonary disease. METHODS: The retrospective study was conducted at the Baoding No.1 Central Hospital, China, and comprised data of patients with acute exacerbation of COPD admitted between June 1, 2020, and June 30, 2022. The patients were divided into two groups based on treatment methods. The group A had been treated with Qingre Bawei capsules in combination with budesonide, while the group B had been treated with budesonide alone. Both the groups had been treated for 2 consecutive weeks. The changes in blood gas indicators, inflammation indicators, and lung function indicators were compared between two groups of patients before and 24 hours after treatment. The time for clinical symptom disappearance and adverse reactions between the two groups of patients was also noted. RESULTS: Of the 120 patients, 60(50%) were in group A; 41(68.3%) males and 19(31.7%) females, with mean age 65.28±4.36 years (range: 47-78 years) and mean course of disease 31.22±4.75 hours (range: 6-65 hours). 60(50%) patients were in group B; 43(71.7%) males and 17(28.3%) females with mean age 65.31±4.31 years (range: 48-78 years) and mean course of disease 31.29±4.71 hours (range: 8-68 hours). The disappearance time of clinical symptoms in group A was better than group B (p<0.05). The levels of blood gas indicators, inflammation indicators, and lung function indicators in both groups significantly improved (p<0.05), but the degree of improvement in group A was better than group B (p<0.05); The total effective rate of group A was better than group B (p<0.05). None of the patients in either group experienced any significant adverse reaction. CONCLUSIONS: Qingre Bawei capsules combined with budesonide had a significantly better therapeutic effect on cases of acute exacerbation of chronic obstructive pulmonary disease compared to budesonide alone.
Asunto(s)
Budesonida , Medicamentos Herbarios Chinos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/efectos adversos , Estudios Retrospectivos , Quimioterapia Combinada , Cápsulas , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Progresión de la Enfermedad , Resultado del Tratamiento , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Volumen Espiratorio Forzado/efectos de los fármacosRESUMEN
Immunoglobulin A nephropathy (IgAN) is a chronic, immune-mediated kidney disease characterized by the deposition of galactose-deficient immunoglobulin A1 (Gd-IgA1) in the kidneys. Excess Gd-IgA1 production in patients with IgAN is located within the mucosa-associated lymphoid tissue, particularly within the lamina propria in the distal ileum. Nefecon® is a targeted-release formulation of the corticosteroid budesonide, which became the first treatment approved by the US Food and Drug Administration (FDA; brand name, TARPEYO®) and European Medicines Agency (EMA; KINPEYGO®) for patients with primary IgAN at risk of rapid disease progression, after demonstrating clinically significant reduction of proteinuria in an interim analysis of the Phase III NefIgArd trial. After showing a significant reduction in estimated glomerular filtration rate decline in the full 2-year analysis of the trial, Nefecon was granted full approval by the FDA to reduce the loss of kidney function. Nefecon was specifically designed to deliver budesonide to the distal ileum, selectively targeting excess Gd-IgA1 production in the gut-associated lymphoid tissue. In this review, we describe the properties of Nefecon and the evidence to date that confirms its localized treatment effect. We also present unpublished evidence from Phase I trials investigating the pharmacokinetics and cortisol suppression effects of Nefecon in healthy participants. These studies demonstrated that Nefecon has a distinct pharmacokinetic profile from other budesonide products, allowing for targeted, localized action in the distal ileum. When considered alongside existing clinical trial data showing the effect of Nefecon on gut-associated biomarkers, available evidence indicates that Nefecon has a selective immunomodulatory mechanism of action and a direct disease-modifying effect in patients with IgAN, while having low systemic exposure and adverse effects.
