Topical Budesonide Research Articles

Hold the Foam: Why Topical Budesonide Remains Relevant for IBD Therapy

Hold the Foam: Why Topical Budesonide Remains Relevant for IBD Therapy

A87 A NEW ERA: CIRCUMFERENTIAL ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY ESOPHAGEAL NEOPLASM AND BARRET’S ERADICATION

Abstract Background Endoscopic submucosal dissection (ESD) has become increasingly important over the last few years as the treatment of choice for early gastrointestinal malignancies. Esophageal adenocarcinoma is among the most rapidly rising malignancies associated with a poor 5-year survival rate. ESD is emerging as a novel minimally invasive treatment for superficial esophageal neoplasms. However, with increasing circumference of dissection, the rate of stricture increases with over 90% stricture rate reported with complete circumferential ESD (cESD). Currently, for superficial Barrett’s neoplasms the dysplastic lesion is resected and subsequent eradication of remaining Barrett’s is with radiofrequency ablation over multiple sessions. Aims To report on a case of cESD for intramucosal carcinoma and Barrett’s eradication with one procedure with the application of prophylactic dual steroid treatment (DST) for prevention of stricture. Methods We present the case of a 62-year-old female with C1M5 Barrett’s esophagus with pathology confirming high grade dysplasia with a focus suspicious for intramucosal adenocarcinoma. Staging CT excluded metastatic disease. Repeat endoscopy with magnification revealed multiple areas with highly irregular vascular and surface patterns with premature loss of acetowhitening reaction consistent with multifocal at least high-grade dysplasia. Subsequently, the entire segment of Barrett’s was removed via cESD. Histopathologic analysis of the resected tissue confirmed multifocal high grade disease with margins negative for dysplasia or intestinal metaplasia. The patient was started on DST with oral prednisone and topical (swallowed) budesonide along with sucralfate as prophylactic measures to prevent luminal stricturing. Results During the re-epithelization period the patient required 2 prophylactic dilations. Five months post-ESD, full clinical, endoscopic and histopathologic healing had been observed. There was complete squamous re-epithelization with normal squamous mucosa without stricture. The patient remains on a yearly endoscopic surveillance protocol. Conclusions cESD represents a novel therapeutic strategy for the definitive histologic and endoscopic eradication of superficial esophageal neoplasms along with remaining Barrett’s. In this patient, there were no complications and significant stricturing was prevented with DST. Multiple prior studies have assessed single steroid therapy as a therapeutic option for strictures. In this report, DST represents a novel regime in preventing severe strictures post cESD. Longer term follow-up and further reports are needed to confirm these findings. Funding Agencies None

Budesonide ММХ in the treatment of ulcerative colitis: real world clinical practice

Rationale: Mild and moderate ulcerative colitis (UC) is conventionally treated with oral and rectal 5-aminosalicylic acid (5-ASA) formulations and, if ineffective, with systemic glucocorticosteroids. A huge disadvantage of systemic steroids is that with highly efficacy they have severe side effects and the development of hormone-dependency requiring their withdrawal. The main goal of UC treatment is to achieve clinical and endoscopic remission, and possibility to stop steroids. The introduction of multimatrix (MMX) budesonide (Cortiment®), a new topical steroid for UC treatment, widens the therapeutic armamentarium and allows in some cases to refrain from systemic agents, avoiding their side effects and achieving the necessary treatment goals.Aim: To evaluate the efficacy of topical steroid budesonide MMX for remission induction of UC in the real clinical practice.Materials and methods: We have analyzed 122 specially designed case report forms filled in from September 2018 to March 2019 in healthcare centers of Moscow, Voronezh, Lipetsk, Krasnodar, and Krasnoyarsk Regions of Russian Federation. The case report forms included anonymized data on the UC patients treated with budesonide MMX. The results of treatment were analyzed for various severity and extension of UC and depending on budesonide MMX monotherapy or combined therapy with rectal 5-ASA formulations. Treatment was considered effective if clinical and endoscopic remission was achieved.Results: Total efficacy in terms of improvement of clinical parameters (improvement/remission) after 4 weeks of treatment was 95% (118 patients), with clinical remission induced in 42.6% (52 patients). Positive changes over time in the endoscopic findings (improvement/remission) within the same time period were observed in 93% (60 patients), with endoscopic remission in 24.1% (21 patients).Conclusion: Budesonide MMX allows for a rapid clinical improvement and/or clinical remission in the majority of the patients with mild and moderate UC of predominantly left-sided location.

