Budesonide Treatment Research Articles

Effect of Budesonide Added to Large-Volume, Low-pressure Saline Sinus Irrigation for Chronic Rhinosinusitis

Recent studies suggest that budesonide added to saline nasal lavage can be an effective treatment for patients with chronic rhinosinusitis (CRS). To evaluate the incremental effect of adding budesonide to large-volume, low-pressure saline sinus irrigation. This double-blind, placebo-controlled, randomized clinical trial was conducted at a quaternary care academic medical center between January 1, 2016, and February 16, 2017. A total of 80 adult patients with CRS were enrolled; 74 completed baseline assessments; and 61 remained in the trial to complete all analyses. Data analysis was conducted from March 2017 to August 2017. All study participants were provided with a sinus rinse kit including saline and identical-appearing capsules that contained either budesonide (treatment group) or lactose (control group). Patients were instructed to dissolve the capsules in the saline and use the resulting solution to irrigate both nasal cavities, using half the solution for each cavity, once daily for 30 days. The primary outcome measure was the change in Sino-Nasal Outcome Test (SNOT-22) scores, pretreatment to posttreatment, in the budesonide group compared with the control group. Secondary outcome measures included patient-reported response to treatment, as measured with a modification of the Clinical Global Impressions scale, and endoscopic examination scored by the Lund-Kennedy grading system. Of the 74 participants who completed baseline assessments (37 in each study arm), mean (SD) age, 51 (14.7) years, 50 (68%) were women. Of the 61 who remained in the trial to complete all analyses, 29 were randomized to budesonide treatment, and 32 to saline alone. The average change in SNOT-22 scores was 20.7 points for those in the budesonide group and 13.6 points for those in the control group, for a mean difference of 7 points in favor of the budesonide group (95% CI, -2 to 16). A total of 23 participants (79%) in the budesonide group experienced a clinically meaningful reduction in their SNOT-22 scores compared with 19 (59%) in the control group, for a difference of 20% (95% CI, -2.5% to 42.5%). The average change in endoscopic scores was 3.4 points for the budesonide group and 2.7 points for the control group. There were no related adverse events. This study shows that budesonide in saline nasal lavage results in clinically meaningful benefits beyond the benefits of saline alone for patients with CRS. Given the imprecision in the treatment effect, further research is warranted to define the true effect of budesonide in saline nasal lavage. ClinicalTrials.gov Identifier: NCT02696850.

Budesonide for the Induction and Maintenance of Remission in Crohn's Disease: Systematic Review and Meta-Analysis for the Cochrane Collaboration.

BackgroundBudesonide is an oral glucocorticoid designed for the treatment of inflammatory bowel disease (IBD) that may reduce systemic adverse events (AEs). This review examined the efficacy and safety of budesonide for the induction and maintenance of clinical remission in Crohn’s disease (CD).MethodsMEDLINE, EMBASE, other electronic databases, reference lists and conference proceedings were searched to November 2017 to identify randomized controlled trials of budesonide. Outcomes were the induction and maintenance of remission at eight weeks and one year, respectively, as well as corticosteroid-related AEs and abnormal adrenocorticotropic hormone (ACTH) tests. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random effects models.ResultsThirteen induction and 10 maintenance trials were included. Budesonide 9 mg/day was more effective than placebo (RR 1.93; 95% CI, 1.37–2.73; GRADE: moderate) but less effective than conventional steroids (RR 0.85; 95% CI, 0.75–0.97; GRADE: moderate) to induce remission. Corticosteroid-related AEs occurred less often with induction doses of budesonide than steroids (RR 0.64; 95% CI, 0.54–0.76; GRADE: moderate); budesonide did not increase AEs relative to placebo (RR 0.97; 95% CI, 0.76–1.23; GRADE: moderate). Budesonide 6 mg/day was not different from placebo for maintaining remission (RR 1.13; 95% CI, 0.94–1.35; GRADE: moderate). Both induction (GRADE: low for 3 mg/day, moderate for 9 mg/day) and maintenance budesonide treatment (GRADE: very low for 3 mg/day, low for 6 mg/day) increased the risk of an abnormal ACTH test compared with placebo, but less than conventional steroids (GRADE: very low for both induction and maintenance).ConclusionFor induction of clinical remission, budesonide was more effective than placebo, but less effective than conventional steroids. Budesonide was not effective for the maintenance of remission. Budesonide was safer than conventional steroids, but the long-term effects on the adrenal axis and bone health remain unknown.