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Budesonida , Glomerulonefritis por IGA , Humanos , Glomerulonefritis por IGA/tratamiento farmacológico , Budesonida/farmacología , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Budesonida/química , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/administración & dosificaciónRESUMEN
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent medical condition. Type 2 inflammation signs CRSwNP in western countries. Type 2 inflammation leads to nasal airflow limitation. Budesonide aqueous nasal spray (BANS) is an intranasal corticosteroid (INCS); it has been launched in the early 1980s. BANS is indicated for treating allergic rhinitis, nonallergic rhinitis, and nasal polyps (both as treatment and prevention after surgery). Consolidated evidence documented its efficacy in treating CRSwNP. In addition, BANS is safe with negligible local and systemic side effects. Recent guidelines for patients with CRSwNP recommend using INCS as the first line in many situations. In particular, patients may assess the perception of symptoms' severity using the Visual Analog Scale (VAS). A score >5/10 means uncontrolled symptoms in both diseases and requires adequate treatment. BANS could appropriately be used in patients with uncontrolled symptoms and/or moderate/severe nasal obstruction. In addition, BANS may adequately integrate surgery and biologics for CRSwNP management. In conclusion, BANS represents a valuable option in managing patients with type 2-mediated CRSwNP.
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Administración Intranasal , Budesonida , Pólipos Nasales , Rociadores Nasales , Rinitis , Sinusitis , Humanos , Sinusitis/tratamiento farmacológico , Sinusitis/complicaciones , Pólipos Nasales/tratamiento farmacológico , Enfermedad Crónica , Rinitis/tratamiento farmacológico , Budesonida/uso terapéutico , Budesonida/administración & dosificación , Resultado del Tratamiento , RinosinusitisRESUMEN
Eosinophilic esophagitis (EoE) is a chronic Th2-mediated inflammatory disease of the esophagus driven by dietary or inhalant allergens which if left untreated, leads to fibrosis and poor esophageal function. Although the inflammation in the esophagus is dominated by eosinophils, there are also elevated levels of T and B cells. Blood samples from ten patients with EoE before and after treatment with orodispersible budesonide and 10 healthy controls were compared using cytometry by time-of-flight. An antibody panel was designed that covers the major immunological cell populations with a particular focus on eosinophils. The data was analyzed with multivariate methods and cluster analysis. Correlation analysis was done between immune markers and endoscopic, histological, and symptomatologic assessments. Our analysis revealed that patients with EoE had lower levels of effector memory T cells after treatment with orodispersible budesonide to the same level as healthy subjects. In addition, more suppressive eosinophils were present in the circulation of EoE patients before treatment and more immature eosinophils were present after treatment. Furthermore, levels of galectin-10+ eosinophils correlated with histological findings in esophageal tissue from EoE patients. In all patients, the peak eosinophils were decreased after treatment with orodispersible budesonide. Intriguingly, 90% of the patients had remission in the histological assessment and 50% improved in the endoscopic assessment. This study reports a detailed immune profile in patients with EoE before and after treatment with orodispersible budesonide and it is a step toward finding blood-based immune parameters that could be useful to monitor response to treatment.
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Budesonida , Esofagitis Eosinofílica , Eosinófilos , Humanos , Budesonida/uso terapéutico , Budesonida/administración & dosificación , Esofagitis Eosinofílica/inmunología , Esofagitis Eosinofílica/tratamiento farmacológico , Masculino , Femenino , Eosinófilos/inmunología , Adulto , Persona de Mediana Edad , Adulto Joven , Administración Oral , Esófago/inmunología , Esófago/patología , Células Th2/inmunología , AdolescenteRESUMEN
BACKGROUND: Limited data exist for management strategies targeting immunotherapy-related enteritis (irEnteritis). Systemic corticosteroids are commonly used but often are limited by adverse events. Enteric corticosteroids such as budesonide offer an attractive alternative; however, the ileocolonic release of enteric-coated budesonide has limited utility for diffuse enteritis. Open-capsule budesonide (OCB) is a novel therapeutic approach that offers drug delivery throughout the small bowel. We report outcomes in patients treated with OCB for confirmed or suspected irEnteritis. METHODS: This retrospective cohort included all individuals treated with OCB for irEnteritis at Memorial Sloan Kettering from July 2018 to August 2023. Primary outcomes included clinical response, clinical remission, and corticosteroid-free remission following OCB. Secondary outcomes were OCB-related adverse events and efficacy by gastrointestinal toxicity location. RESULTS: 19 patients (53% female) with irEnteritis were treated with OCB. All patients presented with diarrhea; 15 (79%) reported anorexia with median 6 kg weight loss. 17 patients (89%) underwent esophagogastroduodenoscopy with biopsies revealing enteritis in all; 8 (42%) had concomitant colitis. 15 (79%) patients were treated previously with systemic corticosteroids: 8 (53%) were corticosteroid-dependent while 7 (47%) demonstrated non-response. 18 patients (95%) achieved clinical response, 15 (79%) attained clinical remission, and 11 (58%) had corticosteroid-free remission. Response to OCB was rapid with improvement noted after a median 4 days. 14 (74%) patients restored their pre-irEnteritis weight by OCB cessation. One mild, self-resolving adverse event was reported. CONCLUSIONS: OCB is a safe and effective therapy for irEnteritis. OCB avoids systemic immunosuppression and successfully achieves clinical response and remission even in patients previously nonresponsive to systemic corticosteroids. Future studies are needed to optimize indications and duration.