1756 Evolution of Esophageal Lichen Planus to Esophageal Leukoplakia

INTRODUCTION: To describe a case of esophageal lichen planus which appeared to evolve to leukoplakia (aka epidermoid metaplasia). CASE DESCRIPTION/METHODS: A 70 yo female with a prior history of lichen planus, presented from another institution for ongoing care related to proximal esophageal stricturing. The patient had well-documented lichen planus involving the oral and vaginal mucosae and axillary areas. Dysphagia had been ongoing for greater than a decade and prior endoscopic exams revealed the proximal esophagus to be of small caliber with proximal esophageal strictures/rings. Biopsies had shown nonspecific change. On some occasions an ultrathin gastroscope was required to traverse the proximal esophagus. The patient underwent numerous sessions of Savary dilation and given oral lichen planus, it was assumed that this process was also responsible for the proximal esophageal pathology. She was treated with periodic esophageal dilation and topical budesonide. Recently after the above therapy, dysphagia had resolved, and the patient was ingesting a normal diet. The esophagus was found to be of more normal caliber endoscopically (strictures were no longer evident) and prominent whitish proximal esophageal plaques were now noted (Figure 1). Proximal esophageal biopsies now revealed hyperorthokeratosis with hypergranulosis, but no inflammatory process or Civatte bodies (apoptotic keratinocytes). As such, recent endoscopic and pathologic findings were thought to be most consistent with esophageal leukoplakia/epidermoid metaplasia. Topical budesonide was continued for her oral lichen planus, but it was now recommended that it be administered in a "swish and spit" manner. Given the association of esophageal leukoplakia with squamous dysplasia and squamous cell carcinoma, the patient was placed in an endoscopic surveillance program. She has recently remained asymptomatic from the esophageal perspective. DISCUSSION: Lichen planus and leukoplakia (epidermoid metaplasia) involving the esophagus are distinct clinical, endoscopic and pathologic processes- both of which appear to have a female predominance, and potential association with squamous cell carcinoma. The esophageal disease in patient under discussion appeared to evolve from one of these processes to the other, raising the specter of an association between these disorders.

Effect of commercial nasal steroid preparation on bacterial growth.

Topical budesonide (Pulmicort; AstraZeneca AB, Sodertalje, Sweden) is commonly used in the management of chronic rhinosinusitis (CRS). Although its use is due to its perceived anti-inflammatory effect, studies have suggested that it may also have antibacterial properties. To make the hydrophobic steroid molecule suitable for topical administration, pharmaceutical excipients are used in commercial steroid formulations. Herein we investigated the antibacterial action of commercial budesonide and its excipients. Planktonic and biofilm forms of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) were treated with Pulmicort or its excipients at clinically relevant concentrations. Bacterial growth was determined by optical density, resazurin assays, colony-forming unit counts, and Giemsa staining. Minimum inhibitory concentration (MIC) studies assessed excipients' potentiation of antibiotics. Experiments were conducted in triplicate and results analyzed using one-way analysis of variance. There was significant reduction in planktonic and biofilm growth of S aureus and MRSA on exposure to budesonide (p < 0.0001) and its excipients (p < 0.0001). Excipient ethylene diamine-tetraactic acid (EDTA) demonstrated an antibacterial property even at the low concentrations used in topical preparations (p < 0.0001). With amoxicillin, excipients exhibited a potential additive/synergistic effect on MIC, whereas erythromycin and aminoglycosides showed an antagonistic action. The commercial product Pulmicort has a direct antibacterial effect on the planktonic and biofilm forms of S aureus and MRSA. This effect is at least in part mediated through the excipient EDTA in the product. Excipients also influenced the antimicrobial activity of antibiotics depending on the bacterial strain and antibiotic tested.