Sa1760 - Novel Microscopic Colitis Disease Activity Index Reflects High Efficacy of Oral Once Daily Budesonide Treatment in Lymphocytic Colitis: Post-HOC Analysis of a Randomized, Double-Blind, Double-Dummy, Multicenter, Trial

Sa1760 - Novel Microscopic Colitis Disease Activity Index Reflects High Efficacy of Oral Once Daily Budesonide Treatment in Lymphocytic Colitis: Post-HOC Analysis of a Randomized, Double-Blind, Double-Dummy, Multicenter, Trial

Effects of fluticasone propionate and budesonide on the expression of immune defense genes in bronchial epithelial cells

BackgroundCOPD patients have increased risk of pneumonia when treated with fluticasone propionate (FP), whereas this is generally not the case with budesonide (BUD) treatment. We hypothesized that BUD and FP differentially affect the expression of immune defense genes. MethodsHuman bronchial epithelial 16HBE cells and air-liquid interface (ALI)-cultured primary bronchial epithelial cells (PBECs) were pre-treated with clinically equipotent concentrations of BUD or FP (0.16–16 nM BUD and 0.1–10 nM FP), and the expression of immune defense genes was studied at baseline and after exposure to rhinovirus (RV16). ResultsUsing microfluidic cards, we observed that both BUD and FP significantly suppressed CXCL8, IFNB1 and S100A8 mRNA expression in unstimulated 16HBE cells. Interestingly, BUD, but not FP, significantly increased lactotransferrin (LTF) expression. The difference between the effect of BUD and FP on LTF expression was statistically significant and confirmed by qPCR and at the protein level by western blotting. RV16 infection of ALI-cultured PBECs significantly increased the expression of CCL20, IFNB1 and S100A8, but not of LTF or CAMP/LL-37. In these RV16-exposed cells, LTF expression was again significantly higher upon pre-treatment with BUD than with FP. The same was observed for S100A8, but not for CCL20, IFNB1 or CAMP/LL-37 expression. ConclusionsTreatment of human bronchial epithelial cells with BUD results in significantly higher expression of specific immune defense genes than treatment with FP. The differential regulation of these immune defense genes may help to explain the clinical observation that BUD and FP treatment differ with respect to the risk of developing pneumonia in COPD.

Downregulation of Guanylate Cyclase Enzyme in Human Asthma model to Investigate NO‐sGc‐ cGMP as a Therapeutic Pathway in Asthma

Asthma is characterized by airway smooth muscle hypersensitivity. Common treatments include β‐adrenergic agonist therapy, such as budesonide, to induce airway smooth muscle relaxation via increased cAMP. However, 70% of patients develop resistance to such therapies. Nitric oxide is a locally produced smooth muscle relaxant that operates via stimulation of soluble guanylate cyclase (sGc) to increase cGMP production. In this study, the NO‐sGc‐cGMP pathway was investigated as an alternate pharmacologic pathway for asthma therapy. Previous studies have found that asthma patients are insensitive to NO signaling and have used sGc drugs to directly stimulate the enzyme. The objective of this study was to examine the expression of the two sGc subunits, α and β, within smooth muscle cells isolated from asthma patients in order to understand how NO‐sGC‐cGMP signaling may be disrupted. Further, we examined how budesonide treatment altered sGc expression. RNA sequencing data showed increased mRNA for both sGc subunits in asthmatic patients and that budesonide downregulated the gene expression of both subunits. We hypothesized that this increased gene expression was in part due to a lack of cGMP signaling due to decreased protein levels that is further impaired with steroids such as budesonide. To examine sGc, we measured the protein levels of both the α and β subunits of sGC by western blot in cultured smooth muscle cells. Fatal asthma and non‐asthma donor derived primary airway smooth muscle cells were cultured with and 24 hours of budesonide treatment. Statistical analysis of western blotting was performed by ANOVA. Densitometry of sGC western blots indicated a 2‐fold downregulation of the α (p<0.0001) and 1.5 fold downregulation of the β (p<0.05) subunits in asthmatic compared to normal patients. No significant changes were observed with normal or asthmatic patients with budesonide treatment (p>0.05), indicating no effect of steroids on the NO‐sGc‐cGMP pathway. A downregulation of sGc protein levels in asthmatic patients would lower cGMP production, which could explain the lack of NO responsiveness in these patients and would contribute to increased airway constriction in fatal asthma. These results indicate the NO‐sGc‐cGMP pathway as a potential new therapeutic pathway in asthma, and future work will examine cGMP levels.Support or Funding InformationSupported by R25ES020721 and ASPET SURF Intern ProgramThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Glucocorticoid‐Driven Transcriptomes in Human Airway Epithelial Cells: Insight from Primary Cells and Cell Lines