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Budesonida , Enteritis , Inhibidores de Puntos de Control Inmunológico , Humanos , Femenino , Budesonida/uso terapéutico , Budesonida/farmacología , Enteritis/tratamiento farmacológico , Masculino , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , AdultoRESUMEN
OBJECTIVES: To evaluate the cost-effectiveness of budesonide/formoterol reliever and maintenance therapy compared with salmeterol/fluticasone plus salbutamol as reliever therapy for asthma patients ≥12 years from the societal perspective in China. METHODS: A Markov model was developed with three health states (non-exacerbation, exacerbation, and death) with a lifetime horizon. The exacerbation rates were obtained from a prospective cohort study conducted in Chinese asthma patients. Healthcare resources utilization data were estimated based on current clinical asthma management guidelines. Asthma-related mortality, cost input and utility values were derived from public database and literature. Model robustness was assessed with one-way sensitivity and probabilistic sensitivity analyses. RESULTS: Compared with salmeterol/fluticasone plus salbutamol, budesonide/formoterol reliever and maintenance therapy led to fewer exacerbation events (13.6 vs. 15.9) and 0.0077 quality-adjusted life years (QALY) gain at an additional cost of ¥196.38 over lifetime. The base case incremental cost-effectiveness ratio (ICER) was ¥25,409.98 per QALY gained. The variables that had most impact on the model output included drug costs and medication adherence. At a willingness-to-pay threshold of ¥257,094/QALY (3 times of gross domestic product per capita in China in 2022), the probability of budesonide/formoterol maintenance and reliever therapy being cost-effective versus salmeterol/fluticasone plus as-needed salbutamol was 83.00%. CONCLUSION: From the societal perspective, budesonide/formoterol reliever and maintenance therapy is likely to be a cost-effective option compared with salmeterol/fluticasone plus as-needed salbutamol for Chinese asthma patients ≥12 years.
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Asma , Análisis Costo-Beneficio , Combinación Fluticasona-Salmeterol , Cadenas de Markov , Años de Vida Ajustados por Calidad de Vida , Humanos , Asma/tratamiento farmacológico , China , Combinación Fluticasona-Salmeterol/uso terapéutico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Budesonida/uso terapéutico , Budesonida/economía , Budesonida/administración & dosificación , Antiasmáticos/uso terapéutico , Antiasmáticos/economía , Fumarato de Formoterol/uso terapéutico , Fumarato de Formoterol/administración & dosificación , Modelos Econométricos , Niño , Adulto Joven , Estudios Prospectivos , Recursos en Salud/economía , Recursos en Salud/estadística & datos numéricos , Servicios de Salud/estadística & datos numéricos , Servicios de Salud/economía , Broncodilatadores/uso terapéutico , Broncodilatadores/economía , Broncodilatadores/administración & dosificación , Quimioterapia Combinada , Análisis de Costo-Efectividad , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control. METHODS: From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment. RESULTS: A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group. CONCLUSIONS: In the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.