Diagnostic and Therapeutic Long-term Management of Eosinophilic Esophagitis- Current Concepts and Perspectives for Steroid Use.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus, which requires short- and long-term treatment. In addition, patients under long-term treatment for any chronic condition should have a structured follow-up. The mainstays in EoE treatment are drugs (such as swallowed topical corticosteroids [STC] and proton pump inhibitors), dietary exclusions, and endoscopic dilations. STC are the most widely used treatment and have proven efficacy in inducing clinical, endoscopic and histological remission in active EoE. However, data regarding maintaining disease remission and long-term management are limited. Ongoing disease activity and relapses despite STC treatment are frequently observed. This sheds light on the urgent need for adequate maintenance strategies, which have not been well defined. In terms of follow-up concepts, to date neither guidelines nor consensus recommendations have been published. To summarize the current knowledge on long-term diagnostic and therapeutic STC management of EoE, we conducted a literature search using PubMed and Embase applying the following key search items: Eosinophilic esophagitis, eosinophils, esophagus, swallowed topical corticosteroids, fluticasone, budesonide, long-term, treatment, therapy, and follow-up. In addition, we present empirically developed long-term management concepts applied at two large EoE centers, with a special focus on STC treatments. Finally, we highlight areas of future research and perspectives regarding the long-term management of EoE.

Budesonide with multi-matrix technology as second-line treatment for ulcerative colitis: evaluation of long-term cost-effectiveness in the Netherlands

Aims: Budesonide with multi-matrix technology (MMX) is an oral corticosteroid, shown to have high topical activity against ulcerative colitis (UC) while maintaining low systemic bioavailability with few adverse events. The aim of this study was to evaluate the cost-effectiveness of budesonide MMX versus commonly used corticosteroids, in the second-line treatment of active mild-to-moderate UC in the Netherlands.Materials and methods: An eight-state Markov model with an 8 week cycle length captured remission, four distinct therapy stages, hospitalization, possible colectomy and mortality. Remission probability for budesonide MMX was based on the CORE-II study. Population characteristics were derived from the Dutch Inflammatory Bowel Disease South Limburg cohort (n = 598) and included patients with proctitis (39%), left-sided (42%) and extensive disease (19%). Comparators (topical budesonide foam and enema, oral budesonide and prednisolone) were selected based on current Dutch clinical practice. Treatment effects were evaluated by network meta-analysis using a Bayesian framework. Cost-effectiveness analysis was performed over a 5 year time horizon from a societal perspective, with costs, health-state and adverse event utilities derived from published sources. Outcomes were weighted by disease extent distribution and corresponding comparators.Results: Budesonide MMX was associated with comparable quality-adjusted life year (QALY) gain versus foam and oral formulations (+0.01 QALYs) in the total UC population, whilst being cost-saving (EUR 366 per patient). Probabilistic sensitivity analysis evaluated an 86.6% probability of budesonide MMX being dominant (cost-saving with QALY gain) versus these comparators. Exploratory analysis showed similar findings versus prednisolone.Limitations: Differing definitions of trial end-points and remission across trials meant indirect comparison was not ideal. However, in the absence of head-to-head clinical data, these comparisons are reasonable alternatives and currently offer the only comparison of second-line UC treatments.Conclusions: In the present analysis, budesonide MMX was shown to be cost-effective versus comparators in the total UC population, for the second-line treatment of active mild-to-moderate UC in the Netherlands.

The efficacy of a novel budesonide chitosan gel on wound healing following endoscopic sinus surgery.