RATIONALEGlucocorticoids are stress response hormones that act on the glucocorticoid receptor (GR) to execute effects, including repression of inflammatory gene expression. The molecular mechanisms for this process are still elusive, indeed controversial. This is, to a large extent, due the knowledge gap in understanding the functional impacts of the key glucocorticoid‐modulated genes in relevant tissues. Identification of such genes may be problematic because the effects of glucocorticoids on gene expression are context‐dependent and show variable effects between different cell types. This confounds the identification of key gene expression features within the glucocorticoid‐response. The current study addresses this by comparing the glucocorticoid‐driven transcriptomes in 3 variants of human airway epithelial cells, a critical player in airway inflammation and physiological responses to glucocorticoid. These include two airway epithelial cell lines, pulmonary type II A549 and bronchial epithelial BEAS‐2B cells, and primary human bronchial epithelial (HBE) cells.METHODSGene expression profiling of RNA extracted from A549, BEAS‐2B and HBE cells following budesonide treatment for 6 h was performed using Affymetrix PrimeView microarrays. Genes showing significant induction (fold ≥ 2, P ≤ 0.05) or repression (fold ≤ 0.5, P ≤ 0.05) compared to untreated cells, in any of the cell types were used for further analyses. Representative genes were validated using qPCR. Gene ontology and Ingenuity Pathway Analysis (IPA) were performed using differentially regulated genes in each cell variant.RESULTSUsing stringent (fold ≥ 2 or ≤ 0.5, P ≤ 0.05) cutoff criteria, only 17 and 8 of genes induced or repressed, respectively, by glucocorticoid were common to all 3 epithelial cell variants. While a major fraction of the significantly modulated genes was apparently unique to each cell variant, hierarchical clustering revealed greater commonality than was suggested by the stringent cut‐off. Applying less stringent cut‐offs (fold ≥ 1.25 or ≤ 0.8) within the pool of genes identified by stringent cut‐off revealed 93 induced and 82 repressed genes that were in common among all 3 cell variants. Validation of 52 budesonide‐induced genes using qPCR confirmed, for most of the genes, the grouping scheme determined by applying the less stringent cut‐off. Gene ontology (GO) analysis of the genes induced in common showed enrichment of transcriptional control, proliferation/apoptosis and signaling terms. Equally, the GO term growth factor activity was profoundly enriched with budesonide‐repressed genes across all variants.CONCLUSIONSThe current comparative transcriptome analysis revealed a surprisingly large variance among 3 variants of airway epithelial cells in response to glucocorticoids. Despite this, the common gene expression features obtained by such analysis represent unbiased listing of potentially key molecular players in glucocorticoid response. While many of these genes, and the associated pathways, are consistent with anti‐inflammatory effects of glucocorticoids, a significant fraction are associated with developmental, proliferative, and metabolic GO terms. The functional impacts for many other genes are still unclear, and, therefore should be given priority for further functional analysis. Filling such gaps is essential for advancing knowledge of glucocorticoid biology.Support or Funding InformationSupported by: The Lung Association Alberta & NWT, AstraZeneca, Canadian Institutes of Health Research.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Risk of osteoporosis in microscopic colitis