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Asma , Alcoholes Bencílicos , Clorobencenos , Combinación de Medicamentos , Humanos , Masculino , Femenino , Alcoholes Bencílicos/administración & dosificación , Alcoholes Bencílicos/uso terapéutico , Estudios Retrospectivos , Asma/tratamiento farmacológico , Persona de Mediana Edad , Clorobencenos/administración & dosificación , Clorobencenos/uso terapéutico , Adulto , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Administración por Inhalación , Androstadienos/administración & dosificación , Androstadienos/uso terapéutico , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Antiasmáticos/uso terapéutico , Antiasmáticos/administración & dosificación , Anciano , Fumarato de Formoterol/administración & dosificación , Resultado del Tratamiento , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Combinación Budesonida y Fumarato de Formoterol/administración & dosificación , Combinación Budesonida y Fumarato de Formoterol/uso terapéutico , Pruebas de Función Respiratoria , Eosinófilos/efectos de los fármacosRESUMEN
Acute pancreatitis (AP) is a sudden inflammation of the pancreas which often manifests as a mild disease but can be associated with high morbidity and mortality. Drug-induced AP is rare and most likely underdiagnosed. Vedolizumab is a human monoclonal antibody with gut-selective integrin antagonist effect, and it is used for treatment of inflammatory bowel disease (IBD). Budesonid is a glucocorticoid which is released in the colon and it is also used in IBD treatment. This is a case report where vedolizumab or budesonide caused acute pancreatitis in a young man with ulcerative colitis.
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Anticuerpos Monoclonales Humanizados , Budesonida , Colitis Ulcerosa , Fármacos Gastrointestinales , Pancreatitis , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Pancreatitis/inducido químicamente , Budesonida/efectos adversos , Budesonida/uso terapéutico , Fármacos Gastrointestinales/efectos adversos , Fármacos Gastrointestinales/uso terapéutico , Adulto , Enfermedad Aguda , Antiinflamatorios/efectos adversos , Antiinflamatorios/uso terapéutico , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversosRESUMEN
BACKGROUND: Budesonide, capable of reducing vascular permeability, suppressing mucus secretion, and alleviating edema and spasms, is widely used in China for combined infectious disease treatment. This study assesses budesonide's efficacy and safety as an adjunct to azithromycin in pediatric Mycoplasma pneumonia management in China, aiming to establish a strong theoretical foundation for its clinical application. METHODS: We conducted a comprehensive search for qualifying studies across 5 English databases and 4 Chinese databases, covering publications until October 31, 2023. Endpoint analyses were performed using standard software (Stata Corporation, College Station, TX). This study was conducted in compliance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: A total of 24 randomized controlled trials were involved in the current study, including 2034 patients. Our findings indicate that the combination of budesonide with azithromycin for the treatment of pediatric Mycoplasma pneumonia delivers superior therapeutic efficacy (Intravenous: odds ratio [OR], 0.156, Pâ <â .001; Sequential: OR, 0.163, Pâ =â .001; Oral: OR, 0.139, Pâ <â .001), improved pulmonary function (Forced expiratory volume in 1 second: weighted mean differences [WMD], -0.28, Pâ =â .001; Peak expiratory flow: WMD, -0.554, Pâ =â .002; Forced vital capacity: WMD, -0.321, Pâ <â .001), diminished lung inflammation (IL-6: WMD, 4.760, Pâ =â .002; c-reactive protein: WMD, 5.520, Pâ <â .001; TNF-α: WMD, 9.124, Pâ <â .001), reduced duration of fever, faster resolution of cough and rales, all without increasing the occurrence of adverse events. CONCLUSION: The combination of budesonide and azithromycin demonstrates enhanced therapeutic effectiveness, promotes improved pulmonary function, shortens the duration of symptoms, and effectively mitigates the overexpression of inflammatory factors like c-reactive protein, TNF-α, and IL-6, all without an associated increase in adverse reactions in pediatric mycoplasma pneumonia.