Adhesion formation and ostial stenosis are common causes of surgical failure after endoscopic sinus surgery (ESS). Postoperative topical steroid application has been shown to improve wound healing. Chitosan-dextran gel (CD gel) is an effective hemostatic nasal dressing. This study aims to determine the effect of the addition of budesonide to CD gel on postoperative ostial stenosis and adhesion formation following ESS. This prospective, blinded, randomized controlled trial was conducted between October 2012 and April 2015. Thirty-six patients over 18 years undergoing ESS were randomized to receive either: no treatment, CD gel, CD gel with 1 mg/ 2 mL budesonide, or topical steroid cream to their left or right sinuses (different treatment each side). Each sinus ostium and endoscopic features of wound healing was measured intraoperation, and 2 weeks, 3 months, and 12 months postoperation. Data was analyzed using the analysis of variance (ANOVA) and post hoc Tukey honestly significant difference (HSD) tests. There was a significant reduction in stenosis within all 3 sinuses ostia sites when CD + budesonide was compared to control, with the greatest effect seen at 12 months: The mean ± standard deviation (SD) percentage of baseline areas at 12 months were 76% ± 6.2% vs 37% ± 23.5%, 76% ± 6.3% vs 52% ± 4.9%, and 83% ± 6.5% vs 58% ± 5.0% (all p < 0.05), for CD + budesonide compared to control in the frontal, sphenoid, and maxillary sinuses, respectively. The incidence of adhesions was 4% in the CD + budesonide group compared to 15% in the control group. This study has shown that CD gel, when combined with topical budesonide solution, improves long-term sinus ostial patency and prevents ostial stenosis post-ESS.

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.

Is topical high-volume budesonide sinus irrigation safe?

Is topical high-volume budesonide sinus irrigation safe?

Six-Food Elimination Diet and Topical Steroids are Effective for Eosinophilic Esophagitis: A Meta-Regression.

Topical corticosteroids or six-food elimination diet is recommended as initial therapy for eosinophilic esophagitis (EoE). We aimed to summarize published manuscripts that report outcomes of these therapies for EoE. We performed a systematic review in MEDLINE, Web of Science, and Embase of published manuscripts describing topical fluticasone, topical budesonide, and six-food elimination diet as therapies for EoE. We conducted meta-analysis of symptom improvement and the change in peak mucosal eosinophil count, with heterogeneity between studies examined with meta-regression analysis. Systematic review yielded 51 articles that met inclusion criteria. Summary histologic response rates were 68.3% [95% prediction limits (PL) 16.2-96.0%] for fluticasone, 76.8% (95% PL 36.1-95.1%) for budesonide, and 69.0% (95% PL 31.9-91.4%) for six-food elimination diet. Corresponding decreases in eosinophil counts were 37.8 (95% PL 19.0-56.7), 62.5 (95% PL 125.6 to -0.67, and 44.6 (95% PL 26.5-62.7), respectively. Symptom response rates were 82.3% (95% PL 68.1-91.1%), 87.9% (95% PL 42.7-98.6%), and 87.3% (95% PL 64.5-96.3%), respectively. Meta-regression analyses decreased the initially large estimate of residual heterogeneity and suggested differences in histologic response rate associated with study populations' baseline eosinophil count and age. The literature describing topical corticosteroids and six-food elimination diet consists of small studies with diverse methods and population characteristics. Meta-analysis with meta-regression shows initial histologic and symptomatic response rates on the same order of magnitude for topical corticosteroids and six-food elimination diet, but heterogeneity of study designs prevents direct comparison of modalities.

Managing immune checkpoint-inhibitor-induced severe autoimmune-like hepatitis by liver-directed topical steroids.