ABSTRACTObjectives: Patients with microscopic colitis (MC) have several risk factors for osteoporosis. The prevalence of osteopenia and osteoporosis in MC is unknown. The primary purpose of this study was to evaluate bone mineral status in MC.Methods: Patients with MC and disease activity within the last 2 years were included. Bone turnover markers were analyzed and bone mineral density (BMD) was measured with Dual Energy X-ray Absorptiometry (DXA) at inclusion and after one year. Medical history, demographics, risk factors for osteoporosis, disease activity and treatment with cumulative budesonide dosage at least 3 years before inclusion was registered. Adrenal function was tested by adrenocortico-tropic hormone (ACTH) and an ACTH stimulation test at inclusion. Results were compared with age and sex-matched controls.Results: Fifty MC patients (44 women) were included. Median age 67 (range 45–93); median disease duration 28 month (range 2–163); median cumulative budesonide dosage 702 mg (range 0–5400). No difference in number of patients with osteoporosis or osteopenia and BMD was detected between groups. The bone mineral formation marker specific alkaline phosphatase was lower in MC than controls 12 (5–69) µg/l versus 16 (10–35) µg/l (p < 0.005). Patients more often smoked (34% versus 10%, p = 0.001). Disease duration and cumulative budesonide dose was associated with lower BMD and T-score in hip (Spearman’s rho; p < 0.05) with a cut of point of 2500 mg budesonide predicting osteopenia. Budesonide treatment did not affect adrenal gland function.Conclusion: The risk of osteoporosis in patients with MC is not increased. However, DXA scan is recommended in MC patients with known risk factors or active disease requiring longstanding budesonide treatment. Supplementation of calcium and vitamin-D in patients treated with budesonide is recommended.

Comparison of Nebulized Budesonide and Intravenous Dexamethasone Efficacy on Tracheal Tube Cuff Leak in Intubated Patients admitted to Intensive Care Unit.

Background:Tracheal intubation is a common action in intensive care unit (ICU); however, it may cause laryngeal edema or laryngotracheal injury which leads to edema. The cuff-leak test is usually done to define the upper airway patency. Considering the point that laryngeal edema would be treated by anti-inflammatory agents, our aim was to evaluate the impact of nebulized budesonide on ICU patients’ relief and comparison between nebulized budesonide efficacy and intravenous (IV) dexamethasone.Materials and Methods:In our clinical trial, 270 intubated patients from ICU were randomly selected and divided into three groups (each group was included 90 patients) as follows: IV dexamethasone, nebulized budesonide, and placebo group. All the patients were monitored at 0, 12, 24, 36, and 48 h of starting follow-up. Hemodynamic parameters and cuff-leak ratio were measured and data were analyzed using SPSS (ver. 20).Results:Our findings revealed that dexamethasone and budesonide treatment approaches were beneficial for an increase of cuff-leak volume (P < 0.001). Furthermore, the superiority of mentioned methods in patients’ relief was significant compared with placebo group (P < 0.001). Moreover, hemodynamic parameters were not altered and were within the normal range in both dexamethasone and budesonide groups (P > 0.05).Conclusion:Our findings demonstrated that the use of budesonide and dexamethasone is beneficial in intubated ICU patients, and the above-mentioned approaches can reduce the complications of tracheal intubation. Furthermore, budesonide could be a trustworthy substitute treatment strategy instead of IV dexamethasone.

Montelukast Reduces Serum Levels of Eosinophil-Derived Neurotoxin in Preschool Asthma.

PurposeSeveral markers for eosinophilic inflammation have been proposed to predict response to asthma treatment. However, definitive criteria for treatment decisions have not yet been established. We investigate a potentially useful relatively non-invasive biomarker, eosinophil-derived neurotoxin (EDN), to predict favorable responses to budesonide or montelukast, common treatment for children with asthma.MethodsYoung children (1 to 6 years old) were enrolled in this randomized, parallel, 2-group, open-label trial. Criteria for eligibility included: 1) being symptomatic during the run-in period; and 2) having a serum EDN (sEDN) level ≥ 53 ng/mL, with positive specific immunoglobulin E to house dust mite. Eligible patients were randomly placed into 2 groups: the BIS group received budesonide inhalation suspension (BIS) 0.5 mg once daily; the MONT group received montelukast 4 mg once daily. Ineligible patients were invited to receive montelukast 4 mg once daily (OBS group). Treatment period was 12 weeks.ResultsAsthma control days increased significantly in the BIS and MONT groups (P < 0.000) over the 12-week study period. There was no significant change in sEDN in the BIS group but there was a significant decrease in the MONT group (P < 0.000). Patients in the OBS group with high EDN levels (< 53 ng/mL) showed a significant decrease due to MONT treatment (P = 0.023). Rescue medication usage significantly decreased in the BIS and MONT groups (P < 0.000).ConclusionsEDN is a useful relatively non-invasive biomarker for predicting responses to montelukast and budesonide treatment of preschool children with beta2-agonist responsive recurrent wheeze and multiple-trigger wheeze (Trial registry at UMIN Clinical Trials Registry, UMIN000008335).