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Antibacterianos , Azitromicina , Budesonida , Quimioterapia Combinada , Neumonía por Mycoplasma , Humanos , Azitromicina/administración & dosificación , Azitromicina/uso terapéutico , Neumonía por Mycoplasma/tratamiento farmacológico , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Niño , China , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Administración por Inhalación , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Preescolar , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer with an aggressive metastatic phenotype and very poor clinical prognosis. Interestingly, a lower occurrence of PDAC has been described in individuals with severe and long-standing asthma. Here we explored the potential link between PDAC and the glucocorticoid (GC) budesonide, a first-line therapy to treat asthma. METHODS: We tested the effect of budesonide and the classical GCs on the morphology, proliferation, migration and invasiveness of patient-derived PDAC cells and pancreatic cancer cell lines, using 2D and 3D cultures in vitro. Furthermore, a xenograft model was used to investigate the effect of budesonide on PDAC tumor growth in vivo. Finally, we combined genome-wide transcriptome analysis with genetic and pharmacological approaches to explore the mechanisms underlying budesonide activities in the different environmental conditions. RESULTS: We found that in 2D culture settings, high micromolar concentrations of budesonide reduced the mesenchymal invasive/migrating features of PDAC cells, without affecting proliferation or survival. This activity was specific and independent of the Glucocorticoid Receptor (GR). Conversely, in a more physiological 3D environment, low nanomolar concentrations of budesonide strongly reduced PDAC cell proliferation in a GR-dependent manner. Accordingly, we found that budesonide reduced PDAC tumor growth in vivo. Mechanistically, we demonstrated that the 3D environment drives the cells towards a general metabolic reprogramming involving protein, lipid, and energy metabolism (e.g., increased glycolysis dependency). This metabolic change sensitizes PDAC cells to the anti-proliferative effect of budesonide, which instead induces opposite changes (e.g., increased mitochondrial oxidative phosphorylation). Finally, we provide evidence that budesonide inhibits PDAC growth, at least in part, through the tumor suppressor CDKN1C/p57Kip2. CONCLUSIONS: Collectively, our study reveals that the microenvironment influences the susceptibility of PDAC cells to GCs and provides unprecedented evidence for the anti-proliferative activity of budesonide on PDAC cells in 3D conditions, in vitro and in vivo. Our findings may explain, at least in part, the reason for the lower occurrence of pancreatic cancer in asthmatic patients and suggest a potential suitability of budesonide for clinical trials as a therapeutic approach to fight pancreatic cancer.
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Budesonida , Proliferación Celular , Metabolismo Energético , Neoplasias Pancreáticas , Humanos , Budesonida/farmacología , Budesonida/uso terapéutico , Ratones , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Metabolismo Energético/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Animales , Línea Celular Tumoral , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Ensayos Antitumor por Modelo de Xenoinjerto , Movimiento Celular/efectos de los fármacosAsunto(s)
Budesonida , Esofagitis Eosinofílica , Suspensiones , Humanos , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/diagnóstico , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Budesonida/efectos adversos , Administración Oral , Resultado del Tratamiento , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: Microscopic colitis has been increasingly recognized as a cause of chronic diarrhoea. We aimed to characterize the role of disease-related factors and treatments on the clinical outcomes of microscopic colitis. METHODS: We retrospectively reviewed the medical records of patients with microscopic colitis who were treated at the University of Chicago and Oregon Health & Science University between August 2010 and May 2016. Patient characteristics and treatments were evaluated as predictors of clinical outcomes using univariate and multivariate analyses. Clinical remission was defined as no symptoms associated with microscopic colitis based on physician assessment and histologic remission was defined as no evidence of histological inflammation of microscopic colitis. RESULTS: Seventy-two patients with microscopic colitis were included in the study (28 with lymphocytic colitis and 44 with collagenous colitis). Non-steroidal anti-inflammatory drugs, proton pump inhibitors and selective serotonin reuptake inhibitors were used in 23 (31.9%), 14 (19.4%) and 15 (20.8%), respectively, at the time of diagnosis. Among 46 patients with adequate follow-up data, 25 (54.3%) patients achieved clinical remission. Response to budesonide (p = .0002) and achieving histologic remission (p = .0008) were associated with clinical remission on univariate analysis. On multivariate analysis, budesonide response (p = .0052) was associated with clinical remission (odds ratio 25.00, 95% confidence interval 2.63-238.10). Among 22 patients who underwent a follow-up colonoscopy, five patients (22.7%) achieved histologic remission. All patients with histologic remission maintained clinical remission without medication, whereas only two patients (11.8%) were able to discontinue medical therapy when histologic inflammation was present (p = .0002). CONCLUSIONS: In the present cohort of patients with microscopic colitis, a favourable response to budesonide was significantly associated with long-term clinical remission, and all patients achieving histological remission were able to maintain clinical remission without further medical therapy. Larger studies are required to confirm these findings.