3073 Background: The CTLA4-antibody ipilimumab, and PD-1-antibodies pembrolizumab as well as nivolumab have revolutionized antineoplastic therapies. Induction of autoimmune-like drug-induced liver injury (DILI) is within the spectrum of adverse reactions of these new drugs and has been observed in about 1-5 % of patients, developing predominantly within the first 6 to 12 weeks after start of treatment. Immediate application of systemic steroids and a permanent discontinuation of immune checkpoint-inhibition therapy are recommended for any alanine aminotransferase increase ≥ WHO grade 3. In severe autoimmune-like DILI the permanent discontinuation of the immune checkpoint inhibitor is recommended, as drug re-exposure might be associated with a significant risk of a fulminant DILI. Methods: We report six patients with severe grade 3 autoimmune-like DILI (according to Common Terminology Criteria for Adverse Events 4.3) treated with long-term application of budesonide, a liver-directed topical steroid. Results: Immune checkpoint inhibitors were stopped and methylprednisolone was applied initially with a dose of 1 mg/kg body weight and tapered thereafter. To reduce systemic steroids and to minimize the exposure time to systemic steroids, the topical steroid budesonide 3 mg three times per day was additionally given in combination with N-acetylcysteine and ursodeoxycholic acid. Under this multimodal approach transaminases normalized and the respective immune-checkpoint inhibitor could be re-started without re-manifestation of DILI under the continuous treatment with budesonide. Conclusions: Budesonide - a liver-directed topical steroid - might be an interesting approach to target liver related autoimmune adverse reactions induced by immune checkpoint inhibitors without compromising their anti-cancer effect. We were able to safely and effectively re-introduce and continue immune checkpoint inhibitors under the continuous application of the topical steroid without showing any further liver toxicity.

Efficacy and safety of rectal 5-aminosalicylic acid versus corticosteroids in active distal ulcerative colitis: a systematic review and network meta-analysis

Topical 5-aminosalicylic acid (5-ASA) and corticosteroids are used frequently in the treatment of active distal ulcerative colitis (UC). Our study aimed to determine the efficacy and safety of different topical drugs used to treat active distal UC. A random-effects model within a Bayesian framework was utilized to compare treatment effects and safety as odds ratios (ORs) with corresponding 95% credible intervals (CrI). The surface under the cumulative ranking area (SUCRA) and median rank (MR) with corresponding 95% CrI were calculated to rank the treatment outcomes. In the induction of clinical and endoscopic remission, most regimens showed significant advantages over placebo except topical budesonide 0.5 mg/d and hydrocortisone 100 mg/d. According to SUCRA and MR values, rectal 5-ASA 1.5 to 2.0 g/d + Beclomethasone dipropionate (BDP) 3 mg/d rendered the highest probability of being the best regimen to achieve clinical and endoscopic remission, followed by the separate use of 5-ASA 4 g/d and BDP 3 mg/d. The occurrence of adverse events was not significantly different between each treatments and placebo. In conclusion, the combined use of topical 5-ASA and BDP proved to be the best choice for active distal UC and further well-designed researches are warranted to assess its efficacy and safety.

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.

Esophageal involvement is frequent in lichen planus: study in 32 patients with suggestion of clinicopathologic diagnostic criteria and therapeutic implications.

Lichen planus (LP) is a classic skin disease that can involve the skin, hair, and nails, as well as the oral and genital mucosa. Histopathology is characterized by a T-lymphocytic, lichenoid, and interface dermatitis. Multiple case reports and small case series have shown that LP can involve the esophagus. However, the diagnostic criteria, incidence, and best treatment options remain uncertain. This study aimed to refine the diagnostic criteria, estimate prevalence, and present an outlook on treatment options to prevent long-term sequelae. Thirty-two consecutive patients with LP of the skin, hair, nails, oral mucosa, and/or genital mucosa underwent a comprehensive clinicopathologic assessment. Esophagogastroduodenoscopy was performed, and biopsies were evaluated histologically, immunohistochemically, and by direct immunofluorescence. Patients diagnosed with esophageal lichen planus (ELP) were followed up prospectively where possible. In total, 20 of 32 patients had ELP. Ten of these 20 patients were classified as having proven ELP, with clear-cut endoscopically visible lesions; the other 10 were classified as having probable ELP. Eight of 10 patients with proven ELP were started on new or additional therapy because of esophageal findings. Treatment with a topical budesonide formulation or systemic corticosteroids was successful in most patients with proven ELP and reversed functional esophageal stenosis. ELP can be found in more than 50% of patients with proven mucocutaneous LP when clinical and pathologic findings are correlated carefully. Topical or systemic corticosteroids are the first-line therapy for ELP. Timely medical therapy seems to prevent scarring stenosis of the esophagus.