Considerations on the treatment of IgA nephropathy on the basis of the results of the latest studies (STOP-IgAN, TESTING, NEFIGAN)

IgA nephropathy is an immune-mediated chronic glomerulonephritis with a great variability in clinical presentation and outcome. The disease can progress to end-stage renal failure in 25% of patients. For this reason we should identify patients with potential to progress. Most important risk factors for progression are persistent proteinuria, hypertension, decreased renal function and some histological lesions. The actually suggested treatment is summarized in KDIGO Clinical Practice Guideline from 2012. They suggest to give firstly non-specific supportive treatment (especially renin-angiotensin system blocking agents). Recommendation about steroid/immunosuppression treatment is based on low level of evidence. Recently three studies were organised concerning benefits and risk of steroid/immunosuppressive treatment added together with specific supportive treatment. In the STOP-IgAN study, systemic steroid/immunosuppressive treatment significantly decreased proteinuria but did not stop progression. In the TESTING study, systemic steroid treatment significantly decreased proteinuria and progression. However, the study was recently discontinued due to several severe side effects of steroid treatment. Involvement of intestinal mucosal immunity in the pathogenesis of IgA nephropathy suggested the NEFIGAN study with budesonide treatment. Budesonide releases corticosteroid in distal small intestine and colon. Proteinuria was significantly decreased and renal function remained stabile. High number of withdrawals owing to adverse effects is a major concern implying a substantial systemic effect of budesonide. We need further information on the characteristics of patients who most likely benefit from steroid/immunosuppressive treatment given after or together with specific supportive treatment. Orv Hetil. 2017; 158(49): 1946-1952.

Decreased frequency of adenoidectomy by a 12-week nasal budesonide treatment

ObjectiveThere is little evidence on the role of topical budesonide in reducing the frequency of adenoidectomy, although it was reported that topical budesonide can effectively ameliorate the symptoms of adenoid hypertrophy (AH). This study was aimed to investigate the possibility and safety of alternatives to adenoidectomy with a 12-week treatment with nasal budesonide.Materials and methodsOne hundred patients with AH were randomized to receive either a double-blind budesonide (1 mg once daily) or placebo treatment for 2 weeks by transnasal nebulization. A further 12-week open study, budesonide spray (64 μg per nostril at bedtime) was administered to the treatment group. During the final 12 weeks of follow-up, the frequency of adenotonsillectomy, side effects, the degree of nasal obstruction, nasal discharge, and snoring were assessed.ResultsOut of the 100 total enrolled patients, 92 children with AH completed the study. After the 2-week treatment with transnasal budesonide nebulization, the symptoms of AH significantly decreased compared to the control group. Responders (n=26) who had initially improved showed significantly decreased symptoms of AH, and the frequency of adenotonsillectomy during the follow-up (14 and 26 weeks) was compared with that of the control group and non-responders (n=21) who did not respond to the initial 2-week budesonide therapy. The 12-week nasal budesonide treatment did not suppress the growth rate of children’s height or cause other side effects.ConclusionAH children who had improved after an initial 2-week budesonide therapy can achieve clinical improvements and decreased frequency of adenoidectomy following the therapy with a 12-week treatment with nasal budesonide.

Effects of inhaled corticosteroids on the expression of TNF family molecules in murine model of allergic asthma