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Budesonida , Colitis Microscópica , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Colitis Microscópica/tratamiento farmacológico , Colitis Microscópica/patología , Colitis Microscópica/diagnóstico , Budesonida/uso terapéutico , Resultado del Tratamiento , Adulto , Inducción de Remisión , Antiinflamatorios no Esteroideos/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico , Colitis Linfocítica/tratamiento farmacológico , Colitis Linfocítica/patología , Colitis Colagenosa/tratamiento farmacológico , Colitis Colagenosa/patología , Colitis Colagenosa/diagnóstico , ColonoscopíaRESUMEN
Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that affects the gastrointestinal tract. The major hurdles impeding IBD treatment are the low targeting efficiency and short retention time of drugs in IBD sites. Nanoparticles with specific shapes have demonstrated the ability to improve mucus retention and cellular uptake. Herein, mesoporous silica nanoparticles (MSNs) with various morphologies were used to deliver budesonide (BUD) for the treatment of IBD. The therapeutic efficacy is strongly dependent on their shapes. The system comprises different shapes of MSNs as carriers for budesonide (BUD), along with Eudragit S100 as the enteric release shell. The encapsulation of Eudragit S100 not only improved the stability of MSNs-BUD in the gastrointestinal tract but also conferred pH-responsive drug release properties. Then, MSNs efficiently deliver BUD to the colon site, and the special shape of MSNs plays a critical role in enhancing their permeability and retention in the mucus layer. Among them, dendritic MSNs (MSND) effectively reduced myeloperoxidase (MPO) activity and levels of inflammatory cytokines in the colon due to long retention time and rapid release in IBD sites, thereby enhancing the therapeutic efficacy against colitis. Given the special shapes of MSNs and pH-responsivity of Eudragit S100, BUD loaded in the voids of MSND (E@MSNs-BUD) could penetrate the mucous layer and be accurately delivered to the colon with minor side effects. This system is expected to complement current treatment strategies for the IBD.
Asunto(s)
Budesonida , Portadores de Fármacos , Enfermedades Inflamatorias del Intestino , Nanopartículas , Dióxido de Silicio , Budesonida/química , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Budesonida/farmacocinética , Nanopartículas/química , Nanopartículas/uso terapéutico , Animales , Dióxido de Silicio/química , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Portadores de Fármacos/química , Ratones , Ácidos Polimetacrílicos/química , Liberación de Fármacos , Humanos , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antiinflamatorios/administración & dosificación , Porosidad , Concentración de Iones de HidrógenoRESUMEN
Delayed-release (DR) budesonide received expedited approval from the US Food and Drug Administration (FDA) as a treatment for reducing proteinuria in individuals with primary IgA nephropathy (IgAN) who are at significant risk of disease progression. The approval was based on clinical trials primarily involving patients with an estimated glomerular filtration rate (eGFR) greater than 30 mL/min/1.73 m2. However, the efficacy of DR budesonide in reducing kidney function decline, especially in patients with an eGFR less than 30 mL/min/1.73 m2 and proteinuria less than 1 g/d, remains unclear. We report the case of a 43-year-old man with a long-term history of hypertension and biopsy-proven IgAN who experienced a progressive increase in proteinuria and serum creatinine, along with a decline in eGFR to 28 mL/min/1.73 m2 despite maximal supportive management. Following therapy with DR budesonide, a decreasing trend in proteinuria and a stabilization of eGFR were observed in the recent measurements. While initial data suggested the effectiveness of DR budesonide primarily in patients with an eGFR over 30 mL/min/1.73 m2, our case demonstrates the potential of DR budesonide for use in scenarios beyond its currently approved indications. This underscores the need for additional research on patients with advanced stages of chronic kidney disease.