Treatment of Caustic Ingestion Associated Esophageal Stricture with Budesonide

We present the images from the upper endoscopy of a 5-year-old patient who developed an esophageal stricture from caustic ingestion. These images are from before and after a two-week course of topical budesonide. Her remarkable improvement suggests that we need more studies to investigate topical steroid use for caustic esophageal injury.

Esophageal Lichen Planus: Efficacy of Topical Steroid-Based Therapies: 2016 ACG Presidential Poster Award

Introduction: Background & Aims: Esophageal lichen planus (ELP) is an idiopathic inflammatory disorder characterized by significant esophageal stricturing. Esophageal lichen planus is a rare, diffi cult to diagnose, and likely an under recognized disease. Less than 100 cases have been described in case reports and series. As a result, there is no standardized approach to therapy and treatment strategies vary. Approaches which have been used on a case to case basis include steroids (systemic and topical), immunomodulators and endoscopic dilation. Our study examined the utility of topical steroid therapy (fluticasone and budesonide) on the management of esophageal lichen planus in a large cohort of patients. Methods: A retrospective chart review was conducted of patients diagnosed with ELP who underwent baseline and follow up endoscopy pre and post topical steroid therapy between 1995 and 2016 at Mayo Clinic, Rochester MN. Patients were reviewed for symptomatic response to therapy using the Dakkak-Bennett dysphagia score. Pre and post endoscopic findings were assessed. Additional baseline demographic, endoscopic, and histologic data were also obtained. Results: 40 patients met the inclusion criteria. A significant reduction in median dysphagia score from 1 to 0 after steroid therapy (p < 0.001) was noted. 62% of patients reported resolution of their dysphagia after receiving topical corticosteroids. An endoscopic response to steroid therapy was seen in 72.5% on follow up endoscopy. Conclusion: To our knowledge this is the largest study examining the efficacy of topical swallowed budesonide and fluticasone in patients with esophageal lichen planus. Our data suggest that this therapy both positively affects dysphagia as well as mucosal appearance. Adverse events included esophageal candidiasis which affected 10% and responded to therapy in all.Table 1: Characteristics of 40 patients with esophageal lichen planusTable 2: Barium Swallow and Endoscopic FindingsFigure 1Figure 2

Topical steroids in eosinophilic esophagitis: Systematic review and meta-analysis of placebo-controlled randomized clinical trials.

Eosinophilic esophagitis (EoE) is a clinicopathologic condition characterized by symptoms of esophageal dysfunction in the presence of eosinophil-predominant inflammation of esophageal mucosa. Topical steroids are recommended as first line pharmacologic therapy in EoE. We aimed to determine the efficacy of topical steroids in inducing histologic and clinical remission in children and adults with EoE. We performed a systematic search of the MEDLINE, EMBASE, Scopus, and Cochrane library databases for studies investigating the efficacy of topical steroids in EoE. We collected data on the number of patients, dose and duration of therapy, complete and partial histological response, and clinical improvement. We performed meta-analysis of placebo-controlled randomized clinical trials using Review Manager version 5.2. We used funnel plots to evaluate for publication bias. Five studies that included 174 patients with EoE were included in the meta-analysis. Topical fluticasone was administered in three studies involving 114 patients, and topical budesonide in two studies involving 60 patients. Patients treated with topical steroids, as compared with placebo, had higher complete histological remission (odds ratio [OR] 20.81, 95% confidence interval [CI] 7.03, 61.63) and partial histological remission (OR 32.20, 95% CI 6.82, 152.04). There was a trend towards improvement in clinical symptoms with topical steroids as compared with placebo but it did not reach statistical significance (OR 2.72, 95 %CI 0.90, 8.23). Topical corticosteroids seem to be effective in inducing histological remission but may not have similar significant impact in improving clinical symptoms of EoE. Studies with large sample size are needed to uniformly validate symptom improvement in EoE.