ABSTRACTBackground: The tumor necrosis factor superfamily member LIGHT (the official gene symbol approved by NCBI Gene Database), an inflammatory factor secreted by T cells after allergen exposure, recently discovered to play crucial roles in asthmatic airway remodeling. However, it is unclear whether LIGHT could be controlled by inhaled corticosteroids, a key component of asthma management. This study was to investigate the effects and potential mechanisms of inhaled budesonide on the expressions of LIGHT and its receptors (LTβR and HVEM) of lung tissues in ovalbumin-sensitized mice. Materials and Methods: Thirty-three BALB/c mice were randomly divided into the control, asthma model, and budesonide treatment groups (11 in each group). Mice were sensitized and challenged by OVA to develop mouse model of chronic asthma, and treated with aerosolized budesonide before OVA challenge. Bronchoalveolar lavage fluid (BALF) and lungs were obtained after the final OVA challenge. Protein and mRNA Levels of LIGHT, LTβR, and HVEM in the lungs were investigated by immunohistochemistry, image analysis, and real-time PCR. Expressions of IL-6 and IFN-γ in BALF were measured by ELISA. Results: Inhaled budesonide significantly reduced protein and mRNA levels of lung LIGHT, LTβR, and HVEM in asthmatic mice. Correspondingly, the number of eosinophils and neutrophils and IL-6 levels in BALF after budesonide treatment were found to be decreased, whereas the IFN-γ levels in BALF were increased. Moreover, the expressions of LIGHT and HVEM mRNA showed positive correlation with IL-6 levels in the treatment group. Conclusions: Inhaled budesonide can down-regulate the expressions of LIGHT, LTβR, and HVEM in the lungs of asthmatic mice, and LIGHT/LTβR/HVEM interactions may be a potentially key target for asthma treatment.

Effects of the combined extracts of Herba Epimedii and Fructus Ligustrilucidi on airway remodeling in the asthmatic rats with the treatment of budesonide

BackgroundAsthma is characterized by chronic airway inflammation, leading to structura1 changes in the airway, collectively termed airway remodeling. Airway remodeling is thought to contribute to airway hyper responsiveness and irreversible airflow limitation. The combination of Herba Epimedii (HE) and Fructus Ligustri Lucidi (FLL) decoction and the systemic administration of glucocorticoids (GC) had a synergistic inhibitory action on airway inflammation in the asthmatic model rats. However, the effects of the combination on airway remodeling have not been studied and compared. In the present study, we investigated the effects of the co-administration of combined extracts of HE and FLL with inhaled GC (budesonide) on airway remodeling in the rat asthmatic model induced by ovalbumin (OVA).MethodsMale Sprague-Dawley rats were sensitized to intraperitoneal OVA followed by repetitive OVA challenge for 7 weeks. Treatments included extracts of HE and FLL (Extracts for short, 100 mg/kg by gastric perfusion), budesonide (1 mg budesonide suspension in 50 ml sterile physiological saline, 3 rats in an ultrasonic nebulizer by nebulized inhabation with a flow of 1.6 ml/min for 30 min), and co-administration of extracts of HE and FLL with budesonide (Co-administration for short) for 4 weeks. Lung histomorphometry and bronchoalveolar lavage fluid (BALF) cell count were assessed 24 h after the final OVA challenge. Levels of interleukin (IL)-4, IL-5 and IgE were measured by ELISA. Expressions of Collagen I and Collagen III were tested by immunohistology. Expressions of transforming growth factor (TGF) -β1, TGF-β2 and Smads mRNA were measured by quantitative real-time PCR.ResultsExtracts, budesonide and Co-administration significantly reduced allergen-induced increases in the serum levels of IL-4, IL-5 and IgE, the number of eosinophils in BALF, goblet cell hyperplasia, Collagen III integral optical density (IOD) and the mRNA expression of TGF-β2 and Smad2. Extracts and Co-administration could depress the IOD level of Collagen I and the positive area of Collagen I and Collagen III. Budesonide and Co-administration significantly alleviated the thickening of airway wall. Only Co-administration significantly decreased collagen deposition according to the morphometry of Masson’s-stained lung sections, the thickening of airway smooth muscle layer, the number of lymphocytes in BALF and the mRNA expression of TGF-β1 and Smad3, and this was associated with a significant increase in levels of Smad7 mRNA.ConclusionsThe findings suggested that the combination of budesonide and the herbal extracts had a better synergistic effect on airway remodeling in OVA-reduced asthma rats than the single use of budesonide.