Asunto(s)
Budesonida , Preparaciones de Acción Retardada , Progresión de la Enfermedad , Tasa de Filtración Glomerular , Glomerulonefritis por IGA , Proteinuria , Insuficiencia Renal Crónica , Humanos , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Masculino , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/complicaciones , Adulto , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Proteinuria/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéuticoRESUMEN
BACKGROUND: Benign tracheal stenosis is relatively rare but remains a significant chronic disease due to its drastic symptoms including dyspnoea and inspiratory stridor, and consequent negative effect on quality of life. Traditionally, the surgical approach by resection of the stenotic tracheal segment has been the therapy of choice. However, endoscopic techniques have arisen and may offer a safe and less invasive alternative. OBJECTIVES: The aim of the retrospective study was to evaluate procedure-related safety and outcome of endoscopic treatment of benign tracheal stenosis at a single centre. METHODS: The study included all patients at our institution who between 2013 and 2022 had received endoscopic treatment of benign tracheal stenosis by rigid tracheoscopy, radial incision by electric papillotomy needle and dilation (endoscopic tracheoplasty) followed by triamcinolone acetonide as a local submucosal injection and additionally, from 2020, budesonide inhalation. RESULTS: A total of 22 patients were treated in a total of 38 interventions, each resulting in immediate improvement of symptoms. There were no peri-interventional complications or mortality. Of the 38 interventions, 11 received no triamcinolone acetonide administration, resulting in a 54.5% recurrence rate after an average of 21.1 (±18.0) months, while 27 had local triamcinolone acetonide, with a 37% recurrence rate. Since 2020, we additionally initiated post-interventional budesonide inhalation as recurrence prophylaxis for newly admitted patients and patients with recurrences(n = 8), of whom only one (12.5%) has to date experienced a recurrence. CONCLUSION: Our results indicate that endoscopic tracheoplasty offers a safe and successful, minimally invasive alternative to open surgery for patients with benign tracheal stenosis. We recommend local administration of triamcinolone into the mucosa as an additional treatment to decrease the risk of recurrence. However, given the uncontrolled study design and low sample size, safety and effectiveness cannot be conclusively demonstrated. Nonetheless, our findings suggest promising avenues for further investigation. Further studies on the additional benefit of inhaled corticosteroids are warranted.
Asunto(s)
Estenosis Traqueal , Humanos , Estenosis Traqueal/cirugía , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Endoscopía/métodos , Adulto , Triamcinolona Acetonida/administración & dosificación , Triamcinolona Acetonida/uso terapéutico , Resultado del Tratamiento , Dilatación/métodos , Recurrencia , Anciano , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Calidad de Vida , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéuticoRESUMEN
BACKGROUND: Post-operative sore throat (POST) has an incidence ranging from 21 to 80%. To prevent the development of POST, several pharmacological measures have been tried. Aim of this study was to compare the efficacy of preoperative zinc, magnesium and budesonide gargles in reducing the incidence and severity of POST in patients who underwent endotracheal intubation for elective surgeries. METHODS: We conducted a prospective, randomized, double-blind, controlled equivalence trial in 180 patients admitted for elective surgical procedures under general anaesthesia. Patients were randomised into three groups; group Z received 40 mg Zinc, group M received 250 mg Magnesium Sulphate and group B received 200 µg Budesonide in the form of 30 ml tasteless and colourless gargle solutions. Sore throat assessment and haemodynamic recording was done postoperatively at immediate recovery (0 h) and 2, 4, 6, 8, 12 and 24 h post-operatively. POST was graded on a four-point scale (0-3). RESULTS: POST score was comparable at all recorded time points i.e. 0,2,4,6,8,12 and 24 h. Maximum incidence was seen at 8 h in group B (33.3%) and the minimum incidence was at 24 h in group Z (10%) (p > 0.05). It was found that the incidence of POST was more in the surgeries lasting longer than 2 h in all groups. This difference was found to be statistically significant in Groups M and B. The incidence of POST was found to be comparable between laparoscopic and open procedures. CONCLUSION: Magnesium, zinc and budesonide have an equivocal effect in the prevention of POST at different time points. The incidence of sore throat increases significantly in surgeries lasting more than two hours if magnesium or budesonide have been used as premedicant. Duration of surgery is an independent predictor for POST. TRIAL REGISTRATION: CTRI/2021/05/033741 Date-24/05/2021(Clinical Trial Registry of India).