Characterization of a novel high-dose ovalbumin-induced murine model of allergic sinonasal inflammation.

Few efficacious topical therapies exist for chronic rhinosinusitis (CRS). The lack of a reproducible mouse model of CRS limits the pilot testing of potential novel anti-inflammatory therapies. Although the ovalbumin-induced mouse model of sinonasal inflammation is commonly used, it is difficult to reproduce and can generate variable histologic results. In this study, we explore a variation of this model in different strains of mice and explore various inflammatory cytokines as reproducible molecular markers of inflammation. Allergic sinonasal inflammation was generated in BALB/c and C57BL/6 mice using intraperitoneal high-dose injections of ovalbumin (Ova; Sigma Chemical Co.) followed by 10 days of high-dose intranasal sensitization. Real-time polymerase chain reaction (RT-PCR) for eotaxin, interleukin 4 (IL-4), and IL-13 were measured from sinonasal mucosa. We also pilot tested a known topical budesonide to characterize the anti-inflammatory response. Histological sections were analyzed for epithelial thickness and eosinophilia. Both BALB/c and C57BL/6 mice consistently showed increases in T helper 2 (Th2) cytokines after sensitization with high-dose Ova (p < 0.0001) when compared to controls. There were also significant increases in epithelial thickening in Ova-sensitized mice and eosinophilia in both BALB/c and C57BL/6 strains. In addition, topical budesonide significantly reduced anti-inflammatory cytokines, eosinophilia, and epithelial thickness. Our variation of the ovalbumin-induced mouse model of sinonasal inflammation in both BALB/c and C57BL/6 mice provides an efficacious model for testing potential topical anti-inflammatory therapies for CRS. The utilization of sinonasal mucosal Th2 cytokines along with histologic markers provides a consistent and quantifiable marker of inflammation in assessing the efficacy of candidate drugs.

A prospective open clinical trial of a proton pump inhibitor, elimination diet and/or budesonide for eosinophilic oesophagitis

Elimination diets and high-dose proton pump inhibitors (PPI) are advocated as first-line treatments in patients with eosinophilic oesophagitis (EoE). To record the treatment outcome for patients with EoE prospectively managed according to a clinical algorithm. Patients with oesophageal eosinophilia commenced esomeprazole 40 mg twice daily for 8 weeks. Those in histological remission were re-classified as PPI-responsive oesophageal eosinophilia. Nonresponders were offered the 6-food elimination diet with a PPI, or topical budesonide monotherapy (1 mg orally twice daily as an aqueous gel). Once disease control was achieved remission was reassessed at 3 months (all modalities) and an additional 6 months (diet group). Of 107 patients who completed 8 weeks of PPI, 25 (23%) were PPI-responsive. 56 of 81 (69%) of patients with EoE chose the elimination diet with PPI. 29 (52%) had complete remission, 23 completed dietary reintroduction and food triggers were identified in 20 (36%). 25 chose budesonide with 23/25 (92%) responding. Remission was sustained in >85% of patients at 3 months with all treatment modalities. At 9 months, only 10/18 (55%) of patients who responded to the elimination diet with PPI remained complaint and sustained remission. Many patients previously diagnosed with EoE will respond to PPI. Initial response >50% is possible with the elimination diet plus PPI, but many will fail to undergo food reintroduction, or will cease the diet and relapse, resulting in only one in four patient sustaining remission at 9 months. Budesonide is very effective short term, but longer term study is needed.