Enteric-coated budesonide for the induction and maintenance of remission of Crohn’s disease in children

Objective: These studies evaluated the safety and efficacy of enteric-coated budesonide for the induction and maintenance of remission of mild-to-moderate Crohn’s disease (CD) in children.Methods: The consecutive, multicenter, open-label, non-comparative studies enrolled patients aged 6–17 years. In the induction study, patients with active CD of the ileum and/or ascending colon received budesonide 9 mg or 6 mg once daily for 8 weeks; in the maintenance study, patients in remission received budesonide 6 mg once daily for 12 weeks. The primary objective was assessment of safety, including glucocorticosteroid-related side effects and serum cortisol levels. Efficacy was assessed using the Pediatric Crohn’s Disease Activity Index (PCDAI), and health-related quality of life (HRQoL) using the IMPACT-III questionnaire.Results: In the induction study (n = 108), most adverse events were related to CD, commonly abdominal pain; possible glucocorticosteroid-related effects included acne and increased appetite but without significant weight gain. Subnormal morning cortisol levels were observed in 32 of 103 patients after 8 weeks. Budesonide reduced disease activity from baseline (mean ± standard deviation, 9.1 ± 8.5 vs. 19.1 ± 10.1, p < .001) with 58.1% of patients reaching remission (PCDAI <10); HRQoL improved (p < .001). In the maintenance study (n = 50), mean disease activity worsened (p = .047) with HRQoL unchanged (p = .33).Conclusions: Budesonide treatment was generally well tolerated, although the potential for adrenal suppression was noted. Budesonide was effective for induction of remission in children with mild-to-moderate CD but not for maintaining remission (ClinicalTrials.gov identifiers: NCT01444092, NCT01453946).

To investigate the correlation of nasal secretions of eosinophils and lung function after the treatment of budesonide in the allergic rhinitis patients

Objective:To identify the relationship between nasal secretion eosinophilia and pulmonary function of patients with AR after treatment of intranasal budesonide.Method:Fifty patients with moderate to severe AR were selected, and compared to 50 normals, all had pulmonary function and nasal secretion of eosinophil number check, experimental group of AR received budesonide+loratadine treatment for 3 months, and then had lung function and nasal secretion eosinophil again, analysised the trends of change between two. Result:Eosinophils of AR patients was higher than its of control group (P<0.05), lung function index MMEF and nasal secretion eosinophilia of 50 AR patients had a negative relationship(r=-0.945，P<0.05).Treated with eosinophils the number of nasal secretion eosinophilia of AR decreased 10 + 5.6, the difference compared to the before of the treatment was statistically significant(P<0.05), compared to the normal control group was significant(P<0.05). After the treatment of budesonide, the trends of change between nasal secretion eosinophils and pulmonary function was a positive correlation(r=0.803,P<0.01). Conclusion:The higher the number of eosinophils in nasal secretions of patients with AR, the more obvious the decline of lung function. After the treatment with budesonide, the more eosinophils decreased in patients with AR, the more obvious the improvement of pulmonary function.

Clozapine induced diarrhea

IntroductionClozapine (CZP) is the only antipsychotic approved for resistant schizophrenia 1. Due to its side effects, CZP is not the first therapeutic option in a psychotic episode. Its anticholinergic effects often cause constipation, however, diarrhea have also been described in literature.ObjectivesWe describe a patient with two episodes of severe diarrhea after clozapine initiation, which lead to CZP discontinuation.AimsDiscuss about the differential diagnosis of diarrhea in CZP patients and the needing of a further studies for clarify the more appropriate management in CZP induced diarrhea.MethodsWe present a case report of a 46 years man diagnosed with schizoaffective disorder who presented two episodes of severe diarrhea with fever, which forced his transfer to internal medicine and UCI after CZP initiation.ResultsAt the first episode analytical, radiological and histological findings led to Crohn's disease diagnosis, which required budesonide and mesalazine treatment. In the second episode, the digestive team concluded that the episode was due to clozapine toxicity despite the controversial findings (clostridium toxin and Crohn's compatible biopsies)ConclusionsDiarrhea caused by CZP has been controversial in the literature. However due to the severity of digestive episodes and the paucity of alternative treatments further studies for a better understanding of its physiopathology are warranted.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Risk of pneumonia with budesonide-containing treatments in COPD: an individual patient-level pooled analysis of interventional studies

BackgroundConcerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk. Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors.MethodsAstraZeneca-sponsored, parallel-group, double-blind, randomized controlled trials meeting the following criteria were included: >8 weeks’ duration; ≥60 patients with COPD; inhaled budesonide treatment arm (budesonide/formoterol or budesonide); and non-budesonide-containing comparator arm (formoterol or placebo). Primary and secondary outcomes were time to first pneumonia treatment-emergent serious adverse event (TESAE) and treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox regression models stratified by study.ResultsEleven studies were identified; 10,570 out of 10,574 randomized patients receiving ≥1 dose of study treatment were included for safety analysis (budesonide-containing, n=5,750; non-budesonide-containing, n=4,820). Maximum exposure to treatment was 48 months. The overall pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83, 1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36). The annual incidence of pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide-containing treatments, respectively. Comparing budesonide/formoterol with non-budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1.00 (95% CI: 0.69, 1.44) and 1.21 (95% CI: 0.93, 1.57), respectively. For budesonide versus placebo, HRs were 1.57 for pneumonia TESAEs (95% CI: 0.90, 2.74) and 1.07 for pneumonia TEAEs (95% CI: 0.83, 1.38).ConclusionThis pooled analysis found no statistically significant increase in overall risk for pneumonia TESAEs or TEAEs with budesonide-containing versus non-budesonide-containing treatments. However, a small increase in risk with budesonide-containing treatment cannot be ruled out; there is considerable heterogeneity in study designs and patient characteristics, particularly in the early budesonide studies, and each study contributes <40 pneumonia TESAEs.

Safety of long-term intranasal budesonide delivered via the mucosal atomization device for chronic rhinosinusitis.

Although short-term use (≤2 months) of atomized topical nasal steroids has been shown to be safe and effective, the long-term safety has yet to be demonstrated. The aim of this study was to determine the impact of long-term topical budesonide treatment via the mucosal atomization device (MAD) on the hypothalamic-pituitary-adrenal axis (HPAA) and intraocular pressure (IOP). A cross-sectional study of patients with chronic rhinosinusitis (CRS), with or without nasal polyposis, managed with daily nasal budesonide via MAD was conducted at a tertiary rhinology center. Patients using systemic steroids within 3 months of assessment were excluded. HPAA impact was assessed using the cosyntropin stimulation test for adrenal function and a survey of relevant symptomatology. Patients also underwent tonometry to assess for elevated IOP potentially related to corticosteroid use. A total of 100 CRS patients were recruited with a mean budesonide treatment duration of 23.5 months (range, 6-37 months). Stimulated cortisol response was diminished in 3 patients (3%). No patients with adrenal suppression had relevant symptomatology. IOP was elevated in 6 patients (6%). These findings suggest that there is a risk of adrenal suppression and raised IOP associated with the long-term use of topical nasal budesonide via MAD. Otolaryngologists should consider periodic surveillance for these adverse events in this patient cohort.

Covering the Cover

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Efficacy and Limitations of Budesonide as a Second-Line Treatment for Patients With Autoimmune Hepatitis

Many patients with autoimmune hepatitis (AIH) develop steroid-specific side effects or require doses of steroids that are unacceptable for long-term treatment. We investigated the efficacy of budesonide as an alternative steroid for patients previously treated with prednisolone who developed side effects or were unable to reduce their dose of prednisolone below acceptable levels. We also report the effects of more than 12 months of budesonide treatment in a large cohort of patients with AIH. We performed a retrospective analysis of data from 60 patients (51 female) with AIH who were treated initially with prednisolone (mean time, 47 mo) but then switched to budesonide, managed at a single center in Germany from 2001 through June 2016. Patients were evaluated after 6 months, 12 months, 24 months, 36 months, and at the last follow-up evaluation; response to treatment with budesonide was assessed based on normal serum levels of aminotransferases and IgG (biochemical response). Thirty patients were switched to budesonide therapy because of prednisolone-induced side effects and 30 patients switched because of prednisolone dependency. Overall, a biochemical response was detected in 55% of patients after 6 months of budesonide treatment, in 70% after 12 months, and in 67% after 24 months. At the last follow-up evaluation (mean time, 63 mo) 23patients (38%) still were receiving budesonide treatment. Fifteen patients (25%) had switched back to prednisolone therapy because of insufficient response to budesonide or its side effects. Fifteen patients with osteopenia at the beginning of budesonide treatment were followed up and evaluated by dual-energy X-ray absorptiometry. After a median of 24 months of budesonide treatment, bone mineral density had improved in 6 patients, remained stable in 8 patients, and worsened in 1 patient. We performed a retrospective analysis of patients with AIH that confirmed the therapeutic value of budesonide beyond 12 months of treatment in patients who are intolerant to or dependent on prednisolone. Although budesonide-induced side effects appear to be mild in real life, effectiveness was limited in a considerable proportion of patients; close monitoring is advised.