Asunto(s)
Budesonida , Sulfato de Magnesio , Faringitis , Complicaciones Posoperatorias , Cuidados Preoperatorios , Zinc , Humanos , Faringitis/prevención & control , Faringitis/etiología , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Método Doble Ciego , Femenino , Masculino , Estudios Prospectivos , Adulto , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Cuidados Preoperatorios/métodos , Zinc/administración & dosificación , Persona de Mediana Edad , Sulfato de Magnesio/administración & dosificación , Intubación Intratraqueal , Magnesio/administración & dosificación , Incidencia , Procedimientos Quirúrgicos Electivos , Adulto Joven , Anestesia General/métodosRESUMEN
OBJECTIVES: Oral viscous budesonide (OVB) is a common medication used to treat eosinophilic esophagitis (EoE). It is typically mixed with Splenda to produce a slurry, but other delivery vehicles have been used in clinical practice. We aimed to evaluate outcomes of pediatric EoE patients treated with OVB using different drug delivery vehicles. METHODS: We performed a retrospective chart review of pediatric EoE patients treated with OVB. The primary aim was to evaluate rates of histologic remission (defined by <15 eosinophils per high power field in both mid and distal esophagus) after 6-12 weeks of OVB treatment for each delivery vehicle. Secondary aims were to evaluate histologic response and endoscopic response and remission of different delivery vehicles, and to compare the efficacy of different treatment regimens. RESULTS: A total of 111 patients were included in the study. Median treatment duration was 3.4 months. Overall rate of histologic remission with OVB was 52.6%. There was no difference in rates of histologic remission (p = 0.313) or response (p = 0.195 and p = 0.681 in mid and distal esophagus, respectively) among the different vehicle types or treatment regimens. Similarly, there was no difference in endoscopic remission and response among the different vehicle types (p = 0.853 and p = 0.727) or treatment regimens (p = 0.244 and p = 0.157). Patients who achieve histologic remission were more likely to be non-Hispanic Caucasian. CONCLUSION: Our findings suggest there is no difference in histologic and endoscopic outcomes with various delivery vehicles or combination therapy with OVB in the treatment of EoE. More palatable and cost-effective vehicles can be used to treat EoE.
Asunto(s)
Budesonida , Esofagitis Eosinofílica , Vehículos Farmacéuticos , Inducción de Remisión , Humanos , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/patología , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Estudios Retrospectivos , Masculino , Femenino , Niño , Preescolar , Inducción de Remisión/métodos , Resultado del Tratamiento , Adolescente , Esófago/patología , Administración OralRESUMEN
BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled corticosteroids (budesonide, beclomethasone, or fluticasone propionate) in preventing bronchopulmonary dysplasia (BPD) for premature infants. METHOD: Electronic databases, including PubMed, EMBASE, Web of science, Scopus, and Cochrane library, were searched from databases inception to January 2022 for eligible randomized controlled trials. Clinical outcomes such as BPD, mortality, BPD or death, adverse events, and neurodevelopmental outcomes were assessed. RESULTS: Overall, budesonide was significantly associated with a reduction in BPD at 36 weeks' postmenstrual age (RR 0.48; 95 % CI [0.38, 0.62]) and patent ductus arteriosus (PDA) (RR 0.75; 95 % CI [0.63, 0.89]) compared with control treatments. Early longer duration inhalation of budesonide alone was associated with a lower risk of BPD at 36 weeks' postmenstrual age and PDA compared with controls. Early shorter duration intratracheal instillation of budesonide with surfactant as vehicle was associated with a lower risk of BPD at 36 weeks' postmenstrual age and all-cause mortality compared with surfactant. There was no statistically significant difference between budesonide and control groups regarding neurodevelopmental impairment. Beclomethasone and fluticasone propionate did not show any superior or inferior effect on clinical outcomes compared to control treatments. CONCLUSION: These findings suggest that budesonide, especially intratracheal instillation of budesonide using surfactant as a vehicle, is a safe and effective option in preventing BPD for preterm infants. More well-design large-scale trials with long-term follow-ups are necessary to verify the present findings.